Hip geometric parameters are associated with radiographic and clinical hip osteoarthritis: Findings from a cross-sectional study in UK Biobank.

OBJECTIVE: To examine the extent to which geometric parameters derived from dual-energy x-ray absorptiometry (DXA) scans in the UK Biobank study are related to hip osteoarthritis (HOA) independently of sex, age and body size. DESIGN: Femoral neck width (FNW), diameter of the femoral head (DFH) and hip axis length (HAL) were derived automatically from left hip DXA scans in UK Biobank using outline points placed around the hip by a machine-learning program. Correlations were calculated between geometric parameters, age, height, and weight. Logistic regression was used to examine the relationship of geometric parameters with radiographic HOA, hospital diagnosed HOA (HESOA), and Cox proportional hazards model to evaluate the relationship with total hip replacement (THR). Analyses were adjusted for sex, age, height, weight, and geometric parameters. RESULTS: The study consisted of 40,312 participants. In age and sex-adjusted analyses, FNW, HAL and DFH were related to increased risk of radiographic HOA. In a model adjusted for age, sex, height, weight and other geometric parameters, both FNW and HAL retained independent relationships with radiographic HOA [FNW: odds ratios 2.38 (2.18-2.59), HAL: 1.25 (1.15-1.36)], while DFH was now protective [0.55 (0.50-0.61)]. Only FNW was independently related to HESOA [2.20 (1.80-2.68)] and THR [hazard ratios 2.51 (1.89-3.32)]. CONCLUSION: Greater FNW and HAL were independently related to an increased risk of radiographic HOA, whereas greater DFH appeared to be protective. Greater FNW was independently associated with HESOA and THR. These results suggest that DXA-derived geometric parameters, particularly FNW, could help determine HOA and THR risk.

Enhanced Transport at High Plasma Pressure and Subthreshold Kinetic Ballooning Modes in Wendelstein 7-X.

High-performance fusion plasmas, requiring high pressure ß, are not well understood in stellarator-type experiments. Here, the effect of ß on ion-temperature-gradient-driven (ITG) turbulence is studied in Wendelstein 7-X (W7-X), showing that subdominant kinetic ballooning modes (KBMs) are unstable well below the ideal MHD threshold and get strongly excited in the turbulence. By zonal-flow erosion, these subthreshold KBMs (stKBMs) affect ITG saturation and enable higher heat fluxes. Controlling stKBMs will be essential to allow W7-X and future stellarators to achieve maximum performance.

High bone mass and cam morphology are independently related to hip osteoarthritis: findings from the High Bone Mass cohort.

BACKGROUND: High bone mass (HBM, BMD Z-score ≥ + 3.2) and cam morphology (bulging of lateral femoral head) are associated with greater odds of prevalent radiographic hip osteoarthritis (rHOA). As cam morphology is itself a manifestation of increased bone deposition around the femoral head, it is conceivable that cam morphology may mediate the relationship between HBM and rHOA. We therefore aimed to determine if individuals with HBM have increased odds of prevalent cam morphology. In addition, we investigated whether the relationship between cam and prevalent and incident osteoarthritis was preserved in a HBM population. METHODS: In the HBM study, a UK based cohort of adults with unexplained HBM and their relatives and spouses (controls), we determined the presence of cam morphology using semi-automatic methods of alpha angle derivation from pelvic radiographs. Associations between HBM status and presence of cam morphology, and between cam morphology and presence of rHOA (or its subphenotypes: osteophytes, joint space narrowing, cysts, and subchondral sclerosis) were determined using multivariable logistic regression, adjusting for age, sex, height, weight, and adolescent physical activity levels. The association between cam at baseline and incidence of rHOA after an average of 8 years was determined. Generalised estimating equations accounted for individual-level clustering. RESULTS: The study included 352 individuals, of whom 235 (66.7%) were female and 234 (66.5%) had HBM. Included individuals contributed 694 hips, of which 143 had a cam deformity (20.6%). There was no evidence of an association between HBM and cam morphology (OR = 0.97 [95% CI: 0.63-1.51], p = 0.90) but a strong relationship was observed between cam morphology and rHOA (OR = 3.96 [2.63-5.98], p = 5.46 × 10-11) and rHOA subphenotypes joint space narrowing (OR = 3.70 [2.48-5.54], p = 1.76 × 10-10), subchondral sclerosis (OR = 3.28 [1.60-6.60], p = 9.57 × 10-4) and osteophytes (OR = 3.01 [1.87-4.87], p = 6.37 × 10-6). Cam morphology was not associated with incident osteoarthritis (OR = 0.76 [0.16-3.49], p = 0.72). CONCLUSIONS: The relationship between cam morphology and rHOA seen in other studies is preserved in a HBM population. This study suggests that the risk of OA conferred by high BMD and by cam morphology are mediated via distinct pathways.

Cam morphology but neither acetabular dysplasia nor pincer morphology is associated with osteophytosis throughout the hip: findings from a cross-sectional study in UK Biobank.

OBJECTIVES: To examine whether acetabular dysplasia (AD), cam and/or pincer morphology are associated with radiographic hip osteoarthritis (rHOA) and hip pain in UK Biobank (UKB) and, if so, what distribution of osteophytes is observed. DESIGN: Participants from UKB with a left hip dual-energy X-ray absorptiometry (DXA) scan had alpha angle (AA), lateral centre-edge angle (LCEA) and joint space narrowing (JSN) derived automatically. Cam and pincer morphology, and AD were defined using AA and LCEA. Osteophytes were measured manually and rHOA grades were calculated from JSN and osteophyte measures. Logistic regression was used to examine the relationships between these hip morphologies and rHOA, osteophytes, JSN, and hip pain. RESULTS: 6,807 individuals were selected (mean age: 62.7; 3382/3425 males/females). Cam morphology was more prevalent in males than females (15.4% and 1.8% respectively). In males, cam morphology was associated with rHOA [OR 3.20 (95% CI 2.41-4.25)], JSN [1.53 (1.24-1.88)], and acetabular [1.87 (1.48-2.36)], superior [1.94 (1.45-2.57)] and inferior [4.75 (3.44-6.57)] femoral osteophytes, and hip pain [1.48 (1.05-2.09)]. Broadly similar associations were seen in females, but with weaker statistical evidence. Neither pincer morphology nor AD showed any associations with rHOA or hip pain. CONCLUSIONS: Cam morphology was predominantly seen in males in whom it was associated with rHOA and hip pain. In males and females, cam morphology was associated with inferior femoral head osteophytes more strongly than those at the superior femoral head and acetabulum. Further studies are justified to characterise the biomechanical disturbances associated with cam morphology, underlying the observed osteophyte distribution.

Subregional statistical shape modelling identifies lesser trochanter size as a possible risk factor for radiographic hip osteoarthritis, a cross-sectional analysis from the Osteoporotic Fractures in Men Study.

OBJECTIVE: Statistical shape modelling (SSM) of hip dual-energy X-ray absorptiometry (DXA) scans has identified relationships between hip shape and radiographic hip OA (rHOA). We aimed to further elucidate shape characteristics related to rHOA by focusing on subregions identified from whole-hip shape models. METHOD: SSM was applied to hip DXAs obtained in the Osteoporotic Fractures in Men Study. Whole-hip shape modes (HSMs) associated with rHOA were combined to form a composite at-risk-shape. Subsequently, subregional HSMs (cam-type and lesser trochanter modes) were built, and associations with rHOA were examined by logistic regression. Subregional HSMs were further characterised, by examining associations with 3D-HSMs derived from concurrent hip CT scans. RESULTS: 4,098 participants were identified with hip DXAs and radiographs. Composite shapes from whole-hip HSMs revealed that lesser trochanter size and cam-type femoral head are related to rHOA. From sub-regional models, lesser trochanter mode (LTM)1 [OR 0.74; 95%CI 0.63.0.87] and cam-type mode (CTM)3 [OR 1.27; 1.13.1.42] were associated with rHOA, associations being similar to those for whole hip HSMs. 515 MrOS participants had hip DXAs and 3D-HSMs derived from hip CT scans. LTM1 was associated with 3D-HSMs that also represented a larger lesser trochanter [3D-HSM7 (beta (ß)-0.23;-0.33,-0.14) and 3D-HSM9 (ß0.36; 0.27.0.45)], and CTM3 with 3D-HSMs describing cam morphology [3D-HSM3 (ß-0.16;-0.25,-0.07) and 3D-HSM6 (ß 0.19; 0.10.0.28)]. CONCLUSION: Subregional SSM of hip DXA scans suggested larger lesser trochanter and cam morphology underlie associations between overall hip shape and rHOA. 3D hip modelling suggests our subregional SSMs represent true anatomical variations in hip shape, warranting further investigation.

DXA-derived hip shape is related to osteoarthritis: findings from in the MrOS cohort.

OBJECTIVE: Statistical shape modelling (SSM) of radiographs has been used to explore relationships between altered joint shape and hip osteoarthritis (OA). We aimed to apply SSM to Dual-energy X-ray Absorptiometry (DXA) hip scans, and examine associations between resultant hip shape modes (HSMs), radiographic hip OA (RHOA), and hip pain, in a large population based cohort. METHOD: SSM was performed on baseline hip DXA scans from the Osteoporotic Fractures in Men (MrOS) Study. Associations between the top ten HSMs, and prevalent RHOA from pelvic radiographs obtained 4.6 years later, were analysed in 4100 participants. RHOA was defined as Croft score ≥2. Hip pain was based on pain on walking, hip pain on examination, and Western Ontario and McMaster Universities Arthritis Index (WOMAC). RESULTS: The five HSMs associated with RHOA showed features of either pincer- or cam-type deformities. HSM 1 (increased pincer-type deformity) was positively associated with RHOA [1.23 (1.09, 1.39)] [odds ratio (OR) and 95% CI]. HSM 8 (reduced pincer-type deformity) was inversely associated with RHOA [0.79 (0.70, 0.89)]. HSM 10 (increased cam-type deformity) was positively associated with RHOA [1.21 (1.07, 1.37)]. HSM 3 and HSM 4 (reduced cam-type deformity) were inversely associated with RHOA [0.73 (0.65, 0.83) and 0.82 (0.73, 0.93), respectively]. HSM 3 was inversely related to pain on examination [0.84 (0.76, 0.92)] and walking [0.88, (0.81, 0.95)], and to WOMAC score [0.87 (0.80, 0.93)]. CONCLUSIONS: DXA-derived measures of hip shape are associated with RHOA, and to a lesser extent hip pain, possibly reflecting their role in the pathogenesis of hip OA.

Stellarator Turbulence: Subdominant Eigenmodes and Quasilinear Modeling.

Owing to complex geometry, gyrokinetic simulations in stellarator geometry produce large numbers of subdominant unstable and stable, near-orthogonal eigenmodes. Here, results based on the full eigenmode spectrum in stellarator geometry are presented for the first time. In the nonlinear state of a low-magnetic-shear ion-temperature-gradient-driven case, a multitude of these modes are active and imprint the system. Turbulent frequency spectra are broadband as a consequence, in addition to a nonlinear, narrow signature at electron frequencies. It is shown that successful quasilinear, mixing-length transport modeling is possible in stellarators, where it is essential to account for all subdominant unstable modes.

Survival of plant pathogens in static piles of ground green waste.

Ground green waste is used as mulch in ornamental landscapes and for tree crops such as avocados. Survival of Armillaria mellea, Phytophthora cinnamomi, Sclerotinia sclerotiorum, and Tylenchulus semipenetrans was assessed for 8 weeks within unturned piles of either recently ground or partially composted green waste. S. sclerotiorum survived at the pile surface and at 10, 30, and 100 cm within the pile for the entire 8 weeks in both fresh green waste (FGW) and aged green waste (AGW). A. mellea and T. semipenetrans did not survive more than 2 days in FGW, while P. cinnamomi persisted for over 21 days in FGW. AGW was less effective in reducing pathogen viability than FGW, most likely because temperatures in AGW peaked at 45 degrees C compared with 70 degrees C in FGW. Survival modeling curves based on pile temperatures indicate the time to inactivate 10 propagules of pathogens was 11, 30, 363, and 50 days for A. mellea, P. cinnamomi, S. sclerotiorum, and T. semipenetrans, respectively. Sclerotia-forming pathogens pose the greatest risk for escape; to ensure eradication of persistent fungi, green waste stockpiles should be turned intermittently to mix pile contents and move pathogen propagules to a location within the pile where they are more likely to be killed by heat, microbial attack, or chemical degradation.

Devices and pressure sources for administration of nasal continuous positive airway pressure (NCPAP) in preterm neonates.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is used to support preterm infants recently extubated, those experiencing significant apnoea of prematurity and those with respiratory distress soon after birth as an alternative to intubation and ventilation. This review focuses exclusively on identifying the most effective pressure source and interface for NCPAP delivery in preterm infants. OBJECTIVES: To determine which technique of pressure generation and which type of nasal interface for NCPAP delivery most effectively reduces the need for additional respiratory support in preterm infants extubated to NCPAP following intermittent positive pressure ventilation (IPPV) for respiratory distress syndrome (RDS) or in those treated with NCPAP soon after birth. SEARCH STRATEGY: The strategy included searches of MEDLINE (1966 - 2006), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006) CINAHL, abstracts from conference proceedings, cross-referencing of previous reviews and the use of expert informants. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing different techniques of NCPAP pressure generation and/or nasal interfaces in preterm infants extubated to NCPAP following IPPV for RDS or treated with NCPAP soon after birth. DATA COLLECTION AND ANALYSIS: Data was extracted and analysed by the first three authors. Dichotomous results were analysed using the relative risk (RR), risk difference (RD) and number needed to treat (NNT). MAIN RESULTS: 1. Preterm infants being extubated to NCPAP following a period of IPPV for RDS:Meta-analysis of the results from Davis 2001 and Roukema 1999a demonstrated that short binasal prongs are more effective at preventing re-intubation than single nasal or nasopharyngeal prongs [typical RR 0.59 (CI: 0.41, 0.85), typical RD -0.21 (CI: -0.35, -0.07), NNT 5 (CI: 3, 14)]. In one study comparing short binasal prong devices (Sun 1999), the re-intubation rate was significantly lower with the Infant Flow Driver than with the Medicorp prong [RR 0.33 (CI: 0.17, 0.67), RD -0.32 (CI: -0.49, -0.15), NNT 3 (CI: 2, 7)]. The other study comparing short binasal prong devices (Infant Flow Driver versus INCA prongs, Stefanescu 2003) demonstrated no significant difference in the re-intubation rate but did show a significant reduction in the total days in hospital in the Infant Flow Driver group [MD -12.60 (95% CI: -22.81, -2.39) days].2. Preterm infants primarily treated with NCPAP soon after birth:In the one trial identified, Mazzella 2001 found a significantly lower oxygen requirement and respiratory rate in those randomised to short binasal prongs when compared with CPAP delivered via nasopharyngeal prong. The requirement for intubation beyond 48 hours from randomisation was not assessed.3. Studies randomising preterm infants to different NCPAP systems using broad inclusion criteriaThe studies of Rego 2002 and Buettiker 2004 did not examine the primary outcomes of this review. Of the secondary outcomes, Rego 2002 demonstrated a significantly higher incidence of nasal hyperaemia with the use of the Argyle prong compared with Hudson prongs [RR 2.39 (95% CI: 1.27, 4.50), RD 0.28 (95% CI: 0.10, 0.46)]. One study comparing different techniques of pressure generation is awaiting further assessment as it is currently available in abstract form only. AUTHORS' CONCLUSIONS: Short binasal prong devices are more effective than single prongs in reducing the rate of re-intubation. Although the Infant Flow Driver appears more effective than Medicorp prongs the most effective short binasal prong device remains to be determined. The improvement in respiratory parameters with short binasal prongs suggests they are more effective than nasopharyngeal CPAP in the treatment of early RDS. Further studies incorporating longer-term outcomes are required. Studies are also needed to determine the optimal pressure source for the delivery of NCPAP.

Comparison between abdominal fat measured by CT and anthropometric indices as prediction factors for mortality and morbidity after colorectal surgery.

AIM: This study aims to determine which anthropometric (body mass index (BMI), waist-hip-ratio (WHR) and waist-to-height ratio (WHtR)) and radiological (visceral fat area (VFA) measured by CT scan) measurements of adiposity correlated better with postoperative outcome of colorectal cancer (CRC) surgery. We also assessed which of these measurements best predicted overall survival (OS) and disease-free survival (DFS). METHODS: Data from 90 consecutive Caucasian CRC patients who underwent surgery for colorectal cancer between 2010 and 2011 with a median follow-up of 53.25 months were analysed. The correlations of different adiposity measurements and postoperative outcomes were determined using logistic regression models and multivariate analyses. RESULTS: Higher WHtR (p = 0.007) and VFA (p = 0.01) significantly increased the risk of overall morbidity, especially of Clavien-Dindo III or IV. The WHtR correlated best with VFA (p <0.0001), which is considered the gold standard for measuring visceral fat, whereas BMI (p = 0.15) was not a good predictor of postoperative morbidity. Multivariate analyses showed consistently significant results for postoperative complications for VFA in combination with all of the other variables analysed and for WHtR, confirming that VFA and WHtR were reliable independent prognostic factors of morbidity. VFA had a significant effect on OS (p = 0.012) but did not correlate with DFS (p = 0.51). CONCLUSIONS: Both VFA and WHtR independently provided predictive data for potential postoperative complications after CRC surgery. In case CT scan was used for diagnostic purposes, VFA should be used in routine clinical practice.

Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation.

BACKGROUND: Cathepsin K (catK), a lysosomal cysteine protease, was identified in a gene-profiling experiment that compared human early plaques, advanced stable plaques, and advanced atherosclerotic plaques containing a thrombus, where it was highly upregulated in advanced stable plaques. METHODS AND RESULTS: To assess the function of catK in atherosclerosis, catK(-/-)/apolipoprotein (apo) E(-/-) mice were generated. At 26 weeks of age, plaque area in the catK(-/-)/apoE(-/-) mice was reduced (41.8%) owing to a decrease in the number of advanced lesions as well as a decrease in individual advanced plaque area. This suggests an important role for catK in atherosclerosis progression. Advanced plaques of catK(-/-)/apoE(-/-) mice showed an increase in collagen content. Medial elastin fibers were less prone to rupture than those of apoE(-/-) mice. Although the relative macrophage content did not differ, individual macrophage size increased. In vitro studies of bone marrow derived-macrophages confirmed this observation. Scavenger receptor-mediated uptake (particularly by CD36) of modified LDL increased in the absence of catK, resulting in an increased macrophage size because of increased cellular storage of cholesterol esters, thereby enlarging the lysosomes. CONCLUSIONS: A deficiency of catK reduces plaque progression and induces plaque fibrosis but aggravates macrophage foam cell formation in atherosclerosis.

Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial.

BACKGROUND: Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. METHODS: In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. RESULTS: AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. CONCLUSION: AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT02014727; PACTR201402000719423.

High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index.

OBJECTIVES: High Bone Mass (HBM) is associated with (a) radiographic knee osteoarthritis (OA), partly mediated by increased BMI, and (b) pelvic enthesophytes and hip osteophytes, suggestive of a bone-forming phenotype. We aimed to establish whether HBM is associated with radiographic features of OA in non-weight-bearing (hand) joints, and whether such OA demonstrates a bone-forming phenotype. METHODS: HBM cases (BMD Z-scores≥+3.2) were compared with family controls. A blinded assessor graded all PA hand radiographs for: osteophytes (0-3), joint space narrowing (JSN) (0-3), subchondral sclerosis (0-1), at the index Distal Interphalangeal Joint (DIPJ) and 1st Carpometacarpal Joint (CMCJ), using an established atlas. Analyses used a random effects logistic regression model, adjusting a priori for age and gender. Mediating roles of BMI and bone turnover markers (BTMs) were explored by further adjustment. RESULTS: 314 HBM cases (mean age 61.1years, 74% female) and 183 controls (54.3years, 46% female) were included. Osteophytes (grade≥1) were more common in HBM (DIPJ: 67% vs. 45%, CMCJ: 69% vs. 50%), with adjusted OR [95% CI] 1.82 [1.11, 2.97], p=0.017 and 1.89 [1.19, 3.01], p=0.007 respectively; no differences were seen in JSN. Further adjustment for BMI failed to attenuate ORs for osteophytes in HBM cases vs. controls; DIPJ 1.72 [1.05, 2.83], p=0.032, CMCJ 1.76 [1.00, 3.06], p=0.049. Adjustment for BTMs (concentrations lower amongst HBM cases) did not attenuate ORs. CONCLUSIONS: HBM is positively associated with OA in non-weight-bearing joints, independent of BMI. HBM-associated OA is characterised by osteophytes, consistent with a bone-forming phenotype, rather than JSN reflecting cartilage loss. Systemic factors (e.g. genetic architecture) which govern HBM may also increase bone-forming OA risk.

Identification of genes potentially involved in rupture of human atherosclerotic plaques.

Although rupture of an atherosclerotic plaque is the major cause of acute vascular occlusion, the exact molecular mechanisms underlying this process are still poorly understood. In this study, we used suppression subtractive hybridization to make an inventory of genes that are differentially expressed in whole-mount human stable and ruptured plaques. Two libraries were generated, one containing 3000 clones upregulated and one containing 2000 clones downregulated in ruptured plaques. Macroarray analysis of 500 randomly chosen clones showed differential expression of 45 clones. Among the 25 clones that showed at least a 2-fold difference in expression was the gene of perilipin, upregulated in ruptured plaques, and the genes coding for fibronectin and immunoglobulin lambda chain, which were downregulated in ruptured plaques. Reverse transcriptase-polymerase chain reaction analysis on 10 individual ruptured and 10 individual stable plaques showed a striking consistency of expression for the clones SSH6, present in 8 ruptured and 2 stable plaques, and perilipin, expressed in 8 ruptured plaques and completely absent in stable plaques. Localization studies of both perilipin mRNA and protein revealed expression in cells surrounding the cholesterol clefts and in foam cells of ruptured atherosclerotic plaques. No expression was observed in nondiseased artery, and only a few cells in the shoulder region of stable plaques tested positive for perilipin. In conclusion, this study shows that it is possible to identify genes that are differentially expressed in whole-mount stable or ruptured atherosclerotic plaques. This approach may yield several potential regulators of plaque destabilization.

An interview guide for clinicians to identify a young disabled person's motivation to work.

BACKGROUND: The percentage of young people with disabilities who are employed is relatively low. Motivation is considered to be an important factor in facilitating or hindering their ability to obtain employment. OBJECTIVE: We aimed to develop a topic list that could serve as an interview guide for professionals in occupational health care which would aid them in their discussion of work motivation-related issues with this group. METHODS: We systematically searched Pubmed, PsychInfo and Picarta. Studies were included if they described aspects of work motivation and/or instruments that assess work motivation. Based on the results of our literature survey, we developed a list of topics that had been shown to be related to work motivation. RESULTS: Our search resulted in 12 articles describing aspects of work motivation and 17 articles describing instruments that assess work motivation. The aspects that we found were intrinsic motivation, extrinsic motivation, goal setting, self-efficacy, expectancy, values and work readiness. Based on this information we developed an interview guide that includes seven topic areas: intrinsic motivation, extrinsic motivation, goal setting, expectancy, values, self- efficacy, and work readiness. CONCLUSION: The topics within the interview guide and the literature survey data that is presented will shed light on the role that motivation plays on the work participation among young people with disabilities.

Mental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the Copenhagen Study in the rest of Denmark.

BACKGROUND: Our previous investigation of the prevalence of mental illness among the biological and adoptive relatives of schizophrenic adoptees in Copenhagen, Denmark, showed a significant concentration of chronic schizophrenia (5.6%) and what Bleuler called "latent schizophrenia" (14.8%) in the biological relatives of chronic schizophrenic adoptees, indicating the operation of heritable factors in the liability for schizophrenic illness. METHODS: We now report the results of a replication of that study in the rest of Denmark (the "Provincial Sample"). RESULTS: In this sample, the corresponding prevalences were 4.7% and 8.2%. In the combined "National Sample" of adoptees with chronic schizophrenia, that disorder was found exclusively in their biological relatives and its prevalence overall was 10 times greater than that in the biological relatives of controls. CONCLUSIONS: This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors.

Thought disorder in schizophrenic and control adoptees and their relatives.

BACKGROUND: Previous research showed significantly elevated levels of thought disorder in the relatives of persons with schizophrenia, as well as in the persons with schizophrenia themselves. Comparisons of schizophrenic and control adoptees and their respective relatives provide a method for minimizing the confounding of genetic and environmental sources of familial resemblance and for elucidating whether the elevated levels of thought disorder in persons with schizophrenia and their relatives reflect the influence of shared genetic factors, shared environmental factors, or both. The present study provides the first such adoption-sample data on an operationally defined measure of thought disorder. METHODS: Speech samples elicited by standard interview questions from schizophrenic and control adoptees and their respective biological and adoptive relatives were tape-recorded. Verbatim transcripts of these speech samples were scored, while unaware of the personal or family diagnoses of the subjects, using the Thought Disorder Index (TDI). RESULTS: The mean TDI scores were significantly higher in schizophrenic than in control adoptees and in biological relatives of the schizophrenic adoptees than in the biological relatives of the control adoptees, whereas the respective groups of adoptive relatives did not differ significantly. The differences were most marked for the samples of biological sibs and half sibs, which were larger and more representative than the samples of parents. CONCLUSION: Results suggest that the elevated TDI scores in the relatives of persons with schizophrenia that have been found in other studies reflect the operation of genes increasing the liability for schizophrenia, rather than the rearing experiences that were shared in common with schizophrenic probands.

Winter birth and biological family history in adopted schizophrenics.

To investigate relationships between birth season and biological family history in schizophrenia, this study used a sample of schizophrenics that had the advantages of (a) particularly thorough diagnostic assessments of schizophrenics' relatives, including information from direct interviews as well as chart reviews, and (b) schizophrenic probands who were adopted at early age, mitigating the usual confounding of genetic and postnatal environmental influences of the family. Adopted schizophrenics with no biological family history of schizophrenia-spectrum disorders were significantly more likely to be born in winter months than were either (a) their own biological relatives, including their sibs and half-sibs, (b) schizophrenics with a positive family history for schizophrenia-spectrum disorders, or (c) people in the general population. Family-history-positive schizophrenics and their schizophrenic relatives were, in turn, significantly less likely than their own non-schizophrenic biological relatives to be born in the winter; schizophrenics in these families tended to be born in the milder-weather seasons, particularly the spring and fall. Results suggest that environmental factors associated with winter birth may be etiologically important in schizophrenia, particularly for cases in which familial liability factors are weak. By contrast, a familial, probably genetic, liability factor may be especially important in schizophrenics born in mild weather.

Immunolocalization of eicosanoid enzymes and growth factors in human myometrium and fetoplacental tissues in failed labor inductions.

OBJECTIVE: To investigate the correlation between myometrial-derived eicosanoids and growth factors during the onset of parturition. METHODS: Myometrial samples were obtained from patients who were delivered by cesarean for failed induction or abnormal fetal heart rate tracings but who experienced normal labor progression until the occurrence of the abnormal tracing. Placentas and fetal membranes were obtained from patients with normal labor, no labor, and failed labor progression. The tissues were processed and sections were immunostained for cyclooxygenases, prostacyclin synthetase (PGI2-S), thromboxane A2 synthetase (TXA2-S), 5-lipoxygenase, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and EGF receptor, using specific antibodies directed against these molecules. RESULTS: Myometrial and fetoplacental tissues from women with normal labor, no labor, and failed labor contain immunoreactive cyclooxygenases, 5-lipoxygenase, TXA2-S, PGI2-S, EGF, TGF-alpha, and EGF receptor. However, their immunostaining intensity, with the exception of EGF receptor, decreased substantially in myometrium from women with failed labor induction compared with those having normal labor progression. No difference was noted in the immunostaining intensity of growth factors and eicosanoid enzymes in the fetoplacental membranes from these patients, except for cyclooxygenases, which were prominent in fetal membranes from normal labor compared with failed labor and no labor. CONCLUSION: Myometrial-derived eicosanoids and growth factors may be important in processes of parturition because reduction in their production in the myometrium is correlated with failed labor induction. Because of the regulatory action of growth factors in eicosanoid biosynthesis in uterine and fetoplacental tissues, EGF/TGF-alpha may indirectly influence the process of parturition by regulating eicosanoid production in the myometrium.

Macrophage secretory products and sperm zona pellucida binding.

OBJECTIVE: To determine if exposure of human gametes to macrophage secretory products reduces sperm binding to the zona pellucida, and to determine which cytokine(s) may be responsible for this effect. METHODS: A human macrophage cell line was cultured and either activated with lipopolysaccharide for 2 hours and then washed or left unactivated. Culture-conditioned media from activated or unactivated cells was used in hemizona assay. Hemizonae were incubated with sperm suspended in culture medium from either unactivated macrophages or activated macrophages, with the matching hemizona incubated with sperm suspended in control medium. Matching hemizonae were incubated with sperm suspended in unactivated macrophage medium paired with sperm suspended in activated macrophage culture medium. Conditioned medium from activated macrophages was found to have elevated levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, and transforming growth factor-beta, therefore, gametes were also exposed to these cytokines followed by the hemizona assay. After each incubation, the number of sperm tightly bound to the outer surface of each hemizona was determined. RESULTS: Exposure of gametes to activated and unactivated macrophage culture-conditioned media significantly decreases sperm binding to the zona pellucida, with medium from activated macrophages inducing the greatest effect (P < .05). Exposure of sperm to TNF-alpha significantly impaired sperm binding (P < .05), whereas other cytokines tested had no effect. CONCLUSION: These results suggest that macrophage secretory products in the basal and activated state may be a factor in endometriosis-associated infertility through the interference of sperm binding to the zona pellucida, and that TNF-alpha is a key cytokine responsible for this effect.