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Identification of treatment-specific predictors of drug therapies for bipolar disorder (BD) is important because only about half of individuals respond to any specific medication. However, medication response in pediatric BD is variable and not well predicted by clinical characteristics.
A total of 121 youth with early course BD (acute manic/mixed episode) were prospectively recruited and randomized to 6 weeks of double-blind treatment with quetiapine (n = 71) or lithium (n = 50). Participants completed structural magnetic resonance imaging (MRI) at baseline before treatment and 1 week after treatment initiation, and brain morphometric features were extracted for each individual based on MRI scans. Positive antimanic treatment response at week 6 was defined as an over 50% reduction of Young Mania Rating Scale scores from baseline. Two-stage deep learning prediction model was established to distinguish responders and non-responders based on different feature sets.
Pre-treatment morphometry and morphometric changes occurring during the first week can both independently predict treatment outcome of quetiapine and lithium with balanced accuracy over 75% (all p < 0.05). Combining brain morphometry at baseline and week 1 allows prediction with the highest balanced accuracy (quetiapine: 83.2% and lithium: 83.5%). Predictions in the quetiapine and lithium group were found to be driven by different morphometric patterns.
These findings demonstrate that pre-treatment morphometric measures and acute brain morphometric changes can serve as medication response predictors in pediatric BD. Brain morphometric features may provide promising biomarkers for developing biologically-informed treatment outcome prediction and patient stratification tools for BD treatment development.
Mental health problems often begin in early childhood. However, the associations of various individual and contextual risk factors with mental health in the preschool period are incompletely understood, particularly in low- to middle-income countries (LMICs) where multiple risk factors co-exist. To address this gap, we prospectively followed 981 children in a South African birth cohort, the Drakenstein Child Health Study, assessing pre-and postnatal exposures and risk factors. The predictive value of these factors for child mental health (assessed by the Child Behavior Checklist) was modeled using structural equation modeling. We identified two key pathways to greater externalizing behavior: (1) prenatal exposure to substances (alcohol and smoking) directly predicted increased externalizing behavior (β = 0.24, p < 0.001); this relationship was partially mediated by an aspect of infant temperament (negative emotionality; β = 0.05, p = 0.016); (2) lower socioeconomic status and associated maternal prenatal depression predicted more coercive parenting, which in turn predicted increased externalizing behavior (β = 0.18, p = 0.001). Findings in this high-risk LMIC cohort cohere with research from higher income contexts, and indicate the need to introduce integrated screening and intervention strategies for maternal prenatal substance use and depression, and promoting positive parenting across the preschool period.
Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, n-3 long-chain PUFA (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Using a two-by-two design, uninfected mice were conditioned on either an n-3 PUFA-sufficient (n-3FAS) or -deficient (n-3FAD) diet for 6 weeks. One week post-infection, mice were randomised to either n-3 LCPUFA supplemented (n-3FAS/n-3+ and n-3FAD/n-3+) or continued on n-3FAS or n-3FAD diets for 3 weeks. Mice were euthanised and fatty acid status, lung bacterial load and pathology, cytokine, lipid mediator and immune cell phenotype analysed. n-3 LCPUFA supplementation in n-3FAS mice lowered lung bacterial loads (P = 0·003), T cells (P = 0·019), CD4+ T cells (P = 0·014) and interferon (IFN)-γ (P < 0·001) and promoted a pro-resolving lung lipid mediator profile. Compared with n-3FAS mice, the n-3FAD group had lower bacterial loads (P = 0·037), significantly higher immune cell recruitment and a more pro-inflammatory lipid mediator profile, however, significantly lower lung IFN-γ, IL-1α, IL-1β and IL-17, and supplementation in the n-3FAD group provided no beneficial effect on lung bacterial load or inflammation. Our study provides the first evidence that n-3 LCPUFA supplementation has antibacterial and inflammation-resolving benefits in TB when provided 1 week after infection in the context of a sufficient n-3 PUFA status, whilst a low n-3 PUFA status may promote better bacterial control and lower lung inflammation not benefiting from n-3 LCPUFA supplementation.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
We critically review potential involvement of trimethylamine N-oxide (TMAO) as a link between diet, the gut microbiota and CVD. Generated primarily from dietary choline and carnitine by gut bacteria and hepatic flavin-containing mono-oxygenase (FMO) activity, TMAO could promote cardiometabolic disease when chronically elevated. However, control of circulating TMAO is poorly understood, and diet, age, body mass, sex hormones, renal clearance, FMO3 expression and genetic background may explain as little as 25 % of TMAO variance. The basis of elevations with obesity, diabetes, atherosclerosis or CHD is similarly ill-defined, although gut microbiota profiles/remodelling appear critical. Elevated TMAO could promote CVD via inflammation, oxidative stress, scavenger receptor up-regulation, reverse cholesterol transport (RCT) inhibition, and cardiovascular dysfunction. However, concentrations influencing inflammation, scavenger receptors and RCT (≥100 µm) are only achieved in advanced heart failure or chronic kidney disease (CKD), and greatly exceed pathogenicity of <1–5 µm levels implied in some TMAO–CVD associations. There is also evidence that CVD risk is insensitive to TMAO variance beyond these levels in omnivores and vegetarians, and that major TMAO sources are cardioprotective. Assessing available evidence suggests that modest elevations in TMAO (≤10 µm) are a non-pathogenic consequence of diverse risk factors (ageing, obesity, dyslipidaemia, insulin resistance/diabetes, renal dysfunction), indirectly reflecting CVD risk without participating mechanistically. Nonetheless, TMAO may surpass a pathogenic threshold as a consequence of CVD/CKD, secondarily promoting disease progression. TMAO might thus reflect early CVD risk while providing a prognostic biomarker or secondary target in established disease, although mechanistic contributions to CVD await confirmation.
This report is on the synthesis by electrospinning of multiferroic core-shell nanofibers of strontium hexaferrite and lead zirconate titanate or barium titanate and studies on magneto-electric (ME) coupling. Fibers with well-defined core–shell structures showed the order parameters in agreement with values for nanostructures. The strength of ME coupling measured by the magnetic field-induced polarization showed the fractional change in the remnant polarization as high as 21%. The ME voltage coefficient in H-assembled films showed the strong ME response for the zero magnetic bias field. Follow-up studies and potential avenues for enhancing the strength of ME coupling in the core–shell nanofibers are discussed.
Many MRI studies have cited major depression, with or without anti-depressive treatment, associated with structural plasticity changing in several brain regions. Few of these studies researched the effect of the anti-depressive treatment, electroconvulsive therapy (ECT), on depression.
To assess the influence of ECT on the brain structure change during the treatment process by utilizing the voxel-based morphometry (VBM) analysis.
To determine whether ECT alter brain structure.
We performed HAMD ratings and MRI scans on 12 depressive patients during ECT, analyzing the data by VBM with SPM8 software's family-wise error correction (FWE).
The researchers found volumes changes in white matter in 37 regions between pre-ECT and post-ECT1, but only one region changing between pre-ECT and post-ECT8. Seven regions changing in grey matter between pre-ECT and post-ECT 1⌧but none regions changing between pre-ECT and post-ECT8.
The density changes in several brain regions after a single ECT stimuli, but return to the original level after completing the eighth ECT. Our finding supports that ECT may play a temporary role in treating major depression but do not permanently alter the structures of brain.
The Department of Health in the UK wants the National Health Service to make £20 Billion worth of efficiency savings by 2015 to reinvest.
In the UK the General Hospitals use paper records which are then scanned to create electronic records while Psychiatric Hospitals require that information to be typed on to their electronic records and these electronic records are not available to each other.
Therefore liaison psychiatry assessments require a written entry to be made in the Medical notes and a second entry typed on to the psychiatric electronic patient record which requires a full psychiatric history.
This duplication in typing information was consuming a considerable amount of this Teams time and resources which could have instead been spent with patients.
To identify how much time is spent by Staff typing information on to the psychiatric electronic patient records.
We electronically checked for the preceding three months the amount of time spent typing information on to the electronic records after every liaison psychiatry assessment.
We were then able to obtain the average for every week.
On average about 36 to 40 hours were spent every week typing information on to the electronic records.
Liaison Psychiatry should dispense with the requirement for information to be duplicated on to the electronic patient records and should instead scan the written entry made in the Medical notes.
This should lead to a saving of about £50,000, enough to employ an additional member of Staff every week.
The present study examined empathy deficits in toddlerhood (age 14 to 36 months) as predictors of antisocial personality disorder (ASPD) symptoms and psychopathy measured by the Levenson Self-Report Psychopathy scale (Levenson, Kiehl, & Fitzpatrick, 1995) in adulthood (age 23 years) in 956 individuals from the Colorado Longitudinal Twin Study. Consistent with the hypothesis that antisocial behavior is associated with “active” rather than “passive” empathy deficits, early disregard for others, not lack of concern for others, predicted later ASPD symptoms. Early disregard for others was also significantly associated with factor 1 of the Levenson Self-Report Psychopathy Scale, which includes items assessing interpersonal and affective deficits, but not with factor 2, which includes items assessing impulsivity and poor behavioral control. The association between early disregard for others and psychopathy factor 2 was near zero after controlling for the shared variance between psychopathy factors 1 and 2. These results suggest that there is a propensity toward adulthood ASPD symptoms and psychopathy factor 1 that can be assessed early in development, which may help identify individuals most at risk for stable antisocial outcomes.
Experimental and simulation data [Moreau et al., Plasma Phys. Control. Fusion 62, 014013 (2019); Kaymak et al., Phys. Rev. Lett. 117, 035004 (2016)] indicate that self-generated magnetic fields play an important role in enhancing the flux and energy of relativistic electrons accelerated by ultra-intense laser pulse irradiation with nanostructured arrays. A fully relativistic analytical model for the generation of the magnetic field based on electron magneto-hydrodynamic description is presented here. The analytical model shows that this self-generated magnetic field originates in the nonparallel density gradient and fast electron current at the interfaces of a nanolayered target. A general formula for the self-generated magnetic field is found, which closely agrees with the simulation scaling over the relevant intensity range. The result is beneficial to the experimental designs for the interaction of the laser pulse with the nanostructured arrays to improve laser-to-electron energy coupling and the quality of forward hot electrons.
In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters.
Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups.
Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive.
In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.
The aim of this retrospective review was to assess the overall burden and trend in spinal tuberculosis (TB) at tertiary hospitals in the Western Cape Province of South Africa. All spinal TB cases seen at the province's three tertiary hospitals between 2012 and 2015 were identified and clinical records of each case assessed. Cases were subsequently classified as bacteriologically confirmed or clinically diagnosed and reported with accompanying clinical and demographic information. Odds ratios (OR) for severe spinal disease and corrective surgery in child vs. adult cases were calculated. A total of 393 cases were identified (319 adults, 74 children), of which 283 (72%) were bacteriologically confirmed. Adult cases decreased year-on-year (P = 0.04), however there was no clear trend in child cases. Kyphosis was present in 60/74 (81%) children and 243/315 (77%) adults with available imaging. Corrective spinal surgery was performed in 35/74 (47%) children and 80/319 (25%) adults (OR 2.7, 95% confidence interval 1.6–4.5, P = 0.0003). These findings suggest that Western Cape tertiary hospitals have experienced a substantial burden of spinal TB cases in recent years with a high proportion of severe presentation, particularly among children. Spinal TB remains a public health concern with increased vigilance required for earlier diagnosis, especially of child cases.
The effects of obesity on reproduction have been widely reported in humans and mice. The present study was designed to compare the reproductive performance of lean and fat chicken lines, divergently selected for abdominal fat content. The following parameters were determined and analyzed in the two lines: (1) reproductive traits, including age at first egg and total egg numbers from generations 14 to 18, absolute and relative testicular weights at 7, 14, 25, 30, 45 and 56 weeks of age, semen quality at 30, 45 and 56 weeks of age in generation 18, and fertility and hatchability from generations 14 to 18; (2) reproductive hormones at 7, 14, 25, 30, 45 and 56 weeks of age in generation 18; (3) and the relative mRNA abundance of genes involved in reproduction at 7, 14, 25, 30, 45 and 56 weeks of age in generation 18. In females, birds in the lean line laid more eggs from the first egg to 40 weeks of age than the birds in the fat line. In male broilers, the birds in the lean line had higher absolute and relative testicular weights at 7, 14 and 25 weeks of age, but lower absolute and relative testicular weights at 56 weeks of age than the birds in the fat line. Male birds in the lean line had greater sperm concentrations and larger numbers of motile and morphologically normal sperms at 30, 45 and 56 weeks of age than the birds in the fat line. Fertility and hatchability were also higher in the lean line than in the fat line. Significant differences in the plasma levels of reproductive hormones and the expression of reproduction-associated genes were also found at different ages in the lean and fat birds, in both males and females. These results suggest that reproductive performance is better in lean birds than in fat birds. In view of the unique divergent lines used in this study, these results imply that selecting for abdominal fat deposition negatively affects the reproductive performance of birds.
An outbreak of respiratory diphtheria occurred in two health districts in the province of KwaZulu-Natal in South Africa in 2015. A multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. Fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. Of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. The case fatality was 27%. Ninety-three household contacts, 981 school or work contacts and 595 healthcare worker contacts were identified and given prophylaxis against Corynebacterium diphtheriae infection. A targeted vaccination campaign for children aged 6–15 years was carried out at schools in the two districts. The outbreak highlighted the need to improve diphtheria vaccination coverage in the province and to investigate the feasibility of offering diphtheria vaccines to healthcare workers.
Retreatment of tuberculosis (TB) often fails in China, yet the risk factors associated with the failure remain unclear. To identify risk factors for the treatment failure of retreated pulmonary tuberculosis (PTB) patients, we analyzed the data of 395 retreated PTB patients who received retreatment between July 2009 and July 2011 in China. PTB patients were categorized into ‘success’ and ‘failure’ groups by their treatment outcome. Univariable and multivariable logistic regression were used to evaluate the association between treatment outcome and socio-demographic as well as clinical factors. We also created an optimized risk score model to evaluate the predictive values of these risk factors on treatment failure. Of 395 patients, 99 (25·1%) were diagnosed as retreatment failure. Our results showed that risk factors associated with treatment failure included drug resistance, low education level, low body mass index (<18·5), long duration of previous treatment (>6 months), standard treatment regimen, retreatment type, positive culture result after 2 months of treatment, and the place where the first medicine was taken. An Optimized Framingham risk model was then used to calculate the risk scores of these factors. Place where first medicine was taken (temporary living places) received a score of 6, which was highest among all the factors. The predicted probability of treatment failure increases as risk score increases. Ten out of 359 patients had a risk score >9, which corresponded to an estimated probability of treatment failure >70%. In conclusion, we have identified multiple clinical and socio-demographic factors that are associated with treatment failure of retreated PTB patients. We also created an optimized risk score model that was effective in predicting the retreatment failure. These results provide novel insights for the prognosis and improvement of treatment for retreated PTB patients.
Dilated cardiomyopathy in children causes heart failure and has a poor prognosis. Health-related quality of life in this patient group is unknown. Moreover, results may provide detailed information of parents’ sense of their child’s functioning. We hypothesised that health-related quality of life, as rated by parents, and the paediatric heart failure score, as assessed by physicians, have both predictive value on outcome.
Methods and results
In this prospective study, health-related quality of life was assessed by parent reports: the Infant Toddler Quality of Life questionnaire (0–4 years) or Child Health Questionnaire-Parent Form 50 (4–18 years) at 3–6-month intervals. We included 90 children (median age 3.8 years, interquartile range (IQR) 0.9–12.3) whose parents completed 515 questionnaires. At the same visit, physicians completed the New York University Pediatric Heart Failure Index. Compared with Dutch normative data, quality of life was severely impaired at diagnosis (0–4 years: 7/10 subscales and 4–18 years: 8/11 subscales) and ⩾1 year after diagnosis (3/10 and 6/11 subscales). Older children were more impaired (p<0.05). After a median follow-up of 3 years (IQR 2–4), 15 patients underwent transplantation. Using multivariable time-dependent Cox regression, “physical functioning” subscale and the Heart Failure Index were independently predictive of the risk of death and heart transplantation (hazard ratio 1.24 per 10% decrease of predicted, 95% confidence interval (CI) 1.06–1.47 and hazard ratio 1.38 per unit, 95% CI 1.19–1.61, respectively).
Physical impairment rated by parents and heart failure severity assessed by physicians independently predicted the risk of death or heart transplantation in children with dilated cardiomyopathy.
Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia.
A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).
Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB.
IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.