Sticklebacks show consistent prey-share hierarchies within but not between patchy and sequential prey distributions

This work was supported by the School of Biology’s Experimental Research Project (BL4201) program, (module BL4201: Experimental Research Project) at the University of St Andrews, UK.When animals compete, hierarchies can emerge. If the outcome of competition under different conditions is dependent upon different sets of attributes, then we may expect to see hierarchies that are domain-specific, rather than domain general. We tested this idea by comparing prey share hierarchies within shoals of sticklebacks Gasterosteus aculeatus as they foraged for patchily-distributed or for drifting prey. We found that prey share was correlated across pairs of patch- and pairs of drift-foraging trials, but not between the two conditions, suggesting that separate repeatable but independent prey share hierarchies arise for each for each type of prey distribution. We discuss possible underlying mechanisms and ecological implications of this finding.PostprintPeer reviewe

Chemical composition of Some Components of the Arrestment Pheromone of the Black-Legged Tick, Ixodes scapularis (Acari : Ixodidae) and Their Use in Tick Control

Chemical analysis (high-performance liquid chromatography) and bioassay demonstrated the presence of compounds that seem to be components of the Ixodes scapularis arrestment pheromone. Only two purines, guanine and xanthine, were found in acidified saline extracts made from cast skins after molting of fed nymphs, fed larvae, and fecal/excretory exudates deposited by unfed adults on substrates in their environment. The ratio of guanine to xanthine was 10.6:1 in an extract from the nymphal skins versus 0.95:1 in an extract from the larval skins. Guanine, xanthine, and traces of a third purine, tentatively identified as 8-azaguanine, were found in extracts made from filter paper strips or washings from glass vials contaminated with tick feces and excreta left by unfed adults. 8-azaguanine may be a product of microbial degradation of the other purines rather than a natural product from the ticks. Low concentrations of ammonia also were detected in saline extracts of excreta from feeding ticks. Hematin also was found in NH4OH extracts of the black fecal/excretory exudates deposited by the unfed ticks. Hematin was tentatively identified by comparison of spectra with that of the authentic standard. Bioassays demonstrated a strong positive arrestment response to cast skins found to contain a mixture of guanine and xanthine and to black fecal/excretory exudates containing guanine, xanthine, the putative 8-azaguanine, and hematin. A Noldus video tracking system using a CCD video camera and Ethovision Pro tracking software showed statistically significant increases in the frequency of visits to the treated zone versus the control. Ticks were significantly more likely to assemble in response to the tick exudates within as little as 3 h compared with the controls. Previous bioassay studies also showed strong positive responses to guanine, xanthine, other purines, and hematin. Comparisons with the arrestment pheromones of other tick species are described. The inclusion of the pheromone components in a permethrin-impregnated oily matrix, Last Call, increased the lethal activity of the product to 95% compared with only 65% in the formulation with permethrin alone. More detailed knowledge of I. scapularis arrestment pheromone may be useful for improving the efficacy of this tick-killing technology even further

The Case for Gun Policy Reforms in America

Debates about gun control often drift towards general arguments about whether guns make us safer or less safe, and gun control is equated with restricting gun ownership. However, with recent Supreme Court decisions overturning laws which ban firearm possession in the District of Columbia and Chicago, current gun control policies in the U.S. do not disarm lawabiding adults over the age of 21. Rather, gun control laws today focus on one or more of four general objectives. These laws aim to:Define conditions that prohibit a person from possessing firearms;Implement regulations to prevent prohibited persons from possessing firearms;Restrict carrying of concealed firearms outside the home; andRegulate the design of firearms to enhance public and personal safety.In this report we draw upon research evidence to suggest how improvements in each of these types of gun policies could enhance public safety in the United States

Implementation of the integrated management of childhood illness with parasitological diagnosis of malaria in rural Ghana: health worker perceptions.

BACKGROUND: Timely and appropriate management of febrile illness among children under five years of age will contribute to achieving Millennium Development Goal-4. The revised World Health Organization-Global Malaria Programme's policy on test-based management of malaria must integrate effectively into the Integrated Management of Childhood Illness (IMCI). This study reports on perceptions of health workers on the health system factors influencing effective delivery of test-based diagnosis of malaria with IMCI. METHODS: A qualitative study was conducted among a range of health workers at different levels of the health system in the Brong Ahafo Region of Ghana. Interview transcripts were transferred into Nvivo 8 software for data management and analysis. A frame-work approach at two levels was used in the analysis, which included the processes required for implementation of test-based management of malaria and the health systems context. RESULTS: Forty-nine in-depth interviews were conducted. The National Health Insurance Scheme (NHIS) was perceived to have led to an increase in health facility attendance, thereby increasing the workload of health workers. Workload was reported as the main reason that health workers were not able to complete all of the examinations included in the IMCI algorithm. The NHIS financing guidelines were seen to be determining diagnosis and treatment practices by health-care givers. Concern was expressed about the erratic supply of malaria rapid diagnostic test kits (RDTs), the quality of RDTs related to potential false negative results when clinical symptoms were consistent with malaria. IMCI was seen as important but practically impossible to fully implement due to workload. CONCLUSIONS: Implementation of the WHO-revised IMCI guideline is confronted with a myriad of health systems challenges. The perceptions of front-line health workers on the accuracy and need for RDTs together with the capacity of health systems to support implementation plays a crucial role. The NHIS financing guidelines of diagnostics and treatments are influencing clinical decision-making in this setting. Further study is needed to understand the impact of the NHIS on the feasibility of integrating test-based management for malaria into the IMCI guidelines

Adenoidectomy for otitis media with effusion (OME) in children

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Adenoidectomy has often been used as a potential treatment for this condition. OBJECTIVES: To assess the benefits and harms of adenoidectomy, either alone or in combination with ventilation tubes (grommets), for OME in children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 January 2023. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared adenoidectomy (alone, or in combination with ventilation tubes) with either no treatment or non-surgical treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes (determined following a multi-stakeholder prioritisation exercise): 1) hearing, 2) otitis media-specific quality of life, 3) haemorrhage. SECONDARY OUTCOMES: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function, 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We included 10 studies (1785 children). Many of the studies used concomitant interventions for all participants, including insertion of ventilation tubes or myringotomy. All included studies had at least some concerns regarding the risk of bias. We report results for our main outcome measures at the longest available follow-up. We did not identify any data on disease-specific quality of life for any of the comparisons. Further details of additional outcomes and time points are reported in the review. 1) Adenoidectomy (with or without myringotomy) versus no treatment/watchful waiting (three studies) After 12 months there was little difference in the proportion of children whose hearing had returned to normal, but the evidence was very uncertain (adenoidectomy 68%, no treatment 70%; risk ratio (RR) 0.97, 95% confidence interval (CI) 0.65 to 1.46; number needed to treat to benefit (NNTB) 50; 1 study, 42 participants). There is a risk of haemorrhage from adenoidectomy, but the absolute risk appears small (1/251 receiving adenoidectomy compared to 0/229, Peto odds ratio (OR) 6.77, 95% CI 0.13 to 342.54; 1 study, 480 participants; moderate certainty evidence). The risk of persistent OME may be slightly lower after two years in those receiving adenoidectomy (65% versus 73%), but again the difference was small (RR 0.90, 95% CI 0.81 to 1.00; NNTB 13; 3 studies, 354 participants; very low-certainty evidence). 2) Adenoidectomy (with or without myringotomy) versus non-surgical treatment No studies were identified for this comparison. 3) Adenoidectomy and bilateral ventilation tubes versus bilateral ventilation tubes (four studies) There was a slight increase in the proportion of ears with a return to normal hearing after six to nine months (57% adenoidectomy versus 42% without, RR 1.36, 95% CI 0.98 to 1.89; NNTB 7; 1 study, 127 participants (213 ears); very low-certainty evidence). Adenoidectomy may give an increased risk of haemorrhage, but the absolute risk appears small, and the evidence was uncertain (2/416 with adenoidectomy compared to 0/375 in the control group, Peto OR 6.68, 95% CI 0.42 to 107.18; 2 studies, 791 participants). The risk of persistent OME was similar for both groups (82% adenoidectomy and ventilation tubes compared to 85% ventilation tubes alone, RR 0.96, 95% CI 0.86 to 1.07; very low-certainty evidence). 4) Adenoidectomy and unilateral ventilation tube versus unilateral ventilation tube (two studies) Slightly more children returned to normal hearing after adenoidectomy, but the confidence intervals were wide (57% versus 46%, RR 1.24, 95% CI 0.79 to 1.96; NNTB 9; 1 study, 72 participants; very low-certainty evidence). Fewer children may have persistent OME after 12 months, but again the confidence intervals were wide (27.2% compared to 40.5%, RR 0.67, 95% CI 0.35 to 1.29; NNTB 8; 1 study, 74 participants). We did not identify any data on haemorrhage. 5) Adenoidectomy and ventilation tubes versus no treatment/watchful waiting (two studies) We did not identify data on the proportion of children who returned to normal hearing. However, after two years, the mean difference in hearing threshold for those allocated to adenoidectomy was -3.40 dB (95% CI -5.54 to -1.26; 1 study, 211 participants; very low-certainty evidence). There may be a small reduction in the proportion of children with persistent OME after two years, but the evidence was very uncertain (82% compared to 90%, RR 0.91, 95% CI 0.82 to 1.01; NNTB 13; 1 study, 232 participants). We noted that many children in the watchful waiting group had also received surgery by this time point. 6) Adenoidectomy and ventilation tubes versus non-surgical treatment No studies were identified for this comparison. AUTHORS' CONCLUSIONS: When assessed with the GRADE approach, the evidence for adenoidectomy in children with OME is very uncertain. Adenoidectomy may reduce the persistence of OME, although evidence about the effect of this on hearing is unclear. For patients and carers, a return to normal hearing is likely to be important, but few studies measured this outcome. We did not identify any evidence on disease-specific quality of life. There were few data on adverse effects, in particular postoperative bleeding. The risk of haemorrhage appears to be small, but should be considered when choosing a treatment strategy for children with OME. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children

Interleukin-21 Is Critically Required in Autoimmune and Allogeneic Responses to Islet Tissue in Murine Models

OBJECTIVE-Type 1 diabetes is an incurable chronic autoimmune disease. Although transplantation of pancreatic islets may serve as a surrogate source of insulin, recipients are subjected to a life of immunosuppression. Interleukin (IL)-21 is necessary for type 1 diabetes in NOD mice. We examined the efficacy of an IL-21-targeted therapy on prevention of diabetes in NOD mice, in combination with syngeneic islet transplantation. In addition, we assessed the role of IL-21 responsiveness in islet allograft rejection in mouse animal models. RESEARCH DESIGN AND METHODS-NOD mice were treated with IL-21R/Fc, an IL-21-neutralizing chimeric protein. This procedure was combined with syngeneic islet transplantation to treat diabetic NOD mice. Survival of allogeneic islet grafts in IL-21R-deficient mice was also assessed. RESULTS-Evidence is provided that IL-21 is continually required by the autoimmune infiltrate, such that insulitis was reduced and reversed and diabetes inhibited by neutralization of IL-21 at a late preclinical stage. Recovery from autoimmune diabetes was achieved by combining neutralization of IL-21 with islet transplantation. Furthermore, IL-21-responsiveness by CD8+ T-cells was sufficient to mediate islet allograft rejection. CONCLUSIONS-Neutralization of IL-21 in NOD mice can inhibit diabetes, and when paired with islet transplantation, this therapeutic approach restored normoglycemia. The influence of IL-21 on a graft-mounted immune response was robust, since the absence of IL-21 signaling prevented islet allograft rejection. These findings suggest that therapeutic manipulation of IL-21 may serve as a suitable treatment for patients with type 1 diabetes. Diabetes 60:867-875, 20111151sciescopu

Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2.

The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. DJH was supported by a Kay Kendall Leukaemia Fund Intermediate Fellowship from the UK.This is the author accepted manuscript. The final version is available from the National Academy of Sciences via http://dx.doi.org/10.1073/pnas.160055711

Using positive behavioural support as a treatment for trauma symptoms with a man with intellectual disabilities

Background. There is robust evidence that psychological therapies are an effective treatment for trauma-related symptoms, including post-traumatic stress disorder. However, there are relatively few studies involving people with intellectual disabilities, and no studies drawing on positive behavioural support as the mechanism for the delivery of treatment. Method and materials. This study was a descriptive case report of a young man with intellectual disabilities who had a history of early trauma. His challenging behaviour was associated with demand avoidance. A positive behavioural support plan, incorporating psychological therapies and medication, was developed, implemented and is described. Results. Over time, challenging behaviours reduced and were eventually extinguished. This was associated with an increase in engagement in a variety of activities and a reduction in trauma-related symptoms. Discussion. Using positive behaviour support plans as the organisational framework for the adaptation and delivery of both psychological therapies and medication for complex cases is advantageous. Excellent team working is necessary to ensure that interventions are successful

Gene Dosage–limiting Role of Aire in Thymic Expression, Clonal Deletion, and Organ-specific Autoimmunity

Inactivation of the autoimmune regulator (Aire) gene causes a rare recessive disorder, autoimmune polyendocrine syndrome 1 (APS1), but it is not known if Aire-dependent tolerance mechanisms are susceptible to the quantitative genetic changes thought to underlie more common autoimmune diseases. In mice with a targeted mutation, complete loss of Aire abolished expression of an insulin promoter transgene in thymic epithelium, but had no effect in pancreatic islets or the testes. Loss of one copy of Aire diminished thymic expression of the endogenous insulin gene and the transgene, resulting in a 300% increase in islet-reactive CD4 T cells escaping thymic deletion in T cell receptor transgenic mice, and dramatically increased progression to diabetes. Thymic deletion induced by antigen under control of the thyroglobulin promoter was abolished in Aire homozygotes and less efficient in heterozygotes, providing an explanation for thyroid autoimmunity in APS1. In contrast, Aire deficiency had no effect on thymic deletion to antigen controlled by a systemic H-2K promoter. The sensitivity of Aire-dependent thymic deletion to small reductions in function makes this pathway a prime candidate for more subtle autoimmune quantitative trait loci, and suggests that methods to increase Aire activity would be a potent strategy to lower the incidence of organ-specific autoimmunity

Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US$11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings