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Abstract Background Burkholderia mallei and B. pseudomallei are two closely related species of highly virulent bacteria that can be difficult to detect. Pathogenic Burkholderia are endemic in many regions worldwide and cases of infection, sometimes brought by travelers from unsuspected regions, also occur elsewhere. Rapid, sensitive methods for identification of B. mallei and B. pseudomallei are urgently needed in the interests of patient treatment and epidemiological surveillance. Methods Signature sequences for sensitive, specific detection of pathogenic Burkholderia based on published genomes were identified and a qPCR assay was designed and validated. Results A single-reaction quadruplex qPCR assay for the detection of pathogenic Burkholderia, which includes a marker for internal control of DNA extraction and amplification, was developed. The assay permits differentiation of B. mallei and B. pseudomallei strains, and probit analysis showed a very low detection limit. Use of a multicopy signature sequence permits detection of less than 1 genome equivalent per reaction. Conclusions The new assay permits rapid detection of pathogenic Burkholderia and combines enhanced sensitivity, species differentiation, and inclusion of an internal control for both DNA extraction and PCR amplification.

Recent work has shown evidence for the prognostic significance of tumor infiltrating B cells (B-TIL) in high grade serous ovarian carcinoma (HGSOC), the predominant histological subtype of ovarian cancer. However, it remains unknown how the favorable prognosis associated with B-TIL relates to the current standard treatments of primary debulking surgery (PDS) followed by chemotherapy or (neo-)adjuvant chemotherapy (NACT) combined with interval debulking surgery. To address this, we analyzed the prognostic impact of B-TIL in relationship to primary treatment and tumor infiltrating T cell status in a highly homogenous cohort of HGSOC patients. This analysis involved a combined approach utilizing histological data and high-dimensional flow cytometry analysis. Our findings indicate that while HGSOC tumors pre-treated with NACT are infiltrated with tumor-reactive CD8 + and CD4 + TIL subsets, only B-TIL and IgA plasma blasts confer prognostic benefit in terms of overall survival. Importantly, the prognostic value of B-TIL and IgA plasma blasts was not restricted to patients treated with NACT, but was also evident in patients treated with PDS. Together, our data point to a critical prognostic role for B-TIL in HGSOC patients independent of T cell status, suggesting that alternative treatment approaches focused on the activation of B cells should be explored for HGSOC., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Frenotomy of the lingual and maxillary labial frenula in neonates is considered a safe procedure and is increasingly performed globally. However, there is no consistent evidence for the indication and effectiveness of this intervention. In this clinical lesson, we show that frenotomy of the lingual and maxillary labial frenula in neonates is controversial and can have serious complications. We describe a patient that, in addition to pain and the risk of infection, was in a life-threatening haemorrhagic shock after frenotomy of the lingual and maxillary labial frenula. Frenotomy should only be considered after a multi-disciplinary approach of neonates with breastfeeding problems in whom a medical cause is excluded and no contraindications have been identified.

Channelling of glucose via glycogen, known as the glycogen shunt, may play an important role in the metabolism of brain tumours, especially in hypoxic conditions. We aimed to dissect the role of glycogen degradation in glioblastoma (GBM) response to ionising radiation (IR). Knockdown of the glycogen phosphorylase liver isoform (PYGL), but not the brain isoform (PYGB), decreased clonogenic growth and survival of GBM cell lines and sensitised them to IR doses of 10-12 Gy. Two to five days after IR exposure of PYGL knockdown GBM cells, mitotic catastrophy and a giant multinucleated cell morphology with senescence-like phenotype developed. The basal levels of the lysosomal enzyme alpha-acid glucosidase (GAA), essential for autolysosomal glycogen degradation, and the lipidated forms of gamma-aminobutyric acid receptor-associated protein-like (GABARAPL1 and GABARAPL2) increased in shPYGL U87MG cells, suggesting a compensatory mechanism of glycogen degradation. In response to IR, dysregulation of autophagy was shown by accumulation of the p62 and the lipidated form of GABARAPL1 and GABARAPL2 in shPYGL U87MG cells. IR increased the mitochondrial mass and the colocalisation of mitochondria with lysosomes in shPYGL cells, thereby indicating reduced mitophagy. These changes coincided with increased phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase 2, slower ATP generation in response to glucose loading and progressive loss of oxidative phosphorylation. The resulting metabolic deficiencies affected the availability of ATP required for mitosis, resulting in the mitotic catastrophy observed in shPYGL cells following IR. PYGL mRNA and protein levels were higher in human GBM than in normal human brain tissues and high PYGL mRNA expression in GBM correlated with poor patient survival. In conclusion, we show a major new role for glycogen metabolism in GBM cancer. Inhibition of glycogen degradation sensitises GBM cells to high-dose IR indicating that PYGL is a potential novel target for the treatment of GBMs., (© 2022. The Author(s).)

Introduction: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma., Patients and Methods: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation., Results: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n = 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n = 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p = 0.006), without OS differences., Conclusion: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes., Competing Interests: Conflict of interest statement All authors declare no direct conflict with this work. For unrelated conflicts, K.P.M.S. has an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, AbbVie and Pierre Fabre and has received honoraria from Merck Sharp & Dohme, Novartis and Roche. L.Z. has an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Sun Pharma; has received research funding from Novartis; has received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre and Roche and has received travel support from Amgen, Bristol Myers Squibb, Novartis, Pierre Fabre, Sanofi and Sun Pharma. E.W.K. has an advisory role for Bristol Myers Squibb, Merck, Novartis and Pierre Fabre; has received research funding from Bristol Myers Squibb and has received travel support from Roche. C.A. has received travel support from Amgen, Bristol Myers Squibb and Roche. D.B.J. has an advisory role for Array BioPharma, Bristol Myers Squibb, Incyte, Merck and Novartis; has received research funding from Bristol Myers Squibb and Incyte and has received travel support from Genentech. Adriana H. is an employee of AstraZeneca with stock options in the company, has received honoraria from Novartis; has an advisory role for L.E.K. Consulting and has received travel support from Roche. J.M. has received honoraria from Amgen, Bristol Myers Squibb, Merck-Pfizer, MSD, Novartis and Pierre Fabre; has an advisory role for Amgen, Merck-Pfizer, Merck Sharp & Dohme, Novartis and Pierre Fabre and has received travel support from Bristol Myers Squibb, L'Oreal, MSD, Pierre Fabre and Ultrasun. P.B. has received travel support from MSD. Y.J.L.J. has received travel support from Bristol Myers Squibb, MSD and Pfizer. V.A. has received honoraria from Bristol Myers Squibb, Genentech, Merck Serono, Merck Sharp & Dohme, Novartis and Pierre Fabre; has an advisory role for Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre and Roche and has received travel support from Bristol Myers Squibb, Merck Sharp & Dohme, OncoSec and Pierre Fabre. P.A.A. has an advisory role for 4SC, Alkermes, Amgen, Array BioPharma, Bristol Myers Squibb, Genentech, Genmab, Idera, Immunoscore, Incyte, Italfarmaco, MedImmune, Merck Serono, Merck Sharp & Dohme, Nektar, NewLink Genetics, Novartis, Pierre Fabre, Sandoz, Sanofi, Sun Pharma, Syndax and Ultimovacs; has received research funding from Array BioPharma, Bristol Myers Squibb and Genentech; has received travel support from Merck Sharp & Dohme and is a stockowner of PrimeVax. Andrew H. has received honoraria from Merck and Novartis and has an advisory role for Novartis and Pierre Fabre. A.M.M. has an advisory role for Bristol Myers Squibb, MSD Oncology, Novartis, Pierre Fabre and Roche. G.V.L. is a consultant advisor for Aduro Biotech, Inc., Amgen Inc., Array BioPharma Inc., Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Highlight Therapeutics S.L., Merck Sharp & Dohme, Novartis Pharma AG, QBiotics Group Limited, Regeneron Pharmaceuticals, Inc. and SkylineDX B.V. C.L. had received honoraria from Amgen, Bristol Myers Squibb, Incyte, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre and Roche; has an advisory role for Amgen, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, Roche and Sanofi; has received research funding from Bristol Myers Squibb and Roche and has received travel support from Bristol Myers Squibb and Merck Sharp & Dohme. A.A.M.v.d.V. has an advisory role for Bristol Myers Squibb, Eisai, Ipsen, MSD Oncology, Merck, Novartis, Pfizer, Pierre Fabre, Roche and Sanofi and has received research funding from Bayer and travel support from Bayer, MSD Oncology, Novartis and Roche. M.S.C. has an advisory role for Amgen, Bristol Myers Squibb, Eisai, IDEAYA Biosciences, Merck and Co, Merck Sharp & Dohme, Nektar, Novartis, Pierre Fabre, Roche, Sanofi and QBiotics and has received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme and Novartis. S.S. has received honoraria from AstraZeneca, Bristol Myers Squibb, Merck and Merck Serono; has an advisory role for Amgen, Bristol Myers Squibb, MSD, Novartis and Roche outside the submitted work and has received research funding from Amgen, AstraZeneca, Endocyte, Genentech and Merck Sharp & Dohme. E.G.E.d.V. has an advisory role for Daiichi Sankyo, NSABP and Sanofi; has received research funding from Amgen, AstraZeneca, Bayer, Chugai Pharma, CytomX Therapeutics, G1 Therapeutics, Genentech, Nordic Nanovector, Radius Health, Regeneron, Roche, Servier and Synthon and is the chair of ESMO Cancer Medicines Working Group, chair of RECITS committee and member of the ESMO-MCBS working group. C.U.B. has received research funding from Bristol Myers Squibb, Novartis and NanoString; has an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, Genmab and Pierre Fabre and is a stockowner of Uniti Cars. M.J. has an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, AstraZeneca, Tesaro and Pierre Fabre., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

CD103-positive tissue resident memory-like CD8 + T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Infiltration of CD8CD103 immune cell subsets was independent of clinicopathological factors. Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification. A survival benefit of CD8CD103 TRM was observed only in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Reprogrammed glucose metabolism is a hallmark of cancer making it an attractive therapeutic target, especially in cancers with high glucose uptake such as non-small cell lung cancer (NSCLC). Tools to select patients with high glucose uptake in the majority of tumor lesions are essential in the development of anti-cancer drugs targeting glucose metabolism. Type 2 diabetes mellitus (T2DM) patients may have tumors highly dependent on glucose uptake. Surprisingly, this has not been systematically studied. Therefore, we aimed to determine which patient and tumor characteristics, including concurrent T2DM, are related to high glucose uptake in the majority of tumor lesions in NSCLC patients as measured by 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) scans. Methods: Routine primary diagnostic 18 F-FDG PET/CT scans of consecutive NSCLC patients were included. Mean standardized uptake value (SUVmean) of 18 F-FDG was determined for all evaluable tumor lesions and corrected for serum glucose levels according to the European Association of Nuclear Medicine Research Ltd guidelines. Patient characteristics potentially determining degree of tumor lesion glucose uptake in the majority of tumor lesions per patient were investigated. Results: The cohort consisted of 102 patients, 28 with T2DM and 74 without T2DM. The median SUVmean per patient ranged from 0.8 to 35.2 (median 4.2). T2DM patients had higher median glucose uptake in individual tumor lesions and per patient compared to non-diabetic NSCLC patients (SUVmean 4.3 vs 2.8, P < 0.001 and SUVmean 5.4 vs 3.7, P = 0.009, respectively). However, in multivariable analysis, high tumor lesion glucose uptake was only independently determined by number of tumor lesions ≥1 mL per patient (odds ratio 0.8, 95% confidence interval 0.7-0.9). Conclusions: 18 F-FDG PET/CT scans can identify sub-groups of NSCLC patients with high glucose uptake in the majority of their tumor lesions. T2DM patients had higher tumor lesion glucose uptake than non-diabetic patients. However, this was not independent of other factors such as the histological subtype and number of tumor lesions per patient., Competing Interests: Competing Interests: All authors have made substantial contributions to conducting the study and drafting, revising and approving the manuscript. All authors have declared that no competing interest exists that might interfere with the objective presentation of the research findings contained in the submitted study. The authors received no financial support for the research, authorship, and/or publication of this manuscript., (© The author(s).)

Background: Given the role of childhood aggressive behavior (AGG) in everyday child development, precise and accurate measurement is critical in clinical practice and research. This study aims to quantify agreement among widely used measures of childhood AGG regarding item content, clinical concordance, correlation, and underlying genetic construct., Methods: We analyzed data from 1254 Dutch twin pairs (age 8-10 years, 51.1% boys) from a general population sample for whom both parents completed the A-TAC, CBCL, and SDQ at the same occasion., Results: There was substantial variation in item content among AGG measures, ranging from .00 (i.e., mutually exclusive) to .50 (moderate agreement). Clinical concordance (i.e., do the same children score above a clinical threshold among AGG measures) was very weak to moderate with estimates ranging between .01 and .43 for mother-reports and between .12 and .42 for father-reports. Correlations among scales were weak to strong, ranging from .32 to .70 for mother-reports and from .32 to .64 for father-reports. We found weak to very strong genetic correlations among the measures, with estimates between .65 and .84 for mother-reports and between .30 and .87 for father-reports., Conclusions: Our results demonstrated that degree of agreement between measures of AGG depends on the type (i.e., item content, clinical concordance, correlation, genetic correlation) of agreement considered. Because agreement was higher for correlations compared to clinical concordance (i.e., above or below a clinical cutoff), we propose the use of continuous scores to assess AGG, especially for combining data with different measures. Although item content can be different and agreement among observed measures may not be high, the genetic correlations indicate that the underlying genetic liability for childhood AGG is consistent across measures., (© 2020 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Aggression in children has genetic and environmental causes. Studies of aggression can pool existing datasets to include more complex models of social effects. Such analyses require large datasets with harmonized outcome measures. Here, we made use of a reference panel for phenotype data to harmonize multiple aggression measures in school-aged children to jointly analyze data from five large twin cohorts., Methods: Individual level aggression data on 86,559 children (42,468 twin pairs) were available in five European twin cohorts measured by different instruments. A phenotypic reference panel was collected which enabled a model-based phenotype harmonization approach. A bi-factor integration model in the integrative data analysis framework was developed to model aggression across studies while adjusting for rater, age, and sex. Finally, harmonized aggression scores were analyzed to estimate contributions of genes, environment, and social interaction to aggression. The large sample size allowed adequate power to test for sibling interaction effects, with unique dynamics permitted for opposite-sex twins., Results: The best-fitting model found a high level of overall heritability of aggression (~60%). Different heritability rates of aggression across sex were marginally significant, with heritability estimates in boys of ~64% and ~58% in girls. Sibling interaction effects were only significant in the opposite-sex twin pairs: the interaction effect of males on their female co-twin differed from the effect of females on their male co-twin. An aggressive female had a positive effect on male co-twin aggression, whereas more aggression in males had a negative influence on a female co-twin., Conclusions: Opposite-sex twins displayed unique social dynamics of aggressive behaviors in a joint analysis of a large, multinational dataset. The integrative data analysis framework, applied in combination with a reference panel, has the potential to elucidate broad, generalizable results in the investigation of common psychological traits in children., (© 2020 Association for Child and Adolescent Mental Health.)

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.

Socioeconomic status (SES) affects the development of childhood behavioral problems. It has been frequently observed that children from low SES background tend to show more behavioral problems. There also is some evidence that SES has a moderating effect on the causes of individual differences in childhood behavioral problems, with lower heritability estimates and a stronger contribution of environmental factors in low SES groups. The aim of the present study was to examine whether the genetic architecture of childhood behavioral problems suggests the presence of protective and/or harmful effects across socioeconomic strata, in two countries with different levels of socioeconomic disparity: the Netherlands and the United Kingdom. We analyzed data from 7-year-old twins from the Netherlands Twin Register (N = 24,112 twins) and the Twins Early Development Study (N = 19,644 twins). The results revealed a nonlinear moderation effect of SES on the contribution of genetic and environmental factors to individual differences in childhood behavioral problems. The heritability was higher, the contribution of the shared environment was lower, and the contribution of the nonshared environment was higher, for children from high SES families, compared to children from low or medium SES families. The pattern was similar for Dutch and UK families. We discuss the importance of these findings for prevention and intervention goals.

Parallel meta-analysis is a popular approach for increasing the power to detect genetic effects in genome-wide association studies across multiple cohorts. Consortia studying the genetics of behavioral phenotypes are oftentimes faced with systematic differences in phenotype measurement across cohorts, introducing heterogeneity into the meta-analysis and reducing statistical power. This study investigated integrative data analysis (IDA) as an approach for jointly modeling the phenotype across multiple datasets. We put forth a bi-factor integration model (BFIM) that provides a single common phenotype score and accounts for sources of study-specific variability in the phenotype. In order to capitalize on this modeling strategy, a phenotype reference panel was utilized as a supplemental sample with complete data on all behavioral measures. A simulation study showed that a mega-analysis of genetic variant effects in a BFIM were more powerful than meta-analysis of genetic effects on a cohort-specific sum score of items. Saving the factor scores from the BFIM and using those as the outcome in meta-analysis was also more powerful than the sum score in most simulation conditions, but a small degree of bias was introduced by this approach. The reference panel was necessary to realize these power gains. An empirical demonstration used the BFIM to harmonize aggression scores in 9-year old children across the Netherlands Twin Register and the Child and Adolescent Twin Study in Sweden, providing a template for application of the BFIM to a range of different phenotypes. A supplemental data collection in the Netherlands Twin Register served as a reference panel for phenotype modeling across both cohorts. Our results indicate that model-based harmonization for the study of complex traits is a useful step within genetic consortia., (Copyright © 2019 Luningham, McArtor, Hendriks, van Beijsterveldt, Lichtenstein, Lundström, Larsson, Bartels, Boomsma and Lubke.)

Type 2 diabetes mellitus (T2DM) is associated with a higher risk of cancer and cancer-related mortality. Increased blood glucose and insulin levels in T2DM patients may be, at least in part, responsible for this effect. Indeed, lowering glucose and/or insulin levels pharmacologically appears to reduce cancer risk and progression, as has been demonstrated for the biguanide metformin in observational studies. Studies investigating the influence of sulfonylurea derivatives (SUs) on cancer risk have provided conflicting results, partly due to comparisons with metformin. Furthermore, little attention has been paid to within-class differences in systemic and off-target effects of the SUs. The aim of this systematic review is to discuss the available preclinical and clinical evidence on how the different SUs influence cancer development and risk. Databases including PubMed, Cochrane, Database of Abstracts on Reviews and Effectiveness, and trial registries were systematically searched for available clinical and preclinical evidence on within-class differences of SUs and cancer risk. The overall preclinical and clinical evidence suggest that the influence of SUs on cancer risk in T2DM patients differs between the various SUs. Potential mechanisms include differing affinities for the sulfonylurea receptors and thus differential systemic insulin exposure and off-target anti-cancer effects mediated for example through potassium transporters and drug export pumps. Preclinical evidence supports potential anti-cancer effects of SUs, which are of interest for further studies and potentially repurposing of SUs. At this time, the evidence on differences in cancer risk between SUs is not strong enough to guide clinical decision making., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Theoretical studies propose an association between family violence and low self-control in adolescence; however, empirical findings of this association are inconclusive. The aim of the present research was to systematically summarize available findings on the relation between family violence and self-control across adolescence. We included 28 studies with 143 effect sizes, representing more than 25,000 participants of eight countries from early to late adolescence. Applying a three-level meta-analysis, taking dependency between effect sizes into account while retaining statistical power, we examined the magnitude and direction of the overall effect size. Additionally, we investigated whether theoretical moderators (e.g., age, gender, country), and methodological moderators (e.g., time lag between family violence and self-control, informant) influenced the magnitude of the association between family violence and self-control. Our results revealed that family violence and self-control have a small to moderate significant negative association ( r = -0.191). This association did not vary across gender, country, and informants. The strength of the association, however, decreased with age and in longitudinal studies. This finding provides evidence that researchers and clinicians may expect low self-control in the wake of family violence, especially in early adolescence. Recommendations for future research in the area are discussed.

This study provides a synthesis of meta-analyses and systematic reviews on non-pharmacological treatments for childhood aggression. Treatments referred to universal prevention, selective prevention, indicated prevention, or intervention (Mrazek and Haggerty, 1994). Seventy-two meta-analyses and systematic reviews met the inclusion criteria. We describe their characteristics, effect sizes across types of treatments, and the effects of various moderators. For universal and selective prevention, effects were mostly absent or small; for indicated prevention and interventions, effects were mostly small or medium. Only two moderators had a positive effect on treatment effectiveness, namely pre-test levels of aggression and parental involvement. These results identified similarities between indicated prevention and intervention treatments, on the one hand, and universal prevention and selective prevention, on the other. Our findings suggest that research distinguishing between targets of treatments (i.e., factors associated with childhood aggression vs. present aggressive behaviors) would be promising. Moreover, to further increase effectiveness of treatments for childhood aggression, individual differences warrant scientific attention., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of the present meta-analysis was to investigate the strength of the association between parent-reported and observed parenting, and to investigate which specific characteristics of participants, questionnaires, or observational procedures moderate this association. A systematic search of relevant peer-reviewed articles published between January 2000 and December 2014 yielded 36 articles (N = 8,510) and 89 effect sizes. Results from a 3-level random-effects meta-analysis demonstrated a weak, yet significant, overall association of r = .17 between parent-reported and observed parenting. The magnitude of the effect size depended on questionnaire length (larger effect for more items) and the type of parenting investigated (largest effects for negative parent behaviors, next largest effects for positive parent behaviors, and smallest effect for controlling parent behaviors). In conclusion, this study shows that the strength of the association between parent-reported and observed parenting is small but significant. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

To prevent overweight and obesity the implementation of an integrated community-wide intervention approach (ICIA) is often advocated. Evaluation can enhance implementation of such an approach and demonstrate the extent of effectiveness. To be able to support professionals in the evaluation of ICIAs we studied barriers to and facilitators of ICIA evaluation. In this study ten professionals of two Dutch municipalities involved in the evaluation of an ICIA participated. We conducted semi-structured interviews (n = 12), observed programme meetings (n = 4) and carried out document analysis. Data were analyzed using a thematic content approach. We learned that evaluation is hampered when it is perceived as unfeasible due to limited time and budget, a lack of evaluation knowledge or a negative evaluation attitude. Other barriers are a poor understanding of the evaluation process and its added value to optimizing the programme. Sufficient communication between involved professionals on evaluation can facilitate evaluation, as does support for evaluation of ICIAs together with stakeholders at a strategic and tactical level. To stimulate the evaluation of ICIAs, we recommend supporting professionals in securing evaluation resources, providing tailored training and tools to enhance evaluation competences and stimulating strategic communication on evaluation.

Background . Limited physical activity (PA) is a risk factor for childhood obesity. In Netherlands, as in many other countries worldwide, local policy officials bear responsibility for integrated PA policies, involving both health and nonhealth domains. In practice, its development seems hampered. We explore which obstacles local policy officials perceive in their effort. Methods . Fifteen semistructured interviews were held with policy officials from health and nonhealth policy domains, working at strategic, tactic, and operational level, in three relatively large municipalities. Questions focused on exploring perceived barriers for integrated PA policies. The interviews were deductively coded by applying the Behavior Change Ball framework. Findings . Childhood obesity prevention appeared on the governmental agenda and all officials understood the multicausal nature. However, operational officials had not yet developed a tradition to develop integrated PA policies due to insufficient boundary-spanning skills and structural and cultural differences between the domains. Tactical level officials did not sufficiently support intersectoral collaboration and strategic level officials mainly focused on public-private partnerships. Conclusion . Developing integrated PA policies is a bottom-up innovation process that needs to be supported by governmental leaders through better guiding organizational processes leading to such policies. Operational level officials can assist in this by making progress in intersectoral collaboration visible.

Background . Integrated community-wide intervention approaches (ICIAs) are implemented to prevent childhood obesity. Programme evaluation improves these ICIAs, but professionals involved often struggle with performance. Evaluation tools have been developed to support Dutch professionals involved in ICIAs. It is unclear how useful these tools are to intended users. We therefore researched the facilitators of and barriers to ICIA programme evaluation as perceived by professionals and their experiences of the evaluation tools. Methods . Focus groups and interviews with 33 public health professionals. Data were analysed using a thematic content approach. Findings . Evaluation is hampered by insufficient time, budget, and experience with ICIAs, lack of leadership, and limited advocacy for evaluation. Epidemiologists are regarded as responsible for evaluation but feel incompetent to perform evaluation or advocate its need in a political environment. Managers did not prioritise process evaluations, involvement of stakeholders, and capacity building. The evaluation tools are perceived as valuable but too comprehensive considering limited resources. Conclusion . Evaluating ICIAs is important but most professionals are unfamiliar with it and management does not prioritise process evaluation nor incentivize professionals to evaluate. To optimise programme evaluation, more resources and coaching are required to improve professionals' evaluation capabilities and specifically the use of evaluation., Competing Interests: The authors declare that there are no competing interests regarding the publication of this paper.

Background: Increased dependence on Western diets and low physical activity have largely contributed to weight gain and associated chronic diseases in the Canadian Inuit population. The purpose of this study was to systematically review factors influencing dietary and physical activity behaviors to guide health promotion interventions and provide recommendations for future studies., Method: We conducted a systematic literature review to identify relevant articles. Searches were conducted between May 2014 and July 2014, and inclusive of articles published up until July 2014. Articles were searched using four databases: PubMed, PsycINFO, SocINDEX, and Psychology and Behavioral Sciences Collection. Eligible studies focused on diet and/or physical activity or determinants of diet and/or physical activity in Canadian Inuit population, and were published in English., Results: A total of 45 articles were included in the analysis. A detailed appraisal of the articles suggested that many Inuit have disconnected from the traditional ways of life, including harvesting and processing of traditional food species and the associated physical activity. In the last two decades there has been a significant shift from consumption of healthy traditional foods to energy-dense store-bought foods particularly among younger Inuit (<50 years of age). Additionally, low socioeconomic status (SES) and high transportation cost affect food accessibility and contribute to poor dietary choices in the population. However, a few articles that described the mediating role of psychosocial factors reported that higher SES, increased healthful food knowledge, and self-efficacy towards healthy dietary behavior, were associated with greater intentions to make healthier food choices and participate in physical activity., Conclusion: It is evident that the rapid social, cultural, and environmental changes in the Arctic have altered dietary and physical activity behaviors of Canadian Inuit. However, our understanding is limited on how these behaviours might be influenced in the face of these changes. Prospective studies are needed to advance our knowledge of cognitive and environmental determinants of Inuit energy balance-related behaviours. These studies can inform the development of health promotion interventions in the population.

In Fiji and other Pacific Island countries, obesity has rapidly increased in the past decade. Therefore, several obesity prevention policies have been developed. Studies show that their development has been hampered by factors within Fiji's policy landscape such as pressure from industry. Since policymakers in the Fijian national government are primarily responsible for the development of obesity policies, it is important to understand their perspectives; we therefore interviewed 15 policymakers from nine Fijian ministries. By applying the "attractor landscape" metaphor from dynamic systems theory, we captured perceived barriers and facilitators in the policy landscape. A poor economic situation, low food self-sufficiency, power inequalities, inappropriate framing of obesity, limited policy evidence, and limited resource sharing hamper obesity policy developments in Fiji. Facilitators include policy entrepreneurs and policy brokers who were active when a window of opportunity opened and who strengthened intersectoral collaboration. Fiji's policy landscape can become more conducive to obesity policies if power inequalities are reduced. In Fiji and other Pacific Island countries, this may be achievable through increased food self-sufficiency, strengthened intersectoral collaboration, and the establishment of an explicit functional focal unit within government to monitor and forecast the health impact of policy changes in non-health sectors.

Background: The aim of this paper is to describe the research aims, concepts and methods of the research Consortium Integrated Approach of Overweight (CIAO). CIAO is a concerted action of five Academic Collaborative Centres, local collaborations between academic institutions, regional public health services, local authorities and other relevant sectors in the Netherlands. Prior research revealed lacunas in knowledge of and skills related to five elements of the integrated approach of overweight prevention in children (based upon the French EPODE approach), namely political support, parental education, implementation, social marketing and evaluation. CIAO aims to gain theoretical and practical insight of these elements through five sub-studies and to develop, based on these data, a framework for monitoring and evaluation., Methods/design: For this research program, mixed methods are used in all the five sub-studies. First, problem specification through literature research and consultation of stakeholders, experts, health promotion specialists, parents and policy makers will be carried out. Based on this information, models, theoretical frameworks and practical instruments will be developed, tested and evaluated in the communities that implement the integrated approach to prevent overweight in children. Knowledge obtained from these studies and insights from experts and stakeholders will be combined to create an evaluation framework to evaluate the integrated approach at central, local and individual levels that will be applicable to daily practice., Discussion: This innovative research program stimulates sub-studies to collaborate with local stakeholders and to share and integrate their knowledge, methodology and results. Therefore, the output of this program (both knowledge and practical tools) will be matched and form building blocks of a blueprint for a local evidence- and practice-based integrated approach towards prevention of overweight in children. The output will then support various communities to further optimize the implementation and subsequently the effects of this approach.

Objectives: Although 'integrated' public health policies are assumed to be the ideal way to optimize public health, it remains hard to determine how far removed we are from this ideal, since clear operational criteria and defining characteristics are lacking., Methods: A literature review identified gaps in previous operationalizations of integrated public health policies. We searched for an approach that could fill these gaps., Results: We propose the following defining characteristics of an integrated policy: (1) the combination of policies includes an appropriate mix of interventions that optimizes the functioning of the behavioral system, thus ensuring that motivation, capability and opportunity interact in such a way that they promote the preferred (health-promoting) behavior of the target population, and (2) the policies are implemented by the relevant policy sectors from different policy domains., Conclusion: Our criteria should offer added value since they describe pathways in the process towards formulating integrated policy. The aim of introducing our operationalization is to assist policy makers and researchers in identifying truly integrated cases. The Behavior Change Wheel proved to be a useful framework to develop operational criteria to assess the current state of integrated public health policies in practice., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Childhood obesity is a 'wicked' public health problem that is best tackled by an integrated approach, which is enabled by integrated public health policies. The development and implementation of such policies have in practice proven to be difficult, however, and studying why this is the case requires a tool that may assist local policy-makers and those assisting them. A comprehensive framework that can help to identify options for improvement and to systematically develop solutions may be used to support local policy-makers., Discussion: We propose the 'Behavior Change Ball' as a tool to study the development and implementation of integrated public health policies within local government. Based on the tenets of the 'Behavior Change Wheel' by Michie and colleagues (2011), the proposed conceptual framework distinguishes organizational behaviors of local policy-makers at the strategic, tactical and operational levels, as well as the determinants (motivation, capability, opportunity) required for these behaviors, and interventions and policy categories that can influence them. To illustrate the difficulty of achieving sustained integrated approaches, we use the metaphor of a ball in our framework: the mountainous landscapes surrounding the ball reflect the system's resistance to change (by making it difficult for the ball to roll). We apply this framework to the problem of childhood obesity prevention. The added value provided by the framework lies in its comprehensiveness, theoretical basis, diagnostic and heuristic nature and face validity., Summary: Since integrated public health policies have not been widely developed and implemented in practice, organizational behaviors relevant to the development of these policies remain to be investigated. A conceptual framework that can assist in systematically studying the policy process may facilitate this. Our Behavior Change Ball adds significant value to existing public health policy frameworks by incorporating multiple theoretical perspectives, specifying a set of organizational behaviors and linking the analysis of these behaviors to interventions and policies. We would encourage examination by others of our framework as a tool to explain and guide the development of integrated policies for the prevention of wicked public health problems.

Objective: The objective of the Get Tested Why Not campaign is to increase access to chlamydia and gonorrhea testing and sexual health information, with specific focus on youth., Participants: Individuals between the ages of 15-29 are most affected by chlamydia and gonorrhea infections in Ottawa and were identified as the target population. Youth from the target population were engaged in the development and launch of the campaign., Setting: Development of the campaign began in 2009 and led to a launch on March 21, 2011. Social media promotion as well as traditional advertising approaches developed awareness of the campaign within the target population., Intervention: The campaign consists of a bilingual, youth-friendly website and texting service. After assessing appropriateness of testing, clients can download a requisition form for urine-based chlamydia and gonorrhea testing and submit a sample at one of 26 laboratories across Ottawa., Outcomes: During year 1 of the campaign, there were 13,385 website hits and 104 specimens submitted for chlamydia and gonorrhea testing. The majority (57.6%, n=60) of requisitions were submitted by members of the target population (age 15-29). Of the requisitions submitted, 95 (91.3%) were negative, 4 (3.9%) were positive and 5 (4.8%) were cancelled due to lab errors., Conclusion: The campaign is reaching the target population and has demonstrated a positive impact on knowledge and intended behaviours of users. The use of technology has expanded testing options, thereby potentially broadening Ottawa Public Health's reach to clients who may be less likely to test through traditional testing approaches.

The childhood obesity epidemic can be best tackled by means of an integrated approach, which is enabled by integrated public health policies, or Health in All Policies. Integrated policies are developed through intersectoral collaboration between local government policy makers from health and nonhealth sectors. Such intersectoral collaboration has been proved to be difficult. In this study, we investigated which resources influence intersectoral collaboration. The behavior change wheel framework was used to categorize motivation-, capability-, and opportunity-related resources for intersectoral collaboration. In-depth interviews were held with eight officials representing 10 non-health policy sectors within a local government. Results showed that health and non-health policy sectors did not share policy goals, which decreased motivation for intersectoral collaboration. Awareness of the linkage between health and nonhealth policy sectors was limited, and management was not involved in creating such awareness, which reduced the capability for intersectoral collaboration. Insufficient organizational resources and structures reduced opportunities for intersectoral collaboration. To stimulate intersectoral collaboration to prevent childhood obesity, we recommend that public health professionals should reframe health goals in the terminology of nonhealth policy sectors, that municipal department managers should increase awareness of public health in non-health policy sectors, and that flatter organizational structures should be established.

This study explored the health beliefs about eating habits and physical activity (PA) of Surinamese immigrants of Indian (Hindustani) descent to examine how health education messages to prevent obesity can be made more culturally sensitive. Indians are known for their increasing obesity incidence and are highly vulnerable for obesity-related consequences such as cardiovascular diseases and diabetes. Therefore they might benefit from culturally sensitive health education messages that stimulate healthy eating habits and increase PA levels. In order to examine how health education messages aimed at preventing obesity could be adapted to Indian culture, we interviewed eight Hindustanis living in The Netherland, and conducted two focus groups (n = 19) with members from a Surinamese Hindustani community. Results showed cultural implications that might affect the effectiveness of health education messages: karma has a role in explaining the onset of illness, traditional eating habits are perceived as difficult to change, and PA was generally disliked. We conclude that health education messages aimed at Hindustani immigrants should recognize the role of karma in explaining the onset of illness, include more healthy alternatives for traditional foods, pay attention to the symbolic meaning of food, and suggest more enjoyable and culturally sensitive forms of PA for women.

Experts stress the need to bring the childhood obesity epidemic under control by means of an integrated approach. The implementation of such an approach requires the development of integrated enabling policies on public health by local governments. A prerequisite for developing such integrated public health policies is intersectoral collaboration. Since the development of integrated policies is still in its early stages, this study aimed to answer the following research question: "What interventions can promote intersectoral collaboration and the development of integrated health policies for the prevention of childhood obesity?" Data were collected through a literature search and observations of and interviews with stakeholders. Based on a theoretical framework, we categorized potential interventions that could optimize an integrated approach regarding children's physical activity and diet. The intervention categories included education, persuasion, incentivization, coercion, training, restriction, environmental restructuring, modeling, and enablement.