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Consumption of sugar-sweetened beverages (SSB) by infants and young children are less explored in Asian populations. The Growing Up in Singapore Towards healthy Outcomes cohort study examined associations between SSB intake at 18 months and 5 years of age, with adiposity measures at 6 years of age. We studied Singaporean infants/children with SSB intake assessed by FFQ at 18 months of age (n 555) and 5 years of age (n 767). The median for SSB intakes is 28 (interquartile range 5·5–98) ml at 18 months of age and 111 (interquartile range 57–198) ml at 5 years of age. Association between SSB intake (100 ml/d increments and tertile categories) and adiposity measures (BMI standard deviation scores (sd units), sum of skinfolds (SSF)) and overweight/obesity status were examined using multivariable linear and Poisson regression models, respectively. After adjusting for confounders and additionally for energy intake, SSB intake at age 18 months were not significantly associated with later adiposity measures and overweight/obesity outcomes. In contrast, at age 5 years, SSB intake when modelled as 100 ml/d increments were associated with higher BMI by 0·09 (95 % CI 0·02, 0·16) sd units, higher SSF thickness by 0·68 (95 % CI 0·06, 1·44) mm and increased risk of overweight/obesity by 1·2 (95 % CI 1·07, 1·23) times at age 6 years. Trends were consistent with SSB intake modelled as categorical tertiles. In summary, SSB intake in young childhood is associated with higher risks of adiposity and overweight/obesity. Public health policies working to reduce SSB consumption need to focus on prevention programmes targeted at young children.
Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.
Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.
This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = −0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = −0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10−8, 95% CI 7.0–14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.
This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.
The combined derivative method (accompanying paper) was tested with a large number of experimental patterns to illustrate its use in various difficult problems commonly arising in peak search analysis of X-ray diffraction data. Patterns obtained with various step sizes, resolution, counting statistical noise, and profile widths were used. The precision in 2θ determination and overlap resolution are in good agreement with those previously obtained from calculated profiles, raise identification of noise as diffraction peaks was eliminated by using a convolution range proportional to the full width at half maximum. Peak search results (both 2θ and intensity) were also compared to those obtained by profile fitting to illustrate the different characteristics of these two methods.
A method for resolving overlapping X-ray fluorescence spectra by curve fitting is described. The profile shape of an experimental fluorescence line obtained by wavelength dispersive method is represented by a simple pseudo-Voigt function, i.e. a sum of an asymmetric Gaussian and Lorentzian, each of equal width. Results showed that the pseudo-Voigt function matched the experimental profiles with high reliability. The relative Gaussian and Lorentzian contents and the asymmetry of the profiles depended upon the analyzing crystal, coliimating system and the 2θ peak position. For fixed crystal and collimator the smaller the 2θ, the larger the Gaussian content and the lower the asymmetry. The original Gaussian and Loretzian components of the exact Voigt function calculated from the parameters of the fitted pseudo-Voigt function explain the broadening effects of the X-ray emission lines and the instrumental aberrations on observed spectra. Curve fitting method with the psuedo- Voigt function has been used successfully to analyze overlapping fluorescence spectra. Examples and applications include a thin film sample where the Kα and the Kβ lines of adjacent transition elements overlap, and a strontium zirconium oxide specimen where the Zr Kα and the Sr Kβ lines strongly interfere. Concentrations obtained from the resolved individual peak intensities of Zr and Sr Kα lines are within ±1% of the true values.
With the increase in long-term survival of post-transplant children, there is a paradigm shift in the emphasis of post-transplant care. We describe de novo cardiovascular abnormalities, which occurred in otherwise asymptomatic paediatric liver transplant recipients, who received liver allografts between 1991 and 2014 at the National University Hospital, Singapore, detected during routine post-transplant monitoring. A total of 96 paediatric liver transplants were performed in 90 children. After transplant, 7/90 (7.8%) recipients were identified with new-onset aortopathy. Glycogen storage disease type I (42.9% versus 2.4%; p<0.001) and recipient Epstein-Barr virus seropositivity (85.7 versus 31.0%, p=0.004) were significant risk factors for aortopathy on univariate analysis. On multivariate analysis, only glycogen storage disease type I remained as the significant risk factor (odds ratio 51.3 [95% confidence intervals: 1.1–2498.1, p=0.047]). Liver transplant is a double-edged sword that reverses certain cardiopulmonary complications of end-stage liver disease but may induce de novo structural cardiac injury in the form of aortic dilation.
Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders.
In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments.
After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4).
PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
To complement our environmental scan of academic emergency medicine departments, we conducted a similar environmental scan of the academic pediatric emergency medicine programs offered by the Canadian medical schools.
We developed an 88-question form, which was distributed to pediatric academic leaders at each medical school. The responses were validated via email to ensure that the questions were answered completely and consistently.
Fourteen of the 17 Canadian medical schools have some type of pediatric emergency medicine academic program. None of the pediatric emergency medicine units have full departmental status, while nine are divisions, two are sections, and three have no status. Canadian academic pediatric emergency medicine is practised at 13 major teaching hospitals and one specialized pediatric emergency department. There are 394 pediatric emergency medicine faculty members, including 13 full professors and 64 associate professors. Eight sites regularly take pediatric undergraduate clinical clerks, and all 14 provide resident education. Fellowship training is offered at 10 sites, with five offering advanced pediatric emergency medicine fellowship training. Half of the sites have at least one physician with a Master’s degree in education, totalling 18 faculty members across Canada. There are 31 clinical researchers with salary support at nine universities. Eleven sites have published peer-reviewed papers (n=423) in the past five years, ranging from two to 102 per site. Annual academic budgets range from $10,000 to $2,607,515.
This comprehensive review of academic activities in pediatric emergency medicine across Canada identifies the variability across the country, including the recognition of sites above and below the national average, which may prompt change at individual sites. Sharing these academic practices may inspire sites to provide more support to teachers, educators, and researchers.
The patterns of comorbidity among mental disorders have led researchers to model the underlying structure of psychopathology. While studies have suggested a structure including internalizing and externalizing disorders, less is known with regard to the cross-national stability of this model. Moreover, little data are available on the placement of eating disorders, bipolar disorder and psychotic experiences (PEs) in this structure.
We evaluated the structure of mental disorders with data from the World Health Organization Composite International Diagnostic Interview, including 15 lifetime mental disorders and six PEs. Respondents (n = 5478–15 499) were included from 10 high-, middle- and lower middle-income countries across the world aged 18 years or older. Confirmatory factor analyses (CFAs) were used to evaluate and compare the fit of different factor structures to the lifetime disorder data. Measurement invariance was evaluated with multigroup CFA (MG-CFA).
A second-order model with internalizing and externalizing factors and fear and distress subfactors best described the structure of common mental disorders. MG-CFA showed that this model was stable across countries. Of the uncommon disorders, bipolar disorder and eating disorder were best grouped with the internalizing factor, and PEs with a separate factor.
These results indicate that cross-national patterns of lifetime common mental-disorder comorbidity can be explained with a second-order underlying structure that is stable across countries and can be extended to also cover less common mental disorders.
It is important to identify molecular candidates involved in morphological and functional changes in the female reproductive system. We have discovered several candidate genes that were significantly altered in chick oviducts by exogenous estrogen and those candidates included dexamethasone (DEX)-induced RAS-related protein 1 (RASD1). RAS-related protein 1, a member of the Ras family of monomeric G proteins, is involved in various cellular processes including cell growth, proliferation and differentiation, as well as a cell-signaling protein regulating hormonal actions. Although the RASD1 gene was first identified as a DEX (a corticosteroid) inducible gene, there is evidence that it is also an estrogen-responsive gene. However, hormone-mediated expression and biological functions of RASD1 in the avian female reproductive system are poorly understood. Therefore, we tested the hypothesis that RASD1 may be involved in the development and remodeling of the chicken reproductive system as an estrogen-responsive gene. Here we demonstrate differential expression of RASD1 gene and candidate microRNAs (miRNAs) targeting chicken RASD1 transcripts in chicken oviducts in response to diesthylstilbestrol (DES, a synthetic non-steroidal estrogen) and the estrogen-mediated molting process. Result of the present study indicated that expression of RASD1 messenger RNA (mRNA) increased in the developing oviducts of chicks treated with DES, particularly in the glandular (GE) and luminal (LE) epithelia of the magnum and the shell gland. Also, during induced molting by zinc feeding, RASD1 expression changed in concert with changes in concentrations of estrogen in blood of laying hens. Our results revealed that expression of RASD1 mRNA decreased as the oviduct regressed and then increased as the oviduct underwent re-growth and recrudescence in hens. Furthermore, RASD1 mRNA was expressed predominantly in GE and LE of the oviduct of laying hens during regeneration of the oviduct after induced molting, but not during the period of regression of the oviduct during molting. In addition, the relative expression of candidate miRNAs (miR-30a-5p, miR-30b-5p, miR-30c-5p and miR-30d) regulating RASD1 transcripts changed in response to estrogen stimulation of chick oviducts. These results indicate that transcription of the RASD1 gene and miRNAs regulating post-transcriptional aspects of expression of RASD1 are modulated by estrogen which is critical for growth, development, remodeling and maintenance of function of the chicken oviduct.
Subjective well-being incorporates elements of life satisfaction, happiness and optimism. It is increasingly relevant in the assessment of population health and economic development. There are strong continuities in well-being from youth into later life. Despite its significance, few global surveys capture subjective well-being. This paper describes patterns of well-being among young people in five Eastern European countries [Belarus, Bosnia and Herzegovina (BiH), the Former Yugoslav Republic of Macedonia, Serbia and Ukraine] and investigates association between demographic factors and well-being.
Nationally representative household surveys, including large Roma population samples, were conducted as part of UNICEF's Multiple Indicator Cluster Survey programme. Young people aged 15–24 years (N = 11 944) indicated their satisfaction with life, happiness and expectations about the future. Multilevel logistic regressions were conducted to determine the impact of individual-level predictors while accounting for country- and cluster-level variability.
Around 40% of young people considered themselves very happy or very satisfied with their life overall. Three quarters reported optimism. Yet well-being varied greatly between countries, with youth in BiH and Ukraine reporting lowest levels of well-being. Current marriage, increasing wealth, higher education, rural residence and not having children were associated with greater well-being.
Patterns of well-being in youth vary substantially between countries and are only partly accounted for by standard demographic characteristics. Despite higher rates of adolescent marriage and childbearing, and lower levels of educational attainment and employment, Roma youth had similar levels of well-being to the general population.
Islands are widely considered to be model systems for studying fundamental questions in ecology and evolutionary biology. The fundamental state factors that vary among island systems – geologic history, size, isolation and age – form the basis of mature phenomenological and predictive theory. In this review, we first highlight classic lines of inquiry that exemplify the historical and continuing importance of islands. We then show how the conceptual power of islands as ‘natural laboratories’ can be improved through functional classifications of both the biological properties of, and human impact on, insular systems. We highlight how global environmental change has been accentuated on islands, expressly because of their unique insular properties. We review five categories of environmental perturbation: climate change, habitat modification, direct exploitation, invasion and disease. Using an analysis of taxonomic checklists for the arthropod biotas of three well-studied island archipelagos, we show how taxonomists are meeting the challenge of biodiversity assessment before the biodiversity disappears. Our aim is to promote discussion on the tight correlations of the environmental health of insular systems to their continued importance as singular venues for discovery in ecology and evolutionary biology, as well as to their conservation significance as hotspots of endemism.
Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.
Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.
The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.
PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.
Although specific phobia is highly prevalent, associated with impairment, and an important risk factor for the development of other mental disorders, cross-national epidemiological data are scarce, especially from low- and middle-income countries. This paper presents epidemiological data from 22 low-, lower-middle-, upper-middle- and high-income countries.
Data came from 25 representative population-based surveys conducted in 22 countries (2001–2011) as part of the World Health Organization World Mental Health Surveys initiative (n = 124 902). The presence of specific phobia as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition was evaluated using the World Health Organization Composite International Diagnostic Interview.
The cross-national lifetime and 12-month prevalence rates of specific phobia were, respectively, 7.4% and 5.5%, being higher in females (9.8 and 7.7%) than in males (4.9% and 3.3%) and higher in high- and higher-middle-income countries than in low-/lower-middle-income countries. The median age of onset was young (8 years). Of the 12-month patients, 18.7% reported severe role impairment (13.3–21.9% across income groups) and 23.1% reported any treatment (9.6–30.1% across income groups). Lifetime co-morbidity was observed in 60.5% of those with lifetime specific phobia, with the onset of specific phobia preceding the other disorder in most cases (72.6%). Interestingly, rates of impairment, treatment use and co-morbidity increased with the number of fear subtypes.
Specific phobia is common and associated with impairment in a considerable percentage of cases. Importantly, specific phobia often precedes the onset of other mental disorders, making it a possible early-life indicator of psychopathology vulnerability.
Background: Radiotherapy with procarbazine, lomustine, and vincristine improves overall survival (OS) in patients with 1p19q co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma. Methods: This retrospective analysis investigated outcomes in patients with 1p19q co-deleted/partially deleted oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma. OS and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and prognostic factors using the Cox proportional hazard model. Results: A total of 106 patients (between December 1997 and December 2013) were included. Median age was 40 years (19-66), 58 were male (55%), Eastern Cooperative Oncology Group performance status was 0 in 80 patients (75%). 1p19q status was co-deleted in 66 (62%), incompletely co-deleted in 27 (25%), and 1p or 19q loss alone in four (4%) and nine (8%) patients, respectively. Isocitrate dehydrogenase-1 R132H mutation was found in 67 of 85 patients with sufficient material. Upfront treatment was given in 72 (68%) patients and temozolomide alone in 52 (49%). Median time to radiotherapy in 47 patients (44%) was 34.7 months and 41.2 months in 9 patients with co-deleted/incompletely co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma who received upfront temozolomide alone. Median OS was not reached and 5-year OS was 91% for all groups (median follow-up, 5.1 years). On multivariable analysis for all patients, receipt of therapy upfront versus none (p=0.04), PS 1 versus 0 (p<0.001) and 1p19q co-deletion/incomplete deletion versus 1p or 19q loss alone (p=0.005) were prognostic for PFS. Isocitrate dehydrogenase-1 status was not prognostic for PFS. Conclusions: With similar survival patterns in low-grade/anaplastic gliomas, molecular characteristics may be more important than histological grade. Longer follow-up and results of prospective trials are needed for definitive guidance on treatment of these patients.
Although there is robust evidence linking childhood adversities (CAs) and an increased risk for psychotic experiences (PEs), little is known about whether these associations vary across the life-course and whether mental disorders that emerge prior to PEs explain these associations.
We assessed CAs, PEs and DSM-IV mental disorders in 23 998 adults in the WHO World Mental Health Surveys. Discrete-time survival analysis was used to investigate the associations between CAs and PEs, and the influence of mental disorders on these associations using multivariate logistic models.
Exposure to CAs was common, and those who experienced any CAs had increased odds of later PEs [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.9–2.6]. CAs reflecting maladaptive family functioning (MFF), including abuse, neglect, and parent maladjustment, exhibited the strongest associations with PE onset in all life-course stages. Sexual abuse exhibited a strong association with PE onset during childhood (OR 8.5, 95% CI 3.6–20.2), whereas Other CA types were associated with PE onset in adolescence. Associations of other CAs with PEs disappeared in adolescence after adjustment for prior-onset mental disorders. The population attributable risk proportion (PARP) for PEs associated with all CAs was 31% (24% for MFF).
Exposure to CAs is associated with PE onset throughout the life-course, although sexual abuse is most strongly associated with childhood-onset PEs. The presence of mental disorders prior to the onset of PEs does not fully explain these associations. The large PARPs suggest that preventing CAs could lead to a meaningful reduction in PEs in the population.