Interferon lambda protects the female reproductive tract against Zika virus infection

Zika virus infections can cause devastating congenital birth defects but the underlying interactions with the host immune system are not well understood. Here, the authors examine the immune basis of vaginal protection and susceptibility to Zika viral infection, and identify a hormonal dependent role for interferon-lambda-mediated protection against disease

Research Opportunities in Interdisciplinary Ground-Water Science

The U.S. Geological Survey (USGS) has a long-standing reputation for providing unbiased scientific leadership and excellence in the field of ground-water hydrology and geological research. This report provides a framework for continuing this scientific leadership by describing six interdisciplinary topics for research opportunities in ground-water science in the USGS. These topics build on recommendations of the National Research Council (2000) contained in the report, “Investigating Groundwater Systems on Regional and National Scales,” and emphasize research topics that would benefit from the integrated capabilities of all parts of the USGS. Understanding the relations between ground water and the geological characteristics of aquifers within which ground water resides, and the relation of ground water to surface-water resources and terrestrial and aquatic biota is increasingly important and presents a considerable opportunity to draw on expertise throughout the USGS, including the science disciplines of biology, geography, geology, and hydrology. The National Research Council (2000) also emphasizes that USGS regional and national assessments of ground-water resources should focus on aspects that foster the sustainability of the resource. The need for a comprehensive program addressing the sustainability of ground-water resources can be stated very concisely—we need enough ground water of good quality to sustain our lives, our economy, and our aquatic ecosystems. Although societal needs for high-quality, objective ground-water science are increasing, current funding for USGS regional ground-water programs is about 40 percent of the funding available 20–25 years ago. Given the current challenges of budgetary constraints, however, this report provides a flexible set of interrelated research topics that enhance the ability of the USGS to focus limited fiscal resources on developing ground-water science tools and methods that provide high-quality, objective scientific information

Method overtness, forensic autopsy, and the evidentiary suicide note: A multilevel national violent death reporting system analysis

© 2018 Rockett et al. Objective Higher prevalence of suicide notes could signify more conservatism in accounting and greater proneness to undercounting of suicide by method. We tested two hypotheses: (1) an evidentiary suicide note is more likely to accompany suicides by drug-intoxication and by other poisoning, as less violent and less forensically overt methods, than suicides by firearm and hanging/suffocation; and (2) performance of a forensic autopsy attenuates any observed association between overtness of method and the reported presence of a note. Methods This multilevel (individual/county), multivariable analysis employed a generalized linear mixed model (GLMM). Representing the 17 states participating in the United States National Violent Death Reporting System throughout 2011–2013, the study population comprised registered suicides, aged 15 years and older. Decedents totaled 32,151. The outcome measure was relative odds of an authenticated suicide note. Results An authenticated suicide note was documented in 31% of the suicide cases. Inspection of the full multivariable model showed a suicide note was more likely to manifest among drug intoxication (adjusted odds ratio [OR], 1.70; 95% CI, 1.56, 1.85) and other poisoning suicides (OR, 2.12; 1.85, 2.42) than firearm suicides, the referent. Respective excesses were larger when there was no autopsy or autopsy status was unknown (OR, 1.86; 95% CI, 1.61, 2.14) and (OR, 2.25; 95% CI, 1.86, 2.72) relative to the comparisons with a forensic autopsy (OR, 1.62, 95% CI, 1.45, 1.82 and OR, 2.01; 95% CI, 1.66, 2.43). Hanging/suffocation suicides did not differ from the firearm referent given an autopsy. Conclusions Suicide requires substantial affirmative evidence to establish manner of death, and affirmation of drug intoxication suicides appears to demand an especially high burden of proof. Findings and their implications argue for more stringent investigative standards, better training, and more resources to support comprehensive and accurate case ascertainment, as the foundation for developing evidence-based suicide prevention initiatives

Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

OBJECTIVE: To use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside. METHODS: Rasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008-December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility. RESULTS: The Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated. CONCLUSIONS: These two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

Patients with iatrogenic Creutzfeldt-Jakob disease due to administration of cadaver-sourced growth hormone during childhood are still being seen in the UK 30 years after cessation of this treatment. Of the 77 patients who have developed iatrogenic Creutzfeldt-Jakob disease, 56 have been genotyped. There has been a marked change in genotype profile at polymorphic codon 129 of the prion protein gene (PRNP) from predominantly valine homozygous to a mixed picture of methionine homozygous and methionine-valine heterozygous over time. The incubation period of iatrogenic Creutzfeldt-Jakob disease is significantly different between all three genotypes. This experience is a striking contrast with that in France and the USA, which may relate to contamination of different growth hormone batches with different strains of human prions. We describe the clinical, imaging, molecular and autopsy features in 22 of 24 patients who have developed iatrogenic Creutzfeldt-Jakob disease in the UK since 2003. Mean age at onset of symptoms was 42.7 years. Gait ataxia and lower limb dysaesthesiae were the most frequent presenting symptoms. All had cerebellar signs, and the majority had myoclonus and lower limb pyramidal signs, with relatively preserved cognitive function, when first seen. There was a progressive decline in neurological and cognitive function leading to death after 5-32 (mean 14) months. Despite incubation periods approaching 40 years, the clinical duration in methionine homozygote patients appeared to be shorter than that seen in heterozygote patients. MRI showed restricted diffusion in the basal ganglia, thalamus, hippocampus, frontal and the paracentral motor cortex and cerebellar vermis. The electroencephalogram was abnormal in 15 patients and cerebrospinal fluid 14-3-3 protein was positive in half the patients. Neuropathological examination was conducted in nine patients. All but one showed synaptic prion deposition with numerous kuru type plaques in the basal ganglia, anterior frontal and parietal cortex, thalamus, basal ganglia and cerebellum. The patient with the shortest clinical duration had an atypical synaptic deposition of abnormal prion protein and no kuru plaques. Taken together, these data provide a remarkable example of the interplay between the strain of the pathogen and host prion protein genotype. Based on extensive modelling of human prion transmission barriers in transgenic mice expressing human prion protein on a mouse prion protein null background, the temporal distribution of codon 129 genotypes within the cohort of patients with iatrogenic Creutzfeldt-Jakob disease in the UK suggests that there was a point source of infecting prion contamination of growth hormone derived from a patient with Creutzfeldt-Jakob disease expressing prion protein valine 129

Multiparameter MR Imaging in the 6-OPRI

BACKGROUND AND PURPOSE: Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. MATERIALS AND METHODS: VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. RESULTS: On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. CONCLUSIONS: Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology

Mortality from all cancers and lung, colorectal, breast and prostate cancer by country of birth in England and Wales, 2001–2003

Mortality from all cancers combined and major cancers among men and women aged 20 years and over was compared by country of birth with that of the whole of England and Wales as the reference group. Population data from the 2001 Census and mortality data for 2001–2003 were used to estimate standardised mortality ratios. Data on approximately 399 000 cancer deaths were available, with at least 400 cancer deaths in each of the smaller populations. Statistically significant differences from the reference group included: higher mortality from all cancers combined, lung and colorectal cancer among people born in Scotland and Ireland, lower mortality for all cancers combined, lung, breast and prostate cancer among people born in Bangladesh (except for lung cancer in men), India, Pakistan or China/Hong Kong, lower lung cancer mortality among people born in West Africa or the West Indies, higher breast cancer mortality among women born in West Africa and higher prostate cancer mortality among men born in West Africa or the West Indies. These data may be relevant to causal hypotheses and in relation to health care and cancer prevention

Virtual Guidance Ultrasound: A Tool to Obtain Diagnostic Ultrasound for Remote Environments

Astronauts currently acquire ultrasound images on the International Space Station with the assistance of real-time remote guidance from an ultrasound expert in Mission Control. Remote guidance will not be feasible when significant communication delays exist during exploration missions beyond low-Earth orbit. For example, there may be as much as a 20- minute delay in communications between the Earth and Mars. Virtual-guidance, a pre-recorded audio-visual tutorial viewed in real-time, is a viable modality for minimally trained scanners to obtain diagnostically-adequate images of clinically relevant anatomical structures in an autonomous manner. METHODS: Inexperienced ultrasound operators were recruited to perform carotid artery (n = 10) and ophthalmic (n = 9) ultrasound examinations using virtual guidance as their only instructional tool. In the carotid group, each each untrained operator acquired two-dimensional, pulsed, and color Doppler of the carotid artery. In the ophthalmic group, operators acquired representative images of the anterior chamber of the eye, retina, optic nerve, and nerve sheath. Ultrasound image quality was evaluated by independent imaging experts. RESULTS: Eight of the 10 carotid studies were judged to be diagnostically adequate. With one exception the quality of all the ophthalmic images were adequate to excellent. CONCLUSION: Diagnostically-adequate carotid and ophthalmic ultrasound examinations can be obtained by untrained operators with instruction only from an audio/video tutorial viewed in real time while scanning. This form of quick-response-guidance, can be developed for other ultrasound examinations, represents an opportunity to acquire important medical and scientific information for NASA flight surgeons and researchers when trained medical personnel are not present. Further, virtual guidance will allow untrained personnel to autonomously obtain important medical information in remote locations on Earth where communication is difficult or absent

Discerning suicide in drug intoxication deaths: Paucity and primacy of suicide notes and psychiatric history

Objective A paucity of corroborative psychological and psychiatric evidence may be inhibiting detection of drug intoxication suicides in the United States. We evaluated the relative importance of suicide notes and psychiatric history in the classification of suicide by drug intoxication versus firearm (gunshot wound) plus hanging/suffocation—the other two major, but overtly violent methods. Methods This observational multilevel (individual/county), multivariable study employed a generalized linear mixed model (GLMM) to analyze pooled suicides and undetermined intent deaths, as possible suicides, among the population aged 15 years and older in the 17 states participating in the National Violent Death Reporting System throughout 2011–2013. The outcome measure was relative odds of suicide versus undetermined classification, adjusted for demographics, precipitating circumstances, and investigation characteristics. Results A suicide note, prior suicide attempt, or affective disorder was documented in less than one-third of suicides and one-quarter of undetermined deaths. The prevalence gaps were larger among drug intoxication cases than gunshot/hanging cases. The latter were more likely than intoxication cases to be classified as suicide versus undetermined manner of death (adjusted odds ratio [OR], 41.14; 95% CI, 34.43–49.15), as were cases documenting a suicide note (OR, 33.90; 95% CI, 26.11–44.05), prior suicide attempt (OR, 2.42; 95% CI, 2.11–2.77), or depression (OR, 1.61; 95% CI, 1.38 to 1.88), or bipolar disorder (OR, 1.41; 95% CI, 1.10–1.81). Stratification by mechanism/cause intensified the association between a note and suicide classification for intoxication cases (OR, 45.43; 95% CI, 31.06–66.58). Prior suicide attempt (OR, 2.64; 95% CI, 2.19–3.18) and depression (OR, 1.48; 95% CI, 1.17–1.87) were associated with suicide classification in intoxication but not gunshot/hanging cases. Conclusions Without psychological/psychiatric evidence contributing to manner of death classification, suicide by drug intoxication in the US is likely profoundly under-reported. Findings harbor adverse implications for surveillance, etiologic understanding, and prevention of suicides and drug deaths

The influences of stomatal size and density on rice abiotic stress resilience

A warming climate coupled with reductions in water availability and rising salinity are increasingly affecting rice (Oryza sativa) yields. Elevated temperatures combined with vapour pressure deficit (VPD) rises are causing stomatal closure, further reducing plant productivity and cooling. It is unclear what stomatal size (SS) and stomatal density (SD) will best suit all these environmental extremes. To understand how stomatal differences contribute to rice abiotic stress resilience, we screened the stomatal characteristics of 72 traditionally bred varieties. We found significant variation in SS, SD and calculated anatomical maximal stomatal conductance (gsmax ) but did not identify any varieties with SD and gsmax as low as transgenic OsEPF1oe plants. Traditionally bred varieties with high SD and small SS (resulting in higher gsmax ) typically had lower biomasses, and these plants were more resilient to drought than low SD and large SS plants, which were physically larger. None of the varieties assessed were as resilient to drought or salinity as low SD OsEPF1oe transgenic plants. High SD and small SS rice displayed faster stomatal closure during increasing temperature and VPD, but photosynthesis and plant cooling were reduced. Compromises will be required when choosing rice SS and SD to tackle multiple future environmental stresses