Pathologic angiogenesis is responsible for much of the vision loss that stems from several chorioretinal vascular diseases including neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Because vascular endothelial growth factor (VEGF) serves as a pivotal angiogenic molecule, it has emerged as the primary target for therapeutic drugs. Current anti-VEGF therapy is dominated by bevacizumab, ranibizumab, and aflibercept, all of which have been available for more than a decade, but new drugs, both biosimilars (Byooviz and Cimerli) and drugs whose primary aim is to decrease treatment burden (brolucizumab, faricimab, and the ranibizumab port delivery system), have been approved. Recent failures (conbercept, abicipar, and KSI-301) emphasize the complexity of drug development and the difficulties faced by innovators. Most therapies under development, including tyrosine kinase inhibitors and gene therapy, include VEGF-A blockade as their primary function and aim to extend durability rather than increase peak efficacy. But even as many new drugs look to extend durability, cost containment with mandated use of biosimilars serves to balance the therapeutic landscape.

Heat-stressed lactating dairy cattle exhibit unique metabolic symptoms; many of which are undoubtedly involved in heat-induced subfertility. Because of its known systemic effects, we hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of insulin and progesterone during heat stress. Multiparous lactating Holstein cows (n=6) were studied during four experimental periods: 1) thermoneutral (TN; d 1-5), 2) TN + hyperinsulinemic-hypoglycemic clamp (d 6-10), 3) heat stress (HS; d 16-20), and 4) HS + euglycemic clamp (d 21-25). Blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Analysis of GABA concentrations from all four treatment periods yielded no differences. In direct comparison to TN concentrations, plasma GABA tended to be decreased during HS (16.57±2.64 vs 13.87±2.28 ng/ml, respectively, P = 0.06). Both milk production and plasma insulin were moderately correlated with plasma GABA (r=0.35, P<0.01; r = -0.32, P<0.01). Plasma progesterone was correlated with plasma GABA concentrations during TN but not HS. These results are the first to indicate that peripheral GABA could be involved in regulating aspects of production and reproduction during heat stress. More research is needed to determine its precise role(s).

Field studies were conducted in 2016, 2017, and 2020 in south-central and the Coastal Bend regions of Texas to determine the effects of various biostimulants and soil additives on corn growth and yield. In south-central Texas, the use of pop-up fertilizer (9-30-0 + Zn) either alone or in combination with either 2% N, bifenthrin, or bifenthrin + pyraclostrobin resulted in the greatest corn vigor but a yield response was only noted with pop-up fertilizer alone at 28062 or 46771 ml ha-1 in one year. In the Coastal Bend region, leaf tissue analysis showed that only Fe was affected with the use of any soil additive. Bacillus licheniformis + bacillus megaterium + bacillus pumilus increased Fe leaf tissue content by 20% over the untreated check. Radicoat seed coating at 438 ml ha-1 reduced corn plant stand by 10% and Pseudomonas brassicaceanum reduced corn height when compared with the untreated check; however, no differences in test weight or yield from the untreated check were noted with any soil additive. Little if any impacts of the use of biostimulants or soil amendments were seen in these studies.

Objectives Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design Population-based retrospective cohort study. Setting US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions None. Main Outcome Measures A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post-COVID-19 vaccines with that of post-Influenza vaccines. Results COVID-19 vaccines, when compared to the Influenza vaccines, are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormalities, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmias, fetal cardiac arrest, fetal vascular malperfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, preeclampsia, premature delivery, preterm premature rupture of membrane, fetal death/stillbirth, and premature baby death (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions Pregnancy complications and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.

This review seeks to explain four features of viral respiratory illnesses that have perplexed many generations of microbiologists: (1) the seasonal occurrence of viral respiratory illness; (2) the occurrence of respiratory illness year-round in the Tropics; (3) the rapid response of illness to temperature drops in temperate regions; (4) the explosive arrival and rapid termination of epidemics caused by influenza and other respiratory viruses. I discuss the inadequacy of the popular explanations of seasonality, and propose a simple hypothesis, called Temperature Dependent Viral Tropism (TD-VT), that is compatible with the above and other features of respiratory illness. TD-VT notes that viruses can often transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining the mobility of their hosts) and suggests that most endemic respiratory viruses accomplish this by developing thermal sensitivity, in the sense that they normally replicate rapidly only at temperatures below normal body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. I review biochemical and tissue-culture studies that found that “wild” respiratory viruses often show natural thermal sensitivity within a range that supports organ-specific tropism within the human body, and I discuss the evident tendency for viral strains to adapt their thermal sensitivity to their local climate and season. I also explore the possible misinterpretation of early experiments where volunteers were inoculated nasally with viral samples and then chilled. Next, I discuss the practical implications of the TD-VT hypothesis for preventing and treating respiratory illness. Finally, I note that the hypothesis is very testable and make suggestions for the most important experiments to increase our understanding of the seasonality and pathogenicity of viral respiratory illness.

Various dietary supplements have been shown to extend the life span of Drosophila melanogaster, including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of the target of rapamycin (TOR) and/or phosphatidylinositol 3-kinase (PI3K). Using a single, comparatively long-lived y w test strain, screening was performed in male flies supplemented either throughout adulthood or in a few cases beginning in middle or late adult life, with concentrations spanning 4-6 orders of magnitude in most cases. Supplementation with PP242 and deferiprone, an iron chelator, beginning in late adult life had no positive effect on life span. Lifelong supplementation with Ku-0063794, LY294002, PX-866-17OH, Torin2 and WYE-28 had no effect at any dose. Rapamycin, spermidine and wortmannin all had significant life-shortening effects at the highest doses tested. AZD8055, PI-103 hydrochloride and WYE-132 yielded slight beneficial effects at 1-2 doses, but only 100 nM AZD8055 was confirmed to have a minor (1.3%) effect in a replicate experiment, which was encompassed by other control groups within the same study. These compounds had no effect on fly fecundity (egg-laying) or fertility (development of progeny to adulthood), but equivalent doses of rapamycin abolished fertility. The solvent DMSO had no significant effect on life span at the concentrations used to solubilize most compounds in the fly medium, but it drastically curtailed both survival and fertility at higher concentrations. 2-hydroxypropyl-β-cyclodextrin also failed to extend the life span when provided throughout adulthood or beginning in mid-adult life. Collectively, the results suggest that inhibition of the TOR/PI3K pathway and autophagy through dietary intervention is not a straightforward anti-aging strategy in Drosophila, and that further extension of life is difficult in comparatively long-lived flies.

In the last years, new findings and new methods (stable isotopes of oxygen, zinc and nitrogen, 2D and 3D modelling, geometric morphometric analyses of the teeth) have enhanced our knowledge of the Neogene shark fauna and its palaeobiology. Several papers deal with the large Otodus (Megselachus) species, including the construction of a 3D model as well as insights into lifestyle and diet. In addition, skeletal remains of Carcharias gustrowensis, Carcharodon hastalis, Keasius parvus and a natural tooth set of Carcharodon hubbelli have been described in the last 13 years, and the dentition of the Neogene species Carcharoides catticus, Megachasma applegatei and Parotodus benedenii have been reconstructed. Stable isotope analyses of the teeth from the Neogene species of Araloselachus, Carcharias, Carcharodon, Galeocerdo, Hemipristris, and Mitsukurina have given insights into the trophic position of these genera during the Neogene, and shark teeth preserved near skeletal remains of prey animals (mammals) and shark bite traces on these remains provide direct evidence of trophic interactions. Tooth shape, fossil locality and palaeoenvironment have been used to better understand the taxa Carcharhinus dicelmai, Megalolamna paradoxodon, Pachyscyllium dachiardii and P. distans. Among extant species, Galeorhinus galeus can be traced back to the Eocene. The following taxa can be traced back to the Oligocene: ?Alopias superciliosus, and Rhincodon typus. Species already present in the Miocene include: Alopias vulpinus, Carcharhinus amblyrhynchoides, C. amblyrhynchos, C. albimarginatus, C. amboinensis, C. brachyurus, C. brevipinna, C. falciformis, C. glaucus, C. leucas, C. limbatus, C. longimanus, C. macloti, C. obscurus, C. perezi, C. sealei, ?Carcharodon carcharias, Centrophorus granulosus, Cetorhinus maximus, Dalatias licha, Deania calcea, Galeocerdo cuvier, , Glyphis glyphis, Heptranchias perlo, Isurus paucus, Lamna nasus, Negaprion brevirostris, Odontaspis ferox, Pseudocarcharias kamoharai, Sphyrna media, S. mokarran. First appearing in the Pliocene are: Scymnodon ringens, Somniosus rostratus, Zameus squamulosus. For some extant species (Carcharias taurus, Hexanchus griseus, Isurus oxyrinchus, Notorynchus cepedianus, Sphyrna zygaena) it is not clear if the assigned Neogene teeth represent the same species. Applying these new methods to more fossil shark taxa, a detailed search for shark fossils, as well as better knowledge of the dentition of extant species (especially those with minute-sized teeth) will further enhance knowledge of the evolution and palaeobiology of sharks.

Surface temperature influences human health directly and alters the biodiversity and productivity of the environment. While previous research has identified that the composition of urban landscapes influences the physical properties of the environment such as surface temperature, a generalizable and flexible framework is needed that can be used to compare cities across time and space. This study employs the Structure of Urban Landscapes (STURLA) classification combined with remote sensing of New York City’s (NYC) surface temperature. These are then linked using machine learning and statistical modeling to identify how greenspace and the built environment influence urban surface temperature. It was observed that areas with urban units composed of largely the built environment hosted the hottest temperatures while those with vegetation and water were coolest. Likewise, this is reinforced by borough-level spatial differences in both urban structure and heat. Comparison of these relationships over the period between2008 and 2017 identified changes in surface temperature that are likely due to the changes in prevalence in water, lowrise buildings, and pavement across the city. This research reinforces how human alteration of the environment changes ecosystem function and offers units of analysis that can be used for research and urban planning.

Natural cycles underpin the very stuff of life. In this commentary we consider unnatural cycles: that is, anthropogenic activities which have a circularity, but whose nature is to have a detrimental effect on human health, exacerbating existing problems. Natural cycles have feedback loops, some of which have recently come to light, with an understanding that everything is connected in some way. In health, feedback loops are imperative in homeostatic mechanisms. However, in the unnatural cycle the feedback loops serve to reinforce (and in some cases amplify) negative problems. We offer a commentary on an unnatural cycle moving from air quality to lung function and back to air quality; we call this the lung disease unnatural cycle. We suggest where links occur, and where wider consideration of interactions between various disciplines can lead to breaking this unnatural (or vicious) cycle, changing it to a healthy cycle where individual health can be improved, along with better global scale outcomes. We suggest that many activities within this unnatural cycle occur within silos. However, the improved cycle incorporates joint activities at geological, health, and financial levels, to the mutual benefit of all, breaking the unnatural cycle, and improving health, life and financial costs.

This review seeks to explain four features of viral respiratory illnesses that have perplexed generations of virologists: (1) the seasonal timing of respiratory illness; (2) the common viruses causing respiratory illness worldwide, including year-round disease in the Tropics; (3) the rapid response of outbreaks to weather, specifically temperature; (4) the rapid arrival and termination of epidemics caused by influenza and other viruses. The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called Temperature Dependent Viral Tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ-specific viral tropism within the human body, whereby they replicate most rapidly at temperatures below body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. Biochemical and tissue-culture studies show that “wild” respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the existence of respiratory illness in the Tropics year-round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. The TDVT hypothesis has important practical implications for preventing and treating respiratory illness including Covid-19. TVDT is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.

We introduce a new class of Vertex Operator Algebras Y+ and their duals, which generalize the standard W-algebras WN of type sl(N). These algebras can be defined in terms of junctions of boundary conditions and interfaces in the GL-twisted N = 4 Super Yang Mills gauge theory. The aim of these technical calculations is to find the relation of these ortho-symplectic Y-algebras to truncations of even W\infinity.

The challenge of campus design, like other aspects of contemporary environmental design, reveals a serious problem in education and practice. The foundational design theories of a century ago have been exposed as an obsolete way of thinking about cities, human nature, biological nature, and even the nature of mathematical and physical structures. Yet in practice, these discredited models persist, obscured by new theoretical language and extravagant “neoplastic” forms, but embodying persistent though untested ideologies and driven by systems inertia. This paper considers the campus design typology (including business campuses, commercial districts, hospitals, and schools) as a design paradigm for pedestrian public space with implications for human flourishing and well-being. We propose a specific human-oriented design method to encourage the well-being of occupants and improve the outcomes for creative development, education, and health.

Background: Stress among prison inmates is a neglected psychological health issues, but this phenomenon seems worse in Ghana’s prisons. This study examined the stress levels, predictors and management strategies utilized among inmates at Ankaful Prison Complex. Method: This survey sampled 1,160 inmates using the census approach at the Ankaful Prison Complex with a self-developed questionnaire for the data collection. Frequency counts, one-way ANOVA, and multiple regression analysis were applied to the data. Results: The findings indicate that more than half of the inmates were moderately or highly stressed. Specifically, inmates at the Maximum-Security Prison were the most stressed, followed by Annex Prison, Communicable Disease Prison, and the least, Main Camp Prison inmates. Inmate engagement in exercises, sporting activities, visit and chat with colleagues, and family connectedness outside the prison were stress management strategies. Inmates’ self-reported stress levels were influenced by the prison of custody and state of depression. Conclusion: The moderate to high stress levels identified among inmates of Ankaful Prison Complex are influenced by person-environment factors. Management of Ankaful Prisons Complex is encouraged to initiate health screening services for inmates on common mental health challenges like stress and promote functional stress reduction interventions to improve prisoners’ mental health and overall wellbeing

Aging is a major risk factor for Alzheimer's disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems® to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood-brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models.

Osteoarthritis is a painful, disabling condition which is increasing in prevalence as a result of an ageing population. With no recognised disease limiting therapeutics, arthroplasty of the hip and knee is the most common and effective treatment for lower limb osteoarthritis, however lower limb arthroplasty has a finite life-span and a proportion of patients will require revision arthroplasty. With increasing life expectancy and an increasing proportion of younger (<65 years) patients undergoing arthroplasty, the demand for revision arthroplasty after implant failure is also set to increase. Statins are cholesterol modulating drugs widely used for cardiovascular risk reduction which have been noted to have pleiotropic effects including potentially influencing arthroplasty survival. In vitro studies have demonstrated pleiotropic effects in human bone cells, including enhancement of osteoblastogenesis following simvastatin exposure, and in vivo studies have demonstrated that intraperitoneal simvastatin can increase peri-implant bone growth in rats following titanium tibial implant insertion. There is evidence also that statins may also influence osseointegration, enhancing bone growth at the bone-implant interface, subsequently improving the functional survival of implants. Data from the Danish Hip Arthroplasty Registry and Clinical Practice Research Datalink in the UK suggest a reduction in the risk of lower limb revision arthroplasty in statin ever-users vs never users, and a time dependent effect of statin administration on reduction in risk of revision. In this article we review the clinical and scientific evidence linking statins and risk of revision arthroplasty.

The Ni-Co-Cr-W-Mo system is critical for the design of nickel-based super-alloys. This system stabilizes different topologically close packed (TCP) phases in many of the commercially super-alloys with high W and Mo contents. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermodynamic calculations are applied to investigate the thermodynamics of the precipitates in two different W content Ni-Co-Cr-W-Mo super-alloys. Computational thermodynamics verified experimental observation of the f u phase formation as a function of temperature and alloy chemistry, but the kinetics for the precipitation of M6C phase do not agree with the experimental findings. The major precipitates of alloy 1 at temperatures 700 and 750 °C during long time exposure are M23C6, γ′ phase, and MC, and alloy 2 are M23C6, γ′ phase, MC, M6C and u phase. The W addition is found to promote the precipitation of M6C and u phase during exposure. The M6C has higher W and lower Ni content than that of u phase, meanwhile, M6C is an unstable phase would transform into M12C after 5000 h exposure at 750 °C. A great quantity of needle-like u phases precipitated after exposure at 750 °C for 5000h, which have no effect on the impact property of alloy 2.

A chiral sodium glicerophosphate is successfully exploited as catalyst in Michael addition of methyl malonate to a number of chalcones. The reactions furnished the target adducts in satisfactory yields and good enantiomeric excesses. A tentative of computational study is presented aiming to understand the reaction mechanism.

Enteropathogens, namely Salmonella and Campylobacter, are a concern in global public health and have been attributed in numerous risk assessments to a poultry source. During the last decade a large body of research addressing this problem has been published. The literature reviewed contains review articles on certain aspects of poultry production chain, however in the past decade there hasn’t been a review on the through production chain, farm to fork, production of poultry. This review, a pool of 514 articles were selected for relevance via a systematic screening process (from >7500 original search articles). These studies identified a diversity of management and intervention strategies for the elimination or reduction of enteropathogens in poultry production. Many studies were laboratory or limited field trials with implementation in true commercial operations being problematic. Entities considering using commercial anti-enteropathogen products and interventions are advised to perform an internal validation and fit for purpose trial as Salmonella and Campylobacter serovars and biovars may have regional diversity. Future research should focus on non-chemical application within the processing plant and how synergistic through chain intervention may contribute to reducing the overall carcass burden of enteropathogen, coupled with increased consumer education on safe handling and cooking of poultry.

There is increasing interdisciplinary interest in phytoplankton community dynamics as the growing environmental problems of water quality (particularly eutrophication) and climate change demand attention. This has led to a pressing need for improved biophysical and causal understanding of Phytoplankton Functional Type (PFT) optical signals, in order that satellite radiometry may be used to detect ecologically relevant phytoplankton assemblage changes. This understanding can best be achieved with biophysically and biogeochemically consistent phytoplankton Inherent Optical Property (IOP) models, as it is only via modelling that phytoplankton assemblage characteristics can be examined systematically in relation to the bulk optical waterleaving signal. The Equivalent Algal Populations (EAP) model is used here to investigate the source and magnitude of size- and pigment- driven PFT signals in the water-leaving reflectance, as well as the potential to detect these using satellite radiometry. This model places emphasis on explicit biophysical modelling of the phytoplankton population as a holistic determinant of IOPs, and a distinctive attribute is its comprehensive handling of the spectral and angular character of phytoplankton scattering. Selected case studies and sensitivity analyses reveal that phytoplankton spectral scattering is the primary driver of the PFT-related signal. Key findings are that the backscattering-driven signal in the 520 to 600 nm region is the critical PFT identifier at marginal biomass, and that while PFT information does appear at blue and red wavelengths, it is compromised by biomass/gelbstoff ambiguity in the blue and low signal in the red, due primarily to absorption by water. These findings are hoped to provide considerable insight into the next generation of PFT algorithms.

Optical power splitters play a crucial role as the fundamental building blocks for many integrated optical devices. They should have low losses, broad bandwidth, and a high tolerance to fabrication errors. Adiabatic optical power splitters inherently possess these qualities while being compatible with foundry processes well-suited for mass-production. The long device lengths of adiabatic power splitters, however, are a limiting factor to achieve compact device sizes, which must be reduced. Here, we use a polynomial taper profile optimization algorithm to design 1×2 and 2×2 adiabatic power splitters with significantly shorter lengths than their adiabatic counterparts. The best performing 1×2 and 2×2 power splitters have 20 μm and 16 μm coupling lengths, respectively. Our designs have minimum feature sizes ranging from 140 nm to 200 nm, and our measurements averaged across 9 different chips show excellent consistency in performance for devices with 180 nm and 200 nm minimum features. Both the 1×2 and 2×2 adiabatic optical power splitters have excess losses less than 0.7 dB over a 100 nm bandwidth, with a standard deviation lower than 0.3 dB. Furthermore, our measurements show greater than 20 dB extinction ratios over 130 nm bandwidth. We also demonstrate the design of 1×2 power splitters with arbitrary splitting ratios, where splitting ratios ranging from 50:50 to 94:6 were achieved with standard deviations between 2% and 6%.

Urban trees are often more sun- and wind-exposed than their forest-grown counterparts. These environmental differences can impact how many species grow – impacting trunk taper, crown spread, branch architecture, and other aspects of tree form. Given these differences, windthrow models derived from traditional forest production data sources may not be appropriate for urban forest management. Additionally, visual abnormalities historically labeled as “defects” in timber production may not have a significant impact on tree failure potential. In this study, we look at urban tree failures associated with Hurricane Irma in Tampa, Florida, USA. We used spatial analysis to determine if patterns of failure existed among our inventoried trees. We also looked at risk assessment data to determine which visual defects were the most common and the most likely to be associated with branch or whole-tree failure. Results indicate that there was no spatial pattern associated with the observed tree failures – trees failed or withstood the storm as individuals. While some defects like decay and dead wood were associated with increased tree failure, other defects like weak branch unions and poor branch architecture were less problematic.

This work presents the results regarding the synthesis of tungsten nanoparticles (W NPs) by magnetron sputtering combined with gas aggregation (MSGA) when H2 mixed with Ar is used as working gas, the amount of H2 being increased up to 82%. The results show that up to 40% H2 in discharge the synthesis rate increases over 60 times, rapidly decreasing for over 50% H2 in discharge. The W dust is still produced in H2 dominated discharge (82%), the deposition rate being small but not negligible (20 mg/hour). The obtained WNPs are isolated, with the diameter decreasing from 50 nm to 15 nm when the amount of H2 in discharge is smaller than 41%. Over this value, the particles tend to agglomerate, forming structures similar to film-like deposits. Also, the diameter of the deposited spots on substrates is dependent on the H2 content in discharge. This allows the efficient coating of substrates with dimensions up to 26 mm by translating them in front of the MSGA cluster source exit aperture. Supplementary, for 41% H2 in discharge, the influence of synthetic air leaks (0-5%) in discharge was investigated. The deposition rate decreases rapidly (ceasing for around 4% air in discharge) and the obtained nanoparticles tend to agglomerate (at 2% air content, the dust deposit has the aspect of a near continuous film). Chemical composition investigations show a pronounced tendency of oxidation, nitridation and oxynitride formation in the presence of air leaks.

Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote proinflammatory pathways also contributing to procoagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing molecular and clinical effects of inflammatory processes on the micro- and microvas-culature with a focus on peripheral artery disease.

In an outstanding article published in 2008, Suzuki obtained a nice generalization of the Banach contraction principle from which derived a characterization of metric completeness. Although Suzuki’s theorem has been successfully generalized and extended in several directions and contexts, we here show by means of a simple example that the problem of achieving, in an obvious way, its full extension to the framework of w-distances does not have an emphatic response. Motivated by this fact we introduce the concept of presymmetric w-distance on metric spaces, we give some properties and examples of this new structure and show that it provides a reasonable setting to obtain a real and hardly forced w-distance generalization of Suzuki’s theorem. This is realized in our main result, which is a fixed point theorem that involves presymmetric w-distances and certain contractions of Suzuki-type. We also discuss the relationship between our main result and the well-known w-distance full generalization of the Banach contraction principle, due to Suzuki and Takahashi. Connected to this approach we prove another fixed point result that compare with our main result through some examples. Finally, we state a characterization of metric completeness by using our fixed point results.

Here we present an overview of speleothem δ18O records from South America, which mostly are available in the Speleothem Isotopes Synthesis and Analysis (SISAL_v1) database. South American tropical and subtropical δ18O time series are primarily interpreted as being driven by the amount effect and, consequently show the past history of the convection intensity of convergence zones such as the Intertropical Convergence Zone and the South America Monsoon System. We investigate past hydroclimate scenarios in South America related to the South American Monsoon System in three different time scales: Late Pleistocene, Holocene and the last two millennia. The precession driven insolation is the main driver of convective variability over the continent during the last 250 kyrs, including the Holocene period. However a dipole is observed between the west and east portions of the continent. Records located in the central region of Brazil appear to be weakly affected by insolation driven variability and more susceptible to the South Atlantic Convergence Zone. Cold episodic events in Northern Hemisphere increase the activity of the South American Monsoon System on all time scales, in turn increasing rainfall amounts in South America, as was documented during Heinrich events in the late Pleistocene and Bond events in the Holocene, as well as during the Little Ice Age.

AgW materials exhibit excellent properties and are widely used as contact materials in low- and medium-voltage switches. In this study, a pre-sintering and infiltration method was employed to pre-sinter W powder with Cu, Ni, and (Cu+Ni) addition in the low temperature range of 950–1050 °C. The low-temperature sintering behaviours of W skeletons with different additives were investigated. Subsequently, AgW70, AgW75, AgW80, and AgW85 materials were prepared through infiltration at 1050 °C. The microstructure morphology and physical properties of high-W contact materials were investigated using a metallographic microscope and scanning electron microscope. The mechanism of low-temperature sintering-infiltration of high-W contact materials was elucidated. The results indicated that pure W and 1% Cu-added W skeletons experience minimal linear shrinkage within the temperature range of 950–1050 °C. The linear shrinkage curves of W skeletons with different additives coincided under the conditions of 950–1000 °C/90 min. At 1050 °C, after sintering for 150 min, the particle boundaries in the W skeleton were fully spheroidised, with a dihedral angle of 120°. At 1050 °C and after 150 min of infiltration, cross-sectional micrographs of the AgW material revealed the presence of irregular Ni layers, where Ni spatially enveloped/encapsulated Ag. With an increase in the W content, the electrical conductivity and relative density of AgW(70–85) materials decreased, whereas the hardness of the materials increased.

In this study, the team employed full-scale crash tests to investigate the impact of post-densification technology on the safety performance of separated central median W-beam barriers under low compaction conditions. By precisely simulating the design and construction environment of the central median, the study comprehensively evaluated the barrier's containment, redirection, buffering, and anti-intrusion performances, as well as the deformation of both the barrier and vehicles under various collision scenarios. The results indicate that under low compaction soil conditions, the A-level separated central median barriers reinforced with post-densification technology effectively meet the specified protection requirements. By comparing the influence of soil strength variations on barrier performance under simulated rainfall conditions, it was confirmed that enhancing soil compaction significantly improves soil stability, effectively increases the overall strength and stability of the barriers, reduces deformation, and significantly enhances safety performance. This study not only validates the effectiveness of the reinforcement scheme but also provides new perspectives for the scientific research of safety barriers and offers crucial technical support for the optimal design of road safety protection facilities.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

The cost to train a basic qualified U.S. Navy fighter aircraft pilot is nearly $10M. The training includes primary, intermediate, and advanced stages, with the advanced stage involving extensive flight training and being very expensive as a result. Despite the screening tests in place and early-stage attrition taking place, 4.5% of aviators undergo attrition in this most expensive stage. Key reasons for aviator attrition include poor flight scores, voluntary withdrawals, and medical causes. Reduction in late-stage attrition offers several financial and operational benefits to the U.S. Navy. To that end, this research leverages feature extraction and machine-learning techniques on the very sparse flight test grades of student aviators to identify those with a high risk of attrition early in training. Using about 10 years of historical U.S. Navy pilot training data, trained models accurately predicted 50% of attrition with a 4% false positive rate. Such models could help the U.S. Navy save nearly $20M a year in attrition costs. In addition, machine-learning models were trained that can recommend a suitable training aircraft type for each student aviator. These capabilities could help better answer the need for pilots and reduce the time and cost to train them.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

Understanding the relationships between land cover/urban structure patterns and air pollutants is key to sustainable urban planning and development. In this study, we employ a mobile monitoring method to collect PM_2.5 and BC data in the city of Philadelphia, PA during the summer of 2019 and apply the Structure of Urban Landscapes (STURLA) methodology to examine relationships between urban structure and atmospheric pollution. We find that, while PM_2.5 and BC vary by STURLA class, many of the differences in pollutant concentrations between classes are not significant. However, we also find that the proportions in which STURLA components are present throughout the urban landscape can be used to predict urban air pollution. Among frequently sampled STURLA classes, gpl hosted the highest PM_2.5 concentrations on average (16.60 _± 4.29 µg/m³), while tgbwp hosted the highest BC concentrations (2.31 _± 1.94 µg/m³). Furthermore, STURLA combined with machine learning modeling was able to correlate PM_2.5 (R²= 0.68, RMSE 2.82 µg/m³) and BC (R² = 0.64, RMSE 0.75 µg/m³) concentrations with the urban landscape and spatially interpolate concentrations where sampling did not take place. These results demonstrate the efficacy of the STURLA methodology in modeling relationships between air pollution and land cover/urban structure patterns.

Cohesion in the refractory metals Cr, Mo, and W is phenomenologically described in this work via a n-body energy functional with a set of physically motivated parameters that were optimized to reproduce selected experimental properties characteristic of perfect and defective crystals. The functional contains four terms accounting for the hard-core repulsion, the Thomas-Fermi kinetic energy repulsion and for contributions to the binding energy of s and d valence electrons. Lattice dynamics, molecular statics, and molecular dynamics calculations show that this model describes satisfactorily thermodynamic properties of the studied metals whereas, unlike other empirical approaches from the literature, predictions of phonon dispersion relations and of surface and point defect energetics reveal in fair good agreement with experiments. These results suggest that the present model is well adapted to large-scale simulations and whenever total energy calculations of thermodynamic properties are unfeasible

Solidification cracking is a major obstacle when joining dissimilar alloys using additive manufacturing. In this work, location-specific solidification cracking susceptibility has been investigated using an integrated computational materials engineering (ICME) approach for a graded alloy formed by mixing P91 steel and Inconel 740H superalloy. An alloy derived from a mixture of 26 wt.% P91 steel and 74 wt.% Inconel 740H, with high configurational and total entropy, was fabricated using wire-arc additive manufacturing. Microstructure characterization revealed intergranular solidification cracks, which increased in length along with the build height. With inputs from experiments, such as secondary dendrite arm spacing, the DICTRA (diffusion-controlled transformations) module within the Thermo-Calc software was used to model location-specific solidification cracking susceptibility. The top region, with the highest cooling rate, has the highest solidification cracking susceptibility and is in good agreement with the experimentally observed crack length. From Scheil simulations, it was deduced that pronounced segregation of Nb and Cu within the cracks increased the solidification range by suppressing the solidus temperature. The overall solidification cracking susceptibility and freezing range was highest for the 26 wt.% P91 alloy amongst the mixed compositions between P91 steel and 740H superalloy, proving that solidification characteristics play a major role in alloy design for additive manufacturing.

Quantitative dynamic strain measurements of the ground would be useful for engineering scale problems such as monitoring for natural hazards, soil-structure interaction studies and non-invasive site investigation using full waveform inversion (FWI). Distributed Acoustic Sensing (DAS), a promising technology for these purposes, needs to be better understood in terms of its directional sensitivity, spatial position, and amplitude for application to engineering-scale problems. This study investigates whether the physical measurements made using DAS are consistent with the theoretical reception patterns and experimental measurements of ground strain made by geophones. Results show that DAS and geophone measurements are consistent in both phase and amplitude for broadband (10s of Hz), high amplitude (10s of microstrain) and complex wavefields originating from different positions around the array when: (1) the DAS channels and geophone locations are properly aligned, (2) the DAS cable provides good deformation coupling to the internal optical fiber, (3) the cable is coupled to the ground through direct burial and compaction, and (4) laser phase noise is mitigated in the DAS measurements. The theoretical relationship between DAS-measured and point-wise strain for vertical and horizontal active sources is introduced using 3D elastic finite-difference simulations. The implications of using DAS strain measurements are discussed including directionality and magnitude differences between the actual and DAS-measured strain fields. A method for spatially aligning the DAS channels with the geophone locations at tolerances less than the spatial resolution of the DAS system is proposed.

This is a study on fractals existing in music. The application case is the composition DIAPHONIES of Michael Paouris. Sliding-window fractal analysis indicate areas of continuous fractality dipped in non-fractal areas of possibly deterministic and stochastic nature. Diverging cases of pronounced non-fractal areas are addressed and also areas of mixed fractality and non-fractality. Many segments exhibit persistency-P (2

Gas chromatography-coupled mass spectrometry (GC-MS) has been used in biomedical research to analyze volatile, non-polar, and polar metabolites in a wide array of sample types. Despite advances in technology, missing values are still common in metabolomics datasets and must be properly handled. We evaluated the performance of ten commonly used missing value imputation methods with metabolites analyzed on an HR GC-MS instrument. By introducing missing values into the complete (i.e., data without any missing values) NIST plasma dataset we demonstrate that Random Forest (RF), Glmnet Ridge Regression (GRR), and Bayesian Principal Component Analysis (BPCA) shared the lowest Root Mean Squared Error (RMSE) in technical replicate data. Further examination of these three methods in data from baboon plasma and liver samples demonstrated they all maintained high accuracy. Overall, our analysis suggests that any of the three imputation methods can be applied effectively to untargeted metabolomics datasets with high accuracy. However, it is important to note that imputation will alter the correlation structure of the dataset, and bias downstream regression coefficients and p-values.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

As brachycephalic dog breed ownership increases, there is a growing concern for the welfare of these breeds due to extreme brachycephalism. Understanding the motivations and behaviours of those choosing to own these breeds is important if we wish to address these concerns. The aim of this study was to investigate how owners of brachycephalic and non-brachycephalic dog breeds use social media dog breed groups to discuss common health issues. The purpose of Facebook posts in relation to common health issues, owner awareness of health issues, and the role of Facebook facilitated social support were explored between brachycephalic and non-brachycephalic dog owners. Twelve Facebook breed groups were selected (brachycephalic breed groups, n=6, non-brachycephalic breed groups, n=6). Using key word searches we extracted the first twenty posts from each group. Thematic analysis revealed three overarching themes: advice seeking, advice giving and community bonding mechanisms. Whilst the purpose of posting did not differ between groups, non-brachycephalic owners appeared to display greater awareness of breed-specific health issues, whilst social support played a more prominent role in brachycephalic groups. This research highlights that social media groups can act as platforms for knowledge exchange and emotional support. These could be utilised by owners, veterinarians and welfare organisations to more effectively enhance dog health and wellbeing.

Density Functional Theory (DFT) full potential linearized augmented plane wave (FP-LAPW) method with the Modified Becke-Johnson (mBJ) approximation is used to perform spin polarised calculations of the transition metal perovskites MoScO₃ and WScO₃. Both depict half metallic behaviour with semiconducting and metallic in the minority and majority spins respectively. MoScO₃ and WScO₃ have indirect R− Γ band gaps in the minority spin channels of 3.61 and 3.82eV respectively. Moreover, they both show substantial magnetic moments of 2.99μ_B. In addition, we calculate the dielectric function, optical conductivity and the optical constants, namely, the refractive index, the reflectivity, the extinction and absorption coefficients.

We study the changes in quantum Fisher information (QFI) values for one quantum system consisting of a superposition of W and GHZ states. In a recent work [6], QFI values of this mentioned system studied. In this work, we extend this problem for the changes of QFI values in some noisy channels. We show the change in QFI depending on noise parameters. We report interesting results for different type of decoherence channels.

In this work, anchoring of cinchona derivatives to trifunctional cores (hub approach) was demonstrated to obtain size-enlarged organocatalysts. By modifying the cinchona skeleton in different positions, we prepared four C3-symmetric size-enlarged cinchona derivatives (hub-cinchonas), which were tested as organocatalysts and their catalytic activities were compared with the parent cinchona (hydroquinine) catalyst. We showed that in the hydroxyalkylation reaction of indole, hydroquinine provides good enantioselectivities (up to 73% ee), while the four new size-enlarged derivatives gave significantly lower values (up to 29% ee) in this reaction. Anchoring cinchonas to trifunctional cores was found to facilitate nanofiltration-supported catalyst recovery using PolarClean alternative solvent. The C3-symmetric size-enlarged organocatalysts were completely rejected by all the applied membranes, whereas the separation of hydroquinine was found to be insufficient using organic solvent nanofiltration. Furthermore, the asymmetric catalysis was successfully demonstrated in the case of Michael reaction of 1,3-diketones and trans-β-nitrostyrene using Hub3-cinchona (up to 96% ee) as a result of the positive effect of the C3-symmetric structure using a bulkier substrate. This means an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction.

Eating disorder (ED) symptoms often co-occur with nonsuicidal self-injury (NSSI). This comorbidity is consistent with evidence that trait negative urgency increases risk for both of these phenomena. We previously found that impaired late-stage negative emotional response inhibition (i.e., negative emotional action termination or NEAT) might represent a neurocognitive mechanism for heightened negative urgency among people with NSSI history. The current study evaluated whether relations between negative urgency and ED symptoms similarly reflect deficits in this neurocognitive process. One hundred and five community adults completed an assessment of ED symptoms, negative urgency, and an emotional response inhibition task. Results indicated that, contrary to predictions, negative urgency and NEAT contributed independent variance to the prediction of ED symptoms, while controlling for demographic covariates and NSSI history. Worse NEAT was also uniquely associated with restrictive eating, after accounting for negative urgency. Our findings suggest that difficulty inhibiting ongoing motor responses triggered by negative emotional reactions (i.e., NEAT) may be a shared neurocognitive characteristic of ED symptoms and NSSI. However, negative urgency and NEAT dysfunction capture separate variance in the prediction of ED-related cognitions and behaviors, distinct from the pattern of results we previously observed in NSSI.

Quantitative research on positive aspects of work-life integration and the well-being of families with children with disabilities is scarce, especially in the national context. The aim of this study was to examine the contributions of some personal and environmental resources in explaining work-to-family (WFF) and family-to-work (FWF) facilitation and mental health of parents of children with disabilities residing in Croatia. The mediational role of WFF and FWF in the relationship between the resources and mental health was tested, while controlling for some general socio-demographic variables. A total of 571 employed parents of a child/children with disabilities completed an online self-assessment questionnaire. The results showed higher WFF (19%) was predicted by higher levels of social support at work, a higher level of education, posttraumatic growth (PTG) of personal strength, and recovery management. Higher FWF (46%) was predicted by higher levels of social support in the family, PTG of personal strength, the emotional regulation strategy of reorienting to planning, optimism, a lower age, the male gender, a greater number of children, and a higher level of education. A higher level of mental health (47%) was predicted directly by higher levels of optimism, recovery management, FWF, emotional regulation strategies of positive refocusing and planning, and a greater number of children, and indirectly by all the predictors of FWF, through a higher level of FWF (but not WFF).

Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae), an indigenous plant to the Middle East region, is well-known as a medicinal plant for treating many human ailments. The current study aimed at exploring the polyphenols profile of T.nilotica alcohol soluble fraction of aqueous extract, assessing its in-vivo antifibrotic activity and the possible underlying mechanism, to unravel the impact of quantitative difference of sulphated polyphenols content on the antifibrotic activity of T.nilotca grown in two different habitats. Polyphenols profiling of T. nilotica extracts was performed using HPLC-HRESI-QTOF-MS-MS. The major polyphenol components included sulphated flavonoids, phenolic acids and free aglycones. The antifibrotic activity was evaluated through carbon tetrachloride-induced liver fibrosis in rats. Biochemical evaluations revealed that both fractions ameliorated the increased levels of hepatic aminotransferases, lipid peroxidation, hydroxyproline, α-smooth muscle actin (α-SMA), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB). Moreover, both fractions reduced catalase activity (CAT) and enhanced hepatic glutathione (GSH) content. Histopathological imaging undoubtedly confirmed such results. In conclusion, T. nilotica polyphenols rich fraction exhibited potential antifibrotic activity in rats. Significant alterations in GSH levels were recorded based on sulphated polyphenol metabolites content.

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

Fabrics comprised of porous fibers could provide effective passive protection against chemical and biological (CB) threats whilst maintaining high air permeability (breathability). Here, we fabricate hierarchically porous fibers consisting of regenerated silk fibroin (RSF) and activated-carbon (AC) prepared through two fiber spinning techniques in combination with ice-templating – namely cryogenic solution blow spinning (Cryo-SBS) and cryogenic wet-spinning (Cryo-WS). The Cryo-WS RSF fibers had exceptionally small macropores (as low as 0.1 µm) and high specific surface areas (SSAs) of up to 79 m2 g-1. The incorporation of AC could further increase the SSA to 210 m2 g-1 (25 wt. % loading) whilst also increasing adsorption capacity for volatile organic compounds (VOCs).

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

1) Background: We analyzed the corpus of three geoscientific journals to investigate if there are enough locational references in research articles to apply a geographical search method, on the example of New Zealand. 2) Methods: Based on all available abstracts and all freely available papers of the New Zealand Journal of Geology and Geophysics, the New Zealand Journal of Marine and Freshwater Research, and the Journal of Hydrology, New Zealand, we searched title, abstracts and full texts for place name occurrences that match records from the official Land Information New Zealand (LINZ) gazetteer. We generated ISO standard compliant metadata records for each article including the spatial references and make them available in a public catalogue service. This catalogue can be queried for articles based on authors, titles, keywords, topics as well as by spatial reference. We visualize the results in a map to show which area the research articles are about. 3) Results: We outline the methodology and technical framework for the geo-referencing of the journal articles and the platform design for this knowledge inventory. The results indicate that the use of well-crafted abstracts for journal articles with carefully chosen place names of relevance for the article provides a guideline for geographically referencing unstructured information like journal articles and reports in order to make such resources discoverable through geographical queries. 4) Conclusion: This approach can actively support integrated holistic assessment of water resources and support decision making.

In this review, we provide an overview of the current knowledge on the different sexual systems and sex determining mechanisms in bivalves, with a focus on the various epigenetic and genetic factors that may be involved. The final section of the review provides recent discoveries on sex-specific mitochondrial genes in bivalves possessing the unconventional system of doubly uniparental inheritance of mitochondria (which is found in several members of the orders Mytiloida, Unionoida, Veneroida and Nuculanoida). The genes involved in this developmental pathway could represent the first sex determination system in animals in which mitochondrially-encoded genes are directly involved.

Doxorubicin (Dox) is a commonly used chemotherapeutic that can adversely affect skeletal muscle, including causing muscle atrophy. Dox is known to induce an event known as mitochondrial permeability transition (MPT) in cardiac muscle and this plays an important role in Dox-mediated cardiac toxicity. Further to this, recent evidence identifies MPT as a mechanism of atrophy in skeletal muscle, suggesting that MPT may underlie some of the Dox-related toxicity in skeletal muscle. To test this hypothesis, we used cultured human primary myotubes, C2C12 myotubes, and single adult mouse flexor digitorum brevis (FDB) muscle fibers in experiments involving Dox treatment with or without inhibitors of MPT. Dox treatment of myotubes caused myonuclear translocation of the mitochondrial protein apoptosis inducing factor (AIF) and increased mitochondrial reactive oxygen species (mROS), consistent with the known consequences of MPT. Furthermore, Dox caused atrophy in C2C12 myotubes grown on patterned plates, human primary myotubes, and single muscle fibers from adult mice. Notably, Dox-induced atrophy could be prevented by a wide variety of agents that inhibit MPT, as well as by inhibiting mROS or Caspase 3. In conclusion, our results indicate that MPT plays an important role in driving Dox-mediated skeletal muscle atrophy.

The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilia length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilia length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield the Michael type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the reaction. The study of the variation of the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

In this paper, we introduce a new generalization of the r-Stirling numbers of the second kind based on the q-numbers via an exponential generating function. We investigate their some properties and derive several relations among q-Bernoulli numbers and polynomials, and newly de…ned (q, r, w)-Stirling numbers of the second kind. We also obtain q-Bernstein polynomials as a linear combination of (q, r, w)-Stirling numbers of the second kind and q-Bernoulli polynomials in w.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

Hospitalizations for patients with diabetes and dementia take a significant health and economic toll on older adults in the United States. The present study sought to examine the differences in hospitalization characteristics and outcomes associated with diabetes and dementia separately and together using discharge record data of Los Angeles County residents aged 50+ from the California Department of Health Care Access and Information for the period 2019-2021. Results from multiple linear regression analyses indicated that when compared to those with no diabetes or dementia, patients with diabetes alone exhibited the highest total charges, while those with comorbid diabetes and dementia exhibited lower charges (p≤.05). Results of a multinomial logistic regression found that patients with comorbid diabetes and dementia had the highest odds of having a length of stay of 7+ days (AOR=1.49; 95% CI=1.44-1.53). A matched-case control analysis found that comorbid diabetes and dementia was associated with significantly lower odds of hypertensive disease than diabetes alone (MOR=0.81; 95% CI=0.67-0.97). These results highlight the complexity of factors affecting variation in hospitalization outcomes across these distinct disease profiles. Findings suggest a need to carefully consider this complexity when developing health policies or strategies to improve hospitalization outcomes involving these disease conditions.

Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral or fungal infections are well recognized to activate the coagulation system, COVID-19 associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. Von Willebrand Factor (VWF) and its protease, ADAMTS13 play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS13 has been reported. Also, an imbalance between ADAMTS13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment and improve clinical prognosis.

We have previously reported that a single test measuring oVEMP n10 to 4000Hz stimuli (either bone-conducted vibration (BCV) or air-conducted sound (ACS)) provides a definitive diagnosis of semicircular canal dehiscence (SCD) in 22 CT-verified patients with a sensitivity of 1.0 and specificity of 1.0. Such a single short screening test has great advantages of speed, minimizing testing time and the exposure of patients to stimulation. However some studies of the 4000Hz test for SCD have reported sensitivity and sensitivity values somewhat less that what we reported.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

Tungsten and its alloys are considered as a key component in high temperature environment. Self-passivating W-Si-xY alloys with different Y contents made from the powders milled for different times were prepared by mechanical alloying (MA) and spark plasma sintering (SPS). Their microstructures and oxidation resistance were investigated. It is found that the oxidation resistance of the alloys with low Y contents (0Y and 2Y) made from 20 h-milled powders is worse than that of the alloys made from 4 h-milled powders. It is because the protective WO3/SiO2 composite layer is discontinuous. While the alloys with high Y contents (4Y and 6Y) made from 4 h and 20 h-milled powders show good oxidation resistance. Even, the thickness of the oxide layer of the alloys with 4Y and 6Y made from 20 h-milled powders after oxidation at 1000 ℃ for 2 h is 84.0 μm and 70.7 μm, less than that made from 4 h-milled powders. This is due to the size and distribution of W5Si3, Y2Si2O7 aggregates and W-Y-O melt. The synergistic effects of Y contents and milling time on the microstructures and oxidation resistance of the alloys are revealed.

Quantum Fisher Information (QFI) is a very useful concept for analyzing situations that require phase sensitivity. It become a popular topic especially in Quantum Metrology domain. In this work, we study the changes in quantum Fisher information (QFI) values for one relative arbitrary phased quantum system consisting of a superposition of N Qubits W and GHZ states. In a recent work [7], QFI values of this mentioned system for N qubits were studied. In this work, we extend this problem for the changes of QFI values in some noisy channels for the studied system. We show the changes in QFI depending on noise parameters. We report interesting results for different type of decoherence channels. We show the general case results for this problem.

In recent years, the treatment of locally-advanced rectal cancer (LARC) has been spotlighted in a number of landmark, practice-changing trials, heralding in the age of so-termed “total neoadjuvant therapy” (TNT). However, the lack of a common control arm, standard inclusion criteria, or, indeed, definition of TNT necessitates further study in this field, particularly using real-world data. We conducted a retrospective analysis of all patients treated for LARC at a single Canadian academic cancer centre between July 1st 2019 and July 14th 2022. This includes the June 2020 incorporation of TNT. 290 patients were included in the final analysis, and 124 variables were collected on each patient, including demographics, treatment type, adverse events, response to treatment, surgery versus watchful waiting and survival. Our findings demonstrate that both TNT and non-TNT regimens are highly toxic, with regards to both overall toxicity and grade 2+ adverse effects. 62 (96.9%) of patients on TNT experienced toxicities, compared to 186 (82.3%) of the non-TNT patients. Grade 2+ toxicities were 46 (71.9%) and 143 (63.3%), respectively. TNT, however, was associated with improved rates of complete response, compared to non-TNT treatment regimens (44% vs 24%). These findings suggest that TNT harbours both benefit and risk in a real-world population, and both of these aspects should be considered when deciding on a treatment approach for an individual patient. More work in the area is needed to determine longer term survival, as well as impact of surgery versus organ preservation approach on patient outcomes.

The aim of this study was to evaluate the psychometric evidence of the original and brief version of the Santa Clara Strength of Religious Faith Questionnaire (SCSRFQ) in Spanish in a sample of 245 Peruvian adolescents and adults (mean age = 21.04 years, SD = 3.07, 47.8% male and 52.2% female), selected by non-probabilistic convenience sampling. Additionally, the Coronavirus Anxiety Scale and the Satisfaction with Life Scale were applied. Confirmatory Factor Analysis, internal consistency reliability methods, hierarchical sequence of variance models and Graded Response Model were used. Results indicate that both versions of the SCSRFQ showed robust psychometric properties: adequate unidimensional structure, adequate difficulty and discrimination parameters, and significant relationships with the measures of fear of COVID-19 and satisfaction with life. The original version of the SCSRFQ showed evidence of strict measurement invariance by gender and age; whereas the short version showed strict invariance by gender and configural invariance by age. Both versions showed acceptable reliability indices. In conclusion, the original and brief versions of the SCSRFQ show evidence of psychometric indicators that support their use to assess the strength of religious faith

Background: Bacteria, among the earliest life forms on Earth, are integral to both human health and environmental ecosystems. They contribute to essential processes such as digestion, nutrient absorption, and immune defense, and play key roles in the biogeochemical cycles that sustain life. Objective: This paper explores the indispensable role of bacteria in human life and environmental health, emphasizing their contributions to digestion, nutrient absorption, immune protection, and ecosystem functioning. It also discusses advances in understanding the human microbiome and their implications for health and therapeutic interventions. Methods: The study reviews existing literature on the human microbiome, probiotics, and the role of bacteria in environmental nutrient cycling. It analyses experimental evidence and case studies, particularly focusing on the impact of fecal microbiota transplantation (FMT) as a therapeutic tool. Metagenomic analysis techniques are examined to highlight the diversity and functionality of gut bacteria. Results: Bacteria are found to be essential for breaking down food, providing vital nutrients, and protecting against pathogens. They play a critical role in maintaining a healthy immune system and are involved in the biogeochemical cycles necessary for ecosystem health. Metagenomic analysis reveals significant variations in bacterial populations associated with health and disease, emphasizing the importance of a balanced microbiota. FMT shows promise as an effective treatment for various diseases, including gastrointestinal, metabolic, and neurological disorders. Conclusions: Bacteria are crucial for human health and environmental stability. Maintaining a balanced microbiota is vital for overall well-being, and interventions such as probiotics and FMT can offer significant health benefits. Future research should focus on further understanding the complex interactions between bacteria and their hosts to develop targeted therapies for various health conditions.

Scaffold guided breast tissue regeneration (SGBTR) can both transform reconstructive and cosmetic breast surgery. Implant-based surgery is the most common method. However, there are inherent limitations as there is replacement of tissue rather than regeneration. Regenerating autologous soft tissue has the potential to provide a more like-for-like reconstruction with minimal morbidity. Our SGBTR approach regenerates soft tissue by implanting additively manufactured bioresorbable scaffolds filled with autologous fat graft. A pre-clinical large animal study was conducted implanting 100 ml breast scaffolds (n=55) made from medical-grade polycaprolactone in 11 minipigs for 12 months. Various treatment groups were investigated where immediate or delayed autologous fat graft, as well as platelet rich plasma were added to scaffolds. Computed Tomography and Magnetic Resonance Imaging was performed on explanted scaffolds to determine volume and distribution of regenerated tissue. Histological analysis was performed to confirm tissue type. At 12 months we were able to regenerate and sustain a mean soft tissue volume of 60.9 4.5 ml (95% CI) across all treatment groups. There was no evidence of capsule formation. There were no immediate or long-term post-operative complications. In conclusion, we were able to regenerate clinically relevant soft tissue volumes utilizing SGBTR in a pre-clinical large animal model.

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulate disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified 3 MTBC lineages of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (N=149 and N=127). We found a significant interaction between a SNP in PPIAP2 and the Uganda lineage (combined p=4x10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

Greenhouse gas (GHG) emission-induced climate change, particularly occurring since the mid-20th century has been considerably affecting short-term weather conditions, such as increasing weather variability, and incidence of extreme weather-related events. Milk production is sensitive to such changes. In this study, we use spatial panel econometric models, Spatial Error Model (SEM) and Spatial Durbin Model (SDM), with a panel dataset at the state-level varying over seasons, to estimate the relationship between weather indicators and milk productivity, in an effort to reduce the bias of omitted climatic variables that can be time-varying and spatially correlated and cannot be directly captured by conventional panel data models. We find an inverse U-shaped effect of summer heat stress on milk production per cow (MPC), indicating that milk production reacts positively to a low-level increase in summer heat stress, and then MPC declines as heat stress continues increasing beyond a threshold value of 72. Additionally, fall precipitation exhibits an inverse U-shaped effect on MPC, showing that milk yield increases at a decreasing rate until fall precipitation rises to 14 inches and then over that threshold milk yield declines at an increasing rate. We also find that, relative to conventional panel data models, spatial panel econometric models could improve prediction performance by leading to smaller in-sample and out-sample root mean squared errors. Our study contributes to the literature by exploring the feasibility of promising spatial panel models and resulting in estimating weather influences on milk productivity with high model predicting performance.

Freezing of gait (FOG), a debilitating symptom of Parkinson’s disease (PD), can be safely studied using the stepping in place (SIP) task. However, clinical, visual identification of FOG during SIP is subjective and time consuming, and automatic FOG detection during SIP currently requires measuring center of pressure on dual force plates. This study examines whether FOG elicited during SIP in 10 individuals with PD could be reliably detected using kinematic data measured from wearable inertial measurement unit sensors (IMUs). A general, logistic regression model (AUC = 0.81) determined that three gait parameters together were overall the most robust predictors of FOG during SIP: arrhythmicity, swing time coefficient of variation, and swing angular range. Participant-specific models revealed varying sets of gait parameters that best predicted FOG for each participant, highlighting variable FOG behaviors, and demonstrated equal or better performance for 6 out of the 10 participants, suggesting the opportunity for model personalization. The results of this study demonstrated that gait parameters measured from wearable IMUs reliably detected FOG during SIP, and the general and participant-specific gait parameters allude to variable FOG behaviors that could inform more personalized approaches for treatment of FOG and gait impairment in PD.

Minirhizotron tubes were installed to monitor root growth dynamics of mature Shiraz grapevines in a rootstock trial established in the hot climate Riverina region of New South Wales, Australia. The vertical root distribution and seasonal root growth dynamics of Shiraz on own-roots and Shiraz grafted on the rootstocks Ramsey, 140 Ruggeri and Schwarzmann was studied for five seasons across a seven-year period to a depth of 60 cm. New root production was significantly influenced by genotype, soil depth, season, growth stage and year. Soil moisture and soil tem-perature were monitored at 10, 30 and 60 cm in the last two seasons. Soil moisture at 30 cm and soil temperature at all three depths were significant predictors of root growth. New root numbers were significantly higher in 140 Ruggeri than the other rootstocks. To the depth studied, 140 Ruggeri roots were evenly distributed from the topsoil down, whereas the majority of roots of Schwarzmann and Shiraz were located at intermediate depths in the 10-40 cm ad 20-40 cm zones respectively, while Ramsey roots were found at 20 cm or below. Depending on genotype, root growth occurred across several phenological stages but tended to peak at flowering. In some years we observed root growth in early and late winter at rates exceeding that of autumn, and this was associated with warmer temperatures during this period. Overall, seasonal rooting dynamics were responsive to abiotic factors but dominated by genotype.

Objective: Racial/ethnic disparities in infant mortality (IM) continue to persist in the United States, with Black/African Americans (AA) being disproportionally affected with threefold increase in mortality compared to Whites. Epidemiologic data have identified maternal characteristics as risk IM such as eclampsia, maternal education, smoking, maternal weight, maternal SES, and family structure. Understanding the cause of causes including the method of labor and delivery and the racial heterogeneity may facilitate intervention mapping in narrowing the Black White IM risk differences. We aimed to assess the temporal/racial trends and the methods of delivery, mainly vaginal versus cesarean section (C-section) as exposure function of IM. Methods: The United States linked Birth/Infant Death records (2007-2016) were used with a cross-sectional ecologic design. The analysis involved chi squared statistic, incidence rate estimation, and period percent change. Results: Of the 40,445,070 births between 2007 and 2016, cumulative mortality incidence was 249,135 (1.16 per 1000). The IM rate was highest among Black/AA (11.41 per 1000), intermediate among Whites (5.19 per 1000), and lowest among Asian /Pacific Islanders (4.24 per 1000). The cumulative incidence rate difference, comparing vaginal to cesarean procedure was 1.73 per 1000 infants, implying excess IM with C-section. Compared to C-section, there was a 31% decreased risk of IM among mothers with vaginal delivery, rate ratio (RR) = 0.69, 95% CI 0.64-0.74. Racial disparities was observed in the method of delivery associated with IM. Black/AA mothers with vaginal delivery had a 6% decreased risk of IM compared to C-section, RR = 0.94, 95%CI 0.92-0.95, while Whites with vaginal delivery had a 38% decrease risk of IM relative to C-section, RR= 0.68, 95%CI 0.67-0.69, p<0.001. Conclusion: Infant mortality varied by race, with Black/AA disproportionally affected which is explained in part by labor and delivery procedures, suggesting reliable and equitable intrapartum assessment of Black/AA mothers during labor.

An efficient stereoselective three-component reaction for the synthesis of spiro[4H-chromene-3,3’-oxindole] derivatives was realized through an organocatalyzed cascade Knoevenagel/Michael/cyclization reaction using a quinidine-derived squaramide as the catalyst. Under the optimized conditions, the reactions of isatins, malononitrile, and sesamol yield the desired spirooxindoles in good yields (75–87%) and moderate to high ee values (up to 90% ee). Two pairs of selected enantiomers were subjected to evaluate their antiproliferative activities on three types of human cancer cell lines using the MTT assay. The results indicated that stereoselectivity and electrical effect showed significant impact on activity. Enanotiomer R-3f exhibited optimal cytotoxic activity against U2OS cell line, which was close to the inhibitory activity of positive control, Adriamycin.

Over the last several decades there has been an arms race to acquire credentials as higher education has shifted from an elitist system to mass education. From an individual perspective, given the higher education system and labor market conditions, it is rational to pursue advanced qualifications. However, whether the education system delivers improvements in human capital or is principally a signaling mechanism is questionable. Estimates of the proportion of labor market rewards due to signaling range as high as 80%, suggesting that education is not only expensive but inefficient. In an increasingly transactional environment in which education providers are highly motivated by financial considerations, this situation is only likely to be exacerbated by the rapid developments in AI. The use of AI has the potential to make learning more effective but, given that many students see credential acquisition as transactional, it may reduce both human capital and the value of the signaling effect. If the credibility of the credentials offered is further damaged, the sustainability of the higher education sector in its present form and scale may well be unsustainable. We examine the evidence on credential inflation, returns to education and mismatch of graduates to jobs before analyzing how AI is likely to affect these trends. We then suggest possible responses of prospective students, education providers and employers to the growing adoption of AI in both education and the workplace. We conclude that the current offerings of generalist degrees, as opposed to vocational qualifications, are not sustainable and that to survive, even in a downsized form, the sector must respond to this disruptive technology by changing both the nature of its offerings and its methods of ensuring that the credentials they offer reflect genuine student learning.

Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration result in accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long-COVID), as well as treatment options are discussed.

In this work, we introduce the class of h-MN-convex functions by generalizing the concept of MN-convexity and combining it with h-convexity. Namely, let M : [0, 1] → [a, b] be a Mean function given by M (t) = M (t; a, b); where by M (t; a, b) we mean one of the following functions: A_t (a, b) := (1 − t) a + tb, G_t (a, b) = a^1−tb^t and H_t (a, b) := $\frac{ab}{ta+\left(1-t\right)b}=\frac{1}{A_t\left(\frac{1}{a},\frac{1}{b}\right)}$ with the property that M (0; a, b) = a and M (1; a, b) = b. Let I, J be two intervals subset of (0, ∞) such that (0, 1) ⊆ J and [a, b] ⊆ I. Consider a non-negative function h : J → (0, ∞), a function f : I → (0, ∞) is said to be h-MN-convex (concave) if the inequality f (M (t; x, y)) ≤ (≥) N (h(t); f (x), f (y)), holds for all x, y ∈ I and t ∈ [0, 1]. In this way, nine classes of h-MN-convex functions are established, and therefore some analytic properties for each class of functions are explored and investigated. Characterizations of each type are given. Various Jensen’s type inequalities and their converses are proved.

This study aims to identify modern bureaucratic government phenomenon expressed in W.H. Auden’s poem “The Unknown Citizen” (UC). This phenomenon will be revealed through the use of figures of speech, symbols and imagery in the poem. This poem is chosen as the object of the study since phenomenon happened in the poem represents people’s life and government practice in the modern era. Government, in the poem, seems to be very dominant. Its bureaucratic apparatus is powerful. Through its sophisticated technology, the bureau of statistics is able to detect the citizen’s identity. But, ironically, it could have not identified UC’s name as he lived in the world. He, then, was honored by the state by being erected the marble monument. The poem is analyzed by applying phenomenological criticism. The analysis finds that the representation of modern government is expressed through symbols emphasized by dramatic irony and supported by the use of internal sensation imagery. UC is the allegory of the average person with his bravery he sacrifices for the country. The state ought to give him an honor. In this poem Auden, actually, wants to write a parody for establishing monuments in some countries to honor the struggles of their soldiers who died in the World War I. Those monuments are really tombs since the function of a monument is a state’s thanksgiving for their sacrifice.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

Stream chemistry effectively integrates watershed ecosystem processes on both spatial and temporal scales. Streams of coastal areas integrate a more homogeneous, flat topography wherein there can be interactions between the stream and the body of water into which it drains, especially where tidal fluxes occur. The present study assessed water quality of Thompson Bayou, which comes to the campus of the University of West Florida in a wetland after flowing through 4 km of commercial and private property with associated impacts on water quality. Sampling was carried out for one year at eight discrete sites along Thompson Bayou from the UWF campus to the Escambia River. We used a portable field meter to measure temperature, pH, dissolved O2 (DO), and specific conductivity (SC). Except for temperature, all variables exhibited a spatial pattern of significant variation with distance, with consistent increases in DO and SC as the stream approached the river. These variables also exhibited a temporal pattern of significant seasonal variation, including—and especially—temperature. Data suggest that spatial and temporal patterns of water quality of Thompson Bayou are determined by (1) processing of water by the wetland, (2) interactions of the stream channel with upland forest stands, and (3) the tidal hydrology of the Escambia River.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, using the Rosen and Israelit model of a nonsingular universe. In doing so we are in addition to obtaining a wavelength 10^30 times greater than Planck’s length so we can calculate DE, may be able to with the help of the Rosen and Israelit model have a first approximation as to the arrow of time, and a universe with massive gravity. We have left the particulars of the nonsingular starting point undefined but state that the Rosen and Israelit model postulates initial temperatures of 10^-180 Kelvin and also a value of about Planck temperature, at 10^-3 centimeters radii value which may satisfy initial conditions asked by t’Hooft for describing an arrow of time. A key assumption is that the DE is formed at 10^-3 cm, after an expansion of 10^30 times in radii, from the Planck length radius nonsingular starting point. The given starting point for DE in this set of assumptions is where there is a change in the cosmic acceleration, to a zero value, according to Rosen and Israel, with time t = 1.31 times 10^-42 seconds. Which may be where we may specify a potential magnitude, V, which has ties into inflaton physics. The particulars of the model from Rosen and Israelit allow a solution to be found, without discussion of where that nonsingular starting point came from, a point the author found in need of drastic remedies and fixes.

Parkinson’s Disease (PD) is a neurodegenerative and progressive disease that impacts the nerve cells in the brain and varies from person to person. The exact cause of PD is still unknown, and the diagnosis of PD does not include a specific objective test with certainty. Although deep learning has made great progress in medical neuroimaging analysis, these methods are very susceptible to biases present in neuroimaging datasets. An innovative decorrelated deep learning technique is introduced to mitigate class bias and scanner bias while simultaneously focusing on finding distinguishing characteristics in resting-state functional MRI (rs-fMRI) data, which assist in recognizing the PD with good accuracy. The decorrelation function reduces the non-linear correlation between features and bias in order to learn bias-invariant features. The Parkinson’s Progression Markers Initiative (PPMI) dataset, referred to as a single scanner imbalanced dataset in this study used to validate our method. The imbalanced dataset problem affects the performance of the deep learning framework by overfitting to the majority class. To resolve this problem, we propose a new Decorrelated Convolutional Neural Networks (DcCNN) framework by applying decorrelation-based optimization to Convolutional Neural Networks(CNN). An analysis of evaluation metrics comparisons shows that integrating the decorrelation function boosts the performance of PD recognition by removing class bias. Specifically, our DcCNN model performs significantly better than existing traditional approaches to tackle the imbalance problem. Finally, the same framework can be extended to create scanner invariant features without significantly impacting the performance of a model. The obtained dataset is a multi-scanner dataset which leads to scanner bias due to the differences in acquisition protocols and scanners. The multi-scanner dataset is a combination of two datasets, namely PPMI and FTLDNI - frontotemporal lobar degeneration neuroimaging initiative (NIFD) dataset. The results of t-distributed stochastic neighbor embedding (t-SNE) and scanner classification accuracy of our proposed Feature Extraction-DcCNN (FE-DcCNN) model validated the effective removal of scanner bias. Our method achieves an average accuracy of 77.80% on a multi-scanner dataset for differentiating PD from healthy control, which is superior to the DcCNN model trained on a single scanner imbalanced dataset.

Starting with unitary quantum dynamics, we investigate how to add quantum measurements. Quantum measurements have four essential components: the furcation, the witness production, an alignment projection, and the actual choice decision. The first two components still lie in the domain of unitary quantum dynamics. The decoherence concept explains the third contribution. It can be based on the requirement that witnesses reaching the end of time on the wave function side and the conjugate one have to be identical. In this way, it also stays within the quantum dynamics domain. The surjection hypothesis explains the actual choice decision. It is based on a two boundary interpretation applied to the complete quantum universe. It offers a simple way to reduce these seemingly random projections to purely deterministic unitary quantum dynamics, eliminating the measurement problem.

The aim of the study was to assess the intensity of the impact of the Křoví mining facility on the environment. The impact of the exploitation of rock deposits in Křoví on the atmosphere, lithosphere, biosphere, hydrosphere and anthroposphere was presented. Vulnerability to natural hazards was also assessed. The multi-criteria Analytic Hierarchy Process (AHP) method and the Leopold matrix were used to assess the impact. The assessment of the impact of raw material extraction in the quarry was carried out by competent experts. It has been found that the lithosphere and biosphere are under the greatest pressure due to land use and surface transformation (including deforestation). The increased susceptibility of the area to natural hazards was noted due to vibrations caused by increased truck traffic (transportation of excavated material). The total value of the matrix indicates the average intensity of the mining facility's impact on the environment. The location of the deposit above the water table of the Bílý potok river means that the extraction of the mineral has a minor impact on the water conditions in the area. Changes in topography and vegetation, and soil degradation are temporary and reversible. Once the mining operations have ceased, the site should be reclaimed and the program of reforestation and habitat restoration implemented to help mitigate adverse impacts on the biosphere.

Gap junctions (GJ) and connexins play integral roles in cellular physiology and have been found to be involved in multiple pathophysiological states from cancer to cardiovascular disease. Studies over the last 60 years have demonstrated the utility of altering GJ signaling pathways in experimental models, which has led to them being attractive targets for therapeutic intervention. A number of different mechanisms have been proposed to regulate GJ signaling, including channel blocking, enhancing channel open state, and disrupting protein-protein interactions. The primary mechanism for this has been through the design of numerous peptides as therapeutics, that are either currently in early development or are in various stages of clinical trials. Despite over 25 years of research into connexin targeting peptides, the overall mechanisms of action are still poorly understood. In this overview, we discuss published connexin targeting peptides, their reported mechanisms of action and the potential for these molecules in the treatment of disease.

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wild type cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.

A Clinical Prognostic Index (CPI) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included. Overall survival was 11.9 months and 9.4 months in the HCC group and metastatic groups, respectively. In the combined dataset, Child-Pugh Score (CPS) (p=0.002), serum albumin (p=0.039) and presence of extrahepatic disease (p=0.012) were significant predictors of early death on multivariable analysis and were included in the CPI (total score 0 to 5). Median survival was 23.8, 9.1, 4.5 and 2.6 months for patients with 0, 1-2, 3 and 4-5 points, respectively. In the HCC dataset, CPS (p&lt;0.001) and gross tumor volume (p=0.013) were predictive of early death. In the metastatic dataset, serum albumin (p&lt;0.001) and primary disease site (p=0.003) were predictive of early death. The AUC for the combined, HCC, and metastatic datasets are 0.78, 0.84, 0.80 respectively. Poor liver function (defined by CPS and serum albumin) and extrahepatic disease were most predictive of early death, providing clinically important expected survival information for patients and caregivers.

Abstract: Ambulatory cancer centers face fluctuating patient demand and deploy specialized personnel who have variable availability. This undermines operational stability through misa-lignment of resources to patient needs, resulting in overscheduled clinics, budget deficits, and wait times exceeding provincial targets. We describe deployment of a Learning Health System framework for operational improvements within the entire ambulatory center. Known methods of value stream mapping, operations research and statistical process control were applied to achieve organizational high performance that is data-informed, agile and adaptive. We transitioned from a fixed template model by individual physician to a caseload management by disease site model that is realigned quarterly. We adapted a block schedule model for the ambulatory oncology clinic to align the regional demand for specialized services with optimized human and physical resources. We demonstrated improved utilization of clinical space, increased weekly consistency and im-proved distribution of activity across the workweek. Increased value, represented as the ratio of monthly encounters per nursing worked hours, and increased percentage of services delivered by full-time nurses were benefits realized in our cancer system. The creation of a data-informed demand capacity model enables application of predictive analytics and business intelligence tools that will further enhance clinical responsiveness..

The philosophy of testing statistical hypothesis is a natural consequence and functional extension of mathematical analysis of Probability. Along with the concept of recurrence when applied to random sequences and functions, it leads to the analysis of a priori and posterior which implies testing statistical hypothesis. Testing statistical hypothesis also involves algebraic, functional and dimensional considerations, which are found in the works of Laplace. Aspects of mathematical analysis such as universality of solutions, Laws of Large Numbers, Entropy, Information, and various functional dependencies are the main factors explained in the five properties that lead to implication of testing statistical hypothesis. Various interesting examples with modern scientific significance from genetics, astrophysics, and other areas give methodological access to answers of different problems and phenomena which are involved in the logic of testing statistical hypothesis.

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

Steel fibre reinforced concrete (SFRC) consists of short hooked steel fibres randomly distributed and oriented within the cementitious matrix. The contribution of fibre in bridging cracks to provide the stress transfer required relies upon the orientation of the fibre in the concrete. Bridging fibre aligned with a crack are less effective than those inclined to it. Therefore, understanding the pull-out behaviour of misaligned fibre is a key factor to quantify and optimize the design of SFRC in the structural applications. In the laboratory a single oriented fibre embedded in a solid cylinder of concrete is subjected to a pull-out test where the axis of a tensile force is aligned with the axis of the cylinder. Based upon the observed behaviour this paper presents a new analytical bounding approach to capture the pull-out response of misaligned hooked-end steel fibre embedded in a concrete matrix. The analysis is based upon a transversely isotropic condition assumed for the plasticity that occurs in the cold drawn fibre. The model accounts for the influence of fibre diameter and the combined strengths of the steel and concrete. The model predictions have also been compared with other experimental results published in the literature. The results showed that the model can predict pull-out loads reasonably for different fibre orientations between bounds of failure derived from the strengths of the two constituents. A critical orientation is observed at maximum strength. Therein, an understanding of the pull-out behaviour of misaligned, hooked-end fibres is necessary to optimize the strength of concrete from this method of reinforcement.

We first of all define the arrow of time. Definition of the arrow of time will allow choosing different initial starting points. One of the issues we will also discuss is the interconnection be-tween the arrow of time, entropy and quantum information. Seth Lloyd in his 2001 work made a linkage between entropy, bits, and information via an axiomatic approach involving time in-tervals. Our take is a bit more general. We will discuss as well the t’Hooft’s statement as to in-itial conditions and times arrow, and how different cosmological models may influence initial conditions. Spoilers alert, if a nonsingular start to expansion existed, this would provide the most straightforward way to avoid a datum from classical relativity. That is, that in the actual equations of classical GR, there is no reason to have time asymmetry. Time asymmetry is built into initial conditions and we will detail several candidates. The first half of the paper brings up cosmology models and forming the arrow of time. The second is related to entropy itself and the problem of information. .

Delivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polar-ized pre-existing viewpoints and norms. In contrast, digital signs are an “in your face in your space” technology that has the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed: increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities.

The authors present a stereotypical case presentation of x-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact Fibroblast Growth Factor 23 (FGF23) which lead to i) low serum phosphate levels, ii) increased fractional excretion of phosphorus, and iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in XLH patients is due to chronic hypophosphatemia. Additionally, XLH patients experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration’s (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

Physical exercise favorably affects visceral adipose tissue (VAT) which is a risk factor for cardiometabolic diseases. However, many people are unable or unwilling to conduct frequent and intensive exercise programs that have favorable effects on VAT. The present study aimed to determine the effect of the time-efficient and joint-friendly whole-body electromyostimulation (WB-EMS) technology on VAT volume in overweight to obese adults with osteoarthritis of the knee. In total 72 women and men 40-70 years old with femuro-tibial knee osteoarthritis were randomly allocated to WB-EMS (n=36) with 1.5 sessions of 20 min/week for 29 weeks or a usual care control group (CG: n=36) with 6 sessions of physiotherapy. Magnetic Resonance Imaging (MRI) using a non-contrast enhanced 2-point Dixon Gradient Echo Volumetric Interpolated Breath-hold Examination determined VAT. Twelve slices covered a total length of approximately 5 cm from mid L2 to mid L3. In summary, VAT volume increased non-significantly in the CG (p=.261) and decreased non-significantly in the WB-EMS group (p=.160). We failed to determine significant WB-EMS-induced effects i.e. group differences for absolute changes on VAT volume (p=.097). Due to the low application volume, present WB-EMS protocols might not be the perfect tool for decreasing VAT in overweight to obese adults.

Diatom identification and counting by light microscopy is a fundamental method in ecological and water quality investigations. Here we present a new variant of this method based on “digital virtual slides”, and compare it to the traditional, non-digitized light microscopy workflow. We analysed three replicates of six samples using two methods: 1) working directly on a light microscope (the “traditional” counting method), and 2) preparing “virtual digital slides” by high-resolution slide scanning and subsequently identifying and labelling individual valves or frustules using a web browser-based image annotation platform (the digital method). Both methods led to comparable results in terms of species richness, diatom indices and diatom community composition. Although counting by digital microscopy was slightly more time consuming, our experience points out that the digital workflow can not only improve the transparency and reusability of diatom counts but it can also increase taxonomic precision. The introduced digital workflow can also be applied for taxonomic inter-expert calibration through the web, and for producing training image sets for deep-learning-based diatom identification, making it a promising and versatile alternative or extension to traditional light microscopic diatom analyses in the future.

Heavy metal contamination of drinking water is a public health concern that requires the development of more efficient bioremediation techniques. Absorption technologies, including biosorption, provide opportunities for improvements to increase the diversity of metal ions removed and overall binding capacity. Microorganisms are a key component in wastewater treatment plants and they naturally bind metal ions through surface macromolecules but with limited capacity. The long-term goal of this work is to engineer capsule polymerases to synthesize molecules with novel functionalities. In previously published work, we showed that the Neisseria meningitidis serogroup W (NmW) galactose-sialic acid (Gal—NeuNAc) heteropolysaccharide binds lead effectively, thereby demonstrating the potential for using this capsular polysaccharide in environmental decontamination applications. In this study, computational analysis of the NmW capsule polymerase galactosyltransferase (GT) domain was used to gain insight into how the enzyme could be modified to enable the synthesis N-acetylgalactosamine-sialic acid (GalNAc—NeuNAc) heteropolysaccharide. Various computational approaches, including molecular modeling with I-TASSER and molecular dynamics simulations (MD) with NAMD, were utilized to identify key amino acid residues in the substrate binding pocket of the GT domain that may be key to conferring UDP-GalNAc specificity. Through these combined strategies and using BshA, a UDP-GlcNAc transferase, as a structural template, several NmW active site residues were identified as mutational targets to accommodate the proposed N-acetyl group in UDP-GalNAc. Thus, a rational approach for potentially conferring new properties to bacterial capsular polysaccharides is demonstrated.

Performing arts used as a method of spreading health information dates back to the origins of storytelling. However, interventions in developing, non-Western countries typically utilise Western entertainment forms. This qualitative investigation assesses responses to an intervention designed around traditional Javanese shadow puppetry (wayang kulit). Semi-structured interviews provided in-depth responses from a sample (n=12) of villagers. Responses analysed both cross-case and within-case, focused on perceptions of the music and storyline, responses to the intervention, and perceived appropriateness of wayang kulit for disseminating a health message. Wayang kulit was considered to be interesting and easy to remember, but concerns remained regarding the reliability of information provided through the drama. The fusion of traditional and modern music and story elements were perceived positively. Some participants were inspired to improve their hygiene practices, although the lack of motivation, or belief that they were unable to change was noted. The performance was generally received positively in terms of the nature of the intervention, the fusion of traditional and Western music and story elements, as well as the use of wayang kulit to spread health information. The study provides guidance for modifications to the production, prior to scaling up.

Functional neurological disorder, or FND, is widely misunderstood, particularly when considering recent research that suggests that the illness has a biological rather than a psychiatric basis. Nonetheless, the long-held view that FND is a purely psychiatric disorder without biological basis, or even a contrived (malingered) illness, remains pervasive both in modern medical care and general society. This is because FND involves an intermittent course of involuntary disability that rapidly alternates with improved neurological control. This has in turn caused shaming, low self-efficacy, and social isolation of the patients. Little research has examined the numerous biomarkers that are shared between FND and canonical neurological disorders and the encouraging outcomes that can follow conventional neurological rehabilitation, modified for this disorder. This review summarizes current research on FND biomarkers and physical rehabilitation results. General healthcare providers would benefit their care for their patients through their improved understanding the illness and recourses for support and treatment that are provided in this review.

The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of ‘checkpoint blockade’ and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient’s own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function. The production of extracellular adenosine is mediated by the cell surface ectoenzymes CD73, CD39 and CD38 and therapeutic agents have been developed to target these as well as the downstream adenosine receptors (A₁R, A_2AR, A_2BR, A₃R) to enhance anti-tumor immune responses. This review will discuss the role of adenosine and adenosine receptor signaling in tumor and immune cells with a focus on their cell-specific function and their potential as targets in cancer immunotherapy.

A novel technique using a W-band metasurface for the purpose of transmissive fine powder layer sensing is presented. The proposed technique may allow for the detection, identification, and characterization of inhomogeneous ultrafine powder layers which are effectively hundreds of times thinner than the incident wavelengths used to sense them. Such a technique may be useful during personnel screening processes (i.e., at an airport) and in industrial manufacturing environments where early detection and quantization of harmful airborne particulates can be a matter of security or safety. To our knowledge, the requisite science involved in such a novel W-band metasurface sensing technique has not been fully explored.

Interleukin-33 (IL-33), a member of the IL-1 cytokine family has been recently associated with the development of autoimmune diseases, including SLE. IL-33 is an alarmin and a pleiotropic cytokine that affects various types of immune cells via binding to its receptor, ST2. In this study, we determine the impact of intraperitoneal IL-33 treatments in young lupus, NZB/W F1 mice. Mice were treated from the age of 6 to 11 weeks. We then assessed the proteinuria level, renal damage, survival rate, and anti-dsDNA antibodies. The induction of regulatory B (Breg) cells and changes in gene expression were also examined. In comparison to the control group, young NZB/W F1 mice administered with IL-33 had a better survival rate as well as reduced proteinuria level and lupus nephritis. IL-33 treatments significantly induced IgM anti-dsDNA antibody, IL-10 expressing Breg cells, and alternatively induced M2 macrophage gene signatures. These results imply that IL-33 exhibit regulatory roles during lupus onset via the expansion of protective IgM anti-dsDNA as well as regulatory cells such as Bregs and M2 macrophages.

Shell nacre from Pinctada species has been extensively researched for managing bone defects. However, there is a gap in the research on using shell nacre as cement with improved physico-chemical properties. To address this, the current study aimed to develop a chemical curable com-posite shell nacre cement (SNC) using shell nacre powder and an organically modified ceramic resin shell nacre containing ladder-structured siloxane methacrylate (SNLSM). Different amounts of shell nacre (24, 48, and 72 weight(wt)%) were added to the SNLSM resin matrix and the effect on the physicochemical properties of the cement was studied. The composite shell nacre cement SNC 72 containing 72 wt% shell nacre exhibited significantly higher mechanical properties (com-pressive strength >100 MPa, flexural strength > 35 MPa) and low linear polymerization shrinkage (0.4%) than other compositions. SNC 72 was radiopaque and the exotherm generated during the curing of the cement was minimal. Direct contact of cured SNC 72 with L929 cells revealed the non-cytotoxic nature of the cement. Overall, the results of the study proved that the composite SNC 72 would be a promising candidate for bone defect management.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).