Two Cheers For Diversity: An Experimental Study Of Micro-level Heterogeneity In Problemistic Search

In this paper, we argue for an expanded view of problemistic search. Recent behavioral theory research suggests that individual search preferences influence problemistic search. We draw on this to challenge the view of problemistic search as a centrally directed organizational process that proceeds sequentially from local to distant search. We argue that search activities in organizations are heterogeneous – some individuals will first engage in local search while others may move directly to distant search. We propose that problemistic search at the macroorganizational level is therefore the result of a mix of local and distant search activities at the micro-level that shifts towards distant search in response to negative performance evaluation. We test this idea in a laboratory experiment using a repetitive task and performance feedback

The Dynamics of Transmission and Spatial Distribution of Malaria in Riverside Areas of Porto Velho, Rondônia, in the Amazon Region of Brazil

The study area in Rondônia was the site of extensive malaria epidemic outbreaks in the 19th and 20th centuries related to environmental impacts, with large immigration flows. The present work analyzes the transmission dynamics of malaria in these areas to propose measures for avoiding epidemic outbreaks due to the construction of two Hydroelectric Power Plants. A population based baseline demographic census and a malaria prevalence follow up were performed in two river side localities in the suburbs of Porto Velho city and in its rural vicinity. The quantification and nature of malaria parasites in clinical patients and asymptomatic parasite carriers were performed using microscopic and Real Time PCR methodologies. Anopheles densities and their seasonal variation were done by monthly captures for defining HBR (hourly biting rate) values. Main results: (i) malaria among residents show the riverside profile, with population at risk represented by children and young adults; (ii) asymptomatic vivax and falciparum malaria parasite carriers correspond to around 15% of adults living in the area; (iii) vivax malaria relapses were responsible for 30% of clinical cases; (iv) malaria risk for the residents was evaluated as 20–25% for vivax and 5–7% for falciparum malaria; (v) anopheline densities shown outdoors HBR values 5 to 10 fold higher than indoors and reach 10.000 bites/person/year; (vi) very high incidence observed in one of the surveyed localities was explained by a micro epidemic outbreak affecting visitors and temporary residents. Temporary residents living in tents or shacks are accessible to outdoors transmission. Seasonal fishermen were the main group at risk in the study and were responsible for a 2.6 fold increase in the malaria incidence in the locality. This situation illustrates the danger of extensive epidemic outbreaks when thousands of workers and secondary immigrant population will arrive attracted by opportunities opened by the Hydroelectric Power Plants constructions

Characteristic Energy of the Coulomb Interactions and the Pileup of States

Tunneling data on $\mathrm{La_{1.28}Sr_{1.72}Mn_2O_7}$ crystals confirm Coulomb interaction effects through the $\sqrt{\mathrm{E}}$ dependence of the density of states. Importantly, the data and analysis at high energy, E, show a pileup of states: most of the states removed from near the Fermi level are found between ~40 and 130 meV, from which we infer the possibility of universal behavior. The agreement of our tunneling data with recent photoemission results further confirms our analysis.Comment: 4 pages, 4 figures, submitted to PR

Combined magnetic resonance coronary artery imaging, myocardial perfusion and late gadolinium enhancement in patients with suspected coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Cardiovascular Magnetic Resonance (CMR) imaging offers methods for the detection of ischemia and myocardial infarction as well as visualization of the coronary arteries (MRCA). However, a direct comparison of adenosine perfusion (PERF), late gadolinium enhancement (LGE) and MRCA or the results of their combination has not been performed. Aim of the study was to evaluate the feasibility/diagnostic performance of rest/stress perfusion, late gadolinium enhancement and MRCA and their combination in patients with suspected coronary artery disease (CAD) in comparison to invasive angiography.</p> <p>Methods</p> <p>Fifty-four patients (60 ± 10 years, 35 men, CAD 48%) underwent CMR including MRCA (steady state free precession, navigator whole heart approach, spatial resolution 0.7 × 0.7 × .0.9 mm, trigger delay and temporal resolution adjusted individually), stress PERF (adenosine 140 μg/min/kg), rest PERF (SSFP, 3 short axis, 1 saturation prepulse per slice) and LGE (3D inversion recovery technique) using Gd-BOPTA. Images were analyzed visually. Stenosis >50% in invasive angiography was considered significant.</p> <p>Results</p> <p>Mean study time was 68 ± 11 minutes. Sensitivity for PERF, LGE, MRCA and the combination of PERF/LGE and PERF/LGE/MRCA was 87%, 50%, 91%, 88% and 92%, respectively and specificity 88%, 96%, 46%, 88% and 56%, respectively. If image quality of MRCA was excellent (n = 18) the combination of MRCA/PERF/LGE yield a sensitivity of 86% and specificity of 91%. However, no test or combination improved diagnostic performance significantly compared to PERF alone.</p> <p>Conclusion</p> <p>In patients with CAD, the combination of stress PERF, LGE and MRCA is feasible. When compared to invasive angiography, adenosine stress perfusion outperforms CMR coronary angiography in direct comparison and yields the best results with non-significant improvement in combination with LGE and significant deterioration in combination with MRCA. MRCA may be of additional value only in a minority of patients with excellent image quality.</p

SEASONAL DISTRIBUTION OF MALARIA VECTORS (DIPTERA: CULICIDAE) IN RURAL LOCALITIES OF PORTO VELHO, RONDÔNIA, BRAZILIAN AMAZON

We conducted a survey of the malaria vectors in an area where a power line had been constructed, between the municipalities of Porto Velho and Rio Branco, in the states of Rondônia and Acre, respectively. The present paper relates to the results of the survey of Anopheles fauna conducted in the state of Rondônia. Mosquito field collections were performed in six villages along the federal highway BR 364 in the municipality of Porto Velho, namely Porto Velho, Jaci Paraná, Mutum Paraná, Vila Abunã, Vista Alegre do Abunã, and Extrema. Mosquito captures were performed at three distinct sites in each locality during the months of February, July, and October 2011 using a protected human-landing catch method; outdoor and indoor captures were conducted simultaneously at each site for six hours. In the six sampled areas, we captured 2,185 mosquitoes belonging to seven Anopheles species. Of these specimens, 95.1% consisted of Anopheles darlingi, 1.8% An. triannulatus l.s., 1.7% An. deaneorum, 0.8% An. konderi l.s., 0.4 An. braziliensis, 0.1% An. albitarsis l.s., and 0.1% An. benarrochi. An. darlingi was the only species found in all localities; the remaining species occurred in sites with specific characteristics

Exclusion of PINK1 as candidate gene for the late-onset form of Parkinson's disease in two European populations

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recently, mutations in the PINK1 (PARK6) gene were shown to rarely cause autosomal-recessively transmitted, early-onset parkinsonism. In order to evaluate whether PINK1 contributes to the risk of common late-onset PD we analysed PINK1 sequence variations. A German (85 patients) and a Norwegian cohort (90 patients) suffering from late-onset PD were screened for mutations and single nucleotide polymorphisms (SNPs) in the PINK1 gene. Both cohorts consist of well-characterized patients presenting a positive family history of PD in ~17%. Investigations were performed by single strand conformation polymorphism (SSCP), denaturating high performance liquid chromatography (DHPLC) and sequencing analyses. SNP frequencies were compared by the χ(2 )test RESULTS: Several common SNPs were identified in our cohorts, including a recently identified coding variant (Q115L) in exon 1. Genotyping of the Q115L variation did not reveal significant frequency differences between patients and controls. Pathogenic mutations in the PINK1 gene were not identified, neither in the German nor in the Norwegian cohort. CONCLUSION: Sequence variation in the PINK1 gene appears to play a marginal quantitative role in the pathogenesis of the late-onset form of PD, in German and Norwegian cohorts, if at all

Generation of subject-specific, dynamic, multisegment ankle and foot models to improve orthotic design: a feasibility study

ABSTRACT: BACKGROUND: Currently, custom foot and ankle orthosis prescription and design tend to be based on traditional techniques, which can result in devices which vary greatly between clinicians and repeat prescription. The use of computational models of the foot may give further insight in the biomechanical effects of these devices and allow a more standardised approach to be taken to their design, however due to the complexity of the foot the models must be highly detailed and dynamic. METHODS: Functional and anatomical datasets will be collected in a multicentre study from 10 healthy participants and 15 patients requiring orthotic devices. The patient group will include individuals with metarsalgia, flexible flat foot and drop foot. Each participant will undergo a clinical foot function assessment, 3D surface scans of the foot under different loading conditions, and detailed gait analysis including kinematic, kinetic, muscle activity and plantar pressure measurements in both barefoot and shod conditions. Following this each participant will undergo computed tomography (CT) imaging of their foot and ankle under a range of loads and positions while plantar pressures are recorded. A further subgroup of participants will undergo magnetic resonance imaging (MRI) of the foot and ankle. Imaging data will be segmented to derive the size of bones and orientation of the joint axes. Insertion points of muscles and ligaments will be determined from the MRI and CT-scans and soft tissue material properties computed from the loaded CT data in combination with the plantar pressure measurements. Gait analysis data will be used to drive the models and in combination with the 3D surface scans for scaling purposes. Predicted plantar pressures and muscle activation patterns predicted from the models will be compared to determine the validity of the models. DISCUSSION: This protocol will lead to the generation of unique datasets which will be used to develop linked inverse dynamic and forward dynamic biomechanical foot models. These models may be beneficial in predicting the effect of and thus improving the efficacy of orthotic devices for the foot and ankle

Global profiling of co- and post-translationally N-myristoylated proteomes in human cells

Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development and progression of a range of human diseases. Here, we report the global N-myristoylated proteome in human cells determined using quantitative chemical proteomics combined with potent and specific human N-myristoyltransferase (NMT) inhibition. Global quantification of N-myristoylation during normal growth or apoptosis allowed the identification of >100 N-myristoylated proteins, >95% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for >70 substrates simultaneously across the proteome. Small-molecule inhibition through a conserved substrate-binding pocket is also demonstrated by solving the crystal structures of inhibitor-bound NMT1 and NMT2. The presented data substantially expand the known repertoire of co- and post-translational N-myristoylation in addition to validating tools for the pharmacological inhibition of NMT in living cells