An Exploration of the Peri-Diagnostic Experiences of Lesbian, Gay and Bisexual People With Dementia Using the Candidacy Framework.

OBJECTIVES: How dementia affects lesbian, gay, bisexual, trans, queer people or those with other minoritised sexual/gender identities (LGBTQ+) is not well understood. Furthermore, existing research often excludes the voices of LGBTQ+ people living with dementia and focuses instead on their care partners. This study addresses this evidence gap by drawing on the ESRC/NIHR funded DETERMIND cohort, consisting of 940 newly diagnosed people with dementia, to explore the peri-diagnostic experiences of people living with dementia who identify as LGBTQ+. METHODS: We recruited five people (who identified as lesbian, gay or bisexual [LGB]) and completed semi-structured interviews with them and their partner caregivers (n = 3) discussing their experiences of (1) engaging with dementia health care services, (2) receiving a dementia diagnosis, and (3) the support they were offered after diagnosis. Interviews were shaped by the Candidacy Framework, a theoretical model for understanding accessibility of health services, and an inductive thematic analysis was employed to develop common themes. FINDINGS: Participants did not routinely disclose their LGBTQ+ identities to health service professionals, despite feeling this was an essential aspect of who they are. They relied on their resilience of overcoming previous experiences of lifetime discrimination to navigate complicated dementia care systems. The importance of 'chosen families' as informal support networks for LGBTQ+ people living with dementia was highlighted, particularly given the lack of formal care services they felt comfortable accessing. All participants were concerned about their future care needs and whether they would receive home-based or community-based support that respected their LGBTQ+ identities. CONCLUSIONS: This study adds to the limited evidence base that can be used to inform future research, policy and practice seeking to address inequalities across the dementia care pathway. We only interviewed people who identified as LGB so generalizability to the whole LGBTQ+ population is limited, however our data suggest dementia health care professionals should encourage and support disclosures of LGBTQ+ identities so that inclusive care and support planning can be provided to LGBTQ+ people at every stage of dementia.

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.

PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.

Hormone replacement therapy and the risk of melanoma in post-menopausal women.

STUDY QUESTION: Is hormone replacement therapy (HRT) associated with an increased risk of melanoma skin cancer or prognostic outcomes amongst post-menopausal women? SUMMARY ANSWER: Whilst we found evidence of an association with melanoma risk, the lack of dose-response and associations observed with recent use, localised disease and intravaginal oestrogens suggests this is a non-causal association. WHAT IS KNOWN ALREADY: Evidence on HRT and melanoma risk remains inconclusive, with studies providing conflicting results. Furthermore, evidence on melanoma survival is sparse, with only one previous study reporting protective associations with HRT use, likely attributable to immortal time bias. STUDY DESIGN, SIZE, DURATION: We conducted a nation-wide population-based case-control study and a retrospective cohort study utilising the Danish healthcare registries. Case-control analyses included 8279 women aged 45-85 with a first-ever diagnosis of malignant melanoma between 2000 and 2015, matched by age and calendar time to 165 580 population controls. A cohort of 6575 patients with a diagnosis of primary malignant melanoma between 2000 and 2013 and followed through 2015 was examined to determine if HRT use had an impact on melanoma survival outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on prescriptions dispensed since 1995, ever-use of HRT was defined as having filled at least one prescription for HRT prior to the index date. In total, 2629 cases (31.8%) and 47 026 controls (28.4%) used HRT. Conditional logistic regression was used to calculate odds ratios (ORs) for melanoma risk according to HRT use, compared with non-use, adjusting for potential confounders. For cohort analyses, Cox proportional hazards models was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for second melanoma incidence and all-cause mortality associated with HRT. MAIN RESULTS AND THE ROLE OF CHANCE: High use of HRT was associated with an OR of 1.21 (95% CI 1.13-1.29) for melanoma risk, with no evidence of a dose-response pattern. Results were most pronounced amongst recent high users (OR, 1.28; 95% CI 1.17-1.41), for localised disease (OR, 1.25; 95% CI 1.15-1.36) and for intravaginal oestrogen therapy (OR, 1.38; 95% CI 1.13-1.68). Compared with non-use, there was no evidence of an association for secondary melanoma for post-diagnostic new-use (fully adjusted HR, 1.56; 95% CI 0.64-3.80) or continuous HRT use (fully adjusted HR, 1.26; 95% CI 0.89-1.78). Similar associations were observed for all-cause mortality. LIMITATIONS, REASONS FOR CAUTION: Despite the large sample size and the use of robust population-based registries with almost complete coverage, we lacked information on some important confounders including sun exposure. WIDER IMPLICATIONS OF THE FINDINGS: Whilst we cannot rule out an association between HRT use and melanoma risk, the associations observed are also compatible with increased healthcare utilisation and thus increased melanoma detection amongst HRT users. No association between HRT use and melanoma survival outcomes was observed. This should provide some reassurance to patients and clinicians, particularly concerning the use of HRT in patients with a history of melanoma. STUDY FUNDING/COMPETING INTEREST(S): B.M.H. is funded by a Cancer Research UK Population Research Postdoctoral Fellowship. The funding source had no influence on the design or conduct of this study. A.P. reports participation in research projects funded by Alcon, Almirall, Astellas, Astra-Zeneca, Boehringer-Ingelheim, Servier, Novo Nordisk and LEO Pharma, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this article. The other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Psychoneurometric assessment of dispositional liabilities for suicidal behavior: phenotypic and etiological associations.

BACKGROUND: Can core genetic liabilities for suicidal behavior be indexed using psychological and neural indicators combined? The current work addressed this question by examining phenotypic and genetic associations of two biobehavioral traits, threat sensitivity (THT) and disinhibition (DIS) - operationalized as psychoneurometric variables (i.e., composites of psychological-scale and neurophysiological measures) - with suicidal behaviors in a sample of adult twins. METHODS: Participants were 444 identical and fraternal twins recruited from an urban community. THT was assessed using a psychological-scale measure of fear/fearlessness combined with physiological indicators of reactivity to aversive pictures, and DIS was assessed using scale measures of disinhibitory tendencies combined with indicators of brain response from lab performance tasks. Suicidality was assessed using items from structured interview and questionnaire protocols. RESULTS: THT and DIS each contributed uniquely to prediction of suicidality when assessed psychoneurometrically (i.e., as composites of scale and neurophysiological indicators). In addition, these traits predicted suicidality interactively, with participants high on both reporting the greatest degree of suicidal behaviors. Biometric (twin-modeling) analyses revealed that a high percentage of the predictive association for each psychoneurometric trait (83% for THT, 68% for DIS) was attributable to genetic variance in common with suicidality. CONCLUSIONS: Findings indicate that psychoneurometric assessments of biobehavioral traits index genetic liability for suicidal behavior, and as such, can serve as innovative targets for research on core biological processes contributing to severe psychopathology, including suicidal proclivities and actions.

Post-diagnostic oral bisphosphonate use and colorectal cancer mortality: a population-based cohort study within the UK Clinical Practice Research Datalink.

BACKGROUND: We conducted the first study to investigate post-diagnostic oral bisphosphonates use and colorectal cancer-specific mortality. METHODS: Colorectal cancer patients were identified from the National Cancer Data Repository (1998-2007) and linked to the UK Clinical Practice Research Datalink, providing prescription records, and Office of National Statistics mortality data. Time-dependent Cox regression models investigated colorectal cancer-specific mortality in post-diagnostic bisphosphonate users. RESULTS: Overall, in 4791 colorectal cancer patients, there was no evidence of an association between bisphosphonate use and colorectal cancer-specific mortality (adjusted hazard ratio=1.11; 95% confidence interval 0.80, 1.54) or with drug frequency or type. CONCLUSIONS: In this novel population-based cohort study, post-diagnostic bisphosphonate use was not associated with longer rates of colorectal cancer survival.

Gender differences in the structure of risk for alcohol use disorder in adolescence and young adulthood.

BACKGROUND: Gender differences in the prevalence of alcohol use disorder (AUD) have motivated the separate study of its risk factors and consequences in men and women. However, leveraging gender as a third variable to help account for the association between risk factors and consequences for AUD could elucidate etiological mechanisms and clinical outcomes. METHOD: Using data from a large, community sample followed longitudinally from 17 to 29 years of age, we tested for gender differences in psychosocial risk factors and consequences in adolescence and adulthood after controlling for gender differences in the base rates of AUD and psychosocial factors. Psychosocial factors included alcohol use, other drug use, externalizing and internalizing symptoms, deviant peer affiliation, family adversity, academic problems, attitudes and use of substances by a romantic partner, and adult socio-economic status. RESULTS: At both ages of 17 and 29 years, mean levels of psychosocial risks and consequences were higher in men and those with AUD. However, the amount of risk exposure in adolescence was more predictive of AUD in women than men. By adulthood, AUD consequences were larger in women than men and internalizing risk had a stronger relationship with AUD in women at both ages. CONCLUSIONS: Despite higher mean levels of risk exposure in men overall, AUD appears to be a more severe disorder in women characterized by higher levels of adolescent risk factors and a greater magnitude of the AUD consequences among women than men. Furthermore, internalizing symptoms appear to be a gender-specific risk factor for AUD in women.

Age of onset and course of major depressive disorder: associations with psychosocial functioning outcomes in adulthood.

BACKGROUND: Major depressive disorder (MDD) that onsets by adolescence is associated with various deficits in psychosocial functioning. However, adolescent-onset MDD often follows a recurrent course that may drive its associated impairment. METHOD: To tease apart these two clinical features, we examined the relative associations of age of onset (adolescent versus adult) and course (recurrent versus single episodes) of MDD with a broad range of psychosocial functioning outcomes assessed in early adulthood. Participants comprised a large, population-based sample of male and female twins from the Minnesota Twin Family Study (MTFS; n = 1252) assessed prospectively from ages 17 to 29 years. RESULTS: A recurrent course of MDD predicted impairment in several psychosocial domains in adulthood, regardless of whether the onset was in adolescence or adulthood. By contrast, adolescent-onset MDD showed less evidence of impairment in adulthood after accounting for recurrence. Individuals with both an adolescent onset and recurrent episodes of MDD represented a particularly severe group with pervasive psychosocial impairment in adulthood. CONCLUSIONS: The negative implications of adolescent-onset MDD for psychosocial functioning in adulthood seem to be due primarily to its frequently recurrent course, rather than its early onset, per se. The results highlight the importance of considering both age of onset and course for understanding MDD and its implications for functioning, and also in guiding targeted intervention efforts.

Gene-environment interplay between parent-child relationship problems and externalizing disorders in adolescence and young adulthood.

BACKGROUND: Previous studies have shown that genetic risk for externalizing (EXT) disorders is greater in the context of adverse family environments during adolescence, but it is unclear whether these effects are long lasting. The current study evaluated developmental changes in gene-environment interplay in the concurrent and prospective associations between parent-child relationship problems and EXT at ages 18 and 25 years. METHOD: The sample included 1382 twin pairs (48% male) from the Minnesota Twin Family Study, participating in assessments at ages 18 years (mean = 17.8, s.d. = 0.69 years) and 25 years (mean = 25.0, s.d. = 0.90 years). Perceptions of parent-child relationship problems were assessed using questionnaires. Structured interviews were used to assess symptoms of adult antisocial behavior and nicotine, alcohol and illicit drug dependence. RESULTS: We detected a gene-environment interaction at age 18 years, such that the genetic influence on EXT was greater in the context of more parent-child relationship problems. This moderation effect was not present at age 25 years, nor did parent-relationship problems at age 18 years moderate genetic influence on EXT at age 25 years. Rather, common genetic influences accounted for this longitudinal association. CONCLUSIONS: Gene-environment interaction evident in the relationship between adolescent parent-child relationship problems and EXT is both proximal and developmentally limited. Common genetic influence, rather than a gene-environment interaction, accounts for the long-term association between parent-child relationship problems at age 18 years and EXT at age 25 years. These results are consistent with a relatively pervasive importance of gene-environmental correlation in the transition from late adolescence to young adulthood.

Work stress and cancer researchers: an exploration of the challenges, experiences and training needs of UK cancer researchers.

Work stress is a significant issue for many UK healthcare professionals, in particular those working in the field of oncology. However, there have been very few attempts to explore the challenges, experiences or training needs of researchers working in cancer research. In doing so, we will be better positioned to support and develop these researchers. Eighteen UK oncology researchers from a variety of backgrounds took part in a semi-structured interview. Interviews were transcribed and analysed using thematic analysis. The analysis identified two overarching themes: logistical research issues (workload, accessing/recruiting participants, finances) and sensitive research issues (emotional demands, professional boundaries, sensitivity around recruitment). One cross-cutting theme, supportive strategies (support and training, coping mechanisms), was seen to influence both logistical and sensitive research issues. While further research is needed to fully understand the causes and impact of work stress on cancer researchers, three specific issues were highlighted: emotional demands are relevant to quantitative and mixed methods researchers as well as those engaged in qualitative research; the researchers' background (experience; clinical/non-clinical) was influential and an exploration of effective coping strategies is required; and there is a clear need for adequate support systems and training to be available, particularly for early career researchers.

Primary blast lung injury at a NATO Role 3 hospital.

BACKGROUND: Primary blast lung injury (PBLI) is defined as lung contusion from barotrauma following an explosive mechanism of injury (MOI). Military data have focused on PBLI characteristics following evacuation from the combat theatre; less is known about its immediate management and epidemiology in the deployed setting. We conducted a quality improvement project to describe the prevalence, clinical characteristics, management strategies and evacuation techniques for PBLI patients prior to evacuation. METHODS: Patients admitted to a Role 3 hospital in southwest, Afghanistan, from January 2008 to March 2013 with a blast MOI were identified through the Department of Defense Trauma Registry; International Classification of Diseases 9 codes and patient record review were used to identify the PBLI cohort from radiology reports. Descriptive statistics and Fishers exact test were used to report findings. RESULTS: Prevalence of PBLI among blast injured patients with radiology reports was 11.2% (73/648). The population exhibited high Injury Severity Scores median 25 (IQR 14-34) and most received a massive blood transfusion (mean 33.4±38.3 total blood products/24 h). The mean positive end expiratory pressure (PEEP) requirement was 6.2±3.7 (range 5-15) cm H2O and PaO2 to FiO2 ratio was 297±175.2 (66-796) mm Hg. However, 16.6% of patients had a PaO2 to FiO2 ratio <200, 13.3% required PEEP ≥10 cm H2O and one patient required specialised evacuation for respiratory failure. A dismounted MOI (72.8%) and evacuation from point of injury by the Medical Emergency Response Team (62.3%) appeared to be associated with worse lung injury. Only eight of the 73 PBLI patients died and of the five with retrievable records, none died from respiratory failure. CONCLUSIONS: PBLI has a low prevalence and conventional lung protective ventilator management is generally appropriate immediately after injury; application of advanced modes of ventilation and specialised evacuation assistance may be required. PBLI may be a marker of underlying injury severity since all deaths were not due to respiratory failure. Further work is needed to determine exact MOI in mounted and dismounted casualties.

ß-Blocker usage and colorectal cancer mortality: a nested case-control study in the UK Clinical Practice Research Datalink cohort.

BACKGROUND: Epidemiological and laboratory studies suggest that ß-blockers may reduce cancer progression in various cancer sites. The aim of this study was to conduct the first epidemiological investigation of the effect of post-diagnostic ß-blocker usage on colorectal cancer-specific mortality in a large population-based colorectal cancer patient cohort. PATIENTS AND METHODS: A nested case-control analysis was conducted within a cohort of 4794 colorectal cancer patients diagnosed between 1998 and 2007. Patients were identified from the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with a colorectal cancer- specific death (data from the Office of National Statistics death registration system) were matched to five controls. Conditional logistic regression was applied to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) according to ß-blocker usage (data from GP-prescribing records). RESULTS: Post-diagnostic ß-blocker use was identified in 21.4% of 1559 colorectal cancer-specific deaths and 23.7% of their 7531 matched controls, with little evidence of an association (OR = 0.89 95% CI 0.78-1.02). Similar associations were found when analysing drug frequency, ß-blocker type or specific drugs such as propranolol. There was some evidence of a weak reduction in all-cause mortality in ß-blocker users (adjusted OR = 0.88; 95% CI 0.77-1.00; P = 0.04) which was in part due to the marked effect of atenolol on cardiovascular mortality (adjusted OR = 0.62; 95% CI 0.40-0.97; P = 0.04). CONCLUSIONS: In this novel, large UK population-based cohort of colorectal cancer patients, there was no evidence of an association between post-diagnostic ß-blocker use and colorectal cancer-specific mortality. CLINICAL TRIALS NUMBER: NCT00888797.

Understanding the experience of time for dementia education programme on undergraduate radiography students.

INTRODUCTION: Dementia is a global health priority, which requires the healthcare workforce to have the necessary attitudes and skills to deliver person-centred care to people with dementia. Radiographers have frequent contact with people with dementia, and undergraduate training is potentially an optimal time to deliver dementia education. Time for Dementia is an education programme in which undergraduate healthcare students visit a person with dementia and their carer over a two-year period to gain an in-depth understanding of the condition. The aim of this study was to understand undergraduate radiography students' experiences of undertaking the Time for Dementia (TFD) programme. METHODS: Two focus groups were undertaken with 14 radiography students who were half-way through the TFD programme. Data was analysed using thematic analysis. RESULTS: Three key themes were constructed from the analysis: A Holistic Learning Experience, Transferring Learning into Practice and Preparedness & Expectations. Participants discussed the value from learning directly from people with dementia and their carers, reporting an increase in their awareness and understanding of dementia as well as the impact of caring for somebody with the condition. Participants were able to identify learning to take into practice such as person-centred care, compassion, and patience. Challenges to learning were also identified. CONCLUSIONS: This study suggests that a longitudinal, experiential education programme provides radiography students with the opportunity to develop a more holistic understanding of dementia and the impact it may have on the individual and their family members. IMPLICATIONS FOR PRACTICE: Experiential dementia teaching is of value to radiography students, however preparation and learning support should fit with previous personal and teaching experience.

Factors associated with dementia attitudes in an adolescent cohort: Structural Equation Modelling.

Objective: Dementia-related stigma is a key barrier to people living well with dementia, leading to social isolation and poor well-being. Adolescents represent an under-researched group that will become future carers and healthcare workers for the estimated 83.2 million people who will be living with dementia by 2030. Understanding the factors involved in dementia attitude formation in adolescents is useful for the development of evidence-based anti-stigma initiatives. This study aims to identify predictors of dementia attitudes in adolescents. Methods: This is a cross-sectional study using secondary data analysis. 470 participants aged 12-15 years old from secondary schools in the Southeast of England, United Kingdom completed validated questionnaires relating to dementia attitudes (KIDS and Brief A-ADS) as well as demographic information. Multiple regressions were employed as well as a path analysis via a structural equation model to test for direct and mediatory effects. Results: Multiple regression models revealed that being female, having higher levels of contact with dementia, and higher levels of empathy are positively associated with dementia attitudes in adolescents (p<0.05). Within the accepted structural equation model, empathy was a key mediator between contact and dementia attitudes. Conclusion: This study highlights the pivotal role that contact with dementia can have in influencing dementia attitudes in adolescents with empathy serving as a mediator between contact and dementia attitudes. Interventions that use contact should consider how to stimulate empathetic responses to ultimately shape dementia attitudes.

Maker communities and the COVID-19 pandemic: a longitudinal analysis of Thingiverse's response to supply shortages.

The COVID-19 pandemic profoundly affected various aspects of daily life, particularly the supply and demand of essential goods, resulting in critical shortages. This included personal protective equipment for medical professionals and the general public. To address these shortages, online 'maker communities' emerged, aiming to develop and locally manufacture critical products. While some organized efforts existed, the majority of initiatives originated from individuals and groups on platforms like Thingiverse. This paper presents a longitudinal analysis of Thingiverse, one of the largest maker community websites, to examine the pandemic's effects. Our findings reveal a surge in community output during the initial lockdown periods in major contributing nations (primarily those in the Western Hemisphere), followed by a subsequent decline. Additionally, throughout 2020, pandemic-related products dominated uploads and interactions during this period. Based on these observations, we propose recommendations to expedite the community's ability to support local, national and international responses to future disasters.

Global gene expression analysis of bovine somatic cell nuclear transfer blastocysts and cotyledons.

Low developmental competence of bovine somatic cell nuclear transfer (SCNT) embryos is a universal problem. Abnormal placentation has been commonly reported in SCNT pregnancies from a number of species. The present study employed Affymetrix bovine expression microarrays to examine global gene expression patterns of SCNT and in vivo produced (AI) blastocysts as well as cotyledons from day-70 SCNT and AI pregnancies. SCNT and AI embryos and cotyledons were analyzed for differential expression. Also in an attempt to establish a link between abnormal gene expression patterns in early embryos and cotyledons, differentially expressed genes were compared between the two studies. Microarray analysis yielded a list of 28 genes differentially expressed between SCNT and AI blastocysts and 19 differentially expressed cotyledon genes. None of the differentially expressed genes were common to both groups, although major histocompatibility complex I (MHCI) was significant in the embryo data and approached significance in the cotyledon data. This is the first study to report global gene expression patterns in bovine AI and SCNT cotyledons. The embryonic gene expression data reported here adds to a growing body of data that indicates the common occurrence of aberrant gene expression in early SCNT embryos.

Screw osteolysis in the cementless anatomic modular knee arthroplasty.

A cohort of patients underwent prospective follow-up to delineate the natural history of screw-associated osteolysis in cementless Anatomic Modular Knee arthroplasty. In 1993, fluoroscopically guided radiographs were obtained in 230 patients (280 arthroplasties) to identify occult osteolysis. This cohort was reassessed periodically to identify new or progressive screw-associated osteolysis. At early follow-up, 94 knees (34%) had osteolysis. Osteolysis progressed in all groups, and osteolysis developed in 60 additional knees. At intermediate follow-up, 55% of knees showed radiographic evidence of osteolysis. Osteolysis progressed to a higher grade in a significant percentage of patients, and 23% of arthroplasties were revised. Regular periodic radiographic evaluation is recommended for early recognition of osteolysis.

Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. AIMS: To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. METHODS: We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. RESULTS: In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). CONCLUSIONS: We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.

Which thermometer? Factors influencing best choice for intermittent clinical temperature assessment.

The objectives of this study are (a) to review the current technologies, (b) to examine comparative costing data for six selected representative devices, and (c) to discuss the clinical factors related to selection of devices for intermittent temperature measurement. Financial estimates indicate that mercury-in-glass thermometers are the cheapest devices. Compact electronic and chemical (phase change) thermometers are cheaper alternatives than multi-patient contact thermometers requiring probe covers and infrared sensing models, which are commonly adopted in hospitals and clinical practice. However, time required to obtain readings will influence overall costs. Rigorous independent clinical research studies are now needed to establish which of these alternative technologies are 'fit for purpose'. As a minimum they should offer comparable clinical accuracy and reliability to mercury-in-glass and be suitable for most clinical measurement situations. Furthermore any additional costs should bring demonstrable benefits to the patient, user and healthcare system.

On dispersion above a forest-Measurements and methods.

UNLABELLED: Data collected over a mixed conifer/deciduous forest at the U.S. Department of Energy's Savannah River Site in South Carolina using sonic anemometry reveal that on-site and real-time measurements of the velocity component standard deviations, σv and σw, are preferred for dispersion modeling. Such data are now easily accessible, from the outputs of cost-effective and rugged sonic anemometers. The data streams from these devices allow improvements to conventional methodologies for dispersion modeling. In particular, extrapolation of basic input data from a nearby location to the site of the actual release can be facilitated. In this regard reliance on the velocity statistics σv and σw appears to be preferred to the conventional σθ and σϕ. In the forest situations addressed here, the uncertainties introduced by extrapolating initializing properties (u, θ, σθ, and σϕ, or alternatively, σv and σw) from some location of actual measurement to some nearby location where an actual release occurs are similar to those associated with the spread of the plume itself and must be considered in any prediction of the likelihood of downwind concentration (exposure) exceeding some critical value, i.e., a regulatory standard. Consideration of plume expansion factors related to meander will not necessarily cause predicted downwind maxima within a particular plume to be decreased; however, the probability of exposure to this maximum value at any particular location will be reduced. Three-component sonic anemometers are affordable and reliable, and are now becoming a standard for meteorological monitoring programs subject to regulatory oversight. The time has come for regulatory agencies and the applied dispersion community to replace the traditional discrete sets of dispersion coefficients based on Pasquill stability by the direct input of measured turbulence data. IMPLICATIONS: The continued endorsement of legacy Pasquill-Gifford stability schemes is presently under discussion among professional groups and regulatory agencies. The present paper is an attempt to introduce some rationality, for the case of a forested environment.