Parents’ experiences of health visiting for children with Down syndrome

© MA Healthcare Limited.Children with Down syndrome have an increased likelihoodof experiencing serious health conditions. Health visitors canhave an important role in monitoring and promoting healthand development for young children with Down syndrome.This study aimed to explore parents’ experiences of healthvisiting services for children with Down syndrome. Twentyfour parents of children with Down syndrome aged 0–5 yearscompleted a brief questionnaire about the number and natureof visits from health visitors in the previous 12 months andtheir support needs. Some parents commented that otherprofessionals met the needs of their child, whereas others saidthat they would like more advice and support from healthvisitors. A further exploration of broader health serviceprovision, including health visiting, for young children withDown syndrome is needed.Peer reviewedFinal Accepted Versio

Climate Dynamics: A Network-Based Approach for the Analysis of Global Precipitation

Precipitation is one of the most important meteorological variables for defining the climate dynamics, but the spatial patterns of precipitation have not been fully investigated yet. The complex network theory, which provides a robust tool to investigate the statistical interdependence of many interacting elements, is used here to analyze the spatial dynamics of annual precipitation over seventy years (1941-2010). The precipitation network is built associating a node to a geographical region, which has a temporal distribution of precipitation, and identifying possible links among nodes through the correlation function. The precipitation network reveals significant spatial variability with barely connected regions, as Eastern China and Japan, and highly connected regions, such as the African Sahel, Eastern Australia and, to a lesser extent, Northern Europe. Sahel and Eastern Australia are remarkably dry regions, where low amounts of rainfall are uniformly distributed on continental scales and small-scale extreme events are rare. As a consequence, the precipitation gradient is low, making these regions well connected on a large spatial scale. On the contrary, the Asiatic South-East is often reached by extreme events such as monsoons, tropical cyclones and heat waves, which can all contribute to reduce the correlation to the short-range scale only. Some patterns emerging between mid-latitude and tropical regions suggest a possible impact of the propagation of planetary waves on precipitation at a global scale. Other links can be qualitatively associated to the atmospheric and oceanic circulation. To analyze the sensitivity of the network to the physical closeness of the nodes, short-term connections are broken. The African Sahel, Eastern Australia and Northern Europe regions again appear as the supernodes of the network, confirming furthermore their long-range connection structure. Almost all North-American and Asian nodes vanish, revealing that extreme events can enhance high precipitation gradients, leading to a systematic absence of long-range patterns

Understanding the Interplay Among Regulatory Self-Efficacy, Moral Disengagement, and Academic Cheating Behaviour During Vocational Education: A Three-Wave Study

The literature has suggested that to understand the diffusion of unethical conduct in the workplace, it is important to investigate the underlying processes sustaining engagement in misbehaviour and to study what occurs during vocational education. Drawing on social-cognitive theory, in this study, we longitudinally examined the role of two opposite dimensions of the self-regulatory moral system, regulatory self-efficacy and moral disengagement, in influencing academic cheating behaviour. In addition, in line with the theories highlighting the bidirectional relationship between cognitive processes and behaviour, we aimed to also examine the reciprocal influence of behaviour on these dimensions over time. Overall, no previous studies have examined the longitudinal interplay between these variables. The sample included 866 (62.8% female) nursing students who were assessed three times annually from the beginning of their vocational education. The findings from a cross-lagged model confirmed that regulatory self-efficacy and moral disengagement have opposite influences on cheating behaviour, that regulatory self-efficacy negatively influences not only the engagement in misconduct but also the justification mechanisms that allow the divorce between moral standards and action, and that moral disengagement and cheating behaviour reciprocally support each other over time. Specifically, not only did moral disengagement influence cheating behaviour even when controlling for its prior levels, but also cheating behaviour affected moral disengagement one year later, controlling for its prior levels. These findings suggest that recourse to wrongdoing could gradually lead to further normalising this kind of behaviour and morally desensitising individuals to misconduct

Towards responsible use of cognitive-enhancing drugs by the healthy

In this article, we propose actions that will help society accept the benefits of enhancement, given appropriate research and evolved regulation. Prescription drugs are regulated as such not for their enhancing properties but primarily for considerations of safety and potential abuse. Still, cognitive enhancement has much to offer individuals and society, and a proper societal response will involve making enhancements available while managing their risks

Rescaling quality of life values from discrete choice experiments for use as QALYs: a cautionary tale

Background: Researchers are increasingly investigating the potential for ordinal tasks such as ranking and discrete choice experiments to estimate QALY health state values. However, the assumptions of random utility theory, which underpin the statistical models used to provide these estimates, have received insufficient attention. In particular, the assumptions made about the decisions between living states and the death state are not satisfied, at least for some people. Estimated values are likely to be incorrectly anchored with respect to death (zero) in such circumstances. Methods: Data from the Investigating Choice Experiments for the preferences of older people CAPability instrument (ICECAP) valuation exercise were analysed. The values (previously anchored to the worst possible state) were rescaled using an ordinal model proposed previously to estimate QALY-like values. Bootstrapping was conducted to vary artificially the proportion of people who conformed to the conventional random utility model underpinning the analyses. Results: Only 26% of respondents conformed unequivocally to the assumptions of conventional random utility theory. At least 14% of respondents unequivocally violated the assumptions. Varying the relative proportions of conforming respondents in sensitivity analyses led to large changes in the estimated QALY values, particularly for lower-valued states. As a result these values could be either positive (considered to be better than death) or negative (considered to be worse than death). Conclusion: Use of a statistical model such as conditional (multinomial) regression to anchor quality of life values from ordinal data to death is inappropriate in the presence of respondents who do not conform to the assumptions of conventional random utility theory. This is clearest when estimating values for that group of respondents observed in valuation samples who refuse to consider any living state to be worse than death: in such circumstances the model cannot be estimated. Only a valuation task requiring respondents to make choices in which both length and quality of life vary can produce estimates that properly reflect the preferences of all respondents

Glycerol Hypersensitivity in a Drosophila Model for Glycerol Kinase Deficiency Is Affected by Mutations in Eye Pigmentation Genes

Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency

Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

<p>Abstract</p> <p>Background</p> <p>While standard reductionist approaches have provided some insights into specific gene polymorphisms and molecular pathways involved in disease pathogenesis, our understanding of complex traits such as atherosclerosis or type 2 diabetes remains incomplete. Gene expression profiling provides an unprecedented opportunity to understand complex human diseases by providing a global view of the multiple interactions across the genome that are likely to contribute to disease pathogenesis. Thus, the goal of gene expression profiling is not to generate lists of differentially expressed genes, but to identify the physiologic or pathogenic processes and structures represented in the expression profile.</p> <p>Methods</p> <p>RNA was separately extracted from peripheral blood neutrophils and mononuclear leukocytes, labeled, and hybridized to genome level microarrays to generate expression profiles of children with polyarticular juvenile idiopathic arthritis, juvenile dermatomyositis relative to childhood controls. Statistically significantly differentially expressed genes were identified from samples of each disease relative to controls. Functional network analysis identified interactions between products of these differentially expressed genes.</p> <p>Results</p> <p><it>In silico </it>models of both diseases demonstrated similar features with properties of scale-free networks previously described in physiologic systems. These networks were observable in both cells of the innate immune system (neutrophils) and cells of the adaptive immune system (peripheral blood mononuclear cells).</p> <p>Conclusion</p> <p>Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation.</p

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

Sattler S, Mehlkop G, Graeff P, Sauer C. Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics. Substance Abuse Treatment, Prevention, and Policy. 2014;9(1): 8.Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies

3-Deazaneplanocin A (DZNep), an Inhibitor of the Histone Methyltransferase EZH2, Induces Apoptosis and Reduces Cell Migration in Chondrosarcoma Cells

ObjectiveGrowing evidences indicate that the histone methyltransferase EZH2 (enhancer of zeste homolog 2) may be an appropriate therapeutic target in some tumors. Indeed, a high expression of EZH2 is correlated with poor prognosis and metastasis in many cancers. In addition, 3-Deazaneplanocin A (DZNep), an S-adenosyl-L homocysteine hydrolase inhibitor which induces EZH2 protein depletion, leads to cell death in several cancers and tumors. The aim of this study was to determine whether an epigenetic therapy targeting EZH2 with DZNep may be also efficient to treat chondrosarcomas.MethodsEZH2 expression was determined by immunohistochemistry and western-blot. Chondrosarcoma cell line CH2879 was cultured in the presence of DZNep, and its growth and survival were evaluated by counting adherent cells periodically. Apoptosis was assayed by cell cycle analysis, Apo2.7 expression using flow cytometry, and by PARP cleavage using western-blot. Cell migration was assessed by wound healing assay.ResultsChondrosarcomas (at least with high grade) highly express EZH2, at contrary to enchondromas or chondrocytes. In vitro, DZNep inhibits EZH2 protein expression, and subsequently reduces the trimethylation of lysine 27 on histone H3 (H3K27me3). Interestingly, DZNep induces cell death of chondrosarcoma cell lines by apoptosis, while it slightly reduces growth of normal chondrocytes. In addition, DZNep reduces cell migration.ConclusionThese results indicate that an epigenetic therapy that pharmacologically targets EZH2 via DZNep may constitute a novel approach to treat chondrosarcomas