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Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
During March 27–July 14, 2020, the Centers for Disease Control and Prevention’s National Healthcare Safety Network extended its surveillance to hospital capacities responding to COVID-19 pandemic. The data showed wide variations across hospitals in case burden, bed occupancies, ventilator usage, and healthcare personnel and supply status. These data were used to inform emergency responses.
The rapid spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) throughout key regions of the United States in early 2020 placed a premium on timely, national surveillance of hospital patient censuses. To meet that need, the Centers for Disease Control and Prevention’s National Healthcare Safety Network (NHSN), the nation’s largest hospital surveillance system, launched a module for collecting hospital coronavirus disease 2019 (COVID-19) data. We present time-series estimates of the critical hospital capacity indicators from April 1 to July 14, 2020.
From March 27 to July 14, 2020, the NHSN collected daily data on hospital bed occupancy, number of hospitalized patients with COVID-19, and the availability and/or use of mechanical ventilators. Time series were constructed using multiple imputation and survey weighting to allow near–real-time daily national and state estimates to be computed.
During the pandemic’s April peak in the United States, among an estimated 431,000 total inpatients, 84,000 (19%) had COVID-19. Although the number of inpatients with COVID-19 decreased from April to July, the proportion of occupied inpatient beds increased steadily. COVID-19 hospitalizations increased from mid-June in the South and Southwest regions after stay-at-home restrictions were eased. The proportion of inpatients with COVID-19 on ventilators decreased from April to July.
The NHSN hospital capacity estimates served as important, near–real-time indicators of the pandemic’s magnitude, spread, and impact, providing quantitative guidance for the public health response. Use of the estimates detected the rise of hospitalizations in specific geographic regions in June after they declined from a peak in April. Patient outcomes appeared to improve from early April to mid-July.
Prospectively acquired Canadian cerebrospinal fluid samples were used to assess the performance characteristics of three ante-mortem tests commonly used to support diagnoses of Creutzfeldt–Jakob disease. The utility of the end-point quaking-induced conversion assay as a test for Creutzfeldt–Jakob disease diagnoses was compared to that of immunoassays designed to detect increased amounts of the surrogate markers 14-3-3γ and hTau. The positive predictive values of the end-point quaking-induced conversion, 14-3-3γ, and hTau tests conducted at the Prion Diseases Section of the Public Health Agency of Canada were 96%, 68%, and 66%, respectively.
Acifluorfen is a nonsystemic PPO-inhibiting herbicide commonly used for POST Palmer amaranth control in soybean, peanut, and rice across the southern United States. Concerns have been raised regarding herbicide selection pressure and particle drift, increasing the need for application practices that optimize herbicide efficacy while mitigating spray drift. Field research was conducted in 2016, 2017, and 2018 in Mississippi and Nebraska to evaluate the influence of a range of spray droplet sizes [150 μm (Fine) to 900 μm (Ultra Coarse)], using acifluorfen to create a novel Palmer amaranth management recommendation using pulse width modulation (PWM) technology. A pooled site-year generalized additive model (GAM) analysis suggested that 150-μm (Fine) droplets should be used to obtain the greatest Palmer amaranth control and dry biomass reduction. Nevertheless, GAM models indicated that only 7.2% of the variability observed in Palmer amaranth control was due to differences in spray droplet size. Therefore, location-specific GAM analyses were performed to account for geographical differences to increase the accuracy of prediction models. GAM models suggested that 250-μm (Medium) droplets optimize acifluorfen efficacy on Palmer amaranth in Dundee, MS, and 310-μm (Medium) droplets could sustain 90% of maximum weed control. Specific models for Beaver City, NE, indicated that 150-μm (Fine) droplets provide maximum Palmer amaranth control, and 340-μm (Medium) droplets could maintain 90% of greatest weed control. For Robinsonville, MS, optimal Palmer amaranth control could be obtained with 370-μm (Coarse) droplets, and 90% maximum control could be sustained with 680 μm (Ultra Coarse) droplets. Differences in optimal droplet size across location could be a result of convoluted interactions between droplet size, weather conditions, population density, plant morphology, and soil fertility levels. Future research should adopt a holistic approach to identify and investigate the influence of environmental and application parameters to optimize droplet size recommendations.
Herbicide applications performed with pulse width modulation (PWM) sprayers to deliver specific spray droplet sizes could maintain product efficacy, minimize potential off-target movement, and increase flexibility in field operations. Given the continuous expansion of herbicide-resistant Palmer amaranth populations across the southern and midwestern United States, efficacious and cost-effective means of application are needed to maximize Palmer amaranth control. Experiments were conducted in two locations in Mississippi (2016, 2017, and 2018) and one location in Nebraska (2016 and 2017) for a total of 7 site-years. The objective of this study was to evaluate the influence of a range of spray droplet sizes [150 (Fine) to 900 μm (Ultra Coarse)] on lactofen and acifluorfen efficacy for Palmer amaranth control. The results of this research indicated that spray droplet size did not influence lactofen efficacy on Palmer amaranth. Palmer amaranth control and percent dry-biomass reduction remained consistent with lactofen applied within the aforementioned droplet size range. Therefore, larger spray droplets should be used as part of a drift mitigation approach. In contrast, acifluorfen application with 300-μm (Medium) spray droplets provided the greatest Palmer amaranth control. Although percent biomass reduction was numerically greater with 300-μm (Medium) droplets, results did not differ with respect to spray droplet size, possibly as a result of initial plant injury, causing weight loss, followed by regrowth. Overall, 900-μm (Ultra Coarse) droplets could be used effectively without compromising lactofen efficacy on Palmer amaranth, and 300-μm (Medium) droplets should be used to achieve maximum Palmer amaranth control with acifluorfen.
Germ plasm, a cytoplasmic factor of germline cell differentiation, is suggested to be a perspective tool for in vitro meiotic differentiation. To discriminate between the: (1) germ plasm-related structures (GPRS) involved in meiosis triggering; and (2) GPRS involved in the germ plasm storage phase, we investigated gametogenesis in the marine medaka Oryzias melastigma. The GPRS of the mitosis-to-meiosis period are similar in males and females. In both sexes, five events typically occur: (1) turning of the primary Vasa-positive germ plasm granules into the Vasa-positive intermitochondrial cement (IMC); (2) aggregation of some mitochondria by IMC followed by arising of mitochondrial clusters; (3) intramitochondrial localization of IMC-originated Vasa; followed by (4) mitochondrial cluster degradation; and (5) intranuclear localization of Vasa followed by this protein entering the nuclei (gonial cells) and synaptonemal complexes (zygotene–pachytene meiotic cells). In post-zygotene/pachytene gametogenesis, the GPRS are sex specific; the Vasa-positive chromatoid bodies are found during spermatogenesis, but oogenesis is characterized by secondary arising of Vasa-positive germ plasm granules followed by secondary formation and degradation of mitochondrial clusters. A complex type of germ plasm generation, ‘the follicle cell assigned germ plasm formation’, was found in late oogenesis. The mechanisms discovered are recommended to be taken into account for possible reconstruction of those under in vitro conditions.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Legionnaires’ disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014–2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
The impact of storage on stability and detection of Clostridium difficile toxins in feces is poorly understood. The objective of this study was to investigate the immunological stability of C. difficile toxins in clinical stool specimens under different storage conditions by evaluating this stability using toxin detection by enzyme immunoassay (EIA).
Stool specimens positive for C. difficile infection (CDI) by quantitative polymerase chain reaction (qPCR) were used for EIA testing with the C. difficile Tox A/B II kit. The EIA-positive specimens were stored aerobically under refrigerated (4–10°C) and frozen (−30°C and −80°C) conditions. Measurement of toxin quantity was conducting using optical density (OD) on days 0, 14, 30, 60, 90, and 120 of storage.
Clostridium difficile toxins demonstrated good detection in undiluted stool specimens by EIA up to 120 days of storage. Good detection of the toxins was observed in diluted samples at refrigerated and −80°C temperatures. Dilution detrimentally affected toxin detection at −30°C.
Storage of undiluted clinical stool specimens at refrigerated, −30°C, and −80°C temperatures for up to 120 days has no discernible effect on the immunological stability of C. difficile cytotoxins. However, storage at −30°C has a detrimental effect on C. difficile toxin stability in diluted specimens.
The re-emergence of debates on the decolonisation of knowledge has revived interest in the National Question, which began over a century ago and remains unresolved. Tensions that were suppressed and hidden in the past are now being openly debated. Despite this, the goal of one united nation living prosperously under a constitutional democracy remains elusive. This edited volume examines the way in which various strands of left thought have addressed the National Question, especially during the apartheid years, and goes on to discuss its relevance for South Africa today and in the future. Instead of imposing a particular understanding of the National Question, the editors identified a number of political traditions and allowed contributors the freedom to define the question as they believed appropriate – in other words, to explain what they thought was the Unresolved National Question. This has resulted in a rich tapestry of interweaving perceptions. The volume is structured in two parts. The first examines four foundational traditions: Marxism-Leninism (the Colonialism of a Special Type thesis); the Congress tradition; the Trotskyist tradition; and Africanism. The second part explores the various shifts in the debate from the 1960s onwards, and includes chapters on Afrikaner nationalism, ethnic issues, black consciousness, feminism, workerism and constitutionalism. The editors hope that by revisiting the debates not popularly known among the scholarly mainstream, this volume will become a catalyst for an enriched debate on our identity and our future.
Previous studies have demonstrated that several major psychiatric disorders are influenced by shared genetic factors. This shared liability may influence clinical features of a given disorder (e.g. severity, age at onset). However, findings have largely been limited to European samples; little is known about the consistency of shared genetic liability across ethnicities.
The relationship between polygenic risk for several major psychiatric diagnoses and major depressive disorder (MDD) was examined in a sample of unrelated Han Chinese women. Polygenic risk scores (PRSs) were generated using European discovery samples and tested in the China, Oxford, and VCU Experimental Research on Genetic Epidemiology [CONVERGE (maximum N = 10 502)], a sample ascertained for recurrent MDD. Genetic correlations between discovery phenotypes and MDD were also assessed. In addition, within-case characteristics were examined.
European-based polygenic risk for several major psychiatric disorder phenotypes was significantly associated with the MDD case status in CONVERGE. Risk for clinically significant indicators (neuroticism and subjective well-being) was also associated with case–control status. The variance accounted for by PRS for both psychopathology and for well-being was similar to estimates reported for within-ethnicity comparisons in European samples. However, European-based PRS were largely unassociated with CONVERGE family history, clinical characteristics, or comorbidity.
The shared genetic liability across severe forms of psychopathology is largely consistent across European and Han Chinese ethnicities, with little attenuation of genetic signal relative to within-ethnicity analyses. The overall absence of associations between PRS for other disorders and within-MDD variation suggests that clinical characteristics of MDD may arise due to contributions from ethnicity-specific factors and/or pathoplasticity.