Long-term risk of tuberculosis among migrants according to migrant status: a cohort study.

BACKGROUND: The majority of tuberculosis (TB) cases in low-incidence countries occur in migrants. Only few studies have assessed the long-term TB risk in migrants after immigration, and datasets have not considered this across a range of diverse migrant groups. This nationwide study aimed to investigate long-term TB risk among migrants according to migrant status and region of origin. METHODS: This cohort study included all migrants aged  ≥ 18 years who obtained residence in Denmark from 1993 to 2015, with a mean follow-up of 10.8 years [standard deviation (SD) 7.3]. Migrants were categorized based on legal status of residence and region of origin. Incidence rates (IR) and rate ratios (IRR) were estimated by Poisson regression. RESULTS: A total of 142 314 migrants were included. Across all migrants, the TB risk was highest during year 1 of residence (IR 275/100 000 person-years; 95% CI 249-305) followed by a gradual decline, though TB risk remained high for over a decade. Compared with the Danish-born population, the IRRs after 7-8 years were particularly higher among former asylum seekers (IRR 31; 95% CI 20-46), quota refugees (IRR 31; 95% CI 16-71), and family-reunified with refugees (IRR 22; 95% CI 12-44). Sub-Saharan African migrants also experienced elevated risk (IRR 75; 95% CI 51-109). The proportion of migrants with pulmonary TB was 52.4%. CONCLUSION: All migrant groups experienced an initial high TB risk, but long-term risk remained high in key migrant groups. Most European countries focus TB screening on or soon after arrival. Our study suggests that approaches to TB screening should be adapted, with migrant populations benefiting from long-term access to preventive health services

Symptomatic snapping knee from biceps femoris tendon subluxation: an unusual case of lateral pain in a marathon runner

Snapping biceps femoris syndrome is an uncommon cause of lateral knee pain and may be difficult to diagnose, resulting in unsuccessful surgical intervention. In this report, we present an unusual case of a 37-year-old male marathon runner with unilateral snapping knee secondary to dislocation of the long head of the biceps femoris over the fibular head during knee flexion. The pain was great enough to interfere with his ability to practice sport. Possible causes of symptomatic snapping knee include multiple intra-articular or extra-articular pathology. Biceps femoris snapping over the fibular head is a rare condition. Reported causes include an anomalous insertion of the tendon into the tibia, trauma, and fibular-head abnormality. However, none of those conditions accounted for his symptoms. Failing conservative treatment, the patient underwent surgery for partial resection of the fibular head, with subsequent sudden resolution of symptoms and return to sport. Accurate knowledge and management of this rare condition is mandatory to avoid inappropriate therapy and unnecessary surgical procedures

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Structural Analysis of the Essential Resuscitation Promoting Factor YeaZ Suggests a Mechanism of Nucleotide Regulation through Dimer Reorganization

Extent: 8p.Background: The yeaZ gene product forms part of the conserved network YjeE/YeaZ/YgjD essential for the survival of many Gram-negative eubacteria. Among other as yet unidentified roles, YeaZ functions as a resuscitation promoting factor required for survival and resuscitation of cells in a viable but non-culturable (VBNC) state. Methodology/Principal Findings: In order to investigate in detail the structure/function relationship of this family of proteins we have performed X-ray crystallographic studies of Vibrio parahaemolyticus YeaZ. The YeaZ structure showed that it has a classic actin-like nucleotide-binding fold. Comparisons of this crystal structure to that of available homologues from E. coli, T. maritima and S. typhimurium revealed two distinctly different modes of dimer formation. In one form, prevalent in the absence of nucleotide, the putative nucleotide-binding site is incomplete, lacking a binding pocket for a nucleotide base. In the second form, residues from the second subunit complete the nucleotide-binding site. This suggests that the two dimer architectures observed in the crystal structures correspond to a free and a nucleotide-bound form of YeaZ. A multiple sequence alignment of YeaZ proteins from different bacteria allowed us to identify a large conserved hydrophobic patch on the protein surface that becomes exposed upon nucleotide-driven dimer re-arrangement. We hypothesize that the transition between two dimer architectures represents the transition between the ‘on’ and ‘off’ states of YeaZ. The effect of this transition is to alternately expose and bury a docking site for the partner protein YgjD. Conclusions/Significance: This paper provides the first structural insight into the putative mechanism of nucleotide regulation of YeaZ through dimer reorganization. Our analysis suggests that nucleotide binding to YeaZ may act as a regulator or switch that changes YeaZ shape, allowing it to switch partners between YjeE and YgjD.Inci Aydin, Yumiko Saijo-Hamano, Keiichi Namba, Connor Thomas and Anna Roujeinikov

Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

Using a previously developed enzyme-linked immunosorbent assay (ELISA), the levels of the receptor for urokinase-type plasminogen activator (uPAR) were determined in cytosols and corresponding membrane pellets derived from 878 primary breast tumours. The levels of uPAR in the pellet extracts were more than 3-fold higher than those measured in the cytosols (P< 0.001). Moreover, the uPAR levels in the two types of extracts were weakly, though significantly, correlated with each other (rS= 0.20, P< 0.001). In Cox univariate analysis, high cytosolic levels of uPAR were significantly associated with reduced overall survival (OS) and relapse-free survival (RFS). The levels of uPAR in pellet extracts appeared not to be related with patient survival. In multivariate analysis, elevated levels of uPAR measured in cytosols and pellet extracts were found to be independent predictors of poor OS, not RFS. The prediction of poor prognosis on the basis of high uPAR levels emphasizes its important role in plasmin-mediated degradation of extracellular matrix proteins during cancer invasion and metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Work-life conflict and musculoskeletal disorders: a cross-sectional study of an unexplored association

BACKGROUND: The health consequences of work-family or rather work-life conflict (WLC) have been studied by numerous researchers. The work-related causes of musculoskeletal disorders (MSD) are also well explored. And stress (at work) has been found to be a consequence of WLC as well as a cause of MSD. But very little is known about a potential association between WLC and MSD and the possible mediating role of stress in this relationship. METHODS: Survey data collected in 2007 among the workforces of four large companies in Switzerland were used for this study. The study population covered 6091 employees. As the exposure variable and hypothesized risk factor for MSD, WLC was measured by using a 10-item scale based on an established 18-item scale on work-family conflict. The outcome variables used as indicators of MSD were (low) back pain and neck/shoulder pain. Stress as the assumed intervening variable was assessed by a validated single-item measure of general stress perception. Correlation coefficients (r), standardized regression coefficients (beta) and multiple adjusted odds ratios (OR) were calculated as measures of association. RESULTS: WLC was found to be quite strongly associated with MSD (beta=.21). This association turned out to be substantially confounded by physical strain at work, workload and job autonomy and was considerably reduced but far from being completely eliminated after adjusting for general stress as another identified risk factor of MSD and a proven strong correlate of WLC (r=.44). A significant and relevant association still remained (beta=.10) after having controlled for all considered covariates. This association could be fully attributed to only one direction of WLC, namely the work-to-life conflict. In subsequent analyses, a clear gradient between this WLC direction and both types of MSD was found, and proved to be consistent for both men and women. Employees who were most exposed to such work-to-life conflict were also most at risk and showed a fivefold higher prevalence rate (19%-42%) and also an up to sixfold increased relative risk (OR=3.8-6.3) of suffering greatly from these types of MSD compared with the least exposed reference group showing very low WLC in this direction. Including stress in the regression models again reduced the strength of the association significantly (OR=1.9-4.1), giving an indication for a possible indirect effect of WLC on MSD mediated by stress. CONCLUSION: Future research and workplace interventions for the prevention of MSD need to consider WLC as an important stressor, and the MSD risk factor identified in this study

How accurate is the phenotype? – An analysis of developmental noise in a cotton aphid clone

<p>Abstract</p> <p>Background</p> <p>The accuracy by which phenotype can be reproduced by genotype potentially is important in determining the stability, environmental sensitivity, and evolvability of morphology and other phenotypic traits. Because two sides of an individual represent independent development of the phenotype under identical genetic and environmental conditions, average body asymmetry (or "fluctuating asymmetry") can estimate the developmental instability of the population. The component of developmental instability not explained by intrapopulational differences in gene or environment (or their interaction) can be further defined as internal developmental noise. Surprisingly, developmental noise remains largely unexplored despite its potential influence on our interpretations of developmental stability, canalization, and evolvability. Proponents of fluctuating asymmetry as a bioindicator of environmental or genetic stress, often make the assumption that developmental noise is minimal and, therefore, that phenotype can respond sensitively to the environment. However, biologists still have not measured whether developmental noise actually comprises a significant fraction of the overall environmental response of fluctuating asymmetry observed within a population.</p> <p>Results</p> <p>In a morphometric study designed to partition developmental noise from fluctuating asymmetry in the wing morphology of a monoclonal culture of cotton aphid, <it>Aphis gossipyii</it>, it was discovered that fluctuating asymmetry in the aphid wing was nearly four times higher than in other insect species. Also, developmental noise comprised a surprisingly large fraction (≈ 50%) of the overall response of fluctuating asymmetry to a controlled graded temperature environment. Fluctuating asymmetry also correlated negatively with temperature, indicating that environmentally-stimulated changes in developmental instability are mediated mostly by changes in the development time of individuals.</p> <p>Conclusion</p> <p>The amount of developmental noise revealed in this trait potentially does interfere with a substantial amount of the sensitivity of fluctuating asymmetry to change in temperature. Assuming that some genetic-based variation in individual buffering of developmental instability exists in natural aphid populations, the amount of internal developmental noise determined in this study could also substantially reduce evolvability of the aphid wing. The overall findings here suggest that individual response to the seemingly high cost of stabilizing some aspects of the phenotype may account for the frequent observation of trait and species specificity in levels of fluctuating asymmetry.</p

Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

<p>Abstract</p> <p>Background</p> <p>The ATM protein is activated as a result of ionizing radiation, and genetic variants of the <it>ATM </it>gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for <it>ATM </it>mutations have been reported to have an increased risk of malignancy, especially breast cancer.</p> <p>Materials and methods</p> <p>Norwegian breast cancer patients (272) treated with radiation (252 of which were evaluated for radiation-induced adverse side effects), 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR) were screened for sequence variations in all exons of the <it>ATM </it>gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC) followed by sequencing to determine the nature of the variant.</p> <p>Results and Conclusion</p> <p>A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala) substitution in exon 11 (P-value 0.055) between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06). Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe) where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the <it>ATM </it>gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour recurrence and any of the sequence variants found in the American patient material.</p