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The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry.
We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort.
SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services.
Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08–2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64–1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34–2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70–1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52–1.38, P = 0.50).
In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.
Support for Western Europe’s far-right is majority-male. However, given the sweeping success of the party family, literature on this ‘gender gap’ belies support given to the radical right by millions of women. We examine differences between men and women’s support for far-right parties, focusing on workplace experience, positions on economic and cultural issues, and features of far-right parties themselves. We find that the received scholarship on blue-collar support for far-right populists is a largely male phenomenon, and women in routine nonmanual (i.e. service, sales, and clerical) work are more likely than those in blue-collar work to support the far-right. Moreover, while men who support the far-right tend to be conservative on other moral issues, certain liberal positions predict far-right support among women, at both the voter and party level. Our analysis suggests that gender differences may obscure the socio-structural and attitudinal bases of support for far-right parties and have broader implications for comparative political behavior and gender and politics.
Following the previous article, here we describe the first field demonstration of the ELVIS system, performed at Newport Beach, CA. We examined ocean water to detect microorganisms using the combined holographic and light-field fluorescence microscope and successfully detected both eukaryotes and prokaryotes. The shared field of view provided simultaneous bright-field (amplitude), phase, and fluorescence information from both chlorophyll autofluorescence and acridine orange staining. The entire process was performed in a nearly autonomous manner using a specifically designed sample processing unit (SPU) and custom acquisition software. We also discuss improvements to the system made after the field test that will make it more broadly useful to other types of fluorophores and samples.
Intensified cover-cropping practices are increasingly viewed as a herbicide-resistance management tool but clear distinction between reactive and proactive resistance management performance targets is needed. We evaluated two proactive performance targets for integrating cover-cropping tactics, including (1) facilitation of reduced herbicide inputs and (2) reduced herbicide selection pressure. We conducted corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] field experiments in Pennsylvania and Delaware using synthetic weed seedbanks of horseweed [Conyza canadensis (L.) Cronquist] and smooth pigweed (Amaranthus hybridus L.) to assess winter and summer annual population dynamics, respectively. The effect of alternative cover crops was evaluated across a range of herbicide inputs. Cover crop biomass production ranged from 2,000 to 8,500 kg ha−1 in corn and 3,000 to 5,500 kg ha−1 in soybean. Experimental results demonstrated that herbicide-based tactics were the primary drivers of total weed biomass production, with cover-cropping tactics providing an additive weed-suppression benefit. Substitution of cover crops for PRE or POST herbicide programs did not reduce total weed control levels or cash crop yields but did result in lower net returns due to higher input costs. Cover-cropping tactics significantly reduced C. canadensis populations in three of four cover crop treatments and decreased the number of large rosettes (>7.6-cm diameter) at the time of preplant herbicide exposure. Substitution of cover crops for PRE herbicides resulted in increased selection pressure on POST herbicides, but reduced the number of large individuals (>10 cm) at POST applications. Collectively, our findings suggest that cover crops can reduce the intensity of selection pressure on POST herbicides, but the magnitude of the effect varies based on weed life-history traits. Additional work is needed to describe proactive resistance management concepts and performance targets for integrating cover crops so producers can apply these concepts in site-specific, within-field management practices.
This is the first of two articles on the Extant Life Volumetric Imaging System (ELVIS) describing a combined digital holographic microscope (DHM) and a fluorescence light-field microscope (FLFM). The instrument is modular and robust enough for field use. Each mode uses its own illumination source and camera, but both microscopes share a common objective lens and sample viewing chamber. This allows correlative volumetric imaging in amplitude, quantitative phase, and fluorescence modes. A detailed schematic and parts list is presented, as well as links to open-source software packages for data acquisition and analysis that permits interested researchers to duplicate the design. Instrument performance is quantified using test targets and beads. In the second article on ELVIS, to be published in the next issue of Microscopy Today, analysis of data from field tests and images of microorganisms will be presented.
The comparative effectiveness of antidepressant medication and cognitive-behaviour therapy for the acute treatment of depression is contentious.
To compare the acute outcomes of antidepressant medication, cognitive-behaviour therapy (CBT), and the combination of the two, in adult, depressed patients.
Sixteen electronic databases together with reference lists were searched for randomised and other clinical trials that compared CBT, antidepressants, or their combination.
In the comparison between CBT and antidepressants, 8 studies met inclusion criteria. Five studies met the inclusion criteria for the second comparison between single therapy and combination therapy. In the antidepressant and CBT comparison, effect sizes favoured CBT over antidepressants with a significant advantage for CBT on some outcome measures. Combined treatment appeared more effective than antidepressants. However, combined treatment did not emerge more effective than CBT.
Antidepressants may not be considered more efficacious than CBT for the acute treatment of depressed patients nor can combination therapy be regarded as more effective than CBT alone.
Major depressive disorder (MDD) affects at some point in their lives a tenth of the world's population with a higher incidence in females than males. Like all clinical disorders encountered in adult psychiatry, a diagnosis of MDD is symptom-based and has not been externally validated. Eye movement dysfunctions (EMDs) in the functional psychoses have been extensively reported and their potential as biomarkers highlighted but it is unclear whether there are patterns of EMDs specific to MDD. Abnormal EMs in bipolar affective cases have been observed during face and picture viewing, saccadic control and smooth pursuit tasks. However most studies reporting EMs in affective disorders, have not distinguished between unipolar/MDD and bipolar cases. to address this problem we have compared performance on a broad range of EM tests in patients meeting DSM-IV criteria for MDD with identical measures made in a large sample of bipolar, schizophrenia and undiagnosed individuals. Remarkably a network classifier was able to delineate controls and each patient group using EM performance measures with exceptional sensitivity (94%) and specificity (98%). What is more, probability of illness category was not associated with demographic, symptom, neuropsychological or medication variables. It therefore appears that a unique multivariate eye movement phenotype may be associated with MDD. If verified in further MDD cases these findings could be an enormous advance in helping to assess and/or diagnose individuals with symptoms of MDD or at risk of developing MDD.
To assess potential transmission of antibiotic-resistant organisms (AROs) using surrogate markers and bacterial cultures.
A 1,260-bed tertiary-care academic medical center.
The study included 25 patients (17 of whom were on contact precautions for AROs) and 77 healthcare personnel (HCP).
Fluorescent powder (FP) and MS2 bacteriophage were applied in patient rooms. HCP visits to each room were observed for 2–4 hours; hand hygiene (HH) compliance was recorded. Surfaces inside and outside the room and HCP skin and clothing were assessed for fluorescence, and swabs were collected for MS2 detection by polymerase chain reaction (PCR) and selective bacterial cultures.
Transfer of FP was observed for 20 rooms (80%) and 26 HCP (34%). Transfer of MS2 was detected for 10 rooms (40%) and 15 HCP (19%). Bacterial cultures were positive for 1 room and 8 HCP (10%). Interactions with patients on contact precautions resulted in fewer FP detections than interactions with patients not on precautions (P < .001); MS2 detections did not differ by patient isolation status. Fluorescent powder detections did not differ by HCP type, but MS2 was recovered more frequently from physicians than from nurses (P = .03). Overall, HH compliance was better among HCP caring for patients on contact precautions than among HCP caring for patients not on precautions (P = .003), among nurses than among other nonphysician HCP at room entry (P = .002), and among nurses than among physicians at room exit (P = .03). Moreover, HCP who performed HH prior to assessment had fewer fluorescence detections (P = .008).
Contact precautions were associated with greater HCP HH compliance and reduced detection of FP and MS2.
The number of medical mobile phone applications continues to grow. Although otorhinolaryngology-specific applications represent a small proportion, there are exciting innovations emerging for the specialty. This article will assess the number of applications available and review how they may be used in clinical practice.
The application stores of the two most popular mobile phone platforms, Apple and android, were searched using multiple search terms.
A total of 107 ENT applications were identified and categorised according to intended use. Eight applications were reviewed in more detail and assessed on whether a doctor or allied health professional was involved in their design and if they were evidence-based.
There are a number of ENT-specific smartphone applications currently available. As the technology progresses, their scope has extended beyond being purely for reference. Nevertheless, it remains difficult to assess the validity and security of these applications.
Sub-acute ruminal acidosis (SARA) can reduce the production efficiency and impair the welfare of cattle, potentially in all production systems. The aim of this study was to characterise measurable postmortem observations from divergently managed intensive beef finishing farms with high rates of concentrate feeding. At the time of slaughter, we obtained samples from 19 to 20 animals on each of 6 beef finishing units (119 animals in total) with diverse feeding practices, which had been subjectively classified as being high risk (three farms) or low risk (three farms) for SARA on the basis of the proportions of barley, silage and straw in the ration. We measured the concentrations of histamine, lipopolysaccharide (LPS), lactate and other short-chain fatty acids (SCFAs) in ruminal fluid, LPS and SCFA in caecal fluid. We also took samples of the ventral blind sac of the rumen for histopathology, immunohistopathology and gene expression. Subjective assessments were made of the presence of lesions on the ruminal wall, the colour of the lining of the ruminal wall and the shape of the ruminal papillae. Almost all variables differed significantly and substantially among farms. Very few pathological changes were detected in any of the rumens examined. The animals on the high-risk diets had lower concentrations of SCFA and higher concentrations of lactate and LPS in the ruminal fluid. Higher LPS concentrations were found in the caecum than the rumen but were not related to the risk status of the farm. The diameters of the stratum granulosum, stratum corneum and of the vasculature of the papillae, and the expression of the gene TLR4 in the ruminal epithelium were all increased on the high-risk farms. The expression of IFN-γ and IL-1β and the counts of cluster of differentiation 3 positive and major histocompatibility complex class two positive cells were lower on the high-risk farms. High among-farm variation and the unbalanced design inherent in this type of study in the field prevented confident assignment of variation in the dependent variables to individual dietary components; however, the CP percentage of the total mixed ration DM was the factor that was most consistently associated with the variables of interest. Despite the strong effect of farm on the measured variables, there was wide inter-animal variation.
Organic grain producers are interested in reducing tillage to conserve soil and decrease labor and fuel costs. We examined agronomic and economic tradeoffs associated with alternative strategies for reducing tillage frequency and intensity in a cover crop–soybean (Glycine max L. Merr.) sequence within a corn (Zea mays L.)–soybean–spelt (Triticum spelta L.) organic cropping system experiment in Pennsylvania. Tillage-based soybean production preceded by a cover crop mixture of annual ryegrass (Lolium perenne L. ssp. multiflorum), orchardgrass (Dactylis glomerata L.) and forage radish (Raphanus sativus L.) interseeded into corn grain (Z. mays L.) was compared with reduced-tillage soybean production preceded by roller-crimped cereal rye (Secale cereale L.) that was sown after corn silage. Total aboveground weed biomass did not differ between soybean production strategies. Each strategy, however, was characterized by high inter-annual variability in weed abundance. Tillage-based soybean production marginally increased grain yield by 0.28 Mg ha−1 compared with reduced-tillage soybean. A path model of soybean yield indicated that soybean stand establishment and weed biomass were primary drivers of yield, but soybean production strategy had a measurable effect on yields due to factors other than within-season weed–crop competition. Cumulative tillage frequency and intensity were quantified for each cover crop—sequence using the Soil Tillage Intensity Rating (STIR) index. The reduced-tillage soybean sequence resulted in 50% less soil disturbance compared to tillage-based soybean sequence across study years. Finally, enterprise budget comparisons showed that the reduced-tillage soybean sequence resulted in lower input costs than the tillage-based soybean sequence but was approximately $114 ha−1 less profitable because of lower average yields.
A 73-year-old male with a history of chronic ataxia presented with transient facial droop to the Emergency Department. A CT angiogram and MRI with diffusion weighted imaging (DWI) were negative for stroke. However, incidental note was made of numerous giant arachnoid granulation pits in the posterior fossa predominantly involving the left occipital bone (Figure 1). These arachnoid pits demonstrated multiple foci of herniation of the adjacent cerebellar parenchyma into the pits with gliosis of the herniated parenchyma and focal encephalomalacia of the subjacent cerebellar parenchyma. Review of bone windows on a remote CT brain performed almost 13 years earlier confirmed this to be a longstanding abnormality (Figure 2). The patient’s physical exam was suggestive of cerebellar ataxia with left-sided dysmetria on finger to nose testing and a wide-based unsteady gait.
Dogs harbor numerous zoonotic pathogens, many of which are controlled through vaccination programs. The delivery of these programs can be difficult where resources are limited. We developed a dynamic model to estimate vaccination coverage and cost-per-dog vaccinated. The model considers the main factors that affect vaccination programs: dog demographics, effectiveness of strategies, efficacy of interventions and cost. The model was evaluated on data from 18 vaccination programs representing eight countries. Sensitivity analysis was performed for dog confinement and vaccination strategies. The average difference between modelled vaccination coverage and field data was 3.8% (2.3%–5.3%). Central point vaccination was the most cost-effective vaccination strategy when >88% of the dog population was confined. More active methods of vaccination, such as door-to-door or capture-vaccinate-release, achieved higher vaccination coverage in free-roaming dog populations but were more costly. This open-access tool can aid in planning more efficient vaccination campaigns in countries with limited resources.
Functional gastrointestinal disorders including constipation affect up to 14 % of the world's population. Treatment is difficult and challenging resulting in a need for alternative safe and effective therapies. The present study investigated whether daily consumption of three gold-fleshed kiwifruit could alleviate constipation and improve gastrointestinal discomfort in mildly constipated individuals with and without pain. A total of thirty-two participants were enrolled in a 16-week randomised, single-blind, crossover study. Participants received either three ‘Zesy002’ kiwifruit or 14·75 g Metamucil® (5 g dietary fibre/d (a positive control)) for 4 weeks each with a 4-week washout between treatments. A 2-week washout period was included at the beginning and end of the study. Daily bowel habit diaries were kept throughout the study. The primary outcome measure was differences in the number of complete spontaneous bowel movements (CSBM). Secondary outcome measures were bowel movement frequency and stool form as well as digestive symptoms and comfort. The number of CSBM per week was significantly greater during daily consumption of three kiwifruit compared with the baseline (6·3 v. 3·3; P < 0·05) and the Metamucil® treatment (6·3 v. 4·5; P < 0·05). Stool consistency was also improved, with kiwifruit producing softer stools and less straining (P < 0·05). Gastrointestinal discomfort was also improved compared with baseline for abdominal pain, constipation and indigestion (P < 0·05) during the kiwifruit intervention and constipation during the Metamucil® intervention (P < 0·05). This randomised controlled trial demonstrates that daily consumption of three gold-fleshed kiwifruit is associated with a significant increase of two CSBM per week and reduction in gastrointestinal discomfort in mildly constipated adults.
Background: As with other specialties, Royal College of Physicians and Surgeons of Canada (RCPSC) trainees in Neurosurgery have anecdotally had challenges securing full-time employment. This study presents the employment status, research pursuits, and fellowship choices of neurosurgery trainees in Canadian programs. Methods: RCPSC neurosurgery trainees (n = 143) who began their residency training between 1998 and 2008 were included in this study. Associations between year of residency completion, research pursuits, and fellowship choice with career outcomes were determined by Fisher’s exact test (p < 0.05, statistical significance). Results: In 2015, 60% and 26% of neurosurgery trainees had permanent positions in Canada and the USA, respectively. Underemployment, defined as locum and clinical associate positions, pursuit of multiple unrelated fellowships, unemployment, and career change to non-surgical career, was 12% in 2015. The proportion of neurosurgery trainees who had been underemployed at some point within 5 years since residency completion was 20%. Pursuit of in-folded research (MSc, PhD, or non-degree research greater than 1 year) was significantly associated with obtaining full employment (94% vs. 73%, p = 0.011). However, fellowship training was not significantly associated with obtaining full employment (78% vs. 75%, p = 1.000). Conclusions: Underemployment in neurosurgery has become a significant issue in Canada for various reasons. Pursuit of in-folded research, but not fellowship training, was associated with obtaining full employment.
OBJECTIVES/SPECIFIC AIMS: o To review the community’s recommendations on how to rebuild trust in the Flint community. o To review effective community engagement strategies utilized with the Flint Special Projects for project conceptualization, participant recruitment, data analysis, project oversight, and dissemination. METHODS/STUDY POPULATION: The study population includes nearly two hundred residents representing seniors, youth and diverse ethnicities recruited to participate in eleven focus group meetings. The population also represents the general public who attended informational meetings in Flint, Michigan to learn about the crisis and allow residents to voice their opinions and concerns during the onset of the crisis. The project is a mixed methods community based participatory research effort that utilized community decision making in all phases of the effort such as pre-conception, implementation, dissemination and advocacy to encourage the community’s recommendations are adopted at policy and institutional responsiveness levels. It includes three community engaged research efforts: (project 1) A qualitative analysis of community sentiment provided during 17 recorded legislative, media and community events, and (projects 2-3) two mixed methods efforts utilizing purposive sampling of stakeholders whose voice may not have been heard. RESULTS/ANTICIPATED RESULTS: The project presents a qualitative analysis of the community’s voice during the onset of the man-made disaster when the community first became aware of the emergency manager’s plans to switch the water source. It also reflects current perspectives of community voice since the projects are scheduled to end late February 2019. Findings from a trust measure administered to nearly two hundred residents will be presented, along with a qualitative analysis of focus group findings among segments of the population (seniors, youth, and diverse ethnicities) who may have been left out of narratives on the water crisis. Finally, the project will compare empowerment and resiliency approaches being utilized in Flint, Michigan to recover from the disaster with other approaches grounded in literature and theory. DISCUSSION/SIGNIFICANCE OF IMPACT: Communities of color often experience social determinants of health which negatively impact their health, well-being and human rights. Some Flint citizens are experiencing negative health consequences (i.e., rashes, brain and behavioral sequelle, fertility, etc.) as a result of the disaster, and are uncertain of health outcomes in the future. This is the first project to rigorously document and analyze levels of trust and mistrust in the city of Flint since the water disaster occurred. The qualitative research will guide future clinical research that will benefit this traumatized community experiencing high levels of mistrust (i.e., government, elected officials, etc.). The community engaged methodology involved residents and study participants in all phases of the project including project oversight, validating and analyzing data, and dissemination. This methodology will contribute to existing literature and theory on community based participatory research, community engaged research, team science and citizen science. The approaches empowered a call to action among residents, for example, seniors who attended two senior focus group sessions shared “they are hopeful and have a purpose,” resulting in the creation of a council (with officers) at their housing complex to advocate for the well-being of seniors during the recovery process. Recruitment methodologies were extremely successful due to resident level trust in community leaders and community partner organizations. Finally, the project’s examination of approaches encouraging empowerment and resiliency will provide lessons learned for other communities challenged with crisis.