ENHANCING OFFICER DEVELOPMENT AND RETENTION IN THE NAVY SURFACE WARFARE COMMUNITY

This thesis examines the challenges faced by the Navy Surface Warfare Officer (SWO) community in developing officers with solid judgment and character while addressing the pressing issue of officer retention. By evaluating the existing Surface Warfare Officer Career Manual and the Surface Warfare Officer Requirements Document (SWORD), this research aims to enhance the framework for SWO career trajectories, emphasizing leadership, mentorship, and personal growth. The guiding instructions must emphasize a more comprehensive and dynamic career path for SWOs. The current system has identified shortcomings in providing reliable and continuous mentoring tools to monitor officer progression and offer comprehensive leadership feedback, which is essential for their professional growth. Existing measures in the SWO community have proven insufficient, resulting in lower retention rates than their counterparts in other officer communities. By addressing not only the technical aspects of the profession, but also the personal and leadership dimensions, the SWO community can better retain talented officers, foster a culture of mutual support, and ensure the long-term success of its members. This study proposes a comprehensive framework for Commander, Naval Surface Forces and associated SWO echelons to address technical, personal, and leadership dimensions to improve officer retention rates and overall community capability.Approved for public release. Distribution is unlimited.Lieutenant, United States Nav

Not Just for Scouting Anymore: Digital Badges for Legal Research Skills

American Association of Law Librarie

The Use of Maleic Hydrazide for Effective Hybridization of Setaria viridis

An efficient method for crossing green foxtail (Setaria viridis) is currently lacking. S. viridis is considered to be the new model plant for the study of C4 system in monocots and so an effective crossing protocol is urgently needed. S. viridis is a small grass with C4-NADP (ME) type of photosynthesis and has the advantage of having small genome of about 515 Mb, small plant stature, short life cycle, multiple tillers, and profuse seed set, and hence is an ideal model species for research. The objectives of this project were to develop efficient methods of emasculation and pollination, and to speed up generation advancement. We assessed the response of S. viridis flowers to hot water treatment (48°C) and to different concentrations of gibberellic acid, abscisic acid, maleic hydrazide (MH), and kinetin. We found that 500 μM of MH was effective in the emasculation of S. viridis, whilst still retaining the receptivity of the stigma to pollination. We also report effective ways to accelerate the breeding cycle of S. viridis for research through the germination of mature as well as immature seeds in optimized culture media. We believe these findings will be of great interest to researchers using Setaria

Mitochondrial Rejuvenation After Induced Pluripotency

Background: As stem cells of the early embryo mature and differentiate into all tissues, the mitochondrial complement undergoes dramatic functional improvement. Mitochondrial activity is low to minimize generation of DNA-damaging reactive oxygen species during pre-implantation development and increases following implantation and differentiation to meet higher metabolic demands. It has recently been reported that when the stem cell type known as induced pluripotent stem cells (IPSCs) are re-differentiated for several weeks in vitro, the mitochondrial complement progressively re-acquires properties approximating input fibroblasts, suggesting that despite the observation that IPSC conversion ‘‘resets’ ’ some parameters of cellular aging such as telomere length, it may have little impact on other age-affected cellular systems such as mitochondria in IPSC-derived cells. Methodology/Principal Findings: We have examined the properties of mitochondria in two fibroblast lines, corresponding IPSCs, and fibroblasts re-derived from IPSCs using biochemical methods and electron microscopy, and found a dramatic improvement in the quality and function of the mitochondrial complement of the re-derived fibroblasts compared to input fibroblasts. This observation likely stems from two aspects of our experimental design: 1) that the input cell lines used were of advanced cellular age and contained an inefficient mitochondrial complement, and 2) the re-derived fibroblasts were produced using an extensive differentiation regimen that may more closely mimic the degree of growth and maturatio

Encorafenib plus binimetinib in patients with BRAF(V)(600)-mutant non-small cell lung cancer: Phase II PHAROS study design

BRAF(V600) oncogenic driver mutations occur in 1-2% of non-small cell lung cancers (NSCLCs) and have been shown to be a clinically relevant target. Preclinical/clinical evidence support the efficacy and safety of BRAF and MEK inhibitor combinations in patients with NSCLC with these mutations. We describe the design of PHAROS, an ongoing, open-label, single-arm, Phase II trial evaluating the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with metastatic BRAF(V600) -mutant NSCLC, as first- or second-line treatment. The primary endpoint is objective response rate, based on independent radiologic review (per RECIST v1.1); secondary objectives evaluated additional efficacy endpoints and safety. Results from PHAROS will describe the antitumor activity/safety of encorafenib plus binimetinib in patients with metastatic BRAF(V600)-mutant NSCLC.Lay abstract: Some people with non-small cell lung cancer (NSCLC) have changes in a gene called BRAF (known as 'gene mutations'). One common BRAF mutation is called 'V600'. Combinations of medicines that block proteins encoded by mutant BRAF and another gene called MEK can shrink tumors and slow their progression. We describe the design of PHAROS, a clinical trial investigating encorafenib (mutant BRAF inhibitor) combined with binimetinib (MEK inhibitor) in people with BRAF(V600)-mutant NSCLC that had spread to other parts of the body ('metastatic disease'). People are monitored for side effects and to see if their tumor shrunk. PHAROS includes people treated with encorafenib plus binimetinib as their first treatment for metastatic disease, and people whose cancer progressed after previous anticancer therapy.Pathogenesis and treatment of chronic pulmonary disease

The impact of minimally-invasive esophagectomy operative duration on post-operative outcomes

BackgroundEsophagectomy, an esophageal cancer treatment mainstay, is a highly morbid procedure. Prolonged operative time, only partially predetermined by case complexity, may be uniquely harmful to minimally-invasive esophagectomy (MIE) patients for numerous reasons, including anastomotic leak, tenuous conduit perfusion and protracted single-lung ventilation, but the impact is unknown. This multi-center retrospective cohort study sought to characterize the relationship between MIE operative time and post-operative outcomes.MethodsWe abstracted multi-center data on esophageal cancer patients who underwent MIE from 2010 to 2021. Predictor variables included age, sex, comorbidities, body mass index, prior cardiothoracic surgery, stage, and neoadjuvant therapy. Outcomes included complications, readmissions, and mortality. Association analysis evaluated the relationship between predictor variables and operative time. Multivariate logistic regression characterized the influence of potential predictor variables and operative time on post-operative outcomes. Subgroup analysis evaluated the association between MIE >4 h vs. ≤4 h and complications, readmissions and survival.ResultsFor the 297 esophageal cancer patients who underwent MIE between 2010 and 2021, the median operative duration was 4.8 h [IQR: 3.7–6.3]. For patients with anastomotic leak (5.1%) and 1-year mortality, operative duration was elevated above the median at 6.3 h [IQR: 4.8–8.6], p = 0.008) and 5.3 h [IQR: 4.4–6.8], p = 0.04), respectively. In multivariate logistic regression, each additional hour of operative time increased the odds of anastomotic leak and 1-year mortality by 39% and 19%, respectively.ConclusionsEsophageal cancer is a poor prognosis disease, even with optimal treatment. Operative efficiency, a modifiable surgical variable, may be an important target to improve MIE patient outcomes

Phase II, open-label study of encorafenib plus binimetinib in patients with BRAFV600-mutant metastatic non-small-cell lung cancer

PURPOSE The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAF(V600E/K)-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC).METHODS In this ongoing, open-label, single-arm, phase II study, patients with BRAF(V600E)-mutant metastatic NSCLC received oral encorafenib 450 mg once daily plus binimetinib 45 mg twice daily in 28-day cycles. The primary end point was confirmed objective response rate (ORR) by independent radiology review (IRR). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival, time to response, and safety.RESULTS At data cutoff, 98 patients (59 treatment-naive and 39 previously treated) with BRAF(V600E)-mutant metastatic NSCLC received encorafenib plus binimetinib. Median duration of treatment was 9.2 months with encorafenib and 8.4 months with binimetinib. ORR by IRR was 75% (95% CI, 62 to 85) in treatment-naive and 46% (95% CI, 30 to 63) in previously treated patients; median DOR was not estimable (NE; 95% CI, 23.1 to NE) and 16.7 months (95% CI, 7.4 to NE), respectively. DCR after 24 weeks was 64% in treatment-naive and 41% in previously treated patients. Median PFS was NE (95% CI, 15.7 to NE) in treatment-naive and 9.3 months (95% CI, 6.2 to NE) in previously treated patients. The most frequent treatment-related adverse events (TRAEs) were nausea (50%), diarrhea (43%), and fatigue (32%). TRAEs led to dose reductions in 24 (24%) and permanent discontinuation of encorafenib plus binimetinib in 15 (15%) patients. One grade 5 TRAE of intracranial hemorrhage was reported. Interactive visualization of the data presented in this article is available at the PHAROS dashboard ().CONCLUSION For patients with treatment-naive and previously treated BRAF(V600E)-mutant metastatic NSCLC, encorafenib plus binimetinib showed a meaningful clinical benefit with a safety profile consistent with that observed in the approved indication in melanoma.Pathogenesis and treatment of chronic pulmonary disease