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The present study investigated the extent to which individual differences in humor styles are attributable to genetic and/or environmental factors in an Australian sample. Participants were 934 same-sex pairs of adult twins from the Australian Twin Registry (546 monozygotic pairs, 388 dizygotic pairs) who completed the Humor Styles Questionnaire (HSQ). The HSQ measures four distinct styles of humor — affiliative, self-enhancing, aggressive, and self-defeating. Results revealed that additive genetic and non-shared environmental factors accounted for the variance in all four humor styles, thus replicating results previously obtained in a sample of twins from the United Kingdom. However, a study conducted with a U.S. sample produced different results and we interpret these findings in terms of cross-cultural differences in humor.

Understanding the causes of recent catastrophic ice shelf disintegrations is a crucial step towards improving coupled models of the Antarctic Ice Sheet and predicting its future state and contribution to sea-level rise. An overlooked climate-related causal factor is regional sea ice loss. Here we show that for the disintegration events observed (the collapse of the Larsen A and B and Wilkins ice shelves), the increased seasonal absence of a protective sea ice buffer enabled increased flexure of vulnerable outer ice shelf margins by ocean swells that probably weakened them to the point of calving. This outer-margin calving triggered wider-scale disintegration of ice shelves compromised by multiple factors in preceding years, with key prerequisites being extensive flooding and outer-margin fracturing. Wave-induced flexure is particularly effective in outermost ice shelf regions thinned by bottom crevassing. Our analysis of satellite and ocean-wave data and modelling of combined ice shelf, sea ice and wave properties highlights the need for ice sheet models to account for sea ice and ocean waves. Less sea ice allowed ocean swells to flex weakened ice shelves in Antarctica, contributing to their collapse.

Anti-programmed death (ligand) 1 (anti-PD-(L)1) therapies were first introduced in the metastatic setting and have since been approved and reimbursed for treating early-stage cancers in the adjuvant, perioperative, and neoadjuvant settings in many cancer types. Current evidence supporting anti-PD(L)-1 retreatment after relapse with prior neoadjuvant and/or adjuvant anti-PD(L)1 therapy is limited and inconclusive. There is no guidance for clinicians on how and when to retreat with anti-PD-(L)1 therapies when anti-PD-(L)1 therapy was administered in the neoadjuvant and/or adjuvant setting. This study aimed to reach consensus on factors to guide decision-making regarding retreatment with anti-PD-(L)1 therapies after prior therapy with an anti-PD-(L)1 agent. This modified Delphi study consisted of a clinician survey across 10 countries followed by three real-time virtual Delphi panels involving clinical experts who had completed the survey. Clinical experts were experienced in using anti-PD-(L)1 treatments in early-stage cancers and/or as retreatment of patients with recurrences following early-stage treatment with anti-PD-(L)1 therapies. Of 28 clinicians providing survey responses, 20 participated in one of three Delphi panels. There was consensus that retreatment can be defined as ‘repeated treatment with the same therapeutic class following relapse after or during neoadjuvant and/or adjuvant treatment.’ All three panels agreed that decisions around retreatment should consider ‘prior immune-related adverse events/toxicity,’ ‘time-related factors’ (eg, time since completion of full treatment course and since discontinuation) and ‘previous patient response’ (often referred to by clinicians as tumor response, which may have reflected their experience with metastatic disease). Other factors identified as important included country-specific practices, treatment availability, and reimbursement. Generally, the clinical experts considered that retreatment could be considered from ≥3 to 6 months after stopping initial anti-PD-(L)1 treatment, or from ≥6 months after relapse/recurrence. In conclusion, clinicians across different regions recognized a role for retreating patients with anti-PD-(L)1 therapies after initial anti-PD-(L)1 treatment for early-stage cancers. Consensus was reached on some factors to consider regarding whether and when to retreat, although differences in clinical practice between countries/geographical regions made it difficult to achieve consensus for some more nuanced elements of retreatment. Further evidence could help better inform retreatment decisions.

Weakly basic, poorly soluble chemical agents could be exploited as building blocks for constructing sophisticated molecular devices inside the cells of living organisms. Here, using experimental and computational approaches, we probed the relationship between the biological mechanisms mediating lysosomal ion homeostasis and the self-assembly of a weakly basic small molecule building block (clofazimine) into a functional, mechanopharmaceutical device (intracellular Crystal-Like Drug Inclusions – “CLDIs”) in macrophage lysosomes. Physicochemical considerations indicate that the intralysosomal stabilization of the self-assembled mechanopharmaceutical device depends on the pH max of the weakly basic building block and its affinity for chloride, both of which are consistent with the pH and chloride content of a physiological lysosomal microenvironment. Most importantly, in vitro and in silico studies revealed that high expression levels of the vacuolar ATPase (V-ATPase), irrespective of the expression levels of chloride channels, are necessary and sufficient to explain the cell-type dependent formation, stabilization, and biocompatibility of the self-assembled mechanopharmaceutical device within macrophages.

AimsTo determine disc haemorrhage (DH) prevalence in an elderly UK population—the Bridlington Eye Assessment Project (BEAP).MethodsThirty-degree fundus photographs (3549 participants ≥65 years) were graded for DH/macula changes. Glaucoma evaluation included Goldmann tonometry, 26-point suprathreshold visual-fields and mydriatic slit-lamp assessment for glaucomatous optic neuropathy.ResultsIn all, 3548 participants with photographs in at least one eye. DHs were present in 53 subjects (1.49%), increasing from 1.17% (65- to 69-year age group) to 2.19% (80- to 84-year age group), p = 0.06. DH was found in 9/96 (9.38%) right eyes (RE) with open-angle glaucoma (OAG). Two of twelve RE (16.67%) with normal-tension glaucoma (NTG) had DH. Prevalence in eyes without glaucoma was lower (32/3452, [0.93%]). Reticular pseudodrusen (RPD) occurred in 170/3212 (5.29%) subjects without DH, and 8/131 subjects (6.11%) with OAG. Twenty eyes had NTG, two of whom had RPD (10%) (p = 0.264). Within a logistic regression model, DH was associated with glaucoma (OR 10.2, 95% CI 5.32–19.72) and increasing age (OR 1.05, 95% CI 1.00–1.10, p = 0.03). DH was associated with RPD (p = 0.05) with univariate analysis but this was not statistically significant in the final adjusted model. There was no significant association with gender, diabetes mellitus (DM), hypertension treatment or Age-related Macular Degeneration (AMD) grade.ConclusionDH prevalence is 1.5% in those over 65 years old and significantly associated with glaucoma and increasing age. There appears to be increased RPD prevalence in eyes with DH and NTG with age acting as a confounding factor. Larger studies are required to fully assess the relationship and investigate a possible shared aetiology of choroidal ischaemia.

The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in trauma is not fully defined. This study describes our trauma experience with hydrocortisone-treated patients experiencing CIRCI. We conducted a 5-year retrospective analysis from a Level II trauma center using biochemical and clinical criteria for adrenal insufficiency. Seventy patients met the inclusion criteria for CIRCI. There was a 34 per cent mortality rate despite therapy. Nonsurvivors were older with larger admission base deficits and experienced higher rates of sepsis, bacteremia, and pneumonia. Nonsurvivors had prolonged vent days (mean 53 ± 64 days) when compared with survivors (mean 30 ± 22 days; P = 0.029). Renal replacement therapy was a strong predictor of mortality. Spinal cord-injured patients had high Injury Severity Scores (mean 34 ± 18), elevated baseline Cortisol levels (mean 56 ± 84 vs 18 ± 14; P = 0.004), and required prolonged duration of steroid therapy (30 ± 52 vs 15 ± 15 days; P = 0.080) when compared with the nonspinal cord-injured group. Our data suggest that CIRCI in trauma is associated with significant mortality and morbidity even when patients are treated appropriately.

The advent of immune checkpoint inhibitors (ICIs) for cancer therapy has heralded increasing frequency of immune-related adverse events including endocrinopathies, hepatitis, colitis and rarely myocarditis and myasthenia gravis (MG). The heterogeneity in clinical presentations regardless of organ-specific involvement can lead to delayed recognition and management of these events and adverse health outcomes. We describe a case of ICI-induced subclinical focal myocarditis that was recognised and treated in the broader context of MG. It is essential that patients with ICI-induced MG should be screened and monitored for myocarditis, a potentially fatal complication.

On May 2, 2005, a new in vitro test, QuantiFERON®-TB Gold (QFT-G, Cellestis Limited, Carnegie, Victoria, Australia), received final approval from the U.S. Food and Drug Administration as an aid for diagnosing Mycobacterium tuberculosis infection. This test detects the release of interferon-gamma (IFN-γ) in fresh heparinized whole blood from sensitized persons when it is incubated with mixtures of synthetic peptides representing two proteins present in M. tuberculosis: early secretory antigenic target—6 (ESAT-6) and culture filtrate protein—10 (CFP-10). These antigens impart greater specificity than is possible with tests using purified protein derivative as the tuberculosis (TB) antigen. In direct comparisons, the sensitivity of QFT-G was statistically similar to that of the tuberculin skin test (TST) for detecting infection in persons with untreated culture-confirmed tuberculosis (TB). The performance of QFT-G in certain populations targeted by TB control programs in the United States for finding latent TB infection is under study. Its ability to predict who eventually will have TB disease has not been determined, and years of observational study of substantial populations would be needed to acquire this information. In July 2005, CDC convened a meeting of consultants and researchers with expertise in the field to review scientific evidence and clinical experience with QFT-G. On the basis of this review and discussion, CDC recommends that QFT-G may be used in all circumstances in which the TST is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for health-care workers). This report provides specific cautions for interpreting negative QFT-G results in persons from selected populations. This report is aimed at public health officials, health-care providers, and laboratory workers with responsibility for TB control activities in the United States.