Dungeness crab fishermen perceptions of injury causation and factors in staying safe

Background: Commercial fishing is a hazardous occupation in the United States (US). Injury surveillance data relies heavily on US Coast Guard reports, which capture injuries severe enough to require reporting. The reports do not incorporate the fishermen’s perspective on contributing factors to injuries and staying safe while fishing.  Materials and methods: We conducted a pre-season survey of Dungeness crab fishermen during 2015 to 2016. Community researchers administered surveys to fishermen. Respondents reported their opinions about factors contributing to injuries and staying safe, which were grouped into similar themes by consen- sus. Descriptive statistics were calculated to explore the number of injuries, crew position, age, and years of experience. Chi-square tests compared perceptions of injury causation, staying safe, and other factors.  Results: Four hundred twenty-six surveys were completed. Injury causation perceptions were sorted into 17 categories, and staying safe perceptions were sorted into 13 categories. The most frequently cited causes of injury were heavy workload (86, 21.9%), poor mental focus (78, 19.9%), and inexperience (56, 14.3%). The most frequently cited factors in staying safe while fishing were awareness (142, 36.1%), good and well-maintained fishing gear/vessel (41, 10.4%), and best marine practices (39, 9.9%). Opinions were not significantly associated with experiencing an injury in the past while fishing, but some opinions were significantly associated with crew position, age, and years of experience.  Conclusions: The perceptions of fishermen can be evaluated further and incorporated into training or intervention development. The fishermen-led approach of this project lends itself to developing injury pre- vention strategies that are effective, realistic and suitable. The resources available at FLIPPresources.org, such as informational sheets for new fishermen, sample crew agreements, and first aid kit resources, supply workers in this fishery with real solutions for issues they identified through their survey responses.

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Statistical Approaches for Assessing Outcomes in Community Birth

Community birth includes births that are planned to take place in a private home or in a freestanding birth center; they represent about 2% of all births in the United States. Cesarean birth can be a life-saving intervention for both women and babies, but it should only be used when medically necessary. Planned community births do not always end in a birth as planned at the original location. In some instances, it will be necessary for a woman in a community birth to transfer to a hospital for higher-level treatment. In the first study presented here, we created a propensity score matched cohort of community and hospital births, in order to assess any potential mediating effects of the midwifery model of prenatal care in community birth, compared to standard prenatal care in hospital birth, on the relationship between obesity and cesarean. Our results confirm that obesity is a risk factor for cesarean, and that the absolute risk of cesarean is lower in community birth compared to hospital birth. Women with obesity had higher odds of cesarean compared to women without obesity, both in community and hospital births, but there was no appreciable effect modification by place of birth setting. In the second study, we implemented four predictive modeling algorithms in the development and validation of a predictive model for transfers of care during or immediately after labor from community birth to hospital settings. We demonstrated that the extreme gradient boosting tree model exhibited the best performance metrics of the candidate models, which was validated in the held-back validation set. Primiparity was the most important characteristic in predicting transfer, followed by multiparity with history of cesarean birth only. Through these studies, we expanded on the existing evidence-base on outcomes of community birth in the United States, by applying advanced statistical modeling approaches to observational birth registry data

Hypernasality in singing among children with cleft palate: a preliminary study

The aim of this study was to document differences in hypernasality during speaking and singing among children with cleft palate and to compare nasality score ratings of trained and untrained listeners. Twenty subjects with cleft palate aged between 7 and 12 years participated in this study. Audio recordings were made of the children reading a passage and singing a common local song, both in the Malay language. The degree of hypernasality was judged through perceptual assessment. Three trained listeners (a speech therapist, a classical singer, and a linguistic expert – all academicians) and two untrained listeners (a cleft volunteer worker and a national high school teacher) assessed the recordings using a visual analogue scale (VAS). Inter-rater and intra-rater reliability for hypernasality in both speaking and singing were verified using the intra-class correlation coefficient (ICC). A significant reduction in hypernasality was observed during singing as compared to speaking, indicating that hypernasality reduces when a child with cleft palate sings. The act of singing significantly reduces hypernasality. The outcome of this study suggests that children with cleft palate would benefit from singing exercises to ultimately reduce hypernasality. However, future research is needed to objectively measure nasality in singing compared to speaking. © 2019 International Association of Oral and Maxillofacial Surgeon

KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance

Summary: Lung cancer treatment has benefited greatly through advancements in immunotherapies. However, immunotherapy often fails in patients with specific mutations like KEAP1, which are frequently found in lung adenocarcinoma. We established an antigenic lung cancer model and used it to explore how Keap1 mutations remodel the tumor immune microenvironment. Using single-cell technology and depletion studies, we demonstrate that Keap1-mutant tumors diminish dendritic cell and T cell responses driving immunotherapy resistance. This observation was corroborated in patient samples. CRISPR-Cas9-mediated gene targeting revealed that hyperactivation of the NRF2 antioxidant pathway is responsible for diminished immune responses in Keap1-mutant tumors. Importantly, we demonstrate that combining glutaminase inhibition with immune checkpoint blockade can reverse immunosuppression, making Keap1-mutant tumors susceptible to immunotherapy. Our study provides new insight into the role of KEAP1 mutations in immune evasion, paving the way for novel immune-based therapeutic strategies for KEAP1-mutant cancers