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Src homology 3 (SH3) domains play a critical role in mediating protein–protein interactions (PPIs) involved in cell proliferation, migration, and the cytoskeleton. Despite their abundance in the human proteome, the functions and molecular interactions of many SH3 domains remain unknown, and this is in part due to the lack of SH3-domain-specific reagents available for their study. Affimer proteins have been developed as affinity reagents targeting a diverse range of targets, including those involved in PPIs. In this study, Affimer proteins were isolated against both the N- and C-terminal SH3 domains (NSH3 and CSH3) of growth-factor-receptor-bound protein 2 (Grb2), an adapter protein that provides a critical link between cell surface receptors and Ras signalling pathways. Targeting the CSH3 alone for the inhibition of PPIs appeared sufficient for curtailing Ras signalling in mammalian cell lines stimulated with human epidermal growth factor (EGF), which conflicts with the notion that the predominant interactions with Ras activating Son of sevenless (SOS) occur via the NSH3 domain. This result supports a model in which allosteric mechanisms involved in Grb2-SOS1 interaction modulate Ras activation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prevalence of the 'posterior crescent sign' in symptomatic patients referred for MRI/MR arthrogram of the hip and identify any correlation with imaging features of joint pathology. Materials and methods: Retrospective imaging assessment of a cohort of 1462 hips, from 1380 included MR examinations (82 bilateral) retrieved from a search of all examinations in patients 16–50 years old from June 2018 to June 2021, with median age 45.8 years (range 17.8–50.0) and 936 hips (64%) in women. Radiographic and MR findings related to hip dysplasia, femoroacetabular impingement and osteoarthritis were assessed. Results: Fifty-one hips (3.5%) were positive for the posterior crescent sign, median age of 45.8 years (range 17.8–50.0) and 29 (58%) in women. Radiographic findings included the following: mean lateral centre edge angle (LCEA) 22.2° (± 7.8°) with LCEA < 20° in 15 (31%) and LCEA 20–25° in 17 (35%) and mean acetabular index (AI) of 13.1° (± 5.8°) with AI > 13° in 22 (45%). MR findings included the following: mean anterior acetabular sector angle (AASA) 54.3° (± 9.8°), mean posterior acetabular sector angle (PASA) 92.7° (± 7.0°), labral tear at 3–4 o'clock in 20 (39%), high-grade acetabular chondral loss in 42 (83%) and ligamentum teres abnormality in 20 (39%). Conclusion: The posterior crescent sign occurs in 3.5% of symptomatic young and middle-aged adults on MR. It is associated with overt and borderline hip dysplasia and other findings of hip instability. It is also associated with osteoarthritis in some cases and should be interpreted with caution in these patients. [ABSTRACT FROM AUTHOR]

Spontaneous pulmonary hernia (SPH) is a rare condition. We report a case secondary to extreme coughing and COVID‐19 infection. The patient displayed several clinical features typical of this diagnosis; difficult to manage pain on coughing, flank haematoma and bulging of the chest wall on coughing. Clinicians should be aware of the risk factors and clinical features of SPH to aid diagnosis of this rare condition. [ABSTRACT FROM AUTHOR]

Quantifying the relationships between plant functional traits and ecosystem services has been promoted as an approach to achieving multifunctional grassland systems that balance productivity with other regulating, supporting and cultural services. Establishing trade-offs and synergies between traits and services has largely relied on meta-analyses of studies from different systems and environments. This study demonstrated the value of focused studies of long-term experiments in grassland systems that measure traits and services in the same space and time to better understand the ecological constraints underlying these trade-offs and synergies. An analysis is presented that uses data from the Park Grass Experiment at Rothamsted Research on aboveground productivity, species richness and soil organic carbon stocks to quantify the relationships between these three outcomes and the power of variance in plant functional traits in explaining them. There was a trade-off between plots with high productivity, nitrogen inputs and soil organic carbon and plots with high species richness that was explained by a functional gradient of traits that are indicative of contrasting strategies of resource acquisition of resource conservation. Examples were identified of using functional traits to identify opportunities for mitigating these trade-offs and moving toward more multifunctional systems. [ABSTRACT FROM AUTHOR]

A head and neck computed tomography (CT) angiogram revealed a non-specific large heterogenous lesion in the left aspect of the neck (Fig. Neck haematoma is a rare cause of paediatric lateral neck mass. Infectious processes tend to have a cystic appearance with areas of central hypoattenuation with surrounding contrast enhancement on CT scans.[5] Neck haematomas have been reported to be associated with thyroid, parathyroid or other major head and neck surgeries.[6] Spontaneous neck haematomas are uncommon. Paediatric lateral neck masses can have various aetiologies; diagnosis must be supported by the clinical picture and appropriate medical imaging. [Extracted from the article]

• An AI-based suite of tools for scheduling of retrievals and prediction of outcomes is described. • The database consisted of 2085 cycles with 1591 complete records over 4731 visits. • Algorithms were written using Python, NumPy logistic function, Panda and SKLearn. • The algorithm offers options to level-load the clinical and embryology workflow. • This suite of tools assigns a single day to monitor and a range of three retrieval days. Can workflow during IVF be facilitated by artificial intelligence to limit monitoring during ovarian stimulation to a single day and enable level-loading of retrievals? The dataset consisted of 1591 autologous cycles in unique patients with complete data including age, FSH, oestradiol and anti-Müllerian concentrations, follicle counts and body mass index. Observations during ovarian stimulation included oestradiol concentrations and follicle diameters. An algorithm was designed to identify the single best day for monitoring and predict trigger day options and total number of oocytes retrieved. The mean error to predict the single best day for monitoring was 1.355 days. After identifying the single best day for evaluation, the algorithm identified the trigger date and range of three oocyte retrieval days specified by the earliest and the latest day on which the number of oocytes retrieved was minimally changed with a variance of 0–3 oocytes. Accuracy for prediction of total number of oocytes with baseline testing alone or in combination with data on the day of observation was 0.76 and 0.80, respectively. The sensitivities for estimating the total number and number of mature oocytes based solely on pre-IVF profiles in group I (0–10) were 0.76 and 0.78, and in group II (>10) 0.76 and 0.81, respectively. A first-iteration algorithm is described designed to improve workflow, minimize visits and level-load embryology work. This algorithm enables decisions at three interrelated nodal points for IVF workflow management to include monitoring on the single best day, assign trigger days to enable a range of 3 days for level-loading and estimate oocyte number. [ABSTRACT FROM AUTHOR]

Objectives: The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy.Design: Propensity score-matched retrospective cohort analysis.Setting: Tertiary North American liver transplant centers.Patients: Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009-2019) and controls from the U.S. Acute Liver Failure Study Group registry.Interventions: Molecular adsorbent recirculating system treatment versus standard medical therapy (control).Measurements and Main Results: One-hundred four molecular adsorbent recirculating system patients were propensity score-matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King's College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07-3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone ("model 2"; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05-3.31; p = 0.033), and further adjustment of the "main model" for mechanical ventilation, and grade 3/4 hepatic encephalopathy ("model 3"; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07-3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 µmol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 µmol/L; p ≤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 µmol/L), creatinine (83.1 vs 133.5 µmol/L), and ammonia (111.5 vs 140.0 µmol/L; p ≤ 0.022 for all).Conclusions: Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure. [ABSTRACT FROM AUTHOR]

Military vehicles are sometimes required to transit bridges owned and operated by civilian bridge authorities. Using available data regarding the gross vehicle weight and associated axle loads of military traffic, live load factors, calibrated to the Canadian Highway Bridge Design Code, are proposed for bridge design and evaluation. This paper recommends live load factors for three categories of military vehicles: (i) wheeled-transport vehicles; (ii) wheeled-fighting vehicles; and (iii) tracked-fighting vehicles. The values are derived for interior girders of simply supported slab-on-girder bridges subjected to a single lane of traffic loading and are believed to be generally applicable for other structural elements and bridge types. Inherent differences between fighting vehicles, which are heavily armoured, and transport vehicles, which although armoured have high payloads, suggest that highway bridges should be evaluated separately for military fighting vehicles and military transport vehicles using distinct live load factors. [ABSTRACT FROM AUTHOR]

Lyme disease is the most common vector‐borne disease in temperate zones and a growing public health threat in the United States (US). The life cycles of the tick vectors and spirochete pathogen are highly sensitive to climate, but determining the impact of climate change on Lyme disease burden has been challenging due to the complex ecology of the disease and the presence of multiple, interacting drivers of transmission. Here we incorporated 18 years of annual, county‐level Lyme disease case data in a panel data statistical model to investigate prior effects of climate variation on disease incidence while controlling for other putative drivers. We then used these climate–disease relationships to project Lyme disease cases using CMIP5 global climate models and two potential climate scenarios (RCP4.5 and RCP8.5). We find that interannual variation in Lyme disease incidence is associated with climate variation in all US regions encompassing the range of the primary vector species. In all regions, the climate predictors explained less of the variation in Lyme disease incidence than unobserved county‐level heterogeneity, but the strongest climate–disease association detected was between warming annual temperatures and increasing incidence in the Northeast. Lyme disease projections indicate that cases in the Northeast will increase significantly by 2050 (23,619 ± 21,607 additional cases), but only under RCP8.5, and with large uncertainty around this projected increase. Significant case changes are not projected for any other region under either climate scenario. The results demonstrate a regionally variable and nuanced relationship between climate change and Lyme disease, indicating possible nonlinear responses of vector ticks and transmission dynamics to projected climate change. Moreover, our results highlight the need for improved preparedness and public health interventions in endemic regions to minimize the impact of further climate change‐induced increases in Lyme disease burden. [ABSTRACT FROM AUTHOR]

Background: Acute gallstone disease, primarily biliary colic and acute cholecystitis, represents a significant burden on surgical services. Prolonged waiting times for ultrasonography to confirm a diagnosis contributes to inefficiency and delays surgery. Bedside ultrasound offers an opportunity for clinicians make a diagnosis more promptly and streamline acute surgery. This study evaluated the reliability of bedside ultrasound performed by clinicians following local training and a trial of its introduction into clinical practice. Methods: This was a prospective inter‐rater reliability study of bedside ultrasound scans performed on patients referred for suspected acute gallstone disease. Results were compared with a formal ultrasound scan in the radiology department. Inter‐rater agreement for the finding of gallstones and the imaging diagnosis of acute cholecystitis was assessed. Results: A total of 124 patients underwent bedside ultrasound scan, 87 (70.2%) performed by surgical registrars. Mean patient age was 48 years (range 19–92 years) with 95 females (76.6%). Inter‐rater reliability for the finding of gallstones showed strong agreement with kappa 0.85 (95% confidence interval 0.76–0.95) whereas for the imaging diagnosis of acute cholecystitis there was a minimal agreement with kappa 0.37 (95% confidence interval 0.18–0.56). Sensitivity and specificity for the finding of gallstones on bedside ultrasound was 93% and 92%, respectively. Conclusion: Bedside ultrasound is accurate for the finding of gallstones, but the imaging diagnosis of acute cholecystitis is more challenging. There remains the potential for this to improve the efficiency of surgical assessment in suspected acute gallstone disease and this supports the ongoing provision of bedside ultrasound in surgical services. [ABSTRACT FROM AUTHOR]

Tropical forest loss currently exceeds forest gain, leading to a net greenhouse gas emission that exacerbates global climate change. This has sparked scientific debate on how to achieve natural climate solutions. Central to this debate is whether sustainably managing forests and protected areas will deliver global climate mitigation benefits, while ensuring local peoples' health and wellbeing. Here, we evaluate the 10-y impact of a human-centered solution to achieve natural climate mitigation through reductions in illegal logging in rural Borneo: an intervention aimed at expanding health care access and use for communities living near a national park, with clinic discounts offsetting costs historically met through illegal logging. Conservation, education, and alternative livelihood programs were also offered. We hypothesized that this would lead to improved health and well-being, while also alleviating illegal logging activity within the protected forest. We estimated that 27.4 km² of deforestation was averted in the national park over a decade (~70% reduction in deforestation compared to a synthetic control, permuted P = 0.038). Concurrently, the intervention provided health care access to more than 28,400 unique patients, with clinic usage and patient visitation frequency highest in communities participating in the intervention. Finally, we observed a dose-response in forest change rate to intervention engagement (person-contacts with intervention activities) across communities bordering the park: The greatest logging reductions were adjacent to the most highly engaged villages. Results suggest that this community-derived solution simultaneously improved health care access for local and indigenous communities and sustainably conserved carbon stocks in a protected tropical forest. [ABSTRACT FROM AUTHOR]

Global environmental change is having profound effects on the ecology of infectious disease systems, which are widely anticipated to become more pronounced under future climate and land use change. Arthropod vectors of disease are particularly sensitive to changes in abiotic conditions such as temperature and moisture availability. Recent research has focused on shifting environmental suitability for, and geographic distribution of, vector species under projected climate change scenarios. However, shifts in seasonal activity patterns, or phenology, may also have dramatic consequences for human exposure risk, local vector abundance and pathogen transmission dynamics. Moreover, changes in land use are likely to alter human–vector contact rates in ways that models of changing climate suitability are unlikely to capture. Here we used climate and land use projections for California coupled with seasonal species distribution models to explore the response of the western blacklegged tick (Ixodes pacificus), the primary Lyme disease vector in western North America, to projected climate and land use change. Specifically, we investigated how environmental suitability for tick host‐seeking changes seasonally, how the magnitude and direction of changing seasonal suitability differs regionally across California, and how land use change shifts human tick‐encounter risk across the state. We found vector responses to changing climate and land use vary regionally within California under different future scenarios. Under a hotter, drier scenario and more extreme land use change, the duration and extent of seasonal host‐seeking activity increases in northern California, but declines in the south. In contrast, under a hotter, wetter scenario seasonal host‐seeking declines in northern California, but increases in the south. Notably, regardless of future scenario, projected increases in developed land adjacent to current human population centers substantially increase potential human–vector encounter risk across the state. These results highlight regional variability and potential nonlinearity in the response of disease vectors to environmental change. [ABSTRACT FROM AUTHOR]

Understanding seasonal patterns of activity, or phenology, of vector species is fundamental to determining seasonality of disease risk and epidemics of vector‐borne disease. Spatiotemporal variation in abiotic conditions can influence variation in phenological patterns and life history events, which can dramatically influence the ecological role and human impact of a species. For arthropod vectors of human diseases such as ticks, these phenological patterns determine human exposure risk, yet how abiotic conditions interact to determine suitable conditions for host‐seeking of vector species is difficult to disentangle.Here, we use MaxEnt to model spatial patterns and differences in host‐seeking phenology of the western blacklegged tick (Ixodes pacificus) in California using spatially and temporally refined adult tick occurrence data and similarly refined climate and environmental data. We empirically validate the model using phenological data from field studies conducted at sites across California's latitudinal gradient.We find adult tick host‐seeking activity varies substantially throughout the year, as well as across the large latitudinal gradient in the state. Suitable conditions for host‐seeking are found earlier in fall and later in the spring in northern than in southern California. These seasonal patterns are primarily associated with monthly precipitation, minimum winter temperature, and winter precipitation, with maximum monthly temperature possibly playing a more prominent role in limiting host‐seeking activity earlier in the spring in southern than northern California.Synthesis and applications. Modelling the seasonal activity of the western blacklegged tick, we find both a longer window for host‐feeding and more protracted risk of human exposure to this vector species in northern than southern California. We further identify key environmental factors associated with these patterns, including precipitation and temperature that are otherwise challenging to elucidate in field and laboratory studies over large spatial scales. Moreover, we illustrate how species distribution models, in combination with temporally refined species occurrence and environmental data, can be used to investigate environmental factors predictive of geographic variation in seasonality or phenology of vector species. This produces not only novel ecological insight, but key information for public health practitioners in managing vector‐borne disease transmission and targeting public outreach and interventions. [ABSTRACT FROM AUTHOR]

Deforestation and land use change are among the most pressing anthropogenic environmental impacts. In Brazil, a resurgence of malaria in recent decades paralleled rapid deforestation and settlement in the Amazon basin, yet evidence of a deforestation-driven increase in malaria remains equivocal. We hypothesize an underlying cause of this ambiguity is that deforestation and malaria influence each other in bidirectional causal relationships--deforestation increases malaria through ecological mechanisms and malaria reduces deforestation through socioeconomic mechanisms--and that the strength of these relationships depends on the stage of land use transformation. We test these hypotheses with a large geospatial dataset encompassing 795 municipalities across 13 y (2003 to 2015) and show deforestation has a strong positive effect on malaria incidence. Our results suggest a 10% increase in deforestation leads to a 3.3% increase in malaria incidence (~9,980 additional cases associated with 1,567 additional km² lost in 2008, the study midpoint, Amazon-wide). The effect is larger in the interior and absent in outer Amazonian states where little forest remains. However, this strong effect is only detectable after controlling for a feedback of malaria burden on forest loss, whereby increased malaria burden significantly reduces forest clearing, possibly mediated by human behavior or economic development. We estimate a 1% increase in malaria incidence results in a 1.4% decrease in forest area cleared (~219 fewer km² cleared associated with 3,024 additional cases in 2008). This bidirectional socioecological feedback between deforestation and malaria, which attenuates as land use intensifies, illustrates the intimate ties between environmental change and human health. [ABSTRACT FROM AUTHOR]

Si bien algunos estudios observan que las minorías étnicas urbanas en China perciben salarios más bajos que la mayoría han, otros no constatan la existencia de esa brecha. Para resolver esta contradicción, los autores proponen desglosar las experiencias laborales por grupo étnico minoritario. El análisis de las minorías étnicas sobre un amplio conjunto de datos indica que las «minorías foráneas», como los tibetanos y los grupos túrquicos, sufren una penalización salarial significativa cuando se controlan las covariables, pero no ocurre lo mismo con la totalidad de las minorías. Estas conclusiones son robustas en varias especificaciones y tienen importantes implicaciones teóricas y en materia de políticas. [ABSTRACT FROM AUTHOR]

Persistent human papillomavirus (HPV) infection is the leading cause of cervical cancer. Although the fundamental link between HPV infection and oncogenesis is established, the specific mechanisms of virus-mediated transformation are not fully understood. We previously demonstrated that the HPV encoded E6 protein increases the activity of the proto-oncogenic transcription factor STAT3 in primary human keratinocytes; however, the molecular basis for STAT3 activation in cervical cancer remains unclear. Here, we show that STAT3 phosphorylation in HPV positive cervical cancer cells is mediated primarily via autocrine activation by the pro-inflammatory cytokine Interleukin 6 (IL-6). Antibody-mediated blockade of IL-6 signalling in HPV positive cells inhibits STAT3 phosphorylation, whereas both recombinant IL-6 and conditioned media from HPV positive cells leads to increased STAT3 phosphorylation within HPV negative cervical cancer cells. Interestingly, we demonstrate that activation of the transcription factor NFκB, involving the small GTPase Rac1, is required for IL-6 production and subsequent STAT3 activation. Our data provides new insights into the molecular re-wiring of cancer cells by HPV E6. We reveal that activation of an IL-6 signalling axis drives the autocrine and paracrine phosphorylation of STAT3 within HPV positive cervical cancers cells and that activation of this pathway is essential for cervical cancer cell proliferation and survival. Greater understanding of this pathway provides a potential opportunity for the use of existing clinically approved drugs for the treatment of HPV-mediated cervical cancer. [ABSTRACT FROM AUTHOR]

Infectious diseases are rapidly emerging and many are increasing in incidence across the globe. Processes of land‐use change, notably habitat loss and fragmentation, have been widely implicated in the emergence and spread of zoonoses such as Lyme disease, yet evidence remains equivocal.Here, we discuss and apply an innovative approach from the social sciences; instrumental variables, which seeks to tease out causality from observational data. Using this approach, we revisit the effect of forest fragmentation on Lyme disease incidence, focusing on human interaction with fragmented landscapes. Although human interaction with infected ticks is of clear and fundamental importance to human disease incidence, human activities that influence exposure have been largely overlooked in ecology literature.Using county‐level land‐use and Lyme disease incidence data for ~800 counties from the northeastern United States over the span of a decade, we illustrate (a) that human interaction with fragmented forest landscapes reliably predicts Lyme disease incidence, while ecological measures of forest fragmentation alone are unreliable predictors and (b) that identifying the effect of forest fragmentation on human disease entails addressing the feedback between Lyme disease risk and human decisions to avoid interaction with high‐risk landscapes.Synthesis and applications. Our innovative approach and novel results help to clarify the equivocal literature on the effects of forest fragmentation on Lyme disease and illustrate the key role that human behaviour may be playing in the ecology of Lyme disease in North America. Accounting for human activity and behaviour in the ecology of disease more broadly may result in improved understanding of both the ecological drivers of disease, as well as actionable intervention strategies to reduce disease burden in a changing world. For example, our model results indicate that forest fragmentation by human settlement increases Lyme disease incidence, which has practical implications for land‐use policy aimed at disease reduction. Specifically, our model suggests land‐use regulations that reduce parcel size would be an actionable approach to reduce Lyme disease transmission for policymakers concerned about increasing Lyme disease incidence in the northeastern United States. Our innovative approach and novel results help to clarify the equivocal literature on the effects of forest fragmentation on Lyme disease and illustrate the key role that human behaviour may be playing in the ecology of Lyme disease in North America. Accounting for human activity and behaviour in the ecology of disease more broadly may result in improved understanding of both the ecological drivers of disease, as well as actionable intervention strategies to reduce disease burden in a changing world. For example, our model results indicate that forest fragmentation by human settlement increases Lyme disease incidence, which has practical implications for land‐use policy aimed at disease reduction. Specifically, our model suggests land‐use regulations that reduce parcel size would be an actionable approach to reduce Lyme disease transmission for policymakers concerned about increasing Lyme disease incidence in the northeastern United States. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are life-threatening illnesses requiring intensive care admission and potentially liver transplantation. Artificial extracorporeal liver support (ECLS) systems remove water-soluble and albumin-bound toxins to maintain normal serum chemistry, prevent further hepatic/organ system damage, and create an environment for potential hepatic regeneration/recovery (ALF) or bridge to liver transplantation (ALF and ACLF). Use of artificial ECLS has been studied in both ALF and ACLF. Artificial ECLS systems have been found to be safe and have demonstrated the following benefits: improvement of biochemistries, hemodynamic status, and hepatic encephalopathy. Despite this, only one prospective randomized controlled trial examining the use of high-volume plasma exchange has demonstrated improvement in transplant-free survival. Bioartificial (cell-based) ECLS systems build on the technology of artificial systems, incorporating living hepatocytes in a bioactive platform to further mimic endogenous hepatic detoxification and synthetic functions. Currently, no bioartificial system has been found to confer a mortality benefit; however, these platforms offer the greatest potential for future development. [ABSTRACT FROM AUTHOR]

The article focuses on the history of New England Calvinism during the 19th century. Topics include the split between New Light Calvinists, as founded by Jonathan Edwards and under the teachings of Samuel Hopkins, and Old School Calvinism, and the split of the New Divinity into Taylorism, under the direction of Nathaniel Taylor, and Tylerism, led by Bennet Tyler.

The distribution, abundance and seasonal activity of vector species, such as ticks and mosquitoes, are key determinants of vector-borne disease risk, and are strongly influenced by abiotic and habitat conditions. Despite the numerous species of tick vectors in the heavily populated North American West Coast, all but Ixodes pacificus, the primary vector of the Lyme disease spirochete, is poorly characterized with regard to seasonal activity patterns and fine scale drivers of distribution and abundance, particularly in heavily populated regions of southern California. This lack of knowledge inhibits both scientific understanding and public health efforts to minimize vector exposure and risk of pathogen transmission to humans. Here we address this gap by characterizing the abiotic and habitat drivers of the distribution, abundance, and diversity of the vector tick community using fine scale temporal surveys over two seasons (2014 and 2015) across coastal and inland regions of Santa Barbara County, CA. We also characterize patterns of seasonal activity of the more common vector species to understand seasonality in risk of vector exposure, and specifically focus on human encounter risk using standardized tick drags as our method of collection. Leveraging plot-level habitat and abiotic variables in partial least squares regression analysis, we find the seven different vector species collected in this study have divergent drivers of activity and abundance. For example, I. pacificus is strongly associated with dense forest habitats and cool and moist microclimates, while Dermacentor occidentalis and Dermacentor variabilis, competent vectors of Rocky Mountain Spotted Fever, were found to be more tolerant of higher average temperatures and more open habitats. These results suggest that I. pacificus may be expected to experience reductions in geographic distribution and seasonal activity under projected land cover and climate change in coastal southern California, while D. occidentalis may experience more limited effects. We discuss implications for changing tick-borne disease risk associated with pathogens transmitted by Ixodes as well as Dermacentor species ticks in the western US, and contrast these predictions with eastern North America. [ABSTRACT FROM AUTHOR]

The social welfare of ethnic minorities is a contested subject with a deep politicalised history in contemporary China. This article uses a new large dataset solely looking at ethnic minorities in China, to analyse the impact and outcomes that new urban social and welfare schemes – with notable attention to the basic medical insurance, and the minimum livelihood guarantee allowance (dibao) – have on the livelihoods of minorities. The data suggests that, contrary to the pro-minority rhetoric of the state, minority participation in social welfare programmes is predicated on the incentive set of local government officials. These findings have strong implications for constructing future social welfare policies, and for understanding their potential differential impact on ethnic minority cohorts. [ABSTRACT FROM PUBLISHER]

Local gas transport limitation attributed to the ionomer thin-film in the catalyst layer is a major deterrent to widespread commercialization of polymer-electrolyte fuel cells. So far functionality and limitations of these thin-films have been assumed identical in the anode and cathode. In this study, Nafion ionomer thin-films on platinum(Pt) support were exposed to H 2 and air as model schemes, mimicking anode and cathode catalyst layers. Findings indicate decreased swelling, increased densification of ionomer matrix, and increased humidity-induced aging rates in reducing environment, compared to oxidizing and inert environments. Observed phenomenon could be related to underlying Pt-gas interaction dictating Pt-ionomer behavior. Presented results could have significant implications about the disparate behavior of ionomer thin-film in anode and cathode catalyst layers. [ABSTRACT FROM AUTHOR]

Background: Tick-borne diseases, particularly Lyme disease, are emerging across the northern hemisphere. In order to manage emerging diseases and predict where emergence will likely occur, it is necessary to understand the factors influencing the distribution, abundance and infection prevalence of vector species. In North America, Lyme disease is the most common vector-borne disease and is transmitted by blacklegged ticks. This study aimed to explore the abiotic and environmental drivers of density and infection prevalence of western blacklegged ticks (Ixodes pacificus) in southern California, an understudied and densely populated region of North America. Results: Over the course of this two-year study, densities of I. pacificus adults were consistently positively associated with host availability for juvenile ticks and dense oak woodland habitat. Densities of nymphal and larval I. pacificus, on the other hand were primarily predicted by host availability for juvenile ticks in the first year of the study, and by habitat characteristics such as dense leaf litter in the second year. Infection with the causative agent of Lyme disease, Borrelia burgdorferi (sensu stricto), and related spirochetes was not predicted by the abiotic conditions promoting I. pacificus populations, but rather by diversity of the tick community, and in particular by the presence of two Ixodes tick species that do not generally feed on humans (Ixodes spinipalpis and Ixodes peromysci). Borrelia spp. infection was not detected in the I. pacificus populations sampled, but was detected in other vector species that may maintain enzootic transmission of the pathogen on the landscape. Conclusions: This study identified dense oak woodlands as high-risk habitats for I. pacificus tick encounter in southern California. The shift in relative importance of host availability to habitat characteristics in predicting juvenile tick abundance occurred as California's historic drought intensified, suggesting that habitat providing suitable microclimates for tick survivorship became centrally important to patterns of abundance in the face of deleterious abiotic conditions. These results underscore the need for further investigation of the effects of climate change on tick-borne disease in California. Finally, despite low risk of human Lyme disease infection posed by I. pacificus in southern California, evidence of infection was found in other tick species, suggesting that enzootic transmission of tick-borne borreliae may be occurring in southern California, and involve parallel enzootic cycles with other tick and host species but not necessarily humans. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) lie at the heart of the innate immune system, specialised at recognising danger signals in many forms including foreign material, infection or tissue damage and initiating powerful adaptive immune and inflammatory responses. In barrier sites such as the lung, the instrumental role that DCs play at the interface between the environment and the host places them in a pivotal position in determining the severity of inflammatory disease. The past few years has seen a significant increase in our fundamental understanding of the subsets of DCs involved in pulmonary immunity, as well as the mechanisms by which they are activated and which they may use to coordinate downstream inflammation and pathology. In this review, we will summarise current understanding of the multi-faceted role that DCs play in the induction, maintenance and regulation of lung immunopathology, with an emphasis on allergic pulmonary disease. [ABSTRACT FROM AUTHOR]

This article opens up the 1914 case of smugglers Hira Naran and Dulabh Vira, to consider an illicit trade in gold between the eastern ports of southern Africa, east Africa and southern Asia. From a newly compiled database of two and a half thousand known gold dealers active in southern Africa between 1906 and 1926, it is evident that illicit gold dealing was a significant, if hidden, aspect of the region’s towns and ports. Gold was informally ‘exported’ from Johannesburg by an amorphous, diverse group of runners to Durban and Lourenço Marques. At the ports, Gujarati firms, increasingly marginalised by racial legislation, took a leading role in transmitting gold, or sonū, eastwards across the Indian Ocean. The article shows, rather than discusses in the abstract, how a transnational method can reveal hitherto obscure but important themes in southern African history. The article argues that a half-millennium-old indigenous gold trade between south-east Africa and India, in apparent decline by the 1870s, was invigorated by the growth of the Witwatersrand mining economy. Administrators saw the ports as important sites of regulation and restriction, but failed to rupture the old gold smuggling networks decisively, in ways that posed important, unresolvable questions about the institutional capacity of the South African state at its maritime gateways. [ABSTRACT FROM AUTHOR]

The article discusses what were known as the Assyrian Christian charity collectors from the 1860s through the 1940s, with a particular focus on their role in stealing and the Reverend Dr. M.G. Daniel's role in as an Assyrian charity collector. An overview of the transnational aspects of the Assyrian charity collectors is provided.

The management of climate-resilient grassland systems is important for stable livestock fodder production. In the face of climate change, maintaining productivity while minimizing yield variance of grassland systems is increasingly challenging. To achieve climate-resilient and stable productivity of grasslands, a better understanding of the climatic drivers of long-term trends in yield variance and its dependence on agronomic inputs is required. Based on the Park Grass Experiment at Rothamsted (UK), we report for the first time the long-term trends in yield variance of grassland (1965–2018) in plots given different fertilizer and lime applications, with contrasting productivity and plant species diversity. We implemented a statistical model that allowed yield variance to be determined independently of yield level. Environmental abiotic covariates were included in a novel criss-cross regression approach to determine climatic drivers of yield variance and its dependence on agronomic management. Our findings highlight that sufficient liming and moderate fertilization can reduce yield variance while maintaining productivity and limiting loss of plant species diversity. Plots receiving the highest rate of nitrogen fertilizer or farmyard manure had the highest yield but were also more responsive to environmental variability and had less plant species diversity. We identified the days of water stress from March to October and temperature from July to August as the two main climatic drivers, explaining approximately one-third of the observed yield variance. These drivers helped explain consistent unimodal trends in yield variance—with a peak in approximately 1995, after which variance declined. Here, for the first time, we provide a novel statistical framework and a unique long-term dataset for understanding the trends in yield variance of managed grassland. The application of the criss-cross regression approach in other long-term agro-ecological trials could help identify climatic drivers of production risk and to derive agronomic strategies for improving the climate resilience of cropping systems. [ABSTRACT FROM AUTHOR]

The article focuses on the strategic approaches to the systematic study of the operations encountered by the gaming companies in the U.S. it offers information on the strategic issues affronted by the casino organizations during the legalization of gaming and liberalizing the gaming laws. It informs about the Executive Development Program (EDP) jointly organized by William R. Eadington and Andrew MacDonald , which disscussed challenges faced by the casino managers and executives in the U.S.

Abstract: Human respiratory syncytial virus (HRSV) is a member of the family Paramyxoviridae, and is responsible for serious respiratory illness in infants, the elderly and the immunocompromised. HRSV exists as two distinct lineages known as subgroups A and B, which represent two lines of divergent evolution with extensive genetic and serologic differences. While both subgroup A and B viruses contribute to overall HRSV disease, subgroup A isolates are associated with both increased frequency and morbidity of infections, and reasons for this are unclear. HRSV disease is characterized by virus-mediated cell destruction in combination with extensive inflammatory and immune modulatory responses, and for HRSV subgroup A isolates, several of these signaling pathways are regulated through activation of the transcription factor NF-κB. In contrast, the NF-κB activation characteristics of HRSV subgroup B infection remain untested. Here, we performed a quantitative and comparative analysis of NF-κB activation in response to infection of both continuous and primary cell cultures with HRSV subgroup A and B isolates. Our results showed the model HRSV subgroup A isolate consistently induced increased NF-κB activation compared to its HRSV subgroup B counterpart. The differential NF-κB activation characteristics of HRSV subgroup A and B viruses may contribute to differences in their pathogenesis. [Copyright &y& Elsevier]

Background and aims: Take-all, caused by the fungus Gaeumannomyces graminis var. tritici, is the most damaging root disease of wheat. A severe attack often leads to premature ripening and death of the plant resulting in a reduction in grain yield and effects on grain quality (Gutteridge et al. in Pest Manag Sci 59:215-224, ). Premature death of the plant could also lead to inefficient use of applied nitrogen (Macdonald et al. in J Agric Sci 129(2):125-154, ). The aim of this study was to determine crop N uptake and the amount of residual mineral N in the soil after harvest where different severities of take-all had occurred. Methods: Plant and soil samples were taken at anthesis and final harvest from areas showing good and poor growth (later confirmed to be caused by take-all disease) in three winter wheat crops grown on the same soil type on Rothamsted Farm in SE England in 1995, 2007 and 2008 (harvest sampling only). All crops received fertiliser N in spring at recomended rates (190-200 kg N ha). On each ocassion crops were assessed for severity of take-all infection (TAR) and crop N uptakes and soil nitrate plus ammonium (SMN) was determined. Grain yields were also measured. Results: Grain yields (at 85% dry matter) of crops with moderate infection (good crops) ranged from 4.3 to 13.0 t ha, compared with only 0.9-4.5 t ha for those with severe infection (poor crops). There were significant ( P < 0.05) negative relationships between crop N uptake and TAR at anthesis and final harvest. At harvest, good crops contained 129-245 kg N ha in grain, straw and stubble, of which 85-200 kg N ha was in the grain. In contrast, poor crops contained only 46-121 kg N ha, of which only 22-87 kg N ha was in the grain. Positive relationships between SMN and TAR were found at anthesis and final harvest. The SMN in the 0-50 cm layer following harvest of poor crops was significantly ( P < 0.05) greater than that under good crops, and most (73-93%) was present as nitrate. Conclusions: Localised patches of severe take-all infection decreased the efficiency with which hexaploid wheat plants recovered soil and fertiliser derived N, and increased the subsequent risk of nitrate leaching. The risk of gaseous N losses to the atmosphere from these areas may also have been enhanced. [ABSTRACT FROM AUTHOR]

Abstract: Type I IFNs (IFNα/β) are essential anti-viral cytokines produced in response to the detection of viral components by host pattern recognition receptors. IFNα/β production is transient, and aberrant activation can be hazardous to the host. In this article, we review our current understanding of host negative regulatory mechanisms that control IFNα/β production. [Copyright &y& Elsevier]

Abstract: IL-18 belongs to the IL-1 family of cytokines and has recently regained interest in the context of inflammasome activation. The inflammasome dependent caspase 1 cleaves pro-IL-18 into the active form — similar to what is known for IL-1ß. Still, the action and importance of IL-18 are not completely understood. There are several indications that it plays a pathogenetically important role in chronic inflammatory conditions of epithelial organs (such as skin, gut, kidney) and importantly also in responses against self. Here, we summarise current knowledge on the role of IL-18 in human skin inflammation with a focus on its role in Cutaneous Lupus Erythematosus (CLE). There is evidence that IL-18 plays a role in CLE upstream of TNFα. In CLE but not normal keratinocytes IL-18 strongly induces TNFα release, which then results in apoptosis. Blocking TNFα in vitro prevents apoptosis of keratinocytes but anti-TNFα therapy is not applicable in LE conditions. We will discuss potential approaches to control IL-18 in skin inflammation. [Copyright &y& Elsevier]

Background: Pim-1, 2 and 3 are a group of enzymes related to the calcium calmodulin family of protein kinases. Over-expression of Pim-1 and Pim-2 in mice promotes the development of lymphomas, and up-regulation of Pim expression has been observed in several human cancers. Results: Here we show that the pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells. In vitro mapping showed that Pim-2 predominantly phosphorylated Ser112, while Pim-1 phosphorylated Ser112, but also Ser136 and Ser155 at a reduced rate compared to Ser112. Pim-3 was found to be the least specific for Ser112, and the most effective at phosphorylating Ser136 and Ser155. Pim-3 was also able to phosphorylate other sites in Bad in vitro, including Ser170, another potential in vivo site. Mutation of Ser136 to alanine prevented the phosphorylation of Ser112 and Ser155 by Pim kinases in HEK-293 cells, suggesting that this site must be phosphorylated first in order to make the other sites accessible. Pim phosphorylation of Bad was also found to promote the 14-3-3 binding of Bad and block its association with Bcl-XL. Conclusion: All three Pim kinase family members predominantly phosphorylate Bad on Ser112 and in addition are capable of phosphorylating Bad on multiple sites associated with the inhibition of the pro-apoptotic function of Bad in HEK-293 cells. This would be consistent with the proposed function of Pim kinases in promoting cell proliferation and preventing cell death. [ABSTRACT FROM AUTHOR]

Summary: Background:: Injury is a common cause of emergency department (ED) attendance but there are few data published on the spectrum of paediatric injury in a typical district general hospital (DGH). This study aimed to provide a complete picture of injury presentations to such a centre. Methods:: Prospective questionnaire study of consecutive paediatric attendances at a DGH ED in Scotland (annual attendance 53,500 patients) due to injury or poisoning. Paediatric in this context was defined as less than 14 years on the day of presentation. Admission rates were identified from the hospital information system and information on deaths was sought from the local Procurator Fiscal (the Scottish equivalent of the Coroner). Results:: One thousand three hundred and seventy-eight questionnaires were completed from a potential 10,697 eligible patients. Safety devices (helmets, belts, etc.) were in use in only 99 cases. Cycle helmets were used in 26% of cycle incidents and seat belts were used in 71% of car incidents. Cycling and pedestrian incidents were more common during the summer months and outside school hours. Adult supervision was present in 49% of incidents. Seventy-three percent of incidents at school were unsupervised. There were 5.6 admissions to hospital per day in the 0–13 years age group for all causes, with little seasonal variation in admission rates. There were three deaths during the year, two from SIDS and one due to choking, all in infants. Conclusion:: Trauma is a common cause of ED attendance in children. Preventative measures are still underutilised and could make a significant impact on the incidence of children''s injuries and possibly ED attendances. Cycle helmets could play a major role in injury prevention in school age children in this area. [Copyright &y& Elsevier]

The hepatitis C virus (HCV) nonstructural NS5A protein has been shown to bind to and activate phosphoinositide 3-kinase (PI3K), resulting in activation of the downstream effector serine/threonine kinase Akt/protein kinase B. Here we present data pertaining to the effects of NS5A-mediated Akt activation on its downstream targets. Using a recombinant baculovirus to deliver the complete HCV polyprotein to human hepatoma cells in a tetracycline-regulable fashion, we confirm that expression of the complete HCV polyprotein also activates PI3K and Akt. We further show that this results in the inhibition of the Akt substrate Forkhead transcription factor and the stimulation of phosphorylation of a second key Akt substrate, glycogen synthase kinase-3β (GSK-3β). Phosphorylation of GSK-3β results in its inactivation; consistent with this, we show that expression of the HCV polyprotein results in the accumulation of β-catenin. Finally, we show that levels of β-catenin-dependent transcription are also elevated in the presence of the HCV polyprotein. Given the prevalence of β-catenin mutations in many human tumors, especially colon and hepatocellular carcinomas, these data implicate NS5A-mediated PI3K activation as a contributory factor in the increasingly common association between HCV infection and the development of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Discusses a study indicating that the hepatitis C virus non-structural 5A protein inhibits activating protein-1 function by perturbing Ras-ERK pathway signaling. Association of the hepatitis C virus NS5A protein with a variety of cellular signaling proteins; Signaling pathways targeted by NS5A to inhibit AP1; Comparable inhibition of AP1 reporter activity observed in hepatocyte-derived cell lines.

Schistosomes are parasitic worms that are a prime example of a complex multicellular pathogen that flourishes in the human host despite the development of a pronounced immune response. Understanding how the immune system deals with such pathogens is a daunting challenge. The past decade has seen the use of a wide range of new approaches to determine the nature and function of the immune response to schistosomes. Here, we attempt to summarize advances in our understanding of the immunology of schistosomiasis, with the bulk of the review reflecting the experimental focus on Schistosoma mansoni infection in mice. [ABSTRACT FROM AUTHOR]

Discusses the volatility of table games using the Baccarat. Conduction of high end play; Verification of the formula to determine the number of hands played; Level of departure from the mean win percentage.

Dural arteriovenous fistulae (DAVFs) are a rare form of intracranial arteriovenous malformation. We present the case of a patient who presented in a previously undescribed manner with facial swelling and bruising initially misdiagnosed as cellulitis. He was found subsequently to have DAVFs of the sphenoparietal sinus that had hemorrhaged. The rarity of DAVFs at this location may account for this unique presentation. Successful treatment was achieved by transarterial embolization. [ABSTRACT FROM AUTHOR]

Accurate identification of agricultural pests is a major component of integrated pest management. The seedcorn maggot, Delia platura (Meigen) (Diptera: Anthomyiidae), is a cosmopolitan polyphagous pest species that may be found in high numbers in numerous crops. Two morphologically identical genetic lines of D. platura (H and N) with distinct distributions were recently identified. To date, no study has investigated the reproductive compatibility of the two lines and thus the possibility that they may actually be two unique biological entities. A previous study described the reproductive traits of the two lines and suggested that H‐line females are highly selective toward the male with which they mate, pointing to a possible pre‐mating isolation mechanism between the lines. Using laboratory‐reared colonies originating from the Montérégie region in Québec, Canada, this study investigates the reproductive compatibility of the two D. platura lines. We found that only one of 30 H‐line females was inseminated by an N‐line male, further suggesting mate choice as a pre‐mating isolation mechanism between the lines. However, N‐line females were readily inseminated by H‐line males, suggesting a lack of pre‐mating isolation in this type of cross. The eggs laid by N‐line females mated with H‐line males had a lower hatching rate than the ones laid by females of intraline crosses, suggesting either post‐mating pre‐zygotic or post‐zygotic partial isolation. However, the larvae that did hatch had a comparable developmental success to those from intraline crosses in terms of survival and developmental time from larval hatching to adult emergence, pupal mass, and adult sex ratio, suggesting a lack of post‐zygotic isolation for these life stages. Considering the different biological traits of the two lines, we suggest the use of the 'biotype' terminology to designate the two biological entities and discuss their implications for integrated pest management. [ABSTRACT FROM AUTHOR]

Loss of T lymphocyte proliferation and the emergence of a host response that is dominated by a Th2-type profile are well-established features of human filarial infection. Downregulation and modulation of host T cell responses during lymphatic filariasis has been investigated by implantation of parasite stages into inbred mice. Adherent peritoneal exudate cells (PEC) from mice transplanted with adult or larval Brugia malayi parasites are profoundly anti-proliferative but do not prevent antigen-specific cytokine production by T cells. We demonstrate here that the excretory/secretory (E/S) products of the adult parasite are sufficient to induce PEC that block proliferation if injected daily into mice. We have previously shown that in vivo production of host IL-4 is required for the generation of suppressive cells. Because the induction of host IL-4 is characteristic of infection with nematodes, we asked whether E/S from two other nematode parasites, Nippostrongylus braziliensis and Toxocara canis were also capable of generating a suppressor cell population. Injection of E/S from these two parasites also led to a reduction in T cell proliferation suggesting that this mechanism of down-regulating host responses is a feature common to nematode parasites. [ABSTRACT FROM AUTHOR]

The article offers information on the Bedside ultrasound has been embraced by specialists, particularly in the fields of Emergency Medicine and Obstetrics & Gynaecology. It mentions acceptable rates of diagnostic accuracy for bedside ultrasound performed by surgeons, in comparison to formal departmental ultrasound scans; and also mentions the provision of bedside ultrasound for surgeons is both an exciting opportunity and a challenge for surgeons and surgical trainees.

Human papillomaviruses (HPVs) are small, DNA viruses that cause around 5% of all cancers in humans, including almost all cervical cancer cases and a significant proportion of anogenital and oral cancers. The HPV oncoproteins E5, E6 and E7 manipulate cellular signalling pathways to evade the immune response and promote virus persistence. The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has emerged as a key mediator in a wide range of important biological signalling pathways, including cell proliferation, cell survival and the immune response. While STAT1 and STAT2 primarily drive immune signalling initiated by interferons, STAT3 and STAT5 have widely been linked to the survival and proliferative potential of a number of cancers. As such, the inhibition of STAT3 and STAT5 may offer a therapeutic benefit in HPV-associated cancers. In this review, we will discuss how HPV manipulates JAK/STAT signalling to evade the immune system and promote cell proliferation, enabling viral persistence and driving cancer development. We also discuss approaches to inhibit the JAK/STAT pathway and how these could potentially be used in the treatment of HPV-associated disease. [ABSTRACT FROM AUTHOR]