The MACHO Project Large Magellanic Cloud Variable Star Inventory. VIII. The Recent Star Formation History of the LMC from the Cepheid Period Distribution

We present an analysis of the period distribution of $\sim 1800$ Cepheids in the Large Magellanic Cloud, based on data obtained by the MACHO microlensing experiment and on a previous catalogue by Payne-Gaposchkin. Using stellar evolution and pulsation models, we construct theoretical period-frequency distributions that are compared to the observations. These models reveal that a significant burst of star formation has occurred recently in the LMC ($\sim 1.15\times 10^8$ years). We also show that during the last $\sim 10^8$ years, the main center of star formation has been propagating from SE to NW along the bar. We find that the evolutionary masses of Cepheids are still smaller than pulsation masses by $\sim 7$ % and that the red edge of the Cepheid instability strip could be slightly bluer than indicated by theory. There are $\sim 600$ Cepheids with periods below $\sim 2.5$ days cannot be explained by evolution theory. We suggest that they are anomalous Cepheids; a number of these stars are double-mode Cepheids

Sex-specific relevance of diabetes to occlusive vascular and other mortality : a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies

Background: Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods: In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Findings: Individual participant-level data were analysed from 980793 adults. During 9 center dot 8 million person-years of follow-up, among participants aged between 35 and 89 years, 19686 (25 center dot 6%) of 76965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2 center dot 10, 95% CI 1 center dot 97-2 center dot 24) and tripled risk among women (3 center dot 00, 2 center dot 71-3 center dot 33; x(2) test for heterogeneity p<0 center dot 0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35-59 years: 2 center dot 60, 2 center dot 30-2 center dot 94) than in older individuals (aged 70-89 years: 2 center dot 01, 1 center dot 85-2 center dot 19; p=0 center dot 0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35-59 years had the highest death RR across all age and sex groups (5 center dot 55, 4 center dot 15-7 center dot 44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35-59 years, the excess absolute risk was 0 center dot 05% (95% CI 0 center dot 03-0 center dot 07) per year in women compared with 0 center dot 08% (0 center dot 05-0 center dot 10) per year in men; the corresponding excess at ages 70-89 years was 1 center dot 08% (0 center dot 84-1 center dot 3 2) per year in women and 0 center dot 91% (0 center dot 77-1 center dot 05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation: Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained

Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.

Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development

The Study of Ketamine for Youth Depression (SKY-D): study protocol for a randomised controlled trial of low-dose ketamine for young people with major depressive disorder

Background: Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD). Methods: SKY-D is a double-masked, randomised controlled trial funded by the Australian Government’s National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes. Discussion: Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people. Trial registration: Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513

Master's level in primary health care education - students' and preceptors' perceptions and experiences of the alteration in the clinical areas

Abstract Background Many Western European countries are undergoing reforms with changes in higher education according to the Bologna declaration for Higher European Education Area. In accordance with these changes, the Master's degree was introduced in specialist nurse education in Sweden in 2007, and as a result changed the curriculum and modified theoretical and clinical areas. The aim of this study was to investigate students' and preceptors' perceptions and experiences of Master's level education in primary health care with a focus on the clinical area. Methods A descriptive design and qualitative approach was used. Interviews with ten students and ten preceptors were performed twice, before and after the clinical practice period. Interviews were audio-recorded, transcribed verbatim and themes formulated. Results Students perceived alteration in the content of the education at the Master's level such as more independence and additional assignments. The preceptors perceived benefits with the Master's level but were unsure of how to transform theoretical and abstract knowledge into practice. Writing the Master's thesis was seen by students to take time away from clinical practice. For some students and preceptors the content of the Master's level clinical practice area was experienced as vague and indistinct. The students had not expected supervision to be different from earlier experiences, while preceptors felt higher demands and requested more knowledge. Both students and preceptors perceived that education at the Master's level might lead to a higher status for the nurses' profession in primary health care. Conclusions Students and preceptors experienced both advantages and disadvantages concerning the change in specialist nurse education in primary health care at the Master's level. The altered educational content was experienced as a step forward, but they also questioned how the new knowledge could be used in practice. The relevance of the Master's thesis was questioned. Supervision was seen by students as an introduction to the work of the district nurses' work. Preceptors perceived high demands and did not feel enough qualified for student supervision. Both groups considered it an advantage with the change in education that could result in higher status for nurses working in primary health care.</p

Influence of parental employment status on Dutch and Slovak adolescents' health

BACKGROUND: Recent research shows the possibility that the link between parental employment status and children's health can be affected by different cultural or societal settings. The aim of this study was to explore whether the effect of father's and mother's employment status on several aspects of adolescents' health differs between Slovakia and the Netherlands. METHODS: Two data sets were used: 2616 Slovak adolescents (mean age 14.9) and 2054 Dutch adolescents (mean age 16.3). Self-rated health, GHQ-12, long-term well-being and Rosenberg self-esteem scale were used to assess the health of adolescents. Parental employment status was classified into the following categories: employed, unemployed, disabled, housewife (among mothers only). Logistic regression analyses were done separately for males and females. RESULTS: Results indicate that having an unemployed father negatively influences self-rated health and long-term well-being of Slovak male adolescents, but has no effect on the health of Dutch adolescents. Secondly, having a disabled father has a negative effect on the psychological well-being of Dutch males and the self-rated health of females, but does not influence the health of Slovak adolescents. Thirdly, having a mother who is disabled, unemployed or a housewife has a negative effect on the self-esteem of Slovak adolescents. Fourthly, Dutch males whose mother was a housewife had worse long-term well-being than those with an unemployed mother, whereas Dutch females whose mother was a housewife reported better psychological well-being than those with an employed mother. CONCLUSION: To conclude briefly our results, father's unemployment seems to be a better predictor of health for Slovak adolescents, father's disablement of health for Dutch ones. Mother's employment status seemed to be important for the self-esteem of Slovak adolescents and mother as a housewife for the health of Dutch ones. This suggests that the link between parental employment status and the health of their children may vary between countries, and therefore further studies involving various cultures are needed

LI-RADS: A Conceptual and Historical Review from Its Beginning to Its Recent Integration into AASLD Clinical Practice Guidance

The Liver Imaging Reporting and Data System (LI-RADS®) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver observations in individuals at high risk for hepatocellular carcinoma (HCC). LI-RADS is supported and endorsed by the American College of Radiology (ACR). Upon its initial release in 2011, LI-RADS applied only to liver observations identified at CT or MRI. It has since been refined and expanded over multiple updates to now also address ultrasound-based surveillance, contrast-enhanced ultrasound for HCC diagnosis, and CT/MRI for assessing treatment response after locoregional therapy. The LI-RADS 2018 version was integrated into the HCC diagnosis, staging, and management practice guidance of the American Association for the Study of Liver Diseases (AASLD). This article reviews the major LI-RADS updates since its 2011 inception and provides an overview of the currently published LI-RADS algorithms

Trends and variation in mild disability and functional limitations among older adults in Norway, 1986–2008

An increase in the number of older adults may raise the demand for health and care services, whereas decreasing prevalence of disability and functional limitations among them might counteract this demographic effect. However, the trends in health are inconsistent between studies and countries. In this article, we estimated the trends in mild disability and functional limitations among older Norwegians and analyzed whether they differ between socio-demographic groups. Data were obtained from repeated cross-sectional surveys conducted in 1987, 1991, 1995, 2002, 2005, and 2008, in total 4,036 non-institutionalized persons aged 67 years or older. We analyzed trends using multivariate logistic regression. On average, the age-adjusted trend in functional limitations was −3.3% per year, and in disability 3.4% per year. The risk for functional limitations or disability was elevated for women compared to men, for married compared to non-married, and was inversely associated with educational level The trends were significantly weaker with increasing age for disabilities, whereas none of the trends differed significantly between subgroups of sexes, educational level or marital status. Both functional limitations free and disability-free life expectancy appeared to have increased more than total life expectancy at age 67 during this period. The analysis suggests downward trends in the prevalence of mild disability and functional limitations among older Norwegians between 1987 and 2008 and a compression of lifetime in such health states. The reduced numbers of older people with disability and functional limitations may have restrained the demand for health and care services caused by the increase in the number of older adults