Bicycling

This is not intended to be a research paper; rather it is a journal containing our thoughts, experiences, and knowledge received while doing our bicycling honors project

Pre-control relationship of onchocercal skin disease with onchocercal infection in Guinea Savanna, Northern Nigeria.

BACKGROUND: Onchocerca volvulus infection can result in blindness, itching and skin lesions. Previous research concentrated on blindness. METHODS: A clinical classification system of the cutaneous changes in onchocerciasis was used for the first time in this study within the context of an early ivermectin drug trial in the savanna region of Kaduna State, northern Nigeria. Skin examinations were performed in 6,790 individuals aged 5+ years in endemic communities and 1,343 individuals in nonendemic communities. RESULTS / DISCUSSION: There was increased risk for all forms of onchocercal skin disease in endemic communities with the most common finding being the presence of nodules (1,438 individuals, 21.2%), followed by atrophy (367, 6.1% of those < 50 years), acute papular onchodermatitis, APOD (233, 3.4%), depigmentation (216, 3.2%) and chronic papular onchodermatitis, CPOD (155, 2.3%). A further 645 individuals (9.5%) complained of pruritus but had completely normal skin. APOD was more common in males whereas atrophy, hanging groin and nodules were more common in females. After controlling for age and sex, microfilarial positivity was a risk factor for CPOD, depigmentation, hanging groin and nodules (OR 1.54, p = 0.046; OR 2.29, p = 0.002; OR 2.18, p = 0.002 and OR 3.80, p <0.001 respectively). Comparable results were found using presence of nodules as the marker for infection. Microfilarial load showed similar, though weaker, results. A total of 2621(38.6%) endemic residents had itching with normal skin, or had one or more types of onchocercal skin disease including nodules, which may be considered as a composite index of the overall prevalence of onchocercal skin disease. CONCLUSION: Significant levels of onchocercal skin disease were documented in this savanna area, which subsequently resulted in a reassessment of the true burden of skin disease in onchocerciasis. This paper represents the first detailed report of the association of onchocercal skin disease with markers for onchocercal infection

A Fully Abstract Symbolic Semantics for Psi-Calculi

We present a symbolic transition system and bisimulation equivalence for psi-calculi, and show that it is fully abstract with respect to bisimulation congruence in the non-symbolic semantics. A psi-calculus is an extension of the pi-calculus with nominal data types for data structures and for logical assertions representing facts about data. These can be transmitted between processes and their names can be statically scoped using the standard pi-calculus mechanism to allow for scope migrations. Psi-calculi can be more general than other proposed extensions of the pi-calculus such as the applied pi-calculus, the spi-calculus, the fusion calculus, or the concurrent constraint pi-calculus. Symbolic semantics are necessary for an efficient implementation of the calculus in automated tools exploring state spaces, and the full abstraction property means the semantics of a process does not change from the original

Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions

TIE2-expressing monocytes/macrophages (TEM) are a highly proangiogenic subset of myeloid cells in tumors. Here, we show that circulating human TEMs are already preprogrammed in the circulation to be more angiogenic and express higher levels of such proangiogenic genes as matrix metalloproteinase-9 (MMP-9), VEGFA, COX-2, and WNT5A than TIE2(-) monocytes. Additionally, angiopoietin-2 (ANG-2) markedly enhanced the proangiogenic activity of TEMs and increased their expression of two proangiogenic enzymes: thymidine phosphorylase (TP) and cathepsin B (CTSB). Three "alternatively activated" (or M2-like) macrophage markers were also upregulated by ANG-2 in TEMs: interleukin-10, mannose receptor (MRC1), and CCL17. To investigate the effects of ANG-2 on the phenotype and function of TEMs in tumors, we used a double-transgenic (DT) mouse model in which ANG-2 was specifically overexpressed by endothelial cells. Syngeneic tumors grown in these ANG-2 DT mice were more vascularized and contained greater numbers of TEMs than those in wild-type (WT) mice. In both tumor types, expression of MMP-9 and MRC1 was mainly restricted to tumor TEMs rather than TIE2(-) macrophages. Furthermore, tumor TEMs expressed higher levels of MRC1, TP, and CTSB in ANG-2 DT tumors than WT tumors. Taken together, our data show that although circulating TEMs are innately proangiogenic, exposure to tumor-derived ANG-2 stimulates these cells to exhibit a broader, tumor-promoting phenotype. As such, the ANG-2-TEM axis may represent a new target for antiangiogenic cancer therapies

Analysis of neonatal clinical trials with twin births

<p>Abstract</p> <p>Background</p> <p>In neonatal trials of pre-term or low-birth-weight infants, twins may represent 10–20% of the study sample. Mixed-effects models and generalized estimating equations are common approaches for handling correlated continuous or binary data. However, the operating characteristics of these methods for mixes of correlated and independent data are not well established.</p> <p>Methods</p> <p>Simulation studies were conducted to compare mixed-effects models and generalized estimating equations to linear regression for continuous outcomes. Similarly, mixed-effects models and generalized estimating equations were compared to ordinary logistic regression for binary outcomes. The parameter of interest is the treatment effect in two-armed clinical trials. Data from the National Institute of Child Health & Human Development Neonatal Research Network are used for illustration.</p> <p>Results</p> <p>For continuous outcomes, while the coverage never fell below 0.93, and the type I error rate never exceeded 0.07 for any method, overall linear mixed-effects models performed well with respect to median bias, mean squared error, coverage, and median width. For binary outcomes, the coverage never fell below 0.90, and the type I error rate never exceeded 0.07 for any method. In these analyses, when randomization of twins was to the same treatment group or done independently, ordinary logistic regression performed best. When randomization of twins was to opposite treatment arms, a rare method of randomization in this setting, ordinary logistic regression still performed adequately. Overall, generalized linear mixed models showed the poorest coverage values.</p> <p>Conclusion</p> <p>For continuous outcomes, using linear mixed-effects models for analysis is preferred. For binary outcomes, in this setting where the amount of related data is small, but non-negligible, ordinary logistic regression is recommended.</p

What factors in rural and remote extended clinical placements may contribute to preparedness for practice, from the perspective of students and clinicians?

What factors in rural and remote extended clinical placements may contribute to preparedness for practice, from the perspective of students and clinicians? Michele Daly, David Perkins, Koshila Kumar, Chris Roberts and Malcolm Moore Background: Community based rural education opportunities have expanded in Australia, attracting more medical students to placements in rural and remote settings. Aim: To identify the factors in an integrated, community engaged rural placement that may contribute to preparedness for practice (P4P), from the perspective of students and clinicians Methods: Forty two semi-structured interviews with medical students, supervisors and clinicians analysed thematically. Results: Opportunities for clinical learning, personal and professional development and cultural awareness were reported by students and clinicians as key factors that contribute to preparedness for practice. Potential barriers in rural and remote settings included geographical and academic isolation, perceived educational risk and differing degrees of program engagement. Conclusions: A longitudinal clinical placement in a rural setting may enable development of enhanced competencies leading to P4P. A rural setting can help provide a unique experience through hands-on learning, enhanced personal and professional development opportunities and observation of the cultural and contextual impact on health

Clinical, Epidemiologic, Histopathologic and Molecular Features of an Unexplained Dermopathy

BACKGROUND: Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. METHODS: A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. RESULTS: We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17-93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. CONCLUSIONS: This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation