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Physician-mentored patient rounds (PMPR) were used to assess diagnostic accuracy and treatment plans of preclinical medical students. During 4 PMPR sessions, students gathered patient history, observed a physical exam, analyzed diagnostic tests, and developed treatment plans for a patient with chronic obstructive pulmonary disease. Of 470 students, 99.4% correctly diagnosed the patient. Nearly 78% prescribed long-acting beta-agonists or long-acting muscarinic antagonists. Most included appropriate pharmacologic treatments. Only 47% included smoking cessation in their treatment.

Thirteen entrustable professional activities (EPAs) for entering residency were created to aid medical educators as they prepare preclinical students for their residency and to assess student readiness for residency. The A.T. Still University Kirksville College of Osteopathic Medicine (ATSU-KCOM) developed a program called physician-mentored patient rounds (PMPR), which focuses on EPA 1 and EPA 2.To determine whether PMPRs could be used to assess expected behaviors of EPA 1 (gather a history and perform a physical examination) and EPA 2 (prioritize a differential diagnosis after a clinical encounter).The PMPR sessions at ATSU-KCOM take place over several weeks (30-minute sessions per week), during which students gather a patient's history (sessions 1 and 2), observe a physical examination by the physician mentor (session 2), analyze diagnostic test results (session 3), and formulate a treatment plan (session 4). The PMPRs in this study used a real patient with confirmed chronic obstructive pulmonary disease (COPD). This study did not include the session-4 treatment plan. Between sessions, students completed an assignment to further demonstrate their behaviors as expected in the EPAs. Student responses were analyzed and summarized for physician feedback in the subsequent PMPR session. Students’ diagnostic accuracy was measured at the conclusion of each session.A total of 516 students were included in the study. The PMPR weekly attendance was high (453-475). Although history gathering in the large-group setting was disorderly, diagnostic accuracy over the 3-session period improved. After history taking, 411 students (86.5%) included COPD in the differential diagnosis. A smaller number, 235 students (49.5%), listed COPD as the most likely diagnosis. After the physical examination, 439 included COPD in the differential diagnosis, and 385 listed COPD as the most likely diagnosis. After analysis of diagnostic test results, 468 students listed COPD as the most likely diagnosis.Physician-mentored patient rounds seem to be an effective means to assess preclinical students’ expected behaviors as described in EPA 1 and EPA 2.

A growing body of work suggests that the extreme weather events that drive inland flooding are likely to increase in frequency and magnitude in a warming climate, thus potentially increasing flood damages in the future. We use hydrologic projections based on the Coupled Model Intercomparison Project Phase 5 (CMIP5) to estimate changes in the frequency of modeled 1 % annual exceedance probability (1 % AEP, or 100-year) flood events at 57 116 stream reaches across the contiguous United States (CONUS). We link these flood projections to a database of assets within mapped flood hazard zones to model changes in inland flooding damages throughout the CONUS over the remainder of the 21st century. Our model generates early 21st century flood damages that reasonably approximate the range of historical observations and trajectories of future damages that vary substantially depending on the greenhouse gas (GHG) emissions pathway. The difference in modeled flood damages between higher and lower emissions pathways approaches USD 4 billion per year by 2100 (in undiscounted 2014 dollars), suggesting that aggressive GHG emissions reductions could generate significant monetary benefits over the long term in terms of reduced flood damages. Although the downscaled hydrologic data we used have been applied to flood impacts studies elsewhere, this research expands on earlier work to quantify changes in flood risk by linking future flood exposure to assets and damages on a national scale. Our approach relies on a series of simplifications that could ultimately affect damage estimates (e.g., use of statistical downscaling, reliance on a nationwide hydrologic model, and linking damage estimates only to 1 % AEP floods). Although future work is needed to test the sensitivity of our results to these methodological choices, our results indicate that monetary damages from inland flooding could be significantly reduced through substantial GHG mitigation.

Purpose Tumor hypoxia reduces the efficacy of radiation and chemotherapy as well as altering gene expression that promotes cell survival and metastasis. The growth factor receptor, Her2/neu, is overexpressed in 25–30% of breast tumors. Tumors that are Her2 + may have an altered state of oxygenation, relative to Her2 − tumors, due to differences in tumor growth rate and angiogenesis. Methods Her2 blockade was accomplished using an antibody to the receptor (trastuzumab; Herceptin). This study examined the effects of Her2 blockade on tumor angiogenesis, vascular architecture, and hypoxia in Her2 + and Her2 − MCF7 xenograft tumors. Results Treatment with trastuzumab in Her2 + tumors significantly improved tumor oxygenation, increased microvessel density, and improved vascular architecture compared with the control-treated Her2 + tumors. The Her2 + xenografts treated with trastuzumab also demonstrated decreased proliferation indices when compared with control-treated xenografts. These results indicate that Her2 blockade can improve tumor oxygenation by decreasing oxygen consumption (reducing tumor cell proliferation and inducing necrosis) and increasing oxygen delivery (vascular density and architecture). Conclusions These results support the use of trastuzumab as an adjunct in the treatment of breast tumors with chemotherapy or radiotherapy, as improvements in tumor oxygenation should translate into improved treatment response.

Background Rare variants (RV) in immunoglobulin mu‐binding protein 2 (IGHMBP2) [OMIM 600502] can cause an autosomal recessive type of Charcot‐Marie‐Tooth (CMT) disease [OMIM 616155], an inherited peripheral neuropathy. Over 40 different genes are associated with CMT, with different possible inheritance patterns. Methods and Results An 11‐year‐old female with motor delays was found to have distal atrophy, weakness, and areflexia without bulbar or sensory findings. Her clinical evaluation was unrevealing. Whole exome sequencing (WES) revealed a maternally inherited IGHMBP2 RV (c.1730T>C) predicted to be pathogenic, but no variant on the other allele was identified. Deletion and duplication analysis was negative. She was referred to the Undiagnosed Disease Network (UDN) for further evaluation. Whole genome sequencing (WGS) confirmed the previously identified IGHMBP2 RV and identified a paternally inherited non‐coding IGHMBP2 RV. This was predicted to activate a cryptic splice site perturbing IGHMBP2 splicing. Reverse transcriptase polymerase chain reaction (RT‐PCR) analysis was consistent with activation of the cryptic splice site. The abnormal transcript was shown to undergo nonsense‐mediated decay (NMD), resulting in halpoinsufficiency. Conclusion This case demonstrates the deficiencies of WES and traditional molecular analyses and highlights the advantages of utilization of WGS and functional studies. An 11‐year‐old girl with a clinical presentation consistent with Charcot‐Marie‐Tooth syndrome was referred to the Undiagnosed Diseases Network after her genetic testing, including whole exome sequencing, revealed only a single pathogenic variant in IGHMBP2. Whole genome sequencing revealed a second intronic variant on the other allele of IGHMBP2. This was shown to activate a cryptic splice site and is transcribed to a protein product that undergoes non‐sense mediated decay.

HIP 41378 f is a temperate \\(9.2\\pm0.1 R_{\\oplus}\\) planet with period of 542.08 days and an extremely low density of \\(0.09\\pm0.02\\) g cm\\(^{-3}\\). It transits the bright star HIP 41378 (V=8.93), making it an exciting target for atmospheric characterization including transmission spectroscopy. HIP 41378 was monitored photometrically between the dates of 2019 November 19 and November 28. We detected a transit of HIP 41378 f with NGTS, just the third transit ever detected for this planet, which confirms the orbital period. This is also the first ground-based detection of a transit of HIP 41378 f. Additional ground-based photometry was also obtained and used to constrain the time of the transit. The transit was measured to occur 1.50 hours earlier than predicted. We use an analytic transit timing variation (TTV) model to show the observed TTV can be explained by interactions between HIP 41378 e and HIP 41378 f. Using our TTV model, we predict the epochs of future transits of HIP 41378 f, with derived transit centres of T\\(_{C,4} = 2459355.087^{+0.031}_{-0.022}\\) (May 2021) and T\\(_{C,5} = 2459897.078^{+0.114}_{-0.060}\\) (Nov 2022).