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On November 21, 2022, Dr. Carrie Lee, associate professor and Chair of the Department of National Security and Strategy at the US Army War College, presented on Civil-Military Relations and Political Military Relations in the Context of Threat Resiliency. The key points discussed included the importance of good civil-military relations, how they are critical in establishing resiliency, and some of the threats that require good civil-military relations. Received: 2022-12-05 Revised: 2022-12-07

Inefficient differentiation and insufficient maturation are barriers to the application of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) for research and therapy. Great strides have been made to the former, and multiple groups have reported cardiac differentiation protocol that can generate hPSC-CMs at high efficiency. Although many such protocols are based on the modulation of the WNT signaling pathway, they differ in their timing and in the WNT inhibitors used. Little is currently known about whether and how conditions of differentiation affect cardiac maturation. Here we adapted multiple cardiac differentiation protocols to improve cost-effectiveness and consistency, and compared the properties of the hPSC-CMs generated. Our results showed that the schedule of differentiation, but not the choice of WNT inhibitors, was a critical determinant not only of differentiation efficiency, which was expected, but also CM maturation. Among cultures with comparable purity, hPSC-CMs generated with different differentiation schedules vary in the expression of genes which are important for developmental maturation, and in their structural, metabolic, calcium transient and proliferative properties. In summary, we demonstrated that simple changes in the schedule of cardiac differentiation could promote maturation. To this end, we have optimized a cardiac differentiation protocol that can simultaneously achieve high differentiation efficiency and enhanced developmental maturation. Our findings would advance the production of hPSC-CMs for research and therapy.

Summary: Bicuspid aortic valve (BAV) with ∼1%–2% prevalence is the most common congenital heart defect (CHD). It frequently results in valve disease and aorta dilation and is a major cause of adult cardiac surgery. BAV is genetically linked to rare left-heart obstructions (left ventricular outflow tract obstructions [LVOTOs]), including hypoplastic left heart syndrome (HLHS) and coarctation of the aorta (CoA). Mouse and human studies indicate LVOTO is genetically heterogeneous with a complex genetic etiology. Homozygous mutation in the Pcdha protocadherin gene cluster in mice can cause BAV, and also HLHS and other LVOTO phenotypes when accompanied by a second mutation. Here we show two common deletion copy number variants (delCNVs) within the PCDHA gene cluster are associated with LVOTO. Analysis of 1,218 white individuals with LVOTO versus 463 disease-free local control individuals yielded odds ratios (ORs) at 1.47 (95% confidence interval [CI], 1.13–1.92; p = 4.2 × 10−3) for LVOTO, 1.47 (95% CI, 1.10–1.97; p = 0.01) for BAV, 6.13 (95% CI, 2.75–13.7; p = 9.7 × 10−6) for CoA, and 1.49 (95% CI, 1.07–2.08; p = 0.019) for HLHS. Increased OR was observed for all LVOTO phenotypes in homozygous or compound heterozygous PCDHA delCNV genotype comparison versus wild type. Analysis of an independent white cohort (381 affected individuals, 1,352 control individuals) replicated the PCDHA delCNV association with LVOTO. Generalizability of these findings is suggested by similar observations in Black and Chinese individuals with LVOTO. Analysis of Pcdha mutant mice showed reduced PCDHA expression at regions of cell-cell contact in aortic smooth muscle and cushion mesenchyme, suggesting potential mechanisms for BAV pathogenesis and aortopathy. Together, these findings indicate common variants causing PCDHA deficiency play a significant role in the genetic etiology of common and rare LVOTO-CHD.

BackgroundInduction with four cycles of platinum-based chemotherapy was the standard of care for metastatic non-small cell lung cancer (NSCLC) until the approval of immune checkpoint blockade (ICB) in the first-line setting. Switch maintenance therapy has shown promise in improving survival by exposing patients to novel, non-cross–resistant agents earlier in their treatment course.MethodsWe performed this open-label, three-arm, randomized phase II study (NCT02684461) to evaluate three sequences of consolidation with pembrolizumab and nab-paclitaxel in patients without progressive disease post induction chemotherapy. Consolidation was either sequential with pembrolizumab for four cycles followed by nab-paclitaxel for four cycles (P→A), nab-paclitaxel followed by pembrolizumab (A→P), or concurrent nab-paclitaxel and pembrolizumab for four cycles (AP).ResultsTwenty patients were randomized before the study was closed early due to the approval of first-line checkpoint inhibitors. We found that consolidation is feasible and well tolerated, with 30% of patients experiencing grade 3 toxicity. The median progression-free survival and OS in months (95% CI) in P→A were 10.1 (1.5–NR), 27.6 (1.7–NR); 8.4 (1.2–9.0), 12.7 (4.4–NR) in A→P; and 10.2 (5.1–NR), NR. Quality of life as measured by FACT-L improved in the majority of patients during the course of the study.ConclusionSequential and concurrent consolidation regimens are well tolerated and have encouraging overall survival in patients with metastatic NSCLC.

Four case studies of preservice teachers enrolled in a STEM-focused elementary teacher preparation program are used to document changes in mathematics and science teaching efficacy over the course of one academic year. Qualitative analysis revealed that all four case studies experienced changes in their mathematics and science teaching efficacy beliefs over the course of the year. Participants described unique ways of understanding their growth (or lack thereof) in teaching efficacy, the trajectory of teaching efficacy over the course of the year, and the role of teacher training in changing their efficacy beliefs.

Gay men are a subgroup vulnerable to depression and suicidality. The prevalence of depression among gay men is three times higher than the general adult population. Because depression is a known risk factor for suicide, gay men are also at high risk for suicidality. Despite the high prevalence of depression and suicidality, health researchers and health care providers have tended to focus on sexual health issues, most often human immunodeficiency virus in gay men. Related to this, gay men’s health has often been defined by sexual practices, and poorly understood are the intersections of gay men’s physical and mental health with social determinants of health including ethnicity, locale, education level, and socioeconomic status. In the current article summated is literature addressing risk factors for depression and suicidality among gay men including family acceptance of their sexual identities, social cohesion and belonging, internalized stigma, and victimization. Barriers to gay men’s help seeking are also discussed in detailing how health care providers might advance the well-being of this underserved subgroup by effectively addressing depression and suicidality.

Learning science is a social enterprise that involves students communicating ideas, observations, and findings. Navigating talk between students about scientific concepts and practices is a complex task for teachers. Traditionally, science educators have used a method called microteaching (teaching to peers) as a context for practicing teaching. In this study, science educators created practice sessions called rehearsals, designed for elementary teacher candidates (ETCs) to participate in deliberate teaching episodes using discourse skills followed by instructor feedback. This NSF-supported work explores the use of rehearsals within virtual simulations software called Mursion® (developed as TeachLivE™) as compared to traditional rehearsals by using treatment and comparison groups. This study found that ETCs in both contexts increased in their use of various talk moves between rehearsal timepoints. Compared to the control group, the treatment group was able to address students' ideas and understanding more frequently in the rehearsal settings as well as the classroom setting (practicum). This finding indicates that ETCs felt comfortable utilizing student avatars when practicing specific teaching skills and were able to transfer some of these skills into the classroom setting. Creating valuable teaching experiences in teacher preparation is essential and this study explores the possibility of using a new innovative context as a space for ETCs to practice those skills.

The vertical flow constructed wetland (VFCW) has become an attractive decentralised technology for septage treatment. One of the main purposes of the septage treatment is to reduce the volume of raw septage through dewatering, where the solids content is retained in the wetland bed and the water content is released. The retention of solids forms a layer of sludge deposit at the wetland surface, and the drained water, the so-called leachate, typically contains a lower solids content. This article reports the performance of dewatering and filtration of a pilot-scale VFCW designed for septage treatment. A comparison between two feeding strategies, hydraulic loading rate (HLR) and solids loading rate (SLR), is presented. The dewatering efficiency through drainage was found to be dependent on the solids load. The removal of total solids (TS) and chemical oxygen demand (COD) were excellent as the quality of leachate showed that more than 90% of TS and COD were retained in the system. This study reveals that the feeding based on SLR delivered a more sustainable performance for dewatering and solids removal. The build-up of sludge deposit significantly deteriorated the dewatering efficiency through drainage, but it tended to improve the filtration capacity.

Egg allergy is one of the most common food allergies in children. Most egg-allergic children are able to tolerate egg baked in product (EBP) and will likely outgrow his/her egg allergy. By introducing EBP in the diet of an egg-allergic child, diet can be expanded and family stress can be reduced. Recent evidence suggests that children who tolerate EBP and continue to consume it will have quicker resolution of egg allergy than those who strictly avoid EBP; therefore, we aimed to evaluate the egg-allergic children who underwent EBP oral food challenge (OFC) in our allergy clinic to help define any specific predictors to be used in predicting the outcome of such challenges. We performed a retrospective chart review and 43 egg-allergic patients underwent EBP OFC in our outpatient allergy office from January 2011 to December 2012 were excluded. Nine patients who did not have a prior history of symptomatic egg ingestion. Clinical characteristics and laboratory findings of the remaining 34 patients were all recorded and analyzed. Of the remaining 34 patients, 22 (64.7%) were boys. Average age of first reaction to egg was 12.90 months, with average age at EBP OFC of 71.32 months. The average of the most recent skin-prick test wheal size was 10.10 mm and serum-specific IgE to egg white was 3.21 kU/L. Twenty-eight of the 34 patients (82.4%) passed the EBP OFC. Of the six patients who failed, none required epinephrine. After analysis of all of the clinical characteristics and laboratory findings, no risk factors, such as skin-prick test wheal size, were identified to be associated with an increased risk of failing EBP OFC. EBP OFC is a valuable tool to assess tolerance. As seen in our group of patients, the majority of egg-allergic patients pass EBP OFC. Thus, OFC should be considered as a clinical tool to expand a patient's diet and to improve quality of life as early as possible. Because we were unable to determine any clinical or laboratory predictors helpful to select egg-allergic patients who are likely to pass EBP OFC, additional prospective studies are necessary to determine the ideal egg-allergic patient who is likely to pass EBP OFC.