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There is a social gradient to the determinants of health; low socioeconomic status (SES) has been linked to reduced educational attainment and employment prospects, which in turn affect physical and mental wellbeing. One goal of preventive interventions, such as parenting programs, is to reduce these health inequalities by supporting families with difficulties that are often patterned by SES. Despite these intentions, a recent individual participant data (IPD) meta-analysis of the Incredible Years (IY) parenting program found no evidence for differential benefit by socioeconomic disadvantage (Gardner et al. in Public Health Resesearch 5, 1–144, 2017). However, it did not examine whether this was influenced by engagement in the intervention. Using intervention arm data from this pooled dataset (13 trials; N = 1078), we examined whether there was an SES gradient to intervention attendance (an indicator of engagement). We ran mixed-effects Poisson regression models to estimate incidence rate ratios (IRRs) for program attendance for each of five (binary) markers of SES: low income; unemployment; low education status; teen parent; and lone parent status. The multilevel structure of the data allowed for comparison of within-trial and between-trial effects, including tests for contextual effects. We found evidence that low SES was associated with reduced attendance at parenting programs—an 8–19% reduction depending on the SES marker. However, there was no evidence that this association is impacted by differences in SES composition between trials or by the attendance levels of higher-SES families. The findings underscore the importance of developing and prioritizing strategies that enable engagement in parenting interventions and encourage program attendance by low-SES families. [ABSTRACT FROM AUTHOR]

Purpose : Healthcare settings remain important contexts for the identification of intimate partner violence (IPV); however, identification strategies for IPV are diverse and work in complex ways that may differ across contexts. To understand how, rather than if, IPV identification strategies work, we undertook a systematic review of reviews with realist synthesis. Methods: We undertook a search of five databases for full-text, peer-reviewed systematic reviews addressing identification strategies for IPV in healthcare contexts. We screened titles and full texts in duplicate and independently, appraised included systematic reviews and synthesized them using methods from realist synthesis to develop context-mechanism-outcome configurations (CMOCs). Results: We included 29 reviews reported in 32 publications. Our findings were summarized in four CMOCs at system, system–clinician, clinician and patient levels. CMOCs underscored the role of supportive clinical and practice contexts, patient-provider relationships and continuity of care to ensure the benefits, and reduce the potential harms, of a range of identification strategies. CMOCs also highlighted the importance of supporting clinicians through clinical policies and protocols to ensure a consistent, safe and effective response to IPV. Conclusions: Future work should address how supportive clinical contexts that facilitate effective inquiry, disclosure, and referral to services can be created, acknowledging that what works in one context may not work in another. Included systematic reviews did not permit exploration of how racial and ethnic diversity relate to identification strategies. This is an area requiring urgent research to inform clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic increased the burden of mental disorders worldwide. Peru has been one of the countries most affected by COVID-19, however, studies evaluating the medium and long-term consequences of the pandemic on Peruvians' mental health are recent and represent a new field of study in proliferation. We aimed to estimate the impact of the COVID-19 pandemic on the prevalence and treatment of depressive symptoms using nationally representative surveys in Peru. Methods: Our study is an analysis of secondary data. We carried out a time series cross-sectional analysis based on the National Demographic and Health Survey of Peru, collected using a complex sampling design. The Patient Health Questionnaire-9 was used to measure mild (5–9 points), moderate (10–14 points), and severe (15 points or more) depressive symptoms. The participants were men and women aged 15 years and older, living in urban and rural areas of all regions of Peru. The main statistical analysis used segmented regression with Newey-West standard errors, taking into account that each year of the evaluation was divided into four measures (quarter measure). Results: We included 259,516 participants. An average quarterly increase of 0.17% (95% CI 0.03–0.32%) in the prevalence of moderate depressive symptoms was identified after the onset of the COVID-19 pandemic (approximately an increase of 1583 new cases of moderate depressive symptoms by each quarter). The percentage of cases treated for mild depressive symptoms increased quarterly by an average of 0.46% (95% CI 0.20–0.71%) after the onset of the COVID-19 pandemic (approximately an increase of 1242 new cases treated for mild depressive symptoms by each quarter). Conclusion: In Peru, increases in the prevalence of moderate depressive symptoms and the proportion of cases treated with mild depressive symptoms were found after the COVID-19 pandemic. Therefore, this study is a precedent for future research assessing the prevalence of depressive symptoms and the proportion of cases receiving treatment during the pandemic and post-pandemic years. [ABSTRACT FROM AUTHOR]

Objectives: This study used data from a randomised controlled trial of a school-based mindfulness programme in the UK to investigate the structure and performance of the 10-item Child and Adolescent Mindfulness Measure (CAMM). Method: The study included 7924 children and adolescents aged 11 to 14 years. Participants provided CAMM data at pre-intervention, 7 months (post-intervention) and 1 year. Exploratory factor analysis (EFA) of pre-intervention data was undertaken. Multiple indicators multiple causes (MIMIC) models were fitted to pre-intervention responses to investigate differential item functioning across groups defined by gender, year group and ethnicity. Response shift resulting from receiving the mindfulness programme was investigated by fitting MIMIC models to compare item functioning between the intervention and control arms. Results: EFA results indicated that the 2-factor model was a good fit. Eight items were associated with the first factor, while the remaining two items, which specifically addressed avoiding unwanted thoughts and feelings, were associated with the second factor. MIMIC model findings indicated that girls scored lower (ostensibly less mindful) on 4 items than boys that had the same latent level of mindfulness; as a result of receiving the mindfulness programme, participants scored lower on one item ("At school, I walk from class to class without noticing what I'm doing") after holding latent level of mindfulness constant. Conclusions: Findings indicate that the CAMM has a 2-factor structure in the UK in late childhood and early adolescence. While we did observe some differences in how individual items performed across groups, these differences were small compared to the overall variability in the CAMM scores. Preregistration: Current controlled trials ISRCTN86619085. [ABSTRACT FROM AUTHOR]

Context: Interactions between wildlife and anthropogenic infrastructure, such as roads, fences, and dams, can influence wildlife movement, and potentially cause human-wildlife conflict. In the Galapagos archipelago, two species of critically endangered giant tortoise encounter infrastructure and human-modified vegetation in farms, which could influence movement choices. Objectives: We investigated factors influencing tortoise movement and habitat selection in the agricultural landscape of Santa Cruz Island, Galapagos. Methods: We examined the movement of 27 tortoises collected using GPS tracking between 2014 and 2020, in relation to the location of vegetation, ponds, fences, and roads. Results: We found that tortoises preferred pasture over native vegetation, but there was little difference among their preferences for native vegetation, crops, or invasive vegetation. Tortoises also travelled slower in pasture, and faster in invasive vegetation, compared to crops and native vegetation. Tortoises were more likely to be found closer to ponds than predicted by chance. Our results indicated that most fences were porous to tortoises, with limited impact on their movement. Tortoises were more likely to use areas near roads with low-traffic. Conclusions: Pastures, and ponds are important habitat for tortoises in farms and are likely to be used preferentially by tortoises. Overall, fences and roads did not strongly obstruct tortoise movements, however, this may lead to potential injury to tortoises on roads and property damage for farmers. To best identify priority areas for managing wildlife on farms, we recommend evaluating the combined effects of multiple anthropogenic landscape features on wildlife movements. [ABSTRACT FROM AUTHOR]

Children's mental health is deteriorating while access to child and adolescent mental health services is decreasing. Recent UK policy has focused on schools as a setting for the provision of mental health services, and counselling is the most common type of school-based mental health provision. This study examined the longer-term effectiveness of one-to-one school-based counselling delivered to children in UK primary schools. Data were drawn from a sample of children who received school-based counselling in the UK in the 2015/16 academic year, delivered by a national charitable organisation. Mental health was assessed at baseline, immediately post-intervention, and approximately 1 year post-intervention, using the Strengths and Difficulties Questionnaire (SDQ) completed by teachers and parents. Paired t tests compared post-intervention and follow-up SDQ total difficulties scores with baseline values. Propensity score matching was then used to identify a comparator group of children from a national population survey, and linear mixed effects models compared trajectories of SDQ scores in the two groups. In the intervention group, teacher and parent SDQ total difficulties scores were lower at post-intervention and longer-term follow-up compared to baseline (teacher: baseline 14.42 (SD 7.18); post-intervention 11.09 (6.93), t(739) = 13.78, p < 0.001; follow-up 11.27 (7.27), t(739) = 11.92, p < 0.001; parent: baseline 15.64 (6.49); post-intervention 11.90 (6.78), t(361 = 11.29, p < 0.001); follow-up 11.32 (7.19), t(361) = 11.29, p < 0.001). The reduction in SDQ scores was greater in the intervention compared to the comparator group (likelihood ratio test comparing models with time only versus time plus group-by-time interaction: χ2 (3) = 24.09, p < 0.001), and model-predicted SDQ scores were lower in the intervention than comparator group for 2 years post-baseline. A one-to-one counselling intervention delivered to children in UK primary schools predicted improvements in mental health that were maintained over a 2 year follow-up period. [ABSTRACT FROM AUTHOR]

This commentary accompanies the special issue of Prevention Science on modern meta-analytic methods. The papers that comprise this special issue are considered in terms of the next-generation meta-analytic questions they support: questions about multivariate relationships, drawing on real-life data structures, with improved usability, and answered openly. The contributions to this special issue illustrate a range of methods to address these questions, including meta-analytic structural equation modelling; robust variance estimation and network meta-analysis methods; transportability and causal inference; Bayesian methods; and open science. This special issue collectively represents a step forward in the field's ability to address questions of use to improving human welfare through preventing ill health, supporting uptake of these next-generation methods by applied researchers in prevention science. Future methodological developments in meta-analysis should be synergistic with the questions prevention scientists seek to answer, both creating new possibilities and meeting the challenges of improving human health and wellbeing. [ABSTRACT FROM AUTHOR]

Whole-school interventions are a promising approach to preventing bullying and aggression while promoting broader health. The main analyses from a trial of the INCLUSIVE whole-school intervention reported reductions in bullying victimisation but not aggression and improved mental well-being. Latent transition analysis can examine how interventions 'move' people between classes defined by multiple outcomes over time. We examined at baseline what classes best defined individuals' bullying, aggression and mental well-being and what effects did the intervention have on movement between classes over time? INCLUSIVE was a two-arm cluster-randomised trial with 20 high schools per arm, with 24-month and 36-month follow-ups. We estimated sequential latent class solutions on baseline data. We then estimated a latent transition model including baseline, 24-month and 36-month follow-up measurements. Our sample comprised 8179 students (4082 control, 4097 intervention arms). At baseline, classes were (1) bullying victims, (2) aggression perpetrators, (3) extreme perpetrators and (4) neither victims nor perpetrators. Control students who were extreme perpetrators were equally likely to stay in this class (27.0% probability) or move to aggression perpetrators (25.0% probability) at 24 months. In the intervention group, fewer extreme perpetrators students remained (5.4%), with more moving to aggression perpetrators (65.1%). More control than intervention extreme perpetrators moved to neither victims nor perpetrators (35.2% vs 17.8%). Between 24 and 36 months, more intervention students moved from aggression perpetrators to neither victims nor perpetrators than controls (30.1% vs 22.3%). Our findings suggest that the intervention had important effects in transitioning students to lower-risk classes. [ABSTRACT FROM AUTHOR]

Purpose: Studying mental wellbeing requires the use of reliable, valid, and practical assessment tools, such as the Short version of the Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS). Research on the mental wellbeing of children in care is sparse. The current study aims to: (1) examine the unidimensionality of SWEMWBS; (2) assess measurement invariance of SWEMWBS across children and young people in care compared to their peers not in care; and (3) investigate the latent factor mean differences between care status groups. Methods: We used data from the 2017 School Health Research Network Student Health and Wellbeing (SHW) survey, completed by 103,971 students in years 7 to 11 from 193 secondary schools in Wales. The final data include a total of 2,795 participants (46% boys), which includes all children in care and a sub-sample of children not in care who completed the SWEMWBS scale fully and answered questions about their living situation. Results: Confirmatory factor analysis supported the unidimensionality of SWEMWBS. The SWEMWBS is invariant across groups of young people in foster, residential and kinship care compared to children and young people not in care at configural, metric and scalar levels. Findings from latent mean comparisons showed that young people in care reported lower mental wellbeing than their peers, with those in residential care reporting the lowest scores. Conclusions: Findings suggest that SWEMWBS is a valid scale for measuring differences in mental wellbeing for young people in care similar to the population. [ABSTRACT FROM AUTHOR]

Co-production affords an intervention's target population the opportunity to participate in intervention theory decision-making during the development process. This addresses the over-reliance on developing interventions through academic theories which can be devoid of contextual understanding and result in challenges to implementing school-based health programmes. There is an emergent empirical literature on co-producing school-based health interventions, but an understanding of appropriate theoretical types and processes and stakeholders' experiences is lacking. Through the conduct of a systematic review, this study seeks to understand the types and underlying theories and processes for co-production in school-based health interventions with students aged 11-16. A thematic synthesis explored stakeholders' experiences of the different types of co-production. A systematic search of five electronic bibliographic databases, citation tracking of included studies, and consultation with an expert international panel were employed. Of 27,433 unique papers, 30 papers representing 22 studies were retained to describe types, and 23 papers of 18 studies used to synthesise stakeholders' experiences. Three types were identified: external, individual-level, and system-level capacity-building. Whilst this review showed variability in co-production types, stakeholders involved and processes, shared functions were identified. Students', school staff, facilitators' and researchers' experiences in terms of acceptability, feasibility and undertaking decision-making are discussed. Recommendations for conceptualising and reporting co-production and process evaluations of co-produced school-based health interventions are highlighted. [ABSTRACT FROM AUTHOR]

The UK National Institute for Health and Care Excellence (NICE) considered evidence for voretigene neparvovec (VN; Luxturna®) for the treatment of RPE65-mediated inherited retinal dystrophies (IRD) within its highly specialised technology programme. This paper summarises the evidence provided by the company; the appraisal of the evidence by the Peninsula Technology Appraisal Group, who were commissioned to act as the independent evidence review group (ERG); and the development of the NICE guidance by the appraisal committee. The evidence presented by the company highlighted the significant lifelong burden of IRD for patients and carers. Evidence to support the effectiveness of VN was lacking, but the available evidence showed a modest, sustained improvement across a variety of vision-related outcomes. While patients would remain visually impaired, the committee considered that VN would prevent further deterioration in vision. The modelling approach used by the company had a number of limitations and relied heavily upon a large volume of clinical expert input to produce cost-effectiveness estimates with large uncertainty around long-term effectiveness. The ERG's main concerns revolved around these long-term outcomes and the plausibility of utility values. The NICE committee were convinced that the clinical benefits of VN were important and an appropriate use of national health service resources within a specialised service. The committee concluded that a high unmet need existed in patients with RPE65-mediated IRD and that VN represents a step change in the management of this condition. [ABSTRACT FROM AUTHOR]

A recent increase in the development of online parent programs calls for the need to understand how effective these strategies are for improving children's mental health. We meta-analyzed the effects of online parent programs on children's behavioral problems. Moreover, we explored the combinations of program components to yield stronger program effects. Medline, PsycINFO, Web of Science, and the Cochrane Library were searched. We included peer-reviewed randomized studies evaluating the effect of an online parent program. Effect sizes (Hedges' g) were calculated from post intervention means and standard deviations. We used Qualitative Comparative Analysis (QCA) to identify pathways to effectiveness and individual content and delivery components that seem sufficient or necessary for yielding high effectiveness. Of 2941 articles, 12 articles with a total of 2025 participants met the inclusion criteria. Online parent programs have significant effects on children's behavioral problems (g = − 0.32; 95% CI, − 0.47 to − 0.17), emotional problems (g = − 0.22; 95% CI, − 0.31 to − 0.13), and parental mental health problems (g = − 0.30; 95% CI, − 0.42 to − 0.17). In the QCA, sending parents reminders to work on the program was the only one sufficient component. In conclusion, online support programs reduce children's behavioral and emotional problems and improve parental mental health. Sending parents reminders to work on the program seems to contribute to high effectiveness. Review Registration This study was registered with PROSPERO, number CRD42017080051. [ABSTRACT FROM AUTHOR]

Decision aids (DAs) are evidence-based tools that support shared decision-making (SDM) implementation in practice; this study aimed to identify existing osteoporosis DAs and assess their quality and efficacy; and to gain feedback from a patient advisory group on findings and implications for further research. We searched multiple bibliographic databases to identify research studies from 2000 to 2019 and undertook an environmental scan (search conducted February 2019, repeated in March 2020). A pair of reviewers, working independently selected studies for inclusion, extracted data, evaluated each trial's risk of bias, and conducted DA quality assessment using the International Patient Decision Aid Standards (IPDAS). Public contributors (patients and caregivers with experience of osteoporosis and fragility fractures) participated in discussion groups to review a sample of DAs, express preferences for a new DA, and discuss plans for development of a new DA. We identified 6 studies, with high or unclear risk of bias. Across included studies, use of an osteoporosis DA was reported to result in reduced decisional conflict compared with baseline, increased SDM, and increased accuracy of patients' perceived fracture risk compared with controls. Eleven DAs were identified, of which none met the full set of IPDAS criteria for certification for minimization of bias. Public contributors expressed preferences for encounter DAs that are individualized to patients' own needs and risk. Using a systematic review and environmental scan, we identified 11 decision aids to inform patient decisions about osteoporosis treatment and 6 studies evaluating their effectiveness. Use of decision aids increased accuracy of risk perception and shared decision-making but the decision aids themselves fail to comprehensively meet international quality standards and patient needs, underpinning the need for new DA development. [ABSTRACT FROM AUTHOR]

Child physical abuse is an issue of global concern. Conservative estimates set global prevalence of this type of maltreatment at 25%, its consequences and cost to society escalating with increasing frequency and severity of episodes. Syntheses of the evidence on parenting programs for reducing rates of physical abuse recidivism have, to date, not been able to establish effectiveness. Paucity of data and inconsistent inclusion criteria in past reviews made meta-analysis often impossible or uninformative. The current systematic review updates prior reviews and overcomes some of the methodological issues they encountered by pooling trial-level data from a well-defined scope of trials of parenting interventions aimed at preventing the re-abuse of children by parents with substantiated or suspected physical abuse history. Randomized controlled trials and rigorous non-randomized designs were sought via nine online databases, two trial registries, several clearinghouses and contact with experts. A total of fourteen studies of variable quality were included in this review, four of which had outcomes that enabled meta-analysis. Overall, this review presents evidence supporting the effectiveness of parenting behavioral programs based on social learning theory for reducing hard markers of child physical abuse recidivism. Meta-analysis found that the absolute risk reduction in risk of recidivism was 11 percentage points less for maltreating parents who undergo parenting programs (RD = -0.11, 95% CI [-0.22, -0.004], p = 0.043, I 2 = 28.9%). However, the pooled effect size was not statistically significant when calculated as a risk ratio (0.76, 95% CI [0.54, 1.07], I 2 = 38.4%). Policy makers and practitioners should be made aware that this intervention method is backed by promising evidence featuring modest yet significant reductions in hard markers of child physical abuse, even though the methodological robustness of these findings should be further explored in future research. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is an emerging disease with a poor prognosis and high mortality rate that is even surpassing some types of cancer. This disease has been linked to the concomitant appearance of liver cirrhosis. Bleomycin-induced pulmonary fibrosis is a widely used mouse model that mimics the histopathological and biochemical features of human systemic sclerosis, an autoimmune disease that is associated with inflammation and expressed in several corporal systems as fibrosis or other alterations. To determine the effects on proliferation, redox and inflammation protein expression markers were analyzed by immunohistochemistry. Analyses showed a significant increase in protein oxidation levels by lipoperoxidation bio-products and in proliferation and inflammation processes. These phenomena were associated with the induction of the redox status in mice subjected to 100 U/kg bleomycin. These findings clearly show that the bleomycin model induces histopathological alterations in the liver and partially reproduces the complexity of systemic sclerosis. Our results using the bleomycin-induced pulmonary fibrosis model provide a protocol to investigate the mechanism underlying the molecular alteration found in the liver linked to systemic sclerosis. [ABSTRACT FROM AUTHOR]

Visualization of the thermal field in highly accelerated spatially developing turbulent boundary layers is carried out. Direct Numerical Simulation with high spatial/temporal resolution is performed in sink flow-type boundary layer by prescribing a passive scalar with a Prandtl number of 0.71. The range of the momentum thickness Reynolds number is approximately 320–432. The very strong Favorable Pressure Gradient (FPG) is imposed by a top converging shearless surface, which produces an approximately constant acceleration parameter of K = 4.0 × 10 - 6 . A precursor zone is prescribed upstream of the FPG region in order to generate accurate turbulent inflow information by means of the methodology proposed by Araya et al. (J Fluid Mech 670:518–605, 2011). While evident "signatures" of the very strong FPG have been identified in the velocity field, those "signatures" are much less evident in the temperature field causing a breakdown of the Reynolds analogy provoked by the streamwise pressure gradient (or source of dissimilarity between the momentum and thermal transport). A slow decrease in the thermal boundary layer thickness, δ T , is observed in the FPG zone. Additionally, local maxima of absolute intensities of the thermal fluctuations t RMS ′ exhibit nearly constant values (approx. 14% of T ∞ ) along the composite domain. Conversely, absolute intensities of the streamwise ( u RMS ′ ) show increases on their local maxima, with mild decreases in the transversal components of the velocity ( v RMS ′ and w RMS ′ ). Furthermore, profiles of cross-correlation < u ′ t ′ > at different streamwise stations depict a good collapsing level up to 4% of δ in the wall-normal direction, with peak values displacing farther from the wall in the FPG zone. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is to clarify if a classification based on the time of occurrence of associated malignancies in GIST patients can help in the understanding of the clinical controversies observed in these patients. Methods: We retrospectively reviewed all the patients diagnosed with GIST tumors between January 1999 and October 2016. They were divided into GIST patients associated with other tumors (A-GIST) and those not associated (NA-GIST). A-GIST patients were also divided into four types according to the proposed classification. Results: Of 104 GIST patients, 32 (30.7%) (A-GIST group) had at least one additional primary malignancy. The most frequent location of the associated malignancy was the GI tract (26%). Compared to NA-GIST, A-GIST were more often asymptomatic with a lower risk of recurrence. The main cause of death in NAGIST was GIST itself, being associated tumors the main cause of death in A-GIST group. No differences were found in DFS and OS between A-GIST and NA-GIST. Conclusions: The use of the proposed classification classifies GIST patients with associated malignancies in different subtypes that differ substantially in terms of incidence, type of neoplasms associated, cause of the association and prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Electrospun scaffolds of biopolymers have been used in skin tissue engineering to develop and create artificial skin tissue for replacement dermal substitutes. Moreover, electrospun scaffolds are used to improve wound dressing for assisting the wound healing process. We focus on the polypyrrole/iodine coating viability and observe the cultures of human epidermal keratinocytes (HaCaT) responding to improve scaffolds for skin tissue engineering. For this purpose, polyvinylpyrrolidone polymer was used as a polymer matrix. The FE-SEM analysis showed the morphologies obtained (fibers and spheres) by the different solvents used in polyvinylpyrrolidone solutions due to the polarity of the solvents. The polyvinylpyrrolidone fibers have an average diameter of 135.6 nm ± 1.4 nm, and polyvinylpyrrolidone spheres have diameters of 1.01-1.6 µm. Elemental analysis showed the incorporation of polypyrrole/iodine on polyvinylpyrrolidone scaffolds. An XRD study displayed the amorphous structure of polyvinylpyrrolidone fibers and spheres. Using FTIR, it was possible to identify the functional groups representative of polyvinylpyrrolidone, and the presence of the coating of polypyrrole was demonstrated. Polypyrrole/iodine proved to be a scaffolding with an optimal coating for the cellular growth of HaCaT cells, increasing viability, adhesion, and cell healing.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. As part of a single technology appraisal (ID807) undertaken by the National Institute of Health and Care Excellence, the Evidence Review Group, Warwick Evidence was invited to independently review the evidence submitted by the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized controlled trial in which 771 patients with relapsed or refractory multiple myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-, or fourth-line treatment. Takeda estimated the cost effectiveness of IXA-LEN-DEX using a de-novo partitioned-survival model with three health states (pre-progression, post-progression, and dead). In their first submission, this model was used to estimate the cost effectiveness of IXA-LEN-DEX vs. bortezomib plus dexamethasone (BORT-DEX) in second-line treatment, and of IXA-LEN-DEX vs. LEN-DEX in third-line treatment. To estimate the relative clinical performance of IXA-LEN-DEX vs. BORT-DEX, Takeda conducted network meta-analyses for important outcomes. The network meta-analysis for overall survival was found to be flawed in several respects, but mainly because a hazard ratio input for one of the studies in the network had been inverted, resulting in a large inflation of the claimed superiority of IXA-LEN-DEX over BORT-DEX and a considerable overestimation of its cost effectiveness. In subsequent submissions, Takeda withdrew second-line treatment as an option for IXA-LEN-DEX. The manufacturer's first submission comparing IXA-LEN-DEX with LEN-DEX for third-line therapy employed Tourmaline-MM1 data from third- and fourth-line patients as proxy for a third-line population. The appraisal committee did not consider this reasonable because randomization in Tourmaline-MM1 was stratified according to one previous treatment and two or more previous treatments. A further deficiency was considered to be the manufacturer's use of interim survival data rather than the most mature data available. A second submission from the company focussed on IXA-LEN-DEX vs. LEN-DEX as third- or fourth-line treatment (the two or more previous lines population) and a new patient access scheme was introduced. Covariate modeling of survival outcomes was proposed using the most mature survival data. The Evidence Review Group's main criticisms of the new evidence included: the utility associated with the pre-progression health state was overestimated, treatment costs of ixazomib were underestimated, survival models were still associated with great uncertainty, leading to clinically implausible anomalies and highly variable incremental cost-effectiveness ratio estimates, and the company had not explored a strong assumption that the survival benefit of IXA-LEN-DEX over LEN-DEX would be fully maintained for a further 22 years beyond the observed data, which encompassed only approximately 2.5 years of observation. The appraisal committee remained unconvinced that ixazomib represented a cost-effective use of National Health Service resources. Takeda's third submission offered new base-case parametric models for survival outcomes, a new analysis of utilities, and proposed a commercial access agreement. In a brief critique of the third submission, the Evidence Review Group agreed that the selection of appropriate survival models was problematic and at the request of the National Institute for Health Care and Excellence investigated external sources of evidence regarding survival outcomes. The Evidence Review Group considered that some cost and utility estimates in the submission may have remained biased in favor of ixazomib. As a result of their third appraisal meeting, the committee judged that for the two to three prior therapies population, and at the price agreed in a commercial access agreement, ixazomib had the potential to be cost effective. It was referred to the Cancer Drugs Fund so that further data could accrue with the aim of diminishing the clinical uncertainties. [ABSTRACT FROM AUTHOR]

Background: Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS.Methods: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies.Results: We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression.Conclusions: Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs. [ABSTRACT FROM AUTHOR]

In this work, we introduce a methodology to approximate unknown parameters that appear on a non-linear reaction–diffusion model of tumor invasion. These equations consider that tumor-induced alteration of micro-environmental pH furnishes a mechanism for cancer invasion. A coupled system reaction–diffusion explaining this model is given by three partial differential equations for the non-dimensional spatial distribution and temporal evolution of the density of normal tissue, the neoplastic tissue growth and the excess concentration of H+ ions. The tumor model parameters have a corresponding biological meaning: the reabsorption rate, the destructive influence of H+ ions in the healthy tissue, the growth rate of tumor tissue and the diffusion coefficient. We propose to solve the direct problem using the Finite Element Method (FEM) and minimize an appropriate functional including both the real data (obtained via in-vitro experiments and fluorescence ratio imaging microscopy) and the numerical solution. The gradient of the functional is computed by the adjoint method. [ABSTRACT FROM AUTHOR]

Composite indices have been prominently used in poverty research. However, validity of these indices remains subject to debate. This paper examines the validity of a common type of composite poverty indices using data from a cross-sectional survey of 2477 households in urban and rural KwaZulu-Natal, South Africa. Multiple-group comparisons in structural equation modelling were employed for testing differences in the measurement model across urban and rural groups. The analysis revealed substantial variations between urban and rural respondents both in the conceptualisation of poverty as well as in the weights and importance assigned to individual poverty indicators. The validity of a ‘one size fits all’ measurement model can therefore not be confirmed. In consequence, it becomes virtually impossible to determine a household’s poverty level relative to the full sample. Findings from our analysis have important practical implications in nuancing how we can sensitively use composite poverty indices to identify poor people. [ABSTRACT FROM AUTHOR]

Substance use occurs at higher rates in men who have sex with men (MSM) than the general population, and, as a whole, is quantitatively linked to sexual risk behaviour. However, quantitative studies cannot adequately account for meanings, agency and role of social venue in shaping substance use, especially as regards sexual outcomes. To develop new theoretical constructs linking social venues and substance use in MSM, we systematically reviewed relevant qualitative studies and re-analysed them using a dimensional analysis method of grounded theory. Our analysis yielded an organising dimension of 'littoral spaces' in order to understand the meaning of MSM's substance use in relation to the social venue. This space is characterised as different from everyday life, through the altering of social boundaries; defined by its illegal qualities; and described as 'tribal' and 'ritual'. Substance use behaviours are embedded as performative regimes within these littoral spaces. Interventions for this population do not adequately account for the role of space in substance use behaviours. Harm reduction interventions, and interventions taking an approach focused on 'durable' planning for an entire evening, might offer improved effects. [ABSTRACT FROM AUTHOR]

In this paper, we present a methodology for estimating the effectiveness of a drug, an unknown parameter that appears on an avascular, spheric tumor growth model formulated in terms of a coupled system of partial differential equations (PDEs). This model is formulated considering a continuum of live cells that grow by the action of a nutrient. Volume changes occur due to cell birth and death, describing a velocity field. The model assumes that when the drug is applied externally, it diffuses and kills cells. The effectiveness of the drug is obtained by solving an inverse problem which is a PDE-constrained optimization problem. We define suitable objective functions by fitting the modeled and the observed tumor radius and the inverse problem is solved numerically using a Pattern Search method. It is observed that the effectiveness of the drug is retrieved with a reasonable accuracy. Experiments with noised data are also considered and the results are compared and contrasted. [ABSTRACT FROM AUTHOR]

To understand associations between location of sex and sexual risk, it is most helpful to compare sexual encounters within persons. We systematically reviewed within-subjects comparisons of sexual encounters reported by men who have sex with men (MSM) with respect to location of sex. Within-subjects comparisons of sexual risk and location of sex were eligible if they collected data post-1996 from samples of MSM. We independently screened results and full-text records in duplicate. Of 6,336 deduplicated records, we assessed 138 full-text studies and included six, most of which compared unprotected anal intercourse against other anal intercourse. This small, but high quality, body of evidence suggests that associations between attendance at sex-on-premises venues and person-level sexual risk may be due to overall propensity towards unprotected sex. However, there may be some location factors that promote or are associated with serononconcordant unprotected anal intercourse. Health promoters may wish to focus on person-level characteristics. [ABSTRACT FROM AUTHOR]

Previous event-level analyses have often, but not always, found significant associations between drug use and sexual risk behaviour in men who have sex with men (MSM), but these analyses have rarely considered either multipartner encounters specifically, or other sexual outcomes such as pleasure and control. Using data from an internet-based longitudinal survey of MSM, we tested the association between drug use by respondent and by partners and unprotected anal intercourse (UAI), pleasure and control over sexual activity. Overall respondent substance use was significantly associated with increased odds of UAI, though not with pleasure or control. Respondent use of crystal methamphetamine was significantly associated with both increased odds of UAI and decreased odds of control over sexual activity. This analysis agrees with previous studies of dyadic encounters, and specifically suggests that the association between crystal methamphetamine and sexual risk behaviour may be mediated by loss of control. [ABSTRACT FROM AUTHOR]

The pathogenesis of coxsackieviral infection is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a mouse model of Coxsackievirus B3 infection to characterize the contribution of host genetics to infection survival and to viral hepatitis. Twenty-five AcB/BcA recombinant congenic mouse strains were screened. One, BcA86, was found to be particularly susceptible to early mortality; 100% of BcA86 mice died by day 6 compared with 0% of B6 mice (P=0.0012). This increased mortality was accompanied by an increased hepatic necrosis as measured by serum alanine aminotransferase (ALT) levels (19547±10556 vs 769±109, P=0.0055). This occurred despite a predominantly resistant (C57BL/6) genetic background. Linkage analysis in a cohort (n=210) of (BcA86x C56Bl/10)F2 animals revealed a new locus on chromosome 13 (peak linkage 101.2 Mbp, lod 4.50 and P=0.003). This locus controlled serum ALT levels as early as 48 h following the infection, and led to an elevated expression of type I interferon. Another locus on chromosome 17 (peak linkage 57.2 Mbp) was significantly linked to heart viral titer (lod 3.4 and P=0.046). These results provide new evidence for the presence of genetic loci contributing to the susceptibility of mice to viral hepatitis. [ABSTRACT FROM AUTHOR]

BACKGROUND:To present the long-term results of a prostate cancer (PC) screening trial conducted in a Mediterranean setting.METHODS:A total of 4276 men aged 45-70 years were randomized to screening arm (PSA test performed) and control arm (no tests). Transrectal ultrasonography-guided sextant prostate biopsy was conducted when PSA⩾3 ng ml−1. Date and cause of death were retrieved from death certificates. PC incidence, and disease-specific and overall mortality curves were plotted and comparison between arms was made. Analysis of causes of death was also performed.RESULTS:Median age at randomization was 57.0 years. Median follow-up time was 15.2 years. A total of 241 men were diagnosed with PC, 161 (6.7%) in the screening arm and 80 (4.3%) in the control arm (P<0.01). Eventually, 554 men (13%) died. No difference in all-cause mortality was found between arms (P=0.34). Only 10 men (10/4276, 0.23%) died from PC, no differences between arms (P=0.67). Overall, the main causes of death were malignancy (54.2%), cardiovascular (17.9%) and respiratory (9.2%) diseases. Main cancer causes of death were lung and bronchus cancer (37.2%), colorectum (15.0%) and stomach (9.0%) cancer. PC only accounted for 3.0% of all malignant causes of death (ranked 10th).CONCLUSIONS:Our study failed to demonstrate benefits of PC screening in terms of all-cause and PC-specific mortality after a median follow-up of 15 years. The limited sample size and the low long-term PC mortality observed in our setting were probably the most important factors to explain these results. [ABSTRACT FROM AUTHOR]

The structural elucidation of 2α-cyclodextrin/1-octanethiol, 2α-cyclodextrin/1-octylamine and 2α-cyclodextrin/1-nonanoic acid inclusion complexes by nuclear magnetic resonance (NMR) spectroscopy and molecular modeling has been achieved. The detailed spatial configurations are proposed for the three inclusion complexes based on 2D NMR method. ROESY experiments confirm the inclusion of guest molecules inside the α-cyclodextrin (α-CD) cavity. On the other hand, the host-guest ratio observed was 2:1 for three complexes. The detailed spatial configuration proposed based on 2D NMR methods were further interpreted using molecular modeling studies. The theoretical calculations are in good agreement with the experimental data. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A globally convergent algorithm based on the stabilized sequential quadratic programming (sSQP) method is presented in order to solve optimization problems with equality constraints and bounds. This formulation has attractive features in the sense that constraint qualifications are not needed at all. In contrast with classic globalization strategies for Newton-like methods, we do not make use of merit functions. Our scheme is based on performing corrections on the solutions of the subproblems by using an inexact restoration procedure. The presented method is well defined and any accumulation point of the generated primal sequence is either a Karush-Kuhn-Tucker point or a stationary (maybe feasible) point of the problem of minimizing the infeasibility. Also, under suitable hypotheses, the sequence generated by the algorithm converges Q-linearly. Numerical experiments are given to confirm theoretical results. [ABSTRACT FROM AUTHOR]

Dengue virus is the most significant virus transmitted by arthropods worldwide and may cause a potentially fatal systemic disease named dengue hemorrhagic fever. In this work, dengue virus serotype 4 was detected in the tissues of one fatal dengue hemorrhagic fever case using electron immunomicroscopy and molecular methods. This is the first report of dengue virus polypeptides findings by electron immunomicroscopy in human samples. In addition, not-previously-documented virus-like particles visualized in spleen, hepatic, brain, and pulmonary tissues from a dengue case are discussed. [ABSTRACT FROM AUTHOR]

In the last few years haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) has been shown to have a positive impact on inflammation and oxidative stress biomarkers, but its effect on antioxidant levels and on oxidative damage to biomolecules in the long-term is still unknown. This is a randomised clinical study over 12 months involving 40 patients on haemodialysis, comparing the effect of HFR ( n = 25) dialysis with haemodialysis with polysulfone (HD-PS, n = 15) on oxidative stress. Total antioxidant capacity, enzymatic antioxidant [superoxide dismutase (SOD), catalase and glutathione peroxidase], non-enzymatic (GSH) and biomarkers of oxidative stress (TBARs, carbonyl groups and 8-OH-dG) were evaluated. The antioxidant activity decreased in the lymphocytes of patients dialysed with HFR, with a significant decrease in the enzyme SOD. In the oxidative stress biomarkers, an increase was seen in the levels of 8-OH-dG in patients on HD-PS dialysis but not in those treated with HFR. Throughout the year the changes in antioxidant levels and biomarkers of oxidative damage in patients dialysed with HFR were generally more modest and fluctuated less than those dialysed with HD-PS. Our study indicates that, in general, long-term dialysis with HFR does not modified antioxidant parameters or increases the oxidative damage to biomolecules. The HFR showed to be a biocompatible technique for long-term dialysis. [ABSTRACT FROM AUTHOR]

14-3-3σ, a gene upregulated by p53 in response to DNA damage, exists as part of a positive-feedback loop, which activates p53 and is a human cancer epithelial marker downregulated in various cancer types. 14-3-3σ levels are critical for maintaining p53 activity in response to DNA damage and regulating signal mediators such as Akt. In this study, we identify mammalian constitutive photomorphogenic 1 (COP1) as a novel E3 ubiquitin ligase for targeting 14-3-3σ through proteasomal degradation. We show for the first time that COP9 signalosome subunit 6 (CSN6) associates with COP1 and is involved in 14-3-3σ ubiquitin-mediated degradation. Mechanistic studies show that CSN6 expression leads to stabilization of COP1 through reducing COP1 self-ubiquitination and decelerating COP1's turnover rate. We also show that CSN6-mediated 14-3-3σ ubiquitination is compromised when COP1 is knocked down. Thus, CSN6 mediates 14-3-3σ ubiquitination through enhancing COP1 stability. Subsequently, we show that CSN6 causes 14-3-3σ downregulation, thereby activating Akt and promoting cell survival. Also, CSN6 overexpression leads to increased cell growth, transformation and promotes tumorigenicity. Significantly, 14-3-3σ expression can correct the abnormalities mediated by CSN6 expression. These data suggest that the CSN6-COP1 axis is involved in 14-3-3σ degradation, and that deregulation of this axis will promote cell growth and tumorigenicity. [ABSTRACT FROM AUTHOR]

The effects of activation pretreatments, Rh particle size and content of cerium oxide on Rh/γ-AlO catalysts for the oxidation of methyl tert-butyl ether (MTBE) were investigated. Three different conditions were used for the activation of the catalysts: (1) with air flow, (2) using a mixture of air and MTBE, and (3) by hydrogen reduction followed by oxidation with air. On Rh/γ-AlO catalyst the thermal pretreatments are of great importance for the MTBE oxidation. However, on Rh/γ-AlO-Ce1 catalyst, the total combustion of MTBE was reached at a temperature of 200 °C lower than that obtained with the Rh/γ-AlO catalyst at whatever thermal treatment applied. A Rhº/Rh and Ce/Ce species were identified by XPS suggesting that they are the responsible of the high activity showed by the Rh/γ-AlO-Ce1 catalyst. A particle size effect for MTBE oxidation was observed on Rh/γ-AlO catalysts, large Rh particles are more active than the small ones. [ABSTRACT FROM AUTHOR]

The enhancement of TiO photocatalyst activity will lead to more practical applications of this technology. In this work we studied the effect of rare earth doping of sol-gel synthesized TiO for phenol degradation and we compared the performance with commercial catalyst. Photocatalysts were characterized by nitrogen adsorption to determine textural properties, ultraviolet visible light diffuse reflectance spectrometry (UV-Vis DRS), X-ray diffraction, STEM-EDS (scanning transmission electronic microscopy-energy dispersive X-ray spectroscopy) and XPS (X-ray photoelectron spectroscopy). Main phase for materials calcined at 500 °C was anatase. Residual nitrogen from NHOH used in the sol-gel synthesis was identified by XPS analysis. Ti/Ti ratio increased when TiO was doped with 0.5 wt% of Ce. Anatase phase was stabilized in photocatalysts doped with La even after calcination at 800 °C, for Pr and Nd a mixture of anatase-rutile phases was obtained, whereas for Ce doping only rutile phase was found. For the photocatalytic oxidation of phenol, the best results were obtained for Ce doped TiO, which could be related to the ability of Ce/Ce oxidation/reduction cycle. [ABSTRACT FROM AUTHOR]

This article presents and discusses a critical compilation of accurate, fundamental determinations of stellar masses and radii. We have identified 95 detached binary systems containing 190 stars (94 eclipsing systems, and α Centauri) that satisfy our criterion that the mass and radius of both stars be known within errors of ±3% accuracy or better. All of them are non-interacting systems, and so the stars should have evolved as if they were single. This sample more than doubles that of the earlier similar review by Andersen (Astron Astrophys Rev 3:91–126, 1991), extends the mass range at both ends and, for the first time, includes an extragalactic binary. In every case, we have examined the original data and recomputed the stellar parameters with a consistent set of assumptions and physical constants. To these we add interstellar reddening, effective temperature, metal abundance, rotational velocity and apsidal motion determinations when available, and we compute a number of other physical parameters, notably luminosity and distance. These accurate physical parameters reveal the effects of stellar evolution with unprecedented clarity, and we discuss the use of the data in observational tests of stellar evolution models in some detail. Earlier findings of significant structural differences between moderately fast-rotating, mildly active stars and single stars, ascribed to the presence of strong magnetic and spot activity, are confirmed beyond doubt. We also show how the best data can be used to test prescriptions for the subtle interplay between convection, diffusion, and other non-classical effects in stellar models. The amount and quality of the data also allow us to analyse the tidal evolution of the systems in considerable depth, testing prescriptions of rotational synchronisation and orbital circularisation in greater detail than possible before. We show that the formulae for pseudo-synchronisation of stars in eccentric orbits predict the observed rotations quite well, except for very young and/or widely separated stars. Deviations do occur, however, especially for stars with convective envelopes. The superior data set finally demonstrates that apsidal motion rates as predicted from General Relativity plus tidal theory are in good agreement with the best observational data. No reliable binary data exist, which challenge General Relativity to any significant extent. The new data also enable us to derive empirical calibrations of M and R for single (post-) main-sequence stars above $${0.6\,M_{\odot}}$$. Simple, polynomial functions of Teff, log g and [Fe/H] yield M and R within errors of 6 and 3%, respectively. Excellent agreement is found with independent determinations for host stars of transiting extrasolar planets, and good agreement with determinations of M and R from stellar models as constrained by trigonometric parallaxes and spectroscopic values of Teff and [Fe/H]. Finally, we list a set of 23 interferometric binaries with masses known to be better than 3%, but without fundamental radius determinations (except α Aur). We discuss the prospects for improving these and other stellar parameters in the near future. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the outcome of preperitoneal repair using laparoscopic (TEP) and open (OPM) approach in recurrent inguinal hernia.Methods: We performed a prospective controlled nonrandomized clinical study in 188 patients with 207 recurrent inguinal hernias over a period of 5 years. TEP repair was employed for 86 repairs, and OPM was used in 121 procedures. The main outcome measurements were: recurrence rate, operating time, hospital stay, and postoperative complications.Results: There were three recurrences (1.7%). Two in the OPM group (1.8%) and one (1.3%) in the TEP group [ P=NS (not significant)]. The TEP procedure was faster than OPM for unilateral repair (40.8 vs 46.3 min) (P<0.001). Postoperative complications were more frequent in the OPM group (23.9%) than the TEP group (13.9%) ( P=NS). Hospital stay was significantly shorter in the TEP group (1.2 vs 3.9 days) (P<0.001).Conclusions: Preperitoneal approach (open or laparoscopic) seems to be a good option in recurrent inguinal hernia when these procedures are done by experienced surgeons. [ABSTRACT FROM AUTHOR]

Studies the importance of salinity experienced during embryonic development and initial latval biomass on larval growth in the South American estuarine crab, Chasmagnathus granulata. Changes in biomass from egg laying to premoult zoea; Growth after zoea; Effect of prehatching salinity on biomass of the megalopae.

To study the simultaneous effects of ethanol and cocaine on striatal FOS-like protein, rats were exposed to an (8.7%) ethanol solution for 15 days followed by single or daily cocaine injections (20 mg/kg; IP). Ethanol consumption reduced the induction of the nuclear protein under both temporal regimens of cocaine administration. In contrast, sucrose pair-fed or ad libitum control groups exhibited a robust induction of FOS-like protein throughout the striatum, particularly in dorsal-central quadrants of the caudate putamen. This pattern of combined drug use produced blood ethanol concentrations in the range of 22–370 mg/dl, corresponding with those associated with mild intoxication in humans. Under both cocaine regimens, the presence of ethanol led to the transesterification of cocaine into the active metabolite, cocaethylene (31–121 ng/ml). Plasma levels of this metabolite did not exceed those of cocaine (17–1024 ng/ml), suggesting that under this drug regimen at least, cocaethylene formation is relatively low and perhaps dependent upon specific levels of ethanol and cocaine in hepatic microsomes. In addition, systemic administration of cocaethylene to rats (60 μmol/kg; molar equivalent of 20 mg/kg cocaine) induced widespread FOS-like protein in the caudate putamen. Induction of the transcription factor protein by cocaethylene was similar in magnitude and anatomic distribution to that of cocaine, suggesting that these two drug congeners share common molecular mechanisms of gene expression. [ABSTRACT FROM AUTHOR]

To determine whether extra-retinal mechanisms mediate photoperiodic changes in neonatal rat pineal gland N-acetyltransferase activity, 4-day-old intact or bilateral orbital enucleated rats were killed during the dark phase of the lighting cycle, either in darkness or following 4 hr exposure to fluorescent light. Light suppressed the high nighttime N-acetyltransferase activity equally in intact and enucleated pups. Subsequent studies showed that at least 0.5 hr exposure and nocturnal illuminances of 109 ΜW/cm or greater were required to cause statistically significant reductions in the activity of the enzyme in 4-day-old rats. Taken together, these data indicate that relatively intense environmental light can affect neonatal rat pineal gland biochemistry via extra-retinal mechanisms. [ABSTRACT FROM AUTHOR]

Objective: Little is known about Helicobacter pylori infections and the immune response to urease and CagA in pediatrie populations. Our aims were: 1) to validate serological assays for antibodies against whole cell extract, CagA, and urease of H. pylori; 2) to examine their role in diagnosis of infection in children with recurrent abdominal pain (RAP); and 3) to examine the antibody responses to CagA and urease in children. Methods: An enzyme-linked immunosorbent assay (ELISA) for diagnosis of H. pylori infection using whole cell extracts was validated in 50 children with biopsy-confirmed infection. The IgG and IgA antibody responses against recombinant CagA and urease were compared by ELISA in 82 children with RAP and in 246 age- and sex-matched healthy children. Results: The whole-cell extract ELISA had a sensitivity of 85% and specificity of 87%. Children with RAP were more infected with H. pylori than were healthy control subjects; however, IgG and IgA CagA seropositivity was lower among those with RAP than among asymptomatic children (34% and 23% vs 76% and 55%, respectively; p < 0.0001). In both groups of children, the immune response to urease was low. Conclusion: A serodiagnosis of H. pylori infection using native strains was developed. The difference in the immune response between children with RAP and control subjects suggests that RAP occurs during the acute phase of H. pylori infection. Our results also suggest that urease is a poor immunogen. [ABSTRACT FROM AUTHOR]