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Numbers of Critically Endangered Hooded Vultures ( Necrosyrtes monachus Temminck 1823) are declining across their distribution. The range-edge population in South Africa is one of the smallest populations with only 100-200 mature individuals. In South Africa, Hooded Vultures nest solitarily in loose colonies (mean distance between nests 0.76 km) along water courses. Basic ecological information, such as breeding behaviour, is still lacking for the species. In this study, we examine the relatedness and nest turnover of nesting individuals along the Olifants River and other locations in the Lowveld of South Africa by sampling nests over five consecutive years. A key hypothesis tested is whether communal roosting sites function as information-sharing hubs, a phenomenon that has been seen in Cape Vultures ( Gyps coprotheres ) and other cliff-nesting vultures. Theory suggests that information sharing occurs more frequently between closely related individuals. If true, we expect distance between nests and genetic relatedness to be positively correlated and individuals to use the same nests over multiple years. Naturally moulted feathers ( n  = 108) were collected below nests over five consecutive years, and 14 microsatellite loci markers were used to measure genetic relatedness. Mantel tests performed correlating distance between nests to relatedness coefficient estimators TrioML ( r  = 0.032, R 2  = 0.001, p  = 0.224) and LynchRD ( r  = 0.007, R 2  = 0.00005, p  = 0.403), found no statistical correlation. The Mantel test performed using Nei's genetic distance and distance between nests did show a negative correlation ( r  = -0.108, R 2  = 0.0117, p -value = 0.012), indicating that individuals that were more closely related tended to breed further away. No nest reuse was found in this study. We thus believe that these loose colonies do not act as food-finding hubs, but rather that the Olifants River is an important breeding site for these birds., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Critically endangered Hooded Vultures (Necrosyrtes monachus Temminck, 1823), like many vulture species globally, are experiencing rapid population declines due to anthropogenic factors such as poisonings, human persecution, trading for belief-based use, and habitat loss/degradation. The Hooded Vulture is widespread across sub-Saharan Africa. Although it is considered one of the most abundant vultures in West Africa, this vulture species is less common in East and southern Africa, with the population at the southern-most edge of the distribution (in South Africa and Eswatini) estimated at only 100-200 mature individuals. The distribution of Hooded Vultures has contracted dramatically in southern Africa, with breeding populations largely confined to protected areas such as the Greater Kruger National Park. This study aimed to investigate the genetic diversity of the southern African range-edge population and assess if the recent contraction in the distribution has resulted in the population experiencing a genetic bottleneck. Sixteen microsatellite loci were amplified for samples collected along the Olifants River in the Greater Kruger National Park (n = 30). The genetic diversity in the South African population was compared to samples (n = 30) collected in Ghana, where Hooded Vultures are more abundant. Contrary to expectations, the South African peripheral Hooded Vulture population showed higher levels of heterozygosity (H O  = 0.495) than the Ghanaian population (H O  = 0.315). Neither population showed signs of recent bottleneck events when tested using demographic modelling and Approximate Bayesian computation (ABC). However, both populations showed high levels of inbreeding and relatedness. Our results suggest that despite being a small peripheral population, the South African Hooded Vulture population showed a similar level of genetic diversity as individuals sampled from a core population within the species distribution (in Ghana). This study supports the need for Hooded Vulture conservation efforts in the southern African region and highlights the evolutionary importance of range-edge populations., (© 2024. The Author(s).)

In this latest article in Leslee Thompson's Health Quality 5.0 series, she discusses the slow progress of patient engagement in healthcare over the past two decades, emphasizing the need for co-creation where patients and providers collaborate equally. It explores the challenges of overcoming traditional power dynamics and integrating patient knowledge into healthcare systems. Highlighting examples from around the world, the article identifies five success factors for global impact and stresses the importance of a holistic, inclusive approach to healthcare transformation. Co-creation is presented as essential for building resilient, high-performing health systems centred on patients' needs and experiences., (Copyright © 2024 Longwoods Publishing.)

Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood-brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND.

In recent years, Hooded Vulture populations in West Africa have decreased substantially. However, in some areas within this region, the species is still relatively abundant. To find out more about the situation in West Africa, we assessed the status of Hooded Vultures in Benin, one of the countries where their status is not well known. We conducted road counts on paved and unpaved roads and along small trails over a total of 1451 km. We also conducted interviews with local abattoir watchmen, veterinarians, butchers and foresters to examine potential threats to this species. A total of 52 Hooded Vultures were counted mostly in the departments of Atacora (32) but also in Alibori (10) and Borgou (10). The relative abundance was four Hooded Vultures per 100 km, highlighting the near extirpation of this bird from Benin. A total of 49 interviews revealed that poaching for belief-based use (through shooting and traps) and decreasing food availability remain the most important threats for Hooded Vultures in northern Benin. If these threats are not mitigated, we predict the extirpation of the Hooded Vulture outside protected areas in Benin within the next two decades, possibly even sooner. Conservation measures, including awareness campaigns, and the improvement and enforcement of environmental legislation, must be urgently implemented to improve the protection of this Critically Endangered vulture species., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The future of quality is personal. Health Quality 5.0 moves people-centred, integrated health and social care systems to the forefront of our post-COVID-19 agenda - and that cannot happen without addressing our global workforce crisis. Building back a stronger, healthier workforce is the first of the five big challenges we address in our special series. Starting with the global health workforce crisis is fitting, given it is the most fundamental and formidable barrier to health and quality today. As we put the pieces of the Health Quality 5.0 puzzle together, a picture of a more resilient health system will emerge and a new leadership agenda to get there will take shape., (Copyright © 2024 Longwoods Publishing.)

The work of health leaders is broadening in scope, scale and urgency to respond to massive global changes and challenges - including risks to safe, accessible and high-quality healthcare, threats to planetary health, crises in workforce resiliency and erosion of public trust and confidence. To address these issues and deliver on other imperatives around equity and inclusive service co-production, health leaders must again fashion a new quality improvement (QI) agenda fit for the times and the future, aligned with the move from digitization to personalization. The new era, Health Quality 5.0, must enable and be embedded in an integrated, coordinated and people-centred health system, supported by a learning health system and new QI approaches., (Copyright © 2023 Longwoods Publishing.)

Background: Cutaneous melanoma is a cancer arising in melanocyte skin cells and is the deadliest form of skin cancer worldwide. Although some risk factors are known, accurate prediction of disease progression and probability for metastasis are difficult to ascertain, given the complexity of the disease and the absence of reliable predictive markers. Since early detection and treatment are essential to enhance survival, this study utilizing machine learning (ML) aims to further delineate additional risk factors associated with cutaneous melanoma., Methods: A Bayesian Gaussian Mixture ML model was created with data from 2056 patients diagnosed with cutaneous melanoma and then used to group the patients into six Clusters based on a Silhouette Score analysis. A t-distributed stochastic neighbor embedding (t-SNE) model was used to visualize the six Clusters., Results: Statistical analysis revealed that Cluster 4 showed a significantly higher rate of metastatic disease, as well as higher Breslow depth at diagnosis, compared to the other five Clusters. Compared to the other five Clusters, patients represented in Cluster 4 also had lower healthcare utilization, fewer dermatology clinic visits, fewer primary care providers, and less frequent colonoscopies and mammograms, and were more likely to smoke and less likely to have a prior diagnosis of basal cell carcinoma., Conclusions: This study uncovers gaps in healthcare utilization of services among patient groups with cutaneous melanoma as well as possible implications for management of disease progression. Data-driven analyses emphasize the importance of routine clinic visits to dermatologists and/or primary care physicians (PCPs) for early detection and management of cutaneous melanoma. The findings from this study demonstrate that unsupervised ML methodology may serve to define the best candidate patients to benefit from enhanced dermatology/primary care which, in turn, is expected to improve outcomes for cutaneous melanoma.

Africa is set to experience a three-fold increase in vaccine demand by 2040, yet the continent possesses few domestic capabilities for vaccine production. This lack of production capacity, heavy reliance on foreign aid, disruptions of hard-won immunization progress due to the effects of the COVID-19 pandemic, and fluctuating vaccine market dynamics threaten to hinder ongoing efforts to increase vaccination rates on the continent. In order meet the vaccine demands of a rapidly growing population, and to be able to provide novel vaccines to its population in the future, the African continent must develop a sustainable vaccine manufacturing infrastructure. The African Union, in partnership with the Africa Centres for Disease Control and Prevention, recently set forth its Program for African Vaccine Manufacturing Framework for Action, which sets the goal of Africa producing 60 % of its vaccine needs by 2040. To meet these goals, African governments and their multinational, philanthropic, and private sector partners must work to secure low-cost financing and provide a favourable regulatory environment for nascent African vaccine manufacturers. Doing so will save lives, safeguard the health of the continent's current and future citizens, and contribute to economic growth through the development of local bioeconomies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wilmot James reports a relationship with Aspen Pharmacare Holdings Ltd that includes: funding grants. Stavros Nicolaou reports a relationship with Aspen Pharmacare Holdings Ltd that includes: employment. Luc Debruyne reports a relationship with Biovac Institute that includes: consulting or advisory. Luc Debruyne reports a relationship with Coalition for Epidemic Preparedness Innovations that includes: consulting or advisory., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fungicides and herbicides are two of the most heavily applied pesticide classes in the world, but receive little research attention with regards to their potential impacts on bees. As they are not designed to target insects, the mechanisms behind potential impacts of these pesticides are unclear. It is therefore important to understand their influence at a range of levels, including sublethal impacts on behaviours such as learning. We used the proboscis extension reflex (PER) paradigm to assess how the herbicide glyphosate and the fungicide prothioconazole affect bumblebee olfactory learning. We also assessed responsiveness, and compared the impacts of these active ingredients and their respective commercial formulations (Roundup Biactive and Proline). We found that learning was not impaired by either formulation but, of the bees that displayed evidence of learning, exposure to prothioconazole active ingredient increased learning level in some situations, while exposure to glyphosate active ingredient resulted in bumblebees being less likely to respond to antennal stimulation with sucrose. Our data suggest that fungicides and herbicides may not negatively impact olfactory learning ability when bumblebees are exposed orally to field-realistic doses in a lab setting, but that glyphosate has the potential to cause changes in responsiveness in bees. As we found impacts of active ingredients and not commercial formulations, this suggests that co-formulants may modify impacts of active ingredients in the products tested on olfactory learning without being toxic themselves. More research is needed to understand the mechanisms behind potential impacts of fungicides and herbicides on bees, and to evaluate the implications of behavioural changes caused by glyphosate and prothioconazole for bumblebee fitness., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Conservationists speculated on potential benefits to wildlife of lockdown restrictions because of the COVID-19 pandemic but voiced concern that restrictions impeded nature conservation. We assessed the effects of lockdown restrictions on biodiversity conservation in South Africa, a biodiverse country with economic inequality and reliance on wildlife resources. We solicited expert opinion using the IUCN's Threats Classification Scheme to structure a questionnaire and illustrated responses with individual case studies from government parastatal and non-governmental conservation organisations. The most highly reported threats were biological resource use, residential/commercial developments, invasive species, and human intrusions. The trends reported by 90 survey respondents were supported by case studies using environmental compliance data from parastatal conservation organisations. Lack of tourism revenue and funding were cited as hindrances to conservation. Mechanisms to prevent environmental degradation in the face of global emergencies must be implemented and 'ring-fenced' to ensure conservation is not a casualty during future global crises., (© 2022. The Author(s).)

Herbicides are the most widely used pesticides globally. Although used to control weeds, they may also pose a risk to bee health. A key knowledge gap is how bees could be exposed to herbicides in the environment, including whether they may forage on treated plants before they die. We used a choice test to determine if bumblebees would forage on plants treated with glyphosate at two time periods after treatment. We also determined whether glyphosate and its degradation product aminomethylphosphonic acid were present as residues in the pollen collected by the bees while foraging. Finally, we explored if floral resources (nectar and pollen) remained present in plants after herbicide treatment. In general bees indiscriminately foraged on both plants treated with glyphosate and controls, showing no avoidance of treated plants. Although the time spent on individual flowers was slightly lower on glyphosate treated plants, this did not affect the bees' choice overall. We found that floral resources remained present in plants for at least 5 days after lethal treatment with glyphosate and that glyphosate residues were present in pollen for at least 70 h posttreatment. Our results suggest that bees could be exposed to herbicide in the environment, both topically and orally, by foraging on plants in the period between herbicide treatment and death. Identifying this route of exposure is a first step in understanding the risks of herbicides to bees. The effects of herbicides on bees themselves are uncertain and warrant further investigation to allow full risk assessment of these compounds to pollinating insects. Environ Toxicol Chem 2022;41:2603-2612. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

External, third-party evaluations are undertaken across every industry, including healthcare, to assess performance against an established set of standards. The formality, rigour, timing and outcomes associated with these evaluations vary, and models throughout the world are evolving to meet changing needs. This is aligned with the historic shift from periodic pre-determined accreditations to healthcare organizations being "accreditation ready" every day. Accreditation Canada's continuous quality improvement model empowers and enables organizations to foster a culture and practice of continuous quality improvement., (Copyright © 2022 Longwoods Publishing.)

African wildlife face challenges from many stressors including current and emerging contaminants, habitat and resource loss, poaching, intentional and unintentional poisoning, and climate-related environmental change. The plight of African vultures exemplifies these challenges due to environmental contaminants and other stressors acting on individuals and populations that are already threatened or endangered. Many of these threats emanate from increasing human population size and settlement density, habitat loss from changing land use for agriculture, residential areas, and industry, and climate-related changes in resource availability. Environmental chemicals that are hazardous include legacy chemicals, emerging chemicals of concern, and high-volume-use chemicals that are employed as weed killers and in other agricultural applications. Furthermore, there are differences in risk for species living in close proximity to humans or in areas affected by habitat loss, climate, and industry. Monitoring programs are essential to track the status of nesting pairs, offspring survival, longevity, and lifetime productivity. This is important for long-lived birds, such as vultures, that may be especially vulnerable to chronic exposure to chemicals as obligate scavengers. Furthermore, their position in the food web may increase risk due to biomagnification of chemicals. We review the primary chemical hazards to Old World vultures and the interacting stressors affecting these and other birds. Habitat is a major consideration for vultures, with tree-nesters and cliff-nesters potentially experiencing different risks of exposure to environmental chemicals. The present review provides information from long-term monitoring programs and discusses a range of these threats and their effects on vulture populations. Environ Toxicol Chem 2022;41:1586-1603. © 2022 SETAC., (© 2022 SETAC.)

Blowfly strike or cutaneous myiasis, caused principally by the Australian sheep blowfly Lucilia cuprina is endemic to Australian sheep producing areas and is a major cause of suffering and economic loss. This article reports incidence and control practices as determined by three cross-sectional surveys of Australian sheep farmers covering the years 2003 (n = 1365), 2011 (n = 575) and 2018 (n = 354) with more questions relating to blowfly strike in the latter two surveys. Breech strike was reported at a higher rate than body strike in all survey years. Reported annual incidence of breech strike ranged from 2.2 to 4.7% of sheep nationally with minor differences between ewes and lambs. The incidence of body strike ranged from 1.0 to 7.1% with higher incidence in younger sheep in all years. The use of fixed time routine preventative chemical treatments increased during the survey period (43%, 46% and 66%, in 2003, 2011 and 2018 respectively) with dicyclanil (54%-58%) and cyromazine (23-36%) the main insecticides used for control since 2011. The use of the Mules operation (mulesing) to remove skin wrinkles from the breech area as a preventative modification did not change between 2011 and 2018 (47% in both), however, the use of pain relief at mulesing of replacement ewe lambs increased substantially between 2011 (59%) and 2018 (87%). The most commonly used methods to assist with flystrike control were timing of crutching (clipping of wool from susceptible areas) and shearing, with few respondents destroying maggots from treated sheep (21-26%) and very low use of fly traps (5-8%). Phenotypic selection of ewes for reduced susceptibility to flystrike based on visual traits was practiced by 61% of respondents in 2011 and 56% in 2018. Selection of rams for reduced susceptibility using estimated breeding values increased from 10% in 2011 to 17% in 2018. Breeding for resistance was the most commonly nominated (21%) most important change made to flystrike management in 2018. The results indicate that concern for sheep welfare has increased with almost universal use of pain relief at mulesing. Increased use of selection for blowfly resistance indicates farmer commitment to planning for a future without mulesing, although the practice remains prevalent. An increase in the reliance on preventative chemical treatments increases the risk of insecticide resistance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Agrochemical formulations are composed of two broad groups of chemicals: active ingredients, which confer pest control action, and 'inert' ingredients, which facilitate the action of the active ingredient. Most research into the effects of agrochemicals focusses on the effects of active ingredients. This reflects the assumption that 'inert' ingredients are non-toxic. A review of relevant research shows that for bees, this assumption is without empirical foundation. After conducting a systematic literature search, we found just 19 studies that tested the effects of 'inert' ingredients on bee health. In these studies, 'inert' ingredients were found to cause mortality in bees through multiple exposure routes, act synergistically with other stressors and cause colony level effects. This lack of research is compounded by a lack of diversity in study organism used. We argue that 'inert' ingredients have distinct, and poorly understood, ecological persistency profiles and toxicities, making research into their individual effects necessary. We highlight the lack of mitigation in place to protect bees from 'inert' ingredients and argue that research efforts should be redistributed to address the knowledge gap identified here. If so-called 'inert' ingredients are, in fact, detrimental to bee health, their potential role in widespread bee declines needs urgent assessment.

The sheep body louse (Bovicola ovis) is a parasite of major economic concern in Australia. This article reports lice incidence and control practices on Australian sheep farms as determined by three cross-sectional surveys of the years 2003, 2011 and 2018. The incidence of live lice detected within a flock was similar across the survey years with a slight decline in 2018 (2003: 20%, 2011: 18.6% and 2018: 13.9%). In an average year, most farmers did not see any direct or indirect evidence of lice infestation (2011: 59.3% and 2018: 69.5%), however, over a five-year period 38.9% (2003), 66.3% (in 2011) and 55.8% (in 2018) reported seeing evidence of lice infestation at least once with significant variation between sheep producing regions in 2011. In an average year, nearly three quarters of respondents treated for lice (2011:73.5% and 2018: 73.3%) with the majority treating immediately following shearing and very few treating sheep with long wool. Even higher percentages treated for lice at least once in the preceding five-year period (2011: 86.2% and 2018: 87.5%). Backliner was the most popular method of chemical application for lice control in sheep off-shears or with short wool (2003: 77%, 2011: 73% and 2018: 74.3%). For long wool treatments, hand jetting declined in popularity from 2003 (64%) to 2011 (54%) and 2018 (8.6%) as backliners became more popular (2003: 36%, 2011: 51% and 2018: 60%). The use of benzoylphenyl urea insect growth regulators (IGR) for off-shears/short wool treatment declined from 2003 (92.8%) to 2011 (51%) and 2018 (2.9%) and were largely replaced by neonicotinoids and spinosad for backliner/spray-on products. The use of organophosphates declined for plunge dipping (2003: 83.8%, 2011: 83% and 2018: 7.7%). Spinosad use for plunge dipping off-shears/short wool increased over the survey years (2003, 0%, 2011: 9% and 2018:46.2%). The use of IGRs declined for backliner application on long wool and were mainly replaced by spinosad in 2011 and 2018. Fewer respondents reported suspected resistance to lice control products in 2018 (8%) compared with 2003 (26%) and 2011 (13%) with most reporting suspected resistance to IGR and synthetic pyrethroids and emerging suspicions of resistance to neonicotinoids in 2018. Resistance to lice control products also reduced in importance as a reason for recurring lice infestations between 2011 (ranked 2nd) and 2018 (ranked 6th). Biosecurity was important to sheep producers with the highest ranked reason for recurring lice infestations being from stray or purchased sheep., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cross-sectional surveys of sheep parasite control practices in Australia were conducted in 2004, 2012 and 2019 to document parasite problems, control practices and measure change over time. This article reports the results pertaining to gastrointestinal nematode infection; comparisons between years are mostly descriptive and not based on statistical inference. There was a general increase in the use of grazing management to prepare clean pastures for sheep to control gastrointestinal nematode infections with the largest increases in the use of: cropping, long acting anthelmintics to prepare clean pastures, feeding strategies, selecting rams for resistance to nematodes, and leaving some sheep untreated. The proportion of respondents using faecal worm egg count monitoring (WEC) and the number of WEC monitors per year were similar in 2003 (weaners: 3.0 WEC/year, adult ewes: 2.6 WEC/year) and 2018 (lambs and weaners and adult ewes both 3.1 WEC/year) but lower in 2011(lambs and weaners: 2.0 WEC/year, adult ewes: 2.9 WEC/year), whilst there was a higher number of anthelmintic treatments given in 2011 than 2003 and 2018 which were similar. There was an increase in the proportion of respondents carrying out WEC monitors themselves from 2011 (21%) to 2018 (30%) and a corresponding reduction in the use of private laboratories, government laboratories and veterinarians with regional differences in who carried out WECs. The top three anthelmintic groups used did not differ between the three survey years with macrocyclic lactones the most used followed by benzimidazoles (BZ) and levamisole (LEV) although the percentage of MLs used in 2011 and 2018 was lower than in 2003 with higher proportions of respondents using BZ and LEV groups in the latter two survey years. Moxidectin was in the most commonly used active in all survey years. There was an increase in the use of combination of anthelmintics from different groups, especially for a combination of three anthelmintics (2003: 4.4%, 2011: 19.1%, 2018: 21.5%), with lower use of single anthelmintics in 2011 (57.0%) and 2018 (55.4%) compared with 2003 (74.5%). The use of testing for anthelmintic resistance was generally low across the survey years with a lower proportion of respondents using tests in 2011 and 2018 than in 2003 (2003:48%, 2011: 29%, 2018: 37%). Time of year, results from WEC and seasonal weather condition were the most important factors when deciding when to apply anthelmintic treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Australian Wool Innovation Limited (AWI) commissioned three cross-sectional surveys of sheep producers' sheep parasite control practices over a 15-year period from 2003 to 2018. The aims were to document current sheep parasite incidence and control practices, to measure change in sheep parasite control practices over time and to inform extension messages for sheep industry advisors and sheep farmers. The surveys were conducted in 2004, 2012 and 2019 measuring sheep parasite control practices in the years 2003, 2011 and 2018. The surveys focused on incidence and control of the three major sheep parasite groups; gastrointestinal nematodes, blowflies and lice. The 2003 and 2011 surveys were paper-based and the 2018 survey was accessed via a link to an online survey. This article is the first in a series of four presenting the results of the three surveys and will cover methods, demographics, production systems and general parasite management. Response rates to the surveys declined each year from the peak response rate in 2003 (n = 1365 in 2003; n = 575 in 2011 and n = 354 in 2018). Mean reported rainfall was significantly lower in 2018 (407 mm) than in 2003 (611 mm) and 2011 (650 mm). The demographics of the respondents and their production systems were largely similar between the three surveys for respondent age, median property size, income from wool and sheep meat, proportion of the property area cropped, median sheep dry sheep equivalent (DSEs), ewes as a proportion of the total flock and median cattle DSEs. Month of weaning was more likely to be in summer months for summer dominant rainfall areas and spring for intermediate and winter dominant rainfall areas. There was a marked increase in the proportion of respondents asking for an animal health history when introducing sheep to their flock from 2011 (9%) to 2018 (65%). Similarly, a greater proportion of respondents isolated introduced sheep for at least 2 weeks in 2018 (82%) compared with 2011 (19%). However, there was a decrease in the use of a quarantine lice treatment for introduced sheep from 2011 (50%) to 2018 (21%). Farmers rated themselves, other farmers or member of their staff as most important sources of information on parasite control in both 2011 and 2018. There was a significant increase in the proportion of respondents visiting the ParaBoss suite of websites from 2011 to 2018 confirming their growing importance for information delivery and decision support., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that is important for the development of type 2 inflammatory responses at mucosal surfaces., Objective: In humans, TSLP level has been found to be elevated in the lungs of patients with asthma, and in mouse models, TSLP can promote type 2 airway inflammation, primarily through the activation of dendritic cells. However, the mechanisms underlying its role remain unclear. The objective of this study was to provide a mechanistic analysis of TSLP-mediated type 2 airway inflammation METHODS: To dissect the mechanisms of TSLP-mediated type 2 responses, mice were treated with TSLP and antigen to evaluate cellular immune responses. Flow cytometric analyses were used to follow responses in the airways, and conditional deletion of TSLP receptor and adoptive transfer were used to identify the cellular subsets involved in this inflammatory response., Results: We showed that TSLP can directly promote T H 2-cell differentiation in the lung, independent of the draining lymph nodes. We also identified a population of patrolling monocytes/interstitial macrophages (IMs) (CD11c-expressing IMs) that are both necessary and sufficient for TSLP-mediated T H 2-cell differentiation and airway inflammation. T H 2-cell-driven airway eosinophilia is attenuated by ablation of CD11c-expressing IMs or by selective deficiency of TSLP receptor signaling in these cells. More importantly, CD11c-expressing IMs are sufficient for the induction of acute T H 2-cell responses in the lungs that is independent of dendritic cells and T-cell priming in the draining lymph nodes., Conclusion: These findings indicate a novel mechanistic role for TSLP and CD11c-expressing IMs in the development of acute T H 2-cell-dependent allergic airway inflammation. This work also demonstrates a new role for TSLP in promoting type 2 responses directly in the lung., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Ribonucleotides (rNMPs) incorporated in the nuclear genome are a well-established threat to genome stability and can result in DNA strand breaks when not removed in a timely manner. However, the presence of a certain level of rNMPs is tolerated in mitochondrial DNA (mtDNA) although aberrant mtDNA rNMP content has been identified in disease models. We investigated the effect of incorporated rNMPs on mtDNA stability over the mouse life span and found that the mtDNA rNMP content increased during early life. The rNMP content of mtDNA varied greatly across different tissues and was defined by the rNTP/dNTP ratio of the tissue. Accordingly, mtDNA rNMPs were nearly absent in SAMHD1 -/- mice that have increased dNTP pools. The near absence of rNMPs did not, however, appreciably affect mtDNA copy number or the levels of mtDNA molecules with deletions or strand breaks in aged animals near the end of their life span. The physiological rNMP load therefore does not contribute to the progressive loss of mtDNA quality that occurs as mice age., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

How individuals perceive uncertainties in sequencing results may affect their clinical utility. The purpose of this study was to explore perceptions of uncertainties in carrier results and how they relate to psychological well-being and health behavior. Post-reproductive adults (N = 462) were randomized to receive carrier results from sequencing through either a web platform or a genetic counselor. On average, participants received two results. Group differences in affective, evaluative, and clinical uncertainties were assessed from baseline to 1 and 6 months; associations with test-specific distress and communication of results were assessed at 6 months. Reductions in affective uncertainty (∆x̅ = 0.78, 95% CI: 0.53, 1.02) and evaluative uncertainty (∆x̅ = 0.69, 95% CI: 0.51, 0.87) followed receipt of results regardless of randomization arm at 1 month. Participants in the web platform arm reported greater clinical uncertainty than those in the genetic counselor arm at 1 and 6 months; this was corroborated by the 1,230 questions asked of the genetic counselor and residual questions reported by those randomized to the web platform. Evaluative uncertainty was associated with a lower likelihood of communicating results to health care providers. Clinical uncertainty was associated with a lower likelihood of communicating results to children. Learning one's carrier results may reduce perceptions of uncertainties, though web-based return may lead to less reduction in clinical uncertainty in the short term. These findings warrant reinforcement of clinical implications to minimize residual questions and promote appropriate health behavior (communicating results to at-risk relatives in the case of carrier results), especially when testing alternative delivery models., (© Society of Behavioral Medicine 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bees and the pollination services they deliver are beneficial to both food crop production, and for reproduction of many wild plant species. Bee decline has stimulated widespread interest in assessing hazards and risks to bees from the environment in which they live. While there is increasing knowledge on how the use of broad-spectrum insecticides in agricultural systems may impact bees, little is known about effects of other pesticides (or plant protection products; PPPs) such as herbicides and fungicides, which are used more widely than insecticides at a global scale. We adopted a systematic approach to review existing research on the potential impacts of fungicides and herbicides on bees, with the aim of identifying research approaches and determining knowledge gaps. While acknowledging that herbicide use can affect forage availability for bees, this review focussed on the potential impacts these compounds could have directly on bees themselves. We found that most studies have been carried out in Europe and the USA, and investigated effects on honeybees. Furthermore, certain effects, such as those on mortality, are well represented in the literature in comparison to others, such as sub-lethal effects. More studies have been carried out in the lab than in the field, and the impacts of oral exposure to herbicides and fungicides have been investigated more frequently than contact exposure. We suggest a number of areas for further research to improve the knowledge base on potential effects. This will allow better assessment of risks to bees from herbicides and fungicides, which is important to inform future management decisions around the sustainable use of PPPs., Competing Interests: The authors have declared that no competing interests exist.

DNA polymerase η (pol η) is best known for its ability to bypass UV-induced thymine-thymine (T-T) dimers and other bulky DNA lesions, but pol η also has other cellular roles. Here, we present evidence that pol η competes with DNA polymerases α and δ for the synthesis of the lagging strand genome-wide, where it also shows a preference for T-T in the DNA template. Moreover, we found that the C-terminus of pol η, which contains a PCNA-Interacting Protein motif is required for pol η to function in lagging strand synthesis. Finally, we provide evidence that a pol η dependent signature is also found to be lagging strand specific in patients with skin cancer. Taken together, these findings provide insight into the physiological role of DNA synthesis by pol η and have implications for our understanding of how our genome is replicated to avoid mutagenesis, genome instability and cancer., (© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.)

In-person education and counseling for all people receiving genetic results is the predominant model of disclosure but is challenged by the growing volume of low-impact results generated by sequencing. Evidence suggests that web-based tools may be as effective as in-person counseling at educating individuals about their low-impact results. However, the effects of counseling have not been assessed. To evaluate its utility, carrier results were returned to 459 post-reproductive participants from the ClinSeq cohort within a randomized controlled trial. Participants received education and were randomized to receive counseling or not. Primary outcomes included risk worry, test-related positive experiences, attitudes, and decisional conflict. Secondary outcomes were satisfaction, preferences, and counseling value. There were no differences between participants who received counseling and those who did not in the primary outcomes. Participants who received counseling were more satisfied than those who did not (x¯ = 10.2 and 9.5, respectively, p < 0.002, range: 3-12), although overall satisfaction was high. Most participants (92%) randomized to counseling preferred it and valued it because it provided validation of their reactions and an opportunity for interpersonal interaction. Web-based tools address the challenge of returning low-impact results, and these data provide empiric evidence that counseling, although preferred and satisfying, is not critical to achieving desired outcomes., (Published by Elsevier Inc.)

Of the numerous factors affecting avian metabolic rate, altitude is one of the least studied. We used mass-flow respirometry to measure resting metabolic rate (RMR), evaporative water loss (EWL) and respiratory exchange ratio (RER) in two populations of a small (10-12g) Afrotropical bird, the Cape White-eye (Zosterops virens), in summer and in winter. In total, 51 freshly wild-caught adult Cape White-eyes were measured overnight. Altitude was included as a source of variation in the best approximating models for body mass, whole-animal RMR, RER, whole-animal standard EWL and whole-animal basal EWL. RER was significantly lower in winter, suggesting a greater proportion of lipid oxidation at lower ambient temperatures (T a ). Cape White-eyes were 0.8g heavier at the higher altitude site and 0.5g heavier in winter, suggesting they may have increased their metabolic machinery to cope with cooler temperatures. EWL was generally significantly lower in winter than in summer, suggesting that birds may increase EWL with increasing T a , as the need for evaporative cooling increases. Our results support the argument that the subtle and complex effects of altitude (and ambient temperature) should be taken into account in studies on avian metabolic rate., What Is Already Known: Of the numerous studies known to affect avian metabolic rate, altitude is one of the least studied. Although trends are not always clear, generally, at higher altitudes, avian metabolic rate increases., What the Study Adds: There were statistically significant seasonal and altitudinal differences in various physiological parameters of Cape White-eyes. These results highlight the importance of accounting for altitude in studies of avian metabolic rate., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Legg-Calve-Perthes' disease (LCPD) is an idiopathic disease of the femoral head affecting the pediatric population. The causative factors remains poorly understood and it is associated with significant hip pathology in adult life. Research has demonstrated wide geographical variation in the incidence rates of LCPD with a relatively high incidence occurring in Northern Ireland (NI) shown in a previous study of incidence from the same unit. The number of new diagnoses of LCPD seems to be declining over time. This study aimed to track changes in the incidence of LCPD within the 0- to 14-year-old population over a 15-year period in NI., Methods: An established database was utilized to collate information of any individual between the ages of 0 to 14 years with a diagnosis of LCPD. The data were compared with electronic radiologic records to confirm the diagnosis. Postal code data were used to the determine location of residence and used as a proxy measure of deprivation., Results: The results of this epidemiological study have demonstrated a 61% decrease in the incidence of LCPD over a 15-year period within the pediatric population of NI. Comparison between 2 cohorts reveals no distinguishable change in distribution of age or sex. The relationship between geographical proxy measures of deprivation in NI and LCPD remains evident., Conclusions: The number of new cases of LCPD is decreasing over time. The epidemiological data are unchanged between 2 cohorts over a 15-year period, and this therefore supports a change within the patients' environment relating to this decline. This change could relate to a number of factors including smoking rates, breastfeeding, lead use, and vaccination implementation., Level of Evidence: Level IV-retrospective cohort study.

Collaboration is a powerful force of social change. History has shown us time and time again that when people come together with a shared passion for making things better, high impact change can happen. Minds are opened. Voices are heard. Lives are saved. Our experience at Health Standards Organization (HSO) and Accreditation Canada shows that when people feel involved, empowered and engaged in a meaningful way to bring about improvement, then the chances that it will be sustained over time increase as well. This paper builds on the principles of front-line ownership (FLO) initiatives offered by Gardam et al., addresses the tensions between standards and innovation and reminds us that collaboration is all about people, and people power is what converts theory and ideas into reality - especially in healthcare environments.

Wild-caught animals are regularly used in physiological studies, yet the length of time it takes for completion of their acclimation to laboratory conditions remains largely unknown. In particular, Afrotropical species are relatively understudied compared with temperate and Holarctic species. Thus, we measured a number of metabolic variables in a 10g Afrotropical bird, the Cape White-eye (Zosterops virens), at weekly intervals, over an 8-week period, while birds were acclimating to two different constant thermal environments; 25°C and 29°C. Body mass increased significantly in the first three weeks, remaining approximately constant thereafter, with no significant difference between birds housed at 25°C and those housed at 29°C. However, whole animal resting metabolic rates remained constant throughout the eight-week study period, with values for birds housed at 29°C lower than for birds housed at 25°C. Rather than pointing to a minimum time period necessary for thermal acclimation, these results suggest that in some instances, freshly wild-caught small passerines may not need to be acclimated to laboratory conditions or respirometry equipment, prior to measurements of their resting metabolic rate., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Inflammation induced during infection can both promote and suppress immunity. This contradiction suggests that inflammatory cytokines affect the immune system in a context-dependent manner. Here we show that nonspecific bystander inflammation conditions naive CD4(+) T cells for enhanced peripheral Foxp3 induction and reduced effector differentiation. This results in inhibition of immune responses in vivo via a Foxp3-dependent effect on antigen-specific naive CD4(+) T cell precursors. Such conditioning may have evolved to allow immunity to infection while limiting subsequent autoimmunity caused by release of self-antigens in the wake of infection. Furthermore, this phenomenon suggests a mechanistic explanation for the idea that early tuning of the immune system by infection affects the long-term quality of immune regulation.

Seasonal trends in metabolic parameters are well established in avian populations from highly seasonal environments, however, seasonal trends in metabolism of birds from lower latitudes (and of Afrotropical birds in particular) are not well understood. We investigated seasonal trends in metabolism for a small (10-12g) Afrotropical bird, the Cape White-eye (Zosterops virens), using flow-through respirometry in two summers and two winters. There was no seasonal difference in body mass between consecutive seasons. The lower critical limit of thermoneutrality was lower in winter (23°C) than in summer (28°C), as expected for a small Afrotropical bird. In the first year of the study, mean whole animal basal metabolic rate (BMR) of Cape White-eyes was significantly lower in winter than in summer, while in the second year of the study this trend was reversed, and in the middle two seasons there was no significant difference in BMR. Differences in mean temperature and mean rainfall between seasons could not account for the seasonal trends in BMR. We conclude that seasonal trends in avian BMR may vary between years, within a population., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Seasonal variation in avian metabolic rate is well established in Holarctic and temperate species, while trends in Afrotropical species are relatively poorly understood. Furthermore, given the paucity of data on circannual rhythm in avian metabolism, it is not known whether seasonal measurements made in summer and winter correspond with annual peaks and troughs in avian metabolic rate. Thus, we investigated how mean body mass, resting metabolic rate (RMR) and evaporative water loss (EWL) of a small Afrotropical bird, the Cape white-eye (Zosterops virens), changed monthly over the course of a year at 20°C and 25°C. Mean body mass was 12.2±1.0g throughout the study period. However, both EWL and RMR varied monthly, and peaks and troughs in RMR occurred in March and October respectively, which did not correspond to peaks and troughs in mean monthly outdoor ambient temperatures. These results suggest that measuring RMR at the height of summer and winter may underestimate the flexibility of which birds are capable in terms of their metabolic rate. We encourage further studies on this topic, to establish whether the lag between environmental temperature and RMR is consistent in other species., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Studies have only recently begun to underline the importance of including data on the physiological flexibility of a species when modelling its vulnerability to extinction from climate change. We investigated the effects of a 4°C increase in ambient temperature (Ta), similar to that predicted for southern Africa by the year 2080, on certain physiological variables of a 10-12 g passerine bird endemic to southern Africa, the Cape white-eye Zosterops virens. There was no significant difference in resting metabolism, body mass and intraperitoneal body temperature between birds housed indoors at 4°C above outside ambient temperature and those housed indoors at outside ambient temperature. We conclude that the physiological flexibility of Cape white-eyes will aid them in coping with the 4°C increase predicted for their range by 2080., (© 2015. Published by The Company of Biologists Ltd.)

The few within-species studies on the effects of long-term captivity on avian physiological variables have small samples sizes and contradictory results. Nevertheless, many physiological studies make use of long-term captive birds, assuming the results will be applicable to wild populations. Here we investigated the effects of long-term captivity on a variety of physiological measurements in a relatively small (~12 g) southern African endemic bird, the Cape white-eye (Zosterops virens). Whole animal basal metabolic rate (BMR) and body mass (Mb) were influenced more by long-term captivity than by season, while mass-specific BMR, standard and basal whole animal and mass-specific evaporative water loss (EWL), and respiratory quotient (RQ), were all affected primarily by season, with long-term captivity having less of an effect. We therefore caution that whole animal BMR and Mb of long-term captive birds should not be used as representative of wild populations, and that the origin of study birds should be considered when comparing EWL and RQ of wild and long-term captive birds.

Objectives: Enterobacteriaceae have multiple efflux pumps that confer intrinsic resistance to antibiotics. AcrB mediates clinically relevant multidrug resistance and is required for virulence and biofilm formation, making it an attractive target for the design of inhibitors. The aim of this study was to assess the viability of single transporters as a target for efflux inhibition using Salmonella Typhimurium as the model pathogen., Methods: The expression of resistance-nodulation-division (RND) efflux pump genes in response to the inactivation of single or multiple homologues was measured using real-time RT-PCR. Phenotypes of mutants were characterized by measuring antimicrobial susceptibility, dye accumulation and the ability to cause infection in vitro., Results: The expression of all RND efflux pump genes was increased when single or multiple acr genes were inactivated, suggesting a feedback mechanism that activates the transcription of homologous efflux pump genes. When two or three acr genes were inactivated, the mutants had further reduced efflux, altered susceptibility to antimicrobials (including increased susceptibility to some, but conversely and counterintuitively, decreased susceptibility to some others) and were more attenuated in the tissue culture model than mutants lacking single pumps were., Conclusions: These data indicate that it is critical to understand which pumps an inhibitor is active against and the effect of this on the expression of homologous systems. For some antimicrobials, an inhibitor with activity against multiple pumps will have a greater impact on susceptibility, but an unintended consequence of this may be decreased susceptibility to other drugs, such as aminoglycosides., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Recent reports have highlighted greater complexity, plasticity, and functional diversity of mononuclear phagocytes (MPCs), including monocytes, macrophages, and dendritic cells (DCs), in our organs than previously understood. The functions and origins of MPCs resident within healthy organs, especially in the kidney, are less well understood, whereas studies suggest they play roles in disease states distinct from recruited monocytes. We developed an unbiased approach using flow cytometry to analyze MPCs residing in the normal mouse kidney, and identified five discrete subpopulations according to CD11b/CD11c expression as well as F4/80, CD103, CD14, CD16, and CD64 expression. In addition to distinct marker profiles, these subpopulations have different lineages and expression of genes involved in tissue homeostasis, including angiogenesis. Among them, the CD11b(int)CD11c(int) F4/80(high) subpopulation notably exhibited high capacity to produce a representative anti-inflammatory cytokine, IL-10. Each subpopulation had different degrees of both macrophage (phagocytosis) and DC (Ag presentation) capacities, with a tendency to promote differentiation of regulatory T cells, whereas two of these showed expression of transcription factors reported to be highly expressed by classical DCs, and proclivity to exit the kidney following stimulation with LPS. In summary, resident kidney MPCs comprise discrete subpopulations, which cannot be simply classified into the conventional entities, and they produce anti-inflammatory and tissue-homeostatic factors to differing degrees.

Background: Lifelong surveillance is standard after endovascular repair of abdominal aortic aneurysm (EVAR), but remains costly, heterogeneous and poorly calibrated. This study aimed to develop and validate a scoring system for aortic complications after EVAR, informing rationalized surveillance., Methods: Patients undergoing EVAR at two centres were studied from 2004 to 2010. Preoperative morphology was quantified using three-dimensional computed tomography according to a validated protocol, by investigators blinded to outcomes. Proportional hazards modelling was used to identify factors predicting aortic complications at the first centre, and thereby derive a risk score. Sidak tests between risk quartiles dichotomized patients to low- or high-risk groups. Aortic complications were reported by Kaplan-Meier analysis and risk groups were compared by log rank test. External validation was by comparison of aortic complications between risk groups at the second centre., Results: Some 761 patients, with a median age of 75 (interquartile range 70-80) years, underwent EVAR. Median follow-up was 36 (range 11-94) months. Physiological variables were not associated with aortic complications. A morphological risk score incorporating maximum aneurysm diameter (P < 0·001) and largest common iliac diameter (measured 10 mm from the internal iliac origin; P = 0·004) allocated 75 per cent of patients to a low-risk group, with excellent discrimination between 5-year rates of aortic complication in low- and high-risk groups at both centres (centre 1: 12 versus 31 per cent, P < 0·001; centre 2: 12 versus 45 per cent, P = 0·002)., Conclusion: The risk score uses commonly available morphological data to stratify the rate of complications after EVAR. The proposals for rationalized surveillance could provide clinical and economic benefits., (© 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.)

Of the seven sea turtle species, the critically endangered leatherback sea turtle (Dermochelys coriacea) exhibits the lowest and most variable nest success (i.e., hatching success and emergence success) for reasons that remain largely unknown. In an attempt to identify or rule out causes of low reproductive success in this species, we established the largest sample size (n = 60-70 for most values) of baseline blood parameters (protein electrophoresis, hematology, plasma biochemistry) for this species to date. Hematologic, protein electrophoretic and biochemical values are important tools that can provide information regarding the physiological condition of an individual and population health as a whole. It has been proposed that the health of nesting individuals affects their reproductive output. In order to establish correlations with low reproductive success in leatherback sea turtles from Florida, we compared maternal health indices to hatching success and emergence success of their nests. As expected, hatching success (median = 57.4%) and emergence success (median = 49.1%) in Floridian leatherbacks were low during the study period (2007-2008 nesting seasons), a trend common in most nesting leatherback populations (average global hatching success = ∼50%). One protein electrophoretic value (gamma globulin protein) and one hematologic value (red blood cell count) significantly correlated with hatching success and emergence success. Several maternal biochemical parameters correlated with hatching success and/or emergence success including alkaline phosphatase activity, blood urea nitrogen, calcium, calcium:phosphorus ratio, carbon dioxide, cholesterol, creatinine, and phosphorus. Our results suggest that in leatherbacks, physiological parameters correlate with hatching success and emergence success of their nests. We conclude that long-term and comparative studies are needed to determine if certain individuals produce nests with lower hatching success and emergence success than others, and if those individuals with evidence of chronic suboptimal health have lower reproductive success.

Leatherback sea turtles (Dermochelys coriacea) have low hatching and emergence success compared to other sea turtle species. Postmortem examinations of hatchlings showed degeneration of heart and skeletal muscle that was similar to that found in other neonates with selenium deficient mothers. Selenium deficiency can result from elevated concentrations of bodily mercury. Ingested mercury is detoxified by the liver through mercury-selenium compound formation. In animals persistently exposed to mercury, the liver's ability to detoxify this element may decrease, especially if dietary selenium is insufficient. We measured mercury and selenium concentrations in nesting female leatherbacks and their hatchlings from Florida and compared the levels to hatching and emergence success. Both liver selenium and the liver selenium-to-mercury ratio positively correlated with leatherback hatching and emergence success. This study provides the first evidence for the roles of mercury and selenium in explaining low reproductive success in a globally imperiled species, the leatherback sea turtle., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Naive CD4 T cells can differentiate into a number of functional subsets in response to Ag, including Foxp3(+) induced regulatory T cells (iTregs). The in vivo development and function of iTregs has been primarily demonstrated in systems involving Ag encountered systemically or delivered via the intestinal mucosa. In this study, we demonstrate that de novo Foxp3 expression in naive CD4 T cells is a critical mechanism for establishing tolerance for a tissue-restricted neo-self Ag. Naive CD4 T cells lacking a functional Foxp3 gene cannot achieve tolerance, but can be suppressed in vivo in the presence of wild type naive CD4 T cells. Exposure to nonspecific inflammation during priming undermines tolerance through impaired Foxp3 induction, suggesting that the microenvironment also has a role. These data show that de novo Foxp3 expression is an integral component of establishing and maintaining tolerance among naive peripheral CD4 T cells.

Mice overexpressing the proallergic cytokine thymic stromal lymphopoietin (TSLP) in the skin develop a pathology resembling atopic dermatitis. RabGEF1, a guanine nucleotide exchange factor for Rab5 GTPase, is a negative regulator of IgE-dependent mast cell activation, and Rabgef1-/- and TSLP transgenic mice share many similar phenotypic characteristics, including elevated serum IgE levels and severe skin inflammation, with infiltrates of both lymphocytes and eosinophils. We report here that Rabgef1-/- mice also develop splenomegaly, lymphadenopathy, myeloid hyperplasia, and high levels of TSLP. Rabgef1-/-TSLPR-/- mice, which lack TSLP/TSLP receptor (TSLPR) signaling, had levels of blood neutrophils, spleen myeloid cells, and serum IL-4, IgG1, and IgE levels that were significantly reduced compared with those in Rabgef1-/-TSLPR+/+ mice. However, Rabgef1-/-TSLPR-/- mice, like Rag1- or eosinophil-deficient Rabgef1-/- mice, developed cutaneous inflammation and epidermal hyperplasia. Therefore, in Rabgef1-/- mice, TSLP/TSLPR interactions are not required for the development of epidermal hyperplasia but contribute to the striking myeloid hyperplasia and overproduction of immunoglobulins observed in these animals. Our study shows that RabGEF1 can negatively regulate TSLP production in vivo and that excessive production of TSLP contributes to many of the phenotypic abnormalities in Rabgef1-/- mice. However, the marked epidermal hyperplasia, cutaneous inflammation, and increased numbers of dermal mast cells associated with RabGEF1 deficiency can develop via a TSLPR-independent pathway, as well as in the absence of Rag1 or eosinophils.

In the asymmetric unit of the crystal structure of nicotinamide-succinic acid (2/1), 2C(6)H(6)N(2)O x C(4)H(6)O(4), there are two independent nicotinamide molecules in general positions and two half succinic acid molecules which lie about inversion centres. The structure contains acid-pyridine and amide-amide synthons with nicotinamide molecules forming ladders of alternating R(2)(2)(8) and R(4)(2)(8) rings linked through succinic acid to generate a corrugated hydrogen-bonded sheet. This sheet is a common supramolecular unit found in other 2:1 nicotinamide-dicarboxylic acid cocrystals, but the presence of two crystallographically distinct nicotinamides with anti and syn conformations, forming two distinct sheets within the same structure, is a novel packing feature in this type of material.

We used microarrays and transcriptional profiling of peripheral blood to investigate the host response of 29 individuals who contracted typhoid fever in the Mekong Delta region of Vietnam. Samples were taken over a nine month period encompassing acute disease, convalescence, and recovery. We found that typhoid fever induced a distinct and highly reproducible signature in the peripheral blood that changed during treatment and convalescence, returning in the majority of cases to the "normal" profile as measured in healthy uninfected controls. Unexpectedly, there was a strong, distinct signature of convalescence present at day 9 after infection that remained virtually unchanged one month after acute infection and in some cases persisted as long as nine months despite a complete clinical recovery in all patients. Patients who retain the convalescent signature may be genetically or temporarily incapable of developing an effective immune response and may be more susceptible to reinfection, relapse, or the establishment of a carrier state.

Objective: Describe clinical characteristics and outcomes associated with canine patients undergoing surgical intervention for treatment of acute pancreatitis., Design: Retrospective outcome study from 2001 to 2007., Animals: Thirty-seven dogs., Interventions: None., Measurements and Main Results: The following data were collected for dogs who underwent surgical intervention in the course of treatment for severe acute pancreatitis: preoperative clinicopathologic and physical data, ultrasonographic findings, surgical procedure detail, histopathologic findings, and transfusion requirements. The survival rate was 80.8% in dogs with extrahepatic biliary obstruction, 64.3% in dogs undergoing necrosectomy, and 40.6% with pancreatic abscess. Overall survival was 63.6%. Surgical complications included intraoperative and postoperative hemorrhage in 12 dogs, postoperative development of diabetes mellitus in 3 dogs, exocrine pancreatic insufficiency in 1 dog, and bacterial peritonitis in 2 dogs., Conclusion: Surgical intervention and aggressive postoperative care may be pursued in select dogs with severe acute pancreatitis. In dogs with extrahepatic biliary obstruction secondary to acute pancreatitis, surgical intervention may be associated with a good prognosis whereas dogs with pancreatic abscess formation may have a more guarded prognosis.

This paper describes a novel technique for studying structure-transport correlations in nanoscale multilayer thin films. Here, local current-voltage characteristics from simplified magnetic tunnel junctions are measured in situ on cross-sectional transmission electron microscopy (TEM) samples and correlated directly with TEM images of the microstructure at the tunneling site. It is found that local variations in barrier properties can be detected by a point probe method, and that the tunneling barrier height and width can be extracted.

Background: Patient-controlled analgesia is associated with potentially fatal opioid-related respiratory depression. Opioids are a well-recognized cause of respiratory depression. However, in the postoperative patient, unrecognized pulmonary disease may lead to retention of carbon dioxide, which is further antagonized by opioids and may lead to life-threatening respiratory depression. Therefore, using a method that would provide earlier warnings for respiratory problems could improve patient outcomes., Objective: To assess the efficacy of monitoring postoperative patients who were receiving patient-controlled opioid therapy with capnography modules in addition to the routine use of pulse oximetry to monitor ventilatory status and generate alerts when respiratory parameters exceed hospital-established limits., Method: Postoperative patients receiving patient-controlled analgesia were compared in relation to the use of pulse oximetry and capnography modules and their ability to generate alerts about abnormal respiratory parameters. A total of 634 patients receiving patient-controlled analgesia therapy were studied, of whom 239 (38%) received hydromorphone, 297 (47%) received morphine, and 98 (15%) received fentanyl. All 9 patients experiencing respiratory depression received supplemental oxygen., Results: Of the 634 patients studied, 9 (1.4%) experienced respiratory depression by bradypnea (<6 breaths per minute). Six (67%) events were related to hydromorphone and 3 (33%) were related to morphine. In 7 (78%) events, there was no basal infusion rate and the saturation of peripheral oxygen was >92%. All respiratory depression events occurred within the first 24 hours of patient-controlled analgesia therapy. In all cases, capnography, but not pulse oximetry, alerted the nurse to impending respiratory depression., Conclusions: Capnography was more effective than pulse oximetry in providing early warning of respiratory depression in patients receiving supplemental oxygen. Capnographic monitoring and automatic pausing of patient-controlled analgesia improved postoperative outcomes in situations that could have otherwise been fatal. Use of capnography improved clinician confidence that opioid dosing could be safely continued in postoperative patients for more effective pain management.