Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Psoriasis beyond the skin: an expert group consensus on the management of psoriatic arthritis and common co-morbidities in patients with moderate-to-severe psoriasis

BACKGROUND Psoriatic arthritis (PsA) and co-morbidities of psoriasis represent a significant clinical and economic burden for patients with moderate-to-severe psoriasis. Often these co-morbidities may go unrecognized or undertreated. While published data are available on the incidence and impact of some of them, practical guidance for dermatologists on detection and management of these co-morbidities is lacking. OBJECTIVE To prepare expert recommendations to improve the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis. METHODS A systematic literature review was conducted on some common co-morbidities of psoriasis-cardiovascular (CV) diseases (including obesity, hypertension, hyperglycaemia and dyslipidaemia), psychological co-morbidities (including depression, alcohol abuse and smoking) and PsA-to establish the incidence and impact of each. Data gaps were identified and a Delphi survey was carried out to obtain consensus on the detection and management of each co-morbidity. The expert panel members for the Delphi survey comprised 10 dermatologists with substantial clinical expertise in managing moderate-to-severe psoriasis patients, as well as a cardiologist and a psychologist (see appendix) with an interest in dermatology. Agreement was defined using a Likert scale of 1-7. Consensus regarding agreement for each statement was defined as ≥75% of respondents scoring either 1 (strongly agree) or 2 (agree). RESULTS The expert panel members addressed several topics including screening, intervention, monitoring frequency, and the effects of anti-psoriatic treatment on each co-morbidity. Consensus was achieved on 12 statements out of 22 (3 relating to PsA, 4 relating to psychological factors, 5 relating to CV factors). The panel members felt that dermatologists have an important role in screening their psoriasis patients for PsA and in assessing them for psychological and CV co-morbidities. In most cases, however, patients should be referred for specialist management if other co-morbidities are detected. CONCLUSION This article provides useful and practical guidance for the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis.

Development of an ex vivo protocol to model bone fracture in laying hens resulting from collisions.

Fractures of the keel bone, a bone extending ventrally from the sternum, are a serious health and welfare problem in free range laying hens. Recent findings suggest that a major cause of keel damage within extensive systems is collisions with internal housing structures, though investigative efforts have been hindered by difficulties in examining mechanisms and likely influencing factors at the moment of fracture. The objectives of this study were to develop an ex vivo impact protocol to model bone fracture in hens caused by collision, to assess impact and bird-related factors influencing fracture occurrence and severity, and to identify correlations of mechanical and structural properties between different skeletal sites. We induced keel bone fractures in euthanized hens using a drop-weight impact tester able to generate a range of impact energies, producing fractures that replicate those commonly found in commercial settings. The results demonstrated that impact energies of a similar order to those expected in normal housing were able to produce fractures, and that greater collision energies resulted in an increased likelihood of fractures and of greater severity. Relationships were also seen with keel's lateral surface bone mineral density, and the peak reactive force (strength) at the base of the manubrial spine. Correlations were also identified between the keel and long bones with respect to both strength and bone mineral density. This is the first study able to relate impact and bone characteristics with keel bone fracture at the moment of collision. Greater understanding of these relationships will provide means to reduce levels of breakage and severity in commercial systems.

Factorization of leading chiral logarithms in the pion form factors

In the recently proposed framework of hard pion chiral perturbation theory, the leading chiral logarithms are predicted to factorize with respect to the energy dependence in the chiral limit. We have scrutinized this assumption in the case of vector and scalar pion form factors FV;S(s) by means of standard chiral perturbation theory and dispersion relations. We show that this factorization property is valid for the elastic contribution to the dispersion integrals for FV;S(s) but it is violated starting at three loops when the inelastic four-pion contributions arise.

Comparison of pain-resilient working individuals to population-based case controls with/without momentary low back pain

Background: Few studies have examined the 20% of individuals who never experience an episode of low back pain (LBP). To date, no investigation has been undertaken that examines a group who claim to have never experienced LBP in their lifetime in comparison to two population-based case–control groups with and without momentary LBP. This study investigates whether LBP-resilient workers between 50 and 65 years had better general health, demonstrated more positive health behaviour and were better able to achieve routine activities compared with both case–control groups. Methods: Forty-two LBP-resilient participants completed the same pain assessment questionnaire as a population-based LBP sample from a nationwide, large-scale cross-sectional survey in Switzerland. The LBP-resilient participants were pairwise compared to the propensity score-matched case controls by exploring differences in demographic and work characteristics, and by calculating odds ratios (ORs) and effect sizes. A discriminant analysis explored group differences, while the multiple logistic regression analysis specified single indicators which accounted for group differences. Results: LBP-resilient participants were healthier than the case controls with momentary LBP and achieved routine activities more easily. Compared to controls without momentary LBP, LBP-resilient participants had a higher vitality, a lower workload, a healthier attitude towards health and behaved more healthily by drinking less alcohol. Conclusions: By demonstrating a difference between LBP-resilient participants and controls without momentary LBP, the question that arises is what additional knowledge can be attained. Three underlying traits seem to be relevant about LBP-resilient participants: personality, favourable work conditions and subjective attitudes/attributions towards health. These rationales have to be considered with respect to LBP prevention.

Towards a taxonomy of common factors in psychotherapy-results of an expert survey

BACKGROUND: How change comes about is hotly debated in psychotherapy research. One camp considers 'non-specific' or 'common factors', shared by different therapy approaches, as essential, whereas researchers of the other camp consider specific techniques as the essential ingredients of change. This controversy, however, suffers from unclear terminology and logical inconsistencies. The Taxonomy Project therefore aims at contributing to the definition and conceptualization of common factors of psychotherapy by analyzing their differential associations to standard techniques. METHODS: A review identified 22 common factors discussed in psychotherapy research literature. We conducted a survey, in which 68 psychotherapy experts assessed how common factors are implemented by specific techniques. Using hierarchical linear models, we predicted each common factor by techniques and by experts' age, gender and allegiance to a therapy orientation. RESULTS: Common factors differed largely in their relevance for technique implementation. Patient engagement, Affective experiencing and Therapeutic alliance were judged most relevant. Common factors also differed with respect to how well they could be explained by the set of techniques. We present detailed profiles of all common factors by the (positively or negatively) associated techniques. There were indications of a biased taxonomy not covering the embodiment of psychotherapy (expressed by body-centred techniques such as progressive muscle relaxation, biofeedback training and hypnosis). Likewise, common factors did not adequately represent effective psychodynamic and systemic techniques. CONCLUSION: This taxonomic endeavour is a step towards a clarification of important core constructs of psychotherapy. KEY PRACTITIONER MESSAGE: This article relates standard techniques of psychotherapy (well known to practising therapists) to the change factors/change mechanisms discussed in psychotherapy theory. It gives a short review of the current debate on the mechanisms by which psychotherapy works. We provide detailed profiles of change mechanisms and how they may be generated by practice techniques.

Mitochondrial outer membrane proteome of T.brucei reveals novel factors required to maintain mitochondrial morphology

African trypanosomes, the causative agent of Human African Trypanosomiasis (HAT) are among the earliest diverging eukaryotes that have bona fide mitochondria capable of oxidative phosphorylation. The mitochondrial outer membrane (MOM) of T. brucei is essentially unchartered territory. The beta barrel membrane proteins VDAC, Sam50 and archaic TOM are the only MOM proteins that have been characterized so far. Using biochemical fractionation and correlated protein abundance-profiling we were able to raise the protein inventory of the MOM. Of the 82 candidate proteins two-thirds have never been associated with mitochondria before. The function of 42 proteins remains unknown. Known factors involved in the regulation of mitochondrial morphology are virtually absent in T. brucei. Interestingly, RNAi-mediated ablation of three MOM candidate proteins of unknown function resulted in a collapse of the network-like mitochondrion of insect-stage parasites and therefore directly or indirectly are involved in the regulation of mitochondrial morphology in T. brucei.

Mitochondrial outer membrane proteome of T.brucei reveals novel factors required to maintain mitochondrial morphology.

The mitochondrial outer membrane (MOM) separates the mitochondria from the cytoplasm, serving both as a barrier and as a gateway. Protein complexes residing in the MOM orchestrate protein and tRNA import, metabolite exchange and lipid metabolism. African trypanosomes are among the earliest diverging eukaryotes that have bona fide mitochondria capable of oxidative phosphorylation. The MOM of T. brucei is essentially unchartered territory. It lacks a canonical TOM-complex and proteins are imported across the MOM using ATOM, which is related to both Tom40 and to the bacterial Omp85-protein family. The beta barrel membrane proteins ATOM, VDAC and Sam50 are the only MOM proteins that have been characterized in T. brucei so far. Using biochemical fractionation and correlated protein abundance-profiling we were able to identify a cluster of 82 candidate proteins that can be localized to the trypanosomal MOM with high confidence Two-thirds of these polypeptides have never been associated with mitochondria before. 40 proteins share homology with proteins of known functions. The function of 42 proteins remains unknown. 11 proteins are essential for the disease-causing bloodstream form of T. brucei and therefore may be exploited as novel drug targets. A comparison with the outer membrane proteome of yeast defines a set of 17 common proteins that are likely present in the MOM of all eukaryotes. Known factors involved in the regulation of mitochondrial morphology are virtually absent in T. brucei. Interestingly, RNAi-mediated ablation of three outer membrane proteins of unknown function resulted in a collapse of the network-like mitochondrion of procyclic cells and therefore directly or indirectly are involved in the regulation of mitochondrial morphology in T. brucei.

Decision making in beach volleyball defense: Crucial factors derived from interviews with top-level experts

Objectives: In fast ball sports like beach volleyball, decision-making skills are a determining factor for excellent performance. The current investigation aimed to identify factors that influence the decisionmaking process in top-level beach volleyball defense in order to find relevant aspects for further research. For this reason, focused interviews with top players in international beach volleyball were conducted and analyzed with respect to decision-making characteristics. Design: Nineteen world-tour beach volleyball defense players, including seven Olympic or world champions, were interviewed, focusing on decision-making factors, gaze behavior, and interactions between the two. Methods: Verbal data were analyzed by inductive content analysis according to Mayring (2008). This approach allows categories to emerge from the interview material itself instead of forcing data into preset classifications and theoretical concepts. Results: The data analysis showed that, for top-level beach volleyball defense, decision making depends on opponent specifics, external context, situational context, opponent's movements, and intuition. Information on gaze patterns and visual cues revealed general tendencies indicating optimal gaze strategies that support excellent decision making. Furthermore, the analysis highlighted interactions between gaze behavior, visual information, and domain-specific knowledge. Conclusions: The present findings provide information on visual perception, domain-specific knowledge, and interactions between the two that are relevant for decision making in top-level beach volleyball defense. The results can be used to inform sports practice and to further untangle relevant mechanisms underlying decision making in complex game situations.

NLL QCD contribution of the electromagnetic dipole operator to B -> Xs gamma gamma with a massive strange quark

We calculate the O(αs) corrections to the double differential decay width dΓ77/(ds1ds2) for the process B¯→Xsγγ, originating from diagrams involving the electromagnetic dipole operator O7. The kinematical variables s1 and s2 are defined as si=(pb−qi)2/m2b, where pb, q1, q2 are the momenta of the b quark and two photons. We introduce a nonzero mass ms for the strange quark to regulate configurations where the gluon or one of the photons become collinear with the strange quark and retain terms which are logarithmic in ms, while discarding terms which go to zero in the limit ms→0. When combining virtual and bremsstrahlung corrections, the infrared and collinear singularities induced by soft and/or collinear gluons drop out. By our cuts the photons do not become soft, but one of them can become collinear with the strange quark. This implies that in the final result a single logarithm of ms survives. In principle, the configurations with collinear photon emission could be treated using fragmentation functions. In a related work we find that similar results can be obtained when simply interpreting ms appearing in the final result as a constituent mass. We do so in the present paper and vary ms between 400 and 600 MeV in the numerics. This work extends a previous paper by us, where only the leading power terms with respect to the (normalized) hadronic mass s3=(pb−q1−q2)2/m2b were taken into account in the underlying triple differential decay width dΓ77/(ds1ds2ds3).

Saddlepoint approximations to sensitivities of tail probabilities of random sums and comparisons with Monte Carlo estimators

This article proposes computing sensitivities of upper tail probabilities of random sums by the saddlepoint approximation. The considered sensitivity is the derivative of the upper tail probability with respect to the parameter of the summation index distribution. Random sums with Poisson or Geometric distributed summation indices and Gamma or Weibull distributed summands are considered. The score method with importance sampling is considered as an alternative approximation. Numerical studies show that the saddlepoint approximation and the method of score with importance sampling are very accurate. But the saddlepoint approximation is substantially faster than the score method with importance sampling. Thus, the suggested saddlepoint approximation can be conveniently used in various scientific problems.

Observed management practices in relation to the risk of infection with paratuberculosis and to the spread of Mycobacterium avium subsp. paratuberculosis in Swiss dairy and beef herds

Abstract BACKGROUND: Many studies have been conducted to define risk factors for the transmission of bovine paratuberculosis, mostly in countries with large herds. Little is known about the epidemiology in infected Swiss herds and risk factors important for transmission in smaller herds. Therefore, the presence of known factors which might favor the spread of paratuberculosis and could be related to the prevalence at animal level of fecal shedding of Mycobacterium avium subsp. paratuberculosis were assessed in 17 infected herds (10 dairy, 7 beef). Additionally, the level of knowledge of herd managers about the disease was assessed. In a case-control study with 4 matched negative control herds per infected herd, the association of potential risk factors with the infection status of the herd was investigated. RESULTS: Exposure of the young stock to feces of older animals was frequently observed in infected and in control herds. The farmers' knowledge about paratuberculosis was very limited, even in infected herds. An overall prevalence at animal level of fecal shedding of Mycobacterium avium subsp. paratuberculosis of 6.1% was found in infected herds, whereby shedders younger than 2 years of age were found in 46.2% of the herds where the young stock was available for testing. Several factors related to contamination of the heifer area with cows' feces and the management of the calving area were found to be significantly associated with the within-herd prevalence. Animal purchase was associated with a positive herd infection status (OR = 7.25, p = 0.004). CONCLUSIONS: Numerous risk factors favoring the spread of Mycobacterium avium subsp. paratuberculosis from adult animals to the young stock were observed in infected Swiss dairy and beef herds, which may be amenable to improvement in order to control the disease. Important factors were contamination of the heifer and the calving area, which were associated with higher within-herd prevalence of fecal shedding. The awareness of farmers of paratuberculosis was very low, even in infected herds. Animal purchase in a herd was significantly associated with the probability of a herd to be infected and is thus the most important factor for the control of the spread of disease between farms.

Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE.

Prophylaxis of infectious complications with colony-stimulating factors in adult cancer patients undergoing chemotherapy-evidence-based guidelines from the Infectious Diseases Working Party AGIHO of the German Society for Haematology and Medical Oncology (DGHO).

BACKGROUND Current evidence on myelopoietic growth factors is difficult to overview for the practicing haematologist/oncologist. International guidelines are sometimes conflicting, exclude certain patient groups, or cannot directly be applied to the German health system. This guideline by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO) gives evidence-based recommendations for the use of G-CSF, pegylated G-CSF, and biosimilars to prevent infectious complications in cancer patients undergoing chemotherapy, including those with haematological malignancies. METHODS We systematically searched and evaluated current evidence. An expert panel discussed the results and recommendations. We then compared our recommendations to current international guidelines. RESULTS We summarised the data from eligible studies in evidence tables, developed recommendations for different entities and risk groups. CONCLUSION Comprehensive literature search and expert panel consensus confirmed many key recommendations given by international guidelines. Evidence for growth factors during acute myeloid leukaemia induction chemotherapy and pegfilgrastim use in haematological malignancies was rated lower compared with other guidelines.

Measurement of distributions sensitive to the underlying event in inclusive Z-boson production in pp collisions at √ s=7 TeV with the ATLAS detector

A measurement of charged-particle distributions sensitive to the properties of the underlying event is presented for an inclusive sample of events containing a Z-boson, decaying to an electron or muon pair. The measurement is based on data collected using the ATLAS detector at the LHC in proton–proton collisions at a centre-of-mass energy of 7 TeV with an integrated luminosity of 4.6fb−1. Distributions of the charged particle multiplicity and of the charged particle transverse momentum are measured in regions of azimuthal angle defined with respect to the Z-boson direction. The measured distributions are compared to similar distributions measured in jet events, and to the predictions of various Monte Carlo generators implementing different underlying event models.