Statistical Performance Analysis of an Ant-Colony Optimisation Application in S-NET

Kenneth MacKenzie, Philip K. F. Hölzenspies, Kevin Hammond, Raimund Kirner, Vu Thien Nga Nguyen, Iraneus te Boekhorst, Clemens Grelck, Raphael Poss, Merijn Verstraaten, 'Statistical Performance Analysis of an Ant-Colony Optimisation Application in S-NET'. Paper presented at the 2nd Workshop on Feedback-Directed Compiler Optimization for Multi-Core Architectures. Berlin, Germany, 12 January 2013.We consider an ant-colony optimsation problem implemented on a multicore system as a collection of asynchronous stream- processing components under the control of the S-NET coordina- tion language. Statistical analysis and visualisation techniques are used to study the behaviour of the application, and this enables us to discover and correct problems in both the application program and the run-time system underlying S-NET

Magnetic Resonance Imaging in Malawi: Contributions to Clinical Care, Medical Education and Biomedical Research

Advanced medical imaging technologies are generally unavailable in low income, tropical settings despite the reality that neurologic disorders are disproportionately common in such environments. Through a series of donations as well as extramural research funding support, an MRI facility opened in Blantyre, Malawi in July 2008. Resulting opportunities for studying common tropical disorders, such as malaria and schistosomiasis, in vivo are promising. The subsequent improvements in local patient care were expected and exceptional and include major revisions in basic care protocols that may eventually impact care protocols at facilities in the region that do not have recourse to MRI. In addition, advanced neuroimaging technology has energized the medical education system, possibly slowing the brain drain. Advanced technologies, though potentially associated with significant fiscal opportunity costs, may bring unexpected and extensive benefits to the healthcare and medical education systems involved

Surgical physiology of inguinal hernia repair - a study of 200 cases

BACKGROUND: Current inguinal hernia operations are generally based on anatomical considerations. Failures of such operations are due to lack of consideration of physiological aspects. Many patients with inguinal hernia are cured as a result of current techniques of operation, though factors that are said to prevent hernia formation are not restored. Therefore, the surgical physiology of inguinal canal needs to be reconsidered. METHODS: A retrospective study is describer of 200 patients operated on for inguinal hernia under local anaesthesia by the author's technique of inguinal hernia repair. RESULTS: The posterior wall of the inguinal canal was weak and without dynamic movement in all patients. Strong aponeurotic extensions were absent in the posterior wall. The muscle arch movement was lost or diminished in all patients. The movement of the muscle arch improved after it was sutured to the upper border of a strip of the external oblique aponeurosis (EOA). The newly formed posterior wall was kept physiologically dynamic by the additional muscle strength provided by external oblique muscle to the weakened muscles of the muscle arch. CONCLUSIONS: A physiologically dynamic and strong posterior inguinal wall, and the shielding and compression action of the muscles and aponeuroses around the inguinal canal are important factors that prevent hernia formation or hernia recurrence after repair. In addition, the squeezing and plugging action of the cremasteric muscle and binding effect of the strong cremasteric fascia, also play an important role in the prevention of hernia

Organophosphorous pesticide breakdown products in house dust and children’s urine.

Human exposure to preformed dialkylphosphates (DAPs) in food or the environment may affect the reliability of DAP urinary metabolites as biomarkers of organophosphate (OP) pesticide exposure. We conducted a study to investigate the presence of DAPs in indoor residential environments and their association with children’s urinary DAP levels. We collected dust samples from homes in farmworker and urban communities (40 homes total, n=79 samples) and up to two urine samples from resident children ages 3-6 years. We measured six DAPs in all samples and eight DAP-devolving OP pesticides in a subset of dust samples (n=54). DAPs were detected in dust with diethylphosphate (DEP) being the most frequently detected (>=60%); detection frequencies for other DAPs were 0.05). Detection of DEP, chlorpyrifos, or diazinon, was not associated with DEP and/or DEPþdiethylthiophosphate detection in urine (Kappa coefficients=-0.33 to 0.16). Finally, estimated nondietary ingestion intake from DEP in dust was found to be <=5% of the dose calculated from DEP levels in urine, suggesting that ingestion of dust is not a significant source of DAPs in urine if they are excreted unchanged.This work was supported by EPA (RD 83171001) and NIEHS (PO1 ES009605). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the EPA, NIEHS, or other funders. Additional support was provided by an EPA STAR Doctoral Fellowship (F5D30812), the University of California Institute for Mexico and the United States (UC MEXUS), and the Center for Latino Policy Research at the University of California at Berkeley

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Foreword

The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common proteinprotein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context