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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 the last fifteen years there has been a paradigm shift in the continuum modelling of granular materials; most notably with the development of rheological models, such as the $\mu (I)$-rheology (where $\mu$ is the friction and I is the inertial number), but also with significant advances in theories for particle segregation. This paper details theoretical and numerical frameworks (based on OpenFOAM) which unify these currently disconnected endeavours. Coupling the segregation with the flow, and vice versa, is not only vital for a complete theory of granular materials, but is also beneficial for developing numerical methods to handle evolving free surfaces. This general approach is based on the partially regularized incompressible $\mu (I)$-rheology, which is coupled to the gravity-driven segregation theory of Gray & Ancey (J. Fluid Mech., vol. 678, 2011, pp. 353–588). These advection–diffusion–segregation equations describe the evolving concentrations of the constituents, which then couple back to the variable viscosity in the incompressible Navier–Stokes equations. A novel feature of this approach is that any number of differently sized phases may be included, which may have disparate frictional properties. Further inclusion of an excess air phase, which segregates away from the granular material, then allows the complex evolution of the free surface to be captured simultaneously. Three primary coupling mechanisms are identified: (i) advection of the particle concentrations by the bulk velocity, (ii) feedback of the particle-size and/or frictional properties on the bulk flow field and (iii) influence of the shear rate, pressure, gravity, particle size and particle-size ratio on the locally evolving segregation and diffusion rates. The numerical method is extensively tested in one-way coupled computations, before the fully coupled model is compared with the discrete element method simulations of Tripathi & Khakhar (Phys. Fluids, vol. 23, 2011, 113302) and used to compute the petal-like segregation pattern that spontaneously develops in a square rotating drum.
Biodiversity loss may increase the risk of infectious disease in a phenomenon known as the dilution effect. Circumstances that increase the likelihood of disease dilution are: (i) when hosts vary in their competence, and (ii) when communities disassemble predictably, such that the least competent hosts are the most likely to go extinct. Despite the central role of competence in diversity–disease theory, we lack a clear understanding of the factors underlying competence, as well as the drivers and extent of its variation. Our perspective piece encourages a mechanistic understanding of competence and a deeper consideration of its role in diversity–disease relationships. We outline current evidence, emerging questions and future directions regarding the basis of competence, its definition and measurement, the roots of its variation and its role in the community ecology of infectious disease.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
The administration of naloxone therapy is restricted by scope of practice to Advanced Life Support (ALS) in many Emergency Medical Services (EMS) systems throughout the United States. In Delaware’s two-tiered EMS system, Basic Life Support (BLS) often arrives on-scene prior to ALS, but BLS providers were not previously authorized to administer naloxone. Through a BLS naloxone pilot study, the researchers sought to evaluate BLS naloxone administration and timing compared to ALS.
After undergoing specialized training, BLS providers would be able to appropriately administer naloxone to opioid overdose patients in a more timely manner than ALS providers.
This was a retrospective, observational study using data collected from February 2014 through May 2015 throughout a state BLS naloxone pilot program. A total of 14 out of 72 state BLS agencies participated in the study. Pilot BLS agencies attended a training session on the indications and administration of naloxone, and then were authorized to carry and administer naloxone. Researchers then compared vital signs and the time of BLS arrival to administration of naloxone by BLS and ALS. Data were analyzed using paired and independent sample t-tests, as well as chi-square, as appropriate.
A total of 131 incidents of naloxone administration were reviewed. Of those, 62 patients received naloxone by BLS (pilot group) and 69 patients received naloxone by ALS (control group). After naloxone administration, BLS patients showed improvements in heart rate (HR; P < .01), respiratory rate (RR; P < .01), and pulse oximetry (spO2; P < .01); ALS patients also showed improvement in RR (P < .01), and in spO2 (P = .005). There was no significant improvement in HR for ALS providers (P = .189).
There was a significant difference in arrival time of BLS to the time of naloxone administration between the two groups, with shorter times in the BLS group compared to the ALS group (1.9 minutes versus 9.8 minutes; P < .01); BLS administration was 7.8 minutes faster when compared to ALS administration (95% CI, 6.2-9.3 minutes).
Patients improved similarly and received naloxone therapy sooner when treated by BLS agencies carrying naloxone than those who awaited ALS arrival. All EMS systems should consider allowing BLS to carry and administer naloxone for an effective and potentially faster naloxone administration when treating respiratory compromise related to opiate overdose.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Although academics can receive considerable training in selecting appropriate research designs, types of data to collect, and methods for analyzing data, as well as guidance on preparing scholarly manuscripts, there is a dearth of information on how to initiate and manage partnerships with organizations in order to conduct high-quality applied research, particularly when the research is quantitative in nature. In this article, we provide our own experience-based insights and recommendations to help academics more easily (a) initiate a research relationship with senior organizational leadership, (b) decide early whether to pursue or end a research collaboration with an organization, (c) keep the organization engaged during the study, and (d) maintain the relationship with the organization after data collection is complete. This information is proposed as a complement to traditional organizational research methods and as instrumental in the pursuit of research salient to the interests of organizational practitioners.
As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.
To determine the impact of recurrent Clostridium difficile infection (RCDI) on patient behaviors following illness.
Using a computer algorithm, we searched the electronic medical records of 7 Chicago-area hospitals to identify patients with RCDI (2 episodes of CDI within 15 to 56 days of each other). RCDI was validated by medical record review. Patients were asked to complete a telephone survey. The survey included questions regarding general health, social isolation, symptom severity, emotional distress, and prevention behaviors.
In total, 119 patients completed the survey (32%). On average, respondents were 57.4 years old (standard deviation, 16.8); 57% were white, and ~50% reported hospitalization for CDI. At the time of their most recent illness, patients rated their diarrhea as high severity (58.5%) and their exhaustion as extreme (30.7%). Respondents indicated that they were very worried about getting sick again (41.5%) and about infecting others (31%). Almost 50% said that they have washed their hands more frequently (47%) and have increased their use of soap and water (45%) since their illness. Some of these patients (22%–32%) reported eating out less, avoiding certain medications and public areas, and increasing probiotic use. Most behavioral changes were unrelated to disease severity.
Having had RCDI appears to increase prevention-related behaviors in some patients. While some behaviors are appropriate (eg, handwashing), others are not supported by evidence of decreased risk and may negatively impact patient quality of life. Providers should discuss appropriate prevention behaviors with their patients and should clarify that other behaviors (eg, eating out less) will not affect their risk of future illness.
Passive surveillance for lyssaviruses in UK bats has been ongoing since 1987 and has identified 13 cases of EBLV-2 from a single species; Myotis daubentonii. No other lyssavirus species has been detected. Between 2005 and 2015, 10 656 bats were submitted, representing 18 species, creating a spatially and temporally uneven sample of British bat fauna. Uniquely, three UK cases originate from a roost at Stokesay Castle in Shropshire, England, where daily checks for grounded and dead bats are undertaken and bat carcasses have been submitted for testing since 2007. Twenty per cent of Daubenton's bats submitted from Stokesay Castle since surveillance began, have tested positive for EBLV-2. Phylogenetic analysis reveals geographical clustering of UK viruses. Isolates from Stokesay Castle are more closely related to one another than to viruses from other regions. Daubenton's bats from Stokesay Castle represent a unique opportunity to study a natural population that appears to maintain EBLV-2 infection and may represent endemic infection at this site. Although the risk to public health from EBLV-2 is low, consequences of infection are severe and effective communication on the need for prompt post-exposure prophylaxis for anyone that has been bitten by a bat is essential.
Palmer amaranth and waterhemp have become increasingly troublesome weeds throughout the United States. Both species are highly adaptable and emerge continuously throughout the summer months, presenting the need for a residual PRE application in soybean. To improve season-long control of Amaranthus spp., 19 PRE treatments were evaluated on glyphosate-resistant Palmer amaranth in 2013 and 2014 at locations in Arkansas, Indiana, Nebraska, Illinois, and Tennessee; and on glyphosate-resistant waterhemp at locations in Illinois, Missouri, and Nebraska. The two Amaranthus species were analyzed separately; data for each species were pooled across site-years, and site-year was included as a random variable in the analyses. The dissipation of weed control throughout the course of the experiments was compared among treatments with the use of regression analysis where percent weed control was described as a function of time (the number of weeks after treatment [WAT]). At the mean (i.e., average) WAT (4.3 and 3.2 WAT for Palmer amaranth and waterhemp, respectively) isoxaflutole + S-metolachlor + metribuzin had the highest predicted control of Palmer amaranth (98%) and waterhemp (99%). Isoxaflutole + S-metolachlor + metribuzin, S-metolachlor + mesotrione, and flumioxazin + pyroxasulfone had a predicted control ≥ 97% and similar model parameter estimates, indicating control declined at similar rates for these treatments. Dicamba and 2,4-D provided some, short-lived residual control of Amaranthus spp. When dicamba was added to metribuzin or S-metolachlor, control increased compared to dicamba alone. Flumioxazin + pyroxasulfone, a currently labeled PRE, performed similarly to treatments containing isoxaflutole or mesotrione. Additional sites of action will provide soybean growers more opportunities to control these weeds and reduce the potential for herbicide resistance.
In western Canada, more money is spent on wild oat herbicides than on any
other weed species, and wild oat resistance to herbicides is the most
widespread resistance issue. A direct-seeded field experiment was conducted
from 2010 to 2014 at eight Canadian sites to determine crop life cycle, crop
species, crop seeding rate, crop usage, and herbicide rate combination
effects on wild oat management and canola yield. Combining 2× seeding rates
of early-cut barley silage with 2× seeding rates of winter cereals and
excluding wild oat herbicides for 3 of 5 yr (2011 to 2013) often led to
similar wild oat density, aboveground wild oat biomass, wild oat seed
density in the soil, and canola yield as a repeated canola–wheat rotation
under a full wild oat herbicide rate regime. Wild oat was similarly well
managed after 3 yr of perennial alfalfa without wild oat herbicides.
Forgoing wild oat herbicides in only 2 of 5 yr from exclusively summer
annual crop rotations resulted in higher wild oat density, biomass, and seed
banks. Management systems that effectively combine diverse and optimal
cultural practices against weeds, and limit herbicide use, reduce selection
pressure for weed resistance to herbicides and prolong the utility of
threatened herbicide tools.
Herbicide-resistant Amaranthus spp. continue to cause management difficulties in soybean. New soybean technologies under development, including resistance to various combinations of glyphosate, glufosinate, dicamba, 2,4-D, isoxaflutole, and mesotrione, will make possible the use of additional herbicide sites of action in soybean than is currently available. When this research was conducted, these soybean traits were still regulated and testing herbicide programs with the appropriate soybean genetics in a single experiment was not feasible. Therefore, the effectiveness of various herbicide programs (PRE herbicides followed by POST herbicides) was evaluated in bare-ground experiments on glyphosate-resistant Palmer amaranth and glyphosate-resistant waterhemp (both tall and common) at locations in Arkansas, Illinois, Indiana, Missouri, Nebraska, and Tennessee. Twenty-five herbicide programs were evaluated; 5 of which were PRE herbicides only, 10 were PRE herbicides followed by POST herbicides 3 to 4 wks after (WA) the PRE application (EPOST), and 10 were PRE herbicides followed by POST herbicides 6 to 7 WA the PRE application (LPOST). Programs with EPOST herbicides provided 94% or greater control of Palmer amaranth and waterhemp at 3 to 4 WA the EPOST. Overall, programs with LPOST herbicides resulted in a period of weed emergence in which weeds would typically compete with a crop. Weeds were not completely controlled with the LPOST herbicides because weed sizes were larger (≥ 15 cm) compared with their sizes at the EPOST application (≤ 7 cm). Most programs with LPOST herbicides provided 80 to 95% control at 3 to 4 WA applied LPOST. Based on an orthogonal contrast, using a synthetic-auxin herbicide LPOST improves control of Palmer amaranth and waterhemp over programs not containing a synthetic-auxin LPOST. These results show herbicides that can be used in soybean and that contain auxinic- or HPPD-resistant traits will provide growers with an opportunity for better control of glyphosate-resistant Palmer amaranth and waterhemp over a wide range of geographies and environments.
Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources.
Alongshore variations in coastline curvature or offshore depth profile can create localised regions of shelf-wave propagation with modes decaying outside these regions. These modes, termed localised continental shelf waves (
CSWs) here, exist only at certain discrete frequencies lying below the local maximum frequency, and above the far-field maximum frequency, for propagating shelf waves. The purpose of this paper is to obtain these frequencies and construct, both analytically and numerically, and discuss
CSWs for shelves with arbitrary alongshore variations in offshore depth profile and coastline curvature. If the shelf curvature changes by a small fraction of its value over the shelf section of interest or an alongshore perturbation in offshore depth profile varies slowly over the same length scale then
CSWs can be constructed using WKBJ theory. Two subcases are described: (i) if the propagating region is sufficiently long that the offshore structure of the
CSW varies appreciably alongshore then the frequency and alongshore structure are found from a sequence of local problems; (ii) if the propagating region is sufficiently short that the alongshore change in offshore structure of the
CSW is small then the alongshore modal structure is given in an explicit, uniformly valid form. A separate asymptotic theory is required for curvature perturbations to shelves that are otherwise straight rather than curved. Comparison with highly accurately numerically determined
CSWs shows that both theories are extremely accurate, with the WKBJ theory having a significantly wider range of applicability. An idealised model for the generation of
CSWs is also suggested. A localised time-periodic wind stress generates an evanescent continental shelf wave in the far field of a localised mode where the coast is almost straight and the response on the shelf is obtained numerically. If the forcing frequency is close to that of an
CSW then the wind stress excites energetic motions in the region of maximum curvature, creating a significant localised response possibly far from the forcing region.
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)
JET experiments have compared the efficacy of low- and high-field side ion cyclotron resonance heating (ICRH) as an actuator to deliberately minimise the sawtooth period. It is found that low-field side ICRH with low minority concentration is optimal for sawtooth control for two main reasons. Firstly, low-field side heating means that any toroidal phasing of the ICRH (
or dipole) has a destabilising effect on the sawteeth, meaning that dipole phasing can be employed, since this is preferable due to less plasma wall interaction from Resonant Frequency (RF) sheaths. Secondly, the resonance position of the low-field side ICRH does not have to be very accurately placed to achieve sawtooth control, relaxing the requirement for real-time control of the RF frequency. These empirical observations have been confirmed by hybrid kinetic–magnetohydrodynamic modelling, and suggest that the ICRH antenna design for ITER is well positioned to provide a control actuator capable of having a significant effect on the sawtooth behaviour.
Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in otherwise healthy individuals. Low n-3 PUFA intake has been associated with the presence of NAFLD; however, the relationship between a biomarker of n-3 status – the Omega-3 Index – and liver fat is yet to be elucidated. A total of eighty overweight adults (fifty-six men) completed the anthropometric and biochemical measurements, including the Omega-3 Index, and underwent proton magnetic resonance spectroscopy assessment of liver fat. Bivariate correlations and multiple regression analyses were performed with reference to prediction of liver fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid concentration≥5·5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP) and alanine aminotransferase (ALT) were positively correlated, and HDL and erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration. Regression analysis found that simple anthropometric and demographic variables (waist, age) accounted for 31 % of the variance in liver fat and the addition of traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the predictive power to 43 %. The addition of the novel erythrocyte fatty acid variable (Omega-3 Index) to the model only accounted for a further 3 % of the variance (P=0·049). In conclusion, the Omega-3 Index was associated with liver fat concentration but did not improve the overall capacity of demographic, anthropometric and blood markers to predict NAFLD.