Perturbation expansions of multilocus fixation probabilities for frequency-dependent selection with applications to the Hill-Robertson effect and to the joint evolution of helping and punishment.

Natural populations are of finite size and organisms carry multilocus genotypes. There are, nevertheless, few results on multilocus models when both random genetic drift and natural selection affect the evolutionary dynamics. In this paper we describe a formalism to calculate systematic perturbation expansions of moments of allelic states around neutrality in populations of constant size. This allows us to evaluate multilocus fixation probabilities (long-term limits of the moments) under arbitrary strength of selection and gene action. We show that such fixation probabilities can be expressed in terms of selection coefficients weighted by mean first passages times of ancestral gene lineages within a single ancestor. These passage times extend the coalescence times that weight selection coefficients in one-locus perturbation formulas for fixation probabilities. We then apply these results to investigate the Hill-Robertson effect and the coevolution of helping and punishment. Finally, we discuss limitations and strengths of the perturbation approach. In particular, it provides accurate approximations for fixation probabilities for weak selection regimes only (Ns < or = 1), but it provides generally good prediction for the direction of selection under frequency-dependent selection.

Impaired adipose tissue expandability and lipogenic capacities as ones of the main causes of metabolic disorders.

Obesity is considered a major health problem. However, mechanisms involved and its comorbidities are not elucidated. Recent theories concerning the causes of obesity have focused on a limit to the functional capacity of adipose tissue, comparing it with other vital organs. This assumption has been the central point of interest in our laboratory. We proposed that the failure of adipose tissue is initiated by the difficulty of this tissue to increase its cellularity due to excess in fat contribution, owing to genetic or environmental factors. Nevertheless, why the adipose tissue reduces its capacity to make new adipocytes via mesenchymal cells of the stroma has not yet been elucidated. Thus, we suggest that this tissue ceases fulfilling its main function, the storage of excess fat, thereby affecting some of the key factors involved in lipogenesis, some of which are reviewed in this paper (PPARγ, ROR1, FASN, SCD1, Rab18, BrCa1, ZAG, and FABP4). On the other hand, mechanisms involved in adipose tissue expandability are also impaired, predominating hypertrophy via an increase in apoptosis and a decrease in adipogenesis and angiogenesis. However, adipose tissue failure is only part of this great orchestra, only a chapter of this nightmare.

Olfaction in eating disorders and abnormal eating behavior: a systematic review.

The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders.

In the present study, we have investigated the functional profile of CD4 T cells from patients with common variable immunodeficiency (CVID), including production of cytokines and proliferation in response to bacteria and virus-derived antigens. We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. High levels of endotoxins were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be caused by bacterial translocation. Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. In conclusion, the present study demonstrates that the CD4 T cell exhaustion and functional impairment observed in CVID patients is associated with bacterial translocation and that IVIG treatment resolves bacterial translocation and restores CD4 T cell functions.

Daptomycin-associated eosinophilic pneumonia in two patients with prosthetic joint infection.

Background: Daptomycin is used increasingly to treat prosthetic joint infection (PJI). A possible side effect of this drug is eosinophilic pneumonia. We describe two patients with PJI treated with daptomycin who had this side effect with different clinical presentations. METHODS: Case reports and review of the literature. RESULTS: The first case was a 64-year-old male who received daptomycin as a part of the treatment for PJI caused by methicillin-resistant Staphylococcus epidermidis (MRSE). He developed fever without other symptoms; bronchoalveolar lavage (BAL) revealed eosinophils. The second was a 61-year-old male who also used daptomycin as part of the treatment of PJI caused by MRSE and developed severe lung symptoms. Bronchoalveolar lavage and pleural fluid showed an increased number of eosinophils. CONCLUSION: Daptomycin-induced pneumonia can present with a wide range of symptoms, from fever alone to severe lung symptoms. Surgeons should be aware of this possible side effect when prescribing daptomycin.

The joint R&D project: The case of the first Brazilian microcontroller chip

ABSTRACT The interorganizational cooperation, through joint efforts with various actors, allows the high-tech companies to complement resources, especially in R&D projects. Collaborative projects have been identified in many studies as an important strategy to produce complex products and services in uncertain and competitive environments. Thus, this research aims at deepening the understanding of how the development dynamics of a collaborative R&D project in an industry of high technology occur. In order to achieve the proposed objective, the R&D project of the first microcontroller in the Brazilian semiconductor industry was defined as the object of analysis. The empirical choice is justified by the uniqueness of the case, besides bringing a diversity of actors and a level of complementarity of resources that were significant to the success of the project. Given the motivation to know who the actors were and what the main forms of interorganizational coordination were used in this project, interviews were carried out and a questionnaire was also made, besides other documents related to the project. The results presented show a network of nine actors and their roles in the interorganizational collaboration process, as well as the forms of social and temporal overlapping, used in the coordination of collective efforts. Focusing on the mechanisms of temporal and social integration highlighted throughout the study, the inclusion of R&D projects in the typology for interorganizational projects is proposed in this paper, which was also proposed by Jones and Lichtenstein (2008).

Genes for normal sleep and sleep disorders.

Sleep and wakefulness are complex behaviors that are influenced by many genetic and environmental factors, which are beginning to be discovered. The contribution of genetic components to sleep disorders is also increasingly recognized as important. Point mutations in the prion protein, period 2, and the prepro-hypocretin/orexin gene have been found as the cause of a few sleep disorders but the possibility that other gene defects may contribute to the pathophysiology of major sleep disorders is worth in-depth investigations. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental effects, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep.

Functional calibration procedure for 3D knee joint angle description using inertial sensors.

Measurement of three-dimensional (3D) knee joint angle outside a laboratory is of benefit in clinical examination and therapeutic treatment comparison. Although several motion capture devices exist, there is a need for an ambulatory system that could be used in routine practice. Up-to-date, inertial measurement units (IMUs) have proven to be suitable for unconstrained measurement of knee joint differential orientation. Nevertheless, this differential orientation should be converted into three reliable and clinically interpretable angles. Thus, the aim of this study was to propose a new calibration procedure adapted for the joint coordinate system (JCS), which required only IMUs data. The repeatability of the calibration procedure, as well as the errors in the measurement of 3D knee angle during gait in comparison to a reference system were assessed on eight healthy subjects. The new procedure relying on active and passive movements reported a high repeatability of the mean values (offset<1 degrees) and angular patterns (SD<0.3 degrees and CMC>0.9). In comparison to the reference system, this functional procedure showed high precision (SD<2 degrees and CC>0.75) and moderate accuracy (between 4.0 degrees and 8.1 degrees) for the three knee angle. The combination of the inertial-based system with the functional calibration procedure proposed here resulted in a promising tool for the measurement of 3D knee joint angle. Moreover, this method could be adapted to measure other complex joint, such as ankle or elbow.

A measure of dysfunctional eating-related cognitions in people with psychotic disorders.

Obesity and binge eating disorder are common in individuals with psychotic disorders. Eating and weight-related cognitions are known to influence eating behaviors. The study was designed to assess the psychometric properties of the Mizes Anorectic Cognitions Questionnaire (MAC-R) in patients with psychotic disorders. Binge eating disorder (BED), body mass index (BMI), the MAC-R and the three factor eating questionnaire (TFEQ) were assessed in 125 patients with a diagnosis of schizophrenia or schizoaffective disorder. Whereas the MAC-R has not acceptable psychometric properties, a brief version of the MAC-R (BMAC) has good psychometrical properties and is correlated with TFEQ and BMI. Binge eating disorder is also correlated to the Rigid Weight Regulation and Fear of Weight Gain subscale. The BMAC is a useful brief measure to assess eating and weight related cognitions in people with psychotic disorders.

Functional significance of first metatarso-phalangeal joint arthrodesis : FM101

Introduction: Indications for arthrodesis of the first metatarsophalangeal joint (MTP1) are commonly arthrosis (hallux rigidus), rheumatoid arthritis, failed hallux valgus surgery, severe hallux valgus, infectious arthritis, fractures and neuroarthropathies. Many reports focus on technical and radiological issues but few studies emphasize the functional outcome considering daily activities, sports and expectation of the patient. Method: We retrospectively reviewed the patients who underwent MTP1-arthrodesis from 2002 to 2005 in our institution. Clinical and radiological results were assessed but we specially focussed on the functional outcome. Scoring systems used were the SF-12, EQ-5D, PASI, FFI and AOFAS (10 points given to MTP1 mobility) scales. Results: 61 of 64 consecutive patients were evaluated. Female to male ratio was 49:15, mean age at surgery was 67 years, the average follow up was 29 month. Even if radiological consolidation was incomplete in 18 patients, all patients had a clinically stable and rigid arthrodesis. Mean AOFAS score was 87 (24-100) points at follow up. The FFI was 5.91% (0-66%). Patient satisfaction was excellent in 37 patients (60%), good in 18 (30%), fair in 5(8%) and poor in1 (2%). EQ- 5D was 0.7 (0.4-1).40 patients (66%) estimated their cosmetic result as excellent, 15 (25%) as good, 4(6%) as fair and 2 (3%)as poor. 10 patients (16%) had no shoe wear limitation , 48 (79%) had to wear comfortable shoes and 3 (5%) needed orthopaedic wearing. Professionally 34 patients (56%) had better performances, 18 (26%) had no change and 9 (18%) had aggravation of their capacities but this was due to other health reasons. In sports, 16 patients (26%) had better performances, 35 patients (57%) no change and 10 (17%) were worse as consequence of other health problems for 7. Finally, 56 patients (92%) would recommend the operation and 5 (8%) would not. Conclusion: Experience of clinical practice suggests that the idea of fusing the first MTP joint is initially frequently disregarded by the patients because they fear to be limited by a rigid forefoot. Our results show, in fact, that this procedure can be proposed for numerous pathological situations with the perspective of good to excellent outcome in terms of function and quality of life in the majority of cases.

Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study.

Epidemiological studies have recognized a genetic diathesis for suicidal behavior, which is independent of other psychiatric disorders. Genome-wide association studies (GWAS) on suicide attempt (SA) and ideation have failed to identify specific genetic variants. Here, we conduct further GWAS and for the first time, use polygenic score analysis in cohorts of patients with mood disorders, to test for common genetic variants for mood disorders and suicide phenotypes. Genome-wide studies for SA were conducted in the RADIANT and GSK-Munich recurrent depression samples and London Bipolar Affective Disorder Case-Control Study (BACCs) then meta-analysis was performed. A GWAS on suicidal ideation during antidepressant treatment had previously been conducted in the Genome Based Therapeutic Drugs for Depression (GENDEP) study. We derived polygenic scores from each sample and tested their ability to predict SA in the mood disorder cohorts or ideation status in the GENDEP study. Polygenic scores for major depressive disorder, bipolar disorder and schizophrenia from the Psychiatric Genomics Consortium were used to investigate pleiotropy between psychiatric disorders and suicide phenotypes. No significant evidence for association was detected at any SNP in GWAS or meta-analysis. Polygenic scores for major depressive disorder significantly predicted suicidal ideation in the GENDEP pharmacogenetics study and also predicted SA in a combined validation dataset. Polygenic scores for SA showed no predictive ability for suicidal ideation. Polygenic score analysis suggests pleiotropy between psychiatric disorders and suicidal ideation whereas the tendency to act on such thoughts may have a partially independent genetic diathesis. © 2014 Wiley Periodicals, Inc.

Iowa Water Pollution Control Works and Drinking Water Facilities Financing Programs (Joint Programs of the Iowa Finance Authority and the Iowa Department of Natural Resources), June 30, 2002

State Agency Audit Report State Revolving Fund - Clean Water & Drinking Programs