Gut dysbiosis in cutaneous T-cell lymphoma is characterized by shifts in relative abundances of specific bacterial taxa and decreased diversity in more advanced disease.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) patients often suffer from recurrent skin infections and profound immune dysregulation in advanced disease. The gut microbiome has been recognized to influence cancers and cutaneous conditions; however, it has not yet been studied in CTCL. OBJECTIVES: To investigate the gut microbiome in patients with CTCL and in healthy controls. METHODS: A case-control study was conducted between January 2019 and November 2020 at Northwestern's busy multidisciplinary CTCL clinic (Chicago, Illinois, USA) utilizing 16S ribosomal RNA gene amplicon sequencing and bioinformatics analyses to characterize the microbiota present in fecal samples of CTCL patients (n = 38) and age-matched healthy controls (n = 13) from the same geographical region. RESULTS: Gut microbial α-diversity trended lower in patients with CTCL and was significantly lower in patients with advanced CTCL relative to controls (P = 0.015). No differences in ß-diversity were identified. Specific taxa were significantly reduced in patient samples; significance was determined using adjusted P-values (q-values) that accounted for a false discovery rate threshold of 0.05. Significantly reduced taxa in patient samples included the phylum Actinobacteria (q = 0.0002), classes Coriobacteriia (q = 0.002) and Actinobacteria (q = 0.03), order Coriobacteriales (q = 0.003), and genus Anaerotruncus (q = 0.01). The families Eggerthellaceae (q = 0.0007) and Lactobacillaceae (q = 0.02) were significantly reduced in patients with high skin disease burden. CONCLUSIONS: Gut dysbiosis can be seen in patients with CTCL compared to healthy controls and is pronounced in more advanced CTCL. The taxonomic shifts associated with CTCL are similar to those previously reported in atopic dermatitis and opposite those of psoriasis, suggesting microbial parallels to the immune profile and skin barrier differences between these conditions. These findings may suggest new microbial disease biomarkers and reveal a new angle for intervention.

Depressed Supercooling Point and Increased Glycerol Concentration in Overwintering Adult Tiger Beetles (Cicindelida).

BACKGROUND: Tiger beetles are a widely distributed group including species that may be exposed to sub-freezing temperature overwinter. Despite being well studied, little is known about tiger beetle cold tolerance. OBJECTIVE: We investigated seasonal changes in cold hardiness of two northerly distributed tiger beetle species (Cicindela repanda and Cicindela limbalis). MATERIALS AND METHODS: We monitored the supercooling point (SCP), glycerol concentration, and hemolymph osmolality of adult tiger beetles during a 3.5-month acclimation to winter. RESULTS: SCP decreased during winter acclimation for C. repanda, but not for C. limbalis. Both species modestly increased glycerol concentration, and C. repanda increased hemolymph osmolality by 38%. CONCLUSION: This initial investigation into the cold-hardiness of adult tiger beetles suggests that they are capable of lowering their SCP as winter approaches, which may help them survive sub-freezing winter temperatures. Further assessment of their chill and freeze tolerance and of their overwintering conditions in the field is needed to better understand their winter physiology.

Using the Five Domains Model to develop welfare assessment guidelines for Thoroughbred horses in New Zealand.

This review outlines the processes followed by New Zealand Thoroughbred Racing (NZTR) when developing its Thoroughbred Welfare Assessment Guidelines. It accepted that guidance on welfare management must be based on up-to-date knowledge of how animal welfare is understood scientifically. NZTR established an expert panel to facilitate this process. First, major changes in animal welfare science thinking over the last 40 years were considered. For example, the separate biological function and affective state orientations were later accepted as dynamically interacting elements within the body operating as an integrated whole entity; conceptual problems with the Five Freedoms framework led to the formulation of the Five Provisions and Welfare Aims paradigm and development of the Five Domains Model for assessing nutritional, environmental, health, behavioural and mental facets of animal welfare; and the initial major focus on negative experiences evolved to include both negative and positive experiences. The Five Domains Model was very effective for illustrating up-to-date understanding of animal welfare and its use demonstrated how comprehensive animal welfare assessments may be conducted. The NZTR panel followed a sequential approach that included an update on animal welfare thinking and the Five Provisions and Welfare Aims paradigm; the generic Five Domains Model was refocused specifically on equids; a detailed model assessment of equine welfare practices was conducted; enhanced equine welfare practices were emphasised by comparing them to inadequate welfare practices; guidelines were framed in terms which provide domain-specific advice on provisions that achieve positive welfare; other domain-specific guidelines were focused on welfare-compromising consequences of inadequate provisions; and welfare-appropriate conditions were clarified for all stages of a Thoroughbred's life cycle (in work and rest) to facilitate exercising a life-long duty of care. Finally, the guidelines were expressed in general terms to avoid them becoming overly detailed and unwieldy. They therefore do not address specific welfare issues such as use of whips, bits, spurs and tight nosebands, however the Five Domains Model may also be used for these specific purposes. The guidelines, and the way they were formulated, provide an example of one approach which other organisations may find immediately useful, or which may stimulate them to devise their own approaches when progressing such equine welfare initiatives.

Differences in health outcomes associated with initial adherence to oral antidiabetes medications among veterans with uncomplicated Type 2 diabetes: a 5-year survival analysis.

AIM: To determine the association of adherence to oral antidiabetes medication with macrovascular and microvascular complications, time to insulin therapy, revascularization, admissions, and death among veterans with uncomplicated diabetes. METHODS: This was a retrospective cohort study using the Veterans Affairs Corporate Data Warehouse to examine 159 032 veterans diagnosed with uncomplicated diabetes during 2002-2014 and starting oral antidiabetes therapy for the first time. The first uncomplicated diabetes diagnosis was identified and confirmed by subsequent oral antidiabetes therapy initiation. Adherence was calculated from outpatient pharmacy records using the proportion of days covered over the first year of therapy. Health outcomes were observed up to 5 years beyond the first oral antidiabetes agent fill, and compared according to adherence status using Cox proportional hazards models adjusted for baseline demographic and clinical characteristics. RESULTS: During the first 5 years of oral antidiabetes treatment, people initially non-adherent to oral antidiabetes therapy were more likely to experience myocardial infarction (hazard ratio 1.14, 95% CI 1.03-1.27) and ischaemic stroke (hazard ratio 1.22, 95% CI 1.05-0.1.42), or to die (hazard ratio 1.21; 95% CI 1.15-1.28). Veterans with <20% adherence to oral antidiabetes therapy in the first year had particularly high hazards for ischaemic stroke (hazard ratio 1.78, 95% CI 1.27-2.49) and all-cause death (hazard ratio 1.33, 95% CI 1.17-151). Adherent people were more likely to be diagnosed with a microvascular complication or chronic kidney disease. CONCLUSIONS: People who are non-adherent to treatment were more likely to experience detrimental health outcomes within the first 5 years of antidiabetes therapy. Adherence is paramount to disease management and this should be stressed from the time at which treatment is initiated.

Supporting children facing a parent's cancer diagnosis: a systematic review of children's psychosocial needs and existing interventions.

This review aimed to (1) summarise the psychosocial needs of children/adolescents (0-18 years) with a parent with cancer across the illness trajectory (diagnosis to bereavement) and (2) evaluate existing interventions for this population. Medline, CINAHL, PsychInfo, EMBASE and Social Work Abstracts were systematically searched for articles published from 1985 to 2015. Of 98 full text articles retrieved, 12 reported on children's psychosocial needs, and 12 intervention studies were identified. Each article was appraised in accordance with the Mixed Method Appraisal Tool. Three factors emerged as critical to consider in future intervention development: (1) Children need age-appropriate information about their parent's cancer; (2) Children require support communicating with parents, family members and health professionals and (3) Children need an environment where they feel comfortable sharing positive/negative emotions and can have their experiences normalised among peers. All intervention studies reported at least one positive outcome, however, only five reported significant improvements in child/family functioning based on validated quantitative measure/s. Variability in study design and quality, combined with considerable heterogeneity in intervention characteristics and outcome variables limited the conclusions, which could be drawn. Therefore, further carefully designed and scientifically evaluated interventions for children facing a parent's cancer diagnosis are clearly warranted.

Understanding the school experiences of children and adolescents with serious chronic illness: a systematic meta-review.

BACKGROUND: Serious chronic illness can have a detrimental effect on school attendance, participation and engagement, leaving affected students at risk of failing to meet their developmental potential. An improved understanding of factors that help to explain or mitigate this risk can help educators and health professionals deliver the most effective support. This meta-review critiqued the available evidence examining the link between six chronic illnesses (asthma, cancer, chronic kidney diseases, heart diseases, cystic fibrosis and gastrointestinal diseases) and children's and adolescents' school experiences and outcomes, as well as investigating the medical, school, psychosocial and sociodemographic factors that are linked to poorer or better school outcomes. METHODS: We searched CINAHL, Cochrane Database, EMBASE, ERIC, MEDLINE, ProQuest Theses and Dissertations, and PsycINFO (2000-2015). Systematic and narrative reviews, and meta-analyses, of original studies examining students' subjective school experiences and objective school outcomes were eligible. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria to critically appraise all systematic reviews. The Grading of Recommendations Assessment, Development, and Evaluation system guided our recommendations for practice and research. RESULTS: Eighteen reviews of 172 studies including more than 40 000 students were eligible. Therefore, we chose to conduct a meta-review to provide an overview of the literature on the relationship between chronic illness and school experiences and outcomes. We also explored the associated medical, school, psychosocial and sociodemographic factors affecting the relationship between illness and school experiences and outcomes. CONCLUSION: Students with chronic illness demonstrate mixed school experiences and outcomes that are often worse than students without chronic illness. Modifiable factors, such as students' engagement with school, may be novel yet appropriate targets of educational support to ensure that these students reach their full schooling potential.

Reproductive morphology and its application in testing molecular systematic hypotheses in the family Gobiidae (Teleostei, Gobiiformes).

This study uses histological techniques to make a detailed comparison of the reproductive morphologies of four gobiid genera, Amblyeleotris, Ctenogobiops, Fusigobius and Kraemeria. Three distinct reproductive morphological patterns were observed. All species examined in the genus Fusigobius exhibit either an ovariform or testiform gonad and precursive accessory gonadal structures (pAGS) associated with each of the gonadal lobes, regardless of gonadal state. In contrast, among species of Amblyeleotris, Ctenogobiops and Kraemeria examined, pAGS were not found. Furthermore, Amblyeleotris and Ctenogobiops differ from both Kraemeria and Fusigobius in lacking AGS associated with the testiform gonad. These findings, based solely on reproductive morphology, suggest that Kraemeria and Fusigobius may be more closely related to each other than either is to Amblyeleotris and Ctenogobiops. Findings of this study support the view that reproductive morphological patterns could prove informative in elucidating evolutionary relationships within the family Gobiidae.

Hot electron plasmon-protected solar cell.

A solar cell based on a hot electron plasmon protection effect is proposed and made plausible by simulations, non-local modeling of the response, and quantum mechanical calculations. In this cell, a thin-film, plasmonic metamaterial structure acts as both an efficient photon absorber in the visible frequency range and a plasmonic resonator in the IR range, the latter of which absorbs and protects against phonon emission the free energy of the hot electrons in an adjacent semiconductor junction. We show that in this structure, electron-plasmon scattering is much more efficient than electron-phonon scattering in cooling-off hot electrons, and the plasmon-stored energy is recoverable as an additional cell voltage. The proposed structure could become a prototype of a new generation of high efficiency solar cells.

Nanoscope based on nanowaveguides.

The far field spatial resolution of conventional optical lenses is of the order of the wavelength of light, due to loss in the far field of evanescent, near electromagnetic field components. We show that subwavelength details can be restored in the far field with an array of divergent nanowaveguides, which map the discretized, subwavelength image of an object into a magnified image observable with a conventional optical microscope. We demonstrate in simulations that metallic nanowires, nanocoaxes, and nanogrooves can be used as such nanowaveguides. Thus, an optical microscope capable of subwavelength resolution - a nanoscope - can be produced, with possible applications in a variety of fields where nanoscale optical imaging is of value.

Do positive or negative stressful events predict the development of new brain lesions in people with multiple sclerosis?

BACKGROUND: Stressful life events have long been suspected to contribute to multiple sclerosis (MS) disease activity. The few studies examining the relationship between stressful events and neuroimaging markers have been small and inconsistent. This study examined whether different types of stressful events and perceived stress could predict the development of brain lesions. METHOD: This was a secondary analysis of 121 patients with MS followed for 48 weeks during a randomized controlled trial comparing stress management therapy for MS (SMT-MS) to a waitlist control (WLC). Patients underwent magnetic resonance imaging (MRI) scans every 8 weeks. Every month, patients completed an interview measure assessing stressful life events and self-report measures of perceived stress, anxiety and depressive symptoms, which were used to predict the presence of gadolinium-enhancing (Gd+) and T2 lesions on MRI scans 29-62 days later. Participants classified stressful events as positive or negative. Negative events were considered 'major' if they involved physical threat or threat to the patient's family structure, and 'moderate' otherwise. RESULTS: Positive stressful events predicted decreased risk for subsequent Gd+ lesions in the control group [odds ratio (OR) 0.53 for each additional positive stressful event, 95% confidence interval (CI) 0.30-0.91] and less risk for new or enlarging T2 lesions regardless of group assignment (OR 0.74, 95% CI 0.55-0.99). Across groups, major negative stressful events predicted Gd+ lesions (OR 1.77, 95% CI 1.18-2.64) and new or enlarging T2 lesions (OR 1.57, 95% CI 1.11-2.23) whereas moderate negative stressful events, perceived stress, anxiety and depressive symptoms did not. CONCLUSIONS: Major negative stressful events predict increased risk for Gd+ and T2 lesions whereas positive stressful events predict decreased risk.

Chronicles of informal caregiving in cancer: using 'The Cancer Family Caregiving Experience' model as an explanatory framework.

BACKGROUND: Cancer caregiving has emerged as a dominant focus of research in recent years. A striking feature of this vast amount of literature is that it is static, examining certain points of the cancer trajectory, mostly the diagnosis and palliative care. Only The Cancer Caregiving Experience Model conceptualised the caregiving experience and explored the conceptual implications of cancer family caregiving research. AIM: The data from this paper aim to empirically support the Cancer Caregiving Experience model, by exploring the cancer caregiving experience longitudinally. METHODS: Semi-structured interviews with 53 caregivers were carried out at patient's diagnosis (T1), 3 months (T2), 6 months (T3) and 12 months (T4) post diagnosis. RESULTS: Analysis of 139 interviews generated four themes that reflected a complex and dynamic process. The themes that mapped those of the model were "Primary stressors", "Secondary stressors", "Appraisal", "Cognitive-Behavioural responses" and "Health and Well Being". CONCLUSIONS: The study adds empirical support to The Cancer Caregiving Experience Model and confirms that different primary and secondary stressors influence how the caregivers perceive the caregiving demands, the coping mechanisms they employ and their health and well being during the cancer trajectory. Access to support services should be offered to all the caregivers from as early as the diagnosis period and take into account their specific needs.

Phenotypic convergence is more frequent and stronger in herbivorous freshwater fishes.

Constraints on phenotypic evolution can lead to patterns of convergent evolution, by limiting the 'pool' of potential phenotypes in the face of endogenous (functional, developmental) or exogenous (competition, predation) selective pressures. Evaluation of convergence depends on integrating ecological and morphological data within a robust, comparative phylogenetic context. The staggering diversity of teleost fishes offers a multitude of lineages adapted for similar ecological roles, and therefore, offers numerous replicated evolutionary experiments for exploring phenotypic convergence. However, our understanding of fish feeding systems has been primarily shaped by marine species, with the monolithic exception of freshwater cichlids. Here we use piranhas and pacus (Serrasalmidae) to explore the evolution of different feeding ecologies and their morphological proxies in Neotropical freshwater environments. Specifically, we explore whether convergence is more widespread among plant-eating fishes, arising from strong constraints on phenotypic evolution in herbivores. Using osteological micro-computed tomographic imaging (µCT), we describe the major axes of morphological variation in pacus and piranhas, regarding their diet and feeding behaviors. Next, we evaluated whether herbivorous niches are less labile than other dietary guilds and whether herbivorous species' phenotypes evolve at a slower evolutionary rate than other taxa. We then assess how convergent herbivorous taxa are, using three different suites of morphological characters (dental, jaw, and abdominal morphometrics). Ecologically, herbivory is not a dead end, exhibiting similar observed transition rates as those between carnivores and omnivores. However, we documented widespread convergence in herbivores and that herbivores have slower rates of phenotypic evolution than carnivores. Most instances of convergence are found in herbivorous taxa, specifically in frugivores and folivores. Moreover, instances of 'complete' convergence, indicated by positive convergence metrics observed in more than one morphometric dataset, were only found in herbivores. Herbivores do appear to evolve under constrained circumstances, but this has not limited their ecological lability.

Improving outcomes of renal transplant recipients with behavioral adherence contracts: a randomized controlled trial.

The objective of this randomized controlled trial was to assess the effects of a 1-year behavioral contract intervention on immunosuppressant therapy (IST) adherence and healthcare utilizations and costs among adult renal transplant recipients (RTRs). The sample included adult RTRs who were at least 1 year posttransplant, taking tacrolimus or cyclosporine and served by a specialty pharmacy. Pharmacy refill records were used to measure adherence and monthly questionnaires were used to measure healthcare utilizations. Direct medical costs were estimated using the 2009 Medicare Expenditure Panel Survey. Adherence was analyzed using the GLM procedure and the MIXED procedure of SAS. Rate ratios and 95% confidence intervals were estimated to quantify the rate of utilizing healthcare services relative to treatment assignment. One hundred fifty RTRs were enrolled in the study. Intervention group RTRs (n = 76) had higher adherence than control group RTRs (n = 74) over the study period (p < 0.01). And 76.1% of the intervention group compared with 42.7% of the control group was not hospitalized during the 1-year study period (RR = 1.785; 95% CI: 1.314, 2.425), resulting in cost savings. Thus, evidence supports using behavioral contracts as an effective adherence intervention that may improve healthcare outcomes and lower costs.

The suspected scaphoid injury: resource implications in the absence of magnetic resonance imaging.

INTRODUCTION: Undiagnosed and untreated scaphoid fractures have poorer outcomes and many patients are unnecessarily immobilised for prolonged periods of time to avoid missing occult injuries. Magnetic resonance imaging has a high sensitivity and specificity in detecting occult scaphoid fractures, but many units do not routinely use this imaging modality in the diagnostic pathway. We aimed to determine the patterns of suspected scaphoid injuries, report the process of care, and calculate the costs involved in their management. METHODS: We prospectively identified all adult patients referred to fracture clinic at the Royal Infirmary of Edinburgh with a scaphoid-related injury, between October 2007 and September 2008. Clinical notes were examined retrospectively. We defined three injury groups: true fractures, occult fractures, and suspected scaphoid injuries. We analysed patient demographics, treatment timelines, and the treatment costs involved. RESULTS: Fracture clinic received 537 scaphoid-related referrals. There were 87 true fractures, 43 occult fractures, and 407 suspected injuries, incurring average treatment costs of £1,173, £773, and £384 respectively. Occult fractures accounted for 33% of all confirmed scaphoid fractures. The majority of scaphoid-related referrals (76%) were never proven to have a scaphoid fracture, and many were unnecessarily immobilised. The costs involved in the treatment of suspected scaphoid injuries were found to be higher than the cost of magnetic resonance imaging (£97). CONCLUSION: In this group of suspected scaphoid injury, we believe the introduction of an early magnetic resonance imaging protocol would lead to an earlier definitive diagnosis and potentially a more cost-effective service.

Exploring the benefits of nature-based interventions in socio-economically deprived communities: a narrative review of the evidence to date.

AIM: Socio-economic deprivation encompasses the relative disadvantage experienced by individuals or communities in relation to financial, material or social resources. Nature-based interventions (NBIs) are a public health approach that promote sustainable, healthy communities through engagement with nature and show potential to address inequalities experienced by socio-economically deprived communities. This narrative review aims to identify and evaluate the benefits of NBIs in socio-economically deprived communities. METHOD: A systematic literature search of six electronic publication databases (APA PsycInfo, CENTRAL, CDSR, CINAHL, Medline and Web of Science) was conducted on 5 February 2021 and repeated on 30 August 2022. In total, 3852 records were identified and 18 experimental studies (published between 2015 and 2022) were included in this review. RESULTS: Interventions including therapeutic horticulture, care farming, green exercise and wilderness arts and craft were evaluated in the literature. Key benefits were observed for cost savings, diet diversity, food security, anthropometric outcomes, mental health outcomes, nature visits, physical activity and physical health. Age, gender, ethnicity, level of engagement and perception of environment safety influenced the effectiveness of the interventions. CONCLUSION: Results demonstrate there are clear benefits of NBIs on economic, environmental, health and social outcomes. Further research including qualitative analyses, more stringent experimental designs and use of standardised outcome measures is recommended.

Chronic BMAA exposure combined with TDP-43 mutation elicits motor neuron dysfunction phenotypes in mice.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an average age-of-onset of ∼60 years and is usually fatal within 2-5 years of diagnosis. Mouse models based upon single gene mutations do not recapitulate all ALS pathological features. Environmental insults may also contribute to ALS, and ß-N-methylamino-L-alanine (BMAA) is an environmental toxin linked with an increased risk of developing ALS. BMAA, along with cycasin, are hypothesized to be the cause of the Guam-ALS epicenter of the 1950s. We developed a multihit model based on low expression of a dominant familial ALS TDP-43 mutation (Q331K) and chronic low-dose BMAA exposure. Our two-hit mouse model displayed a motor phenotype absent from either lesion alone. By LC/MS analysis, free BMAA was confirmed at trace levels in brain, and were as high as 405 ng/mL (free) and 208 ng/mL (protein-bound) in liver. Elevated BMAA levels in liver were associated with dysregulation of the unfolded protein response (UPR) pathway. Our data represent initial steps towards an ALS mouse model resulting from combined genetic and environmental insult.

Minimising critical organ irradiation in limited stage Hodgkin lymphoma: a dosimetric study of the benefit of involved node radiotherapy.

BACKGROUND: Chemotherapy plus radiotherapy is the standard of care for patients with limited stage Hodgkin lymphoma (HL). Radiotherapy is evolving from involved field radiotherapy (IFRT) to involved node radiotherapy (INRT) to decrease radiotherapy-related morbidity. In the absence of long-term toxicity data, dose-volume metrics of organs at risk (OAR) provide a surrogate measure of toxicity risk. PATIENTS AND METHODS: Ten female patients with stage I-IIA supradiaphragmatic HL were randomly selected. All patients had pre-chemotherapy computerised tomography (CT) and CT-positron emission tomography staging. Using CT planning, three radiotherapy plans were produced per patient: (i) IFRT, (ii) INRT using parallel-opposed beams and (iii) INRT using volumetric modulated arc therapy (VMAT). Radiotherapy dose was 30.6 Gy in 1.8 Gy fractions. OAR evaluated were lungs, breasts, thyroid, heart and coronary arteries. RESULTS: Compared with IFRT, INRT significantly reduced mean doses to lungs (P < 0.01), breasts (P < 0.01), thyroid (P < 0.01) and heart (P < 0.01), on Wilcoxon testing. Compared with conventional INRT, VMAT improved dose conformality but increased low-dose radiation exposure to lungs and breasts. VMAT reduced the heart volume receiving 30 Gy (V30) by 85%. CONCLUSIONS: Reduction from IFRT to INRT decreased the volumes of lungs, breasts and thyroid receiving high-dose radiation, suggesting the potential to reduce long-term second malignancy risks. VMAT may be useful for patients with pre-existing heart disease by minimising further cardiac toxicity risks.

Nasal cytokine responses to natural colds in asthmatic children.

BACKGROUND: The mechanisms by which viruses induce asthma exacerbations are not well understood. OBJECTIVE: We characterized fluctuations in nasal aspirate cytokines during naturally occurring respiratory viral infections in children with asthma. METHODS: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured using multiplex immune assay. mRNA expression for selected markers of viral infection was measured using RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score. RESULTS: The 16 patients completed a total of 37 weeks of assessment (15 'well' weeks; 22 self-assessed 'sick' weeks). Viral infections were detected in 3 of the 'well' weeks and 17 of the 'sick' weeks (10 rhinovirus, three coronavirus, two influenza A, two influenza B, two respiratory syncytial virus, one parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1ß, CCL7/MCP-3, and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5, and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I, and IRF7 mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that in children with asthma, naturally occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs, and IFN-responsive genes.

A scintillator attenuation spectrometer for intense gamma-rays.

A new type of compact high-resolution high-sensitivity gamma-ray spectrometer for short-pulse intense gamma-rays (250 keV to 50 MeV) has been developed by combining the principles of scintillators and attenuation spectrometers. The first prototype of this scintillator attenuation spectrometer (SAS) was tested successfully in Trident laser experiments at LANL. Later versions have been used extensively in the Texas Petawatt laser experiments in Austin, TX, and more recently in OMEGA-EP laser experiments at LLE, Rochester, NY. The SAS is particularly useful for high-repetition-rate laser applications. Here, we give a concise description of the design principles, capabilities, and sample preliminary results of the SAS.

Maximizing the chances of detecting pathogenic leptospires in mammals: the evaluation of field samples and a multi-sample-per-mammal, multi-test approach.

Identification of wild animals that harbour the causative leptospires, and the identification of the most important of these 'wild reservoirs' (in terms of threat to human health), are key factors in the epidemiology of human leptospirosis. In an epidemiological investigation in the Australian state of Queensland, in 2007-2008, samples were collected from fruit bats (Pteropus conspicillatus) and rodents (to investigate the potential role of fruit bats in the maintenance and transmission of leptospires to ground-dwelling rodents) and checked for pathogenic leptospires. The results of these studies have now been carefully analysed in attempts to see which method of detection and type of test sample were best. The effects of pentobarbitone sodium used to euthanize wild mammals before collection of necropsy samples, on the survival and detection of leptospires in vitro, were also explored. In the earlier field investigation, serum, renal tissue and urine were collected from wild mammals, for the detection of pathogenic leptospires by culture, the microscopic agglutination test (MAT), real-time PCR and silver impregnation of smears. Although 27.6% of the rodents investigated were found leptospire-positive, culture only yielded four isolates, probably because many cultures were contaminated. The main aims of the present study were to quantify the performance of the individual diagnostic tests and examine the reasons behind the high incidence of culture contamination. The results of sensitivity and specificity analyses for the different diagnostic tests indicated that isolation by culture (the definitive diagnostic test for leptospiral shedding) had perfect (100%) sensitivity when compared with the results of the PCR but a low specificity (40%). The MAT performed poorly, with a sensitivity of 50% when compared against the results of culture. The prevalence of leptospiral carriage revealed by the PCR-based investigation of kidney and urine samples (59.2%) was higher than that revealed using any other method and far higher than the 2.0% revealed by culture. The results of the culture of renal tissue agreed fairly well with those of the PCR-based investigation of such tissue, with a Cohen's unweighted kappa coefficient (κ) of 0.5 (P = 0.04). The levels of agreement between other pairs of tests were generally poor. The presence of pentobarbitone sodium, at final concentrations of 27.8 or 167 mg/ml, did not affect the viability or the detection of leptospires in culture, and is therefore unlikely to reduce the chances of isolating leptospires from an animal that has been euthanized with the compound. It appears that collecting multiple samples from each mammal being checked will improve the chances of detecting leptospires (and reduce the chances of reporting an inconclusive result for any of the mammals). For the identification of a leptospiral carrier, however, the use of just two detection methods (culture and PCR) and one type of sample (renal tissue) may give adequate sensitivity and specificity. Given the robustness of PCR to contamination and its high sensitivity (it can give a positive result when DNA from just two leptospiral cells is present in the sample), a PCR-based serotyping method, to allow the combined detection and characterisation of leptospires from field isolates, would be extremely useful.