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Anxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction.
In total, 1937 twins aged 22–25 years, including 538 complete pairs from the Twins Early Development Study took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase, participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase, the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase.
Twin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15, 30 and 15%, respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations 0.4–0.5).
Fear acquisition and extinction are heritable, and share some, but not all of the same genetic influences.
COVID-19 research has been produced at an unprecedented rate and managing what is currently known is in part being accomplished through synthesis research. Here we evaluated how the need to rapidly produce syntheses has impacted the quality of the synthesis research. Thus, we sought to identify, evaluate and map the synthesis research on COVID-19 published up to 10 July 2020. A COVID-19 literature database was created using pre-specified COVID-19 search algorithms carried out in eight databases. We identified 863 citations considered to be synthesis research for evaluation in this project. Four-hundred and thirty-nine reviews were fully assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) and rated as very low-quality (n = 145), low-quality (n = 80), medium-quality (n = 208) and high-quality (n = 151). The quality of these reviews fell short of what is expected for synthesis research with key domains being left out of the typical methodology. The increase in risk of bias due to non-adherence to systematic review methodology is unknown and prevents the reader from assessing the validity of the review. The responsibility to assure the quality is held by both producers and publishers of synthesis research and our findings indicate there is a need to equip readers with the expertise to evaluate the review conduct before using it for decision-making purposes.
To investigate if food security mediated the impact of a nutrition-sensitive agroecology intervention on women’s depressive symptoms.
We used annual longitudinal data (four time points) from a cluster-randomised effectiveness trial of a participatory nutrition-sensitive agroecology intervention, the Singida Nutrition and Agroecology Project. Structural equation modelling estimation of total, natural direct and natural indirect effects was used to investigate food security’s role in the intervention’s impact on women’s risk of probable depression (Center for Epidemiologic Studies Depression Scale > 17) across 3 years.
Rural Singida, Tanzania.
548 food insecure, married, smallholder women farmers with children < 1 year old at baseline.
At baseline, one-third of the women in each group had probable depression (Control: 32·0 %, Intervention: 31·9 %, P difference = 0·97). The intervention lowered the odds of probable depression by 43 % (OR = 0·57, 95 % CI: 0·43, 0·70). Differences in food insecurity explained approximately 10 percentage points of the effects of the intervention on odds of probable depression (OR = 0·90, 95 % CI: 0·83, 0·95).
This is the first evidence of the strong, positive effect that lowering food insecurity has on reducing women’s depressive symptoms. Nutrition-sensitive agricultural interventions can have broader impacts than previously demonstrated, i.e. improvements in mental health; changes in food security play an important causal role in this pathway. As such, these data suggest participatory nutrition-sensitive agroecology interventions have the potential to be an accessible method of improving women’s well-being in farming communities.
ABSTRACT IMPACT: Use of this novel murine model of inflammatory bowel disease (IBD) and C. difficile infection (CDI) will aid in developing new clinical approaches to predict, diagnose, and treat CDI in the IBD population. OBJECTIVES/GOALS: IBD is associated with intestinal inflammation and alterations of the gut microbiota, both of which can diminish colonization resistance to C. difficile. Here, we sought to determine if IBD is sufficient to render mice susceptible to C. difficile colonization and infection in the absence of other perturbations, such as antibiotic treatment. METHODS/STUDY POPULATION: C57BL/6 IL-10-/- mice were colonized with Helicobacter hepaticus to trigger colonic inflammation akin to human IBD. Control mice, not colonized with H. hepaticus, were pretreated with the antibiotic cefoperazone to render the gut microbiota susceptible to CDI. Mice were then gavaged with spores of the toxigenic C. difficile strain VPI 10463 and monitored for C. difficile colonization and disease. The fecal microbiota at the time of C. difficile exposure was profiled by 16S rRNA gene sequencing and analyzed using mothur. Statistical analyses were performed using R. RESULTS/ANTICIPATED RESULTS: Mice with IBD harbored significantly distinct intestinal microbial communities compared to non-IBD controls at the time of C. difficile spore exposure (14 days post-IBD trigger). Mice with IBD were susceptible to persistent C. difficile colonization, while genetically identical non-IBD controls were resistant to C. difficile colonization. Concomitant IBD and CDI was associated with significantly worse clinical and intestinal disease than unaccompanied IBD. DISCUSSION/SIGNIFICANCE OF FINDINGS: Patients with IBD who develop concurrent CDI experience increased morbidity and mortality. These studies in a novel mouse model of IBD and CDI emphasize the dual importance of host responses and alterations of the gut microbiota in susceptibility to C. difficile colonization and infection in the setting of IBD.
Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2–49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2–9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42–49 (95% confidence interval (CI) 52–92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06–1.50, P = 0.010).
Potential effectiveness of harvest weed seed control (HWSC) systems depends upon seed shatter of the target weed species at crop maturity, enabling its collection and processing at crop harvest. However, seed retention likely is influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed-shatter phenology in 13 economically important broadleaf weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after physiological maturity at multiple sites spread across 14 states in the southern, northern, and mid-Atlantic United States. Greater proportions of seeds were retained by weeds in southern latitudes and shatter rate increased at northern latitudes. Amaranthus spp. seed shatter was low (0% to 2%), whereas shatter varied widely in common ragweed (Ambrosia artemisiifolia L.) (2% to 90%) over the weeks following soybean physiological maturity. Overall, the broadleaf species studied shattered less than 10% of their seeds by soybean harvest. Our results suggest that some of the broadleaf species with greater seed retention rates in the weeks following soybean physiological maturity may be good candidates for HWSC.
Seed shatter is an important weediness trait on which the efficacy of harvest weed seed control (HWSC) depends. The level of seed shatter in a species is likely influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed shatter of eight economically important grass weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after maturity at multiple sites spread across 11 states in the southern, northern, and mid-Atlantic United States. From soybean maturity to 4 wk after maturity, cumulative percent seed shatter was lowest in the southern U.S. regions and increased moving north through the states. At soybean maturity, the percent of seed shatter ranged from 1% to 70%. That range had shifted to 5% to 100% (mean: 42%) by 25 d after soybean maturity. There were considerable differences in seed-shatter onset and rate of progression between sites and years in some species that could impact their susceptibility to HWSC. Our results suggest that many summer annual grass species are likely not ideal candidates for HWSC, although HWSC could substantially reduce their seed output during certain years.
Magnetic field-assisted freeze-casting of porous alumina structures is reported. Different freeze-casting parameters were investigated and include the composition of the original slurry (Fe3O4 and PVA content) and the control of temperature during the free casting process. The optimum content of the additives in the slurry were 3 and 6 wt% for PVA and Fe3O4, respectively. These conditions provided the most unidirectional porous structures throughout the length of the sample. The sintering temperature was maintained at 1500 °C for 3 h. The application of a vertical magnetic field (parallel to ice growth direction) with using a cooling rate mode technique was found to enhance the homogeneity of the porous structure across the sample. The current study suggests that magnetic field-assisted freeze-casting is a viable method to create highly anisotropic porous ceramic structures.
Field studies were conducted in 2018 and 2019 in Arkansas, Indiana, Illinois, Missouri, and Tennessee to determine if cover-crop residue interfered with herbicides that provide residual control of Palmer amaranth and waterhemp in no-till soybean. The experiments were established in the fall with planting of cover crops (cereal rye + hairy vetch). Herbicide treatments consisted of a nontreated or no residual, acetochlor, dimethenamid-P, flumioxazin, pyroxasulfone + flumioxazin, pendimethalin, metribuzin, pyroxasulfone, and S-metolachlor. Palmer amaranth took 18 d and waterhemp took 24 d in the cover crop–alone (nontreated) treatment to reach a height of 10 cm. Compared with this treatment, all herbicides except metribuzin increased the number of days until 10-cm Palmer amaranth was present. Flumioxazin applied alone or in a mixture with pyroxasulfone were the best at delaying Palmer amaranth growing to a height of 10 cm (35 d and 33 d, respectively). The herbicides that resulted in the lowest Palmer amaranth density (1.5 to 4 times less) integrated with a cover crop were pyroxasulfone + flumioxazin, flumioxazin, pyroxasulfone, and acetochlor. Those four herbicide treatments also delayed Palmer amaranth emergence for the longest period (27 to 34 d). Waterhemp density was 7 to 14 times less with acetochlor than all the other herbicides present. Yield differences were observed for locations with waterhemp. This research supports previous research indicating that utilizing soil-residual herbicides along with cover crops improves control of Palmer amaranth and/or waterhemp.
While fetal alcohol spectrum disorder (FASD) has primarily been thought of as a neurodevelopmental condition, research is beginning to highlight its ‘whole-body’ implications. Accordingly, the current study sought to provide a snapshot of potential health issues. Caregivers of children (median age of 12 years) with an FASD diagnosis were invited to participate in an online survey. Information relating to sample demographics, FASD status of the child and health outcomes were collected. The prevalence of health conditions reported in the FASD sample was compared against national prevalence data. Multiple linear regression utilising a stepwise approach was used to investigate potential predictors of the number of diagnosed health conditions. Survey data were from an international cohort (n = 197), with the majority of respondents based in Australia (40.2%) or the United States (27.7%). The most commonly reported diagnosed health conditions were eye conditions (44.7%), asthma (34.5%), heart conditions (34.0%) and skin conditions (27.4%). Binomial testing indicated the proportion of children diagnosed with these disorders was generally higher in the current FASD population, compared to national prevalence data. Indicators of metabolic dysfunction including diabetes and obesity were not significantly different compared to national prevalence data. Age of FASD diagnosis, existence of comorbid mental health conditions and the primary caregiver being in paid work were identified as being associated with the prevalence of diagnosed health conditions. Overall, the study has provided an up-to-date snapshot of health problems reported in a sample of children with FASD, confirming their increased risk of adverse health outcomes.
Hand hygiene adherence has been associated with reductions in nosocomial infection. We assessed the effect of improvements in electronically measured hand hygiene adherence on the incidence of hospital-acquired infections.
This quasi-experimental study was conducted in a 555-bed urban safety-net level I trauma center. The preintervention period was January 2015 through June 2016. Baseline electronic hand hygiene data collection took place from April through June 2016. The intervention period was July 2016 through December 2017. An electronic hand hygiene system was installed in 4 locations in our hospital. Performance improvement strategies were implemented that included education, troubleshooting, data dissemination, and feedback. Adherence rates were tracked over time. Rates of hospital-acquired infections were evaluated in the intervention units and in control units selected for comparison. The intervention period was subdivided into the initial and subsequent 9-month periods and were compared to the baseline period.
Electronically measured hand hygiene rates improved significantly from baseline to intervention, from 47% 77% adherence. Rates >70% continued to be measured 18 months after the intervention. Interrupted time series analysis indicated a significant effect of hand hygiene on healthcare facility-onset Clostridioides difficile infection rates during the first 9 months of the intervention. This trend continued during the final 9 months of the intervention but was nonsignificant. No effects were observed for other hospital-acquired infection rates.
Implementation of electronic hand hygiene monitoring and performance improvement interventions resulted in reductions in hospital-onset Clostridioides difficile infection rates.
Depression is a major public health problem in European countries, and health systems need to ensure access to effective psychological and pharmacological treatments. Research suggests that improvements in depression care require “complex interventions” that implement change in several areas simultaneously.
We describe an observational study of the implementation of a “stepped care” model to provide care for all adults presenting with a new case of depression in a mixed urban-rural area of Scotland with a population of 76,000 people.
A team of 5.2 clinicians provided care for about 1,000 new cases of depression each year. “Guided Self-Help” was the baseline intervention for all patients, supplemented where necessary with pharmacological treatment and Cognitive Behavioural or Interpersonal Therapy.
Service delivery systems were reformed to provide: specialist treatment in primary care settings using primarily non-medical clinicians, comprehensive electronic clinical records, continuous outcome monitoring and intensive investment in staff training and support.
Clinical outcomes (measured by the Personal Health Questionnaire, Social and Work Adjustment Scale and EQ-5D) showed significant improvement despite relatively brief clinician contact (2.5 hours over 4.6 contacts). Savings of more than 50% were made on the antidepressant drug budget. Service user satisfaction ratings were high.
Population needs for depression care can be met using “stepped care” models such as that described above. A randomised controlled study of this approach would be required to fully test the model.
Selenium (Se) is an essential element for human health. However, our knowledge of the prevalence of Se deficiency is less than for other micronutrients of public health concern such as iodine, iron and zinc, especially in sub-Saharan Africa (SSA). Studies of food systems in SSA, in particular in Malawi, have revealed that human Se deficiency risks are widespread and influenced strongly by geography. Direct evidence of Se deficiency risks includes nationally representative data of Se concentrations in blood plasma and urine as population biomarkers of Se status. Long-range geospatial variation in Se deficiency risks has been linked to soil characteristics and their effects on the Se concentration of food crops. Selenium deficiency risks are also linked to socio-economic status including access to animal source foods. This review highlights the need for geospatially-resolved data on the movement of Se and other micronutrients in food systems which span agriculture–nutrition–health disciplinary domains (defined as a GeoNutrition approach). Given that similar drivers of deficiency risks for Se, and other micronutrients, are likely to occur in other countries in SSA and elsewhere, micronutrient surveillance programmes should be designed accordingly.
Clozapine is the most effective antipsychotic medication, but it has the highest propensity for metabolic side effects. A clozapine clinic was established within an early intervention for psychosis service to facilitate the timely commencement of clozapine and to manage the associated adverse effects. This study describes the changes in the weight, body mass index (BMI), waist circumference and blood pressure after 6 months in young people commenced on clozapine.
This was a prospective cohort study of all young people, aged 15–24 years, commenced on clozapine within an early intervention service in Melbourne, Australia, between 01.04.2016 and 30.06.2018. Continuous data were analyzed with paired t-test and categorical with Wilcoxon signed-rank test.
Twenty-six young people received 6 months of treatment with clozapine, of whom the mean age was 19.8 years (s.d. ±3.1) and 66.7% were male. After 6 months, the mean weight gain was 5.1 kg (s.d. ±10.1 kg) and over half (53.8%) gained clinically significant weight. The proportion of young people classified as either overweight or obese rose from 69.2% to 88.5% (p = 0.006). The proportion of young people with a waist circumference above the recommended parameters increased from 57.9% to 78.9% (p = 0.008). Hypertension was present in 30%, and after 6 months, 45% had hypertension (p = 0.64). Metformin was prescribed to 34.6%, typically to those with the greatest and most rapid weight gain.
Among young people with treatment resistant psychosis, clozapine is associated with significant metabolic side effects in the early stages of commencement. More interventions aimed at attenuating this weight gain are needed.
The fluid–structure interactions (FSI) of compliant lifting surfaces is complicated by free-surface and multiphase flows such as cavitation and ventilation. This paper describes the dynamic FSI response of a flexible surface-piercing hydrofoil in dry, wetted, ventilating and cavitating conditions. Experimental modal analysis is used to quantify the resonant frequencies and damping ratios of the fluid–structure system in each flow regime. The generalized hydrodynamic stiffness, fluid damping and fluid added mass are also determined as ratios to the corresponding structural modal forces. Added mass increases with increasing partial immersion of the hydrofoil and decreases in the presence of gaseous cavities. In particular, modal frequencies were observed to increase significantly in fully ventilated flow compared to fully wetted flow. The modal frequencies varied non-monotonically with speed in fully wetted flow. Gaseous cavities reduced the modal added mass and reduced the fluid disturbing force. Modal damping increases non-monotonically with increasing immersion depth. Forward speed causes the fluid damping force to increase with an approximately quadratic functional behaviour, consistent with a series expansion of the Morison equation, although damping identification became increasingly difficult at high flow speeds. The results indicate that fluid damping is greater than the associated structural damping in a quiescent liquid, and increasingly so with increasing immersion, suggesting viscous dissipation as a dominant mechanism. A preliminary investigation of modal vibration as a means of controlling the size and stability of ventilated cavities indicates that low-order modes encourage the formation of ventilation, while higher-order modes encourage the washout and elimination of ventilation.
Compliant lift-generating surfaces have widespread applications as marine propellers, hydrofoils and control surfaces, and the fluid–structure interactions (FSI) of such systems have important effects upon their performance and stability. Multi-phase flows like cavitation and ventilation alter the hydrodynamic and hydroelastic behaviours of lifting surfaces in ways that are not yet completely understood. This paper describes experiments on one rigid and two flexible variants of a vertical surface-piercing hydrofoil in wetted, ventilating and cavitating conditions. Tests were conducted in a towing tank and a free-surface cavitation channel. This work, which is Part 1 of a two-part series, examines the passive, or flow-induced, fluid–structure interactions of the hydrofoils. Four characteristic flow regimes are described: fully wetted, partially ventilated, partially cavitating and fully ventilated. Hydroelastic coupling is shown to increase the hydrodynamic lift and yawing moments across all four flow regimes by augmenting the effective angle of attack. The effective angle of attack, which was derived using a beam model to account for the effect of spanwise twisting deflections, effectively collapses the hydrodynamic load coefficients for the three hydrofoils. A generalized cavitation parameter, using the effective angle of attack, is used to collapse the lift and moment coefficients for all trials at a single immersed aspect ratio, smoothly bridging the four distinct flow regimes. None of the hydrofoils approached the static divergence condition, which occurs when the hydrodynamic stiffness negates the structural stiffness, but theory and experiments both show that ventilation increases the divergence speed by reducing the hydrodynamic twisting moment about the elastic axis. Coherent vortex shedding from the blunt trailing edge of the hydrofoil causes vortex-induced vibration at an approximately constant Strouhal number of 0.275 (based on the trailing edge thickness), and leads to amplified response at lock-in, when the vortex-shedding frequency approaches one of the resonant modal frequencies of the coupled fluid–structure system.
Evidence on whether nutritional supplementation affects physical activity (PA) during early childhood is limited. We examined the long-term effects of lipid-based nutrient supplements (LNS) on total PA, moderate-to-vigorous PA (MVPA) and sedentary behaviour (SB) of children at 4–6 years using an accelerometer for 1 week. Their mothers were enrolled in the International Lipid-based Nutrient Supplement-DYAD randomised controlled trial in Ghana, assigned to daily LNS or multiple micronutrients (MMN) during pregnancy through 6 months postpartum or Fe and folic acid (IFA) during pregnancy and placebo for 6 months postpartum. From 6 to 18 months, children in the LNS group received LNS; the other two groups received no supplements. Analysis was done with intention to treat comparing two groups: LNS v. non-LNS (MMN+ IFA). Of the sub-sample of 375 children fitted with accelerometers, 353 provided sufficient data. Median vector magnitude (VM) count was 1374 (interquartile range (IQR) 309), and percentages of time in MVPA and SB were 4·8 (IQR 2) and 31 (IQR 8) %, respectively. The LNS group (n 129) had lower VM (difference in mean −73 (95 % CI −20, −126), P = 0·007) and spent more time in SB (LNS v. non-LNS: 32·3 v. 30·5 %, P = 0·020) than the non-LNS group (n 224) but did not differ in MVPA (4·4 v. 4·7 %, P = 0·198). Contrary to expectations, provision of LNS in early life slightly reduced the total PA and increased the time in SB but did not affect time in MVPA. Given reduced social-emotional difficulties in the LNS group previously reported, including hyperactivity, one possible explanation is less restless movement in the LNS group.
This study gives details of a rare case of petrous apicitis that presented as Gradenigo's syndrome and was managed surgically.
This study presents a case report and review of the literature.
A four-year-old female was admitted for failure to thrive following recent sinusitis. Physical examination was positive for right sided facial pain, photophobia and right abducens nerve palsy. Subsequent magnetic resonance imaging revealed a 1.3 × 1.7 × 1.4 cm abscess encompassing the right Meckel's cave. A computed tomography scan showed petrous apicitis and otomastoiditis, confirming Gradenigo's syndrome. The patient was taken to the operating theatre for right intact canal wall mastoidectomy with myringotomy and tube placement. She was discharged on six weeks of ceftriaxone administered by a peripherally inserted central catheter line. At a two-week post-operative visit, she showed notable improvement in neuropathic symptoms.
This study presents a rare case of petrous apicitis managed surgically without the need for a craniotomy or transcochlear procedure.
We implemented a cleaning process for mobile patient equipment (MPE) and determined its success using adenosine trisphosphate (ATP) monitoring and data feedback. Following education for staff and ATP data feedback, the data suggest that the MPE cleaning program we implemented was successful.