Free energy computation of particles with membrane-mediated interactions via Langevin dynamics.

We apply well-established concepts of Langevin sampling to derive a new class of algorithms for the efficient computation of free energy differences of fluctuating particles embedded in a ’fast’ membrane, i.e., a membrane that instantaneously adapts to varying particle positions. A geometric poten- tial accounting for membrane-mediated particle interaction is derived in the framework of variational hybrid models for particles in membranes. Recent explicit representations of the gradient of the geometric interaction poten- tial allows to apply well-known gradient based Markov Chain Monte-Carlo (MCDC) methods such as Langevin-based sampling

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

Effect of Intensive Training on Mood With No Effect on Brain-Derived Neurotrophic Factor

Purpose Monitoring mood state is a useful tool for avoiding non-functional overreaching (NFOR). Brain derived neurotrophic factor (BDNF) is implicated in stress-related mood disorders. The purpose of the present study was to investigate the impact of intensified training-induced mood disturbance on plasma BDNF concentrations at rest and in response to exercise.  Methods Eight cyclists performed 1 week of normal (NT), 1 week of intensified (INT) and 1 week of recovery (REC) training. Fasted blood samples were collected before and after exercise, on day 7 of each training week and were analyzed for plasma BDNF and cortisol concentrations. A 24-item Profile Of Mood State questionnaire was administered on day 7 of each training week and global mood score (GMS) was calculated. Results Time trial performance was impaired during INT (p=0.01) and REC (p=0.02) compared with NT. Basal plasma cortisol (NT=153±16 ng/ml, INT=130±11 ng/ml, REC=150±14 ng/ml) and BDNF (NT=484±122 pg/ml, INT=488±122 pg/ml, REC=383±56 pg/ml) concentrations were similar between training conditions. Likewise, similar exercise-induced increases in cortisol and BDNF concentrations were observed between training conditions. GMS was 32% greater during INTvs.NT (P<0.001). Conclusion Consistent with a state of functional overreaching (FOR), impairments in performance and mood state with INT were restored after one week of REC. These results support evidence that mood changes before plasma BDNF concentrations as a biochemical marker of FOR and that cortisol is not a useful marker for predicting FOR

GAS GENERATION MEASUREMENTS OF SCRAP PU/U MATERIALS USING A BELL JAR

ABSTRACT A bell jar is used to determine containment vessel pressurization due to gas generation from plutonium/uranium materials. Seventy eight food pack cans containing plutonium and uranium oxide bearing materials have been tested to date. Minimal change in pressure (increase or decrease) occurred in fifty one cases, depressurization occurred in seventeen cases, and pressurization occurred in ten cases. Pressurization is considered linked to the presence of certain impurities such as magnesium oxide

Phase I Study of Celecoxib with Concurrent Irinotecan, Cisplatin, and Radiation Therapy for Patients with Unresectable Locally Advanced Non-Small Cell Lung Cancer

Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclooxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II–III non-small cell lung cancer (NSCLC). Methods and Materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea). Grade 3 toxicities were leukopenia (five patients), fatigue (3), pneumonitis (2), dyspnea (1), pain (1), and esophageal stricture (1). Interestingly, pulmonary fibrosis (a late toxicity) was no more severe in the higher-dose (400-mg) group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial). Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusion: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal tissue toxicity

Gender plays no role in student ability to perform on computer-based examinations

BACKGROUND: To see if there is a difference in performance when students switch from traditional paper-and-pencil examinations to computer-based examinations, and to determine whether there are gender differences in student performance in these two examination formats. METHODS: This study involved first year medical students at the University of Illinois at Urbana-Champaign over three Academic Years 2002–03/2003–04 and 2003–05. Comparisons of student performance by overall class and gender were made. Specific comparisons within courses that utilized both the paper-and-pencil and computer formats were analyzed. RESULTS: Overall performance scores for students among the various Academic Years revealed no differences between exams given in the traditional pen-and-paper and computer formats. Further, when we looked specifically for gender differences in performance between these two testing formats, we found none. CONCLUSION: The format for examinations in the courses analyzed does not affect student performance. We find no evidence for gender differences in performance on exams on pen-and-paper or computer-based exams

The Leiden Convention coronary coding system: translation from the surgical to the universal view

Aims: The Leiden Convention coronary coding system structures the large variety of coronary anatomical patterns; isolated and in congenital heart disease. It is widely used by surgeons but not by cardiologists as the system uses a surgeons' cranial view. Since thoracic surgeons and cardiologists work closely together, a coronary coding system practical for both disciplines is mandatory. To this purpose, the 'surgical' coronary coding system was adapted to an 'imaging' system, extending its applicability to different cardiac imaging techniques.Methods and results: The physician takes place in the non-facing sinus of the aortic valve, oriented with the back towards the pulmonary valve, looking outward from the sinus. From this position, the right-hand sinus is sinus 1, and the left-hand sinus is sinus 2. Next, a clockwise rotation is adopted starting at sinus 1 and the encountered coronary branches described. Annotation of the normal anatomical pattern is 1R-2LCx, corresponding to the 'surgical' coding system. The 'imaging' coding system was made applicable for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), echocardiography, and coronary angiography, thus facilitating interdisciplinary use. To assess applicability in daily clinical practice, images from different imaging modalities were annotated by cardiologists and cardiology residents and results scored. The average score upon evaluation was 87.5%, with the highest scores for CT and MRI images (average 90%).Cardiolog

Tolerability of gefitinib in patients receiving treatment in everyday clinical practice

Gefitinib (‘Iressa’, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, has recently been approved in several countries for use in advanced or metastatic non-small-cell lung cancer (NSCLC). In contrast to chemotherapies, which are generally used at or near their maximum-tolerated dose (MTD), gefitinib is used at an optimal biological dose (250 mg day−1), which is substantially below its MTD, minimising the risk of adverse events without compromising efficacy. Tolerability data from the compassionate use of gefitinib in the ‘Iressa’ Expanded Access Programme support the favourable safety profile of the agent reported in Phase I and II trials. In both settings, the majority of adverse drug reactions were mild/moderate and consisted mainly of grade 1/2 diarrhoea and skin rash. Although skin rash has been suggested to predict response to gefitinib, available data do not support this hypothesis. Overall, these tolerability data demonstrate that gefitinib has a relatively benign side-effect profile and is a well-tolerated treatment option for patients with previously treated NCSLC, who currently have few alternatives

Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations

Observations of the lower atmosphere from the 2021 WiscoDISCO campaign

The mesoscale meteorology of lake breezes along Lake Michigan impacts local observations of high-ozone events. Previous manned aircraft and UAS observations have demonstrated non-uniform ozone concentrations within and above the marine layer over water and within shoreline environments. During the 2021 Wisconsin's Dynamic Influence of Shoreline Circulations on Ozone (WiscoDISCO-21) campaign, two UAS platforms, a fixed-wing (University of Colorado RAAVEN) and a multirotor (Purdue University DJI M210), were used simultaneously to capture lake breeze during forecasted high-ozone events at Chiwaukee Prairie State Natural Area in southeastern Wisconsin from 21&ndash;26&nbsp;May&nbsp;2021​​​​​​​. The RAAVEN platform (data DOI: https://doi.org/10.5281/zenodo.5142491, de Boer et al., 2021) measured temperature, humidity, and 3-D winds during 2&thinsp;h flights following two separate flight patterns up to three times per day at altitudes reaching 500&thinsp;m above ground level (a.g.l.). The M210 platform (data DOI: https://doi.org/10.5281/zenodo.5160346, Cleary et al., 2021a) measured vertical profiles of temperature, humidity, and ozone during 15&thinsp;min flights up to six times per day at altitudes reaching 120&thinsp;ma.g.l. near a Wisconsin DNR ground monitoring station (AIRS ID: 55-059-0019). This campaign was conducted in conjunction with the Enhanced Ozone Monitoring plan from the Wisconsin DNR that included Doppler lidar wind profiler observations at the site (data DOI: https://doi.org/10.5281/zenodo.5213039, Cleary et al., 2021b). &nbsp;</p