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Results of a co-morbid insomnia and depression study of eszopiclone and fluoxetine demonstrated that co-therapy produced greater improvements in sleep and depression than fluoxetine monotherapy. To determine if changes in the HAMD17 were due to sleep, individual HAMD17 items were evaluated.
Patients met DSM-IV criteria for MDD and insomnia, with screening HAMD17 >14. All patients received fluoxetine QAM for 10 weeks, and randomly received double-blind eszopiclone 3mg or placebo QHS for 8 weeks, followed by a single-blind placebo 2-week run-out. HAMD17 was completed at Weeks 4, 8, and 10. Individual items were compared with ANCOVA using an LOCF approach.
Mean baseline HAMD17 scores were 22 for each group. At Week 4, differences were noted between treatment groups in the total score, and the individual items of insight, the three insomnia items (p<0.02 vs monotherapy), with a trend for guilt (p=0.07). At Week 8, significant differences between groups were noted in total score (p=0.0005), in the clinician-administered Bech subscale (p<0.001), in the three insomnia items (p<0.001), guilt, work/activities, and anxiety psychic (p<0.05). At Week 10, the total score, guilt, the three insomnia items, work/activities, retardation, agitation, anxiety psychic, general somatic symptoms, and hypochondriasis demonstrated significant improvements (p<0.05 vs monotherapy) despite discontinuation of eszopiclone.
Eszopiclone/fluoxetine co-therapy resulted in significant improvements in the insomnia items of the HAMD17. In addition, several items related to core depressive symptoms were also improved with co-therapy compared with monotherapy.
The aim of the study was to assess the experiences of discrimination as reported by people with mental health problems and to explore the impact of hospitalisation.
306 people with mental health problems provided sociodemographic data and data on discrimination using the discrimination and stigma scale version 12 (DISC-12) with the domains negative experienced discrimination, anticipated discrimination, overcoming stigma and discrimination, and positive experienced discrimination. Logistic regression analysis was used to test the impact of hospitalisation on discrimination, controlled for age, gender, education, employment, diagnosis and having been prescribed medication.
Hospitalisation had a major impact on negative discrimination: People were more likely to be treated unfairly in making or keeping friends, in marriage or divorce, by people in their neighbourhood, in social life, by mental health staff and in terms of privacy, if they had been hospitalised. They were also more likely to be avoided or shunned by people who knew about the mental health problem. People with a history of hospitalisation also reported more anticipated discrimination: They had stopped themselves more often from having a close personal relationship and concealed their mental health problem from others more often than those without a history of hospitalisation. However, people who had been hospitalised also experienced more positive discrimination in terms of being treated more positively in getting welfare benefits or disability pensions and in housing.
Findings suggest that treatment in hospital contributed to a higher extent to experienced discrimination than treatment in the community.
We sought to explore whether obstetric complications (OCs) are more likely to occur in the presence of familial/genetic susceptibility for schizophrenia or whether they themselves represent an independent environmental risk factor for schizophrenia.
The presence of OCs was assessed through maternal interview on 216 subjects, comprising 36 patients with schizophrenia from multiply affected families, 38 of their unaffected siblings, 31 schizophrenic patients with no family history of psychosis, 51 of their unaffected siblings and 60 normal comparison subjects. We examined the familiality of OCs and whether OCs were commoner in the patient and sibling groups than in the control group.
OCs tended to cluster within families, especially in multiply affected families. Patients with schizophrenia, especially those from multiply affected families, had a significantly higher rate of OCs compared to normal comparison subjects, but there was no evidence for an elevated rate of OCs in unaffected siblings.
Our data provides little evidence for a link between OCs and genetic susceptibility to schizophrenia. If high rates of OCs are related to schizophrenia genes, this relationship is weak and will only be detected by very large sample sizes.
The C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with hypertension. Riboflavin acts as a cofactor for MTHFR in one-carbon metabolism which generates methyl groups for utilisation in important biological reactions such as DNA methylation. Supplementation with riboflavin has previously been shown to lower blood pressure in individuals with the MTHFR 677TT genotype. The mechanism regulating this gene-nutrient interaction is currently unknown but may involve aberrant DNA methylation which has been implicated hypertension.
The aims of this study were to examine DNA methylation of hypertension-related genes in adults stratified by MTHFR C677T genotype and the effect of riboflavin supplementation on DNA methylation of these genes in individuals with the MTHFR 677TT genotype.
Materials and Methods:
We measured DNA methylation using pyrosequencing in a set of candidate genes associated with hypertension including angiotensin II receptor type 1 (AGTR1), G nucleotide binding protein subunit alpha 12 (GNA12), insulin-like growth factor 2 (IGF2) and nitric oxide synthase 3 (NOS3). Stored peripheral blood leukocyte samples from participants previously screened for the MTHFR C677T genotype who participated in targeted randomised controlled trials (1.6mg/d riboflavin or placebo for 16 weeks) at Ulster University were accessed for this analysis (n = 120).
There were significant differences in baseline average methylation between MTHFR CC and TT genotypes at NOS3 (p = 0.026) and AGTR1 (p = 0.045) loci. Riboflavin supplementation in the TT genotype group resulted in altered average methylation at IGF2 (p = 0.025) and CpG site-specific alterations at the AGTR1 and GNA12 loci.
DNA methylation at genes related to hypertension were significantly different in individuals stratified by MTHFR genotype group. Furthermore, in MTHFR 677TT genotype individuals, there were concurrent alterations in DNA methylation at genes linked to hypertension in response to riboflavin supplementation. This is the largest study to date to demonstrate an interaction between DNA methylation of hypertension-related genes and riboflavin supplementation in adults with the MTHFR 677TT genotype. Further work using a genome-wide approach is required to better understand the role of riboflavin in altering DNA methylation in these genetically at-risk individuals.
Periconceptional folic acid (FA) has an established role in the prevention of neural tube defects (NTDs), leading to global recommendations for FA supplementation before and in early pregnancy. However, it is unclear whether there are any benefits for offspring brain health arising from continued maternal FA supplementation beyond the first trimester. The aim of this study was to investigate the role of maternal folate nutrition during pregnancy in relation to cognitive performance and brain function in the offspring at 11 years. The children of mothers who had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) were investigated, providing a unique opportunity to examine offspring brain health in relation to maternal folate (the FASSTT Offspring trial; n = 68). Cognitive performance was assessed using the Wechsler Intelligence Scale for Children, Fourth UK Edition (WISC-IV). The WISC-IV measures Full Scale IQ and specific domains of cognitive performance: Verbal Comprehension, Perceptual Reasoning, Working Memory and Processing Speed. Brain function was measured using magnetoencephalography (MEG) in a subset of the child participants (n = 33). The results showed no significant difference in Full Scale IQ between the children of mothers who had received folic acid versus placebo during pregnancy (P = 0.993). Processing Speed subtest scores were however significantly higher in the folic acid group compared with placebo (Symbol Search: P = 0.046 and Cancellation: P = 0.011). The application of MEG analysis showed that at rest, there were differences in brain functioning with significantly lower overall power at Broad band [1–48Hz] (P = 0.041) and a trend (not significant) towards lower power in all other frequency bands (Theta, Mu, Beta, Low Gamma and High Gamma) in children from the FA group compared with placebo. Results for the responses to the language task (congruent and incongruent sentences) in children from the FA group showed significantly lower power within the Theta band [4–8Hz] and significantly higher power within high frequency bands i.e. Beta [13–30 Hz] and High Gamma [49–70 Hz]. This suggested more efficient language processing abilities in these children compared to children of mothers in the placebo group. The findings provide scientific evidence that continuing FA supplementation beyond the periconceptional period that is protective against NTDs, may be beneficial for brain health in the offspring. Furthermore, this study demonstrates that MEG is a useful tool for objective assessment of functional brain activity in healthy children in response to nutrition intervention.
Recurrent aortic arch obstruction following the Norwood procedure is recognised as an important complication. Balloon arch angioplasty is associated with a high recoarctation rate.
We sought to evaluate the prevalence and outcome of stent implantation for recoarctation in children following Norwood or Damus–Kaye–Stansel procedure over the past decade at a single national cardiology centre.
Of 114 children who underwent Norwood procedure or Damus–Kaye–Stansel procedure between January 2003 and June 2013, 80 patients survived. Of these 15 children underwent stent implantation for recoarctation. Six of these patients had previous balloon angioplasty. The median age at stent implantation was 4.4 months (range 2–82 months). The median peak aortic arch gradient at catheterisation decreased from 26mmHg (range 10–70mmHg) to 2mmHg (range 0–20mmHg). The median luminal diameter increased from 4.7 mm (range 3.2–7.9 mm) to 8.6 mm (range 6.2–10.9 mm). The median coarctation index increased by 0.49 (range = 0.24–0.64). A Valeo stent was employed in 11 children, a Palmaz Genesis stent in 2 patients, a MultiLink stent in 1 child, and a Jomed covered stent in 1 child. Two factors were associated with the need for stent placement: previous arch angioplasty (p valve < 0.001, χ-square 11.5) and borderline left ventricle (p = 0.04, χ-square = 4.1). Stent migration occurred in one child. There were two deaths related to poor right ventricular systolic function and severe tricuspid regurgitation. Six patients underwent redilation of the stent with no complications.
The prevalence of recurrent aortic arch obstruction following Norwood/Damus–Kaye–Stansel procedure was 18%. Stent implantation is safe and reliably eliminates the aortic obstruction. Redilation can be successfully achieved to accommodate somatic growth or development of stent recoarctation.
The widespread use of herbicides in cropping systems has led to the evolution of resistance in major weeds. The resultant loss of herbicide efficacy is compounded by a lack of new herbicide sites of action, driving demand for alternative weed control technologies. While there are many alternative methods for control, identifying the most appropriate method to pursue for commercial development has been hampered by the inability to compare techniques in a fair and equitable manner. Given that all currently available and alternative weed control methods share an intrinsic energy consumption, the aim of this review was to compare methods based on energy consumption. Energy consumption was compared for chemical, mechanical, and thermal weed control technologies when applied as broadcast (whole-field) and site-specific treatments. Tillage systems, such as flex-tine harrow (4.2 to 5.5 MJ ha−1), sweep cultivator (13 to 14 MJ ha−1), and rotary hoe (12 to 17 MJ ha−1) consumed the least energy of broadcast weed control treatments. Thermal-based approaches, including flaming (1,008 to 4,334 MJ ha−1) and infrared (2,000 to 3,887 MJ ha−1), are more appropriate for use in conservation cropping systems; however, their energy requirements are 100- to 1,000-fold greater than those of tillage treatments. The site-specific application of weed control treatments to control 2-leaf-stage broadleaf weeds at a density of 5 plants m−2 reduced energy consumption of herbicidal, thermal, and mechanical treatments by 97%, 99%, and 97%, respectively. Significantly, this site-specific approach resulted in similar energy requirements for current and alternative technologies (e.g., electrocution [15 to 19 MJ ha−1], laser pyrolysis [15 to 249 MJ ha−1], hoeing [17 MJ ha−1], and herbicides [15 MJ ha−1]). Using similar energy sources, a standardized energy comparison provides an opportunity for estimation of weed control costs, suggesting site-specific weed management is critical in the economically realistic implementation of alternative technologies.
The intensely active 2017 Atlantic basin hurricane season provided an opportunity to examine how climate drivers, including warming oceans and rising seas, exacerbated tropical cyclone hazards. The season also highlighted the unique vulnerabilities of populations residing on Small Island Developing States (SIDS) to the catastrophic potential of these storms. During 2017, 22 of the 29 Caribbean SIDS were affected by at least one named storm, and multiple SIDS experienced extreme damage. This paper aims to review the multiplicity of storm impacts on Caribbean SIDS throughout the 2017 season, to explicate the influences of climate drivers on storm formation and intensity, to explore the propensity of SIDS to sustain severe damage and prolonged disruption of essential services, to document the spectrum of public health consequences, and to delineate the daunting hurdles that challenged emergency response and recovery operations for island-based, disaster-affected populations. (Disaster Med Public Health Preparedness. 2019;13:5–17)
Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TGs) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations.
Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models.
Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51–2.77, I2 = 45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies.
Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.
Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.
We present polarimetric observations of the 4 ground-state transitions of OH, toward a sample of maser-emitting planetary nebulae (PNe) using the Australia Telescope Compact Array. This sample includes confirmed OH-emitting PNe, confirmed and candidate H2O-maser-emitting PNe. Polarimetric observations provide information related to the magnetic field of these sources. Maser-emitting PNe are very young PNe and magnetic fields are a key ingredient in the early evolution and shaping process of PNe. Our preliminary results suggest that magnetic field strengths may change very rapidly in young PNe.
Four ground-state OH transitions were detected in emission, absorption and maser emission in the Southern Parkes Large-Area Survey in Hydroxyl (SPLASH). We re-observed these OH masers with the Australia Telescope Compact Array to obtain positions with high accuracy (~1 arcsec). According to the positions, we categorised these OH masers into different classes, i.e. star formation, evolved stars, supernova remnants and unknown origin. We found one interesting OH maser source (G336.644-0.695) in the pilot region, which has been studied in detail in Qiao et al. (2016a). In this paper, we present the current stage of the ATCA follow-up for SPLASH and discuss the potential future researches derived from the ATCA data.
We report on interferometric observations of a face-on accretion system around the high mass young stellar object, G353.273+0.641. The innermost accretion system of 100-au radius was resolved in a 45-GHz continuum image taken with the Jansky Very Large Array. Our SED analysis indicated that the continuum could be explained by optically-thick dust emission. 6.7 GHz CH3OH masers associated with the same system were also observed with the Australia Telescope Compact Array. The masers showed a spiral-like, non-axisymmetric distribution with a systematic velocity gradient. The line-of-sight velocity field is explained by an infall motion along a parabolic streamline that falls onto the equatorial plane of the face-on system. The streamline is quasi-radial and reaches the equatorial plane at a radius of 16 au. The physical origin of such a streamline is still an open question and will be constrained by the higher-resolution thermal continuum and line observations with ALMA long baselines.
We sought to evaluate the first-in-man use of a new system for implantation of covered stents in patients with complex structural and CHD.
Methods and results
Retrospective data were collected of the first 13 NuDEL™ delivery systems used in patients. The NuDEL™ comprises a covered Cheatham-Platinum stent mounted on a balloon-in-balloon and pre-loaded in a long delivery sheath. Data were collected from three centres in the United Kingdom and Ireland. A total of 13 covered stents were delivered via 12 NuDEL™ delivery systems in 12 patients. Among them, six patients had coarctation of the aorta, five patients had right ventricular outflow tract stenosis, and one patient had severe stenosis of a Mustard systemic venous baffle. There were no complications, and all the stents were deployed in the desired position with satisfactory haemodynamic results.
The development of a bespoke system of a pre-mounted, pre-loaded covered stent may negate some of the technical challenges that complicate large-calibre stent deployment. Our preliminary results suggest that the NuDEL™ system is a safe and effective means of covered stent deployment in challenging anatomy.
Open-water swimming is increasingly popular, often in water not considered safe for bathing. Limited evidence exists on the associated health risks. We investigated gastrointestinal illness in 1100 swimmers in a River Thames event in London, UK, to describe the outbreak and identify risk factors. We conducted a retrospective cohort study. Our case definition was swimmers with any: diarrhoea, vomiting, abdominal cramps lasting ⩾48 h, nausea lasting ⩾48 h, with onset within 9 days after the event. We used an online survey to collect information on symptoms, demographics, pre- and post-swim behaviours and open-water experience. We tested associations using robust Poisson regression. We followed up case microbiological results. Survey response was 61%, and attack rate 53% (338 cases). Median incubation period was 34 h and median symptom duration 4 days. Five cases had confirmed microbiological diagnoses (four Giardia, one Cryptosporidium). Wearing a wetsuit [adjusted relative risk (aRR) 6·96, 95% confidence interval (CI) 1·04–46·72] and swallowing water (aRR 1·42, 95% CI 1·03–1·97) were risk factors. Recent river-swimming (aRR 0·78, 95% CI 0·67–0·92) and age >40 years (aRR 0·83, 95% CI 0·70–0·98) were protective. Action to reduce risk of illness in future events is recommended, including clarification of oversight arrangements for future swims to ensure appropriate risk assessment and advice is provided.
The free shear layer that separates from the leading edge of a round-nosed plate has been studied under conditions of low (background) and elevated (grid-generated) free stream turbulence (FST) using high-fidelity particle image velocimetry. Transition occurs after separation in each case, followed by reattachment to the flat surface of the plate downstream. A bubble of reverse flow is thereby formed. First, we find that, under elevated (7 %) FST, the time-mean bubble is almost threefold shorter due to an accelerated transition of the shear layer. Quadrant analysis of the Reynolds stresses reveals the presence of slender, highly coherent fluctuations amid the laminar part of the shear layer that are reminiscent of the boundary-layer streaks seen in bypass transition. Instability and the roll-up of vortices then follow near the crest of the shear layer. These vortices are also present under low FST and in both cases are found to make significant contributions to the production of Reynolds stress over the rear of the bubble. But their role in reattachment, whilst important, is not yet fully clear. Instantaneous flow fields from the low-FST case reveal that the bubble of reverse flow often breaks up into two or more parts, thereby complicating the overall reattachment process. We therefore suggest that the downstream end of the ‘separation isoline’ (the locus of zero absolute streamwise velocity that extends unbroken from the leading edge) be used to define the instantaneous reattachment point. A histogram of this point is found to be bimodal: the upstream peak coincides with the location of roll-up, whereas the downstream mode may suggest a ‘flapping’ motion.
Very preterm birth (VPT; <32 weeks of gestation) has been associated with impairments in emotion regulation, social competence and communicative skills. However, the neuroanatomical mechanisms underlying such impairments have not been systematically studied. Here we investigated the functional integrity of the amygdala connectivity network in relation to the ability to recognize emotions from facial expressions in VPT adults.
Thirty-six VPT-born adults and 38 age-matched controls were scanned at rest in a 3-T MRI scanner. Resting-state functional connectivity (rs-fc) was assessed with SPM8. A seed-based analysis focusing on three amygdalar subregions (centro-medial/latero-basal/superficial) was performed. Participants’ ability to recognize emotions was assessed using dynamic stimuli of human faces expressing six emotions at different intensities with the Emotion Recognition Task (ERT).
VPT individuals compared to controls showed reduced rs-fc between the superficial subregion of the left amygdala, and the right posterior cingulate cortex (p = 0.017) and the left precuneus (p = 0.002). The VPT group further showed elevated rs-fc between the left superficial amygdala and the superior temporal sulcus (p = 0.008). Performance on the ERT showed that the VPT group was less able than controls to recognize anger at low levels of intensity. Anger scores were significantly associated with rs-fc between the superficial amygdala and the posterior cingulate cortex in controls but not in VPT individuals.
These findings suggest that alterations in rs-fc between the amygdala, parietal and temporal cortices could represent the mechanism linking VPT birth and deficits in emotion processing.