Type I interferon signaling in hematopoietic cells is required for survival in mouse polymicrobial sepsis by regulating CXCL10

Type I interferon (IFN) α/β is critical for host defense. During endotoxicosis or highly lethal bacterial infections where systemic inflammation predominates, mice deficient in IFN-α/β receptor (IFNAR) display decreased systemic inflammation and improved outcome. However, human sepsis mortality often occurs during a prolonged period of immunosuppression and not from exaggerated inflammation. We used a low lethality cecal ligation and puncture (CLP) model of sepsis to determine the role of type I IFNs in host defense during sepsis. Despite increased endotoxin resistance, IFNAR−/− and chimeric mice lacking IFNAR in hematopoietic cells display increased mortality to CLP. This was not associated with an altered early systemic inflammatory response, except for decreased CXCL10 production. IFNAR−/− mice display persistently elevated peritoneal bacterial counts compared with wild-type mice, reduced peritoneal neutrophil recruitment, and recruitment of neutrophils with poor phagocytic function despite normal to enhanced adaptive immune function during sepsis. Importantly, CXCL10 treatment of IFNAR−/− mice improves survival and decreases peritoneal bacterial loads, and CXCL10 increases mouse and human neutrophil phagocytosis. Using a low lethality sepsis model, we identify a critical role of type I IFN–dependent CXCL10 in host defense during polymicrobial sepsis by increasing neutrophil recruitment and function

Coherent elastic neutrino-nucleus scattering: Terrestrial and astrophysical applications

Coherent elastic neutrino-nucleus scattering (CE$\nu$NS) is a process in which neutrinos scatter on a nucleus which acts as a single particle. Though the total cross section is large by neutrino standards, CE$\nu$NS has long proven difficult to detect, since the deposited energy into the nucleus is $\sim$ keV. In 2017, the COHERENT collaboration announced the detection of CE$\nu$NS using a stopped-pion source with CsI detectors, followed up the detection of CE$\nu$NS using an Ar target. The detection of CE$\nu$NS has spawned a flurry of activities in high-energy physics, inspiring new constraints on beyond the Standard Model (BSM) physics, and new experimental methods. The CE$\nu$NS process has important implications for not only high-energy physics, but also astrophysics, nuclear physics, and beyond. This whitepaper discusses the scientific importance of CE$\nu$NS, highlighting how present experiments such as COHERENT are informing theory, and also how future experiments will provide a wealth of information across the aforementioned fields of physics

Coherent elastic neutrino-nucleus scattering: Terrestrial and astrophysical applications

Coherent elastic neutrino-nucleus scattering (CE$\nu$NS) is a process inwhich neutrinos scatter on a nucleus which acts as a single particle. Thoughthe total cross section is large by neutrino standards, CE$\nu$NS has longproven difficult to detect, since the deposited energy into the nucleus is$\sim$ keV. In 2017, the COHERENT collaboration announced the detection ofCE$\nu$NS using a stopped-pion source with CsI detectors, followed up thedetection of CE$\nu$NS using an Ar target. The detection of CE$\nu$NS hasspawned a flurry of activities in high-energy physics, inspiring newconstraints on beyond the Standard Model (BSM) physics, and new experimentalmethods. The CE$\nu$NS process has important implications for not onlyhigh-energy physics, but also astrophysics, nuclear physics, and beyond. Thiswhitepaper discusses the scientific importance of CE$\nu$NS, highlighting howpresent experiments such as COHERENT are informing theory, and also how futureexperiments will provide a wealth of information across the aforementionedfields of physics.<br

Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery of 187 Novel Risk Variants

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups

Tobacco smoking among people living with a psychotic illness: the second Australian survey of psychosis

OBJECTIVE: The aims of this study were to (a) describe patterns of tobacco smoking among Australians living with a psychotic illness and (b) explore the association between smoking and measures of psychopathology, psychiatric history, psychosocial functioning, physical health, substance use and demographic characteristics. METHODS: Data were from 1812 participants in the 2010 Australian Survey of High Impact Psychosis. Participants were aged 18–64 years and resided in seven mental health catchment sites across five states of Australia. Bivariate statistics were used to compare smokers with non-smokers on the measures of interest, and to compare ICD-10 diagnostic categories on measures of smoking prevalence, nicotine addiction and quitting history. Multivariate logistic regression was used to test whether (a) demographics and psychiatric history were associated with having ever smoked and (b) whether symptoms and psychosocial functioning were independently associated with current smoking, after controlling for demographics, psychiatric history and substance use. RESULTS: The prevalence of current tobacco smoking was 66.6% (72% of men and 59% of women); lifetime prevalence was 81%. In univariate analyses, individuals with a diagnosis of schizophrenia or schizoaffective disorder were most likely to be smoking tobacco (70%) and were more nicotine dependent. Smokers reported worse perceived physical health, lower body mass index and waist circumference, and more lifetime medical conditions. A younger age of illness onset, male gender and low education were associated with having ever smoked. Associations with current smoking included low education, male gender, no formal employment, worse negative symptoms, higher daily caffeine consumption, and alcohol dependence and substance abuse/dependence. CONCLUSIONS: The prevalence of tobacco smoking is high amongst people with a psychotic disorder, and is associated with adverse mental health symptoms as well as high rates of other substance use, poorer subjective physical health, and a higher risk of the many known health consequences of smoking.Jae Cooper, Serafino G. Mancuso, Ron Borland, Tim Slade, Cherrie Galletly and David Castl

A fiber optic strain gage sensor for measuring preload in thick composite bolted joints

Mechanical fastening is a popular choice in joining composites because of the ability to transfer high loads and the ease of assembly and disassembly. In this study, the failure behavior of composite–aluminum single lap bolted joint is investigated. In particular, the effects of varying the preload on the bolt are examined. In order to accurately measure the preload, a specialized sensor that uses a fiber Bragg grating sensor embedded in the bolt is proposed and created. This sensor is realized for the current tests but can be expanded to other applications. An experimental study of bolted single-lap joints varying the tightening torque value has been carried out and, in order to validate the experimental tests, several finite element analyses conducted in ANSYS environment with explicit solver are performed. Comparison between numerical results and experimental tests allows us to determine the effect of bolting parameters on the strength of joint and to verify the effectiveness of the use of the specialized preload sensor