Place of death in patients with lung cancer: a retrospective cohort study from 2004-2013

Introduction: Many patients with cancer die in an acute hospital bed, which has been frequently identified as the least preferred location, with psychological and financial implications. This study looks at place and cause of death in patients with lung cancer and identifies which factors are associated with dying in an acute hospital bed versus at home. Methods and Findings: We used the National Lung Cancer Audit linked to Hospital Episode Statistics and Office for National Statistics data to determine cause and place of death in those with lung cancer; both overall and by cancer Network. We used multivariate logistic regression to compare features of those who died in an acute hospital versus those who died at home. Results: Of 143627 patients identified 40% (57678) died in an acute hospital, 29% (41957) died at home and 17% (24108) died in a hospice. Individual factors associated with death in an acute hospital bed compared to home were male sex, increasing age, poor performance status, social deprivation and diagnosis via an emergency route. There was marked variation between cancer Networks in place of death. The proportion of patients dying in an acute hospital ranged from 28% to 48%, with variation most notable in provision of hospice care (9% versus 33%). Cause of death in the majority was lung cancer (86%), with other malignancies, chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) comprising 9% collectively. Conclusions: A substantial proportion of patients with lung cancer die in acute hospital beds and this is more likely with increasing age, male sex, social deprivation and in those with poor performance status. There is marked variation between Networks, suggesting a need to improve end-of-life planning in those at greatest risk, and to review the allocation of resources to provide more hospice beds, enhanced community support and ensure equal access

Problem-based learning in dental education: what's the evidence for and against... and is it worth the effort?

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.All Australian dental schools have introduced problem-based learning (PBL) approaches to their programmes over the past decade, although the nature of the innovations has varied from school to school. Before one can ask whether PBL is better than the conventional style of education, one needs to consider three key issues. Firstly, we need to agree on what is meant by the term PBL; secondly, we need to decide what “better” means when comparing educational approaches; and thirdly, we must look carefully at how PBL is implemented in given situations. It is argued that PBL fulfils, at least in theory, some important principles relating to the development of new knowledge. It also represents a change in focus from teachers and teaching in conventional programmes to learners and learning. Generally, students enjoy PBL programmes more than conventional programmes and feel they are more nurturing. There is also some evidence of an improvement in clinical and diagnostic reasoning ability associated with PBL curricula. The main negative points raised about PBL are the costs involved and mixed reports of insufficient grounding of students in the basic sciences. Financial restraints will probably preclude the introduction of pure or fully integrated PBL programmes in Australian dental schools. However, our research and experience, as well as other published literature, indicate that well-planned hybrid PBL programmes, with matching methods of assessment, can foster development of the types of knowledge, skills and attributes that oral health professionals will need in the future.T Winning and G Townsen

BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia

BCL2 associated Athano-Gene 1 (BAG1) is a multifunctional protein that has been described to be involved in different cell processes linked to cell survival. It has been reported as deregulated in diverse cancer types. Here, BAG1 protein was found highly expressed in children with acute myeloid leukemia at diagnosis, and in a cohort of leukemic cell lines. A silencing approach was used for determining BAG1's role in AML, finding that its down-regulation decreased expression of BCL2, BCL-XL, MCL1, and phospho-ERK1/2, all proteins able to sustain leukemia, without affecting the pro-apoptotic protein BAX. BAG1 down-regulation was also found to increase expression of BAG3, whose similar activity was able to compensate the loss of function of BAG1. BAG1/BAG3 co-silencing caused an enhanced cell predisposition to death in cell lines and also in primary AML cultures, affecting the same proteins. Cell death was CASPASE-3 dependent, was accompanied by PARP cleavage and documented by an increased release of pro-apoptotic molecules Smac/DIABLO and Cytochrome c. BAG1 was found to directly maintain BCL2 and to protect MCL1 from proteasomal degradation by controlling USP9X expression, which appeared to be its novel target. Finally, BAG1 was found able to affect leukemia cell fate by influencing the expression of anti-apoptotic proteins crucial for AML maintenance

Factors associated with educational aspirations among adolescents: cues to counteract socioeconomic differences?

Background: Our study aims to follow this effort and to explore the association between health, socioeconomic background, school-related factors, social support and adolescents' sense of coherence and educational aspirations among adolescents from different educational tracks and to contribute to the existing body of knowledge on the role of educational aspirations in the social reproduction of health inequalities. We expect that socioeconomic background will contribute to the development of educational aspirations, but this association will be modified by available social and individual resources, which may be particularly favourable for the group of adolescents who are on lower educational tracks, since for them such resources may lead to gaining a higher educational level. Methods: We collected data on the socioeconomic background (mother's and father's education and employment status, doubts about affordability of future study), school-related factors (school atmosphere, school conditions, attitudes towards school), perceived social support, sense of coherence (manageability, comprehensibility, meaningfulness) and the self-rated health of a national sample of Slovak adolescents (n = 1992, 53.5% females, mean age 16.9 years). We assessed the association of these factors with educational aspirations, overall and by educational tracks (grammar schools, specialised secondary schools, vocational schools). Results: We found statistically significant associations with educational aspirations for the factors parental educational level, father's unemployment, doubts about the affordability of future study, school atmosphere, attitude towards school, social support from the father and a sense of coherence. Social support from the mother and friends was not associated with educational aspiration, nor was self-rated health. Besides affinity towards school, the determinants of educational aspirations differed among adolescents on different educational tracks. Educational aspirations of grammar school students were associated with father's education, while the aspirations of their peers on lower educational tracks had a stronger association with mother's education and perceived social support from father and friends. Moreover, a sense of coherence contributes to the reporting of educational aspiration by students on different educational tracks. Conclusions: Characteristics of the school environment, the family and the individual adolescent are all associated with the level of educational aspiration, but in a different way for different educational tracks. Interventions aimed at reducing socioeconomic inequalities in health via the educational system should, therefore, take this variation and the rather pivotal role of the father into account

Hip Fracture Incidence in Relation to Age, Menopausal Status, and Age at Menopause: Prospective Analysis

Using data from the UK Million Women Study, Emily Banks and colleagues investigate the relationships between the incidence of hip fracture and a woman's age, menopausal status, and age at menopause

Evolutionarily Conserved Protein Sequences of Influenza A Viruses, Avian and Human, as Vaccine Targets

10.1371/journal.pone.0001190PLoS ONE21

Human Cytomegalovirus UL18 Utilizes US6 for Evading the NK and T-Cell Responses

Human cytomegalovirus (HCMV) US6 glycoprotein inhibits TAP function, resulting in down-regulation of MHC class I molecules at the cell surface. Cells lacking MHC class I molecules are susceptible to NK cell lysis. HCMV expresses UL18, a MHC class I homolog that functions as a surrogate to prevent host cell lysis. Despite a high level of sequence and structural homology between UL18 and MHC class I molecules, surface expression of MHC class I, but not UL18, is down regulated by US6. Here, we describe a mechanism of action by which HCMV UL18 avoids attack by the self-derived TAP inhibitor US6. UL18 abrogates US6 inhibition of ATP binding by TAP and, thereby, restores TAP-mediated peptide translocation. In addition, UL18 together with US6 interferes with the physical association between MHC class I molecules and TAP that is required for optimal peptide loading. Thus, regardless of the recovery of TAP function, surface expression of MHC class I molecules remains decreased. UL18 represents a unique immune evasion protein that has evolved to evade both the NK and the T cell immune responses

Future oriented group training for suicidal patients: a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>In routine psychiatric treatment most clinicians inquire about indicators of suicide risk, but once the risk is assessed not many clinicians systematically focus on suicidal thoughts. This may reflect a commonly held opinion that once the depressive or anxious symptoms are effectively treated the suicidal symptoms will wane. Consequently, many clients with suicidal thoughts do not receive systematic treatment of their suicidal thinking. There are many indications that specific attention to suicidal thinking is necessary to effectively decrease the intensity and recurrence of suicidal thinking. We therefore developed a group training for patients with suicidal thoughts that is easy to apply in clinical settings as an addition to regular treatment and that explicitly focuses on suicidal thinking. We hypothesize that such an additional training will decrease the frequency and intensity of suicidal thinking.</p> <p>We based the training on cognitive behavioural approaches of hopelessness, worrying, and future perspectives, given the theories of Beck, McLeod and others, concerning the lack of positive expectations characteristic for many suicidal patients. In collaboration with each participant in the training individual positive future possibilities and goals were challenged.</p> <p>Methods/Design</p> <p>We evaluate the effects of our program on suicide ideation (primary outcome measure). The study is conducted in a regular treatment setting with regular inpatients and outpatients representative for Dutch psychiatric treatment settings. The design is a RCT with two arms: TAU (Treatment as Usual) versus TAU plus the training. Follow up measurements are taken 12 months after the first assessment.</p> <p>Discussion</p> <p>There is a need for research on the effectiveness of interventions in suicidology, especially RCT's. In our treatment program we combine aspects and interventions that have been proven to be useful in the treatment of suicidal thinking and behavior.</p> <p>Trial registration</p> <p>ISRCTN56421759</p

The area-based social patterning of injuries among 10 to 19 year olds Changes over time in the Stockholm County

<p>Abstract</p> <p>Background</p> <p>Area-based studies of childhood injuries strongly suggest that neighborhood socio-demographic and economic circumstances impact on various – though not all – types of injuries. The primary aim of this study was to investigate the stability over time of the association between area characteristics and childhood injuries of various causes.</p> <p>Methods</p> <p>Register-based and ecological, the study encompassed Stockholm County's 138 parishes, and considered two time periods (1993–95; 2003–05). Two indices were measured: economic deprivation and social fragmentation, and parishes were allocated to their respective quintile on each index. Data on both unintentional and intentional injuries for children (boys and girls) aged 10–14 and 15–19 respectively were gathered from the County Council's hospital inpatient register. For each period and index, gender, age and cause-specific comparisons were made to assess the rate ratios (with 95% confidence intervals) of being injured using parishes belonging to the best index level as a comparison group. A series of simple and partial Pearson correlations were also calculated to assess the independent contribution of each index.</p> <p>Results</p> <p>Regardless of time period, there were rather few significant rate ratios and, when they occurred, there were both under and excess risks. For instance, in each period, boys from both age groups living in parishes with the highest levels of economic deprivation had lower rate of injury as a motor vehicle rider. Most strikingly, intentional injuries were more frequent during the second time period and in considerable excess among girls aged 15–19 from more economically deprived areas. Also, during that last period, none of the injury causes correlated significantly with the index of social fragmentation after adjustment for economic deprivation (partial correlation).</p> <p>Conclusion</p> <p>Over a ten-year period, differential economic deprivation among parishes has widened more than social fragmentation in Stockholm County. The correlation between those indices is high in both periods of time whilst the association between the levels of each index and injury rates varies depending on group of injuries or time period considered. It is of concern that intentional injuries have increased numerically and are significantly and positively correlated with economic deprivation (net of social fragmentation), in particular among girls.</p

Traits and stress: keys to identify community effects of low levels of toxicants in test systems

Community effects of low toxicant concentrations are obscured by a multitude of confounding factors. To resolve this issue for community test systems, we propose a trait-based approach to detect toxic effects. An experiment with outdoor stream mesocosms was established 2-years before contamination to allow the development of biotic interactions within the community. Following pulse contamination with the insecticide thiacloprid, communities were monitored for additional 2 years to observe long-term effects. Applying a priori ecotoxicological knowledge species were aggregated into trait-based groups that reflected stressor-specific vulnerability of populations to toxicant exposure. This reduces inter-replicate variation that is not related to toxicant effects and enables to better link exposure and effect. Species with low intrinsic sensitivity showed only transient effects at the highest thiacloprid concentration of 100 μg/l. Sensitive multivoltine species showed transient effects at 3.3 μg/l. Sensitive univoltine species were affected at 0.1 μg/l and did not recover during the year after contamination. Based on these results the new indicator SPEARmesocosm was calculated as the relative abundance of sensitive univoltine taxa. Long-term community effects of thiacloprid were detected at concentrations 1,000 times below those detected by the PRC (Principal Response Curve) approach. We also found that those species, characterised by the most vulnerable trait combination, that were stressed were affected more strongly by thiacloprid than non-stressed species. We conclude that the grouping of species according to toxicant-related traits enables identification and prediction of community response to low levels of toxicants and that additionally the environmental context determines species sensitivity to toxicants