Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

During the development of new medicines mutually exclusive specificity appears to be required but hitherto is most often included at the late clinical trial stage. Here, I describe the use of Hedgehog signalling in Drosophila as a model to represent a mutually exclusive relationship within the context and report the identification of CG43658, a putative Rho guanine nucleotide exchange factor and orthologue of the Charcot-Marie-Tooth disease associated gene ARHGEF10. Furthermore, a Computer that is able to consider the whole and describe the sum of everything in it absolutely in unambiguous terms is a useful tool. Here I describe such a computer with a suggestion for an application to examine any component in the context where a medicine is sought. Taken, together I would like to propose this method as a fundamental necessity and improvement upon current existing methods related not only to Hedgehog signalling but plausibly to life science research and the search for medicines in general.

This paper explores the tuning and results of two-part models on rich datasets provided through the Casualty Actuarial Society (CAS). These data sets include BI (bodily injury), PD (property damage) and COLL (collision) coverage, each documenting policy characteristics and claims across a four year period. The datasets are explored, including summaries of all variables, then the methods for modeling are set forth. Models are tuned and the tuning results are displayed, after which we train the final models and seek to explain select predictions. All of the code will be made available on GitHub. Data was provided by a private insurance carrier to the CAS after anonymizing the data set. This data is available to actuarial researchers for well-defined research projects that have universal benefit to the insurance industry and the public. Our hope is that the methods demonstrated here can be a good foundation for future ratemaking models to be developed and tested more efficiently.

Complex modeling has received significant attention in recent years and is increasingly used to explain the statistical phenomenon with increasing and decreasing fluctuations such as the similarity or difference of spike protein charge patterns of coronaviruses. Different from the existing covariance or correlation coefficient methods in traditional integer dimension construction, this study proposes a simplified novel fractional dimension derivation with the exact Excel tool algorithm. It involves the fractional center moment extension to covariance, which ends up a complex covariance coefficient that is better than the Pearson correlation coefficient, in the sense that the nonlinearity relationship can be further depicted. The spike protein sequences of coronaviruses were obtained from the GenBank and GISAID database, including the coronaviruses from pangolin, bat, canine, swine (three variants), feline, tiger, SARS-CoV-1, MERS, and SARS-CoV-2 (including the strains of Wuhan, Beijing, New York, German, and UK variant B.1.1.7) were used as the representative examples in this study. By examining the values above and below the average/mean based on the positive and negative charge patterns of the amino acid residues of the spike proteins from coronaviruses, the proposed algorithm provides deep insights into the nonlinear evolving trends of spike proteins for understanding the viral evolution and identifying the protein characteristics associated with viral fatality. The calculation results demonstrate that the complex covariance coefficient analyzed by this algorithm is capable of distinguishing the subtle nonlinear differences in the spike protein charge patterns with reference to Wuhan strain SARS-CoV-2 for which the Pearson correlation coefficient may overlook. Our analysis reveals the unique convergent (positive correlative) to divergent (negative correlative) domain center positions of each virus. The convergent or conserved region may be critical to the viral stability or viability; while the divergent region is highly variable between coronaviruses suggesting high frequency of mutations in this region. The analyses show that the conserved center region of SARS-CoV-1 spike protein is located at amino acid residues 900, but shifted to the amino acid residues 700 in MERS spike protein, and then to amino acid residues 600 in SARS-COV-2 spike protein, indicating the evolvement of the coronaviruses. Interestingly, the conserved center region of the spike protein in SARS-COV-2 variant B.1.1.7 shifted back to amino acid residues 700, suggesting this variant is more virulent than the original SARS-COV-2 strain. Another important characteristic our study reveals is that the distance between the divergent mean and the maximal divergent point in each of the viruses (MERS>SARS-CoV-1>SARS-CoV-2) is proportional to viral fatality rate. This algorithm may help to understand and analyze the evolving trends and critical characteristics of SARS-COV-2 variants, other coronaviral proteins and viruses.

Objective: Our goal is to develop an online questionnaire to survey the prevalence of suicidal behavior. Methods: We developed a questionnaire with 51 variables and proceeded with validations. Validations were performed using face validity, content validity, and construct validity. Reliability was performed by test-rest. Results: The face validity was 1.0 and the content validity was 0.91. The exploratory factor analysis got KMO = 0.86 and extracted one principal factor. The confirmatory factor analysis demonstrates RMSEA= 0.000 and CFI=1.000. The test-retest had an intraclass correlated coefficient of 0.98. Conclusion: The adequate development questionnaire was validated, and we have an instrument to survey suicide behaviors in the pandemic time.

Marginalised families faced significant challenges during the COVID-19 pandemic. This study explores inequalities in Japanese mothers’ and children’s health and wellbeing and family economic stability before and during the pandemic. Data sources were: nationwide surveys in 2019 and 2021 of families with children using medical institutions across Japan; infant mortality and adolescent suicide rates between 2018 and 2021 from publicly available sources. Outcomes by poor and non-poor families were compared for 2019 and 2021 using simple descriptive statistics. Poor mothers' part-time working increased from 41% to 61% and regular employment was reduced by two-thirds. Well-being of poor mothers worsened from 39% to 55%. Employment opportunities and wellbeing did not change for non-poor mothers. School subsidies among poor families increased from 23% to 55%. The infant mortality rate (IMR) among unemployed families increased significantly from 12.9/1,000 to 18.2/1,000 between 2018 and 2021 compared with a decreasing overall IMR from 1.9/1000 to 1.7/1000. Suicide rates in 10-19 year olds increased over the same period although no socio-economic indicators were available. Inequalities in mothers’ and children’s health and well-being indicators and family economics increased between 2019 to 2021 in Japan. This study cannot attribute cause but suggests a possible role of the pandemic.

Repeated cocaine produces an enhanced locomotor response (sensitization) paralleled by biological adaptations in the brain. Previous studies demonstrated region-specific responsiv-ity of adenosine monophosphate-activated protein kinase (AMPK) to repeated cocaine. AMPK maintains cellular energy homeostasis at the organismal and cellular level. Here we first quanti-fied changes in phosphorylated (active) and total AMPK in the cytosol and synaptosome of the medial prefrontal cortex, nucleus accumbens, and dorsal striatum following acute or sensitizing cocaine injections. Rats were given cocaine (15 mg/kg, IP) or saline for six days with a challenge injection on day seven resulting in four groups: saline-saline, saline-cocaine, cocaine-saline, and cocaine-cocaine. Brain region and cellular compartment selective changes in AMPK and pAMPK were found with some differences associated with acute withdrawal versus ongoing cocaine treatment. Other rats were pretreated with the indirect AMPK activator metformin. Metformin potentiated the locomotor activating effects of acute cocaine but blocked the development of sensi-tization. Sex differences largely obscured protein level treatment group effects, although pAMPK in the NAc shell cytosol was surprisingly reduced by metformin in rats receiving repeated co-caine. These data inform our understanding of AMPK activation dynamics in subcellular com-partments and provide additional support for repurposing metformin for cocaine use disorder.

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th Feb and 15th Feb. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a `delayed positive' test during isolation after initially testing negative, at least 7 days after last possible contact.

JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining disease pre-antiretroviral therapy that has “reemerged” as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we will discuss evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model is providing insights into the pathogenesis of JCPyV CNS disease.

Additive manufacturing (AM) has revolutionized the field of biopolymers by providing a range of opportunities to create complex and intricate structures. Here we provide an overview of developments in biopolymer AM, first in the context of how natural systems have impacted the synthetic processes of AM, and secondly in the context of how synthetically derived structures can be used for biomedical applications. In particular, we explore the range of biopolymers developed for AM, AM techniques for biopolymers, and potential biocompatible medical applications with a focus on four categories of tissue in the human body: skin, bone, heart, and nerve. Despite the current challenges of the technology, exciting results in tissue regeneration, synthetic replacements for natural grafts, and complex dynamic organoids have already come to pass - with many more possible in the future.

Manual visual inspections typically conducted after an earthquake are high-risk, subjective, and time-consuming. Delays from inspections often exacerbate the social and economic impact of the disaster on affected communities. Rapid and autonomous inspection using images acquired from unmanned aerial vehicles offer the potential to reduce such delays. Indeed, a vast amount of re-search has been conducted toward developing automated vision-based methods to assess the health of infrastructure at the component and structure level. Most proposed methods typically rely on images of the damaged structure, but seldom consider how the images were acquired. To achieve autonomous inspections, methods must be evaluated in a comprehensive end-to-end manner, incorporating both data acquisition and data processing. In this paper, we leverage recent advances in computer generated imagery (CGI) to construct a 3D synthetic environment for simulation of post-earthquake inspections that allows for comprehensive evaluation and valida-tion of autonomous inspection strategies. A critical issue is how to simulate and subsequently render the damage in the structure after an earthquake. To this end, a high-fidelity nonlinear finite element model is incorporated in the synthetic environment to provide a representation of earthquake-induced damage; this finite element model, combined with photo-realistic rendering of the damage, is termed herein a physics-based graphics models (PBGM). The 3D synthetic en-vironment with PBGMs provide a comprehensive end-to-end approach for development and validation of autonomous post-earthquake strategies using UAVs, including: (i) simulation of path planning of virtual UAVs and image capture under different environmental conditions; (ii) au-tomatic labeling of captured images, potentially providing an infinite amount of data for training deep neural networks; (iii) availability of the ground truth damage state from the results of the finite-element simulation; and (iv) direct comparison of different approaches to autonomous as-sessments. Moreover, the synthetic data generated has the potential to be used to augment field datasets. To demonstrate the efficacy of PBGMs, models of reinforced concrete moment-frame buildings with masonry infill walls are examined. The 3D synthetic environment employing PBGMs is shown to provide an effective testbed for development and validation of autonomous vision-based post-earthquake inspections that can serve as an important building block for ad-vancing autonomous data to decision frameworks.

Retinoic acid (RA) is the biologically active metabolite of vitamin A and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By miRNA-Sequencing analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression in the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis that miRNAs are important regulators of retinoic acid-induced neuronal outgrowth and regeneration in regeneration-competent species.

Rates of involuntary childness are on the uprise which can bring high medical costs and emotional afflictions. This review explores the emerging roles of CoQ10 - including the ubiquinol form in fertility. PubMed, Science Direct and Google Scholar were searched for RCTs, retrospective or prospective controlled studies published between January 1, 2009, and April 31, 2024. The keywords CoQ10, ubiquinol, fer/sub/infertility, ovarian reserve, oocyte quality, ovulation, amenorrhea, polycystic ovary syndrome, sperm quality, seminal fluid, and IVF were used. A total of 15 publications were identified. From a mechanistic stance CoQ10 appears to improve mitochondrial energetics, attenuate oxidative stress and modifications to DNA, proteins, and lipids. Such mechanisms appear to underpin improvements in oocyte quality/fertilization, markers of sperm quality and more broadly PCOS symptoms and hormone levels which can impact on fertility. The role of the ubiquinol form looks particularly promising, which may be attributed to its bioavailability. Ongoing research is needed but there is scope to raise CoQ10 awareness amongst reproductive health experts.

An optimal withdrawal strategy beginning at age 65 provides a lifetime income from a portfolio, adjusted annually for inflation, while reducing the probability of living in financial ruin to an ac-ceptable level. This paper analyzes the probability of living in financial ruin, potentially for multiple years, rather than just the event of ruin. A stochastic Excel model was developed to simulate the effect of varying investment returns on a portfolio with two asset classes; large company stocks and long-term government bonds. A stochastic model is also applied to retiree mortality. The following variables were analyzed to determine their relative impact on withdrawal strategies: • Withdrawing a constant percentage of the portfolio, • Gender, • Initial asset allocation, • Asset allocation rebalancing methods, and • Low investment return environments. For both genders and most withdrawal rates, an approximately equal initial asset allocation of stocks and bonds, combined with a level rebalancing function, provided the lowest probability of living in financial ruin. Because each investment return followed its own probability distribution function, some retirees experienced financial ruin even in the most conservative simulations.

Competition over environmental and natural resources characteristically lies at the heart of armed conflicts in Africa. It is also common knowledge that some companies dealing in products such as laptops, smart phones and jewellery; import minerals from conflict-affected areas, thereby indirectly fuelling conflicts in these areas or undermining human rights. For a continent endowed with natural resources including minerals, Africa has suffered the brunt of this predicament. This state of affairs has lent impetus to the adoption of several regulations geared towards curbing irresponsible business practices by companies relying on such minerals, the goal being, amongst others, to guarantee the protection of human rights. In May 2017, the European Union adopted Regulations intended to stop the importation of conflict minerals in Europe, debatably making giant strides in the direction of protection of human rights. These Regulations are to come into force in 2021. However, can these regulations advance the much-desired goal of protection of human rights in Africa on issues pertaining to conflict minerals? By analyzing the 2017 EU Regulations in light of previous regulations of a similar nature, the paper concludes that the said regulations constitute a weak normative framework and could in fact have unintended consequences on the fundamental rights of civilians in natural resource-rich conflict areas of Africa.

This paper investigates women’s empowerment and their active involvement in governance aimed at promoting sustainable development. The study focuses on examining the roles and processes of co-creation of nature-based solutions (NBS) for water management in Milan. Three research directions were explored: 1) to determine gender-based roles within local governance; 2) to detect semantic groups of NBS based on stakeholders' gender; c) to analyze gender-based linguistic and conceptual patterns of NBS. To achieve our objectives, we converted a sample of audio-video interviews of local stakeholders into textual data along with metadata indicating speakers' roles and gender. Descriptive statistics were applied to explore the governance's roles. We employed a combination of textual analysis and network analysis to identify thematic groups of NBS, and applied a word embedding approach to uncover linguistic patterns indicative of semantic sub-structures. The findings revealed significant demographic diversity. Male stakeholders perceive sustainable development as a process driven by the circular economy and the coordination of territorial authorities, while female stakeholders envision a transformative approach rooted in science, culture, and collaboration. The semantic sub-structure analysis highlighted a tendency among male governance to emphasize specialized skills, whereas female governance placed greater emphasis on problem definition rather than resolution.

Knowledge regarding egg morphology can aid the selection of postharvest fumigants for insect control. Accordingly, scanning electron microscopy (SEM) was used to examine eggs of spotted lanternfly (SLF), Lycorma delicatula (White) (Hemiptera: Pentatomidae), a pest recently invasive to the mid-Atlantic region of the United States. As the overwintering life stage of SLF, eggs are deposited on a variety of refugia, including many forestry products that can be distributed geographically via travel, commerce, and/or trade. For fumigation to control SLF, and potentially translate into a viable strategy for limiting the spread of SLF by subject pathways, the fumigant must permeate the chorion to react with biomolecules and/or disrupt cellular processes. SLF chorion was characterized by a porous network of aeropyles localized around the operculum, in cranial and caudal relation to the developing nymph, as well as an interstice between the operculum edge and the opercular rim. The confirmation of chorionic ultrastructure that allows for ready gas exchange warrants further investigation of fumigation efficacy, even for those “non-reactive” fumigants, such as phosphine and hydrogen cyanide, which must overcome the suppression of cellular processes coincident with overwintering.

Retinoic acid (RA) is the biologically active metabolite of vitamin A,and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By R-Seq analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression from the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis miRNAs are important regulators of retinoic acid induced neuronal outgrowth and regeneration in regeneration-competent species.

This paper will explore analogs of groups formed by the transformations of two ropes as presented by Minh-Tam Quang Trinh.1 The two operations acting on these ropes are T and S, defined as twists and clockwise turns, respectively. These actions intertwine the ropes, creating tangles. T and S also have the ability to untangle the rope when used in certain combinations. In the two-rope case, these actions expressed as a group presentation were shown to be isomorphic to SL₂(Z). We explored the analog of these opera- tions, T and S, and conjectured the corresponding group to which they are isomorphic. Partial proofs for this conjecture are included and future work would include proving our conjecture as well as generalizing results to k ropes.

Accurate agricultural commodity price models enable efficient allocation of limited natural resources, leading to improved sustainability in agriculture. Because of climate change, price volatility and uncertainty for the sector are expected to increase in the future, increasing the need for improved price modeling. With the emergence of machine learning (ML) algorithms, novel tools are now available to enhance the modeling of agricultural commodity prices. This research uses both univariate and multivariate ML techniques to perform probabilistic price prediction modelling for the Canadian beef industry, taking into account beef production, commodity market, and international trade features to enhance accuracy. We apply multivariate algorithms by using support vector regression (SVR), random forest (RF), and adaboost (AB) and univariate algorithms by using autoregressive integrated moving average (ARIMA), seasonal ARIMA (SARIMA), and the seasonal autoregressive integrated moving average with exogenous factors (SARIMAX). We apply these models to monthly fed steer price data between January 2005 and September 2023 and compare predicted prices with observed prices using several validation metrics. The outcomes indicate that both random forest (RF) and adaboost (AB) in multivariate modeling show superior performance in accurately predicting Alberta fed steer prices in comparison to other algorithms. To better account for the variance of the best model performance, we subsequently adopted a probabilistic approach by considering uncertainty in our best-selected ML model. The beef industry can use these improved price models to minimize resource waste and inefficiency in the sector and improve the long-term sustainability prospects for beef producers in Canada.

Sustainable and Responsible Design (SRD) harnesses design’s potential to address eco-social problems and in doing so challenge the status quo of design education by reframing the social and ecological consequences, boundaries and agencies of design. This critical and transdisciplinary approach frays the edges of traditional design disciplines with embedded and reflexive modes of learning. We describe characteristics of SRD education and present theories of learning to empower students in this complex terrain. The learning associated with SRD education is ecologically engaged, participative, critical, expansive and designerly. We recount case studies of our own experiences advancing sustainable and responsible undergraduate design education in the UK. We identify path constraints such as disciplinary fragility, appropriation, and power dynamics in the design school. The push for a revision of priorities generates tensions where there is often greenwashing rhetoric of sustainability and inclusivity. We describe strategies and tactics to address these tensions. We highlight the agency we have as educators and designers and argue that design education can only meaningfully participate in response to the challenges presented by climate change, other types of ecocide, and social problems when educators make substantive commitments to supporting sustainability literacies and design approaches that serve the interests of diverse stakeholders.

Objective. It is unknown whether the public accurately estimate socioeconomic health inequality and whether they wish to see it reduced or eliminated. Methods. Representative samples of the UK and US indicated the perceived and ideal lifespan of people working in “higher managerial/professional” and “routine” occupations. We present perceived and desired lifespan ratios for each sample and for key socio-demographic variables. Results. The UK public estimated the lifespan of professionals to be 5.9% longer than routine workers (true value of 5.8%), and 67.8% (UK) and 53.7% (US) participants correctly identified that professionals live longer than routine workers. In both populations, the median respondent expressed equal ideal lifespans for routine workers and professional workers. Conclusion. The UK public appear well-appraised on the average lifespan for professionals and routine workers. Across nationalities and most socio-demographic groups, the median respondent was aware of social class inequalities in lifespan and preferred that they be eliminated.

This study explores individual and contextual risk factors for the onset of work interfering with private life (WIL) and private life interfering with work (LIW) among self-employed men and women across European countries. It also studies the relationship between interference (LIW and WIL) and wellbeing among self-employed men and women and the effect of macro level risk factors. Data from the fifth round of European Working Conditions Survey was utilized and a sample of self-employed men and women with active businesses was extracted. Applying multilevel regressions, results show that though business characteristics are important for level of WIL, time demand is the most evident risk factor for WIL and LIW. There is a relationship between wellbeing and WIL and LIW respectively, and time demands is the most important factor in this relationship. Gender equality on the labor market did not relate to level of interference, nor did it mediate the relationship between interference and wellbeing. However, the main and most important risk factor for experiencing WIL and LIW and for how interference relate to wellbeing is gender relation processes in work and life, both on individual and contextual level.

Power grid reliability is crucial to supporting critical infrastructure, but monitoring and maintenance activities are expensive and sometimes dangerous. Remote sensing enables real time data monitoring and collection related to environmental and industrial processes, like the power grid system. Monitoring the power grid successfully involves diverse sources of data including that inherent to the power operation and ambient atmospheric weather data. Detection methods can identify anomalies like arcing, and climate data in particular is becoming increasingly important in order to maintain power supply. Gaussian processes (GPs) are a well-established Bayesian method for analyzing data. However, the computational complexity of GPs limits their scalability. This is a challenge when dealing with remote sensing datasets, where acquiring a significant amount of data is common. Alternatively, traditional machine learning methods perform quickly and accurately, but lack the generalizability innate to GPs. The focus of this review is burgeoning research that leverages Gaussian processes and machine learning in remote sensing applications.

Persistent, non-explosive passive degassing is a common characteristic of active volcanoes. Distinct periodic components in measurable parameters of gas release have been widely identified over timescales ranging from seconds to months. The development and implementation of high temporal resolution gas measurement techniques now enables the robust quantification of high frequency processes operating on timescales comparable to those detectable in geophysical datasets. This review presents an overview of the current state of understanding regarding periodic volcanic degassing, and evaluates the methods available for detecting periodicity, e.g., autocorrelation, variations of the Fast Fourier Transform (FFT), and the continuous wavelet transform (CWT). Periodicities in volcanic degassing from published studies are summarised and statistically analysed, together with analyses of literature-derived datasets where periodicity had not previously been investigated. Finally, an overview of current knowledge on drivers of periodicity is presented and discussed in the framework of four main generating categories, including: (1) non-volcanic (e.g., atmospheric or tidally generated); (2) gas-driven, shallow conduit processes; (3) magma movement, intermediate to shallow storage zone; and (4) deep magmatic processes.

Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabo-lism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, albeit 10-year clinical trial data in Duchenne muscular dystrophy patients suggests a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50> 5000mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.

Prediction and early detection of atrial fibrillation (AF) remain a permanent challenge in everyday practice. Timely identification of an increased risk for AF episodes (which are frequently asymptomatic) is essential in the primary and secondary prevention of cardioembolic events. One of the noninvasive modalities of AF prediction is represented by the electrocardiographic P-wave analysis. This includes the study and diagnosis of interatrial conduction block (Bachmann`s bundle block). Bayés’ Syndrome (named after its first descriptor) denotes the association between interatrial conduction defect and supraventricular arrhythmias (mainly AF) predisposing to cardioembolic events. Our short review presents an update of the most important data concerning this syndrome: brief history, main ECG features, pathophysiological background and clinical implications.

Over the last twenty years, library publishing has emerged in higher education as a new class of publisher. Conceived as a response to commercial publishing practices that have strained library budgets and prevented scholars from openly licensing and sharing their works, library publishing is both a local service program and a broader movement to disrupt the current scholarly publishing arena. It is growing both in numbers of publishers and numbers of works produced. The commercial publishing framework which determines the viability of monetizing a product is not necessarily applicable for library publishers who exist as a common good to address the needs of their academic communities. Like any business venture, however, library publishers must develop a clear service model and business plan in order to create shared expectations for funding streams, quality markers, as well as technical and staff capacity. As the field is maturing from experimental projects to full programs, library publishers are formalizing their offerings and limitations. The anatomy of a library publishing business plan is presented and includes the principles of the program, scope of services, and staffing and governance requirements. Other aspects include production policies, financial structures, and measures of success.

Activation of the N-methyl D-aspartate receptor (NMDAR) results in increased sensitivity of spinal cord and brain pathways that process sensory information, particularly that which relates pain. The NMDAR shows increased activity in fibromyalgia and hence modulation of the NMDAR is a target for therapeutic intervention. A literature review of interventions impacting on the NMDAR shows a number of drugs to be active on the NMDAR mechanism in fibromyalgia patients, with variable clinical effects. Low-dose intravenous ketamine and oral memantine both show clinically useful benefit in fibromyalgia. However, consideration of side-effects, logistics and cost need to be factored into management decisions regarding use of these drugs in this clinical setting. Overall benefits with current NMDAR antagonists appear modest and there is a need for better strategy trials to clarify optimal dose schedules and to delineate potential longer –term adverse events. Further investigation of the role of the NMDAR in fibromyalgia and the effect of other molecules that modulate this receptor appear important to enhance treatment targets in fibromyalgia.

Of the 100,000 railroad bridges in the United States, 50% are over 100 years old. Many of these bridges do not meet the minimum vertical clearance standards, making them susceptible to impacts from over-height vehicles. Impacts can cause structural damage and unwanted disruption to railroad bridge services; rapid notification of the railroad authorities is crucial to ensure that the bridges are safe for continued use and to affect timely repairs. Therefore, researchers have developed approaches to identify these impacts to railroad bridges. Some recent approaches use machine learning to more effectively identify impacts from the sensor data. Typically, the collected sensor data is transmitted to a central location for processing. However, the challenge with this centralized approach is that the transfer of data to a central location can take considerable time, which is undesirable for time-sensitive events like impact detection that require rapid assessment and response to potential damage. To address the challenges posed by the centralized approach, this study develops a framework for edge implementation of machine learning predictions on wireless smart sensors. Wireless sensors are used because of their ease of installation and lower costs compared to their wired counterparts. The framework is implemented on the Xnode wireless smart sensor platform, thus bringing artificial intelligence models directly to the sensor nodes and eliminating the need to transfer data to a central location for processing. This framework is demonstrated using data obtained from events on a railroad bridge near Chicago; results illustrate the efficacy of the proposed edge computing framework for such time-sensitive structural health monitoring applications.

Abstract: Background: Stigma in health can result in a broad range of vulnerabilities and risk for patients and healthcare providers. The media plays a role in people’s understanding of health and stigma is socially constructed through many communication channels including via media framing. Among health issues that were affected by stigma recently were the Monkeypox and Covid-19. Objectives: This research aims to examine how The Washington Post framed stigma around mon-keypox and COVID-19. Guided by the framing theory and stigma theory, online news coverage for monkeypox and COVID-19 were analyzed to understand the construction of social stigma through the media reporting. Methods: This research employed a qualitative content analysis to compare news framing in The Washington Post online news regarding monkeypox and COVID-19. Results: Based on endemic, reassurance, and sexual transmission frames, the The Washington Post predominantly defined Africa as the source of the disease, blames gay communities, and empha-sizes no need to worry about the spread of the monkeypox virus. For the COVID-19 coverage, The Washington Post described China as the source of the coronavirus and constructs the image of panic towards the spread of the virus. Conclusions: The shifts in stigma discourse essentially manifest racism, xenophobia, and sexism in public health. This research affirms that the media reinforces stigma phenomenon in health through framing and offers constructive suggestions for mitigating this issue.

The purpose of this article is to analyze, in a three-stage research, the relationships between environmental expenses, the improvements achieved in 5 environmental variables analyzed and efficiency, from an economic and operational perspective. The stages of this research are analyzing the sustainability reports to determine the level of information, analyzing the economic and operational efficiency, and analyzing the alignment with the environmental priorities of the Eco Ports-ESPO (European Sea Ports Organization). The results reveal that (1) the type of traffic does not condition environmental actions; (2) environmental performance (improvements) depends on environmental expenditures; (3) environmental spending and efficiency in port operations are correlated; and (4) environmental spending and port economic efficiency are correlated.

With climate change projected to increase the frequency and severity of episodic insect outbreak events, assessing potential consequences for soil microbial communities and nutrient dynamics is of importance for understanding forest resilience. The forest tent caterpillar (Malacosoma disstria) is an important defoliator of deciduous tree species in temperate and mixed forests of eastern North America with an invasion cycle every 10-12 years and outbreak events that can last 3-6 years. Following a defoliation episode on trembling aspen (Populus tremuloides) from 2015 to 2017 in Abitibi-Témiscamingue, QC, Canada, we sought to test if defoliation resulted in changes to soil bacterial and fungal communities. We hypothesized an increase in soil microbial biomass due to increased caterpillar frass inputs and potential changes in community structure following the event. Soils were sampled in July 2018, May 2019 and July 2019 from sites that had been subject to defoliation during the outbreak and from sites where no defoliation had been recorded. We assessed soil microbial biomass and fungal to total microbial activity ratio on all sampling dates, and Community Level Physiological Profiles (CLPPs) for 2018 only using a substrate induced respiration method. Contrary to our hypothesis, we observed a significant 50% decrease in microbial biomass (g biomass-C g-1 soil hour-1) in defoliated stands suggesting tree carbon normally allocated towards root exudates was reallocated towards foliage regeneration. We noted a differentiated carbon-based substrate usage following defoliation, but no change in the fungal to total microbial activity ratio. The observed changes in the two years following the defoliation event suggest that defoliation episodes aboveground could trigger changes in soil chemistry belowground with effects on soil microbial communities that may, in turn, feedback to influence forest plant dynamics.

The agricultural sector in Palestine has a significant role in its economy. However, the production of this sector is affected by different kinds of plant diseases, specifically leaf diseases. Automatic agricultural leaf disease detection is essential for the early diagnosis and controls the overall health of fields. Image segmentation techniques, clustering, and deep learning are often used to detect diseased leaves. This study proposes a novel hybrid approach based on image classification. The hybrid approach combines the k-means clustering algorithm with Convolutional Neural Network (CNN), where k-means is used to detect the leaf’s infected area, then CNN is used for specifying the disease. We used the PlantVillage dataset for experimental verification as it contains several crops with different kinds of challenging diseases. We also examined the selection of optimal k-value using the Silhouette coefficient, Elbow method, and Kneedle Algorithm. The Silhouette technique was analyzed using three distance metrics; Euclidean, Manhattan, and Cosine. Its scores for the three-distance metrics were low, near-zero, and failed to produce the optimum k value. Besides, the Elbow method was complicated to use in image segmentation in terms of executing and visualizing the k value in its graph plot. Based on verification results, the Kneedle Algorithm produced better results in the consistency of choosing the optimal k value and showed superiority over other approaches. Therefore, the processed images were segmented with the k-means clustering algorithm with a Kneedle algorithm-based k value. Finally, a Convolutional Neural Network (CNN) is trained to classify the type of disease based on analyzing and testing leaf images. The hybrid model achieved high accuracy of 93.79% in disease identification, confirming the proposed model’s robustness.

Sex dimorphism starts during early embryogenesis and is further manifested in response to hormones during puberty. As this leads to physical divergence that is measurably different between sexes, males enjoy physical performance advantages over females within competitive sport. While this advantage is the underlying basis of the segregation into male and female sporting categories, these sex-based categories do not account for transgender persons who experience incongruence between their biological sex and their experienced gender identity. Accordingly, the International Olympic Committee determined criteria by which a transgender woman may be eligible to compete in the female category, requiring total serum testosterone levels to be suppressed below 10 nmol/L for at least 12 months prior to and during competition. Whether this regulation removes the male performance advantage has not been collectively scrutinized. Here, we aim to review how differences in biological characteristics between biological males and females affect sporting performance and assess whether evidence exists to support the assumption that testosterone suppression in transgender women removes the male performance advantage. In this review, we report that the performance gap between males and females amounts to 10-50% depending on sport. The performance gap is more pronounced in sporting activities relying on muscle mass and strength, particularly in the upper body. Longitudinal studies examining the effects of testosterone suppression on muscle mass and strength in transgender women consistently show very modest changes, where the loss of lean body mass, muscle area and strength typically amounts to approximately 5% after 1 year of treatment. Thus, current evidence shows that the biological advantage enjoyed by transgender women is only minimally reduced when testosterone is suppressed. Sports organizations may therefore be compelled to reassess current policies regarding participation of transgender women in the female category of sport.

Various risks and uncertainties are strengthening the downside of the global economy. This paper aims to estimate the impact of US-China conflict and the WTO Appellate Body's shutdown on global logistics demand and to show the seriousness of the situation. Existing literature studies on protectionism or US-China trade conflict, with a focus on the effects of specific issues or impact on bilateral relations. No research has considered the adverse effects of the WTO Appellate Body's shutdown. This paper considers both US-China conflict and the installation of new NTBs in other countries due to weakened WTO function, and tries to suggest that the combination of tariffs and NTBs can severely reduce international trade and the demand for maritime logistics services, making this paper differs from previous studies. This paper suggests that a catastrophe could occur in global maritime logistics, based on quantitative estimates for the impact of global protectionism. Finally, underlining that the international trade order should not seriously be damaged, this paper proposes that countries around the world should seriously discuss this issue at the 12th WTO Trade Ministers' Meeting in Kazakhstan June 2020.

Chaparral shrublands are the dominant wildland vegetation type in southern California and the most extensive ecosystem in the state. Disturbance by wildfire and climate change have created a dynamic landscape in which biomass mapping is key in tracking the ability of chaparral shrub-lands to sequester carbon. Despite this importance, most national and regional scale estimates do not account for shrubland biomass. Employing plot data from several sources, we built a random forest model to predict above ground live biomass in southern California using remote sensing data (Landsat NDVI) and a suite of geophysical variables. By substituting the NDVI and precipi-tation predictors for any given year we were able to apply the model to each year from 2000-2019. Using a total of 980 field plots, our model had a k-fold cross validation R2 of 0.51 and a RMSE of 3.9. Validation by vegetation type ranged from R2 = 0.17 (RMSE=9.7) for Sierran mixed conifer to R2 = 0.91 (RMSE = 2.3) for sagebrush. Our estimates showed an improvement in accuracy over a two other biomass estimates that included shrublands, with an R2 = 0.82 (RMSE = 4.7) compared to R2 = 0.068 (RMSE = 6.7) for a global biomass estimate and R2 = 0.29 (RMSE = 5.9) for a regional biomass estimate. Given the importance of accurate biomass estimates for resource managers we calculated the mean year 2010 shrubland biomass for the four national forests which ranged from 3.5 kg/m2 (Los Padres) to 2.3 kg/m2 (Angeles and Cleveland). Finally, we compared our estimates to field-measured biomass from the literature summarized by shrubland vegetation type and age class. Our model provides a transparent and repeatable method to generate biomass measure-ments in any year, thereby providing data to track biomass recovery after management actions or disturbances such as fire.

Following the central dogma of molecular biology, gene expression heterogeneity can aid in predicting and explaining the wide variety of protein products, functions, and, ultimately, heterogeneity in phenotypes. There is currently overlapping terminology used to describe the types of diversity in gene expression profiles, and overlooking these nuances can misrepresent important biological information. Here, we describe transcriptome diversity as a measure of the heterogeneity in 1) the expression of all genes within a sample or a single gene across samples in a population (gene-level diversity) or 2) the isoform-specific expression of a given gene (isoform-level diversity). We first overview modulators and quantification of transcriptome diversity at the gene level. Then, we discuss the role alternative splicing plays in driving transcript isoform-level diversity and how it can be quantified. Additionally, we overview computational resources for calculating gene-level and isoform-level diversity for high-throughput sequencing data. Finally, we discuss future applications of transcriptome diversity. This review provides a comprehensive overview of how gene expression diversity arises, and how measuring it determines a more complete picture of heterogeneity across proteins, cells, tissues, organisms, and species.

As consequence of the digital transformation, e-learning methodologies have become an inseparable part of the standard classes in schools and universities, assuming an increasingly significant role in compensating for the difficulties resulting from the COVID-19 pandemic. Numerous pedagogical methodologies and strategies can be easily implemented in high education, promoting students’ motivation and interest in learning. This research study analyses the implementation of gamification pedagogical strategy on 50-60 undergraduate chemical engineering students at the university, by evaluating its effect on the success rate on a specific topic of Chemical Reactions Engineering subject and the motivation effect for the following topics. Our results show a significant positive effect of the gamification strategy on university lectures, increasing up to 25-30 % of the success ratio with an apparent motivation effect. During the subsequent years, the changes in the lifestyle of study also play a role in students’ performance. Therefore, it is necessary to evaluate case studies such as the one presented here to understand better the use of these pedagogical methods and strategies in high education, especially in technical subjects described in this paper.

Abstract: Given the links between parental obesity and eating psychopathology in their children, it is important to understand the mechanisms via which unhealthy relationships with eating are passed from parents to children. The aim was to review research focusing on food-related parenting practices (FPPs) used by parents with overweight/obesity. Web of Science, PubMed and PsycINFO were searched. Twenty studies were included in the review. Single studies suggest differences between parents with healthy-weight vs overweight/obesity with respect to; food accessibility, food availability and modelling. Multiple studies suggest that several parenting strategies do not differ according to parental weight status (child involvement, praise, use of food to control negative emotions, use of food-based threats and bribes, pressure, restriction, meal and snack routines, monitoring, and rules and limits). There was inconclusive evidence with respect to differences in parental control, encouragement and use of unstructured FPPs among parents with healthy-weight vs overweight/obesity. The findings of this review imply some differences between parents with overweight/obesity and healthy-weight and the use of some food-related parenting practices, however they should be interpreted with caution since research remains limited and is generally methodologically weak. The review highlights opportunities for further research and to improve current measures of FPPs and help clarify current study findings.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension, which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary hypertension related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, hypertension per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, such as thiazide diuretics predisposing to skin cancer. As a result, under the light of the similar risk factors and overlapping pathophysiological mechanisms between hypertension and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

Proteases are integral enzymes of the plant immune system. Multiple aspects of defence are regulated by proteases, including the hypersensitive response, pathogen recognition, priming and peptide hormone release. These processes are regulated by unrelated proteases residing at different subcellular locations. In this review we discuss ten prominent plant proteases contributing to the plant immune system, highlighting the diversity of roles they perform in plant defence.

Tyrosine Kinase Inhibitors work by blocking the tyrosine kinases responsible of the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patient and most of them were paediatrics. The 82.4% of patients were men; however, sex-related differences in drugs pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated: as patients ages increased, drug levels decreased. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that Therapeutic Drug Monitoring is a useful method for adjusting a patient treatment schedule depending on drug concentrations in biological fluids. The use of Therapeutic Drug Monitoring in conjunction with Tyrosine Kinase Inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, Tyrosine Kinase Inhibitors Therapeutic Drug Monitoring classification needs to be refined in terms of factors like sexes and ages.

Abdominal aortic aneurysm (AAA) represents an important public health problem with a prevalence between 1.3% and 12.5%. Several population-based randomized trials have evaluated ultrasound screening for AAA providing evidence of a reduction in aneurysm-related mortality in the screened population. The aim of our study was to perform a systematic review and meta-analysis of the risk factors for AAA. We conducted a systematic review of observational studies and we performed a meta-analysis that evaluated the following risk factors: gender, smoking habits, hypertension, diabetes mellitus, Coronary Artery Disease and family history of AAA. Abdominal aortic aneurysm prevalence is higher in smokers and in males. It is important to underline that all countries, where AAA screening was set up, had high income level and the majority belong to Western Europe (United Kingdom, Sweden, Italy, Poland, Spain and Belgium). Abdominal aortic aneurysm screening is fundamental for public health. It would avoid deaths, ruptures, and emergency surgical interventions if abdominal aortic aneurysm was diagnosed early in the population target for screening.

The Galápagos archipelago is a vast reservoir of terrestrial and marine biodiversity and is particularly susceptible to human, animal, and environmental impacts. Climate change, globalization, and the blurring of human-domestic animal-wildlife interfaces are poised to bring new threats and challenges to the region. A One Health perspective that simultaneously considers human, animal, and environmental health is imperative in assessing and mitigating the challenges facing the Galápagos Islands. Many challenges facing biodiversity in the Galápagos Islands can ultimately be linked to anthropogenic factors. In Part I of this review, we reviewed the impacts of invasive species and identified infectious diseases of importance. In Part II of this review, we discuss the impacts of climate change and ocean acidification, and highlight the effects of several direct human activities, including tourism, overfishing, pollution, land use, and human-wildlife conflict. We also review the socioeconomic and political context of the Galápagos Islands, including current challenges in water and energy use, sanitation, and economic stability. We examine the importance of investment in local development for building resiliency and sustainability in the archipelago. Finally, we discuss the impact of the COVID-19 pandemic in the region. Throughout this two-part review, we build a cohesive picture of One Health in the Galápagos Islands by integrating past work, current needs, and emerging threats. We also consider overarching goals for conservation, ecosystem management, and socioeconomic sustainability that have been previously defined by both governmental and non-governmental stakeholders, and identify discrete, implementable, and interdisciplinary recommendations that will facilitate achievement of those goals.

The Galápagos archipelago is a vast reservoir of terrestrial and marine biodiversity, owing in large part to its relatively recent volcanic genesis and colonization by humans. This unique ecological system is particularly susceptible to human, animal, and environmental impacts. Climate change, globalization, and the blurring of human-domestic animal-wildlife interfaces are poised to bring new threats and challenges to the region. A One Health perspective that simultaneously considers human, animal, and environmental health is imperative in assessing and mitigating the challenges facing the Galápagos Islands.In Part I of this review, we provide the historical context for biodiversity in the archipelago; discuss the role of invasive species in habitat destruction, fragmentation, and competition with endemic species; and summarize the established and emerging infectious disease threats. We also discuss the imperative to implement research, surveillance, and preventative measures to identify and manage future threats from a One Health perspective, with a specific emphasis on implications for wildlife health. In Part II, we outline the socioeconomic context of life in the Galápagos Islands, evaluate the current and predicted effects of climate change, and discuss direct anthropogenic factors affecting Galápagos biodiversity, such as tourism, fishing, pollution, and the illegal wildlife trade. We also examine the impact of the COVID-19 pandemic in the region. Throughout this two-part review, we build a cohesive picture of One Health in the Galápagos Islands by integrating past work, current needs, and emerging threats. We also consider overarching goals for conservation, ecosystem management, and socioeconomic sustainability that have been previously defined by both governmental and non-governmental stakeholders, and we identify discrete, implementable, and interdisciplinary recommendations that will facilitate achievement of those goals.

Recent research has suggested that working memory training interventions may benefit children with Developmental Language Disorder (DLD). The current study investigated a short and engaging adaptive working memory intervention that targeted executive skills and aimed to improve both language comprehension and working memory abilities in children with DLD. Forty-seven 6- to 10-year-old children with DLD were randomly allocated to an executive working memory training intervention (n=24) or an active control group (n=23). A pre-test/intervention/post-test/9-month-follow-up design was used. Outcome measures included assessments of language (to evaluate far transfer of the training) and working memory (to evaluate near transfer of the training). Hierarchical multiple regression analyses controlling for pre-intervention performance and age found group to be a significant predictor of sentence comprehension and of performance on six untrained working memory measures at post-intervention and 9-month follow-up. Children in the intervention group showed significantly higher language comprehension and working memory scores at both time points than children in the active control group. The intervention programme showed potential to improve working memory and language comprehension in children with DLD and demonstrated several advantages: it involved short sessions over a short period; caused little disruption in the school day; and was enjoyed by children.

This study introduces and demonstrates a comprehensive, accurate, unbiased approach to robust quantitative comparison of Electronic Nicotine Delivery Systems (ENDS) appropriate for establishing substantial equivalence (or lack thereof) between tobacco products. The approach is demonstrated across a family of thirteen pen- and pod-style ENDS products. Methods employed consist of formulating a robust emissions surface regression model, quantifying the empirical accuracy of the model as applied to each product, evaluating relationships between product design characteristics and maximum emissions characteristics, and presenting results in formats useful to researchers, regulators, and consumers. Results provide a response surface to characterize emissions (total particulate matter and constituents thereof) from each ENDS appropriate for use in a computer model and for conducting quantitative exposure comparisons between products. Results demonstrate that emissions vary as a function of puff duration, flow rate, E-Liquid composition, and device operating power. Further, results indicate that regulating design characteristics of ENDS devices and consumables may not achieve desired public health outcomes; it is more effective to regulate maximum permissible emissions directly. Three emissions outcome measures (yield per puff, mass concentration and constituent mass ratio) are recommended for adoption as standard quantities for reporting by manufacturers and research laboratories. The approach provides a means of (a) quantifying and comparing maximal emissions from ENDS products spanning their entire operating envelope, (b) comparative evaluation of ENDS devices and consumable design characteristics, and (c) establishing comparative equivalence of maximal emissions from ENDS. A consumer-oriented product emissions dashboard is proposed for comparative evaluation of ENDS exposure potential. Maximum achievable power dissipated in the coil of ENDS is identified as a potentially effective regulatory parameter.

The steep decline in the price of wind and solar photovoltaics provides a possibility to decarbonize electricity deeply and affordably. This study uses HOMER Pro energy modeling tool to model an optimized grid-connected renewable energy system for a community in southern Alberta, Canada. The study's goal is to identify the best renewable energy technology combinations that can provide electricity at the lowest levelized cost of energy (LCOE) and has lesser greenhouse gas emission as compared to the electricity produced by traditional fossil fuel. Gleichen, is a small town in southern Alberta and is near to numerous commercial wind and solar projects given the region’s high quality renewable resources. “Tri-brid” systems consisting of wind turbines, solar photovoltaics, and battery energy storage systems (BESS) are considered and compared based on electricity prices, net present cost, and greenhouse gas emissions savings. This tri-brid system is connected to the grid to sell excess electricity generated or buying electricity when there is less or no availability of solar and wind. The tri-brid energy system has an estimated LCOE of 0.0705 CAD/kWh which is competitive with the price of electricity generated by natural gas and coal which is 0.127 CAD/kWh.

It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is further unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular mammals. Because of SARS-CoV-2’s evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for prevention of human-to-animal transmission have so far focused mostly on these animal groups. Here, we summarize recent studies and reports that show that a wide range of distantly related mammals are likely susceptible to SARS-CoV-2 and that susceptibility or resistance to the virus is in general not predictable, or only to some extent, by phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the SARS-CoV-2 susceptibility/resistance for each of the >5,500 mammal species, we argue that sanitary precautions should be taken when interacting with any mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important for protecting these (sometimes endangered) animals from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild animals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. For wildlife fieldworkers interacting directly or indirectly with mammals, we recommend sanitary precautions such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans.

Despite great strides in the development of contraceptive technologies, the United States has one of the highest teen pregnancy rates in the world. Many investigators have aimed to examine the relationship between religion and the sexual health behaviors of college students to determine how social factors may influence the use of contraception amongst college students. Thus, we aimed to examine the differences in current contraceptive method and age of first contraceptive usage among sexually active female college students with different religious affiliations and strengths of religiosity. It was hypothesized that there would be no difference in current contraceptive methods among different religious affiliations and strengths of religions, and that there would be a difference in age of first contraceptive usage among different religious affiliations and strengths of religiosity. Two-hundred twenty-four college aged females completed a 20-question survey about sexual health and religious practices. Chi-squared tests were implemented to determine if the frequencies of responses across religious affiliations and strengths of religiosity. Significant differences in the frequency of responses for age of first contraceptive usage were observed across different strengths of religiosity (p=0.016) and for the self-perceived impact of religion on sexual health across different religious affiliations (p=0.033) and strengths of religiosity (p=0.005). All other differences were found not to be statistically significant. It was determined that increased strengths of religiosity resulted in delayed onset of contraceptive us-age and that both different religious affiliations and greater strengths of religiosity lead to different self-perceived impacts of religion on sexual health.

COS production is carried out enzymatically using chitosanase, but this process is expensive. Production costs can be reduced by using crude enzyme chitosanase, and the resulting COS has depolymerization &lt; 20 and molecular weight &lt; 3900 Da. Sources of crude enzyme chitosanase come from the soil, sediment, and fishery waste. Chitosanase is produced from bacteria and molds isolated from the source or direct isolation process for extracellular enzymes, especially from fishery waste. Microorganisms in the soil produce chitosanase as a biocontrol and self-defense agent. Bacteria and molds have been isolated, including Bacillus cereus, Bacillus mycoides, Paenibacillus sp., and Penicillium janthinellum. Fishery waste, especially parts of the digestive tract, is a source of chitosanase because of its relation to its nature and food, such as small fish, frogs, and several types of crustaceans. In addition, fishery waste can be used as a carbon and nitrogen source (C/N) in microorganism culture media. The chitin content becomes a stimulant for the synthesis of chitosanase by microorganisms. Crude enzyme chitosanase has an active site that hydrolyzes chitosan by breaking glycosidic bonds and producing glucosamine units (GlcN) and N-acetyl glucosamine (GlcNAc). This mechanism can take place through two events, namely inverting and retaining. Crude enzyme chitosanase can break glycosidic bonds, especially with the same groups, for example, bonds between glucosamine or N-acetyl glucosamine. The COS produced is of the partially acetylated COS (paCOS) type, which still contains an acetyl group. The degree of deacetylation is a significant factor in the resulting COS product, COS with the fully deacetylated COS (fdCOS) type of chitosan with a high degree of deacetylation. Other factors to consider are the raw material of chitosan, the incubation time, the screening process, and the production of microorganism cultures.

Milk and dairy foods are naturally rich sources of a wide range of nutrients, and when consumed according to recommended intakes contribute essential nutrients across all stages of the life cycle. Since then, seminal studies recommendations with respect to intake of saturated fat have been consistent and clear; limit total fat intake to 30% or less total dietary energy, with a specific recommendation for intake of saturated fat to less than 10% of total dietary energy. However, recent work has re-opened the debate on intake of saturated fat in particular, with suggestions that recommended intakes be considered not at a total fat intake within the diet, but at a food specific level. A large body of evidence exists examining the impact of dairy consumption on markers of metabolic health, both at a total dairy intake and also at a food level, with mixed findings to date, but suggests that the impact of saturated fat intake on health differs both across food groups and even between foods within the same good group such as dairy. Milk and dairy foods contain a range of nutrients and bioactive components in different levels, housed within very different food structures. The interaction of the overall food structure and the nutrients describes the concept of the ‘food matrix effect’ which has been well documented for dairy foods. Studies show that nutrients from different dairy food sources can have different effects on health and for this reason, they should be considered individually rather than grouped as a single food category in epidemiological research. This review examines the current evidence from randomised controlled trials and meta-analyses, with respect to dairy, milk, yoghurt and cheese on aspects of metabolic health, and summarises some of the potential mechanisms for these findings.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

Little is understood about the impact of nebulisation on the viability of SARS-CoV-2. In this study, a range of nebulisers with differing methods of aerosol generation were evaluated to determine SARS-CoV-2 viability following aerosolisation. The aerosol particle size distribution was assessed using an aerosol particle sizer (APS) and SARS-CoV-2 viability was determined after collection into liquid media using All-Glass Impingers (AGI). Viable particles of SARS-CoV-2 were further characterised using the Collison 6-jet nebuliser in conjunction with novel sample techniques in an Andersen size-fractioning sampler to predict lung deposition profiles. Results demonstrate that all the tested nebulisers can generate stable, polydisperse aerosols (Geometric standard deviation (GSD) circa 1.8) in the respirable range (1.2 to 2.2µm). Viable fractions (PFU/particle, the virus viability as a function of total particles produced) were circa 5x10^-3 and were not significantly affected by relative humidity. The novel Andersen sample collection methods successfully captured viable virus particles across all sizes; with most particle sizes below 3.3µm. MMADs (Mass Median Aerodynamic Diameters) were calculated from linear regression of log10-log10 transformed cumulative PFU data, and calculated MMADs accorded well with APS measurements and did not differ across collection method types. This data will be vital in informing animal aerosol challenge models, and infection prevention and control policies.

The Fusarium fujikuroi species complex (FFSC) includes socioeconomically important pathogens that cause disease and/or mycotoxin contamination on numerous crops. Here, we used comparative genomics to elucidate processes underlying the ability of pine-associated and grass-associated FFSC species to colonize tissues of their respective plant hosts. We characterized the identity, possible functions, evolutionary origins, and chromosomal positions of the host-range-associated genes encoded by the two groups of fungi. The 72 and 47 genes identified as unique to the respective genome groups were potentially involved in diverse processes, ranging from transcription, regulation, and substrate transport, through to virulence/pathogenicity. Most emerged early during the evolution of Fusarium/FFSC and were subsequently retained only in some lineages, while some had origins outside Fusarium. Although differences in the densities of these genes were especially noticeable on the conditionally dispensable chromosome of F. temperatum (representing the grass-associates) and F. circinatum (representing the pine-associates), the host-range-associated genes tended to be located towards the subtelomeric regions of chromosomes. Taken together, these results demonstrate that multiple mechanisms drive the emergence of genes in grass- and pine-associated FFSC taxa examined and highlighted the diversity of molecular processes potentially underlying niche-specificity in these and other Fusarium species.

The current economic and political crisis has brought about a change in the environment in which Non-Governmental Development Organizations (NGDOs) have traditionally operated. This change can be summed up as a reduction in the funds they receive and an increase in the population they must serve. The need then arises to have mechanisms that allow an analysis of the good work performed by the NGDOs. Knowing the efficiency of the NGDOs in the management of their previous projects can contribute towards improving their future achievements. The aim of this research is to establish some objective indicators that allow an evaluation of the efficiency of these organizations. Firstly, a detailed analysis of the regulation of the three Agencies is conducted (Spanish-AECID, European- EuropeAid and American -USAID). This allows us to synthesize the indicators of good performance of the NGDO based on the study of the eligibility criteria of public donors. The research concludes with the study of the efficiency following the Promethee Approach. Our results reveals that 44.6% of the NGDOs (33 out of the 74 studied) operate inefficiently, compared to 29.7% which are efficient.

Health communication has been highlighted as a cost-effective preventive intervention in Africa where prevalence of tobacco use is still relatively low compared to other World Health Organization (WHO) regions. This scoping review aims to examine tobacco control health communication interventions in Africa. The review was guided by the PRISMA-ScR checklist. Data was extracted from twenty peer-reviewed papers, WHO Global Health Observatory on Anti-tobacco mass media campaigns for 54 African countries, and six WHO Framework Convention on Tobacco Control reports on Article 12. Data extraction informed by JBI data extraction questions was used for peer review studies while a pre-determined template was used for the other sources. Narrative data synthesis informed by the JBI manual for evidence synthesis was employed. Lack of research that comprehensively address all areas of health communication and Inconsistent use of health communication campaigns was identified. Only an average of 6 countries had ever implemented effective mass media campaigns in a decade while an average of 33 countries consistently failed to conduct campaigns that lasted more than 3 weeks. Although the involvement of key populations was clearly vital to ensure content relevance and message clarity; a lack of health communication informed by young people was observed as they rarely participated in key decision-making despite reportedly being targets of interventions. Clear health communication for tobacco use prevention informed by young people is lacking in African countries. Active participation of young people in developing targeted campaigns is needed to facilitate content relevance and comprehension to ultimately contribute to tobacco use prevention.

In the United States, the ballot measure power was born during the 1990s Progressive Era, ushered in by populists, socialists, and labor activists. Early on, activists used the measure to curb political corruption through campaign finance and other election reforms. Those early efforts also sought to improve labor conditions, minimize the influence of wealthy special interests, and require powerful corporate interests to pay more taxes. While the measure has been used by conservatives and progressives alike, the legacy of the process as a vehicle for progressive change is undeniable. However, the ballot measure landscape of the last two decades is marked by politicians growing increasingly hostile to its use. From requiring supermajorities to pass measures to refusing to implement measures approved by voters, lawmakers have made every attempt to restrict voters’ access to the measure power. In particular, Republican state legislators have become increasingly hostile to the ballot measure process, crafting creative ways to prevent measures from making it to the ballot or to stop voters from approving progressive measures. To fully understand how the measure process has been manipulated in recent years, we examined how legislators have attempted to change the process. Here, we examined a series of hypotheses to determine whether the political party affiliation of the sponsor of proposed ballot measure legislation is a predictor of whether the legislation restricts the ballot measure process. We tested these hypotheses by analyzing data from 2010 to 2022 and conducting empirical tests to determine the relationship between political party affiliation and the restrictiveness of proposed ballot measure legislation. We also analyzed how the patterns of ballot measure legislation affected states where the state government is under unified and split control. In reviewing this legislation, we found that Democrats initially attempted to restrict the ballot measure process. However, as progressives successfully passed more progressive ballot measures, Republicans – and particularly when Republicans held a trifecta in state government – attempted to restrict the ballot measure process far more extensively than any attempts by Democrats. We can draw three significant conclusions from our analysis. First, Democrats are willing to restrict the ballot measure process in some circumstances. This is evident based on conservative attempts to restrict gay marriage and other conservative policy through the ballot measure in the 2000s and Democratic efforts to stop those attacks. Second, Republican attempts to restrict the ballot measure process far outpace any initial attempts by Democrats during the period we studied, especially when Republicans have a trifecta in the state government. This speaks to the long-term Republican strategy of power-grabbing seen not only here, but throughout the political process in recent years. Lastly, our research indicates that as progressives continue to see success with ballot measures, Republican efforts to restrict the ballot measure process are expected to continue.

Hydrogels are used for various biomedical applications due to their biocompatibility, capacity to mimic the extracellular matrix, and ability to encapsulate and deliver cells and therapeutics. However, traditional hydrogels have a few shortcomings, especially regarding their physical properties, thereby limiting their broad applicability. Recently, researchers have investigated the incorporation of nanoparticles (NPs) into hydrogels to improve and add to the physical and biochemical properties of hydrogels. This brief review focuses on papers that describe the use of nanoparticles to improve more than one property of hydrogels. Such multifunctional hydrogel nanocomposites have enhanced potential for various applications, including tissue engineering, drug delivery, wound healing, bioprinting and biowearable devices.

This study explores the impact on the stability of drying and encapsulation of a camu camu extract (CCX) using the non-thermal, high-throughput electrospraying assisted by pressurized gas (EAPG) technique. The dried and encapsulated products by the EAPG processing techniques were compared in terms of total soluble phenolic compounds, antioxidant activity, and storage stability. Whey protein concentrate (WPC) and zein (ZN) were selected as the protective excipients for encapsulation. Dried and encapsulated products were obtained in the form of microparticles, which were smaller and more spherical in the case of the encapsulates. No significant differences were observed in the total polyphenolic content (TSP), and only relatively small differences in the antioxidant capacity were measured among samples. The generated products were subjected to various storage conditions to assess their stability and the preservation of the TSP and the antioxidant properties, i.e. 0% relative humidity (RH) and 4°C; 0% RH and 21°C; 23% RH and 21°C; 56% RH and 21°C; and UV light exposure. The results indicated that ZN encapsulation notably enhanced the retention of total soluble polyphenols and antioxidant activity compared to WPC and dried CCX, especially in the ratio 2:1 (encapsulating polymer: dried CCX). This study demonstrates the potential of protein-based encapsulation, particularly using ZN, for stabilizing bioactive compounds against degradation mechanisms induced by humidity, temperature, or ultraviolet radiation exposure.

Study aimed to evaluate the impact of integrating family planning with maternal, newborn, and child health (FP-MNCH) on uptake of modern contraceptive methods and related health outcomes in two districts of the province of Sindh, Pakistan. Impact of intervention was evaluated using a quasi-experimental control before-after study design. Intervention included capacity building of healthcare providers and outreach workers, ensuring sustained supplies of family planning commodities, data-driven decision-making, and community engagement activities. Data was collected through household surveys at baseline (December2020) and endline (December 2022). The sample size was estimated as 880 married women of reproductive age (MWRA) in each district. The Difference and Difference(DiD) analytical method was used to estimate the impact of intervention adjusted for potential confounding factors. There was statistically significant increase of 11.3% in the current use of MCM in the intervention group compared to the control group (p value <0.001), with increases observed in the uptake of injection , implants, and condoms. Additionally, there was an increase in the proportion of women who had ANC visits (DiD 10.5% p value 0.003), FP counselling during ANC (DiD 15.6% p value < 0.001), LHW visits during pregnancy (DiD 15.1% p value 0.021), PNC check-ups for mother (DiD 25.2% p value <0.001), LHW visits after delivery (DiD 20.4% p value <0.001), and LHW advised for family planning at PNC visit n (DiD 14.5% p value 0.030). This study provides strong evidence for the scaling-up of integrated interventions through existing health care platforms utilizing human resources deployed by the government. This FP-MNCH model has the potential to be adopted in other provinces and at federally administered areas for both health and population planning. This model should be considered for replication in other districts of Sindh to accelerate current level of integration already existing.

We discuss the implementation of a suite of virtual diagnostics at the FACET-II facility currently under commissioning at SLAC National Accelerator Laboratory. The diagnostics will be used for prediction of the longitudinal phase space along the linac, spectral reconstruction of the bunch profile and non-destructive inference of transverse beam quality (emittance) using edge radiation at the injector dogleg and bunch compressor locations. These measurements will be folded in to adaptive feedbacks and ML-based reinforcement learning controls to improve the stability and optimize the performance of the machine for different experimental configurations. In this paper we describe each of these diagnostics with expected measurement results based on simulation data and discuss progress towards implementation in regular operations.

This article aims to assess the benefits of floor-slab insulation measures using extruded polystyrene (XPS) and polyisocyanurate (polyiso) insulation materials at various levels of insulation thicknesses for a detached residential building. The EnergyPlus simulation analysis was carried out within the seven energy zones (represented by eight locations) of South Africa in accordance with the South African national code for building energy efficiency (SANS10400-XA). The energy savings and payback periods due to use of the insulation over a lifecycle period of 50 years were assessed. Cape Town (zone 4) behaved differently from other locations and hardly benefitted from the application of floor-slab insulation measures. Generally, polyiso insulation performed better than XPS, for vertical gap insulation. For vertical gap insulation, lower insulation thicknesses required higher insulation depths to maximize energy savings. Similarly, lower insulation thicknesses required higher perimeter insulation widths to maximize energy savings, for the horizontal perimeter insulation method. The locations that benefitted most from vertical gap floor-slab insulation were Pretoria (zone2), Kimberley (zone6), Nelspruit (zone3), Fraserburg (zone7), Welkom (zone1), Mthatha (zone5), Ixopo (zone5H) and Cape Town (zone4) in that order. This order was almost similar with those for the horizontal perimeter floor-slab insulation and horizontal full floor-slab insulation methods.

The popularity of electronic cigarettes in the United States and around the world has led to a startling rise in youth nicotine use. The Juul e-cigarette was introduced in the U.S. market in 2015 and had captured approximately 13% of the U.S. market by 2017. Unlike many other contemporary electronic cigarette companies, the founders behind the Juul® e-cigarette approached their product launch like a traditional high-tech start-up company, not like a tobacco company. This article presents a case study of Juul’s corporate and product development history in the context of US regulatory actions. The objective of this article is to demonstrate the value of government-curated archives as leading indicators which can (a) provide insight into emergent technologies and (b) inform emergent regulatory science research questions. A variety of sources were used to gather data about the Juul e-cigarette and the corporations that surround it. Sources included government agencies, published academic literature, non-profit organizations, corporate and retail websites, and the popular press. Data was disambiguated, authenticated, and categorized prior to being placed on a timeline of events. A timeline of four significant milestones, nineteen corporate filings and events, twelve US regulatory actions, sixty four patent applications, eighty seven trademark applications, twenty three design patents and thirty two utility patents related to Juul Labs and its associates is presented spanning the years 2004 thought 2020. This work demonstrates the probative value of findings from patent, trademark, and SEC filing literature in establishing a premise for emergent regulatory science research questions which may not yet be supported by traditional archival research literature. The methods presented here can be used to identify key aspects of emerging technologies before products actually enter the market, this shifting policy formulation and problem identification from a paradigm of being reactive in favor of becoming proactive. Such a proactive approach may permit anticipatory regulatory science research and ultimately shorten the elapsed time between market technology innovation and regulatory response.

The RNA-guided endonuclease system CRISPR-Cas9 has been extensively modified since its discovery, allowing its capabilities to be extending far beyond double-stranded cleavage to high fidelity insertions, deletions, and single base edits. Such innovations have been possible due to the modular architecture of CRISPR-Cas9 and the robustness of its component parts to modifications and the fusion of new functional elements. Here, we review the broad toolkit of CRISPR-Cas9-based systems now available for diverse genome editing tasks. We provide an overview of their core molecular structure and mechanism and distil the design principles used to engineer their diverse functionalities. We end by looking beyond the biochemistry and towards the societal and ethical challenges that these CRISPR-Cas9 systems face if their transformative capabilities are to be deployed in a safe and acceptable manner.

Whole-brain radiation therapy and stereotactic radiosurgery are two treatment modalities commonly utilized to treat brain metastases (BMs). The aim of this study is to retrospectively analyze the main radio-oncologic and clinical-demographic aspects of a cohort of BM patients treated with Volumetric Modulated Arc Therapy for radiosurgery (VMAT-RS). This is a cross-sectional observational design study with retrospective review of medical records of patients with brain metastases treated with VMAT- RS between 2012 and 2018. Clinical and demographic data, with special attention to sex, age, primary tumor, brain tumor-related epilepsy (BTRE), number and brain location of BMs, Karnofsky Performance Status (KPS), the updated DS-GPA prognostic index and the survival estimated according to the Kaplan-Meier model from the date of radiosurgery were analyzed. One hundred and twenty-one patients with 229 BMs were treated with VMAT-RS. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. Sixty-eight percent of the patients had lung cancer and 35% of the BMs were in the frontal lobe. Proportion of local control was 88.5%. BTRE prevalence was 30.6%. The median survival time (MST) was 7.7 months. In the multivariate analysis of the Cox Regression model KPS70 (HRKPS&lt;70=2.59; p=0.001) and higher DS-GPA (HRDS-GPAII =0.55, p=0.022; HRDS-GPAIII-IV =0.38, p=0.006) were associated with improved survival. In the univariate analysis, primary tumor, age and the presence of metastases in the posterior fossa (PFBMs) were also significative. In conclusion, the VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The median survival is significantly longer in those with higher KPS and DS-GPA. Other variables such as the type of primary tumor, age and PFBMs could also influence survival, although further studies are needed.

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.

Unlike plants which have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm known effects of microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 hours of exposure to microgravity via a NASA-developed rotary cell culture system. Fluorescence-guided morphometry revealed microgravity-induced loss of the significant reduction (p &lt; 0.0l) to the nuclear to cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on impact of microgravity on cellular drug-response, in view of the growing need for space medicine, as space exploration grows.

In recent years, there is a growing concern about the alarming spread of antimicrobial resistance (AMR) in different environments. Increasingly, many species of bacteria, fungi and viruses are becoming immune to the most commonly used pharmaceuticals. One of the causes of the development of the resistance is the persistence of these drugs, excreted by humans, in municipal and hospital wastewater (WW). Consequently, wastewater treatment plants (WWTPs) are a primary source of antimicrobial resistance genes as novel pollutants. This systematic review sought to examine the relevant literature on pharmaceutical residues (PRs) responsible for AMR in municipal and hospital WW in order to propose a classification of the PRs of greatest concern and provide an updated source for AMR management in WWTPs. Among 546 studies collected from four databases, 18 were included in the present review. The internal and external validity of each study was assessed, and the risk of bias was evaluated on a 20-parameter basis. Results were combined in a narrative synthesis discussing influents and effluents PR concentrations at 88 WWTPs, seasonal variations, differences between hospital and municipal WW, environmental risk assessment values of antimicrobial substances and treatment facilities removal efficiencies. Among the 45 PRs responsible for AMR evaluated in this study, the antibiotics ciprofloxacin, clarithromycin, erythromycin, metronidazole, ofloxacin, sulfamethoxazole and trimethoprim constitute a considerable risk in terms of ubiquitous distribution, worrying concentrations, risk quotients values, and resistance to removal treatments. Gaps in knowledge, data and information reported in this review provide a valuable source for managing AMR in WWTPs.

Necroptosis is an inflammatory form of lytic programmed cell death that is thought to have evolved to defend against pathogens. Genetic deletion of the terminal effector protein – MLKL – shows no overt phenotype in the C57BL/6 mouse strain under conventional laboratory housing conditions. Small molecules that inhibit necroptosis by targeting the kinase activity of RIPK1, one of the main upstream conduits to MLKL activation, have shown promise in several murine models of non-infectious disease and in phase II human clinical trials. This has triggered multi-billion-dollar investments into the emerging class of necroptosis blocking drugs, and the potential utility of targeting the terminal effector is being closely scrutinised. Here we review murine models of disease, both genetic deletion and mutation, that investigate the role of MLKL. We summarize a series of examples from several broad disease categories including ischemia reperfusion injury, sterile inflammation, pathogen infection and haematological stress. Elucidating MLKL’s contribution to mouse models of disease is an important first step to identify human indications that stand to benefit most from MLKL-targeted drug therapies.

The offshore oil and gas working environment is an inherently dangerous one, with risks posed to physical safety on a daily basis. One neglected field of research is the added psychosocial stressors present in this environment. This research examined the experiences of offshore oil and gas workers through one-on-one online interviews which were recorded and transcribed. Transcripts were analysed through qualitative software NVivo, which generated themes and patterns for the responses given to questions which were developed through a focus group. The results of the analysis showed that multiple psychosocial stressors are present for this population, such as fear of speaking up, unsatisfactory company-provided facilities, work-life interference, work status, micromanaging, gender harassment and bullying. In addition, interviews identified that production and time pressures along with fatigue can influence accidents and mistakes. Climate factors also cause discomfort, however these are managed according to best practice by organisations. Due to the timing of the study, COVID-19 was a significant stressor for some, but not all, employees. In conclusion, offshore oil and gas workers face multiple stressors in a dangerous environment that may lead to devastating consequences.

Statistics modules are included in most university degrees, independent of the degree area. They have an important role in preparing students for the real world. The overall goal of this paper is to identify the common statistical issues students face during the transition from secondary education to tertiary education. Drawing upon data from the University College Dublin (UCD) Math Support Center (MSC) and Universidad Rey Juan Carlos (URJC), our approach aims to optimize learning experiences while advancing sustainability objectives. In this paper, we conducted a categorization of statistical concepts taught in university (based on URJC). Using this categorization, UCD MSC tutor comments were categorized and validated, and subsequently descriptive analyses and text mining were used on the UCD MSC comments to achieve a deeper understanding of the statistical issues. Building on this study, we plan to develop a suite of evidence-based sustainable educational applications and games to support undergraduate students internationally in first-and second-year statistical modules. Our findings on students’ main statistical issues contribute to the cultivation of lasting statistical literacy among students. This research advances the sustainability agenda within statistical education.

The rapid expansion of China's A-share market, coupled with the burgeoning volume of financial research reports, presents a unique challenge to traditional stock price prediction methodologies. This study introduces FAST-SCAN, a novel framework designed to leverage natural language processing (NLP) and time series analysis for the efficient and accurate prediction of stock market trends. By integrating advanced sentiment analysis, primarily through the utilization of the RoBERTa model, with dynamic time series forecasting, FAST-SCAN aims to distill actionable insights from the vast corpus of financial research reports. This approach not only enhances the speed and efficiency of financial analysis but also addresses the time-sensitive nature of market-influencing factors, thereby providing a competitive edge in stock price prediction. The framework demonstrates a notable improvement in predictive performance, achieving a 20% annualized return and a 7.19% RankIC, marking a significant advancement over conventional statistical analysis methods. Through its innovative combination of NLP and predictive analytics, FAST-SCAN paves the way for a more informed and strategic approach to investment in the A-share market, emphasizing the importance of timely, data-driven decision-making in the financial industry.

As overeating, overweight and obesity remain public health concerns, it is crucial to design satiety-enhancing foods that suppress appetite and lower snack intake. Existing research identifies oro-sensory targets to promote satiation and satiety within the “satiety cascade” yet it remains unclear as to whether it is ‘chewing’ or ‘oral lubrication’ that might amplify satiation signals.Here we have combined techniques from experimental psychology, food material science and mechanical engineering to measure the role of chewing and lubrication using novel, model foods as preloads on subjective appetite and intake of a salty snack. Three mint flavoured hydrogels were engineered to vary in their texture (fracture stress) and lubrication (inverse of friction coefficient) properties, and a control group received a mint tea. Results showed that snack intake was suppressed by 32% after eating the low chewing/high lubricating preload as compared to the high chewing/low lubricating preload (p<0.05). No other significant effects were found for snack intake. Hunger ratings decreased from t1 to t3 (p<0.05), however differences between conditions were subtle and not significant. Thus, this proof-of-concept study demonstrates that manipulating oral lubrication is a promising new construct to reduce snack intake that merits future research in the oro-sensory satiety domain.

Given the cross-scale interactions of agricultural ecosystems, it is important to collect ecosystem service data at the multiple spatial scales they operate at. Mapping of ecosystem services helps to assess their spatial and temporal distribution and is a popular communication tool of their availability and value. For example, maps can be used to quantify distance between areas of available ecosystem services and their beneficiaries and how services fluctuate with changes in land use patterns over time, allowing identification of synergies and trade-offs. However, a lack of local context and too large a resolution can reduce the utility of these maps, whilst masking heterogeneities in access due to equity dynamics. This review identifies and summarizes eight main methods of ESS mapping found in the literature—remote sensing, biophysical modelling, agent based modelling, economic valuation, expert opinion, user preference, participatory mapping, and photo-elicitation. We consider what spatial scales these methods are utilized at and the transferability of data created by each method. The analysis concludes with a methodological framework for mapping ecosystem services, intended to help researchers identify appropriate methods for a multi-scale research design. The framework is exemplified with an overview of a research project in Ethiopia.

Sex differences are essential factors in disease etiology and manifestation in many diseases such as cardiovascular disease, cancer, and neurodegeneration (1). The biological influence of sex differences (including genomic, epigenetic, hormonal, immunological, and metabolic differences between males and females) and the lack of biomedical studies considering sex differences in their study design has led to several policies. For example, the National Institute of Health’s (NIH) sex as a biological variable (SABV) and Sex and Gender Equity in Research (SAGER)) policies to motivate researchers to consider sex differences (2). However, drug repurposing, a promising alternative to traditional drug discovery by identifying novel uses for FDA-approved drugs, lacks sex-aware methods that can improve the identification of drugs that have sex-specific responses (1,3–5). Sex-aware drug repurposing methods either select drug candidates that are more efficacious in one sex or deprioritize drug candidates based on if they are predicted to cause a sex-bias adverse event (SBAE), unintended therapeutic effects that are more likely to occur in one sex. Computational drug repurposing methods are encouraging approaches to develop for sex-aware drug repurposing because they can prioritize sex-specific drug candidates or SBAEs at lower cost and time than traditional drug discovery. Sex-aware methods currently exist for clinical, genomic, and transcriptomic information (3,6,7). They have not expanded to other data types, such as DNA variation, which has been beneficial in other drug repurposing methods that do not consider sex (8). Additionally, some sex-aware methods suffer from poorer performance because a disproportionate number of male and female samples are available to train computational methods (3). However, there is development potential for several different categories (i.e., data mining, ligand binding predictions, molecular associations, and networks). Low-dimensional representations of molecular association and network approaches are also especially promising candidates for future sex-aware drug repurposing methodologies because they reduce the multiple hypothesis testing burden and capture sex-specific variation better than the other methods (9,10). Here we review how sex influences drug response, the current state of drug repurposing including with respect to sex-bias drug response, and how model organism study design choices influence drug repurposing validation.

With an estimated 3 to 5 million human cases annually and the potential to infect domestic and wild animal populations, influenza viruses are one of the greatest health and economic burdens to our society [1] and pose an ongoing threat of large-scale pandemics. Despite our knowledge of many important aspects of influenza virus biology, there is still much to learn about how influenza viruses replicate in infected cells, for instance how they use entry receptors or exploit host cell trafficking pathways. These gaps in our knowledge are due, in part, to the difficulty of directly observing viruses in living cells. In recent years, advances in light microscopy, including super-resolution microscopy and single-molecule imaging, have enabled many viral replication steps to be visualised dynamically in living cells. In particular, the ability to track single virions and their components, in real time, now allows specific pathways to be interrogated providing new insights to various aspects of the virus-host cell interaction. In this review, we discuss how state-of-the-art imaging technologies, notably quantitative live-cell and super-resolution microscopy, are shedding new nanoscale and molecular insights into influenza virus replication and revealing new opportunities for developing antiviral strategies.

Obesity in Australia is rapidly rising, and is a major public health concern. Obesity increases risk of breast cancer and worse associated outcomes, yet breast screening participation rates in Australia are suboptimal and can be lower in higher risk, obese women. This study qualitatively explored barriers to breast screening participation in obese women in Australia. In-depth interviews (n=29), were conducted with obese women (BMI 30) and key health stakeholders. A disconnect between stakeholders’ and women’s perceptions was found. For women, low knowledge around a heightened need to screen existed, they reported limited desire to prioritize personal health needs, reluctance to screen due to poor body image and prior negative mammographic experiences due to issues with weight. Stakeholders perceived few issues in screening obese women beyond equipment limitations, and health and safety issues. Overall, weight was a taboo topic among our interviewees, indicating that a lack of discourse around this issue may be putting obese women at increased risk of breast cancer morbidity and mortality. Consideration of breast screening policy in obese women is warranted. Targeted health promotion on increased breast cancer risk in obese women is required as is a need to address body image issues and encourage screening participation.

Extensive experimental and theoretical research over the past several decades has culminated in the understanding of the mechanisms behind nanoparticle-mediated enhancements on the mechanical properties of hydrogels. This information is not only crucial to realizing applications that directly benefit from developing hydrogels with high mechanical strength, but also to guide the development of strategies to further enhance hydrogel properties by combining different approaches. In our study, we investigated the effect of combining two approaches – addition of nanoparticles and crosslinking two different polymers (to create double-network hydrogels) – on the mechanical properties of hydrogels. Our studies revealed that these approaches may be combined to synthesize hydrogel composites with enhanced properties; however, both polymers in the double-network hydrogel must strongly interact with the nanoparticles to fully benefit from the addition of nanoparticles. Moreover, the concentration of hydrogel monomers used for the preparation of the double-network hydrogels had a significant effect on the extent of nanoparticle-mediated enhancements; double-network hydrogel nanocomposites prepared using lower monomer concentrations showed higher enhancements in elastic moduli compared to those prepared using high monomer concentrations. Collectively, these results demonstrate that the hypotheses previously developed to understand the role of nanoparticles on the mechanical properties of hydrogel nanocomposites may be extended to double-network hydrogel systems and guide the development of next generation hydrogels with extraordinary mechanical properties through a combination of orthogonal approaches.

Stroke is one of the most prevalent cardiovascular diseases worldwide, both in high-income countries and in medium and low-medium income countries. The WHO report on non-communicable diseases (NCDs) indicates that the highest behavioral risk in NCDs is attributable to incorrect nutrition. The objective of our work is to present an overview of meta-analyses that have investigated the impact of different foods and / or drinks in relationship with the risk of stroke events (ischemic/ hemorrhagic). The papers to be included in the overview were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library and were selected according to PRIMA flow chart. Quality assessment were made according to AMSTAR scale. This overview shows that all primary studies came from countries with high income level. This evidence shows that many countries are not represented. Therefore, different lifestyles, ethnic groups, potentially harmful or virtuous eating habits are not reported. It is important to underline how the choose of foods may help reduce the risk of cardiovascular diseases and stroke in particular.

Introducing children to sustainable and healthy school meals can promote a long-term dietary shift to lower climate impact and improve population health. The aim of the OPTIMAT study was to optimize meals for minimum deviation from the current food supply while reducing greenhouse gases and ensuring nutritional adequacy without increasing cost. Optimized menus were tested in four primary schools in Sweden and effects on daily food consumption and waste evaluated. Pupils received their usual menu plan for three weeks and then the isocaloric optimized menu plan for another three weeks. Nutritional recommendations for a school lunch and a maximum of 500 grams of CO2eq/meal were applied as constraints during linear programming. Pulses, Cereals, Meat and Eggs increased, while Fats and Oils, Dairy, Sauces and Seasonings decreased. The amount of ruminant meat was reduced in favor of other meat products. The new menu was 28% lower in greenhouse gas emissions and slightly less costly than the original. No significant changes in mean food consumption or plate waste were found in interrupted time series analysis between the two periods. This pragmatic approach for combining linear optimization with meal planning could accelerate sustainable development of the meal sector in Sweden and abroad.

Depression and anxiety are the most common mental health disorders worldwide. Internet-Delivered Cogni-tive Behaviour Therapy (ICBT) can reduce barriers to care for broad cross sections of the population. How-ever, People of Diverse Ethnocultural Backgrounds (PDEGs) other than White/Caucasian underutilize mental health services and are underrepresented in clinical trials of psychological interventions. To address this research gap, we adapted an evidence-based ICBT program for PDEGs. The current pilot study explores the effectiveness, satisfaction, and engagement in the adapted ICBT by PDEGs (N=41) when benchmarked against a sample of PDEGs (N=134) drawn from a previous non-adapted version of the ICBT program. Inntent-to-treat analyses showed that the adapted ICBT program is effective in reducing anxiety and de-pression symptoms among PDEGs. Large within-group pre-to-post-treatment Cohen’s effect sizes of d = 1.23, 95% CI [0.68, 1.77] and d = 1.24, 95% CI [0.69, 1.79] were found for depression and anxiety, respectively. Further, 81.8% of the PDEGs who received the adapted ICBT program reported high overall satisfaction, 90.9 % reported increased confidence in managing symptoms, and 70.7% of participants completed the ma-jority of the psychoeducational lessons in the ICBT program. No statistically significant differences in clinical outcomes, engagement, and satisfaction were found between the pilot study and benchmark sample. Future directions for ICBT research with PDEGs are described.

Human papillomavirus (HPV) can potentially compromise both unassisted conception and success rates with assisted reproductive technology (ART). We aimed to evaluate the rates of HPV vaccination among women presenting for fertility care. This was a prospective study analyzing a self-reported intake form completed by all new patients presenting to a fertility clinic. The primary outcome was HPV vaccination status. Among the 523 new patients included in this study 172 (32.9%) were fully vaccinated, 237 (45.3%) were unvaccinated, and 95 (18.2%) patients didn’t respond. There was a significant age difference between fully vaccinated patients (33.1 years) compared to unvaccinated patients (37.4 years) p&lt;0.001 and a significant difference in gravidity between fully vaccinated patients (average 0.65) and unvaccinated patients (average 1.11) p=0.0005. No significant association was found between HPV vaccination status and history of abnormal Pap smears or relationship status (single vs. married). Less than half of patients presenting to our fertility center were vaccinated against HPV, despite being eligible to receive the vaccine. Younger patients with lower gravidity were more likely to be vaccinated against HPV than older patients with higher gravidity. Reproductive Endocrinologists have the opportunity to recommend HPV vaccination for eligible patients presenting for fertility care.

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for pre-sent and future pandemics of viral respiratory pathogens. We review the history of causality as-sessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierar-chy of evidence to integrate clinical, epidemiologic, molecular and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.

Automated charging technologies are becoming increasingly important in the electrification of heavy road freight transport, especially in combination with autonomous driving. This study provides a comprehensive analysis of automated charging technologies for electric heavy-duty vehicles (HDVs). It encompasses the entire spectrum of feasible technologies, including static and dynamic approaches, with each charging technology evaluated for its advantages, potentials, challenges, and technology readiness level (TRL). Static conductive charging methods such as charging robots, underbody-couplers or pantographs show good potential, with pantographs being the most mature option. These technologies are progressing towards higher TRLs, with a focus on standardization and adaptability. While static wireless charging is operational for some prototype solutions, it encounters challenges related to implementation and efficiency. Dynamic conductive charging through an overhead contact line or contact rails holds promise for high-traffic HDV routes with the overhead contact line being the most developed option. Dynamic wireless charging, although facing efficiency challenges, offers potential for seamless integration into roads and minimal wear and tear. Battery swapping is emerging as a practical solution to reduce downtime for charging, with varying levels of readiness across different implementations. To facilitate large-scale deployment further standardization efforts are required. The study emphasizes the necessity for continued research and development to enhance efficiency, decrease costs, and ensure seamless integration into existing infrastructures. Technologies that achieve this best will have the highest potential to significantly contribute to the creation of an efficiently automated and environmentally friendly transport sector.

Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres, on the other hand, are tandem repeats of 5’-TTAGGG-3’ sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity were decreased, and double strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.

Sorghum in Australia is grown in water-limited environments of varying extent, generating substantial genotype × environment interaction (GEI). Much of the yield variation and GEI results from variations in flowering time and tillering through their effects on canopy development. The confounding effects of flowering and tillering complicate the interpretation of breeding trials. In this study, we evaluated the impacts of both flowering time (DTF) and tillering capacity (FTN) on yield of 1741 unique test hybrids derived from three common female testers in 21 yield testing trials (48 tester/trial combinations) across the major sorghum production regions in Australia in three seasons. Contributions of DTF and FTN to genetic variation in grain yield were significant in 14 and 12 tester/trial combinations, respectively. The proportion of genetic variance in grain yield explained by DTF and FTN ranged from 0.2% to 61.0% and from 1.4% to 56.9%, respectively, depending on trials and genetic background of female testers. The relationship of DTF or FTN with grain yield of hybrids was frequently positive, but varied across the genetic background of testers. Accounting for the effects of DTF and FTN using linear models did not substantially increase the between trial genetic correlations for grain yield. The results suggested that other factors affecting canopy development dynamics and grain yield might contribute GEI and/or the linear approach to account for DTF and FTN on grain yield did not capture the complex non-linear interactions.

Based upon the latest molecular phylogenies of Gonyosoma sensu lato, which recovered five clades with robust support, we utilize morphological characters to demonstrate the distinctiveness of each clade, resulting in the resurrection of three genera (Gonyophis Boulenger, 1891 [1], Rhynchophis Mocquard, 1897 [2], and Rhadinophis Vogt, 1922 [3]) and proposal of a new genus and a new tribe. A synopsis of the group, with descriptions and diagnoses, is provided for the five genera and eight species in addition to distribution maps and illustrations of the head of each taxon. An artificial key to the species and genera in the new tribe is presented in addition to estimated origin times for each clade.

Despite the crucial role the COVID-19 vaccine played in curbing the pandemic, a significant portion of Black and African American individuals expressed hesitancy in being vaccinated. This review aimed to identify the determinants of COVID-19 vaccine hesitancy among Black and African American individuals in the USA. The literature search was conducted in December 2022 according to the PRISMA criteria focusing on empirical studies. Data extraction methods, critical appraisal, and secondary thematic analysis were conducted on both quantitative and qualitative studies. Sixteen quantitative studies identified key factors associated with vaccine hesitancy such as confidence in vaccine effectiveness, safety, and trust in the healthcare system. 14 qualitative studies revealed major themes of mistrust, fear, and information needs, including historical mistrust, concerns about the vaccine development process, and contemporary institutional mistrust. The synthesis of quantitative and qualitative findings derived from this review provides a nuanced understanding of determinants of vaccine hesitancy in Black and African American communities in the USA, offering a foundation for the development of evidence-based interventions. Mistrust in the healthcare system, fear, and informational gaps on vaccine safety and effectiveness have been identified as significant barriers to vaccination, demanding targeted interventions.

Hybridization is recognized as a notable driver of evolution and adaptation, which closely related species may exploit in the form incomplete reproductive barriers. Three closely related species of Ceratocystis (i.e., C. fimbriata, C. manginecans and C. eucalypticola) previously have been shown to hybridize by mating naturally occurring self-sterile strains with an unusual laboratory-generated sterile isolate type, which could have impacted conclusions regarding the prevalence of hybridization and inheritance of mitochondria. In the current study we investigated whether interspecific crosses between fertile isolates of these three species are possible, and if so how mitochondria are inherited by the progeny. For this purpose, a PCR-RFLP method and a mitochondrial DNA-specific PCR technique were custom-made and applied in a novel approach of typing complete ascospore drops collected from the fruiting bodies in each cross to distinguish between self-fertilizations and potential hybridization. These markers showed hybridization between C. fimbriata and C. eucalypticola and between C. fimbriata and C. manginecans, while no hybridization was detected in the crosses involving C. manginecans and C. eucalypticola. In both sets of hybrid progeny, we detected biparental inheritance of mitochondria. This study was the first to successfully produce hybrids from a cross involving self-fertile isolates of Ceratocystis, and also provided the first direct evidence of biparental mitochondrial inheritance in the Ceratocystidaceae. This work lays the foundation for further research focused on investigating the role of hybridization in the speciation of Ceratocystis species, and if mitochondrial conflict could have influenced the process.

Therapeutic vaccine studies should be designed to elicit durable, high magnitude, and efficacious T cell responses, all of which can be impacted by the choice of vaccination schedule. Here, we compare different prime-boost intervals (PBI) in a human papillomavirus (HPV) model using HPV16E6E7 Venezuelan equine encephalitis virus replicon particle (VRP) vaccination to address the optimal boosting schedule, quality of immune response, and overall in vivo efficacy. Six different vaccine regimens were tested with each group receiving booster vaccinations at different time intervals. Analysis of T-cell responses demonstrated a significant HPV16 E7 specific CD8+T cell response with minimally a one-week PBI between antigen re-exposure. Significant E7-specific in vivo cytotoxicity was also observed with longer PBIs. Additionally, longer PBIs led to an enhanced memory recall response to tumor challenge, which correlated with differential expansion of T cell memory subsets. Our findings imply that when using alphavirus vector platforms as a vaccination strategy, a one-week PBI is sufficient to induce high magnitude effector T cells with potent anti-tumor activity. However, longer PBIs lead to enhanced long-term protective anti-tumor immunity. These findings have implications for therapeutic vaccine clinical trials in which shorter intervals of prime-boost regimens may lead to suboptimal durable immune responses.

Taking into account the increase in the emission of greenhouse gases produced by ships, during navigation and maneuvering in the port, a direct consequence of the increase in maritime traffic, the international community has developed a broad set of regulations to limit such emissions. The installation in commercial ports of automatic mooring systems by means of vacuum suction cups (AMS), thus reducing considerably the time required to carry out the mooring and unmooring maneuvers of ships, is a factor that is considerably influencing the decrease in Emissions of polluting gases in commercial ports with high traffic. The objective of the present work is to verify the influence of the use of the AMS on the emissions of polluting gases produced in the facilities destined to the traffic of container ships. It examines the CO2 emissions of container ships that call in the only three container ports equipped with AMS: Salalah (Oman), Beirut (Lebanon) and Ngqura (South Africa). Between them, these three ports supported the transit of 6 million TEUS in 2017. The calculation of emissions is made taking into account the time saved when performing the mooring maneuvers using the new AMS system compared with when it is not used. To do this, two different calculation methods are used: EPA and ENTEC to then compare the results of the two and thus obtain the reduction in emissions per TEU in these terminals during the mooring maneuvers. The paper concludes with a discussion on the values of the reductions in emissions obtained and the advantages of the installation of AMS in commercial ports located near population centres.

This study aims to assess the feasibility of delineating and identifying mineral ores from hyperspectral images of tin-tungsten mine excavation faces using machine-learning classification. We compiled a set of hand samples of minerals of interest from a tin-tungsten mine and analyzed two types of hyperspectral images: 1) images acquired with a laboratory set-up under close-to-optimal conditions; and 2) scan of a simulated mine face using a field set-up, under conditions closer to those in the gallery. We have analyzed the following minerals: cassiterite (tin ore), wolframite (tungsten ore), chalcopyrite, malachite, muscovite, and quartz. Classification (Linear Discriminant Analysis, Singular Vector Machines and Random Forest) of laboratory spectra had a very high overall accuracy rate (98%), slightly lower if the 450 – 950 nm and 950 – 1780 nm ranges are considered independently, and much lower (74.5%) for simulated conventional RGB imagery. Classification accuracy for the simulation was lower than in the laboratory but still high (85%), likely a consequence of the lower spatial resolution. All three classification methods performed similarly in this case, with Random Forest producing results of slightly higher accuracy. The user’s accuracy for wolframite was 85%, but cassiterite was often confused with wolframite (user’s accuracy: 70%). A lumped ore category achieved 94.9% user’s accuracy. Our study confirms the suitability of hyperspectral imaging to record the spatial distribution of ore mineralization in progressing tungsten-tin mine faces.

The methyltransferase, KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis we have performed a microarray study in a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and Gene Ontology analysis revealed apoptosis and DNA damage signaling are up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase dependent manner to modulate both histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilized as a biomarker for effective therapeutic targeting.

Buruli ulcer is a chronic ulcerative disease of skin and subcutaneous tissues caused by infection with Mycobacterium ulcerans. Although Australian possums are known to be susceptible to Buruli ulcer, many aspects of the disease in possums, including welfare impacts, remain largely unreported. Severe clinical Buruli ulcer was identified in four common ringtail possums (Pseudocheirus peregrinus) from Melbourne, Victoria. All four possums were euthanised due to welfare concerns and poor prognosis, based on the presence of deep ulcerative lesions to paws, some of which exposed carpal or tarsal bones. These lesions were considered likely to cause partial or complete loss of limb function, which would severely affect the welfare and survival of these wild arboreal animals. Histologically, there was severe ulcerative necrotising pyogranulomatous dermatitis, panniculitis, and myositis, with intralesional acid-fast bacteria. M. ulcerans was detected by real-time PCR in all swabs and biological tissues collected from all four cases. Buruli ulcer may be an important and under-recognised cause of poor possum welfare in endemic areas. In addition to severe cutaneous lesions, infection extends to underlying bones and joints, and the systemic distribution of M. ulcerans throughout all major tissues and internal organs, as observed in these four cases, may further impact the health and fitness of infected possums. Further research is needed to investigate the epidemiology, pathogenesis and impacts of Buruli ulcer in possums, and to inform the design of interventions that may protect the health and welfare of possums and other affected animal species.

The aim of this study was to assess the effect of added cultures of probiotic lactic acid bacteria on physicochemical, textural, and sensory characteristics of fresh cheese as well as their viability. Probiotic strains Lactobacillus acidophilus and L. rhamnosus were evaluated at two inoculation times (before the renneting and salting processes) following a factorial treatment arrangement. The bacterial count (log CFU g-1), acidity determination (% lactic acid), pH and percentage of syneresis were evaluated at 0, 1, 7, 14 and 21 days of refrigerated storage (4–5 °C). The texture profile analysis and an extended preference test were carried out at 21 days of storage. At the end of storage, fresh cheeses containing L. rhamnosus, added prior to the renneting process, had similar acidity values (0.18% lactic acid), pH (5.36) and percentage of syneresis (4.71%) compared to those for the cheeses without probiotics or control. Excluding adhesiveness, no differences were observed in texture profile parameters among the assessed cheeses. The fresh cheese supplemented with L. rhamnosus before the renneting process had a microorganism count greater than 6 logarithmic cycle/g, and the highest preference among treatments. The results from this study suggest that fresh cheese can be an excellent matrix for probiotic microorganisms, in particular L. rhamnosus.

Herdsmen use different techniques, as per varying geographies and cultures, to keep the cohesion within herds and avoid animals getting lost or predated. However, there is no study on the social behaviour of yaks and on herdsmen management practices. Therefore, this ethology study was initiated by ethnographic inquiries. In Manang, the success of the shepherd is dictated by his personal attribute of “Khula man” or open-heartedness. This attribute refers to good intentions and emotions such as empathy that allows the shepherd to focus more on others than on ownself. This cultural method of assessing the skills required to become a successful and knowledgable shepherd guided us to study the effect of cultural values on the herd’s social behavior. We collected data from two herds living at the same settlement (Yak kharka, 4,100 m altitude, Nepal) by equipping them with loggers. One of the herdsman used the tether rope while other did not. Moreover, the Thaku herd had a more proactive shepherd than the Phurba one. In each herd, 17 animals were equipped with one actigraph wgt3x-BT to measure activity using accelerometer and spatial associations using proximity recorder. One of the herds was equipped with GPS (N=11) as well. Using GPS locations and activity, we showed that the two herds were cohesive and synchronised their activities but the herd with the tether rope was more cohesive. The shepherds also have personal knowledge of the social relationships of their herds and use these relationships to keep the group cohesive and to well manage cattle.