This review examines the categorization of Essentially Derived Varieties (EDV) introduced in the 1991 revision of the Convention of the Union internationale pour la protection des obtentions végétales (UPOV). Challenges in the implementation of the concept and progress made on a crop-by-crop basis to provide greater clarity and more efficient implementation are reviewed. The current approach to EDV remains valid provided i) clarity on thresholds can be achieved including through resource intensive research on an individual crop species basis and ii) that threshold clarity does not lead to perverse incentives to avoid detection of essential derivation. However, technological advances leading to new varieties resulting from the simultaneous introduction or change in expression of more than “a few” genes will so challenge the concept to require a new Convention. Revision could include deletion of the concept of essential derivation and revision on a crop-by-crop basis of the breeder exception. Countries that allow utility patents for individual plant varieties per se should consider removing that possibility unless plant breeders utilize those encouragements for risk taking and investment to broaden the germplasm base upon which the long-term sustainability of plant breeding resides.

There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

Astronauts are at risk of losing 1.0 to 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and dietary regimens designed to preserve their musculoskeletal system. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells, the contributions of macrophage colony stimulating factor, activator of NFkB and the calcineurin pathways make in osteoclast differentiation, and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in the microgravity of space, and in conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

Abstract: This article provides a brief review of the ontogeny of chondrocytes and the pathophysiology of osteoarthritis (OA), and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of mesenchymal stem cells for successful transplantation therapy. In response to exercise chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins and antiinflammatory cytokines and decrease their production of proinflammatory cytokines and matrix degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise increases peripheral blood recruitment of bone marrow-derived mesenchymal stem cells (BM-MSC) and upregulates BM-MSC expression of osteogenic and chondrogenic genes, osteogenic micro-RNAs, and osteogenic growth factors. Rodent experiments are uniform in demonstrating that exercise enhances the osteogenic potential of BM-MSC while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interferon (INF)-γ while increasing their production anti-osteoclastogenic cytokines IL-10 and transforming growth factor (TGF)-β. In conclusion, physical exercise done both by stem cell donors and recipients may improve the outcome of mesenchymal stem cell transplantation.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

In an attempt to correct misunderstandings this article brings together the observations on Calcium, Myosin Binding Protein-C and Hypertrophic Cardiomyopathy in the basic function of cardiac muscle. A finding of many years ago is reiterated in a novel enzyme kinetic format with defined rate limiting step which makes CaATP the apparent substrate of the actomyosin cross-bridge. The relationship of these kinetics to recent observations on disruption of myosin binding protein-C is described along with how this bears on the understanding of the related cardiomyopathies.

Objective: To determine the effect of birth season climate on adult total serum IgE (TSIgE) levels. Study design: The study is a retrospective chart review with the following inclusion criteria: TSIgE measurement, age ≥16, and northeastern Tennessee birthplace. Main outcome measures include TSIgE levels, birth season climatic conditions, and regional pollen-producing plant and pollen counts. Results: The records of 1,274 women (mean age 40.8 ± 17.5, age range 16-96) and 762 men (mean age 38.1 ± 17, age range 16-82) seen in our Allergy Clinic were reviewed. Persons born in the spring and summer, the seasons with the highest pollen counts and the most favorable climatic conditions for plant growth, had nearly twice the odds of having TSIgE levels >1σ above the mean of the study group when compared to those born in the fall or winter (odds ratio (OR) 1.75, 95% confidence interval (CI) 0.96-3.17 and OR 1.93, 95% CI 1.04-3.57, respectively); odds were highest for those born in March (OR 2.55, 95% CI 1.37-4.74) and July (OR 2.38, 95% CI 1.25-4.51) and lowest for those born in November (OR 0.11, 95% CI 0.0068-1.79). When averaged over the 95-years of study and five 30-year climate cycles TSIgE levels increased linearly as the seasons progressed from fall to summer (r²= 0.9475, P=0.0266). Of the climatic factors, TSIgE levels correlated most strongly with levels of precipitation (r²= 0.9145, P=0.0437). Conclusion: Climatic conditions that increase birth season exposure to environmental allergens may have a life-long effect on TSIgE production.

Systemic inflammation plays a central role in many diseases and is, therefore, an important therapeutic target. In a scoping review, we assessed the evidence base for anti-inflammatory effects of pre-, pro- and synbiotics in children. Of 1254 clinical trials published in English in Ovid Medline and Cochrane Library PubMed from January 2003 through September 2022, 29 were included in the review. In 6 studies of healthy children (n=1552), one reported that fructo-oligosaccharides added to infant formula significantly reduced pro-inflammatory biomarkers and one study of a single strain probiotic reported both anti- and pro-inflammatory effects. No effects were seen in the remaining two single-strain and one multi-strain probiotic and one synbiotic study. In 23 studies of children with diseases (n=1550), prebiotics were tested in 3, single-strain in 16 and multi-strain probiotics in 6 and synbiotics in 2 studies. Significantly reduced inflammatory biomarkers were reported in 7/10 studies of atopic/allergic conditions, 3/5 studies of auto-immune diseases, 1/2 studies of preterm infants, 1 study of overweight/obesity, 2/2 studies of severe illness and 2/3 studies of other diseases. However, often only one or two of several biomarkers were improved, increased pro-inflammatory biomarkers occurred in 5 of these studies and a probiotic increased inflammatory biomarkers in a study of newborns with congenital heart disease. The evidence base for the effects of pre-, pro- and synbiotics on systemic inflammation in children is weak. Further research is needed to determine if anti-inflammatory effects depend on the specific pre-, pro- and synbiotic preparations, health status and biomarkers studied.

Very heavy stratiform precipitation (> 200 mm/per day) occurred in the Hokitika region on the west coast of the South Island of New Zealand on 18 June 2015, under north-westerlies with small CAPE (< 25 J/kg). Analyses of model simulations and observations showed that this heavy rainfall was due to cold front lifting enhanced by orographic lifting over the Southern Alps. At 1.5 km grid-length, the model terrain underestimated the average height of the 103 tallest mountains over the South Island by ~ 800 m. This leads to weaker orographic lifting and mountain blocking, and a faster-moving and stronger cold front in the Hokitika region. As a result, large errors in the heavy rainfall prediction occur. By increasing either the resolved or the sub-grid mountain heights, the simulated rainfall errors were largely reduced through stronger orographic lifting and mountain blocking, and a better simulation of the cold front movement and strength. All the experiments have the same “flow-over” regime with mountain waves and/or wave breaking (Fm ranges 0.61 – 1.21). However, the rainfall amount and distribution on the windward side of mountains altered significantly. Our new findings were that the Southern Alps can have significant indirect effects on heavy rainfall by altering the speed and strength of the cold front, in addition to the well-known direct dynamical effects (i.e., orographic lifting and mountain blocking). A combination of these direct and indirect effects makes the heavy rainfall simulation sensitive to mountain heights even under the same “flow-over” regime.

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target.

The involvement of the angiotensin II type 1 receptor in the Frank-Starling Law of the Heart, where the various activations are very limited, allows simple analysis of the kinase systems involved and thence extrapolation of the mechanism to that of angiotensin control of activation of cardiac and skeletal muscle contraction. The involvement of phosphorylation of the myosin light chain in the control of contraction is accepted but not fully understood. The involvement of troponin-I phosphorylation is also indicated but of unknown mechanism. There is no known signal for activation of myosin light chain kinase or Protein Kinase C-βII other than Ca²⁺/calmodulin but the former is constitutively active and thus has to be under control of a regulated inhibitor, the latter kinase may also be the same. Ca²⁺/calmodulin is not activated in Frank-Starling, i.e. there are no diastolic or systolic [Ca²⁺] changes. I suggest here that that the regulated inhibition is by myosin light chain phosphatase and/or β-arrestin. Angiotensin activation is by translocation of the β-arrestin from the sarcoplasm to the PM thus reducing its kinase inhibition action in the sarcoplasm, this reduced inhibition has been wrongly attributed to a mythical downstream agonist property of β-arrestin.

Olfactory dysfunction affects often has severe consequences on patients’ quality of life. The most common complaint in these patients is their reduced enjoyment of food in both patients with olfactory loss and parosmia. How the different types of olfactory dysfunction differ in relation to food and cooking habits, sensory awareness, and food-related quality of life has not yet received much attention. By applying questionnaires on cooking, food, olfactory function, weight changes, sensory awareness, and food-related quality of life, we investigate how various aspects of eating differ between participants with olfactory loss (n=271), parosmia(n=251), and normosmic controls(n=166). Cooking habits in olfactory dysfunction revealed pronounced differences as compared with normosmic controls. Cooking with olfactory dysfunction was associated with e.g., a lack of comfort and inspiration for cooking and an inability to make new foods successfully. Significant differences in cooking were also found between olfactory loss and parosmia. Food items were less familiar in participants with olfactory loss and parosmia, while the ratings of liking food items differed between olfactory loss and parosmia, indicating the importance of adapting ingredients in meals separately for olfactory loss and parosmia. Parosmia was associated with a higher incidence of weight loss, but we found no difference in the food-related quality of life between participants with olfactory loss and parosmia. While olfactory loss and parosmia have wide-ranging consequences on patients’ cooking and food habits, adapting meals to include ‘safer food items’ and integrating multisensory stimulation may be a possible avenue for improving the enjoyment of food.

Infant electrocardiograms (ECG) and heart rates (HR) are very useful biosignals for psychological research and clinical work, but can be hard to analyze properly, particularly long form (≥5 minutes) recordings taken in naturalistic environments. Infant HRs are typically much faster than adult HRs, and so some of the underlying frequency assumptions made about adult ECGs may not hold for infants. However, the bulk of publicly available ECG approaches focus on adult data. Here, existing open-source ECG approaches are tested on infant datasets. The best performing open-source method is then modified to maximize its performance on infant data (e.g., including a 15Hz high pass filter, adding local peak correction). The HR signal is then subsequently analyzed, developing an approach for cleaning data with separate sets of parameters for the analysis of cleaner and noisier HR. A Signal Quality Index (SQI) for HR is also developed, providing insight into where a signal is recoverable and where it is not, allowing for more confidence in analysis performed on naturalistic recordings. The tools developed and reported in this paper provide a base for future analysis of infant ECG and related biophysical characteristics. Of particular importance, the proposed solutions outlined here can be efficiently applied to real-world large datasets.

Climate change, biodiversity loss, and other social and environmental problems pose grave risks. Progress so far has been incremental and insufficient, and as a result scientists, global policy experts, and the general public increasingly conclude that bold change is required across all sectors of society. At least two kinds of bold change are conceivable: reform of existing societal systems (e.g., financial, economic, legal, and governance systems), including their institutions, policies, rules, and priorities; and transformation, understood as the de novo development of and migration to new, improved systems. This paper is the second in a series of three that together propose a novel science-driven research and development program aimed at societal transformation. Moreover, the series advances a conceptual framework and formal mechanics by which societal transformation might be approached. Two of the underlying hypotheses are that new societal systems can be developed in a science-driven process to be fit for purpose, and system fitness can be compared across designs. Societies are viewed as superorganisms, and systems are viewed as a societal cognitive architecture. The first paper in the series provides definitions, aims, hypotheses, and a worldview. This paper discusses motivations, the role of science in societal transformation, a theory of change, and fitness metrics. The proposed R&amp;D program and theory of change are sound, viable, and affordable. The local-global-viral strategy invites the global science community to play a unique co-leadership role with local communities in the development, testing, and monitoring of new societal systems. Systems are implemented via a novel civic club model, where participation is voluntary. Clubs grow and replicate based on merit and aided by club networks, whose systems are also viewed as societal cognitive architectures. Benefits of the program and strategy are discussed.

This paper applies conceptualization from Paulo Freire, Tracey Nicholls, and bell hooks to develop a framework to understand art- and media-based communication of knowledge. Increasing use of art and digital media in research and formal educational settings emphasize knowledge-communication intent, and the theory attempts to rationalize why individuals potentially devalue, discard, or misconstrue messaging. Drawing upon two case studies: children’s literature, and existing scholarship on true crime as a media genre, the framework proposes art and media consumption based on perceived task-applicability of art and media. Stemming from the complex nature of socially-imposed, self-determined, and art- & media-instated tasks that an individual may face throughout their lifetime, an individual may be drawn to Freirean power and privilege - even fictional depictions - as societal structures can grant power and privilege with universal task-applicability. Potential usage of this framework towards participatory, qualitative inquiries conclude the paper, in attempt to support future art and media designed with knowledge-communication intent.

Abstract: A two-year study of pearl millet-groundnut cropping systems across two fertilizer levels was conducted at the INRAN/TARNA research station in Maradi, Niger in the Sahelian zone of West Africa. The objective of this study was to identify the best cropping system with and without fertilizer application to optimize pearl millet and groundnut yields, land use efficiency, and economics as measured by value-to-cost ratio. The experiment was conducted with three replications, and ten treatments combination of five pearl millet and groundnut cropping systems (pearl millet and groundnut sole crops, and three pearl millet – groundnut intercrops), and two fertilizer levels. Sole cropping produced the highest pearl millet grain by over 300 kg ha-1 and groundnut pod yields by over 500 kg ha-1, but all the intercropping systems had a LER above 1.0 with land use efficiency increased by 19 to 41%, also intercropping increased diversity, and reduced risk. Fertilizer application increased yields in all cropping systems by 200 to 600 kg ha-1. Government subsidy increased the value-to-cost ratio by 0.5 to 2, 5 units, and was required for economic response for pearl millet sole and intercrops in 2022. The groundnut sole cropping system had the greatest economic response to fertilizer application. Based on the risky environment and multiple end uses needed by producers, the intercrop system M-G: 1:3:1 with fertilizer application is usually the best option to optimize pearl millet and groundnut production.

In the recent years, intelligent data-driven faultdiagnosis methods on gearboxes have been successfully developedand popularly applied in the industries. Currently, most ofthe machine learning techniques require that the training andtesting data are from the same distribution. However, thisassumption is difficult to be met in the real industries, sincethe gearbox operating conditions usually change in practice,which results in significant data distribution gap and diagnosticperformance deteriorations in applying the learned knowledgeon the new conditions. This paper proposes a deep learning-based domain adaptation method to address this issue. Theraw current signals are directly used as the model inputs fordiagnostics, which are easy to collect in the real industries andfacilitate practical applications. The maximum mean discrepancymetric is introduced to the deep neural network, the optimizationof which guarantees the extraction of generalized machineryhealth condition features across different operating conditions.The experiments on a real-world gearbox condition monitoringdataset validate the effectiveness of the proposed method, whichoffers a promising tool for cross-domain diagnosis in the realindustries.

Background: Elevated respiratory rates (RR) have been described in several disease states, such as pneumonia, asthma and bronchiolitis. Despite this, there are few studies defining the range of RR found in healthy children. Available age percentiles for RR have been generated using methods that have the potential themselves to alter the rate. Aim: The aim of this study was to develop accurate percentile charts of RR specific for age in healthy children for potential use in pre-hospital care (first-aid), clinical medicine and for reference in respiratory research. Method: A newly developed optical respiratory sensor was used to measure RR which placed no restrictions on respiratory excursion. This technique enabled recording in awake children without the artefact of the observer’s presence on the subject’s RR. A cross-sectional sample of healthy children was obtained from maternity wards, childcare centres and schools in Brisbane, Queensland, Australia. Results: RR were observed in 560 awake and 103 sleeping children of which data from 343 awake and 94 sleeping children was used to create reference ranges for healthy children from newborn to 13 years of age. The recorded rates were significantly higher when children were awake compared to asleep. During quiet sleep, RR decreased from 40 (interquartile range 7) bpm at one month to 20 (interquartile range 3) in children aged 3 years. In awake children, RR ranged from a median of 40 bpm (interquartile range 18) at 1 year to 12 bpm (interquartile range 11) at 13 years respectively. Conclusion: The optical sensor was found to be an appropriate respiratory transducer, capable of measuring RR and reducing artefact by the subjective responses of alert children. The centile charts will be helpful as an aid to detecting abnormal RR in children and will contribute to further systematic reviews related to this vital sign.

I have recently reiterated that the cross-bridge is a calcium ATPase that is inhibited by magnesium and this arises because in normal hearts Myosin binding Protein-C prevents the use of MgATP as rate limiting substrate ensuring that Ca²⁺ replaces Mg²⁺ in the excitation pathway. Here I revisit the studies on [Ca²⁺] dependency of ATPase and tension under diastolic stretch with a different conclusion on Hill coefficients. This reveals the underlying mechanisms of the Frank-Starling Law and Hypertrophic myopathy are not the same, the former being kinase controlled.

The Greenland Ice Sheet is now the largest land ice contributor to global sea level rise, largely driven by increased surface meltwater runoff from the ablation zone, i.e. areas of the ice sheet where annual mass losses exceed gains. This small but critically important area of the ice sheet has expanded in size by ~50% since the early 1960s, and satellite remote sensing is a powerful tool for monitoring the physical processes that influence its surface mass balance. This review synthesizes key remote sensing methods and scientific findings from satellite remote sensing of the Greenland Ice Sheet ablation zone, covering progress in 1) radar altimetry, 2) laser (lidar) altimetry, 3) gravimetry, 4) multispectral optical imagery and, 5) microwave and thermal imagery. Physical characteristics and quantities examined include surface elevation change, gravimetric mass balance, reflectance, albedo, and mapping of surface melt extent and glaciological facies and zones. The review concludes that future progress will benefit most from methods that combine multi-sensor, multi-wavelength, and cross-platform datasets designed to discriminate the widely varying surface processes in the ablation zone. Specific examples include fusing laser altimetry, radar altimetry, and optical stereophotogrammetry to enhance spatial measurement density, cross-validate surface elevation change, and diagnose radar elevation bias; fusing optical imagery, radar imagery, and microwave scatterometry to discriminate between snow, liquid water, refrozen meltwater, and bare ice near the equilibrium line altitude; combining optical reflectance with laser altimetry to map supraglacial lake, stream, and crevasse bathymetry; and monitoring the inland migration of snowlines, surface melt extent, and supraglacial hydrologic features.

Balance requires constant adjustments in muscle activation to attain force steadiness. Creating appropriate training can be challenging. The purpose of this study was to examine the effects of two weeks front squat instability training using a water-filled training tube on force steadiness during an instability challenge. Control (CON, n= 13) and experimental (EXP, n=17) subjects completed pre and post testing for EMG variability by completing one set of 10 repetitions with a stable and unstable training tube. Electrodes were placed bilaterally on the anterior deltoid, paraspinal and vastus lateralis muscles. CON subjects completed 2 weeks of training using a stable training tube, while EXP subjects trained with a water-filled instability tube. EMG data were integrated for each contraction and force steadiness computed using the natural log of coefficient of variation. CON results showed no changes in force steadiness for any condition. EXP showed significant reductions in EMG activation variability across all muscles. These results indicate a significant training effect in reducing muscle activation variability in subjects training with a water-filled instability training device. Improvements seen in these healthy subjects supports development of training implements for a more clinical population to help improve force steadiness.

(1) Background: in the context of sustainable development goals (SDGs), this work explores the repair direction of future cultivated land protection policies based on the Smith policy implementation model from the historical evolution to ensure that the cultivated land protection policy does not deviate during the implementation process. (2) Methods: this paper uses literature research and inductive deduction methods to sort out the evolution process of Chinese cultivated land protection policy, summarize the successful experience of transferring the focus of cultivated land protection in chronological order, and conclude the repair direction of Chinese cultivated land protection. (3) Results: although the Chinese cultivated land protection policy in the historical evolution has through three significant phases, there are still certain issues in the development trend of Chinese cultivated land protection policy based on regional division of labor for grain transportation and sales. (4) Conclusion: directly utilizing feedback from farmers as stakeholders will contribute to the maturity and improvement of cultivated land protection policies in the specific implementation of cultivated land protection policies.

Monitoring the health of coral reefs is essential to understand the damaging impacts of anthropo-genic climate change. Non-invasive methods to survey coral reefs are the most desirable and op-tics-based surveys, ranging from simple photography to multispectral satellite imaging are well es-tablished. Herein, we review these techniques, focusing on their value for coral monitoring and health diagnosis. A new, low-cost hyperspectral imaging technique using linear variable filters is also described. This system is capable of simultaneously producing hyperspectral and photogrammetric outputs, which provides integrated information of reef structure and physiology.

Tomato (Solanum lycopersicum), an important vegetable crop, is a host for numerous pests and pathogens. Consequently, tomato breeders are striving to improve pest resistance. Many acces-sions of the wild relative S. habrochaites display high resistance towards arthropod pests such as spider mites and whiteflies and the presence of the sesquiterpene hydrocarbon 7-epi zingiberene in its trichomes has been associated with arthropod resistance. Consequently, tomato breeders are attempting to introgress 7-epi zingiberene from wild to cultivated tomato, which requires the ability to quantify zingiberene. 7-Epi zingiberene has conjugated double bonds causing it to ab-sorb uv light. In fact, de Freitas, et al. [1] have claimed that measurement of absorbance at 270 nm of tomato leaflet washes can be used to quantify zingiberene. However, this claim has never been critically evaluated. We initially evaluated the use of uv absorbance to estimate zingiberene content of leaflet washes from an interspecific hybrid tomato BC4F2 generation that was segre-gating widely for presence and abundance of zingiberene. When absorbances at 270 nm were compared with zingiberene measured by gas chromatography the resulting relationship did not obey the Beer-Lambert law. Consequently, we examined in detail aspects of the uv-absorbance of zingiberenoids by: 1) obtaining uv absorbance spectra for three isolated zingiberenoids and de-termining the relationship between the abundance of each isolated compound and absorbance at single wavelengths; 2) obtaining uv absorbance spectra of leaflet washes of relevant wild acces-sions and parents; 3) obtaining average absorbance spectra for interspecific generations of tomato that were segregating for abundance of zingiberenoids and determining their λmax values in the 250-280 nm region; 4) evaluating by regression the relationship between absorbance at a single wavelength and the concentration of zingiberene and when present, its derivatives, as measured by gas chromatography in several interspecific hybrid generations; and 5) exploring the potential use of absorbances at multiple wavelengths to improve estimates of concentrations of zingi-berenoids. Results indicated that isolated zingiberenoids as well as leaflet washes of wild tomatoes that contain zingiberenoids have broad absorbance spectra in the uv region with a λmax of 264 nm. The relationship between abundance of isolated zingiberenoids and absorbance at a single wavelength of 264 nm did obey the Beer-Lambert Law. Average absorbance spectra for leaflet washes from BC3F5 generation plants sampled by two methods, as well as from a BC5F1 and a BC3F3 generation showed subtle shifts in the λmax away from 264 nm. Furthermore, the rela-tionship between absorbance at 264 nm and zingiberenoid content of these generations did not obey the Beer-Lambert Law in that in each case regression of absorbance on zingiberenoid content of the leaflet washes resulted in non-zero intercept estimates that varied considerably among generations and sampling methods. Use of multiple wavelengths for estimation zingiberenoids in these breeding generations was explored and inclusion of additional absorbances at one or two wavelengths identified by stepwise regression always improved estimates of zingiberenoid content from absorbance data. However, the identified wavelength(s) differed among generations. Taken together the results indicate that measurement of absorbance of tomato leaflet washes at a single wavelength is not a reliable quantitative estimate of zingiberenoids in the leaflet wash. These estimates can be improved by utilizing absorbance at multiple wavelengths, but the par-ticular wavelengths will likely vary among generations. Lastly, measurement of absorbance may be a useful tool in identifying those relatively rare individuals in a generation that is widely segregating for zingiberenoid content. However, even in this situation the determination of the actual zingiberene content e.g., for comparison with the donor parent, would need to be back-stopped by a valid quantitative method such as gas chromatography.

The quest for sustainable health, environmental protection and conservation of beneficial organisms makes the use of biopesticides a desirable option. This research aimed to identify botanicals used in the management of farm and household pest in Plateau State, Nigeria. A cross sectional study was carried out using semi-structured questionnaires and on the spot face-to-face interviews. The main issues captured include the pest, plants used to managed the pest, parts used, cultivation status, availability, effect on pest, formulation methods and modes of application. The quantitative data were analyzed using the Frequency of Citation (FC), Relative Frequency of Citation RFC (%) and Use Value (UV). A total of 45 plant species belonging to 42 genera, 20 orders and 30 families were found to be useful in the management of 15 different pests. The FC, RFC(%) and UV values identified the most popularly used plants as: Hyptis suaveolens, Vernonia amygdalina, Azadirachta indica, Canarium schweinfurthii and Euphorbia unispina and Erythrophloem africanum. Plants that showed broad activity include Azadirachta indica (7 uses), Erythrophloem africanum, Khaya senegalensis and Vernonia amygdalina. The perception of the respondents indicated that most of the biopesticides are available, affordable, effective, eco-friendly and safe. This survey provides a pathway for formulation of biopesticides.

Bioenergy produced from perennial feedstocks such as woody biomass could serve as an opportunity to strengthen local and regional economies and also jointly produce various environmental services. In order to assess the potential for biomass- based bioenergy, it’s essential to characterize the interest that potential biomass suppliers have in such an endeavor. In the U.S. Great Plains region, this largely means assessing relevant perceptions of farmers and ranchers. We conducted a series of farmer and rancher oriented focus groups in North Dakota, South Dakota, Nebraska and Kansas to qualitatively explore opinions about the role that trees can play in agriculture and interest in woody biomass systems within existing Northern Great Plains (NGP) farms and ranches. Our findings suggest that farmer and ranchers generally value the role that trees, or tree-based practices like windbreaks can play in agriculture particularly on marginal farmland in terms of conservation or crop protection. Yet relative to the potential of trees as a biomass crop there is a distinct lack of knowledge and skepticism. Farmers and ranchers also noted variable degrees of risk concern and uncertainty regarding investing in tree-based systems, as well as a number of perceived external market related constraints to integrating trees within their managed systems. Most of the participants recognized that if biomass production or an increase in tree planting and management in general were to expand in the NGP region, government programs would likely be required to provide much needed technical guidance and financial incentives. As the NGP regional bioeconomy continues to emerge and expand, private and public investment relative to niche bioenergy feedstocks such as woody biomass should address the type of information needs that farmers and ranchers have relative to integrating biomass production into existing farm and ranch systems.

Weathering and erosion transport minerals and organics toward the sea or lake bottoms over geologic time. The finest solids are deposited in lower, less turbulent areas, such as lake bottoms and continental shelves. They sometimes stack up to thicknesses of kilometers, and begin compacting. These sediment sections are called shales, and as initially deposited in water, shales can have porosities up to 50-80{\%} water, As they are buried, many alteration products from oil to slate are produced due to overburden and temperature increasess, making them important to study. A preceeding paper \cite{1} showed that pressure solution is the primary mechanism for porosity reduction, with possible mechanical compaction at shallow depths. Without naming the mineral(s) involved, it postulated that the greater the product of the water and pore interfaces, the faster the reaction would proceed. This term is $ \varphi^{4m/3}(1-\varphi)^{4n/3}$ , where $\varphi$ is porosity and m and n are numbers close to unity. The large exponents, {\em 4/3}, recognize that the reaction occurs at the molecular scale at which the surfaces are rough. A second term, $\exp^{(-E/RT)}$ , indicates that the reaction is impeded by a quantum energy barrier, E, with diminished impeding power as increased available thermal energy, represented by the absolute temperature, T, becomes available at greater depths in the Earth. These two factors combine to allow porosity $\varphi$ to reduce with time, or equivalently for the fraction of solids, $(1-\varphi)$, to increase with time,$\left. \frac{\partial(ln(1-\varphi) ) }{\partial t } \right |_{\sigma} = (\varphi )^{4m/3}( 1-\varphi )^{4n/3}Ae^{-E/(RT)}$. { \em Here it is shown that this equation can cover quantitatively any actual deposition rates which may have been experienced by the six sections studied, the actual deposition rates being unknown for these cases. Hence a time-depth depositional history for any new shale section, known in detail, would allow determination of the parameters m, n, E and a lumped proportionality constant A. This was accomplished by showing that, for a wide range of depositional rates, r, the range of E for any of the studied sections is small compared to laboratory measurements of quartz solution\cite{2}, 24+-15kJ/mol. Results were obtained over this range of r's using the previously determined m and n, and porosity and temperature profiles. The presently existing porosity profiles necessarily incorporate any overpressure or underpressure conditions that may have existed in the past or currently, as the net difference between overburden and pore pressure is a primary driving force for pressure solution. $SiO_2$ usually comprises 20-50{\%} of shales. In conclusion, pressure solution of quartz can account for vertical compaction of shales quantitatively in the studied examples. Separately, a quasi-eqivalent method for discussing reduced porosities in Macron 2 versus Macron 1 as increased vertical stress, rather than additional horizontal stress, is illustrated. Experiments are suggested to clarify the pressure solution mechanism. The role of horizontal forces is discussed. From a global point of view, shale compaction by pressure solution is a quantified step in the cycling of continental rocks, beginning with rifting.

We follow the PRISMA extension for scoping reviews to review the emerging international body of empirical evidence on consumers’ attitudes and willingness to pay (WTP) for novel foods produced with New Plant Engineering Techniques (NPETs). NPETs include genome/gene editing, cisgenesis, intragenesis, RNA interference and others. These novel foods are often beneficial for the environment and human health and more sustainable under increasingly prevalent climate extremes. These techniques can also improve animal welfare and disease resistance when applied to animals. Despite these promising attributes, evidence suggests that many, but not all, consumers discount these novel foods relative to conventional ones. Our review sorts out findings to identify conditioning factors that can increase the acceptance of and WTP for these novel foods in a significant segment of consumers. International patterns of acceptance are identified. We also analyze how information and knowledge interact with consumer acceptance of these novel foods and technologies. Heterogeneity of consumers—across cultures and borders and in attitudes towards science and innovation—emerges as a key determinant of acceptance and WTP. Acceptance and WTP tend to increase when socially beneficial attributes—as opposed to producer-oriented cost-saving attributes—are generated by NPETs. NPET-improved foods are systematically less discounted than transgenic foods. Most of the valuation estimates are based on hypothetical experiments and surveys and await validation through revealed preferences in actual purchases in food retailing environments.

There is growing interest in characterizing the viromes of diverse mammalian species, particularly in the context of disease emergence. However, little is known about virome diversity in aquatic mammals, in part due to difficulties in sampling. We characterized the virome of the exhaled breath (or blow) of the Eastern Australian humpback whale (Megaptera novaeangliae). To achieve an unbiased survey of virome diversity a meta-transcriptomic analysis was performed on 19 pooled whale blow samples collected via a purpose-built Unmanned Aerial Vehicle (UAV, or drone) approximately 3km off the coast of Sydney, Australia during the 2017 winter annual northward migration from Antarctica to northern Australia. To our knowledge, this is the first time that UAVs have been used to sample viruses. Despite the relatively small number of animals surveyed in this initial study, we identified six novel virus species from five viral families. This work demonstrates the potential of UAVs in studies of virus disease, diversity, and evolution.

This study focused on the optimization of the flexural strength of bio-composite samples of palm kernel, whelks, clams, periwinkles shells and bamboo fiber, reinforced with resin for engineering applications. The aim of the study was to: formulate different samples of bio-composite reinforce with resin for engineering applications and to evaluate the flexural strength, of the fabricated composite. The hand lay-up technique was used for the composites produced by incorporating different percentage compositions of the shells/fiber (10%, 15%, 20%, 25% and 30%) into varied proportions of epoxy resin and catalyst. The cured samples after 24hours were subjected to tensile, impact, flexural and water absorption test. The experiments were conducted using Taguchi optimization method L25 (5x5) with five design parameters and five level combinations in Minitab 18 statistical software. The results showed that the average values of flexural was 114.87MPa when compared to the unreinforced of 72.33MPa bio-composite. The study recommended that agricultural waste like palm kernel shells, whelk shells, clams, periwinkle shells and bamboo fiber, should be converted into important engineering applications.

The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

COVID-19 affected health and wellbeing globally. Graduating nursing students face a variety of stressors and entering the nursing profession during the pandemic added additional stress. Mood, perceived stress, resilience, and coping were assessed in an Australian sample of 112 graduating nursing students, who completed the Brunel Mood Scale (BRUMS), Perceived Stress Scale (PSS-4), and Brief Resilient Coping Scale (BRCS). Mean BRUMS scores for tension, fatigue, and confusion were significantly above population norms, and vigour scores significantly below. Mean PSS-4 scores were reflective of population norms, but showed higher levels of stress for younger and on-campus students compared to those who were older or who studied externally. BRCS data showed that 82.1% of the graduating nursing students were medium or high resilient copers. Mood profiles suggested that 19.6% of participants had elevated mental health risk, 23.2% showed potential risk of burnout, and only 17.9% reported mood profiles associated with positive mental health. High mean tension scores reported by the graduating nursing students indicated apprehension about joining the profession, although stress, resilience and coping scores suggested they were adequately managing the additional stressors generated by a global pandemic.

The method of regularized stokeslets is widely-used to model microscale biological propulsion. The method is usually implemented with only the single layer potential, with the double layer potential being neglected, despite this formulation often not being justified a priori due to non-rigid surface deformation. We describe a meshless approach enabling inclusion of the double layer which is applied to several Stokes flow problems in which neglect of the double layer is not strictly valid: the drag on a spherical droplet with partial slip boundary condition, swimming velocity and rate of working of a force-free spherical squirmer, and trajectory, swimmer-generated flow and rate of working of undulatory swimmers of varying slenderness. The resistance problem is solved accurately with modest discretization on a notebook computer with the inclusion of the double layer ranging from no-slip to free slip limits; neglect of the double layer potential results in up to 24% error, confirming the importance of the double layer in applications such as nanofluidics, in which partial slip may occur. The squirming swimmer problem is also solved for both velocity and rate of working to within a few percent error when the double layer potential is included, but the error in the rate of working is above 250% when the double layer is neglected. The undulating swimmer problem by contrast produces a very similar value of the velocity and rate of working for both slender and non-slender swimmers, whether or not the double layer is included, which may be due to the deformation’s `locally rigid body’ nature, providing empirical evidence that its neglect may be reasonable in many problems of interest. Inclusion of the double layer enables us to confirm robustly that slenderness provides major advantages in efficient motility despite minimal qualitative changes to the flow field and force distribution.

Additive manufacturing (AM) provides customization of the microstructure and mechanical properties of components. Selective laser melting (SLM) is the commonly used technique for processing high strength Aluminum alloys. Selection of SLM process parameters could control the microstructure of fabricated parts and their mechanical properties. However, process parameter limits and defects inside the as-built parts present obstacles to customized part production. This study is the second part of a comprehensive work that investigates the influence of SLM process parameters on the quality of as-built Al6061 and AlSi10Mg parts. The microstructure of both materials was characterized for different parts processed over a wide range of SLM process parameters. The optimized SLM parameters were investigated to eliminate the internal microstructure defects. Mechanical properties of the parts were illustrated by regression models generated with design of experiment (DOE) analysis. The results reported in this study were compared to previous studies, illustrating how the process parameters and powder characteristics could affect the quality of produced parts.

Cultural tourism in Tanzania presents a diverse tapestry of traditions, varied ethnic groups, and historical accounts. This article aims to pinpoint areas for further exploration in the cultural tourism sector of Tanzania and analyze their potential impacts. The study conducted a systematic review of the literature following established inclusion criteria as well as the Preferred Reporting Items for Systematic Reviews and meta-analysis guidelines. A total of 21 articles focused on Tanzania Cultural Heritage Tourism from sources such as Google Scholar and web databases were examined, revealing several research gaps, including theoretical, contextual and methodological aspects. Furthermore, the research offers insights into theoretical implications and recommends avenues for future studies that could advance the field by addressing these knowledge gaps providing valuable direction to new researchers interested in exploring these specific areas as well as practitioners seeking a comprehensive understanding of various aspects related to Tanzania's cultural heritage tourism

Up to forty percent of dairy cows develop metritis or endometritis when pathogenic bacteria infect the uterus after parturition. However, resilient cows remain healthy even when exposed to the same pathogens. Here, we provide a perspective on the mechanisms that dairy cows use to prevent postpartum uterine disease. We suggest that resilient cows prevent the development of uterine disease using the three complimentary defensive strategies of avoiding, tolerating and resisting infection with pathogenic bacteria. Avoidance maintains health by limiting the exposure to pathogens. Avoidance mechanisms include intrinsic behaviors to reduce the risk of infection by avoiding pathogens or infected animals, perhaps signaled by the fetid odor of uterine disease. Tolerance improves health by limiting the tissue damage caused by the pathogens. Tolerance mechanisms include neutralizing bacterial toxins, protecting cells against damage, enhancing tissue repair, and reprogramming metabolism. Resistance improves health by limiting the pathogen burden. Resistance mechanisms include inflammation driven by innate immunity and adaptive immunity, with the aim of killing and eliminating pathogenic bacteria. Farmers can also help cows prevent the development of postpartum uterine disease by avoiding trauma to the genital tract, reducing stress, and feeding animals appropriately during the transition period. Understanding the mechanisms of avoidance, tolerance and resistance to pathogens will inform strategies to generate resilient animals and prevent uterine disease.

Additive manufacturing (AM) of high strength Al alloys promises to enhance the performance of critical components related to various aerospace and automotive applications. The key advantage of AM is its ability to generate lightweight, robust, and complex shapes. However, the characteristics of the as-built parts may represent an obstacle to satisfy the part quality requirements. The current study investigates the influence of selective laser melting (SLM) process parameters on the quality of parts fabricated from different Al alloys. A design of experiment (DOE) is used to analyze relative density, porosity, surface roughness, and dimensional accuracy according to the interaction effect between the SLM process parameters. The results show a range of energy densities and SLM process parameters for the AlSi10Mg and Al6061 alloys needed to achieve “optimum” values for each performance characteristic. A process map is developed for each material by combining the optimized range of SLM process parameters for each characteristic to ensure good quality of the as-built parts. The second part of this study investigates the effect of SLM process parameters on the microstructure and mechanical properties of the same Al alloys. This comprehensive study is also aimed at reducing the amount of post-processing needed.

Widely used estimates of food-insecure populations are likely to be biased upwards, lacking adjustment for global increases in sedentary behavior in recent decades. We first construct a household model to account for sedentary choices during leisure and work time decisions. The model rationalizes increasing sedentary behavior from the household by accounting for increasing returns to cognitive human capital vs physical capital, alongside increased productivity of more sedentary activities both at work and at home. The household model then informs an empirical model that makes use of our unique international pseudo-panel data on sitting time, which serves as a proxy for sedentarism. We econometrically estimate a transfer function linking sedentarism to widely available covariates, which then are used to make out-of-sample predictions and can be applied to a large set of countries. The estimated sedentary time can be used to adjust the physical activity level reflected in the minimum dietary energy requirement used to determine a cutoff for food insecurity.

The lab-on-a-chip concept, enabled by microfluidic technology, promises the integration of multi-ple discrete laboratory techniques into a miniaturised system. Research into microfluidics has generally focused on the development of individual elements of the total system (often with rela-tively limited functionality), without full consideration for integration into a complete fully opti-mised and miniaturised system. Typically, the operation of many of the reported lab-on-a-chip devices is dependent on the support of a laboratory framework. In this paper, a demonstrator platform for routine laboratory analysis is designed and built, which fully integrates a number of technologies into a single device with multiple domains such as fluidics, electronics, pneumatics, hydraulics, and photonics. This facilitates the delivery of breakthroughs in research, by incorpo-rating all physical requirements into a single device. To highlight this proposed approach, this demonstrator microsystem acts as a fully integrated biochemical assay reaction system. The re-sulting design determines enzyme kinetics in an automated process and combines reservoirs, three-dimensional fluidic channels, optical sensing, and electronics in a low-cost, low-power and portable package.

Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintaining protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensuring cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, focusing on cardioprotection, neuroprotection, and cancer. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.

If given the correct remotely sensed information, machine learning can accurately describe soil moisture conditions in a heterogeneous region at the large scale based on soil moisture readings at the small scale through rule transference across scale. This paper reviews an approach to increase soil moisture resolution over a sample region over Australia using the Soil Moisture Active Passive (SMAP) sensor and Landsat 8 only and a validation experiment using Sentinal-2 and the Advanced Microwave Scanning Radiometer (AMSR-E) over Nevada. This approach uses an inductive localized approach, replacing the need to obtain a deterministic model in favor of a learning model. This model is adaptable to heterogeneous conditions within a single scene unlike traditional polynomial fitting models and has fixed variables unlike most learning models. For the purposes of this analysis, the SMAP 36 km soil moisture product is considered fully valid and accurate. Landsat bands coinciding in collection date with a SMAP capture are down sampled to match the resolution of the SMAP product. A series of indices describing the Soil-Vegetation-Atmosphere Triangle (SVAT) relationship are then produced, including two novel variables, using the down sampled Landsat bands. These indices are then related to the local coincident SMAP values to identify a series of rules or trees to identify the local rules defining the relationship between soil moisture and the indices. The defined rules are then applied to the Landsat image in the native Landsat resolution to determine local soil moisture. Ground truth comparison is done via a series of grids using point soil moisture samples and air-borne L-band Multibeam Radiometer (PLMR) observations done under the SMAPEx-5 campaign. This paper uses a random forest due to its highly accurate learning against local ground truth data yet easily understandable rules. The predictive power of the inferred learning soil moisture algorithm did well with a mean absolute error of 0.054 over an airborne L-band retrieved surface over the same region.

We investigate the determinants of U.S. bilateral imports of olive oil and their dynamics from shocks in foreign supplies and changes in U.S. olive oil demand, using an augmented gravity framework that leads to an equilibrium of bilateral trade flows from olive oil exporters to the U.S. market. The empirical specification is applied at the disaggregated HS-6 level in a panel dataset, and three estimation techniques (truncated OLS, PPML, Heckman), for which the latter two account for zero trade flows, the extensive margin of trade and the potential censored distribution of exports with zero trade flows. We run Reset and HPC tests to qualify our results. On the supply side, exporters’ capacity to exports, multilateral trade resistance, and immigrants’ networks into the US are strong determinants of the bilateral trade flows for both aggregate olive oil exports and for virgin olive oil exports, On the consumer side, U.S. GDP, the import unit value, and immigrant network effects are robust determinants of bilateral flows as well for aggregate and virgin olive oil trade flows. Migrants’ stock, exporters’ GDP and population, and total exports revenues increase the probability of an exporter entering the U.S. market. We could not find robust evidence of consumer behavior being influenced by popular press measures of the emergence of Mediterranean diet and olive oil, or measures of cultural globalization of U.S. consumers.

The stringency of GMO regulation affects trade of agricultural products among countries. On that account, our investigation attempts to shed the light on the complexity of the impact of genetically modified organisms (GMO) regulations among countries on bilateral trade with a focus on GMO approvals. We develop a framework extending Xiong and Beghin (2014) and their decomposition of export supply and imports demand effects. Our approach encompasses the supplemental effect of GMO regulation laxity in production on the exporter’s productivity. It decomposes three effects that impact bilateral trade flows between trade partners: productivity in the source country, sorting cost from bilateral dissimilarity in regulations, and stringency impact on import demand. We estimate the model using a panel dataset of corn trade and two econometric approaches (PPML, Heckman sample-selection). We find that GMO laxity in production of exporters has the most prominent and robust effect of enhancing bilateral trade of corn. The effect of GMO laxity in demand appears to be smaller than the export booster effect of GMO adoption. Finally, bilateral dissimilarity in regulations does not appear to matter, once we account for the impact of GMO in production of the exporters and laxity in demand differentiated for importer and exporters. Hence, GMO approval regulations have dominating multilateral effects rather than bilateral ones.

The Cochran–Mantel–Haenszel (CMH) methodology is a suite of tests applicable to particular tables of count data. Inference is conditional on the treatment and outcome totals on each stratum being known before sighting the data. The CMH tests are important for analyzing randomised blocks data when the responses are categorical rather than continuous. This overview will first review the traditional CMH tests and then explore new alternative presentations of the ordinal CMH tests. Next the ordinal CMH tests will be extended so they can be used to test for higher moment effects. Finally unconditional analogues of the extended CMH tests will be developed.

This report presents a framework for analysing the risk of alien taxa under South Africa's National Environmental Management: Biodiversity Act of 2004, and the Alien and Invasive Species Regulations of 2014. While the report was initially designed to meet a specific South Africa need, the risk analysis processes developed can, we believe, be transferred to any specified geographic region. In outlining a series of questions related to a taxon’s likelihood of invasion and the consequences thereof, i.e. the potential impacts, the report provides a structure for collating data relevant to the process of listing taxa as well as a process for developing recommendations that is both mathematically sound, transparent, and that explicitly takes uncertainty into account. The framework is based on collating information according to international standards in biological invasions (specifically the IUCN Environmental Impact Classification of Alien Taxa Scheme, the CBD's scheme for classifying invasion pathways, and the Unified Framework for Biological Invasions proposed by Blackburn et al. 2011). The risk analysis framework is currently being implemented in South Africa in an effort to underpin national regulatory lists of invasive species.

Amorphous Indomethacin has enhanced bioavailability over its’ crystalline forms, yet amorphous forms can still possess a wide variety of structures. Here, Empirical Potential Structure Refinement (EPSR) has been used to provide accurate molecular models on the structure of five different amorphous Indomethacin samples, that are consistent with their high energy x-ray diffraction patterns. It is found that the majority of molecules in amorphous Indomethacin are non-bonded or bonded to one neighboring molecule via a single hydrogen bond, in contrast the doubly bonded dimers found in the crystalline state. The EPSR models further indicate a substantial variation in hydrogen bonding between different amorphous forms, leading to a diversity of chain structures not found in any known crystal structures. The majority of hydrogen bonds are associated with the carboxylic acid group, although a significant number of amide hydrogen bonding interactions are also found in the models. Evidence of some dipole-dipole interactions are also observed in the more structurally ordered models. The results are consistent a distribution of Z-isomer intra-molecular type conformations in the more disordered structures, that dis-tort when stronger inter-molecular hydrogen bonding occurs. The findings are supported by 1H and 2H NMR studies of the hydrogen bond dynamics in amorphous Indomethacin.

Earth’s extinction crisis is escalating, and threat classification schemes are increasingly important for assessing which human activities are the most prominent drivers of species declines. However, a quantitative understanding of the conservation responses needed to abate threatening processes, and avoid species extinctions, is often lacking. Here, we provide a threat abatement framework which groups threats based on the shared conservation goal of the actions needed to abate their impact. We apply this framework to Australia’s threatened species to quantify the relative importance of achieving different conservation response goals. Our analysis shows the most important conservation responses across Australia are habitat retention and restoration, due to the combined impact of threatening processes causing habitat destruction and degradation (e.g. logging, mining, urbanisation and agriculture), which affects the majority (86%) of Australia’s threatened species and the effective control of invasive species (82%). Most species also require conservation responses focussed on improved fire management (66%). We show that implementing responses in isolation will be inadequate for abating species extinctions as almost all species (89%) require multiple, integrated management responses to redress their threats. We also acknowledge that already small and potentially genetically compromised taxa may require more direct interventions (e.g. captive insurance populations or genetic rescue). Our analysis highlights the necessity of addressing multiple threats at appropriate geographic scales across Australia. Our threat abatement framework ensures that core conservation actions can be identified and aid recovery of threatened species, and can be applied to other geographic regions and conservation contexts.

The article concerns a relatively small but important fragment of John Paul II's pastoral activity, namely his pilgrimages to Poland: the nature of these pilgrimages, their historical background and teaching - especially to the extent that went beyond the immediate and Polish context. The text is the result not only of reading papal statements, but also of personal observation of the political and social atmosphere. The first two parts contain a concise description of the Pope's eight pilgrimages to Poland (before and after the political transformation). The third highlights out the main universal themes raised by the Pope: the dignity of the person, truth and freedom. During consecutive pilgrimages to Poland, he deepened and expanded the themes of his teaching. This collection of his sermons and speeches to Poles constitutes a comprehensive (devoid of redundant repetitions and omissions) treatment of important social, philosophical and theological issues. John Paul II, when speaking to Poles and about Poles, did not lose his universal perspective; he appealed both to Christians and to all people of good will. Papal pilgrimages to Poland are a significant part of modern Polish history, and their message is a valuable intellectual and spiritual gift.

This study used 10 replicate pens per treatment in a randomized complete block design and each pen contained 8 steers (initial BW = 305 ± 30.4 kg; n=80 steers/treatment) to determine if a phytogenic feed additive (PFA) with essential oils and plant extracts (PHYTOsolvan 200; DOSTOFARM, Westerstede, Germany) influences measures of growth or growth efficiency during the feedlot receiving phase in auction-derived beef steers. No steers were removed from the study; one steer from the control treatment was treated for respiratory disease. No mortality was noted in the present experiment. No appreciable differences were noted for BW, ADG, DMI, or feed conversion efficiency from d 1 to 29, 29 to 53, or during the cumulative receiving period (P ≥ 0.12). Performance based NEm and NEg were not influenced by dietary treatment (P ≥ 0.79). The ratio of observed-to-expected dietary net energy was not impacted by dietary treatment (P ≥ 0.71). These were healthy, high-growth potential Northern Plains steers. There was minimal morbidity (0.63%) and no mortality noted during the 53 d receiving study. Steers performed well and met growth performance expectations (the ratio of observed-to-expected NEm = 1.00), hence, it was not anticipated that the phytogenic compound would appreciably influence growth or health outcomes under the conditions of this experiment.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) lymphocytes eliminates cells infected with viruses. Antiviral ADCC requires three components: 1) antibody; 2) effector lymphocytes with the Fc-IgG receptor CD16A; and 3) viral proteins in infected cell membranes. Fc-afucosylated antibodies bind with greater affinity to CD16A than fucosylated antibodies; individuals’ variation in afucosylation contributes to differences in ADCC. Current assays for afucosylated antibodies involve expensive methods. We report an improved bioassay for antibodies that support ADCC which encompasses afucosylation. This assay utilizes externalization of CD107a by NK-92-CD16A cells after antibody recognition. We used anti-CD20 monoclonal antibodies, GA101 WT or glycoengineered (GE), 10% or ~50% afucosylated, and CD20-positive Raji target cells. CD107a increased detection 7-fold compared to flow cytometry to detect Raji-bound antibodies. WT and GE antibody effective concentrations (EC50s) for CD107a externalization differed by 20-fold, with afucosylated GA101-GE more detectable. The EC50s for CD107a-externalization vs. 51Cr cell death were similar for NK-92 CD16A and blood NK cells. Notably, the %CD107a-positive cells negatively correlated with dead Raji cells and was nearly undetectable at high NK:Raji ratios required for cytotoxicity. This bioassay is very sensitive and adaptable to assess anti-viral antibodies but unsuitable as a surrogate assay to monitor cell death after ADCC.

In this study, I will present some documentary evidence that Carlos Drummond de Andrade’s poem “A Máquina do Mundo” [The Machine of the World] (1949) was based on prior reflections contained in a forgotten newspaper article entitled “Poesia e Pesadelo” [Poetry and Nightmare] (1949). In that article, Drummond critically analyzed some of the theses of Stephen Spender's essay “What Is Modern in Modern Poetry” (1948), which had just been published in The Tiger's Eye magazine. As soon as he read Spender's text, Drummond wrote “Poetry and Nightmare” and began to elaborate a narrative poem whose protagonist would be a machine. All the documentary evidence indicates that Drummond took Spender's lessons as touchstones for the elaboration of the narrative and allegorical structure of “The Machine of the World.” According to the interpretation I am proposing here, Drummond, in writing the machine poem, put into practice at least six lessons drawn from Spender’s essay, namely: 1) the modern poet must represent the tension between the external machinelike landscape and the landscape of the inner world of the creative imagination; 2) he must also represent the machinelike, ugly, and urban world around him in a beautiful and poetic way; 3) he must avoid the misconceptions of excessive utopian visionarism, as well as creeping realism; 4) he must reject the imperative of political engagement, whose principle of action states that poetry has a transformative mission in society; 5) he must free himself from the obsession with free verse as the only form of modern poetry and start using the traditional fixed forms; 6) he must understand machines as poetic symbols of human passions, and not just as exotic objects foreign to human reality. My conclusion is that, after reading Spender’s essay, Drummond changed his aesthetic and philosophical understanding of what defines the essence of modern poetry, both in terms of form and content.

INTRODUCTION There have been several advances in the treatment of hepatitis C virus (HCV) infection which have resulted in major reductions in the morbidity and mortality from liver-associated disease. These are not widely available in the Caribbean, due in part, to lack of knowledge of the epidemiology of infections with HCV. As efforts are made to eliminate HCV from the region, these and other existing barriers such as lack of an established database on HCV must be addressed. This review seeks to identify gaps in the knowledge of HCV in the Caribbean with respect to seroprevalence, genotype distribution and general epidemiologic characteristics. MATERIALS AND METHODS The literature for the period January 1, 2005, to October 2022, was reviewed to gather country specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases. The usage pattern of HCV drugs was determined from data obtained from Pharmacists and Infectious Diseases Specialists across the region. RESULTS The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate prevalence. Notably, data from specific countries were limited. The prevalence of HCV among intravenous drug users (21.9-58.8%); persons living with HIV/AIDS (0.8 to 58.5%); prisoners (32.8-64%) and men who have sex with men (MSM) (0.8-6.9%) was generally higher than in the general population (0.8-2.3%). Genotype 1 (83% was most prevalent followed by genotypes 2 (7.2%) and 3(2.1%), respectively. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (Sofosbuvir/velpatasvir), and Harvoni (Ledipasvir/sofosbuvir). Some of these drugs, are only available in the private sector and are sourced externally whenever needed. CONCLUSION There is a paucity of current data on the seroprevalence of HCV in the Caribbean and well-designed prospective studies are indicated to drive the implementation of treatment and control programs for HCV in the region. Barriers which need to be first overcome include unavailability and high cost of drugs used to treat HCV infections, injecting drug use and limited access to medical care and laboratory testing.

The emission of black carbon (BC) particles, which cause atmospheric warming by affecting radiation budget in the atmosphere, is the result of an incomplete combustion process of organic materials. The recent wildfire event during the summer 2019-2020 in South-Eastern Australia was unprecedented in scale. The wildfires lasted for nearly 3 months over large areas of the two most populated states of New South Wales and Victoria. This study on the emission and dispersion of BC emitted from the biomass burnings of the wildfires using the Weather Research Forecast – Chemistry (WRF-Chem) model is aimed to determine the extent of the BC spatial dispersion and ground concentration distribution and the effect of BC on air quality and radiative transfer at the top of the atmosphere, the atmosphere and on the ground. The predicted aerosol concentration and AOD are compared with the observed data from the New South Wales Department of Planning and Environment (DPE) aethalometer and air quality network and from remote sensing data. The BC concentration as predicted from WRF-Chem model is in general less than the observed data as measured from the aethalometer monitoring network, but the spatial pattern corresponds well, and the correlation is relatively high. The total BC emission into the atmosphere during the event and the effect on radiation budget were also estimated. This study shows that the summer 2019-2020 wildfires affect not only the air quality and health impact on the east coast of Australia but also short-term weather in the region via aerosol interactions with radiation and cloud.

Emerging information on the interactions between the COVID-19 pandemic and global food systems has highlighted how the pandemic is accentuating food crises across Africa. Less clear, however, are how the impacts differ between farming systems. Drawing on 50 key informant interviews with farmers, village leaders and extension officers, in South Africa and Tanzania, we identify the effects of COVID-19 and associated measures to curb the spread of the disease on farming production systems, the coping mechanisms adopted by farmers, and explore their longer-term plans for adaptation. We focus on a diverse range of production systems, from small-scale mixed farming systems in Tanzania, to large-scale corporate farms in South Africa. Our findings highlight how COVID-19 restrictions have interrupted the supply chains of agricultural inputs and commodities, increasing the storage time for produce, decreasing income and purchasing power, and reducing labour availability. Farmers’ responses were heterogeneous, with highly diverse small-scale farming systems and those less engaged with international markets least affected by the associated COVID-19 measures. Large-scale farmers were most able to access capital to buffer short-term impacts, whereas smaller-scale farms shared labour, diversified to subsistence produce and sold assets. However, compounded shocks, such as recent extreme climate events, limited the available coping options, particularly for smaller-scale and emerging farmers. The study highlights the need to understand the characteristics of farm systems to better equip and support farmers, particularly in contexts of uncertainty. We propose that policy actions should focus on (i) providing temporary relief and social support and protection to financially vulnerable stakeholders, (ii) job assurance for farmworkers, and engaging an alternative workforce in farming, (iii) investing in farming infrastructure, such as storage facilities, digital communication tools, and extension services, and iv) supporting diversified agroecological farming systems.

This paper investigates whether currency risk is priced differently in the different sectors (industrial, financial, and basic materials) of equity markets in a sample of developed United States of America (USA) and developing economies (Brazil, India, Poland, and South Africa). The paper makes use of the following techniques: (i) Univariate Autoregressive Fractionally Integrated Moving Average and Exponential General Autoregressive Conditional Heteroskedastic (ARFIMA-EGARCH), (ii) the Markov-Switching method (MS), and (iii) the Canonical Vine Copulas (C-Vine) techniques. Using a sample of daily data made of the foreign exchange rate against the domestic currency and equity market sectors; our findings show that there is an asymmetry effect between equities markets and the foreign exchange rate: there is a heterogeneous, strong, and positive dependence between the two. Higher equities prices are associated with depreciation of local currencies, according to US dollar (USD) exchange rates. In addition, we find that the selected emerging economies are pricing a positive and considerable currency risk. The pricing of currency risk has a varied effect in both regimes representing the states of the economy. In fact, when currency risk pricing has a beneficial impact on certain sectors of the economy, investors predict better returns.

Our objective was to evaluate whether pregnancy is prolonged by use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in preterm birth rate. Rather than considering a dichotomous outcome (preterm vs term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, P &lt;0.01). Newborns of screened subjects had significantly shorter NICU stay but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We concluded that screening with the PreTRM test followed by interventions for screen-positive pregnancies can prolong pregnancy and reduce NICU-LOS.

Global climate change requires urgent solutions. Ambitious tree-planting initiatives, many already underway, aim to sequester enormous quantities of carbon, partly compensating for the anthropogenic CO₂ emissions that are a major cause of rising global temperatures. However, poorly planned and executed tree-planting could actually increase CO₂ emissions and have long-term, deleterious impacts on biodiversity, landscapes and livelihoods. Here, we highlight the main environmental risks of large-scale tree planting and propose ten golden rules, based on some of the most recent ecological research, to implement forest ecosystem restoration that maximizes rates of both carbon sequestration and biodiversity recovery, while simultaneously improving livelihoods. These are: i) Protect existing forest first; ii) Work together (involving all stakeholders); iii) Maximize biodiversity recovery to meet multiple goals; iv) Select appropriate areas; v) Use natural regeneration wherever possible; vi) Select species to maximise biodiversity; vii) Use resilient plant material (with appropriate genetic variability and provenance); viii) Plan ahead for infrastructure, capacity and seed supply; ix) Learn by doing (using an adaptive management approach); and x) Make it pay (ensuring the economic sustainability of the project). We focus on the design of long-term strategies to tackle the climate and biodiversity crises and support livelihood needs. We emphasize the role of local communities and their dependence on benefits from successful reforestation programmes that restore ecosystem functioning and deliver a diverse range of forest products and services. While there is no simple and universal recipe for forest restoration, it is now crucial to build on the public and private interest in this topic to ensure interventions provide effective, long-term carbon sinks and maximise benefits for biodiversity and people.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Dust storms and wildfires occur frequently in southeastern Australia. Their effects on ecology, environment and population exposure have been the focus of many studies recently. Dust storms do not emit ground-sequestered carbon but wildfires emit significant quantities of carbon into the atmosphere. However, both natural events promote phytoplankton growth in water bodies because carbon, and other trace elements such as iron, deposit on the surface water of oceans. Carbon dioxide is reabsorbed by phytoplankton via photosynthesis. The carbon balance cycle due to dust storms and wildfires are not well known. Recent studies on the carbon emission of the 2019-2020 summer wildfires in eastern Australia indicated that this megafire event emitted approximately 715 million tonnes of CO2 (195 Tg C) into the atmosphere from burned forest areas. The projected increase in the frequency of wildfires due to climate change alters what was a carbon neutral process of reabsorbing emitted carbon by the forests, and subsequently cannot be achieved. With the result of net loss of sequestered carbon to the atmosphere, subsequently further promotes a warming climate. This study focusses on the association of dust storms and wildfires in southeastern Australia with phytoplankton growth in the Tasman Sea due to the February 2019 dust storm event and the 2019-2020 Black Summer wildfires. Central Australia and western New South Wales were the sources of the dust storm emission (11 to 16 February 2019) and the Black Summer wildfires occured along the coast of New South Wales and Victoria (from early November 2019 to early Januaray 2020). The results show the similarities and differences in the deposition of particulate matter, phytoplankton growth and carbon reabsorption patterns in the Tasman Sea from these events. Using WRF-Chem model, during the 5 days dust storm event in February 2019, approximately ~1230 tons of total dust were predicted to be deposited in the Tasman Sea while ~132,000 tons of PM10 were deposited in the early stage of the wildfires from 1 to 8 November 2019.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds would advance rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize the unstable organocopper compounds. The bidentate ligands can chelate to the same copper atom via ?2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via ?1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via ?2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure-reactivity relationships.

Most Neotropical Psittacidae have a diploid number of 2n=70, and a dichotomy in chromosome patterns. Long-tailed species have biarmed macrochromosomes, while short - tailed ones have telo/acrocentric macrochromosomes. However, the use of chromosome painting with chicken and white hawk probes has demonstrated that karyotype evolution in Psittacidae includes a high number of inter/intrachromosomal rearrangements. Hence, to determine the phylogeny of Long and Short-Tailed species, and to propose a putative ancestral karyotype for this group, we constructed homology maps of Pyrrhura frontalis (PFR) and Amazona aestiva (AAE) and compared them to other previously analyzed long-tailed species. Chromosomes were analyzed by conventional staining and fluorescent in situ hybridization (FISH) using whole chromosome paints of G. gallus (GGA) and L. albicollis (LAL). Conventional staining showed a karyotype with 2n=70 in both species, with biarmed macrochromosomes in Pyrrhura frontalis and telo/acrocentric chromosomes in Amazona aestiva. Comparison of the results with the putative avian ancestral karyotype (PAK) showed fusions in P. frontalis of PAK1p/PAK4q (PFR1) and PAK6/PAK7 (PFR6) with a paracentric inversion in PFR6. However, in A. aestiva there was only the fusion between PAK6/7 (AAE7) with a paracentric inversion. Hybridizations with LAL probes confirmed these results. The results indicate that PFR retained a more basal karyotype than Anodorhynchus hyacinthinus (AHY), Ara macao (AMA) and Ara chloropterus (ACH), because these three species show the fusion PAK8/PAK9 that is not seen in PFR. Hence, we suggest that the ancestral karyotype of species with biarmed chromosomes have the fusions PAK1p/PAK4 and PAK6/PAK7 and, additionally, a pericentric inversion of PAK6/PAK7, while the fusion PAK8/PAK9 would have appeared in the common ancestor of Anodorhynchus hyacinthinus, Ara macao and Ara chloropterus. However, the species A. aestiva shows a characteristic plesiomorphic trait, since PAK1p/PAK4q and PAK8/9 fusions are absent. Our results base on chromosome rearrangements suggest the classification following the criterium of tail length may no reflect the real phylogenetic history of Neotropical Psittacidae.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

One of the main challenges of cultured meat is reducing the costs of production, often described as scaling. The main components of the cultivation process include: cells, media, scaffolds and bioreactors. This work presents an alternative to current stainless steel or glass bioreactors and uses food-grade plant-based scaffolds. Bioreactors must be sterile and leak-free to maintain a proper environment for cell growth. Thermoplastic films are a popular material for constructing these fluidic systems, but traditional methods of welding these film are expensive and do not allow rapid prototyping resulting in high research and development costs for companies. In this study, a laser welding method was developed to join thermoplastic films in a way that prevents contamination and leaks, affording effective macro-fluidics fabrication. This technique was tested using polyethylene (PET) films and a laser cutter operating with settings calibrated for the material to be welded or cut. The laser welding method was found to produce strong, leak-free seals in PET films with minimal heat-induced damage to the films. The ability to design fluidics, chambers and ports of various size. Using this method afforded the incorporation of plant-based scaffolds from food-grade plants (Rice). The laser welding method developed in this study provides a reliable, contamination-free method for the rapid fabrication of fluidic systems for cell cultivation. This technique has the potential to be compatible with a vast range of cell types and scaffolds and to be widely adopted in tissue engineering for regenerative medicine and food applications such as cultured meat.

Daily exposure of skin to environmental stressors leads to molecular and morphological changes ascribed as premature aging. These stressors include solar radiation, industrial pollution, fossil fuel and carbon emissions, which cause cellular damage that induces an inflammatory response in skin. Several inflammatory components are known to be involved in triggering the senescence-associated secretory phenotype (SASP) which is known to accelerate aging. It is hypothesized that preventing induction of inflammation by environmental stressors can prevent premature aging. Since it is known that nicotinamide (Nam) has anti-inflammatory properties, we tested whether Nam can inhibit environmental stressor-induced inflammation. Exposure of keratinocytes to UVB, urban dust, diesel exhaust, and cigarette smoke extract stimulated production of the inflammatory mediators PGE2, IL-6, and IL-8 and induced gene expression patterns associated with apoptosis, DNA repair, and cell cycle control. In all cases, Nam treatment significantly inhibited these stress-induced responses. Nam also reduced IL-8 levels stimulated by the combination of topically applied particulate matter (PM2.5) and UV exposure in 3D skin equivalents. Under 5% 02 conditions that more closely mimic physiological 02 levels, Nam had a heightened inhibitory effect on UVB-induced PGE2 levels in keratinocytes. In a UV-challenge study, treatment with Nam reduced skin surface IL-1RA/IL-1 inflammatory biomarkers and erythema that were induced by solar simulated radiation. These findings provide a body of evidence that Nam can mitigate in part the skin’s inflammatory response elicited by exposure to environmental stressors. This supports the potential that Nam can inhibit premature aging and help maintain skin’s functionality and appearance.

Alcohol abuse can result in detrimental multisystem effects. Chronic alcohol abuse is known to be associated with pathophysiological changes in multiple organs often resulting in life threatening clinical outcomes e.g. breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, alcohol-induced cardiomyopathy and heart failure as well as central nervous system disorders. In this review article, we will discuss the multisystemic effects of alcohol abuse and explore in greater detail alcohol’s impact on two main systems that result in pathophysiological changes i.e. the cardiovascular and central nervous systems.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

A simple approach to enable water-management agencies employing free data to achieve the goal of using a single set of predictive equations for water-quality retrievals with satisfactory accuracy is proposed. Multiple regression-derived equations based on surface reflectance, band ratios, and environmental factors as predictor variables for concentrations of Total Suspended Solids (TSS), Total Nitrogen (TN), and Total Phosphorus (TP) were derived using a hybrid forward-selection method that considers Variance Inflation Factor (VIF) in the forward-selection process. Landsat TM, ETM+, and OLI/TIRS images were jointly utilized with environmental factors, such as wind speed and water surface temperature, to derive the single set of equations. The coefficients of determination of the best-fitting resultant equations varied from 0.62 to 0.79. Among all chosen predictor variables, ratio of reflectance of visible red (Band 3 for Landsat TM and ETM+, or Band 4 for Landsat OLI/TIRS) to visible blue (Band 1 for Landsat TM and ETM+, or Band 2 for Landsat OLI/TIRS) has a strong influence on the predictive power for TSS retrieval. Environmental factors including wind speed, remote sensing-derived water surface temperature, solar altitude, and time difference (in days) between the image acquisition and water sampling were found important in water-quality parameter estimation.

Abstract: Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We inves-tigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different hepatoma cell lines: HepG2, Huh7 and McA-RH7777 (McA). Cells were treated for 48 hours with fatty acids (0 or 200μM), glucose (5mM or 11mM) and fructose (0mM, 2mM or 8mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (P<0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11mM glucose plus fatty acids (P=0.004, fatty acid x glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (P<0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (P=0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (P<0.001 for fatty acid x insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (P<0.001 insulin x cell type interaction). Hence glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.

The efficiency of producing embryos using in vitro technologies in livestock species rarely exceeds the 30 to 40% threshold, indicating that the proportion of oocytes that fail to develop after in vitro fertilization and culture is considerably large. Considering that the intrinsic quality of the oocyte is one of the main factors affecting blastocyst yield, the precise identification of non-invasive cellular or molecular markers that predict oocyte competence is of major interest to research and practical applications. The aim of this review was to explore the current literature on different non-invasive markers associated with oocyte quality in the bovine model. Apart from some controversial findings, the presence of cycle-related structures in ovaries, a follicle size between 6 and 10 mm, large number of surrounding cumulus cells, slightly expanded investment without dark areas, large oocyte diameter (>120 microns), dark cytoplasm, and the presence of a round and smooth first polar body have been associated to better competence. In addition, the combination of oocyte and zygote selection by BCB test and spindle imaging have the potential to further optimize the identification of oocytes with better developmental competence for in vitro-derived technologies in livestock species.

Forty percent of patients with acute coronary occlusion myocardial infarction (OMI) do not present with STEMI criteria, which delays their treatment and increases morbidity and mor-tality. The need to identify these patients promptly is crucial, and this sets the stage for the pro-posed reclassification. Many of these patients can be identified by other ECG and clinical fea-tures. Background/Objectives: We sought to evaluate STEMI/NSTEMI cases that result in OMI and the consequences of delayed revascularization immediately among NSTEMI patients who have ACO (NSTEMI-OMI). Methods: The study is a retrospective analysis conducted on 334 pa-tients who underwent coronary angiography for acute coronary syndrome at UHC ‘‘Mother Te-resa,’’ Tirana, Albania, during January-May 2023. OMI was defined as an acute culprit lesion with TIMI 0-2 flow, or TIMI 3 flow with highly elevated troponin (cTnI>10.0 ng/mL, hs-cTnI>5000 ng/L). Ejection fraction (EF), total ischemia time, hospital day stay and complications were com-pared between groups. Results: There were 334 patients included of whom NSTEMI-OMI were 98 patients (29.3%) of patients with ACS. 96 patients (40%) of OMI patients did not fulfill the STEMI criteria. Only 11 patients (11%) of STEMI(-)OMI had PCI performed within the first 12 hours vs 76 patients (77%) of STEMI(+)OMI, p<0.001. There was no difference in the percent of patients requiring PCI between the STEMI(+)OMI 98 patients (93%) and STEMI(-)OMI 87 patients (89%) (p<0.001). The overall in-hospital mortality was 19 patients (5.7 %), with subgroup mortality of 14 patients (4.2%) STEMI(+)OMI, two patients (0.6%) STEMI(+) NOMI, three patients (0.9%) STEMI(-)OMI, 0% STEMI(-)NOMI, (p=0.013). Patients with mechanical complications were: 67 patients (46.8%) STEMI(+)OMI and 45 patients (46.4%) STEMI(-)OMI. 26 patients (18.5%) STEMI(+)OMI and 13 patients (13.1%) STEMI(-)OMI developed electrical complications. Conclusions STEMI(-)OMI patients had significant delays in catheterization, yet had angiographic findings, rate of PCI, and complications similar to STEMI(+)OMI. These data add further support to refocusing the paradigm of acute MI to improve recognition and rapid reperfusion of all OMIs, rather than only those with STEMI criteria.

Resistance training increases myofiber hypertrophy, but the morphological adaptations that occur within myofibers remain largely unresolved. Fifteen males with minimal training experience (24±4 years, 17.9±1.4 kg/m2 lean body mass index) performed 10 weeks of conventional, full-body resistance training (2x weekly). Body composition, the radiological density of the vastus lateralis muscle using peripheral quantitative computed tomography (pQCT), and vastus lateralis muscle biopsies were obtained one week prior to and 72 hours following the last training bout. Fiber typing and the quantification of myofibril and mitochondrial areas per fiber were performed using histology/immunohistochemistry (IHC) techniques. Relative myosin heavy chain and actin protein abundances per wet muscle weight as well as citrate synthase (CS) activity assays were also obtained on tissue lysates. Training increased whole-body lean mass, mid-thigh muscle cross-sectional area, various strength metrics, and mean and type II fiber cross sectional areas (fCSA) (p<0.05). Myofibril areas in type I or II fibers were not altered with training, suggesting a proportional expansion with fCSA increases. Relative myosin heavy chain and actin protein abundances also did not change with training. IHC indicated training increased mitochondrial areas in both fiber types (p=0.018). However, CS activity levels remained unaltered with training. Interestingly, although pQCT-derived muscle density increased with training (p=0.036), suggestive of myofibril packing, a positive association existed between training-induced changes in this metric and changes in type I+II myofibril areas (r=0.600, p=0.018). Shorter-term resistance training seemingly involves a proportional expansion of myofibrils and an accelerated expansion of mitochondria in type I and II fibers. Additionally, histological and biochemical techniques should be viewed independently from one another given the lack of agreement between the variables assessed herein. Finally, the pQCT may be a viable tool to non-invasively track morphological changes in muscle tissue.

Synechococcus sp. PCC 11901 reportedly demonstrates the highest, sustained growth of any known cyanobacterium under optimized conditions. Due to its recent discovery our knowledge of its biology, including the factors underlying sustained, fast growth, is limited. Furthermore, tools specific for genetic manipulation of PCC 11901 are not established. Here, we demonstrate that PCC 11901 shows faster growth than other model cyanobacteria, including the fast-growing species Synechococcus elongatus UTEX 2973, under optimal growth conditions for UTEX 2973. Comparative genomics between PCC 11901 and Synechocystis sp. PCC 6803 reveal conservation of most metabolic pathways but PCC 11901 has a simplified electron transport chain and reduced light-harvesting complex. This may underlie its superior light utilization, reduced photoinhibition and higher photosynthetic and respiratory rates. To aid biotechnology applications we developed a vitamin B12 auxotrophic mutant but were unable to generate unmarked knockouts using two negative selectable markers, suggesting that recombinase- or CRISPR-based approaches may be required for repeated genetic manipulation. Overall, this study establishes PCC 11901 as one of the most promising species currently available for cyanobacterial biotechnology and provides a useful set of bioinformatics tools and strains for advancing this field, in addition to insights into the factors underlying its fast growth phenotype.

Eco-agricultural technology is crucial to alleviating agricultural resource scarcity and environ-mental pressures. However, financial constraint affects its successful promotion. Digital finance has a significant impact on farmers, but existing research lacks an exploration of the impact of digital finance on farmers' adoption of eco-agricultural technology. This study focuses on Rice–Crayfish Co-cultivation Technology as an example. It utilizes survey data from 1,063 households in China. An Endogenous Switching Probit model is employed to solve self-selection bias. The results reveal several key findings. First, the average treatment effect on the treated is 51.5%. This indicates that if farmers who use digital finance were to stop using it, the probability of adopting rice–crayfish co-cultivation technology would decrease by 51.5%. Therefore, digital finance is beneficial for farmers in adopting this technology. Second, heterogeneity analysis reveals that digital finance has a greater promoting effect on older farmers, those with lower education levels, and higher proportions of agricultural income. This suggests a greater reliance on digital financial services among vulnerable groups. Third, digital finance promotes farmers' adoption of rice–crayfish co-cultivation technology by alleviating financial constraints, expanding information channels, and increasing social capital accumulation. Overall, the findings offer valuable insights for for-mulating supportive policies.

The grain-to-grain stress vertically in sediments is given by the overburden less the pore fluid pressure, σ, divided by the fraction of the horizontal area which is the supporting matrix , (1 − φ), where φ is the porosity. It is proposed that the fractional reduction of this ratio, Λ, with time is given by the product of φ 4m/3 , (1 − φ) 4n/3 , and one or more Arrhenius functions A exp(−E/RT ) with m and n close to 1. This proposal is tested for shale sections in six wells from around the world for which porosity-depth data are available. Good agreement is obtained above 30-40 C and porosities less than 0.5. Single activation energies for each well are obtained in the range 15-33 kJ/mole, close to pressure solution of quartz, 24 kJ/mol. Values of m and n are in the range 1 to 0.8, indicating nearly fractal pore-matrix spaces and water-wet interfaces. Results are independent of over- or under-pressure of pore water. This model explains shale compaction quantitatively. Given porosity-depth data and accurate activation energy, E, one can infer paleo-geothermal-gradient and from that organic maturity, thus avoiding unnecessary drilling.

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We here evaluated available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide; dulaglutide; exenatide; liraglutide; lixisenatide; tirzepatide) and the phentermine-topiramate combination. To that aim, we analysed the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AER) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AER involving the selected molecules were submitted to FAERS; most involved dulaglutide (n=11,858; 37.6%) and semaglutide (n=8,249; 26.1%). In comparing semaglutide vs the remaining antidiabetics, the AER ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’ and ‘intentional product use issue’ respective PRR values were 4.05, 4.05, 3.60 and 1.80 (all<0.01). The same comparisons of semaglutide vs the phentermine-topiramate combination were not associated with any significant differences. To our best, this is the first study documenting the misusing/abusing potential of semaglutide in comparison with other novel antidiabetics and the phentermine-topiramate combination. Current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

The Rev. Martin Luther King Jr. and Nelson Mandela were two of the world's most iconic civil (political) (human) rights advocates and leaders of all time. Both advocated for, and to varying degrees, applied elements of peaceful protests to the achievement of their goals. Both spent time in jail, often concurrently, but eventually forced their respective countries to extend the same rights that white populations had denied Africans and African Americans. For the US, civil rights, voting rights, right to education, housing and housing loans suggested that equality had been achieved, capped in South Africa by the election of Nelson Mandela as the first majority-rule president, and in the US, by Barack Obama’s election to the presidency. Yet the historical over-policing, police mistreatment and more generally, the judicial system’s inordinate ‘targeting’ of African Americans, with egregious cases running from Emmett Till to Rodney King to Walter Scott to Breonna Taylor to George Floyd to Rayshard Brooks and thousands of others shows the danger of such magical thinking. The now-persistent global wave pursuing human rights, civil rights and the right to be treated equally, primarily driven by the loosely-organized Black Lives Matter (BLM) movement, has become the leading voice in pursuit of equality. Riots such as those in LA, protests in Ferguson and everywhere in summer 2020 has ushered new civil rights campaign. In the US and elsewhere, it has morphed to include historical issues such as monuments to colonialism, the US civil war, slavery and slave owners and traders, institutions, companies and people whose wealth and existence has links to slavery. Instructively, the protests persisted even as COVID-19, the hundred-year plague, continues to ravage the world. Lost in the moment is the absence of central leadership and leaders such as MLK or Mandela. Their charisma and effectiveness has been lacking for 50 years. This paper evaluates whether this has led to inconsistent civil and human rights pursuit for equality, or whether perchance, Mandela and MLK were extraordinary, once-in-a-lifetime transformative leaders uniquely selected by history for their time.

1. Background: The global COVID-19 lockdowns are unique psychological factors, requiring adjustment and coping. This illustrative, South African case study investigated the influence the COVID-19 lockdown context would have on meditation and physical activity. As these were lifestyle patterns the null hypothesis was of no change. 2. Method: The methodology consisted of quantitative and qualitative phases. The quantitative phase was an empirical, case study review of data from the author’s HeartMath and Fitbit electronic devices, as from 9 November 2019 to 31 July 2021. This consisted of coherence and achievement data from the HeartMath Inner Balance application (app), as well as distance and activity data from the Fitbit app. The qualitative phase consisted of the selection and illustration of meditation sessions documented over lockdown. 3. Results: The highly significant increases in physical activity and meditation coherence and achievement collectively indicated significant health promotion over the COVID-19 Lockdown period. Subtle energetic, experiential descriptions of meditation apprehensions resonated and supported these quantitative findings. 4. Conclusions: COVID-19 lockdown has meant transformation, humility, and reordering of priorities. The meditation descriptions amplified information from the HeartMath and Fitbit electronic devices, together co-creating conscious, embodied, relationship science for discussion, instruction, and further research.

South Africa is a water stressed country experiencing mass urbanisation especially towards coastal cities. The country is already enduring the impacts of global warming and climate change with risk of water scarcity in many areas. The risk was evident with Cape Town near encounter with ‘Day Zero’ i.e., the day when water supplies would have been switched off and residents required to queue for daily water rations. The drought exposed the inadequa-cies of the existing water supply system. Paradoxically, in the same drought period, vast amounts of unutilized stormwater that could have augmented water supply run unabated into the ocean through rivers around the city. The study determined that the problem was not necessarily water shortage but lack of adequate water storage. This study investigated the suitability of coastal reservoirs for stormwater harvesting on the over 3000 km South African coastline. The objective was to identify suitable locations for coastal reservoirs. The study un-dertook a systematic process of selecting several candidate locations and eliminating unsuita-ble sites based on international best practice i.e., coastal topography, climate, hydrology, fluvi-al environment, catchment size and river water quality. Nine candidate sites were identified and ranked based on suitability and associated benefits. The identified locations in order of ranking include Knysna River, Berg River, Buffalo River, Kowie River, Thukela River, Orange River, Port of Richards Bay, Port of Durban, and Lourens River. The Knysna site, with a mean annual precipitation of 600 - 800 mm/annum and mean annual runoff of 100 - 500 Mm3/annum, was determined to be the most optimal location.

Kluyveromyces marxianus (K. marxianus) is a newly emerging industrially relevant yeast. It is known to possess a highly efficient Non-Homologous End Joining (NHEJ) pathway that promotes random integration of non-homologous DNA fragments into its genome. The nature of the integration events was traditionally analyzed by Southern blot hybridization. However, the precise DNA sequence at the insertion sites were not fully explored. We transformed a PCR product of the Saccharomyces cerevisiae URA3 gene (ScURA3) into an uracil auxotroph K. marxianus wildtype strain and picked 24 stable Ura+ transformants for sequencing analysis. We took advantage of rapid advances in DNA sequencing technologies and developed a method using a combination of Illumina MiSeq and Oxford Nanopore sequencing. This approach enables us to uncover the Gross Chromosomal Rearrangements (GCRs) that are associated with the ScURA3 random integration. Moreover, it will shine a light on understanding DNA repair mechanisms in Eukaryotes, which could potentially provide insights for cancer research.

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases but requires incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in similar PLGA 50:50 microparticles (~1 μm diameter) surface modified with CPDI-02 (CPDI-02-MP) increases long-term OVA-specific mucosal and systemic antibodies. We found that, compared to MP surface modified with inactive, scrambled scCPDI-02 (scCPDI-02-MP), intranasal administration of CPDI-02-MP in 50 μL sterile PBS greatly increased titers of short-term (14 days post-immunization) and long-term (90 days post-immunization) antibodies against encapsulated LPS-free OVA in nasal lavage fluids, bronchoalveolar lavage fluids, and sera of young, naïve female C57BL/6 mice. Thus, surface modification of biodegradable microparticles with CPDI-02 is likely to increase long-term mucosal and systemic antibodies against encapsulated protein antigen after respiratory and possibly other routes of mucosal immunization.

Objective: Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated clearance, another PF of PK origin, either alone or in combination with concentrations. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.

In the cold deserts of the McMurdo Dry Valleys (MDV) the suitability of soil for microbial life is determined by both contemporary processes and legacy effects. Climatic changes and accompanying glacial activity have caused local extinctions and geochemical changes to soil ecosystems over several million years, while high elevation refugia may have escaped these disturbances and existed under relatively stable conditions. This study describes the impact of historical glacial and lacustrine disturbance events on microbial communities across the MDV. Soil bacterial communities from 17 sites representing either putative refugia or sites disturbed during the Last Glacial Maximum (LGM) (22-17kya) were characterized using 16S metabarcoding. Regardless of geographic distance, several putative refugia sites at elevations above 600 meter displayed highly similar microbial communities. At a regional scale, community composition was found to be influenced by elevation and geographic proximity more so than soil geochemical properties. These results suggest that despite the extreme conditions, diverse microbial communities exist in these putative refugia that have presumably remained undisturbed at least through the last glacial maximum. We suggest that similarities in microbial communities can be interpreted as evidence for historical climate legacies on an ecosystem-wide scale.

Empirical equations representing, interpolating and smoothing groups of measurement results by regression methods are in widespread use in metrology and other fields of science and engineering. Standard equations for the propagation of measurement uncertainties to values computed from such equations are available but suffer from a lack of general acceptance and are only infrequently applied in practice. One reason for the slow uptake is the lack of clear methods to account for systematic error. In this paper, uncertainty propagation equations in terms of covariance matrices are generalized to allow for systematic errors in least-squares regression, and effects of the resulting uncertainties are investigated analytically. A stochastic ensemble model of systematic error is proposed for the computation of the non-diagonal elements of the weight matrix of the Generalized Least-Squares method (GLS) from the measurement uncertainty. A GLS projector formalism is described which separates the effects of measurement scatter on values calculated by the equation from those on the related “residuals”, i.e., the residual errors in the fitted data. The same projectors act similarly on the associated uncertainties and covariance matrices and permit the effects of systematic errors on the simulation covariance to be quantified. It is demonstrated that, in order to include systematic errors in the uncertainty estimates of GLS, covariance matrices may be substituted by novel, specifically defined dispersion matrices that are not specified yet by the GUM[1]. Systematic measurement errors may be estimated from various sources; a particularly easy way suggested here involves analyzing the structure in the regression residuals. It is demonstrated that GLS projectors exhibit inherent features of “error blindness” also with respect to systematic errors. [1] GUM: Guide to the Expression of Uncertainty in Measurement, http://www.bipm.org/en/publications/guides

Based upon a radically new approach, this paper describes a 2-box absolute flow model that calculates the CO₂ transfer between the atmosphere and a terrestrial / ocean mixing reservoir. Given the inputs of anthropogenic fossil fuel emissions (CO2ff), atmospheric CO₂ mixing-ratio and nuclear weapons bomb yields, the model calculates atmospheric d¹³C and Δ¹⁴C time-series, with the level of agreement for d¹³C being to within ± 0.05 ‰, for Δ¹⁴C to within ± 3‰, spanning 200 years. The model contains only seven internal parameters which are varied to optimize the fit. Yet according to conventional wisdom, this model should not work. It is commonly held that the ¹³C and ¹⁴C isotopic forms of carbon bypass seawater carbonate chemistry, resulting in very different absorption properties (Revelle factor) as compared to ¹²C. This study rejects this assumption, and uses the same residence time and reservoir mixing properties for all isotopes. The paper includes an analysis justifying why the isotopic bypass of the Revelle factor is not significant. The study describes the use of the model to track CO2ff takeup using two separate measures, a) the amount of molecular CO2ff remaining in the atmosphere and b) the amount of atmospheric growth attributable to CO2ff, thereby resolving discrepancies in published values.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Historically, the evaluation and assessment of the clinical response to treatment for canine back pain is subjective and relies on owner and clinician assessment of pain. This study evaluated the use of sequential infrared thermal images as a measure of the response of canine patients with back pain to a prescribed series of photobiomodulation therapy (PBMT) treatments. Qualifying participants had histories of pain and dysfunction associated with spinal osteoarthritis or intervertebral disk disease, or of non-specific uni- or bilateral back pain along the paravertebral epaxial muscles. Each patient was initially thermally imaged prior to PBMT treatment and then received multiple PBMT treatments delivered to the appropriate spinal area on days 1, 2, 3, and 4. Participants were reimaged on day 7. Thermal images provided an objective measure of superficial temperature changes over the area of PBMT treatment of each patient after the PBMT regimen. The temperature correlated with statistically significant changes in Colorado State University Canine Chronic Pain Scale scoring (CPS) and owner assessment using the Canine Brief Pain Inventory (CBPI), which includes a Pain Severity Score (PSS) and Pain Interference Score (PIS). The correlation of objective thermal imaging data with more subjective outcome measures suggests thermal imaging may be a valuable additional tool in monitoring therapy outcome.

Although total nett CO₂ atmospheric flow can be estimated with reasonable accuracy, the contributing gross fluxes between the atmosphere and the earth's surface are poorly understood. This paper presents a method, driven by the objective of simplicity, by which the global outflow and inflow of CO₂ between atmosphere and a globally equivalent "mixing reservoir" can be estimated, using the isotopes ¹⁴C and ¹³C as tracers. It has been asserted that the isotopic carbon in CO₂ cannot be directly used as a tracer in flow studies because it is not subject to the Revelle factor. Evidence is provided showing that this view is mistaken. The model contains 7 key parameters which are used to create synthetic records of Δ¹⁴C and d¹³C spanning 200 years or more, including during the period of atmospheric weapons testing and its decay known as the "bomb pulse". By optimising the fit between these computed values and the historical records of d¹³C and Δ¹⁴C, all seven key parameters are determined. The effective "mixing reservoir" is thereby determined to have a size around six times that of the atmosphere, with global outflux rising from 39.7 GTC yr-1 in 1750 to 58.9 GTC/yr in 2020, this figure probably not including annually cycled carbon.

Floods and droughts are driven, in part, by spatial patterns of extreme rainfall. Heat waves are driven by spatial patterns of extreme temperature. It is therefore of interest to design statistical methodologies that allow the identification of likely patterns of extreme rain or temperature from observed historical data. The standard work-horse for identifying patterns of climate variability in historical data is Principal Component Analysis (PCA) and its variants. But PCA optimizes for variance not spatial extremes, and so there is no particular reason why the first PCA spatial pattern should identify, or even approximate, the types of patterns that may drive these phenomena, even if the linear assumptions underlying PCA are correct. We present an alternative pattern identification algorithm that makes the same linear assumptions as PCA, but which can be used to explicitly optimize for spatial extremes. We call the method Directional Component Analysis (DCA), since it involves introducing a preferred direction, or metric, such as `sum of all points in the spatial field'. We compare the first PCA and DCA spatial patterns for US rainfall anomalies on a 6 month timescale, using the sum metric for the definition of DCA in order to focus on total rainfall anomaly over the domain, and find that they are somewhat different. The definitions of PCA and DCA result in the first PCA spatial pattern having the larger explained variance of the two patterns, while the first DCA spatial pattern, when scaled appropriately, has a higher likelihood and greater total rainfall anomaly, and indeed is the pattern with the highest total rainfall anomaly for any given likelihood. In combination these two patterns yield more insight into rainfall variability and extremes than either pattern on its own.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Tuberculosis (TB) remains a global healthcare crisis with an estimated 10 million new cases and 1.4 million deaths per year TB is caused by infection with the major human pathogen Mycobacte-rium tuberculosis, which is difficult to rapidly diagnose and treat. There is an urgent need for new methods of diagnosis, sufficient in vitro models which capably mimic all physiological condi-tions of the infection, and high-throughput drug screening platforms. Microfluidic-based tech-niques provide single-cell analysis which reduces experimental time, the cost of reagents, and have been extremely useful for gaining insight into monitoring microorganisms. This review out-lines the field of microfluidics and discusses the use of this novel technique so far in M. tuberculo-sis diagnostics, research methods, and drug discovery platforms. The practices of microfluidics have promising future applications for diagnosing and treating TB.

This paper presents a new implementation of a 2-box absolute flow model, enabling the calculation of CO₂ transfer between the atmosphere and a mixing reservoir representing the combined effect of the terrestrial and ocean regions. The model uses published values of anthropogenic CO₂ fossil fuel emissions (CO2ff), atmospheric CO₂ mixing ratio and nuclear weapons bomb yields, to compute atmospheric d¹³C and Δ¹⁴C time-series. The level of agreement between the calculated values and the accepted values for d¹³C is within ± 0.05 ‰, and for Δ¹⁴C is within ± 3‰, spanning 200 years. The model contains only seven internal parameters; these are varied to optimize the fit, leading to reasonable parameter values, indicating the validity of the method. In addition, the model shows how a rising CO₂ exchange influx fluctuating with surface temperature is compatible with a nett atmospheric CO₂ sink. The study demonstrates that a single CO₂ residence time applies to both the ¹⁴C bomb pulse and the anthropogenic flux, contrary to the conventional view that "bomb radiocarbon and anthropogenic CO₂ do not behave identically." [Joos 1994 Nature 370, 181–182]. It is shown that the difference in behaviour, claimed to be due to seawater chemistry, is not significant in practice since fluctuating bulk carbon dominates fluctuating isotopic ratio. A new analysis of the airborne fraction indicates that the assumption of a time-dependent exchange influx results in a similar residence time for bulk CO₂ as for ¹⁴C in the nuclear bomb pulse, reinforcing the view that the ¹²C, ¹³C and ¹⁴C carbon isotopic forms of CO₂ behave similarly in the carbon cycle.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

Ionizing radiation exposure is known to induce molecular and cellular injury, inflicting a cascade of potentially catastrophic events leading to tissue and organ damage. Metabolomic analysis allows for the identification and quantification of small molecules downstream of genomic changes induced by radiation exposure. We aimed to characterize metabolomic changes that underscore the prefinal stage of lethally irradiated rhesus nonhuman primates (NHPs). Peripheral blood was drawn at baseline, post-exposure as well as at the preterminal stage of NHPs (immediately prior to death in moribund NHPs), which did not survive exposure with 7.2 Gy total-body radiation (LD70/60). Herein, we analyzed global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in plasma samples of NHPs collected at various timepoints in relation to irradiation. The overall goal was to identify metabolic shifts present immediately prior to death. Our findings, for the first time, show that radiation induced significant time dependent metabolic perturbations when compared to pre-irradiation samples, particularly in the glycerophospholipid metabolism and steroid hormone biosynthesis and metabolism pathways. These findings provide valuable insights for identifying biomarkers for lethality, which may be helpful for triage during a mass casualty scenario.

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide; dulaglutide; exenatide; liraglutide; lixisenatide; tirzepatide) and the phentermine-topiramate combination. To that aim, we analysed the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AER) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AER involving the selected molecules were submitted to FAERS; most involved dulaglutide (n=11,858; 37.6%) and semaglutide (n=8,249; 26.1%). In comparing semaglutide vs the remaining nolecules, the AER ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’ and ‘intentional product use issue’ respective PRR values were 4.05, 4.05, 3.60 and 1.80 (all<0.01). The same comparisons of semaglutide vs the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misusing/abusing potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. Current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Quantum-dot cellular automata (QCA) is an emerging transistor-less field-coupled nanocomputing (FCN) approach to ultra-scale ‘nanochip’ integration. In QCA, to represent digital circuitry, electrostatic repulsion between electrons and the mechanism of electron tunnelling in quantum dots are used. QCA technology can surpass conventional complementary metal-oxide semiconductor (CMOS) technology in terms of clock speed, reduced occupied chip area, and energy efficiency. To develop QCA circuits, irreversible majority gates are typically used as the primary components. Recently, some studies have introduced reversible design techniques, using reversible majority gates as the main building block, to develop ultra-energy efficient QCA circuits. However, this approach resulted in time delays, an increase in the number of QCA cells used, and an increase in the chip area occupied. This work introduces a novel hybrid design strategy employing QCA irreversible, reversible, and partially reversible gates to establish an optimal balance between power consumption, delay time, and occupied area. The hybrid technique allows the designer to have more control over the circuit characteristics to meet different system needs. A combination of reversible, irreversible, and innovative partially reversible majority gates is used in the proposed hybrid design method. We have evaluated the hybrid design method by examining the half-adder circuit as a case study. We have developed four hybrid QCA half-adder circuits, each of which simultaneously incorporates various types of majority gates. The QCADesigner-E 2.2 simulation tool was used to simulate the performance and energy efficiency of the half-adders. This tool provides numerical results for the circuit input/output response and heat dissipation at the physical level, within a microscopic quantum mechanical model.

Neural stem cell (NSC) based therapies are at the forefront of regenerative medicine strategies to combat illness and injury of the central nervous system (CNS). In addition to their ability to produce new cells, NSCs secrete a variety of products, known as the NSC secretome, that have been shown to ameliorate CNS disease pathology and promote recovery. As pre-clinical and clinical research to harness the NSC secretome for therapeutic purposes advances, a more thorough understanding of the endogenous NSC secretome can provide useful insight into the functional capabilities of NSCs. In this review, we focus on research investigating the autocrine and paracrine functions of the endogenous NSC secretome across life. We also compare the NSC secretome across species, finding signs of conserved parallels between rodent, human and zebrafish NSC secretomes. Throughout development and adulthood, we find evidence that the NSC secretome is a critical component of how endogenous NSCs regulate themselves and their niche. We also find gaps in current literature, most notably in the clinically relevant domain of endogenous NSC paracrine function in the injured CNS. Future investigations to further define the endogenous NSC secretome and its role in CNS tissue regulation are necessary to bolster our understanding of NSC-niche interactions and to aid in the generation of safe and effective NSC-based therapies.

Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other important viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely studied for virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models to characterize the drivers of syncytium formation and its implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.