Childhood bullying victimisation is associated with use of mental health services over five decades: a longitudinal nationally-representative cohort study

Background: Research supports robust associations between childhood bullying victimisation and mental health problems in childhood/adolescence and emerging evidence shows the impact can persist into adulthood. We examined the impact of bullying victimisation on mental health service use from childhood to midlife. Methods: We performed secondary analysis using the National Child Development Study, the 1958 British Birth Cohort study. We conducted analyses on 9,242 participants with complete data on childhood bullying victimisation and service use at midlife. We used multivariable logistic regression models to examine associations between childhood bullying victimisation and mental health service use ages 16, 23, 33, 42 and 50. We estimated incidence and persistence of mental health service use over time to age 50. Results: Compared to participants who were not bullied in childhood, those who were frequently bullied were more likely to use mental health services in childhood and adolescence (OR: 2.53, 95% CI: 1.88, 3.40), and also in midlife (OR: 1.30, 95% CI: 1.10, 1.55). Disparity in service use associated with childhood bullying victimisation was accounted for by both incident service use through to age 33 by a sub-group of participants, and by persistent use up to midlife. Conclusions: Childhood bullying victimisation adds to the pressure on an already stretched health care system. Policy and practice efforts providing support for victims of bullying could help contain public sector costs. Given constrained budgets and the long-term mental health impact on victims of bullying, early prevention strategies could be effective at limiting both individual distress and later costs

Extreme Differences in Forest Degradation in Borneo: Comparing Practices in Sarawak, Sabah, and Brunei

The Malaysian states of Sabah and Sarawak are global hotspots of forest loss and degradation due to timber and oil palm industries; however, the rates and patterns of change have remained poorly measured by conventional field or satellite approaches. Using 30 m resolution optical imagery acquired since 1990, forest cover and logging roads were mapped throughout Malaysian Borneo and Brunei using the Carnegie Landsat Analysis System. We uncovered ∼364,000 km of roads constructed through the forests of this region. We estimated that in 2009 there were at most 45,400 km(2) of intact forest ecosystems in Malaysian Borneo and Brunei. Critically, we found that nearly 80% of the land surface of Sabah and Sarawak was impacted by previously undocumented, high-impact logging or clearing operations from 1990 to 2009. This contrasted strongly with neighbouring Brunei, where 54% of the land area remained covered by unlogged forest. Overall, only 8% and 3% of land area in Sabah and Sarawak, respectively, was covered by intact forests under designated protected areas. Our assessment shows that very few forest ecosystems remain intact in Sabah or Sarawak, but that Brunei, by largely excluding industrial logging from its borders, has been comparatively successful in protecting its forests.CLASlite is made possible by the Gordon and Betty Moore Foundation, the John D. and Catherine T. MacArthur Foundation, and the Grantham Foundation for the Protection of the Environment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Neuorientierung der Arbeitsmarktpolitik : Die Neuausrichtung der arbeitsmarktpolitischen Instrumente aus dem Jahr 2009 im Blickpunkt: Mehr Flexibilität und größere Handlungsspielräume für die Vermittler?

"This paper deals with the strategic reorientation concerning the instruments of active labor market policy in Germany which came into force at January 1st 2009. The main objective of this reform was to streamline the portfolio of existing instruments and make it more transparent and clearly structured. Moreover, caseworkers in local job offices are to be granted more discretion and flexibility than prior to the reforms. The authors address the question whether the implementation of more discretionary power was successful, and which of the implementation's characteristics prove to be crucial for attaining this goal. To this purpose, expert interviews with caseworkers, their superior officers (team leaders) and members of the board were conducted in 14 local job offices. The study is based on the methodological concept of the socalled 'scientific source text' ('wissenschaftlicher Quellentext') which was used to analyze and interpret the interviews. Empirically, the authors find that the reform did not induce fundamental changes concerning the instruments of active labor market policy while the special budget for the support of job search activities ('Vermittlungsbudget') according to § 45 SGB III can be regarded as an innovation. Caseworkers especially stress the conflict between compliance to the rules and the considerable autonomy involved in the everyday practice of street-level bureaucrats. Rules aimed at structuring discretional leeway in the local job offices (so-called 'Ermessenslenkende Weisungen') help define the relative concept of discretion, because they include instructions already valid before the reforms. Finally, it is remarkable to note that § 16f SGB II does not play an important role after the reform." (Author's abstract, IAB-Doku) ((en))Arbeitsmarktpolitik, Reformpolitik - Erfolgskontrolle, arbeitsmarktpolitische Maßnahme, Arbeitsvermittler, Handlungsspielraum, Aktivierung, berufliche Reintegration, Arbeitslose, Arbeitsvermittlung, Budget, Sozialgesetzbuch II, Sozialgesetzbuch III, freie Förderung, Politikumsetzung

Apoptosis-related gene expression in glioblastoma (LN-18) and medulloblastoma (Daoy) cell lines

The expression of apoptosis genes in a commercial pre-designed low-density array from Applied Biosystems was evaluated in two human brain cancer cell models, LN-18 and Daoy (HTB-186™) in comparison to the reference human primary endothelial cells under basic conditions. Analysis of the gene expression in the cancer cell lines compared to the normal control revealed features reflecting anti-apoptotic and inflammatory characteristics of the former. There was an overall downregulation of apoptosis-stimulating genes in both cancer cell lines, along with an upregulation of certain apoptosis inhibitors. A number of genes demonstrated statistically significant changes in their expressions, including BAX (BCL2-associated X protein); the CARD4/NLR family, CARD domain containing 4; CASP10 (caspase 10, apoptosis-related cysteine peptidase); DAP1 (death-associated protein kinase 1), and BIRC5 (baculoviral IAP repeat-containing 5). Anti-apoptotic potential in both cell lines was demonstrated by changes in the Bax:Bcl-2 ratio and downregulation of the APAF1 gene in LN18 cells. There was also significant downregulation of extrinsic signals and the TNF/FADD/inflammatory cascade, and upregulation of caspase inhibitors (IAPs). These results provided a novel molecular characterization of important human cancer cell lines, which might provide a useful research tool for investigating the experimental model of the CNS cell

Type I Interferon Production Induced by Streptococcus pyogenes-Derived Nucleic Acids Is Required for Host Protection

Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate immune cells to produce inflammatory mediators such as TNF, but also type I interferon (IFN). Here we show that signaling elicited by type I IFNs is required for successful defense of mice against lethal subcutaneous cellulitis caused by S. pyogenes. Type I IFN signaling was accompanied with reduced neutrophil recruitment to the site of infection. Mechanistic analysis revealed that macrophages and conventional dendritic cells (cDCs) employ different signaling pathways leading to IFN-beta production. Macrophages required IRF3, STING, TBK1 and partially MyD88, whereas in cDCs the IFN-beta production was fully dependent on IRF5 and MyD88. Furthermore, IFN-beta production by macrophages was dependent on the endosomal delivery of streptococcal DNA, while in cDCs streptococcal RNA was identified as the IFN-beta inducer. Despite a role of MyD88 in both cell types, the known IFN-inducing TLRs were individually not required for generation of the IFN-beta response. These results demonstrate that the innate immune system employs several strategies to efficiently recognize S. pyogenes, a pathogenic bacterium that succeeded in avoiding recognition by the standard arsenal of TLRs

Transcriptional ontogeny of the developing liver

<p>Abstract</p> <p>Background</p> <p>During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hematopoietic stem cells, the source for a number of blood cells including nucleated erythrocytes. A comprehensive analysis of the transcriptional changes that occur during the early stages of development to adulthood in the liver was carried out.</p> <p>Results</p> <p>We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19 and in the neonate (postnatal day (PND) 7 and 32) compared to that in the adult liver (PND67) using full-genome microarrays. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were under expressed. Comparison of the dataset to a number of previously published microarray datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) under expression of most xenobiotic metabolism genes throughout development, with the exception of a number of transporters associated with either hematopoietic cells or cell proliferation in hepatocytes.</p> <p>Conclusions</p> <p>Overall, these findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical and drug exposure as a function of early life-stages.</p

Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial

Background Agitation is a common, challenging symptom affecting large numbers of people with dementia and impacting on quality of life (QoL). There is an urgent need for evidence-based, cost-effective psychosocial interventions to improve these outcomes, particularly in the absence of safe, effective pharmacological therapies. This study aimed to evaluate the efficacy of a person-centred care and psychosocial intervention incorporating an antipsychotic review, WHELD, on QoL, agitation, and antipsychotic use in people with dementia living in nursing homes, and to determine its cost. Methods and findings This was a randomised controlled cluster trial conducted between 1 January 2013 and 30 September 2015 that compared the WHELD intervention with treatment as usual (TAU) in people with dementia living in 69 UK nursing homes, using an intention to treat analysis. All nursing homes allocated to the intervention received staff training in person-centred care and social interaction and education regarding antipsychotic medications (antipsychotic review), followed by ongoing delivery through a care staff champion model. The primary outcome measure was QoL (DEMQOL-Proxy). Secondary outcomes were agitation (Cohen-Mansfield Agitation Inventory [CMAI]), neuropsychiatric symptoms (Neuropsychiatric Inventory–Nursing Home Version [NPI-NH]), antipsychotic use, global deterioration (Clinical Dementia Rating), mood (Cornell Scale for Depression in Dementia), unmet needs (Camberwell Assessment of Need for the Elderly), mortality, quality of interactions (Quality of Interactions Scale [QUIS]), pain (Abbey Pain Scale), and cost. Costs were calculated using cost function figures compared with usual costs. In all, 847 people were randomised to WHELD or TAU, of whom 553 completed the 9-month randomised controlled trial. The intervention conferred a statistically significant improvement in QoL (DEMQOL-Proxy Z score 2.82, p = 0.0042; mean difference 2.54, SEM 0.88; 95% CI 0.81, 4.28; Cohen’s D effect size 0.24). There were also statistically significant benefits in agitation (CMAI Z score 2.68, p = 0.0076; mean difference 4.27, SEM 1.59; 95% CI −7.39, −1.15; Cohen’s D 0.23) and overall neuropsychiatric symptoms (NPI-NH Z score 3.52, p < 0.001; mean difference 4.55, SEM 1.28; 95% CI −7.07,−2.02; Cohen’s D 0.30). Benefits were greatest in people with moderately severe dementia. There was a statistically significant benefit in positive care interactions as measured by QUIS (19.7% increase, SEM 8.94; 95% CI 2.12, 37.16, p = 0.03; Cohen’s D 0.55). There were no statistically significant differences between WHELD and TAU for the other outcomes. A sensitivity analysis using a pre-specified imputation model confirmed statistically significant benefits in DEMQOL-Proxy, CMAI, and NPI-NH outcomes with the WHELD intervention. Antipsychotic drug use was at a low stable level in both treatment groups, and the intervention did not reduce use. The WHELD intervention reduced cost compared to TAU, and the benefits achieved were therefore associated with a cost saving. The main limitation was that antipsychotic review was based on augmenting processes within care homes to trigger medical review and did not in this study involve proactive primary care education. An additional limitation was the inherent challenge of assessing QoL in this patient group. Conclusions These findings suggest that the WHELD intervention confers benefits in terms of QoL, agitation, and neuropsychiatric symptoms, albeit with relatively small effect sizes, as well as cost saving in a model that can readily be implemented in nursing homes. Future work should consider how to facilitate sustainability of the intervention in this setting

Effects of mental health status during adolescence on primary care costs in adulthood across three British cohorts

PURPOSE: This study examines the association between mental health problems in adolescence and general practice (GP) costs during adulthood up to age 50 in the UK. METHODS: We conducted secondary analyses of three British birth cohorts (individuals born in single weeks in 1946, 1958 and 1970). Data for the three cohorts were analysed separately. All respondents who participated in the cohort studies were included. Adolescent mental health status was assessed in each cohort using the Rutter scale (or, for one cohort, a forerunner of that scale) completed in interviews with parents and teachers when cohort members were aged around 16. Presence and severity of conduct and emotional problems were modelled as independent variables in two-part regression models in which the dependent variable was costs of GP services from data collection sweeps up to mid-adulthood. All analyses were adjusted for covariates (cognitive ability, mother's education, housing tenure, father's social class and childhood physical disability). RESULTS: Adolescent conduct and emotional problems, particularly when coexisting, were associated with relatively high GP costs in adulthood up to age 50. Associations were generally stronger in females than males. CONCLUSION: Associations between adolescent mental health problems and annual GP cost were evident decades later, to age 50, suggesting that there could be significant future savings to healthcare budgets if rates of adolescent conduct and emotional problems could be reduced. TRIAL REGISTRATION: Not applicable

A short isoform of STIM1 confers frequency-dependent synaptic enhancement

Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) Ca2+ content and triggering Ca2+ entry by gating Orai channels. Although crucial for immune cells, STIM1’s role in neuronal Ca2+ homeostasis is controversial. Here, we characterize a splice variant, STIM1B, which shows exclusive neuronal expression and protein content surpassing conventional STIM1 in cerebellum and of significant abundance in other brain regions. STIM1B expression results in a truncated protein with slower kinetics of ER-plasma membrane (PM) cluster formation and ICRAC, as well as reduced inactivation. In primary wild-type neurons, STIM1B is targeted by its spliced-in domain B to presynaptic sites where it converts classic synaptic depression into Ca2+- and Orai-dependent short-term synaptic enhancement (STE) at high-frequency stimulation (HFS). In conjunction with altered STIM1 splicing in human Alzheimer disease, our findings highlight STIM1 splicing as an important regulator of neuronal calcium homeostasis and of synaptic plasticity

ALFALFA HI Data Stacking I. Does the Bulge Quench Ongoing Star Formation in Early-Type Galaxies?

We have carried out an HI stacking analysis of a volume-limited sample of ~5000 galaxies with imaging and spectroscopic data from GALEX and the Sloan Digital Sky Survey, which lie within the current footprint of the Arecibo Legacy Fast ALFA (ALFALFA) Survey. Our galaxies are selected to have stellar masses greater than 10^10 Msun and redshifts in the range 0.025<z<0.05. We extract a sub-sample of 1833 "early-type" galaxies with inclinations less than 70deg, with concentration indices C>2.6 and with light profiles that are well fit by a De Vaucouleurs model. We then stack HI line spectra extracted from the ALFALFA data cubes at the 3-D positions of the galaxies from these two samples in bins of stellar mass, stellar mass surface density, central velocity dispersion, and NUV-r colour. We use the stacked spectra to estimate the average HI gas fractions M_HI/M_* of the galaxies in each bin. Our main result is that the HI content of a galaxy is not influenced by its bulge. The average HI gas fractions of galaxies in both our samples correlate most strongly with NUV-r colour and with stellar surface density. The relation between average HI fraction and these two parameters is independent of concentration index C. We have tested whether the average HI gas content of bulge-dominated galaxies on the red sequence, differs from that of late-type galaxies on the red sequence. We find no evidence that galaxies with a significant bulge component are less efficient at turning their available gas reservoirs into stars. This result is in contradiction with the "morphological quenching" scenario proposed by Martig et al. (2009).Comment: 21 pages, 15 figures. Accepted for publication in MNRAS. Version with high resolution figures available at http://www.mpa-garching.mpg.de/GASS/pubs.ph