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Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
Fermented feeds are being considered as practical alternatives to antimicrobial growth promoters (AGP) supplemented in nursery pig diets. This study aimed to investigate health-promoting effects of fermented barley in weaned pigs challenged with Escherichia coli K88 +. A total of 37 piglets were weaned at 21 ± 1 day of age (6.41 ± 0.47 kg of BW) and assigned to either of the following five treatment groups: (1) unchallenged control (UCC; n = 7), (2) challenged control (CC; n = 7), (3) AGP (CC + 0.1% AGP; n = 7), (4) Ferm1 (challenged and fed homofermentative Lactobacillus plantarum (Homo)-fermented barley; n = 8) and (5) Ferm2 (challenged and fed heterofermentative L. buchneri (Hetero)-fermented barley; n = 8). The control diet included unfermented barley. Barley was fermented with either Homo or Hetero for 90 days under anaerobic conditions. On day 10, all pigs except those in UCC group were orally inoculated with E. coli K88 + (6 × 109 colony forming units/ml). The pre-planned orthogonal test was performed to compare (1) UCC and CC, (2) CC and AGP, (3) CC and Ferm1 + Ferm2, as well as (4) Ferm1 and Ferm2. Challenged control pigs showed shorter (P < 0.05) villus height (VH) in the duodenum and deeper (P < 0.05) crypt depth (CD) in the jejunum than UCC pigs. The AGP group had higher (P < 0.05) VH and lower (P < 0.05) IL-6 gene expression in the jejunum compared with CC group. Compared to CC, Ferm1 and Ferm2 had decreased (P < 0.05) CD in the duodenum, IL-6 gene expression in the jejunum and rectal temperature at 24 h post-challenge. Pigs fed fermented barley diets showed greater (P < 0.05) faecal abundance of Clostridium Cluster IV and Lactobacilli than those fed UCC diet. Ferm2-fed pigs showed lower (P < 0.05) concentrations of band cells, eosinophils and lymphocytes at 6, 24 and 48 h after challenge, respectively, and lower (P < 0.05) faecal abundance of Enterobacteriaceae 24 h after challenge than the Ferm1-fed pigs. In conclusion, the substitution of unfermented barley with fermented barley in a nursery diet showed similar results as those shown by AGP supplementation in terms of enhancing the intestinal morphology and modulating faecal microbiota composition, as well as down-regulating the pro-inflammatory cytokines; therefore, fermented barley can be a possible nutritional strategy for managing nursery pigs fed diets without in-feed AGP.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Infrared signal measurements from a micro-turbojet engine are conducted to understand the characteristics of the engine performance and the infrared signal by varying the exhaust nozzle configuration. A cone type nozzle and five rectangle type nozzles whose aspect ratios vary from one to five are used for this experimental work. As a result, it is confirmed that the thrust and the fuel consumption rate of the engine do not change greatly by varying the exhaust nozzle shape. In the case of the aspect ratio of 5, the specific fuel consumption of the engine is increased by about 3% compared to the reference cone nozzle, but the infrared signal can be reduced by up to 14%. As a result of measuring the temperature distribution of the plume gas, the correlation of infrared signal with plume gas temperature distribution can be understood. In the case of a cone shape, the distribution of plume gas formed to circular shape, and the high-temperature core region of plume gas continued to develop farther to the downstream. However, the temperature distribution was maintained in the rectangular shape as the aspect ratio increased, and the average temperature decreased sharply. As the aspect ratio increases, the plume spreads more widely.
This study of loneliness across adult lifespan examined its associations with sociodemographics, mental health (positive and negative psychological states and traits), subjective cognitive complaints, and physical functioning.
Analysis of cross-sectional data
340 community-dwelling adults in San Diego, California, mean age 62 (SD = 18) years, range 27–101 years, who participated in three community-based studies.
Loneliness measures included UCLA Loneliness Scale Version 3 (UCLA-3), 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Social Isolation Scale, and a single-item measure from the Center for Epidemiologic Studies Depression (CESD) scale. Other measures included the San Diego Wisdom Scale (SD-WISE) and Medical Outcomes Survey- Short form 36.
Seventy-six percent of subjects had moderate-high levels of loneliness on UCLA-3, using standardized cut-points. Loneliness was correlated with worse mental health and inversely with positive psychological states/traits. Even moderate severity of loneliness was associated with worse mental and physical functioning. Loneliness severity and age had a complex relationship, with increased loneliness in the late-20s, mid-50s, and late-80s. There were no sex differences in loneliness prevalence, severity, and age relationships. The best-fit multiple regression model accounted for 45% of the variance in UCLA-3 scores, and three factors emerged with small-medium effect sizes: wisdom, living alone and mental well-being.
The alarmingly high prevalence of loneliness and its association with worse health-related measures underscore major challenges for society. The non-linear age-loneliness severity relationship deserves further study. The strong negative association of wisdom with loneliness highlights the potentially critical role of wisdom as a target for psychosocial/behavioral interventions to reduce loneliness. Building a wiser society may help us develop a more connected, less lonely, and happier society.
Concentrations of total organic carbon (TOC), total petroleum hydrocarbons, polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were determined in 84 near-surface soils (5–20cm depth) taken from a 255km2 area of Glasgow in the Clyde Basin, UK, during July 2011. Total petroleum hydrocarbon range was 79–2,505mgkg–1 (mean 388mgkg–1; median 272mgkg–1) of which the aromatic fraction was 13–74 % (mean 44 %, median 43 %) and saturates were 28–87 % (mean 56 %, median 57 %). ∑16 PAH varied from 2–653mgkg–1 (mean 32.4mgkg–1; median 12.5mgkg–1) and ∑31 PAH range was 2.47–852mgkg–1 (mean 45.4mgkg–1; median 19.0mgkg–1). ∑PCBtri-hepta range was 2.2–1052μgkg–1 (mean 32.4μgkg–1; median 12.7μgkg–1) and the ∑PCB7 range was 0.3–344μgkg–1 (mean 9.8μgkg–1; median 2.7μgkg–1). The concentration, distribution and source of the persistent organic pollutants were compared with those found in urban soils from other cities and to human health assessment criteria for chronic exposure to chemicals in soil. Total concentrations encountered were generally similar to other urban areas that had a similar industrial history. Benzo[a]pyrene concentrations were assessed against four different land use scenarios (irrespective of current land use) using generic assessment criteria resulting in six of 84 samples exceeding the residential criteria. Isomeric PAH ratios and relative abundance of perylene suggest multiple and environmentally modified pyrogenic PAH sources, inferred to be representative of diffuse pollution. ∑PCB7 concentrations were exceeded in 10 % of sites using the Dutch target value of 20μgkg–1. PCB congener profiles were environmentally attenuated and generally dominated by penta-, hexa- and hepta-chlorinated congeners.
Surface sediments from a 160-km stretch of the River Clyde, Scotland, were analysed for persistent organic pollutants to investigate distribution, source and environmental effect. Glasgow's urban tributaries polyaromatic hydrocarbons (PAH) ranged from 2.3 to 4226mgkg–1, total petroleum hydrocarbons (TPH) 72 to 37879mgkg–1 and polychlorinated biphenyls (PCB) 3 to 809μgkg–1, which were more polluted than the upper River Clyde PAH that ranged from 0.1 to 42mgkg–1, TPH 3 to 260mgkg–1 and PCB 2 to 147μgkg–1. Intermediate values of the inner Clyde estuary PAH ranging from 0.6 to 30mgkg–1, and PCB ranging from 5 to 130μgkg–1, were attributed to point sources and sediment transfer from the urban tributaries. Comparison with sediment quality criteria suggested possible adverse effects on aquatic biota. PAH isomeric ratios confirmed a pyrolytic source throughout the Clyde and benzo[a]pyrene/benzo[g,h,i]perylene ratios >0.6 confirmed that upper, urban and estuarine domains all to a lesser or greater extent accumulated PAH from traffic emissions. The degree of chlorination determined from PCB homologues differed in each of the three domains, suggesting variable source or that the process aerobic/anaerobic degradation varied in each of the three domains. The anthropogenic impact of the city of Glasgow can be quantified in that the urban tributary sediment mean values were 60 (PAH), 33 (TPH) and 11 (PCB) times higher than the rural upper Clyde counterpart.
Surface sediments (n=85) from a 160-km river-estuarine transect of the Clyde, UK, were analysed for total mercury (Hg), saturated hydrocarbons and unresolved complex mixtures (UCMs) of hydrocarbons. Results show that sediment-Hg concentration ranges from 0.01 to 1.38mgkg–1 (mean 0.20mgkg–1) and a spatial trend in Hg-content low–high–low–high, from freshwater source, to Glasgow, to estuary, is evident. In summary, sediment-Hg content is low in the upper Clyde (mean of 0.05Hg mgkg–1), whereas sediments from the Clyde in urbanised Glasgow have higher Hg concentrations (0.04 to 1.26mgkg–1; mean 0.45mgkg–1), and the inner estuary sediments contain less Hg (mean 0.06mgkg–1). The highest mean sediment Hg (0.65mgkg–1) found in the outer estuary is attributed to historical anthropogenic activities. A significant positive Spearman correlation between Hg and total organic carbon is observed throughout the river estuary (0.86; P<0.001). Comparison with Marine Scotland guidelines suggests that no sites exceed the 1.5mgkg–1 criterion (Action Level 2); 22 fall between 0.25 and 1.5mgkg–1 dry wt. (Action Level 1) and 63 are of no immediate concern (<0.25mgkg–1 dry wt.). Saturated (n-alkane) hydrocarbons in the upper Clyde are of natural terrestrial origin. By contrast, the urbanised Glasgow reaches and outer estuary are characterised by pronounced and potentially toxic UCM concentrations in sediments (380–914mg/kg and 103–247mgkg–1, respectively), suggesting anthropogenic inputs such as biodegraded crude oil, sewage discharge and/or urban run-off.
Rising sea levels due to climate change can have severe consequences for coastal populations and ecosystems all around the world. Understanding and projecting sea-level rise is especially important for low-lying countries such as the Netherlands. It is of specific interest for vulnerable ecological and morphodynamic regions, such as the Wadden Sea UNESCO World Heritage region.
Here we provide an overview of sea-level projections for the 21st century for the Wadden Sea region and a condensed review of the scientific data, understanding and uncertainties underpinning the projections. The sea-level projections are formulated in the framework of the geological history of the Wadden Sea region and are based on the regional sea-level projections published in the Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5). These IPCC AR5 projections are compared against updates derived from more recent literature and evaluated for the Wadden Sea region. The projections are further put into perspective by including interannual variability based on long-term tide-gauge records from observing stations at Den Helder and Delfzijl.
We consider three climate scenarios, following the Representative Concentration Pathways (RCPs), as defined in IPCC AR5: the RCP2.6 scenario assumes that greenhouse gas (GHG) emissions decline after 2020; the RCP4.5 scenario assumes that GHG emissions peak at 2040 and decline thereafter; and the RCP8.5 scenario represents a continued rise of GHG emissions throughout the 21st century. For RCP8.5, we also evaluate several scenarios from recent literature where the mass loss in Antarctica accelerates at rates exceeding those presented in IPCC AR5.
For the Dutch Wadden Sea, the IPCC AR5-based projected sea-level rise is 0.07±0.06m for the RCP4.5 scenario for the period 2018–30 (uncertainties representing 5–95%), with the RCP2.6 and RCP8.5 scenarios projecting 0.01m less and more, respectively. The projected rates of sea-level change in 2030 range between 2.6mma−1 for the 5th percentile of the RCP2.6 scenario to 9.1mma−1 for the 95th percentile of the RCP8.5 scenario. For the period 2018–50, the differences between the scenarios increase, with projected changes of 0.16±0.12m for RCP2.6, 0.19±0.11m for RCP4.5 and 0.23±0.12m for RCP8.5. The accompanying rates of change range between 2.3 and 12.4mma−1 in 2050. The differences between the scenarios amplify for the 2018–2100 period, with projected total changes of 0.41±0.25m for RCP2.6, 0.52±0.27m for RCP4.5 and 0.76±0.36m for RCP8.5. The projections for the RCP8.5 scenario are larger than the high-end projections presented in the 2008 Delta Commission Report (0.74m for 1990–2100) when the differences in time period are considered. The sea-level change rates range from 2.2 to 18.3mma−1 for the year 2100.
We also assess the effect of accelerated ice mass loss on the sea-level projections under the RCP8.5 scenario, as recent literature suggests that there may be a larger contribution from Antarctica than presented in IPCC AR5 (potentially exceeding 1m in 2100). Changes in episodic extreme events, such as storm surges, and periodic (tidal) contributions on (sub-)daily timescales, have not been included in these sea-level projections. However, the potential impacts of these processes on sea-level change rates have been assessed in the report.
Angiostrongylus cantonensis (rat lungworm), a parasitic nematode, is expanding its distribution. Human infection, known as angiostrongyliasis, may manifest as eosinophilic meningitis, an emerging infectious disease. The range and incidence of this disease are expanding throughout the tropics and subtropics. Recently, the Hawaiian Islands have experienced an increase in reported cases. This study addresses factors affecting the parasite's distribution and projects its potential future distribution, using Hawaii as a model for its global expansion. Specimens of 37 snail species from the Hawaiian Islands were screened for the parasite using PCR. It was present on five of the six largest islands. The data were used to generate habitat suitability models for A. cantonensis, based on temperature and precipitation, to predict its potential further spread within the archipelago. The best current climate model predicted suitable habitat on all islands, with greater suitability in regions with higher precipitation and temperatures. Projections under climate change (to 2100) indicated increased suitability in regions with estimated increased precipitation and temperatures, suitable habitat occurring increasingly at higher elevations. Analogously, climate change could facilitate the spread of A. cantonensis from its current tropical/subtropical range into more temperate regions of the world, as is beginning to be seen in the continental USA.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
It has not been well established whether dietary folate intake reduces the risk of diabetes development. We aimed to clarify the prospective association between dietary folate intake and type 2 diabetes (T2D) risk among 7333 Korean adults aged 40 years or older who were included in the Multi-Rural Communities Cohort. Dietary folate intake was estimated from all 106 food items listed on a FFQ, not including folate intake from supplements. Two different measurements of dietary folate intake were used: the baseline consumption and the average consumption from baseline until just before the end of follow-up. The association between folate intake and T2D risk was determined through a modified Poisson regression model with a robust error estimator controlling for potential confounders. For 29 745 person years, 319 cases of diabetes were ascertained. In multivariable analyses, dietary folate intake was inversely associated with risk of T2D for women, not for men. For women, the incidence rate ratio of diabetes in the third tertile compared with the first tertile was 0·57 (95 % CI 0·38–0·87, Pfor trend=0·0085) in the baseline consumption model and 0·64 (95 % CI 0·43–0·95, Pfor trend=0·0244) in the average consumption model. These inverse associations was found in both normal fasting blood glucose group and impaired fasting glucose group among women. Among non-users of multinutrients and vitamin supplements, the significant inverse association remained. Thus, higher dietary intake of folate is prospectively associated with lower risk of diabetes for women.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
We present a photometric study of the stars in ionizing star clusters embedded in several giant H II regions of M33 (CC93, IC 142, NGC 595, MA2, NGC 604 and NGC 588). Our photometry is based on the HST-WFPC2 images of these clusters. Color-magnitude diagrams and color-color diagrams of these clusters are obtained and are used for estimating the reddenings and ages of the clusters. The luminosity functions (LFs) and initial mass functions (IMFs) of the massive stars in these clusters are also derived. The slopes of the IMFs range from Γ = −0.5 to −2.1. Interestingly, it is found that the IMFs get steeper with increasing galactocentric distance and with decreasing [O/H] abundance.
Anomalous aortic origin of the coronary arteries is associated with exercise-induced ischaemia, leading some physicians to restrict exercise in patients with this condition. We sought to determine whether exercise restriction was associated with increasing body mass index over time. From 1998 to 2015, 440 patients ⩽30 years old were enrolled into an inception cohort. Exercise-restriction status was documented in 143 patients. Using linear mixed model repeated-measures regression, factors associated with increasing body mass index z-score over time, including exercise restriction and surgical intervention as time-varying covariates, were investigated. The 143 patients attended 558 clinic visits for which exercise-restriction status was recorded. The mean number of clinic visits per patient was 4, and the median duration of follow-up was 1.7 years (interquartile range (IQR) 0.5–4.4). The median age at first clinic visit was 10.3 years (IQR 7.1–13.9), and 71% (101/143) were males. All patients were alive at their most recent follow-up. At the first clinic visit, 54% (78/143) were exercise restricted, and restriction status changed in 34% (48/143) during follow-up. The median baseline body mass index z-score was 0.2 (IQR 0.3–0.9). In repeated-measures analysis, neither time-related exercise restriction nor its interaction with time was associated with increasing body mass index z-score. Surgical intervention and its interaction with time were associated with decreasing body mass index z-score. Although exercise restriction was not associated with increasing body mass index over time, surgical intervention was associated with decreasing body mass index z-score over time in patients with anomalous aortic origin of the coronary arteries.