Climate structuring of Batrachochytrium dendrobatidis infection in the threatened amphibians of the northern Western Ghats, India

Batrachochytrium dendrobatidis (Bd) is a pathogen killing amphibians worldwide. Its impact across much of Asia is poorly characterized. This study systematically surveyed amphibians for Bd across rocky plateaus in the northern section of the Western Ghats biodiversity hotspot, India, including the first surveys of the plateaus in the coastal region. These ecosystems offer an epidemiological model system since they are characterized by differing levels of connectivity, edaphic and climatic conditions, and anthropogenic stressors. One hundred and eighteen individuals of 21 species of Anura and Apoda on 13 plateaus ranging from 67 to 1179 m above sea level and 15.89 to 17.92° North latitude were sampled. Using qPCR protocols, 79% of species and 27% of individuals tested were positive for Bd. This is the first record of Bd in caecilians in India, the Critically Endangered Xanthophryne tigerina and Endangered Fejervarya cf. sahyadris. Mean site prevalence was 28.15%. Prevalence below the escarpment was 31.2% and 25.4% above. The intensity of infection (GE) showed the reverse pattern. Infection may be related to elevational temperature changes, thermal exclusion, inter-site connectivity and anthropogenic disturbance. Coastal plateaus may be thermal refuges from Bd. Infected amphibians represented a wide range of ecological traits posing interesting questions about transmission routes

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio

Preliminary Definitions for Sacroiliac Joint Pathologies in the OMERACT Juvenile Idiopathic Arthritis MRI Score (OMERACT JAMRIS-SIJ).

Objective: To develop definitions for the assessment of MRI pathologies of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis (JIA). Methods: An OMERACT consensus-driven methodology consisting of iterative surveys and focus group meetings within an international group of rheumatologists and radiologists. Results: Two domains, inflammation and structural, were identified. Definitions for bone marrow edema, joint space inflammation, capsulitis and enthesitis were derived for joint inflammation; sclerosis, erosion, fatty lesion and ankylosis were defined for assessing structural joint changes. Conclusion: Preliminary consensus-driven definitions for inflammation and structural elements have been derived, underpinning the ongoing development of the JAMRIS-SIJ score

Visible and Invisible Trends in Black Men's Health: Pitfalls and Promises for Addressing Racial, Ethnic, and Gender Inequities in Health

Over the past two decades, there has been growing interest in improving black men's health and the health disparities affecting them. Yet, the health of black men consistently ranks lowest across nearly all groups in the United States. Evidence on the health and social causes of morbidity and mortality among black men has been narrowly concentrated on public health problems (e.g., violence, prostate cancer, and HIV/AIDS) and determinants of health (e.g., education and male gender socialization). This limited focus omits age-specific leading causes of death and other social determinants of health, such as discrimination, segregation, access to health care, employment, and income. This review discusses the leading causes of death for black men and the associated risk factors, as well as identifies gaps in the literature and presents a racialized and gendered framework to guide efforts to address the persistent inequities in health affecting black men

Secondary osteosarcoma arising after treatment for childhood hematologic malignancies

Secondary osteosarcoma arising after the treatment of hematologic malignancies other than Hodgkin's lymphoma is rare. We report two cases of secondary osteosarcoma arising after treatment for childhood hematologic malignancies (non-Hodgkin's lymphoma and lymphoblastic leukemia). A 10-year-old boy, at the age of 3, was diagnosed with non-Hodgkin's lymphoma. He received chemotherapy, radiation, and bone-marrow transplantation and then was in complete remission. At 6 years, he complained of increasing pain of the right thigh and was diagnosed with osteoblastic osteosarcoma. A 26-year-old man, at the age of 6, was diagnosed as having acute lymphoblastic leukemia (ALL). He received chemotherapy, radiation, and peripheral blood stem cell transplantation (PBSCT). At 11 years after PBSCT, he visited with the complaint of left lumbar swelling. He was diagnosed with chondroblastic osteosarcoma. In both cases alkaline phosphatase (ALP) had already increased prior to the onset of the symptom. We should rule out secondary osteosarcoma at the abnormal elevation of ALP during clinical follow-up of patients after treatment of childhood hematologic malignancies

Tales of the unexpected: the selection of British party leaders since 1963

Jeremy Corbyn’s election as Leader of the Labour Party in 2015 stunned observers and practitioners of British politics alike. In this article, we first outline a theoretical framework that purports to explain why political parties operating in parliamentary systems choose the leaders they do. We then examine 32 leadership successions involving five major British parties since 1963, and note that many of these were unexpected, in that they were triggered by unforeseen circumstances, such as the sudden death or resignation of the incumbent. Examining each party in turn, we briefly explain why the winners won and identify at least eight cases (a quarter of our sample) where a candidate widely expected to prevail at the outset was ultimately defeated by a ‘dark horse’, ‘second favourite’ or even ‘rank outsider’. Of these, Corbyn’s election in 2015 was the most unexpected and, consistent with the findings of studies of party leadership conventions in other parliamentary systems, namely Canada and Spain, suggests that ideological and policy concerns are sometimes more important than considerations of party unity and electability, especially when a leadership contest is dominated by party activists

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells

Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines compose a class of compounds that target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo[1,2-a]pyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo[1,2-a]pyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo[1,2-a]pyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical–genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure–activity relationships

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines