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.

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.

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.

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.

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.

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.

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.

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.

[Migration of a ventriculoperitoneal shunt in the liver: A rare complication]. / La perforation hépatique d'un cathéter de dérivation ventriculo-péritonéale : une complication rare.

We report on a case of migration inside the liver of the distal end of a ventriculoperitoneal shunt catheter in an adult patient. A simple laparotomy permitted the surgical removal with no haemorrhagic complication. We discuss the other cases reported in the literature and we outline the need to perform an abdominal CT scan in patients carrying a VP shunt with digestive symptoms.

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.

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.

Clonal growth of human articular cartilage and the functional role of the periosteum in chondrogenesis.

OBJECTIVE: Clinical cartilage repair with transplantation of cultured chondrocytes, the first described technique introduced in 1994, includes a periosteal membrane but today cells are also implanted without the periosteal combination. The aim of this study was to see if the periosteum had more than a biomechanical function and if the periosteum had a biological effect on the seeded cells tested in an agarose system in which the clonal growth in agarose and the external growth stimulation could be analysed. METHODS: Four different experiments were used to study the growth of human chondrocytes in agarose and the periosteal influence. Human chondrocytes were isolated and transferred to either primary or secondary agarose culture. After 4 weeks, the total number of clones >50 microm was counted. Cocultures of chondrocytes and periosteal tissue, cultures of chondrocytes with conditioned medium from chondrocytes, periosteal cells and fibroblast were used to study a potential stimulatory effect on growth and different cytokines and growth factors were analysed. RESULTS: It was found that the human chondrocytes had different growth properties in agarose with the formation of four different types of clones: a homogenous clone without matrix production, a homogenous clone with matrix production, a differentiated clone with matrix production and finally a differentiated clone without matrix production. The periosteum exerted a paracrine effect on cultured chondrocytes in agarose resulting in a higher degree of cloning. The chondrocytes produced significant amounts of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta. The periosteum produced significant amounts of IL-6, IL-8 and TGF-beta. Cocultures of chondrocytes and periosteum demonstrated a potentiation of IL-6 and IL-8 release but not of TGF-beta and GM-CSF. CONCLUSION: Articular chondrocytes are able to form clones of different properties in agarose and the periosteum has a capacity of stimulating chondrocyte clonal growth and differentiation and secretes significant amounts of IL-6, IL-8, GM-CSF and TGF-beta. It may be that the repair of cartilage defects with seeded chondrocytes could benefit from the combination with a periosteal graft. The production of TGF-beta by implanted chondrocytes could influence the chondrogenic cells in the periosteum to start a periosteal chondrogenesis and together with the matrix from implanted chondrocyte production, a repair of cartilaginous appearance may develop; a dual chondrogenic response is possible.

Extremely low birth weight and body size in early adulthood.

AIMS: To determine the body size of extremely low birth weight (ELBW, birth weight 500-999 g) subjects in early adulthood. METHODS: Cohort study examining the height and weight of 42 ELBW survivors free of cerebral palsy between birth and 20 years of age. Weight and height measurements were converted to Z (SD) scores. RESULTS: At birth the subjects had weight Z scores substantially below zero (mean birth weight Z score -0.90, 95% CI -1.25 to -0.54), and had been lighter than average at ages 2, 5, and 8 years. However, by 14, and again at 20 years of age their weight Z scores were not significantly different from zero. At ages 2, 5, 8, 14, and 20 years of age their height Z scores were significantly below zero. Their height at 20 years of age was, however, consistent with their parents' height. As a group they were relatively heavy for their height and their mean body mass index (BMI) Z score was almost significantly different from zero (mean difference 0.42, 95% CI -0.02 to 0.84). Their mean BMI (kg/m2) was 24.0 (SD 5.2); 14 had a BMI >25, and four had a BMI >30. CONCLUSIONS: Despite their early small size, by early adulthood the ELBW subjects had attained an average weight, and their height was consistent with their parents' height. They were, however, relatively heavy for their height.

Early intravenous nutrition for the prevention of neonatal jaundice.

BACKGROUND: The early institution of enteral feeding in the first few days of life is known to impact on the development of unconjugated hyperbilirubinaemia. However, the effect of early intravenous nutrition on neonatal jaundice remains unknown. OBJECTIVES: To determine the effect of early intravenous nutrition on neonatal jaundice. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used including searches of the Cochrane Controlled Trials Register (Cochrane Library: Issue 3, 2002), MEDLINE (1966-December 2002), and EMBASE (1974-December 2002). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating the effect of early intravenous nutrition on unconjugated bilirubin. DATA COLLECTION AND ANALYSIS: The search strategy identified no eligible studies, thus no data were collected. MAIN RESULTS: No studies were identified. REVIEWER'S CONCLUSIONS: Decisions regarding the institution of early intravenous nutrition must continue to be based upon factors others than its effect on neonatal jaundice.

Early postnatal discharge from hospital for healthy mothers and term infants.

BACKGROUND: Length of postnatal hospital stay has declined dramatically in the past thirty years. There is ongoing controversy concerning whether or not staying less time in hospital is harmful or beneficial. OBJECTIVES: The objective of this review was to assess the safety, impact and effectiveness of a policy of early discharge for healthy mothers and term infants, with respect to the health and well-being of mothers and babies, satisfaction with postnatal care, overall costs of health care and broader impacts on families. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (April 2002), the Effective Practice and Organisation of Care Review Group specialised register of clinical trials, the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966 to 2001), CINAHL (1982 to 2001), EMBASE (1988 to 1993) and reference lists of articles. SELECTION CRITERIA: Randomized trials comparing early discharge from hospital of healthy mothers and term infants, of greater than or equal to 2500 grams, with standard care in the settings in which trials were conducted. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were abstracted independently by all five reviewers. MAIN RESULTS: Eight trials were identified involving 3600 women. There was substantial variation in the definition of 'early discharge', and the extent of antenatal preparation and midwife home care following discharge offered to women in intervention and control groups. Five trials recruited and randomized women in pregnancy, three randomized women following childbirth. Post randomization exclusions were high. Protocol violations occurred in both directions. No statistically significant differences in infant or maternal readmissions were found in six trials reporting data on these outcomes. Three trials had mixed results showing either no significant difference or results favouring early discharge for the outcome of maternal depression although none used a well-validated standardised instrument. The results of six trials showed that early discharge had no impact on breastfeeding although significant heterogeneity was present between studies. REVIEWER'S CONCLUSIONS: The findings are inconclusive. There is no evidence of adverse outcomes associated with policies of early postnatal discharge, but methodological limitations of included studies mean that adverse outcomes cannot be ruled out. It remains unclear how important midwifery support at home is to the safety and acceptability of early discharge. Large well-designed trials of early discharge programs incorporating process evaluation to assess the uptake of co-interventions, and using standardised approaches to outcome assessment are needed.

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 will focus exclusively on identifying the most effective pressure source and interface for NCPAP delivery in preterm infants. OBJECTIVES: 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, which technique of pressure generation and which type of nasal interface for NCPAP delivery most effectively reduces the need for additional respiratory support? SEARCH STRATEGY: The strategy included searches of MEDLINE (1966-2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002), 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 the single 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)]. 2. Preterm infants primarily treated with NCPAP soon after birth: 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. No studies comparing different techniques of pressure generation were identified. REVIEWER'S 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.