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Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments (PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure ( β  = 0.27 (0.12–0.43), P  = 0.001, n  = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56–0.93), P  = 0.011). EMA mediated the protective farm effect by 19%. In a nested case–control sample ( n  = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09–0.91), P  = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17–0.84), P  = 0.017) and the relative abundance of the gene encoding butyryl–coenzyme A (CoA):acetate–CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19–0.97), P  = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut–lung axis in humans. Growing up in the rich microbial environment of a farm strongly influences the maturation of the gut microbiome in the first year of life, which helps protect against the development of asthma in children.

Objective To examine the effectiveness of screening for intimate partner violence conducted within healthcare settings to determine whether or not screening increases identification and referral to support agencies, improves women’s wellbeing, decreases further violence, or causes harm. Design Systematic review and meta-analysis of trials assessing effectiveness of screening. Study assessment, data abstraction, and quality assessment were conducted independently by two of the authors. Standardised estimations of the risk ratios and 95% confidence intervals were calculated. Data sources Nine databases searched up to July 2012 (CENTRAL, Medline, Medline(R), Embase, DARE, CINAHL, PsycINFO, Sociological Abstracts, and ASSIA), and five trials registers searched up to 2010. Eligibility criteria for selecting studies Randomised or quasi-randomised trials of screening programmes for intimate partner violence involving all women aged ≥16 attending a healthcare setting. We included only studies in which clinicians in the intervention arm personally conducted the screening, or were informed of the screening result at the time of the consultation, compared with usual care (or no screening). Studies of screening programmes that were followed by structured interventions such as advocacy or therapeutic intervention were excluded. Results 11 eligible trials (n=13 027) were identified. In six pooled studies (n=3564), screening increased the identification of intimate partner violence (risk ratio 2.33, 95% confidence interval 1.39 to 3.89), particularly in antenatal settings (4.26, 1.76 to 10.31). Based on three studies (n=1400), we detected no evidence that screening increases referrals to domestic violence support services (2.67, 0.99 to 7.20). Only two studies measured women’s experience of violence after screening (three to 18 months after screening) and found no reduction in intimate partner violence. One study reported that screening does not cause harm. Conclusions Though screening is likely to increase identification of intimate partner violence in healthcare settings, rates of identification from screening interventions were low relative to best estimates of prevalence of such violence. It is uncertain whether screening increases effective referral to supportive agencies. Screening does not seem to cause harm in the short term, but harm was measured in only one study. As the primary studies did not detect improved outcomes for women screened for intimate partner violence, there is insufficient evidence for screening in healthcare settings. Studies comparing screening versus case finding, or screening in combination with therapeutic intervention for women’s long term wellbeing, are needed to inform the implementation of identification policies in healthcare settings.

Bifidobacterium species are beneficial and dominant members of the breastfed infant gut microbiome; however, their health benefits are partially species-dependent. Here, we characterize the species and subspecies of Bifidobacterium in breastfed infants around the world to consider the potential impact of a historic dietary shift on the disappearance of B. longum subsp. infantis in some populations. Across populations, three distinct patterns of Bifidobacterium colonization emerged: (1) The dominance of Bifidobacterium longum subspecies infantis, (2) prevalent Bifidobacterium of multiple species, and (3) the frequent absence of any Bifidobacterium. These patterns appear related to a country’s history of breastfeeding, with infants in countries with historically high rates of long-duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter-duration breastfeeding. In addition, the timing of infant colonization with B. longum subsp. infantis is consistent with horizontal transmission of this subspecies, rather than the vertical transmission previously reported for other Bifidobacterium species. These findings highlight the need to consider historical and cultural influences on the prevalence of gut commensals and the need to understand epidemiological transmission patterns of Bifidobacterium and other major commensals.

In biodiversity research, the retrieval of genetic material from organisms is a common and essential component for assessing genetic diversity. The welfare of the organism, however, needs to be balanced against the overall goal of the intended research. One sampling technique often applied to retrieve DNA material from small reptiles is the removal of a small portion of the distal end of the tail. While most squamate reptiles have tail autotomy, some species (e.g. many iguanid lizards and snakes) do not regenerate tail tissue. We therefore explored the efficacy of a minimally disruptive technique, buccal swabbing, as an alternative to tissue sampling via tail clipping, particularly for species without tail autotomy, using dwarf chameleons (Bradypodion spp.) as a case study. The two sampling techniques were compared to assess the efficacy of DNA retrieval. We also evaluated the financial implications of each technique. The results indicate that buccal swabs paired with a specialised DNA extraction kit offer a feasible (although expensive), once-off alternative to tissue sampling, but with no material left for biobanking. Deviations in swab type used and the DNA extraction process (i.e. using more affordable extraction procedures) resulted in poor DNA retrieval and unreadable sequences. This finding suggests that buccal swabbing can be a suitable alternative when finances are not constrained, an expensive extraction kit is available, and biobanking is not a concern. For researchers from low- to middle-income economies, this expensive alternative may hamper research progress by placing a financial obstacle in the way, and therefore the next best option is tissue sampling. Significance: This study provides guidance on the efficacy of buccal swabs as a viable alternative to tissue samples collected via tail clipping for DNA retrieval from small reptiles. The results indicate that swabs may be a feasible alternative to tissue samples when finances are not constrained. Deviations in buccal swabbing method (i.e. using more cost-effective alternatives) performed poorly in DNA retrieval and do not offer competitive alternatives to tissue samples. Although buccal swabs were shown to offer an alternative to tissue samples, the financial implications to research in low- to middle-income economies may hinder research goals unnecessarily.

Violence towards others in the community has been identified as a significant problem for a subset of Iraq and Afghanistan veterans. To investigate the extent to which post-traumatic stress disorder (PTSD) and other risk factors predict future violent behaviour in military veterans. A national, multiwave survey enrolling a random sample of all US veterans who served in the military after 11 September 2001 was conducted. A total of 1090 veterans from 50 US states and all military branches completed two survey waves mailed 1 year apart (retention rate = 79%). Overall, 9% endorsed engaging in severe violence and 26% in other physical aggression in the previous year, as measured at Wave 2. Younger age, financial instability, history of violence before military service, higher combat exposure, PTSD, and alcohol misuse at Wave 1 were significantly associated with higher severe violence and other physical aggression in the past year at Wave 2. When combinations of these risk factors were present, predicted probability of violence in veterans rose sharply. Veterans with both PTSD and alcohol misuse had a substantially higher rate of subsequent severe violence (35.9%) compared with veterans with alcohol misuse without PTSD (10.6%), PTSD without alcohol misuse (10.0%) or neither PTSD nor alcohol misuse (5.3%). Using multiple regression, we found that veterans with PTSD and without alcohol misuse were not at significantly higher risk of severe violence than veterans with neither PTSD nor alcohol misuse. There was a trend for other physical aggression to be higher in veterans with PTSD without alcohol misuse. Co-occurring PTSD and alcohol misuse was associated with a marked increase in violence and aggression in veterans. Compared with veterans with neither PTSD nor alcohol misuse, veterans with PTSD and no alcohol misuse were not significantly more likely to be severely violent and were only marginally more likely to engage in other physical aggression. Attention to cumulative effects of multiple risk factors beyond diagnosis--including demographics, violence history, combat exposure, and veterans' having money to cover basic needs like food, shelter, transportation, and medical care--is crucial for optimising violence risk management.

Down’s syndrome (DS) presents with a constellation of cardiac, neurocognitive and growth impairments. Individuals with DS are also prone to severe infections and autoimmunity including thyroiditis, type 1 diabetes, coeliac disease and alopecia areata 1 , 2 . Here, to investigate the mechanisms underlying autoimmune susceptibility, we mapped the soluble and cellular immune landscape of individuals with DS. We found a persistent elevation of up to 22 cytokines at steady state (at levels often exceeding those in patients with acute infection) and detected basal cellular activation: chronic IL-6 signalling in CD4 T cells and a high proportion of plasmablasts and CD11c + Tbet high CD21 low B cells (Tbet is also known as TBX21). This subset is known to be autoimmune-prone and displayed even greater autoreactive features in DS including receptors with fewer non-reference nucleotides and higher IGHV4-34 utilization. In vitro, incubation of naive B cells in the plasma of individuals with DS or with IL-6-activated T cells resulted in increased plasmablast differentiation compared with control plasma or unstimulated T cells, respectively. Finally, we detected 365 auto-antibodies in the plasma of individuals with DS, which targeted the gastrointestinal tract, the pancreas, the thyroid, the central nervous system, and the immune system itself. Together, these data point to an autoimmunity-prone state in DS, in which a steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation all contribute to a breach in immune tolerance. Our findings also open therapeutic paths, as we demonstrate that T cell activation is resolved not only with broad immunosuppressants such as Jak inhibitors, but also with the more tailored approach of IL-6 inhibition. An autoimmune-prone state of steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation contributes to a breach in immune tolerance in individuals with Down’s syndrome.

The secondary compounds of pines (Pinus) can strongly affect the physiology, ecology and behaviors of the bark beetles (Coleoptera: Curculionidae, Scolytinae) that feed on sub-cortical tissues of hosts. Jack pine (Pinus banksiana) has a wide natural distribution range in North America (Canada and USA) and thus variations in its secondary compounds, particularly monoterpenes, could affect the host expansion of invasive mountain pine beetle (Dendroctonus ponderosae), which has recently expanded its range into the novel jack pine boreal forest. We investigated monoterpene composition of 601 jack pine trees from natural and provenance forest stands representing 63 populations from Alberta to the Atlantic coast. Throughout its range, jack pine exhibited three chemotypes characterized by high proportions of α-pinene, β-pinene, or limonene. The frequency with which the α-pinene and β-pinene chemotypes occurred at individual sites was correlated to climatic variables, such as continentality and mean annual precipitation, as were the individual α-pinene and β-pinene concentrations. However, other monoterpenes were generally not correlated to climatic variables or geographic distribution. Finally, while the enantiomeric ratios of β-pinene and limonene remained constant across jack pine's distribution, (-):(+)-α-pinene exhibited two separate trends, thereby delineating two α-pinene phenotypes, both of which occurred across jack pine's range. These significant variations in jack pine monoterpene composition may have cascading effects on the continued eastward spread and success of D. ponderosae in the Canadian boreal forest.

In biodiversity research, the retrieval of genetic material from organisms is a common and essential component for assessing genetic diversity. The welfare of the organism, however, needs to be balanced against the overall goal of the intended research. One sampling technique often applied to retrieve DNA material from small reptiles is the removal of a small por tion of the distal end of the tail. While most squamate reptiles have tail autotomy, some species (e.g. many iguanid lizards and snakes) do not regenerate tail tissue. We therefore explored the efficacy of a minimally disruptive technique, buccal swabbing, as an alternative to tissue sampling via tail clipping, par ticularly for species without tail autotomy, using dwarf chameleons (Bradypodion spp.) as a case study. The two sampling techniques were compared to assess the efficacy of DNA retrieval. We also evaluated the financial implications of each technique. The results indicate that buccal swabs paired with a specialised DNA extraction kit offer a feasible (although expensive), once-off alternative to tissue sampling, but with no material left for biobanking. Deviations in swab type used and the DNA extraction process (i.e. using more affordable extraction procedures) resulted in poor DNA retrieval and unreadable sequences. This finding suggests that buccal swabbing can be a suitable alternative when finances are not constrained, an expensive extraction kit is available, and biobanking is not a concern. For researchers from low- to middle-income economies, this expensive alternative may hamper research progress by placing a financial obstacle in the way, and therefore the next best option is tissue sampling.Significance: This study provides guidance on the efficacy of buccal swabs as a viable alternative to tissue samplescollected via tail clipping for DNA retrieval from small reptiles. The results indicate that swabs may be afeasible alternative to tissue samples when finances are not constrained. Deviations in buccal swabbingmethod (i.e. using more cost-effective alternatives) performed poorly in DNA retrieval and do not offercompetitive alternatives to tissue samples. Although buccal swabs were shown to offer an alternative totissue samples, the financial implications to research in low- to middle-income economies may hinderresearch goals unnecessarily.

Purpose Haploinsufficiency of USP7 , located at chromosome 16p13.2, has recently been reported in seven individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), seizures, and hypogonadism. Further, USP7 was identified to critically incorporate into the MAGEL2-USP7-TRIM27 (MUST), such that pathogenic variants in USP7 lead to altered endosomal F-actin polymerization and dysregulated protein recycling. Methods We report 16 newly identified individuals with heterozygous USP7 variants, identified by genome or exome sequencing or by chromosome microarray analysis. Clinical features were evaluated by review of medical records. Additional clinical information was obtained on the seven previously reported individuals to fully elucidate the phenotypic expression associated with USP7 haploinsufficiency. Results The clinical manifestations of these 23 individuals suggest a syndrome characterized by DD/ID, hypotonia, eye anomalies,feeding difficulties, GERD, behavioral anomalies, and ASD, and more specific phenotypes of speech delays including a nonverbal phenotype and abnormal brain magnetic resonance image findings including white matter changes based on neuroradiologic examination. Conclusion The consistency of clinical features among all individuals presented regardless of de novo USP7 variant type supports haploinsufficiency as a mechanism for pathogenesis and refines the clinical impact faced by affected individuals and caregivers.