Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

CD103-positive tissue resident memory-like CD8+ T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Infiltration of CD8CD103 immune cell subsets was independent of clinicopathological factors. Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification. A survival benefit of CD8CD103 TRM was observed only in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future

Model confidence sets and forecast combination: an application to age-specific mortality

Background: Model averaging combines forecasts obtained from a range of models, and it often produces more accurate forecasts than a forecast from a single model. Objective: The crucial part of forecast accuracy improvement in using the model averaging lies in the determination of optimal weights from a finite sample. If the weights are selected sub-optimally, this can affect the accuracy of the model-averaged forecasts. Instead of choosing the optimal weights, we consider trimming a set of models before equally averaging forecasts from the selected superior models. Motivated by Hansen et al. (2011), we apply and evaluate the model confidence set procedure when combining mortality forecasts. Data & Methods: The proposed model averaging procedure is motivated by Samuels and Sekkel (2017) based on the concept of model confidence sets as proposed by Hansen et al. (2011) that incorporates the statistical significance of the forecasting performance. As the model confidence level increases, the set of superior models generally decreases. The proposed model averaging procedure is demonstrated via national and sub-national Japanese mortality for retirement ages between 60 and 100+. Results: Illustrated by national and sub-national Japanese mortality for ages between 60 and 100+, the proposed model-average procedure gives the smallest interval forecast errors, especially for males. Conclusion: We find that robust out-of-sample point and interval forecasts may be obtained from the trimming method. By robust, we mean robustness against model misspecification

Does the unification of health financing affect the distribution pattern of out‐of‐pocket health expenses in Turkey?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149529/1/ijsw12389_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149529/2/ijsw12389.pd

The role of soluble fiber intake in patients under highly effective lipid-lowering therapy

<p>Abstract</p> <p>Background</p> <p>It has been demonstrated that statins can increase intestinal sterol absorption. Augments in phytosterolemia seems related to cardiovascular disease.</p> <p>Objective</p> <p>We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy.</p> <p>Design</p> <p>In an open label, randomized, parallel-design study with blinded endpoints, subjects with primary hypercholesterolemia (n = 116) were assigned to receive during 12 weeks, a daily dose of 25 g of fiber (corresponding to 6 g of soluble fibers) plus rosuvastatin 40 mg (n = 28), rosuvastatin 40 mg alone (n = 30), sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber (n = 28), or sinvastatin 40 mg plus ezetimibe 10 mg (n = 30) alone.</p> <p>Results</p> <p>The four assigned therapies produced similar changes in total cholesterol, LDL-cholesterol, and triglycerides (p < 0.001 vs. baseline) and did not change HDL-cholesterol. Fiber intake decreased plasma campesterol (p < 0.001 vs. baseline), particularly among those patients receiving ezetimibe (p < 0.05 vs. other groups), and β-sitosterol (p = 0.03 vs. baseline), with a trend for lower levels in the group receiving fiber plus ezetimibe (p = 0.07). Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol (p = 0.003 vs. other groups). Compared to non-fiber supplemented individuals, those treated with fibers had weight loss (p = 0.04), reduced body mass index (p = 0.002) and blood glucose (p = 0.047).</p> <p>Conclusion</p> <p>Among subjects treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects, mainly by reducing phytosterolemia. Additional benefits include improvement in blood glucose and anthropometric parameters.</p

The Mental Vitality @ Work study: design of a randomized controlled trial on the effect of a workers' health surveillance mental module for nurses and allied health professionals

Employees in health care service are at high risk for developing mental health complaints. The effects of mental health complaints on work can have serious consequences for the quality of care provided by these workers. To help health service workers remain healthy and productive, preventive actions are necessary. A Workers' Health Surveillance (WHS) mental module may be an effective strategy to monitor and promote good (mental) health and work performance. The objective of this paper is to describe the design of a three arm cluster randomized controlled trial on the effectiveness of a WHS mental module for nurses and allied health professionals. Two strategies for this WHS mental module will be compared along with data from a control group. Additionally, the cost effectiveness of the approaches will be evaluated from a societal perspective. The study is designed as a cluster randomized controlled trial consisting of three arms (two intervention groups, 1 control group) with randomization at ward level. The study population consists of 86 departments in one Dutch academic medical center with a total of 1731 nurses and allied health professionals. At baseline, after three months and after six months of follow-up, outcomes will be assessed by online questionnaires. In both intervention arms, participants will complete a screening to detect problems in mental health and work functioning and receive feedback on their screening results. In cases of impairments in mental health or work functioning in the first intervention arm, a consultation with an occupational physician will be offered. The second intervention arm offers a choice of self-help e-mental health interventions, which will be tailored based on each individual's mental health state and work functioning. The primary outcomes will be help-seeking behavior and work functioning. Secondary outcomes will be mental health and wellbeing. Furthermore, cost-effectiveness in both intervention arms will be assessed, and a process evaluation will be performed. When it is proven effective compared to a control group, a WHS mental module for nurses and allied health professionals could be implemented and used on a regular basis by occupational health services in hospitals to improve employees' mental health and work functioning. NTR278

Monkeys and Humans Share a Common Computation for Face/Voice Integration

Speech production involves the movement of the mouth and other regions of the face resulting in visual motion cues. These visual cues enhance intelligibility and detection of auditory speech. As such, face-to-face speech is fundamentally a multisensory phenomenon. If speech is fundamentally multisensory, it should be reflected in the evolution of vocal communication: similar behavioral effects should be observed in other primates. Old World monkeys share with humans vocal production biomechanics and communicate face-to-face with vocalizations. It is unknown, however, if they, too, combine faces and voices to enhance their perception of vocalizations. We show that they do: monkeys combine faces and voices in noisy environments to enhance their detection of vocalizations. Their behavior parallels that of humans performing an identical task. We explored what common computational mechanism(s) could explain the pattern of results we observed across species. Standard explanations or models such as the principle of inverse effectiveness and a “race” model failed to account for their behavior patterns. Conversely, a “superposition model”, positing the linear summation of activity patterns in response to visual and auditory components of vocalizations, served as a straightforward but powerful explanatory mechanism for the observed behaviors in both species. As such, it represents a putative homologous mechanism for integrating faces and voices across primates

Esophageal and Gastric Malignancies After Bariatric Surgery: a Retrospective Global Study

Background: Bariatric surgery can influence the presentation, diagnosis, and management of gastrointestinal cancers. Esophagogastric (EG) malignancies in patients who have had a prior bariatric procedure have not been fully characterized. Objective: To characterize EG malignancies after bariatric procedures. Setting: University Hospital, United Kingdom. Methods: We performed a retrospective, multicenter observational study of patients with EG malignancies after bariatric surgery to characterize this condition. Results: This study includes 170 patients from 75 centers in 25 countries who underwent bariatric procedures between 1985 and 2020. At the time of the bariatric procedure, the mean age was 50.2 ± 10 years, and the mean weight 128.8 ± 28.9 kg. Women composed 57.3% (n = 98) of the population. Most (n = 64) patients underwent a Roux-en-Y gastric bypass (RYGB) followed by adjustable gastric band (AGB; n = 46) and sleeve gastrectomy (SG; n = 43). Time to cancer diagnosis after bariatric surgery was 9.5 ± 7.4 years, and mean weight at diagnosis was 87.4 ± 21.9 kg. The time lag was 5.9 ± 4.1 years after SG compared to 9.4 ± 7.1 years after RYGB and 10.5 ± 5.7 years after AGB. One third of patients presented with metastatic disease. The majority of tumors were adenocarcinoma (82.9%). Approximately 1 in 5 patients underwent palliative treatment from the outset. Time from diagnosis to mortality was under 1 year for most patients who died over the intervening period. Conclusion: The Oesophago-Gastric Malignancies After Obesity/Bariatric Surgery study presents the largest series to date of patients developing EG malignancies after bariatric surgery and attempts to characterize this condition.info:eu-repo/semantics/publishedVersio