Psychological distress and risk of myocardial infarction and stroke in the 45 and Up Study: a 1 prospective cohort study

Background The interplay between mental and physical health remains poorly understood. We investigated whether psychological distress is associated with risk of myocardial infarction (MI) and stroke in a population-based prospective study. Methods and Results We included participants without prior stroke/MI from the New South Wales 45 and Up Study. We categorized baseline psychological distress as low, medium, and high/very high on the 10-item Kessler Psychological Distress scale and identified stroke and MI through linkage to hospital admission and mortality records. We obtained sex and age-stratified adjusted and unadjusted hazard ratios for the association between psychological distress and MI and stroke. We investigated for interaction between psychological distress and each of age and sex. Among 221 677 participants, 16.2% and 7.3% had moderate and high/very high psychological distress at recruitment, respectively. During 4.7 (±0.98 SD) years of follow-up, 4573 MIs and 2421 strokes occurred. Absolute risk of MI and stroke increased with increasing psychological distress level. In men aged 45 to 79 years, high/very high versus low psychological distress was associated with a 30% increased risk of MI (fully adjusted hazard ratios, 1.30; 95% CI, 1.12-1.51), with weaker estimates in those aged ≥80 years. Among women, high/very high psychological distress was associated with an 18% increased risk of MI (adjusted hazard ratio, 1.18; 95% CI, 0.99-1.42) with similar findings across age groups. In the age group of participants aged 45 to 79 years, high/very high psychological distress and male sex had a supra-additive effect on MI risk. Similar estimates were observed for stroke, with high/very high psychological distress associated with a 24% and 44% increased stroke risk in men and women, respectively, with no evidence of interaction with age or sex. Conclusions Psychological distress has a strong, dose-dependent, positive association with MI and stroke in men and women, despite adjustment for a wide range of confounders

Time to negative throat culture following initiation of antibiotics for pharyngeal group A Streptococcus: a systematic review and meta-analysis up to October 2021 to inform public health control measures

Background: Public health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12–24 h from antibiotic initiation to prevent onward transmission requires a strong evidence base. Aim: To estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics through a systematic literature review (PROSPERO CRD42021290364) and meta-analysis. Methods: We searched Ovid MEDLINE (1946–), EMBASE (1974–) and Cochrane library. We included interventional or observational studies with ≥ 10 participants reporting rates of GAS throat culture positivity during antibiotic treatment for culture-confirmed GAS pharyngitis, scarlet fever and asymptomatic pharyngeal GAS carriage. We did not apply age, language or geographical restrictions. Results: Of 5,058 unique records, 43 were included (37 randomised controlled studies, three non-randomised controlled trials and three before-and-after studies). The proportion of individuals remaining culture-positive on day 1, day 2 and days 3–9 were 6.9% (95% CI: 2.7–16.8%), 5.4% (95% CI: 2.1–13.3%) and 2.6% (95% CI: 1.6–4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI: 2.5–16.1%) and 1.6% (95% CI: 0.04–42.9%), respectively. Overall, for 9.1% (95% CI: 7.3–11.3), throat swabs collected after completion of therapy were GAS culture-positive. Only six studies had low risk of bias. Conclusions: Our review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 h but highlights the need for further research given methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and asymptomatic individuals

At an important tephrostratigraphic crossroads: cryptotephra in Late Glacial to Early Holocene lake sediments from the Carpathian Mountains, Romania

Understanding the temporal and spatial environmental response to past climate change during the Last Glacial-Interglacial Transition (LGIT, 16-8 ka) across Europe relies on precise chronologies for palaeoenvironmental records. Tephra layers (volcanic ash) are a powerful chronological tool to synchronise disparate records across the continent. Yet, some regions remain overlooked in terms of cryptotephra investigations. Building on earlier work at the same sites, we present the first complete LGIT high-resolution cryptotephra investigation of two lake records in the Carpathian Mountains in Romania, Lake Brazi and Lake Lia. Numerous volcanic glass shards have been recognised as originating from various volcanic regions, including: Iceland (Katla, Askja, and Torfajokull), Italy (Campi Flegrei, Ischia, Lipari, and Pantelleria), and central Anatolia (Acigol and Ericyes). In total, four distinct tephra horizons have now been identified in these records: 1) an LGIT Lipari tephra (11,515–12,885 cal BP, 95.4% range); 2) Askja-S (11,070–10,720 cal BP, 95.4% range); 3) an Early Holocene Lipari tephra,(12,590–10,845 cal BP, 95.4% range) and; 4) an Early Holocene Ischia tephra (11,120–10,740 cal BP, 95.4% range). The use of trace element analysis on selected cryptotephra layers provided additional important information in identifying volcanic source and facilitating correlations. These tephra layers, along with numerous other discrete cryptotephra layers, offer promise as significant future isochrons for comprehending the spatial and temporal fluctuations in past climate change throughout Europe and the Mediterranean area. This research has emphasized the significance of the Carpathian region in expanding the European and Mediterranean tephra lattice and establishing it as a keystone area within the framework

The changing nature of risk and risk management: the challenge of borders, uncertainty and resilience

No abstract available

Analysis of interactions between the epigenome and structural mutability of the genome using Genboree workbench tools

Background: Interactions between the epigenome and structural genomic variation are potentially bi-directional. In one direction, structural variants may cause epigenomic changes in cis. In the other direction, specific local epigenomic states such as DNA hypomethylation associate with local genomic instability. Methods: To study these interactions, we have developed several tools and exposed them to the scientific community using the Software-as-a-Service model via the Genboree Workbench. One key tool is Breakout, an algorithm for fast and accurate detection of structural variants from mate pair sequencing data. Results: By applying Breakout and other Genboree Workbench tools we map breakpoints in breast and prostate cancer cell lines and tumors, discriminate between polymorphic breakpoints of germline origin and those of somatic origin, and analyze both types of breakpoints in the context of the Human Epigenome Atlas, ENCODE databases, and other sources of epigenomic profiles. We confirm previous findings that genomic instability in human germline associates with hypomethylation of DNA, binding sites of Suz12, a key member of the PRC2 Polycomb complex, and with PRC2-associated histone marks H3K27me3 and H3K9me3. Breakpoints in germline and in breast cancer associate with distal regulatory of active gene transcription. Breast cancer cell lines and tumors show distinct patterns of structural mutability depending on their ER, PR, or HER2 status. Conclusions: The patterns of association that we detected suggest that cell-type specific epigenomes may determine cell-type specific patterns of selective structural mutability of the genome

Changes over time in the "healthy soldier effect"

Background: Death rates in military populations outside of combat are often lower than those in the general population. This study considers how this "healthy soldier effect" changes over time.Methods: Standardized mortality ratios were used to compare changes in death rates relative to the Australian population in two large studies of Australian servicemen of the Korean War (n = 17,381) and the Vietnam War era (n = 83,908).Results: The healthy soldier effect was most consistently observed in deaths from circulatory diseases. A large deficit in these deaths in the initial follow-up period (10-20 years) was observed before rates tended to rise to the level seen in the general population. There was no healthy soldier effect in deaths from external causes in enlisted personnel, and these death rates were significantly higher than expected in the initial follow-up period among Korean War veterans and regular Army veterans of the Vietnam War. Those selected for national service during the Vietnam War exhibited the strongest healthy soldier effect of all cohorts assessed.Conclusions: Patterns of the healthy soldier effect over time varied markedly by study cohort and by cause of death studied. In a number of analyses, the healthy soldier effect was still apparent after more than 30 years of follow-up

Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts

<p>Abstract</p> <p>Background</p> <p>Histopathological grading of ependymoma has been controversial with respect to its reproducibility and clinical significance. In a 3-phase study, we reviewed the pathology of 229 intracranial ependymomas from European trial cohorts of infants (2 trials - SFOP/CNS9204) and older children (2 trials - AIEOP/CNS9904) to assess both diagnostic concordance among five neuropathologists and the prognostic utility of histopathological variables, particularly tumor grading.</p> <p>Results</p> <p>In phase 1, using WHO criteria and without first discussing any issue related to grading ependymomas, pathologists assessed and independently graded ependymomas from 3 of 4 trial cohorts. Diagnosis of grade II ependymoma was less frequent than grade III, a difference that increased when one cohort (CNS9204) was reassessed in phase 2, during which the pathologists discussed ependymoma grading, jointly reviewed all CNS9204 tumors, and defined a novel grading system based on the WHO classification. In phase 3, repeat independent review of two cohorts (SFOP/CNS9904) using the novel system was associated with a substantial increase in concordance on grading. Extent of tumor resection was significantly associated with progression-free survival (PFS) in SFOP and AIEOP, but not in CNS9204 and CNS9904. Strength of consensus on grade was significantly associated with PFS in only one trial cohort (AIEOP). Consensus on the scoring of individual histopathological features (necrosis, angiogenesis, cell density, and mitotic activity) correlated with PFS in AIEOP, but in no other trial.</p> <p>Conclusions</p> <p>We conclude that concordance on grading ependymomas can be improved by using a more prescribed scheme based on the WHO classification. Unfortunately, this appears to have utility in limited clinical settings.</p

"Dreaming in colour’: disabled higher education students’ perspectives on improving design practices that would enable them to benefit from their use of technologies"

The focus of this paper is the design of technology products and services for disabled students in higher education. It analyses the perspectives of disabled students studying in the US, the UK, Germany, Israel and Canada, regarding their experiences of using technologies to support their learning. The students shared how the functionality of the technologies supported them to study and enabled them to achieve their academic potential. Despite these positive outcomes, the students also reported difficulties associated with: i) the design of the technologies, ii) a lack of technology know-how and iii) a lack of social capital. When identifying potential solutions to these difficulties the disabled students imagined both preferable and possible futures where faculty, higher education institutions, researchers and technology companies are challenged to push the boundaries of their current design practices

BronchUK: protocol for an observational cohort study and biobank in bronchiectasis

Bronchiectasis has been a largely overlooked disease area in respiratory medicine. This is reflected by a shortage of large-scale studies and lack of approved therapies, in turn leading to a variation of treatment across centres. BronchUK (Bronchiectasis Observational Cohort and Biobank UK) is a multicentre, prospective, observational cohort study working collaboratively with the European Multicentre Bronchiectasis Audit and Research Collaboration project. The inclusion criteria for patients entering the study are a clinical history consistent with bronchiectasis and computed tomography demonstrating bronchiectasis. Main exclusion criteria are 1) patients unable to provide informed consent, 2) bronchiectasis due to known cystic fibrosis or where bronchiectasis is not the main or co-dominant respiratory disease, 3) age <18 years, and 4) prior lung transplantation for bronchiectasis. The study is aligned to standard UK National Health Service (NHS) practice with an aim to recruit a minimum of 1500 patients from across at least nine secondary care centres. Patient data collected at baseline includes demographics, aetiology testing, comorbidities, lung function, radiology, treatments, microbiology and quality of life. Patients are followed up annually for a maximum of 5 years and, where able, blood and/or sputa samples are collected and stored in a central biobank. BronchUK aims to collect robust longitudinal data that can be used for analysis into current NHS practice and patient outcomes, and to become an integral resource to better inform future interventional studies in bronchiectasis