Preschool Behavioral and Social-Cognitive Problems as Predictors of (Pre)adolescent Disruptive Behavior

This article describes preschool social understanding and difficult behaviors (hot temper, disobedience, bossiness and bullying) as predictors of oppositional defiant disorder (ODD) and aggressive conduct disorder (ACD) in a Dutch population sample of (pre)adolescents (N = 1943), measured at age 10–12 and at age 13–15. ODD and ACD were assessed by the Child Behavior Checklist and the Youth Self-Report, preschool behavior was evaluated by the parental questionnaire ‹How was your child as a preschooler? (age 4–5)’. Adjusted for each other, all difficult preschool behaviors except bullying were associated with adolescent ODD, while only bullying significantly predicted adolescent ACD. Furthermore, the results suggest a qualitative difference between ODD and ACD in terms of the social component of the disorders: poor preschool social understanding was associated with the development of ACD but not of ODD; and poor social understanding interacted with difficult preschool behaviors to predict later ACD but not ODD. The associations did not differ between boys and girls, and were roughly similar for preadolescent (age 10–12) and early adolescent (age 13–15) outcomes. The finding that poor social understanding was implicated in the development of ACD but not in the development of ODD may help to demarcate the individuality of each disorder and offer leads for (differential) treatment strategies

Rhabdomyolysis in Community Acquired Bacterial Sepsis – A Retrospective Cohort Study

BACKGROUND AND OBJECTIVES:Rhabdomyolysis is often associated with sepsis and gram positive bacterial pathogens are reported to be the most frequent cause of sepsis induced rhabdomyolysis. We report the pattern of infecting bacterial pathogens and associated causal factors in a South-Indian cohort. DESIGN, SETTING, PARTICIPANTS #ENTITYSTARTX00026; MEASUREMENTS:Retrospective cohort study of adult patients with community acquired bacterial sepsis complicated by rhabdomyolysis from March 2003--August 2008. Rhabdomyolysis was defined as serum creatine kinase >2000 IU/L. The study population was divided into group-I (sepsis with gram positive pathogens), group-II (sepsis with gram negative pathogens) and group-III (culture negative sepsis). RESULTS:103 patients (group I -15, group II- 34 and group III- 54) formed the study cohort. Mean age was 55 years and two-third had diabetes. Mean creatine kinase was 7114 IU/L and mean serum creatinine on admission was 2.4 mg/dl. Causative pathogen of sepsis was identified in 47.5%. Gram negative pathogens were more frequently (33%) associated with rhabdomyolysis than gram positive pathogens (14.5%). Lung was the commonest foci of sepsis (38.8%). 78.6% of the study population had one or more additional causal factor for rhabdomyolysis like statin intake, chronic alcoholism, hypokalemia, hypernatremia and hypophosphatemia. Mortality was 59%. CONCLUSIONS:Gram negative bacterial pathogens were more frequently associated with rhabdomyolysis than gram positive pathogens. Rhabdomyolysis in patients with sepsis is multifactorial and is associated with high mortality

Low Frequency Vibrations Disrupt Left-Right Patterning in the Xenopus Embryo

The development of consistent left-right (LR) asymmetry across phyla is a fascinating question in biology. While many pharmacological and molecular approaches have been used to explore molecular mechanisms, it has proven difficult to exert precise temporal control over functional perturbations. Here, we took advantage of acoustical vibration to disrupt LR patterning in Xenopus embryos during tightly-circumscribed periods of development. Exposure to several low frequencies induced specific randomization of three internal organs (heterotaxia). Investigating one frequency (7 Hz), we found two discrete periods of sensitivity to vibration; during the first period, vibration affected the same LR pathway as nocodazole, while during the second period, vibration affected the integrity of the epithelial barrier; both are required for normal LR patterning. Our results indicate that low frequency vibrations disrupt two steps in the early LR pathway: the orientation of the LR axis with the other two axes, and the amplification/restriction of downstream LR signals to asymmetric organs

A novel blood-based biomarker for detection of autism spectrum disorders

Autism spectrum disorders (ASD) are classified as neurological developmental disorders. Several studies have been carried out to find a candidate biomarker linked to the development of these disorders, but up to date no reliable biomarker is available. Mass spectrometry techniques have been used for protein profiling of blood plasma of children with such disorders in order to identify proteins/peptides that may be used as biomarkers for detection of the disorders. Three differentially expressed peptides with mass–charge (m/z) values of 2020±1, 1864±1 and 1978±1 Da in the heparin plasma of children with ASD that were significantly changed as compared with the peptide pattern of the non-ASD control group are reported here. This novel set of biomarkers allows for a reliable blood-based diagnostic tool that may be used in diagnosis and potentially, in prognosis of ASD

Validation of a score chart to predict the risk of chronic mesenteric ischemia and development of an updated score chart

Background and objective: The objective of this article is to externally validate and update a recently published score chart for chronic mesenteric ischemia (CMI). Methods: A multicenter prospective cohort analysis was conducted of 666 CMI-suspected patients referred to two Dutch specialized CMI centers. Multidisciplinary consultation resulted in expert-based consensus diagnosis after which CMI consensus patients were treated. A definitive diagnosis of CMI was established if successful treatment resulted in durable symptom relief. The absolute CMI risk was calculated and discriminative ability of the original chart was assessed by the c-statistic in the validation cohort. Thereafter the original score chart was updated based on the performance in the combined original and validation cohort with inclusion of celiac artery (CA) stenosis cause. Results: In 8% of low-risk patients, 39% of intermediate-risk patients and 94% of high-risk patients of the validation cohort, CMI was diagnosed. Discriminative ability of the original model was acceptable (c-statistic 0.79). The total score of the updated chart ranged from 0 to 28 points (low risk 19% absolute CMI risk, intermediate risk 45%, and high risk 92%). The discriminative ability of the updated chart was slightly better (c-statistic 0.80). Conclusion: The CMI prediction model performs and discriminates well in the validation cohort. The updated score chart has excellent discriminative ability and is useful in clinical decision making

Assessment of participation bias in cohort studies: systematic review and meta-regression analysis

Abstract The proportion of non-participation in cohort studies, if associated with both the exposure and the probability of occurrence of the event, can introduce bias in the estimates of interest. The aim of this study is to evaluate the impact of participation and its characteristics in longitudinal studies. A systematic review (MEDLINE, Scopus and Web of Science) for articles describing the proportion of participation in the baseline of cohort studies was performed. Among the 2,964 initially identified, 50 were selected. The average proportion of participation was 64.7%. Using a meta-regression model with mixed effects, only age, year of baseline contact and study region (borderline) were associated with participation. Considering the decrease in participation in recent years, and the cost of cohort studies, it is essential to gather information to assess the potential for non-participation, before committing resources. Finally, journals should require the presentation of this information in the papers

Simvastatin Sodium Salt and Fluvastatin Interact with Human Gap Junction Gamma-3 Protein

Finding pleiomorphic targets for drugs allows new indications or warnings for treatment to be identified. As test of concept, we applied a new chemical genomics approach to uncover additional targets for the widely prescribed lipid-lowering pro-drug simvastatin. We used mRNA extracted from internal mammary artery from patients undergoing coronary artery surgery to prepare a viral cardiovascular protein library, using T7 bacteriophage. We then studied interactions of clones of the bacteriophage, each expressing a different cardiovascular polypeptide, with surface-bound simvastatin in 96-well plates. To maximise likelihood of identifying meaningful interactions between simvastatin and vascular peptides, we used a validated photo-immobilisation method to apply a series of different chemical linkers to bind simvastatin so as to present multiple orientations of its constituent components to potential targets. Three rounds of biopanning identified consistent interaction with the clone expressing part of the gene GJC3, which maps to Homo sapiens chromosome 7, and codes for gap junction gamma-3 protein, also known as connexin 30.2/31.3 (mouse connexin Cx29). Further analysis indicated the binding site to be for the N-terminal domain putatively ‘regulating’ connexin hemichannel and gap junction pores. Using immunohistochemistry we found connexin 30.2/31.3 to be present in samples of artery similar to those used to prepare the bacteriophage library. Surface plasmon resonance revealed that a 25 amino acid synthetic peptide representing the discovered N-terminus did not interact with simvastatin lactone, but did bind to the hydrolysed HMG CoA inhibitor, simvastatin acid. This interaction was also seen for fluvastatin. The gap junction blockers carbenoxolone and flufenamic acid also interacted with the same peptide providing insight into potential site of binding. These findings raise key questions about the functional significance of GJC3 transcripts in the vasculature and other tissues, and this connexin’s role in therapeutic and adverse effects of statins in a range of disease states

International trade, global supply chains and compliance

International supply chains require the movement of goods across borders. While moving goods internationally is already operationally complex, the regulatory requirements that need to be met complicate this further. In this chapter, we explain how and why international regulatory issues enter the supply chain. At the basic level, we discuss in some detail concepts such as arm’s length trading, origin, customs declaration and the role of trade agreements. We then introduce, as part of the advanced level, the basic principles of customs supervision in supply chains. Most customs regulations contain principles that are designed to facilitate international business and allow for the postponement of duty and tax payment to the right time and place. In the supply chain literature, these concepts are virtually unknown, but they play an important role in the design of international supply chains in practice. We also introduce a new vision on customs enforcement that was developed as a spin off of several European research projects. In this vision, so-called trusted tradelanes are introduced as the next step in supply chain compliance. We end with the state of the art discussion on the design of trusted tradelanes and the necessary and sufficient conditions that need to be met to achieve this trusted tradelane status. Throughout the chapter, we have included case studies from practice to illustrate specific insights, or offer a basis for further discussion

Towards efficient multimodal Hinterland networks

Terminal operator ECT in the port of Rotterdam sought to establish a multidisciplinary research group that would support the development of a strong multimodal hinterland network concept. This was the start of the ULTIMATE project. ULTIMATE aimed to support the development “towards efficient multimodal hinterland networks”. The Ultimate research agenda consisted of four elements: (1) The operational consequences of integrating transport and cargo handling activities for supply chains. This has resulted in efficient container stacking and barge routing algorithms. (2) Incorporating new business models in the design of hinterland networks. This delivered new insights in the role of information and pricing in hinterland networks. (3) The legal consequences of mixing transport and storage activities by container terminals. The contribution of this element is a more fundamental understanding of the importance of legal concepts in multimodal transport for different actors. (4) The role and position of the port authority vis-a-vis the activities of container terminals. This led to new insights on the role and contribution of a port authority in port and hinterland network development. This chapter discusses some of the main research outcomes of the work for these four research problems