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The efferent branches of the splanchnic sympathetic nerves that enhance interleukin-10 (IL-10) and suppress tumour necrosis factor-α (TNF) levels in the reflex response to systemic immune challenge were investigated in anaesthetized, ventilated rats. Plasma levels of TNF and IL-10 were measured 90 min after intravenous lipopolysaccharide (LPS, 60 µg/kg). Splanchnic nerve section, ganglionic blockade with pentolinium tartrate or β

Infectious disease models are widely used by epidemiologists to improve the understanding of transmission dynamics and disease natural history, and to predict the possible effects of interventions. As the complexity of such models increases, however, it becomes increasingly challenging to robustly calibrate them to empirical data. History matching with emulation is a calibration method that has been successfully applied to such models, but has not been widely used in epidemiology partly due to the lack of available software. To address this issue, we developed a new, user-friendly R package hmer to simply and efficiently perform history matching with emulation. In this paper, we demonstrate the first use of hmer for calibrating a complex deterministic model for the country-level implementation of tuberculosis vaccines to 115 low-and middle-income countries. The model was fit to 9–13 target measures, by varying 19–22 input parameters. Overall, 105 countries were successfully calibrated. Among the remaining countries, hmer visualisation tools, combined with derivative emulation methods, provided strong evidence that the models were misspecified and could not be calibrated to the target ranges. This work shows that hmer can be used to simply and rapidly calibrate a complex model to data from over 100 countries, making it a useful addition to the epidemiologist’s calibration tool-kit.

ImportanceClinical trials remain the cornerstone for determining the safety and efficacy of an intervention. A diverse participant pool in dermatology clinical trials is critical to ensure that results are generalizable among the patient population who will ultimately depend on the efficacy of the intervention. The Skin of Color Society hosted the inaugural Meeting the Challenge Summit: Diversity in Dermatology Clinical Trials in Washington, DC, from June 10 to 11, 2022. The summit was an interactive and collaborative effort to advance discussions regarding the need for broader inclusion of racial and ethnic minority patients in dermatology clinical trials.ObservationsThe summit focused on 3 principal areas: (1) understanding the current clinical trials landscape; (2) breaking down patient, clinician, industry, and regulatory barriers; and (3) effecting change through a diversity-focused strategy. The program hosted thought-provoking panel talks and discussions with various stakeholder groups, including a keynote presentation from the family of Henrietta Lacks.Conclusions and RelevancePanel discussions and insightful presentations from physicians, industry leaders, community trailblazers, and patients fostered new collaborations. The summit provided recommendations and suggested strategies for future initiatives designed to increase the representation of minority individuals in dermatology clinical trials.

Using pattern classification algorithms can help recognise and predict patterns in large and complex multivariate datasets. Utilising competitive learning, self-organising maps (SOMs) are known unsupervised classification tools that are considered very useful in pattern classification and recognition. This technique is based on the principles of vector quantification of similarities and clustering in a high-dimensional space, where the method can handle the analysis and visualization of high-dimensional data. The tool is ideal for analysing a complex combination of categorical and continuous spatial variables, with particular applications to geological features. In this paper, we employ the tool to predict geological features based on airborne geophysical data acquired through the Tellus project in Northern Ireland. SOMs are applied through 8 experiments (iterations), incorporating the radiometric data in combination with geological features, including elevation, slope angle, terrain ruggedness (TRI), and geochronology. The SOMs proved successful in differentiating contrasting bedrock geology, such as acidic versus mafic igneous rocks, while data clustering over intermediate rocks was not as apparent. The presence of a thick cover of glacial deposits in most of the study area presented a challenge in the data clustering, particularly over the intermediate igneous and sedimentary bedrock types. Supplementary material: https://doi.org/10.6084/m9.figshare.c.6603098

The interaction between water and phosphine isolated in solid argon matrices has been investigated. Infrared spectra of matrices containing water and phosphine, as well as their deuterium and

Halide-formic acid complexes have been studied utilising a combined experimental and theoretical approach. Formic acid exists as two conformers, distinguished by the relative rotation about the C-OH bond. Computational investigation of the formic acid isomerisation reaction between the two conformers has revealed the ability of halide anions to catalyse the formation of, and preferentially stabilise, the higher energy conformer. Anion photoelectron spectroscopy has been used to study the halide-formic acid complexes, with the experimental vertical detachment energies compared with simulated photodetachment energies with respect to halide complexes with both formic acid conformers. The existence of experimental spectral features associated with halide complexes of the higher energy formic acid confomer confirms

Anion photoelectron spectroscopy has been used to determine the electron binding energies of the X−⋯C3H6 (X = Cl, Br, I) complexes.

Background Faecal samples are frequently used to characterise the gut microbiota in health and disease, yet there is considerable debate about how representative faecal bacterial profiles are of the overall gut community. A particular concern is whether bacterial populations associated with the gut mucosa are properly represented in faecal samples, since these communities are considered critical in the aetiology of gastrointestinal diseases. In this study we compared the profiles of the faecal and mucosal microbiota from ten healthy volunteers using bacterial culturing (culturomics) and next-generation sequencing targeting the 16S ribosomal nucleic acid (rRNA) gene. Paired fresh rectal biopsies and faecal samples were processed under stringent anaerobic conditions to maintain the viability of the bacteria. Four different sample types were analysed: faecal (F), faecal homogenised (FHg), biopsy tissue (B) and biopsy wash (BW) samples. Results There were no significant statistical differences in either bacterial richness or diversity between biopsy washes (BW) and faecal (F) or faecal homogenised (FHg) samples. Principal coordinates analysis of a Bray–Curtis distance matrix generated from sequence variant tables did not show distinct clustering between these samples (PERMANOVA; p = 0.972) but showed strong clustering of samples from individual donors. However, the rectal biopsy tissue (B) samples had a significantly altered bacterial signature with greater abundance of Proteobacteria and Acidobacteria compared to faecal (F) and faecal homogenised (FHg) samples. A total of 528 bacteria encompassing 92 distinct bacterial species were isolated and cultured from a subset of six volunteer samples (biopsy washes and faeces). This included isolation of 22 novel bacterial species. There was significant similarity between the bacterial species grown in anaerobic culture and those identified by 16S rRNA gene sequencing (Spearman correlation; rho = 0.548, p = 0.001). Conclusion This study showed that the bacterial profiles of paired faecal and rectal biopsy wash samples were very similar, validating the use of faecal samples as a convenient surrogate for rectal biopsy-associated microbiota. Anaerobic bacterial culture results showed similar taxonomic patterns to the amplicon sequence analysis disproving the dogma that culture-based methods do not reflect findings of molecular assessments of gut bacterial composition.

Volumetric laser endomicroscopy (VLE) is an advanced endoscopic imaging tool that can improve dysplasia detection in Barrett’s esophagus (BE). However, VLE scans generate 1200 cross-sectional images that can make interpretation difficult. The impact of a new VLE artificial intelligence algorithm called Intelligent Real-time Image Segmentation (IRIS) is not well-characterized. This is a randomized prospective cross-over study of BE patients undergoing endoscopy who were randomized to IRIS-enhanced or unenhanced VLE first followed by the other (IRIS-VLE vs. VLE-IRIS, respectively) at expert BE centers. The primary outcome was image interpretation time, which served as a surrogate measure for ease of interpretation. The secondary outcome was diagnostic yield of dysplasia for each imaging modality. 133 patients were enrolled. 67 patients were randomized to VLE-IRIS and 66 to IRIS-VLE. Total interpretation time did not differ significantly between groups (7.8 min VLE-IRIS vs. 7 min IRIS-VLE, P = 0.1), however unenhanced VLE interpretation time was significantly shorter in the IRIS-VLE group (2.4 min vs. 3.8 min, P P = 0.06). IRIS-enhanced VLE reduced the time of subsequent unenhanced VLE interpretation, suggesting heightened efficiency and improved dysplasia detection. It was also able to identify all endoscopically non-visible dysplastic areas.

Introduction: Major depressive disorder (MDD) has a significant impact on global burden of disease. Complications in clinical management can occur when response to pharmacological modalities is considered inadequate and symptoms persist (treatment-resistant depression (TRD)). We aim to investigate inflammation, proxied by C-reactive protein (CRP) levels, and body mass index (BMI) as putative causal risk factors for depression and subsequent treatment resistance, leveraging genetic information to avoid confounding via Mendelian Randomization (MR). Methods: We used the European UK Biobank subcohort (n = 451, 025), the mental health questionnaire (MHQ) and clinical records. For treatment resistance, a previously curated phenotype based on GP records and prescription data was employed. We applied univariable and multivariable MR models to genetically predict the exposures and assess their causal contribution to a range of depression outcomes . We used weak and pleiotropy, robust estimation techniques within univariable, multivariable and mediation MR models in order to address our research question with maximum rigour. In addition, we developed a novel statistical procedure to apply pleiotropy robust multivariable MR to one sample data and employed an unfamiliar bootstrap procedure to accurately quantify estimate uncertainty in mediation analysis which outperforms standard approaches. Results: In univariable MR models, genetically predicted BMI was positively associated with depression outcomes, including MDD and TRD, with a larger magnitude in women and with age acting as a moderator of the effect of BMI on PHQ9 (p = 0.011). Multivariable MR analyses suggested an independent causal effect of BMI on TRD not through CRP. Our mediation analyses suggested that the effect of CRP on PHQ9 was partly mediated by BMI. Individuals with TRD (n = 2, 199) observationally had higher CRP and BMI compared with individuals with MDD alone and healthy controls. A positive causal association was noted for both the exposures, but in multivariable analyses only BMI retained statistical significance at the 5% level. Discussion: Our work supportst the assertion BMI exerts a causal effect on a range of clinical and questionnaire-based depression phenotypes, with the effect being stronger in women and in younger individuals. We show that this effect is independent of inflammation proxied by CRP levels as the effects of CRP do not persist when jointly estimated with BMI. This is consistent with previous evidence suggesting that overweight contributed to depression even in the absence of any metabolic consequences. It appears that BMI exerts an effect on TRD that persists when we account for BMI influencing MDD.

Positivity for islet autoantibodies is used for diagnosis of type 1 diabetes. However, the importance of the autoantibody level at diagnosis of type 1 diabetes is not clear. Here, we assessed the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) autoantibody levels, measured using radiobinding assays, on genetic and clinical characteristics at diagnosis of 1536 participants with diabetes who were positive for these autoantibodies. We show that GADA and IA-2A levels had bimodal distributions, but ZnT8A level did not. The comparison of genetic and clinical characteristics between high and low level categories showed high GADA level was associated with older age at diagnosis, female sex and HLA-DR3-DQ2, whereas high IA-2A level was associated with younger age of diagnosis, ZnT8A positivity and HLA-DR4-DQ8. We replicated our findings in an independent cohort of 427 people with type 1 diabetes where autoantibodies were measured using enzyme-linked immunosorbent assays. In conclusion, Islet autoantibody levels provide additional information over positivity in type 1 diabetes at diagnosis. The bimodality of islet autoantibody levels highlights the novel aspect of heterogeneity of type 1 diabetes which may have implications on prediction, treatment and prognosis.Islet autoantibodies are commonly used in the diagnosis and prediction of type 1 diabetes. They are well established as the biomarkers of the underlying autoimmune pathogenesis (1). Autoantibodies to islet cell antigen (ICA), glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), insulin (IAA) and zinc transporter 8 (ZnT8A) are the most commonly used islet autoantibodies at diagnosis (2). As detectable islet autoantibodies overlap between health and disease, a test is usually considered positive for a given islet autoantibody when the antibody level is higher than a 97.5–99th centile of a control population (3; 4). In routine clinical practice, quantitative islet autoantibody results are usually interpreted as positive or negative, and the level of the islet autoantibody, is not thought to be clinically meaningful.Islet autoantibody levels may provide additional information over positivity in type 1 diabetes at diagnosis. Similar to type 1 diabetes, autoantibodies to a specific antigen are commonly used for diagnosis in many other autoimmune diseases (such as TSH receptor antibodies in Graves’ disease and Rheumatoid Factor and Citrullinated Protein in rheumatoid arthritis). For Graves’ disease and rheumatoid arthritis, along with autoantibody positivity for these antigens, autoantibody level at diagnosis is associated with disease severity, prognosis and treatment success (5; 6). Multiple studies have shown a role for islet autoantibody level in the prediction of onset of type 1 diabetes, those with a higher levels of IA-2A, IAA and ICA have an increased risk of developing type 1 diabetes in at-risk populations (1; 7-9). However, it is not clear if the islet autoantibody level at diagnosis of type 1 diabetes, in addition to its interpretation as ‘positive’, is associated with the clinical phenotype similar to other autoimmune diseases.In this study, we undertook an analysis of GADA, IA-2A and ZnT8A levels at diagnosis in a large cohort of participants with type 1 diabetes, assessing the association of islet autoantibody levels on genetic and clinical characteristics at diagnosis in people with type 1 diabetes.

The anion photoelectron spectra of Cl- ⋅⋅⋅CD3 CDO, Cl- ⋅⋅⋅(CD3 CDO)2 , Br- ⋅⋅⋅CH3 CHO, and I- ⋅⋅⋅CH3 CHO are presented with electron stabilisation energies of 0.55, 0.93, 0.48, and 0.40 eV, respectively. Optimised geometries of the singly solvated species featured the halide appended to the CH3 CHO molecule in-line with the electropositive portion of the C=O bond and having binding energies between 45 and 52 kJ mol-1 . The doubly solvated Cl- ⋅⋅⋅(CH3 CHO)2 species features asymmetric solvation upon the addition of a second CH3 CHO molecule. Theoretical detachment energies were found to be in excellent agreement with experiment, with comparisons drawn between other halide complexes with simple carbonyl molecules.

BackgroundMissing data is a common problem in regression modelling. Much of the literature focuses on handling missing outcome variables, but there are also challenges when dealing with missing predictor information, particularly when trying to build prediction models for use in practice.MethodsWe develop a flexible Bayesian approach for handling missing predictor information in regression models. For prediction this provides practitioners with full posterior predictive distributions for both the missing predictor information and the outcome variable, conditional on the observed predictors. We apply our approach to a previously proposed treatment selection model for type 2 diabetes second-line therapies. Our approach combines a regression model and a Dirichlet process mixture model (DPMM), where the former defines the treatment selection model and the latter provides a flexible way to model the joint distribution of the predictors.ResultsWe show that under missing-completely-at-random (MCAR) and missing-at-random (MAR) assumptions (with respect to the missing predictors), the DPMM can model complex relationships between predictor variables, and predict missing values conditionally on existing information. We also demonstrate that in the presence of multiple missing predictors, the DPMM model can be used to explore which variable(s), if collected, could provide the most additional information about the likely outcome.ConclusionsOur approach can provide practitioners with supplementary information to aid treatment selection decisions in the presence of missing data, and can be readily extended to other types of response model.Key MessagesMissing predictor variables present a significant challenge when building and implementing prediction models in clinical practice.Removing individuals with missing information and performing a complete case analysis can lead to imprecision and bias. Multiple imputation approaches typically translate uncertainty through prediction model parameter standard errors, as opposed to a consistent joint probability model.Alternatively, a Bayesian approach using Dirichlet process mixture models (DPMMs) offers a flexible way to model complex joint distributions of predictor variables, which can be used to estimate posterior (predictive) distributions for the missing predictors, conditional on the observed predictors.Using a DPMM, in this way allows uncertainties around missing predictor data to be propagated through to a prediction model of interest using a Bayesian hierarchical framework. This allows prediction models to be developed using datasets with incomplete predictor information (assuming missing-completely-at-random/missing-at-random). Furthermore, predictions can be made on new individuals even if they have incomplete predictor information (under the same assumptions).This approach provides full posterior predictive probability distributions for both missing predictor variables and the outcome variable, allowing a wide range of probabilistic models outputs to be derived to support clinical decision making.

BackgroundUltraviolet radiation (UVR) exposure is commonly reported as a risk factor for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, minimal evaluation of photo-induced SJS/TEN has been conducted. Thus, this review identifies all cases of SJS/TEN that are linked to an acute exposure of UVR and outline the unifying characteristics of these cases. Furthermore, the theoretical pathogenesis, differential diagnoses, and proposed diagnostic criteria are defined.MethodsPubMed, Google Scholar, and other databases and websites were searched from inception to September 2021 to identify studies that met inclusion criteria. The following keywords were utilized: “Stevens-Johnson syndrome” and “toxic epidermal necrolysis” with “ultraviolet,” “photodistributed,” “photo-induced,” “photosensitivity,” and “photo.” One reviewer assessed study characteristics, with confirmation by a second. The risk of bias was assessed independently by another.ResultsThirteen patient cases were identified, all reporting ultraviolet radiation prior to rash onset and an underlying causal drug. Case classifications included 7/13 SJS and 6/13 TEN. All cases described the rash as photodistributed with UVR exposure prior to rash onset (delay of 1-3 days) and a causal drug. 10 cases provided evidence that the photodistributed rash distribution lacked linear demarcation (as in a sunburn) with satellite target-like lesions. No cases described a flu-like prodrome.DiscussionMucositis, palmar and plantar rash, a positive Nikolsky sign, and a prolonged disease course can help distinguish from photosensitive reactions, while a negative direct immunofluorescence test is important to distinguish from other photo-induced disorders.ConclusionPhysicians should be aware that UVR may precipitate SJS/TEN in patients taking susceptible drugs. After a 24-hour delay from UVR exposure, a non-distinct, photodistributed rash appears with no flu-like prodrome and progresses for at least 48 hours to include vesiculobullous eruptions and mucous membrane involvement. Photodistributed SJS/TEN appears to be photo-drug-induced with a unique onset and rash presentation that should be recognized as a distinct diagnosis.

Monitoring how populations respond to sustained conservation measures is essential to detect changes in their population status and determine the effectiveness of any interventions. In the case of sea turtles, their populations are difficult to assess because of their complicated life histories. Ground-derived clutch counts are most often used as an index of population size for sea turtles; however, data are often incomplete with varying sampling intensity within and among sites and seasons. To address these issues, we: (1) develop a Bayesian statistical modelling framework that can be used to account for sampling uncertainties in a robust probabilistic manner within a given site and season; and (2) apply this to a previously unpublished long-term sea turtle dataset (n = 17 years) collated for the Republic of the Congo, which hosts two sympatrically nesting species of sea turtle (leatherback turtle [Dermochelys coriacea] and olive ridley turtle [Lepidochelys olivacea]). The results of this analysis suggest that leatherback turtle nesting levels dropped initially and then settled into quasi-cyclical levels of interannual variability, with an average of 573 (mean, 95% prediction interval: 554–626) clutches laid annually between 2012 and 2017. In contrast, nesting abundance for olive ridley turtles has increased more recently, with an average of 1,087 (mean, 95% prediction interval: 1,057–1,153) clutches laid annually between 2012 and 2017. These findings highlight the regional and global importance of this rookery with the Republic of the Congo, hosting the second largest documented populations of olive ridley and the third largest for leatherback turtles in Central Africa; and the fourth largest non-arribada olive ridley rookery globally. Furthermore, whilst the results show that Congo’s single marine and coastal national park provides protection for over half of sea turtle clutches laid in the country, there is scope for further protection along the coast. Although large parts of the African coastline remain to be adequately monitored, the modelling approach used here will be invaluable to inform future status assessments for sea turtles given that most datasets are temporally and spatially fragmented.

Sex as a biological variable has been the focus of increasing interest. Relatively few studies have focused, however, on differences in peripheral taste function between males and females. Nonetheless, there are reports of sex-dependent differences in chemosensitivity in the gustatory system. The involvement of endogenous changes in ovarian hormones has been suggested to account for taste discrepancies. Additionally, whether sex differences exist in taste receptor expression, activation, and subsequent signaling pathways that may contribute to different taste responsiveness is not well understood. In this study, we show the presence of both the nuclear and plasma membrane forms of estrogen receptor (ER) mRNA and protein in mouse taste cells. Furthermore, we provide evidence that estrogen increases taste cell activation during the application of fatty acids, the chemical cue for fat taste, in taste receptor cells. We found that genes important for the transduction pathway of fatty acids vary between males and females and that these differences also exist across the various taste papillae. In vivo support for the effect of estrogens in taste cells was provided by comparing the fatty acid responsiveness in male, intact female, and ovariectomized (OVX) female mice with and without hormone replacement. In general, females detected fatty acids at lower concentrations, and the presence of circulating estrogens increased this apparent fat taste sensitivity. Taken together, these data indicate that increased circulating estrogens in the taste system may play a significant role in physiology and chemosensory cellular activation and, in turn, may alter taste-driven behavior. NEW & NOTEWORTHY Using molecular, cellular, and behavioral analyses, this study shows that sex differences occur in fat taste in a mouse model. Female mice are more responsive to fatty acids, leading to an overall decrease in intake and fatty acid preference. These differences are linked to sex hormones, as estradiol enhances taste cell responsiveness to fatty acids during periods of low circulating estrogen following ovariectomy and in males. Estradiol is ineffective in altering fatty acid signaling during a high-estrogen period and in ovariectomized mice on hormone replacement. Thus, taste receptor cells are a direct target for actions of estrogen, and there are multiple receptors with differing patterns of expression in taste cells.

Self and relational goals influence health behaviors. This investigation examined how these distinct motivations affect response to persuasive anti-smoking testimonials. While self vs. relational m...

A combined experimental and theoretical approach has been used to investigate X- ⋅⋅⋅CH2 O (X=F, Cl, Br, I) complexes in the gas phase. Photoelectron spectroscopy, in tandem with time-of-flight mass spectrometry, has been used to determine electron binding energies for the Cl- ⋅⋅⋅CH2 O, Br- ⋅⋅⋅CH2 O, and I- ⋅⋅⋅CH2 O species. Additionally, high-level CCSD(T) calculations found a C2v minimum for these three anion complexes, with predicted electron detachment energies in excellent agreement with the experimental photoelectron spectra. F- ⋅⋅⋅CH2 O was also studied theoretically, with a Cs hydrogen-bonded complex found to be the global minimum. Calculations extended to neutral X⋅⋅⋅CH2 O complexes, with the results of potential interest to atmospheric CH2 O chemistry.

Anion photoelectron spectroscopy has been used to investigate the structure and dynamics of CH

Despite research indicating that exerting dominance and control is characteristic of psychopathy, no research has examined the role that feelings of and desire for power plays in psychopathy-related aggression. Borrowing from various literatures and novel conceptualizations, we investigated the contributions of feeling powerful and/or desiring power and distinct psychopathy facets in explaining aggression manifested in different forms (i.e., physical, verbal, indirect) across 4 samples. Results from regression analyses within each sample and a meta-analysis across the samples indicated that the impulsive facet of psychopathy was generally related to multiple forms of aggression, and the unique variance in the affective facet was primarily related to physical aggression across samples. In contrast, the unique variance of the interpersonal facet showed a primary relationship with indirect aggression (e.g., relational, passive). Desiring power made unique contributions in relation to multiple forms of aggression, whereas feeling powerful was generally unrelated and/or negatively related to aggression. In sum, the unique variance in the psychopathy facets showed fairly specialized relationships with forms of aggression, and desire for power may be an independent explanatory construct for multiple forms of aggression proneness. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Gut microbiome disequilibrium is increasingly implicated in host fitness reductions, including for the economically important and disease‐challenged western honey bee Apis mellifera. In laboratory experiments, the antibiotic tetracycline, which is used to prevent American Foulbrood Disease in countries including the US, elevates honey bee mortality by disturbing the microbiome. It is unclear, however, how elevated individual mortality affects colony‐level fitness.We used an agent‐based model (BEEHAVE) and empirical data to assess colony‐level effects of antibiotic‐induced worker bee mortality, by measuring colony size. We investigated the relationship between the duration that the antibiotic‐induced mortality probability is imposed for and colony size.We found that when simulating antibiotic‐induced mortality of worker bees from just 60 days per year, up to a permanent effect, the colony is reduced such that tetracycline treatment would not meet the European Food Safety Authority's (EFSA) honey bee protection goals. When antibiotic mortality was imposed for the hypothetical minimal exposure time, which assumes that antibiotics only impact the bee's fitness during the recommended treatment period of 15 days in both spring and autumn, the colony fitness reduction was only marginally under the EFSA's threshold. Synthesis and Applications. Modelling colony‐level impacts of antibiotic treatment shows that individual honey bee worker mortality can lead to colony mortality. To assess the full impact, the persistence of antibiotic‐induced mortality in honey bees must be determined experimentally, in vivo. We caution that as the domestication of new insect species increases, maintaining healthy gut microbiomes is of paramount importance to insect health and commercial productivity. The recommendation from this work is to limit prophylactic use of antibiotics and to not exceed recommended treatment strategies for domesticated insects. This is especially important for highly social insects as excess antibiotic use will likely decrease colony growth and an increase in colony mortality., Modelling colony‐level impacts of antibiotic treatment shows that individual honey bee worker mortality can lead to colony mortality. To assess the full impact, the persistence of antibiotic‐induced mortality in honey bees must be determined experimentally, in vivo. We caution that as the domestication of new insect species increases, maintaining healthy gut microbiomes is of paramount importance to insect health and commercial productivity. The recommendation from this work is to limit prophylactic use of antibiotics and to not exceed recommended treatment strategies for domesticated insects. This is especially important for highly social insects as excess antibiotic use will likely decrease colony growth and an increase in colony mortality.

Background Variation in host attributes that influence their contact rates and infectiousness can lead some individuals to make disproportionate contributions to the spread of infections. Understanding the roles of such ‘superspreaders’ can be crucial in deciding where to direct disease surveillance and controls to greatest effect. In the epidemiology of bovine tuberculosis (bTB) in Great Britain, it has been suggested that a minority of cattle farms or herds might make disproportionate contributions to the spread of Mycobacterium bovis, and hence might be considered ‘superspreader farms’. Objectives and Methods We review the literature to identify the characteristics of farms that have the potential to contribute to exceptional values in the three main components of the farm reproductive number ‐ Rf: contact rate, infectiousness and duration of infectiousness, and therefore might characterize potential superspreader farms for bovine tuberculosis in Great Britain. Results Farms exhibit marked heterogeneity in contact rates arising from between‐farm trading of cattle. A minority of farms act as trading hubs that greatly augment connections within cattle trading networks. Herd infectiousness might be increased by high within‐herd transmission or the presence of supershedding individuals, or infectiousness might be prolonged due to undetected infections or by repeated local transmission, via wildlife or fomites. Conclusions Targeting control methods on putative superspreader farms might yield disproportionate benefits in controlling endemic bovine tuberculosis in Great Britain. However, real‐time identification of any such farms, and integration of controls with industry practices, present analytical, operational and policy challenges., In the epidemiology of bovine tuberculosis (bTB) in Great Britain, a minority of ‘superspreader farms’ might make disproportionate contributions to the maintenance and spread of infection. A minority of farms act as trading hubs that greatly augment connections in trading networks, herd infectiousness might be increased by the presence of supershedding individuals, and herd infectiousness might be prolonged due to undetected infections or repeated local transmission, via wildlife or fomites. Targeting control methods on putative superspreader farms might yield disproportionate benefits in controlling endemic bovine tuberculosis in Great Britain.

Persuasion research highlights the central role emotions play in driving persuasion processes. This investigation addressed the influence of message factors and risk perceptions in determining how ...

Choking remains a leading cause of accidental death and morbidity worldwide. Currently, there is no device to assist in the resuscitation of a choking victim when standard maneuvers fail. A novel portable non-powered suction device (LifeVac; LifeVac LLC, Nesconset, NY) has been developed and may have potential use in patients with oropharyngeal dysphagia who are at increased risk of choking. The device is FDA registered and distributed worldwide. This case series provides a summary of self-reported data regarding the use of the suction device in adult patients with oropharyngeal dysphagia during real-world choking emergencies recorded between January 2014 and July 2020. Over a 6-year monitoring period the device has been reported to be successful in the resuscitation of 38 out of 39 patients with oropharyngeal dysphagia during choking emergencies. Although the obstruction was removed with the device from the 39th patient, resuscitation was not successful and he succumbed to his injuries. This portable, non-powered suction device may be useful in resuscitating patients with oropharyngeal dysphagia who are choking. The reported cases describe successful use of the device in real-world settings with minimal risk. Resuscitating patients with oropharyngeal dysphagia using this device may be a viable option when abdominal thrusts or back blows fail to resolve a choking emergency.

The cetacean conservationist is often faced with evaluating population trends from abundance data that are either sparse or recorded at different times in different years. The presence of diel or seasonal patterns in the data together with unplanned gaps is often problematic. Such data are typical of those obtained from static acoustic monitoring. We present a simple and transparent non-parametric trend evaluation method, ‘Paired Year Ratio Assessment (PYRA)’ that uses only whole days of data wherever they are present in each of successive pairs of periods of 365 days. We provide a quantitative comparison of the performance of PYRA with traditional generalised additive models (GAMS) and nonparametric randomisation tests that require a greater level of skill and experience for both application and interpretation. We conclude that PYRA is a powerful tool, particularly in the context of identifying population trends which is often the main aim of conservation-targeted acoustic monitoring.

Alpha-glucosidase inhibitor (αGIs)-induced pneumatosis intestinalis (PI) has been narrated in case reports but never systematically investigated. This study aimed to investigate the concurrency of PI and αGIs. A literature search was performed in PubMed, Google Scholar, WorldCat, and the Directory of Open-Access Journals (DOAJ) by using the keywords “pneumatosis intestinalis”, “alpha-glucosidase inhibitors”, and “diabetes”. In total, 29 cases of αGIs-induced PI in 28 articles were included. There were 11 men, 17 women, and one undefined sex, with a median age of 67. The most used αGI was voglibose (44.8%), followed by acarbose (41.4%) and miglitol (6.8%). Nine (31%) patients reported concomitant use of prednisone/prednisolone with or without immunosuppressants. The main symptoms were abdominal pain (54.5%) and distention (50%). The ascending colon (55.2%) and the ileum (34.5%) were the most affected. Nineteen (65.5%) patients had comorbidities. Patients with comorbidities had higher rates of air in body cavities, the portal vein, extraintestinal tissues, and the wall of the small intestine. Only one patient was found to have non-occlusive mesenteric ischemia. Twenty-five patients were treated with conservative therapy alone, and two patients received surgical intervention. All patients recovered. In conclusion, comorbidities, glucocorticoids, and immunosuppressants aggravate αGIs-induced PI. Conservative therapy is recommended when treating αGIs-induced PI.

Located in the midline lamina terminalis of the anterior wall of the third ventricle, the median preoptic nucleus is a thin elongated nucleus stretching around the rostral border of the anterior commissure. Its neuronal elements, composed of various types of excitatory glutamatergic and inhibitory GABAergic neurons, receive afferent neural signals from (1) neighboring subfornical organ and organum vasculosum of the lamina terminalis related to plasma osmolality and hormone concentrations, e.g., angiotensin II; (2) from peripheral sensors such as arterial baroreceptors and cutaneous thermosensors. Different sets of these MnPO glutamatergic and GABAergic neurons relay output signals to hypothalamic, midbrain, and medullary regions that drive homeostatic effector responses. Included in the effector responses are (1) thirst, antidiuretic hormone secretion and renal sodium excretion that subserve osmoregulation and body fluid homeostasis; (2) vasoconstriction or dilatation of skin blood vessels, and shivering and brown adipose tissue thermogenesis for core temperature homeostasis; (3) inhibition of hypothalamic and midbrain nuclei that stimulate wakefulness and arousal, thereby promoting both REM and non-REM sleep; and (4) activation of sympathetic pathways that drive vasoconstriction and heart rate to maintain arterial pressure and the perfusion of vital organs. The small size of MnPO belies its massive homeostatic significance.

This short review focusses on the inflammatory reflex, which acts in negative feedback manner to moderate the inflammatory consequences of systemic microbial challenge. The historical development of the inflammatory reflex concept is reviewed, along with evidence that the endogenous reflex response to systemic inflammation is mediated by the splanchnic sympathetic nerves rather than by the vagi. We describe the coordinated nature of this reflex anti-inflammatory action: suppression of pro-inflammatory cytokines coupled with enhanced levels of the anti-inflammatory cytokine, interleukin 10. The limited information on the afferent and central pathways of the reflex is noted. We describe that the efferent anti-inflammatory action of the reflex is distributed among the abdominal viscera: several organs, including the spleen, can be removed without disabling the reflex. Understanding of the effector mechanism is incomplete, but it probably involves a very local action of neurally released noradrenaline on beta2 adrenoceptors on the surface of tissue resident macrophages and other innate immune cells. Finally we speculate on the biological and clinical significance of the reflex, citing evidence of its power to influence the resolution of experimental bacteraemia.

The first experimental evidence of the structure of the CCl5- gas-phase anion complex is presented in conjunction with results from high-level theoretical calculations. The photoelectron spectrum of the system shows a single peak with a maximum at 4.22 eV. Coupled cluster single double (triple) detachment energies of two stable C3v ion-molecule complexes of the form Cl-···CCl4 were also determined. The first complex found features the Cl- bound linearly in a Cl-···Cl-C bonding arrangement, while the second, less stable minimum has the Cl- positioned at the face of the CCl4 molecule, midway between three chlorine atoms. The calculated detachment energy for the first complex was found to be in excellent agreement with experiment, allowing the structure of CCl5- in the gas phase to be postulated as a noncovalent Cl-···CCl4 anion complex, with the Cl- anion tethered by a typical halogen bond.