Commentary: Ensuring health statistics in conflict are evidence-based

The author argues that measuring mortality in conflict settings is fraught with limitations which mostly result in under-estimation of mortality. Some recent publications on this subject have been based upon convenient surveillance processes, or even press reports. The author calls for vigilance against such studies and argues that war related surveillance-based mortality estimates should include measures of sensitivity and representativeness

Geriatric Medical Care in the Area of the Regional Association Westphalia-Lippe Dokkyo Medical University 5th grade

Dokkyo Medical University 5th YearDokkyo Medical University 5th YearDokkyo Medical University 5th YearDokkyo Medical University 5th YearDokkyo Medical University 5th YearDokkyo Medical University 5th YearDokkyo MedicalUniversity, Division of Languages and HumanitiesWestphalian Wilhelms University, IfASWestphalian Wilhelms University, General PracticeKlinik Maria Frieden, Abt. f. GeriatrieDokkyo Medical University, Office for German-Japanese CooperationDokkyo Medical University, Office for German-Japanese Cooperatio

RegExpBlasting (REB), a Regular Expression Blasting algorithm based on multiply aligned sequences

Background: One of the most frequent uses of bioinformatics tools concerns functional characterization of a newly produced nucleotide sequence (a query sequence) by applying Blast or FASTA against a set of sequences (the subject sequences). However, in some specific contexts, it is useful to compare the query sequence against a cluster such as a MultiAlignment (MA). We present here the RegExpBlasting (REB) algorithm, which compares an unclassified sequence with a dataset of patterns defined by application of Regular Expression rules to a given-as-input MA datasets. The REB algorithm workflow consists in i. the definition of a dataset of multialignments ii. the association of each MA to a pattern, defined by application of regular expression rules; iii. automatic characterization of a submitted biosequence according to the function of the sequences described by the pattern best matching the query sequence. Results: An application of this algorithm is used in the "characterize your sequence" tool available in the PPNEMA resource. PPNEMA is a resource of Ribosomal Cistron sequences from various species, grouped according to nematode genera. It allows the retrieval of plant nematode multialigned sequences or the classification of new nematode rDNA sequences by applying REB. The same algorithm also supports automatic updating of the PPNEMA database. The present paper gives examples of the use of REB within PPNEMA. Conclusion: The use of REB in PPNEMA updating, the PPNEMA "characterize your sequence" option clearly demonstrates the power of the method. Using REB can also rapidly solve any other bioinformatics problem, where the addition of a new sequence to a pre-existing cluster is required. The statistical tests carried out here show the powerful flexibility of the method

Ultrafast changes in lattice symmetry probed by coherent phonons

The electronic and structural properties of a material are strongly determined by its symmetry. Changing the symmetry via a photoinduced phase transition offers new ways to manipulate material properties on ultrafast timescales. However, in order to identify when and how fast these phase transitions occur, methods that can probe the symmetry change in the time domain are required. We show that a time-dependent change in the coherent phonon spectrum can probe a change in symmetry of the lattice potential, thus providing an all-optical probe of structural transitions. We examine the photoinduced structural phase transition in VO2 and show that, above the phase transition threshold, photoexcitation completely changes the lattice potential on an ultrafast timescale. The loss of the equilibrium-phase phonon modes occurs promptly, indicating a non-thermal pathway for the photoinduced phase transition, where a strong perturbation to the lattice potential changes its symmetry before ionic rearrangement has occurred.Comment: 14 pages 4 figure

Stimulus set size modulates the sex–emotion interaction in face categorization

Previous research has shown that invariant facial features—for example, sex—and variant facial features—for example, emotional expressions—interact during face categorization. The nature of this interaction is a matter of dispute, however, and has been reported as either asymmetrical, such that sex cues influence emotion perception but emotional expressions do not affect the perception of sex, or symmetrical, such that sex and emotion cues each reciprocally influence the categorization of the other. In the present research, we identified stimulus set size as the critical factor leading to this disparity. Using faces drawn from different databases, in two separate experiments we replicated the finding of a symmetrical interaction between face sex and emotional expression when larger sets of posers were used. Using a subset of four posers, in the same setups, however, did not provide evidence for a symmetrical interaction, which is also consistent with prior research. This pattern of results suggests that different strategies may be used to categorize aspects of faces that are encountered repeatedly

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

Exploring mediating factors in the association between parental psychological distress and psychosocial maladjustment in adolescence

Abstract: Parental psychopathology is associated with increased psychosocial maladjustment in adolescents. We examined, from a psychosocial perspective, the association between parental psychological distress and psychosocial maladjustment in adolescents and assessed the mediating role of psychosocial covariates. This is a cross-sectional survey and the setting include representative sample of Quebec adolescents in 1999. The participants of the study include 13- and 16-year-old children (N = 2,346) in the Social and Health Survey of Quebec Children and Adolescents. The main outcome measures are internalizing disorders, externalizing disorders, substance use, and alcohol consumption. For statistical analysis, we used structural equation modeling to test for mediation. Internalizing and externalizing disorders were significantly associated with parental psychological distress, but not substance use or alcohol consumption. The higher the parental distress, the higher the risk of adolescent mental health disorders. The association between parental psychological distress and internalizing disorders was mediated by adolescent self-esteem, parental emotional support and extrafamilial social support. As for externalizing disorders, these variables only had an independent effect. In conclusion, A family’s well being is a necessary condition for psychosocial adjustment in adolescence. Beyond the psychiatric approach, psychosocial considerations need to be taken into consideration to prevent negative mental health outcomes in children living in homes with distressed parents

PedGenie: meta genetic association testing in mixed family and case-control designs

<p>Abstract</p> <p>Background-</p> <p>PedGenie software, introduced in 2006, includes genetic association testing of cases and controls that may be independent or related (nuclear families or extended pedigrees) or mixtures thereof using Monte Carlo significance testing. Our aim is to demonstrate that PedGenie, a unique and flexible analysis tool freely available in Genie 2.4 software, is significantly enhanced by incorporating meta statistics for detecting genetic association with disease using data across multiple study groups.</p> <p>Methods-</p> <p>Meta statistics (chi-squared tests, odds ratios, and confidence intervals) were calculated using formal Cochran-Mantel-Haenszel techniques. Simulated data from unrelated individuals and individuals in families were used to illustrate meta tests and their empirically-derived p-values and confidence intervals are accurate, precise, and for independent designs match those provided by standard statistical software.</p> <p>Results-</p> <p>PedGenie yields accurate Monte Carlo p-values for meta analysis of data across multiple studies, based on validation testing using pedigree, nuclear family, and case-control data simulated under both the null and alternative hypotheses of a genotype-phenotype association.</p> <p>Conclusion-</p> <p>PedGenie allows valid combined analysis of data from mixtures of pedigree-based and case-control resources. Added meta capabilities provide new avenues for association analysis, including pedigree resources from large consortia and multi-center studies.</p

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page