Correlation Between Processing Conditions, Microstructure and Mechanical Behavior in Regenerated Silkworm Silk Fibers

Regenerated silkworm fibers spun through a wet-spinning process followed by an immersion postspinning drawing step show a work to fracture comparable with that of natural silkworm silk fibers in a wide range of spinning conditions. The mechanical behavior and microstructure of these high performance fibers have been characterized, and compared with those fibers produced through conventional spinning conditions. The comparison reveals that both sets of fibers share a common semicrystalline microstructure, but significant differences are apparent in the amorphous region. Besides, high performance fibers show a ground state and the possibility of tuning their tensile behavior. These properties are characteristic of spider silk and not of natural silkworm silk, despite both regenerated and natural silkworm silk share a common composition different from that of spider silk

Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial.

BACKGROUND: Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. METHODS/DESIGN: PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. DISCUSSION: This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. TRIAL REGISTRATION: NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014)

Retention latch mechanism for the Wake Shield Facility

The Wake Shield Facility (WSF) is a space transportation system (STS) payload that is scheduled for launch on STS-60 in November, 1993. It is being designed, tested and integrated into the STS by Space Industries Inc. for the University of Houston's Space Vacuum Epitaxy Center, a NASA Center for the Commercial Development of Space. The WSF is composed of two main components: a cross-bay carrier and a free-flying experimental platform. The WSF's primary objective is the epitaxial growth of thin films by controlled beam techniques in the ultra-high vacuum that exists in the wake of the free-flyer. The Retention Latch Mechanism (RLM) has been developed to act as the structural interface between the free-flyer and the carrier

Need and importance of health protection training in Nepal

By investing in health protection, the health of the nation can be safeguarded from future threats of uncontrolled infectious disease epidemics and disasters

Designing for Students: Creating a Robust Interdisciplinary First Year Course

Building a general education program from scratch for a population of first generation and underserved students provided both a challenge and opportunity. Faculty who had limited previous experience teaching and assessing first year students engaged in study of the best practices and research. Faculty designed a four-year general education curriculum that began with a robust First Year Seminar (FYS) course, the focus of this study. This required three-credit hour interdisciplinary humanities course (FYS) was designed to embrace the understanding of what it means to be human, including understanding oneself in relation to the natural world and to others. Full time faculty from all disciplines were selected through a competitive process to teach the FYS course with embedded High Impact Practices (HIPs). Four years of teaching FYS has provided qualitative and quantitative data on the effectiveness of the design, the role of faculty, and application of HIPs. Through the course assessment process and data analysis, faculty have expanded their repertoire of pedagogical strategies to engage the first year student, and as a result, positively influenced teaching in their other courses. This report offers insights on strategies for course design, the role of faculty, and the power of selected HIPs that may be replicated at other institutions

Severe leukoencephalopathy with fulminant cerebral edema reflecting immune reconstitution inflammatory syndrome during HIV infection: a case report

<p>Abstract</p> <p>Introduction</p> <p>Immune reconstitution inflammatory syndrome is a well-known complication in HIV-infected patients after initiation of highly active antiretroviral therapy resulting in rapid CD4⁺cell count recovery and suppression of viral load. Generally, immune reconstitution inflammatory syndrome is based on opportunistic infections, but rare cases of immune reconstitution inflammatory syndrome inducing demyelinization of the nervous system have also been observed.</p> <p>Case presentation</p> <p>A 37-year-old African woman with HIV infection diagnosed at 13 years of age was admitted to the emergency department after experiencing backache, severe headache, acute aphasia and psychomotor slowing for one week. Nine weeks earlier, highly active antiretroviral therapy in this patient had been changed because of loss of efficacy, and a rapid increase in CD4⁺cell count and decrease of HIV viral load were observed. Magnetic resonance imaging of the brain showed extensive white matter lesions, and analysis of cerebrospinal fluid revealed an immunoreactive syndrome. Intensive investigations detected no opportunistic infections. A salvage therapy, including osmotherapy, corticosteroids and treatment of epileptic seizures, was performed, but the patient died from brainstem herniation 48 hours after admission. Neuropathologic examination of the brain revealed diffuse swelling, leptomeningeal infiltration by CD8 cells and enhancement of perivascular spaces by CD8+ cells.</p> <p>Conclusion</p> <p>Immune reconstitution inflammatory syndrome in this form seems to represent a severe autoimmunologic disease of the brain with specific histopathologic findings. This form of immune reconstitution inflammatory syndrome did not respond to therapy, and extremely rapid deterioration led to death within two days. Immune reconstitution inflammatory syndrome may also occur as severe leukoencephalopathy with fulminant cerebral edema during HIV infection with rapid immune reconstitution.</p

Measuring growth, resistance, and recovery after artemisinin treatment of Plasmodium falciparum in a single semi-high-throughput assay

Background: Artemisinin partial resistance (ART-R) has spread throughout Southeast Asia and mutations in Pfkelch13, the molecular marker of resistance, are widely reported in East Africa. Effective in vitro assays and robust phenotypes are crucial for monitoring populations for the emergence and spread of resistance. The recently developed extended Recovery Ring-stage Survival Assay used a qPCR-based readout to reduce the labour intensiveness for in vitro phenotyping of ART-R and improved correlation with the clinical phenotype of ART-R. Here, the assay is extended and refined to include measurements of parasite growth and recovery after drug exposure. Clinical isolates and progeny from two genetic crosses were used to optimize and validate the reliability of a straight-from-blood, SYBR Green-based qPCR protocol in a 96-well plate format to accurately measure phenotypes with this new Growth, Resistance, and Recovery assay (GRRA). Results: The assay determined growth between 6 and 96 h, resistance at 120 h, and recovery from 120 to 192 h. Growth can be accurately captured by qPCR and is shown by reproduction of previous growth phenotypes from HB3 × Dd2. Resistance measured at 120 h continually shows the most consistent phenotype for ring stage susceptibility. Recovery identifies an additional response to drug in parasites that are determined sensitive by replicative viability at 120 h. Comparison of progeny phenotypes for Growth versus Resistance showed a minor but significant correlation, whereas Growth versus Recovery and Resistance versus Recovery showed no significant correlation. Additionally, dried blood spot (DBS) samples matched replicative viability measured from liquid samples demonstrating Resistance can be easily quantified using either storage method. Conclusions: The direct-from-blood qPCR-based methodology provides the throughput needed to quickly measure large numbers of parasites for multiple relevant phenotypes. Growth can reveal fitness defects and illuminate relationships between proliferation rates and drug response. Recovery serves as a complementary phenotype to resistance that quantifies the ability of sensitive parasites to tolerate drug exposure. All three phenotypes offer a comprehensive assessment of parasite-drug interaction each with potential independent genetic determinants of main effect and overlapping secondary effects. By adapting the method to include DBS, readouts can be easily extended to ex vivo surveillance applications

Impact of prior CKD management in a renal care network on early outcomes in incident dialysis patients: a prospective observational study

Abstract Background Effective therapeutic strategies are available to prevent adverse outcomes in patients with chronic kidney disease (CKD) but their clinical results are hindered by unplanned implementation. Coordination of care emerges as a suitable way to improve patient outcomes. In this study, we evaluated the effect of planned and coordinated patient management within a dedicated renal care network comparatively to standard renal care delivered in nephrology departments of teaching hospitals. Methods This observational matched cohort study included 40 patients with CKD stage 4–5 in the network group as compared with a control group of 120 patients matched for age, sex and diabetic status. Main outcome was a composite endpoint of death from cardiovascular cause and cardiovascular events during the first year after dialysis initiation. Results There was no difference between the two groups neither for the primary outcome (40% vs 41%) nor for the occurrence of death from cardiovascular cause or cardiovascular events. Whereas the proportion of patients requiring at least one hospitalization was identical (83.3% vs 75%), network patients experienced less individual hospitalizations than control patients (2.3±2.0 vs 1.6±1.7) during the year before dialysis start. Patients of the network group had a slower renal function decline (7.7±2.5 vs 4.9±1.1 ml/min/1,73m2 per year; p=0.04). Conclusions In this limited series of patients, we were unable to demonstrate a significant impact of the coordinated renal care provided in the network on early cardiovascular events in incident dialysis patients. However, during the predialysis period, there were less hospitalizations and a slower slope of renal function decrease. </jats:sec

Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy

Natalizumab is an approved medication for highly active multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) may occur as a severe side effect of this drug. Here, we describe pathological and radiological characteristics of immune reconstitution inflammatory syndrome (IRIS), which occurs in natalizumab-associated PML after the cessation of therapy, and we differentiate it from ongoing PML. Brain biopsy tissue and MRI scans from five MS patients with natalizumab-associated PML were analyzed and their histology compared with non-MS PML. Histology showed an extensive CD8-dominated T cell infiltrate and numerous macrophages within lesions, and in nondemyelinated white and grey matter, in four out of five cases. Few or no virally infected cells were found. This was indicative of IRIS as known from HIV patients with PML. Outstandingly high numbers of plasma cells were present as compared to non-MS PML and typical MS lesions. MRI was compatible with IRIS, revealing enlarging lesions with a band-like or speckled contrast enhancement either at the lesion edge or within lesions. Only the fifth patient showed typical PML pathology, with low inflammation and high numbers of virally infected cells. This patient showed a similar interval between drug withdrawal and biopsy (3.5 months) to the rest of the cohort (range 2.5–4 months). MRI could not differentiate between PML-associated IRIS and ongoing PML. We describe in detail the histopathology of IRIS in natalizumab-associated PML. PML–IRIS, ongoing PML infection, and MS exacerbation may be impossible to discern clinically alone. MRI may provide some clues for distinguishing different pathologies that can be differentiated histologically. In our individual cases, biopsy helped to clarify diagnoses in natalizumab-associated PML

French multicentre clinical evaluation of helical TomoTherapy® for anal cancer in a cohort of 64 consecutive patients

PURPOSE/OBJECTIVES: To assess feasibility and toxicity of Helical TomoTherapy® for treating anal cancer patients. METHODS: From 2007 to 2011, 64 patients were consecutively treated with TomoTherapy® in three centres for locally advanced squamous-cell anal carcinoma (T2 > 4 cm or N positive). Prescribed doses were 45 Gy to the pelvis including inguinal nodes and 59.4 Gy to the primary site and involved nodes with fractions of 1.8 Gy, five days a week. A positional Megavoltage Computed Tomography was performed before each treatment session. All acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events version 3.0. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Median follow-up was 22.9 months. Fifty-four women and 10 men were treated (median age: 62 years). Nineteen patients (29.7 %) had T2, 16 patients (25.0 %) T3, and 27 patients (42.2 %) T4 tumours. Thirty-nine patients (60.9 %) had nodal involvement. Median tumour size was 45 mm (range, 10–110 mm). Seven patients had a colostomy before treatment initiation. Fifty-seven patients received concomitant chemotherapy (5-FU/cisplatin or 5-FU/mitomycin-based therapy). Forty-seven patients (73.4 %) experienced a complete response, 13 a partial response or local recurrence, and 11 had salvage surgery; among these, six became complete responders, three experienced metastatic failure, and two local failure. At least four patients experienced metastatic recurrence (concomitant to a local failure for one patient). The two-year overall survival was 85.6 % (95 %CI [71.1 %–93.0 %]), and the one-year disease-free survival, and colostomy-free survival were 68.7 % (95 %CI [54.4 %–79.4]), and 75.5 % (95 %CI [60.7 %–85.3 %]) respectively. Overall survival, disease-free survival and colostomy free-survival were significantly better for women than men (p = 0.002, p = 0.004, and p = 0.002 respectively). Acute grade ≥3 toxicity included dermatologic (46.9 % of patients), gastrointestinal (20.3 %), and hematologic (17.2 %) toxicity. Acute grade 4 hematologic toxicity occurred in one patient. No grade 5 event was observed. CONCLUSIONS: TomoTherapy® for locally advanced anal cancer is feasible. In our three centres of expertise, this technique appeared to produce few acute gastrointestinal toxicities. However, high rates of dermatologic toxicity were observed. The therapeutic efficacy was within the range of expectations and similar to previous studies in accordance with the high rates of locally advanced tumours and nodal involvement