A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders

BACKGROUND: The recurrent ~600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. OBJECTIVE: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. METHODS: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. RESULTS: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. CONCLUSIONS: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.

Spin-strain coupling in a 3-D transition metal oxides

ab-initio Hartree Fock (HF), density functional theory (DFT) and hybrid potentials were employed to compute the optimized lattice parameters and elastic properties of perovskite 3-d transition metal oxides. The optimized lattice parameters and elastic properties are interdependent in these materials. An interaction is observed between the electronic charge, spin and lattice degrees of freedom in 3-d transition metal oxides. The coupling between the electronic charge, spin and lattice structures originates due to localization of d-atomic orbitals. The coupling between the electronic charge, spin and crystalline lattice also contributes in the ferroelectric and ferromagnetic properties in perovskites. The cubic and tetragonal crystalline structures of perovskite transition metal oxides of ABO3 are studied. The electronic structure and the physics of 3-d perovskite materials is complex and less well considered. Moreover, the novelty of the electronic structure and properties of these perovskites transition metal oxides exceeds the challenge offered by their complex crystalline structures. To achieve the objective of understanding the structure and property relationship of these materials the first-principle computational method is employed. CRYSTAL09 code is employed for computing crystalline structure, elastic, ferromagnetic and other electronic properties. Second-order elastic constants (SOEC) and bulk moduli (B) are computed in an automated process by employing ELASTCON (elastic constants) and EOS (equation of state) programs in CRYSTAL09 code. ELASTCON, EOS and other computational algorithms are utilized to determine the elastic properties of tetragonal BaTiO3, rutile TiO2, cubic and tetragonal BaFeO3 and the ferromagentic properties of 3-d transition metal oxides. Multiple methods are employed to crosscheck the consistency of our computational results. Computational results have motivated us to explore the ferromagnetic properties of 3-d transition metal oxides. Billyscript and CRYSTAL09 code are employed to compute the optimized geometry of the cubic and tetragonal crystalline structure of transition metal oxides of Sc to Cu. Cubic crystalline structure is initially chosen to determine the effect of lattice strains on ferromagnetism due to the spin angular momentum of an electron. The 3-d transition metals and their oxides are challenging as the basis functions and potentials are not fully developed to address the complex physics of the transition metals. Moreover, perovskite crystalline structures are extremely challenging with respect to the quality of computations as the latter requires the well established methods. Ferroelectric and ferromagnetic properties of bulk, surfaces and interfaces are explored by employing CRYSTAL09 code. In our computations done on cubic TMOs of Sc-Fe it is observed that there is a coupling between the crystalline structure and FM/AFM spin polarization. Strained crystalline structures of 3-d transition metal oxides are subjected to changes in the electromagnetic and electronic properties. The electronic structure and properties of bulk, composites, surfaces of 3-d transition metal oxides are computed successfully.

[Field validation of a real-time PCR test for the detection of Mycoplasma hyopneumoniae in nasal swabs of live pigs]

Enzootic pneumonia (EP) of pigs, caused by Mycoplasma hyopneumoniae has been a notifiable disease in Switzerland since May 2003. The diagnosis of EP has been based on multiple methods, including clinical, bacteriological and epidemiological findings as well as pathological examination of lungs (mosaic diagnosis). With the recent development of a real-time PCR (rtPCR) assay with 2 target sequences a new detection method for M. hyopneumoniae became available. This assay was tested for its applicability to nasal swab material from live animals. Pigs from 74 herds (average 10 pigs per herd) were tested. Using the mosaic diagnosis, 22 herds were classified as EP positive and 52 as EP negative. From the 730 collected swab samples we were able to demonstrate that the rtPCR test was 100% specific. In cases of cough the sensitivity on herd level of the rtPCR is 100%. On single animal level and in herds without cough the sensitivity was lower. In such cases, only a positive result would be proof for an infection with M. hyopneumoniae. Our study shows that the rtPCR on nasal swabs from live pigs allows a fast and accurate diagnosis in cases of suspected EP.

Genomewide association for a dominant pigmentation gene in sheep

Most published genomewide association studies (GWAS) in sheep have investigated recessively inherited monogenic traits. The objective here was to assess the feasibility of performing GWAS for a dominant trait for which the genetic basis was already known. A total of 42 Manchega and Rasa Aragonesa sheep that segregate solid black or white coat pigmentation were genotyped using the SNP50 BeadChip. Previous analysis in Manchegas demonstrated a complete association between the pigmentation trait and alleles of the MC1R gene, setting an a priori expectation for GWAS. Multiple methods were used to identify and quantify the strength of population substructure between black and white animals, before allelic association testing was performed for 49 034 SNPs. Following correction for substructure, GWAS identified the most strongly associated SNP (s26449) was also the closest to the MC1R gene. The finding was strongly supported by the permutation tree-based random forest (RF) analysis. Importantly, GWAS identified unlinked SNP with only slightly lower p-values than for s26449. Random forest analysis indicated these were false positives, suggesting interpretation based on both approaches was beneficial. The results indicate that a combined analytical approach can be successful in studies where a modest number of animals are available and substantial population stratification exists.

A Research Roadmap for Complementary and Alternative Medicine – What We Need to Know by 2020

Background: The CAMbrella coordination action was funded within the Framework Programme 7. Its aim is to provide a research roadmap for clinical and epidemiological research for complementary and alternative medicine (CAM) that is appropriate for the health needs of European citizens and acceptable to their national research institutes and healthcare providers in both public and private sectors. One major issue in the European research agenda is the demographic change and its impact on health care. Our vision for 2020 is that there is an evidence base that enables European citizens to make informed decisions about CAM, both positive and negative. This roadmap proposes a strategic research agenda for the field of CAM designed to address future European health care challenges. This roadmap is based on the results of CAMbrella’s several work packages, literature reviews and expert discussions including a consensus meeting. Methods: We first conducted a systematic literature review on key issues in clinical and epidemiological research in CAM to identify the general concepts, methods and the strengths and weaknesses of current CAM research. These findings were discussed in a workshop (Castellaro, Italy, September 7–9th 2011) with international CAM experts and strategic and methodological recommendations were defined in order to improve the rigor and relevance of CAM research. These recommendations provide the basis for the research roadmap, which was subsequently discussed in a consensus conference (Järna, Sweden, May 9–11th 2012) with all CAMbrella members and the CAMbrella advisory board. The roadmap was revised after this discussion in CAMbrella Work Package (WP) 7 and finally approved by CAMbrella’s scientific steering committee on September 26th 2012. Results: Our main findings show that CAM is very heterogenous in terms of definitions and legal regulations between the European countries. In addition, citizens’ needs and attitudes towards CAM as well as the use and provision of CAM differ significantly between countries. In terms of research methodology, there was consensus that CAM researchers should make use of all the commonly accepted scientific research methods and employ those with utmost diligence combined in a mixed methods framework. Conclusions: We propose 6 core areas of research that should be investigated to achieve a robust knowledge base and to allow stakeholders to make informed decisions. These are: Research into the prevalence of CAM in Europe: Reviews show that we do not know enough about the circumstances in which CAM is used by Europeans. To enable a common European strategic approach, a clear picture of current use is of the utmost importance. Research into differences regarding citizens’ attitudes and needs towards CAM: Citizens are the driver for CAM utilization. Their needs and views on CAM are a key priority, and their interests must be investigated and addressed in future CAM research. Research into safety of CAM: Safety is a key issue for European citizens. CAM is considered safe, but reliable data is scarce although urgently needed in order to assess the risk and cost-benefit ratio of CAM. Research into the comparative effectiveness of CAM: Everybody needs to know in what situation CAM is a reasonable choice. Therefore, we recommend a clear emphasis on concurrent evaluation of the overall effectiveness of CAM as an additional or alternative treatment strategy in real-world settings. Research into effects of context and meaning: The impact of effects of context and meaning on the outcome of CAM treatments must be investigated; it is likely that they are significant. Research into different models of CAM health care integration: There are different models of CAM being integrated into conventional medicine throughout Europe, each with their respective strengths and limitations. These models should be described and concurrently evaluated; innovative models of CAM provision in health care systems should be one focus for CAM research. We also propose a methodological framework for CAM research. We consider that a framework of mixed methodological approaches is likely to yield the most useful information. In this model, all available research strategies including comparative effectiveness research utilising quantitative and qualitative methods should be considered to enable us to secure the greatest density of knowledge possible. Stakeholders, such as citizens, patients and providers, should be involved in every stage of developing the specific and relevant research questions, study design and the assurance of real-world relevance for the research. Furthermore, structural and sufficient financial support for research into CAM is needed to strengthen CAM research capacity if we wish to understand why it remains so popular within the EU. In order to consider employing CAM as part of the solution to the health care, health creation and self-care challenges we face by 2020, it is vital to obtain a robust picture of CAM use and reliable information about its cost, safety and effectiveness in real-world settings. We need to consider the availability, accessibility and affordability of CAM. We need to engage in research excellence and utilise comparative effectiveness approaches and mixed methods to obtain this data. Our recommendations are both strategic and methodological. They are presented for the consideration of researchers and funders while being designed to answer the important and implicit questions posed by EU citizens currently using CAM in apparently increasing numbers. We propose that the EU actively supports an EUwide strategic approach that facilitates the development of CAM research. This could be achieved in the first instance through funding a European CAM coordinating research office dedicated to foster systematic communication between EU governments, public, charitable and industry funders as well as researchers, citizens and other stakeholders. The aim of this office would be to coordinate research strategy developments and research funding opportunities, as well as to document and disseminate international research activities in this field. With the aim to develop sustainability as second step, a European Centre for CAM should be established that takes over the monitoring and further development of a coordinated research strategy for CAM, as well as it should have funds that can be awarded to foster high quality and robust independent research with a focus on citizens health needs and pan-European collaboration. We wish to establish a solid funding for CAM research to adequately inform health care and health creation decision-making throughout the EU. This centre would ensure that our vision of a common, strategic and scientifically rigorous approach to CAM research becomes our legacy and Europe’s reality. We are confident that our recommendations will serve these essential goals for EU citizens.

Pediatric antiretroviral adherence and child disclosure in Botswana

The scale-up of antiretrovirals (ARVs) to treat HIV/AIDS in Africa has been rapid over the last five years. Botswana was the first African nation to roll out a comprehensive ARV program, where ARVs are available to all citizens who qualify. Excellent adherence to these ARVs is necessary to maintain HIV suppression and on-going health of all individuals taking them. Children rely almost entirely on their caregivers for the administration of these medications, and very little research has been done to examine the factors which affect both adherence and disclosure to the child of their HIV status. ^ Methods. This cross-sectional study used multiple methods to examine adherence, disclosure, and stigma across various dimensions of the child and caregiver's lives, including 30 caregiver questionnaires, interviewer-administered 3-day adherence recalls, pharmacy pill counts, and chart reviews. Fifty in-depth interviews were conducted with caregivers, male caregivers, teenagers, and health care providers. ^ Results. Perceived family stigma was found to be a predictor of excellent adherence. After controlling for age, children who live with their mothers were significantly less likely to know their HIV status than children living with any other relative (OR=0.403, p=0.014). Children who have a grandmother living in the household or taking care of them each day are significantly more likely to have optimal adherence than children who don't have grandmother involvement in their daily lives. ^ Discussion. Visible illness plays an intermediary role between adherence and perceived family stigma: Caregivers know that ARVs suppress physical manifestations of HIV, and in an effort to avoid unnecessary disclosure of the child's status to family members, therefore have children with excellent adherence. Grandmothers play a vital role in supporting the care and treatment of children in Botswana. ^

Measuring Service Effectiveness for Families

While most professionals do not dispute the fact that evaluation is necessary to determine whether agencies and practitioners are truly providing services that meet clients’ needs, information regarding consistent measures on service effectiveness in human service organizations is sparse. A national survey of 250 not-for-profit family service organizations in the United States (52.8% return rate) yielded results relevant to client identified needs and agency effectiveness measures in serving today’s families. On an open-ended survey item, 52.3% agencies indicated that poverty represented the most pressing problem among today’s families because other psychological needs also take priority. Over two thirds of these agencies used multiple methods to evaluate their services. Clients’ feedback and outcome measures are the most popular methods. The findings reveal agencies' difficulties in determining what or who decides if the most appropriate services are being provided for the target population. Limited data collected on outcomes and impact may impose additional difficulties in program design and planning.

UNDERSTANDING NURSE CREATED COGNITIVE ARTIFACTS: PERSONALLY-CREATED-COGNITIVE-ARTIFACTS AS EXTERNAL REPRESENTATIONS OF DISTRIBUTED COGNITION

Manuscript 1: “Conceptual Analysis: Externalizing Nursing Knowledge” We use concept analysis to establish that the report tool nurses prepare, carry, reference, amend, and use as a temporary data repository are examples of cognitive artifacts. This tool, integrally woven throughout the work and practice of nurses, is important to cognition and clinical decision-making. Establishing the tool as a cognitive artifact will support new dimensions of study. Such studies can characterize how this report tool supports cognition, internal representation of knowledge and skills, and external representation of knowledge of the nurse. Manuscript 2: “Research Methods: Exploring Cognitive Work” The purpose of this paper is to describe a complex, cross-sectional, multi-method approach to study of personal cognitive artifacts in the clinical environment. The complex data arrays present in these cognitive artifacts warrant the use of multiple methods of data collection. Use of a less robust research design may result in an incomplete understanding of the meaning, value, content, and relationships between personal cognitive artifacts in the clinical environment and the cognitive work of the user. Manuscript 3: “Making the Cognitive Work of Registered Nurses Visible” Purpose: Knowledge representations and structures are created and used by registered nurses to guide patient care. Understanding is limited regarding how these knowledge representations, or cognitive artifacts, contribute to working memory, prioritization, organization, cognition, and decision-making. The purpose of this study was to identify and characterize the role a specific cognitive artifact knowledge representation and structure as it contributed to the cognitive work of the registered nurse. Methods: Data collection was completed, using qualitative research methods, by shadowing and interviewing 25 registered nurses. Data analysis employed triangulation and iterative analytic processes. Results: Nurse cognitive artifacts support recall, data evaluation, decision-making, organization, and prioritization. These cognitive artifacts demonstrated spatial, longitudinal, chronologic, visual, and personal cues to support the cognitive work of nurses. Conclusions: Nurse cognitive artifacts are an important adjunct to the cognitive work of nurses, and directly support patient care. Nurses need to be able to configure their cognitive artifact in ways that are meaningful and support their internal knowledge representations.

El tratamiento de los estudios de caso como herramienta de investigación : Su aporte en el subcampo de las Relaciones Internacionales

Este artículo revisa el papel clave que los métodos de estudio de casos han jugado en el estudio de las relaciones internacionales, especialmente en los estudios de Estados Unidos. Los estudios de caso en el subcampo de Relaciones Internacionales no son los estudios inconexos, a-teóricos e ideográficos que sus críticos censuran. Estos forman un conjunto cada vez más estandarizado y riguroso y, junto con el trabajo estadístico y formal, han contribuido a mejorar de forma acumulativa el entendimiento de la política mundial. El artículo analiza y revisa ejemplos de criterios de selección de casos (incluyendo los menos probables, menos y más similares y los casos desviados); la innovación conceptual; teorías tipológicas, tipologías explicativas, el análisis comparativo cualitativo y el análisis de conjuntos difusos; el proceso de rastreo, y la integración de múltiples métodos

El tratamiento de los estudios de caso como herramienta de investigación : Su aporte en el subcampo de las Relaciones Internacionales

Este artículo revisa el papel clave que los métodos de estudio de casos han jugado en el estudio de las relaciones internacionales, especialmente en los estudios de Estados Unidos. Los estudios de caso en el subcampo de Relaciones Internacionales no son los estudios inconexos, a-teóricos e ideográficos que sus críticos censuran. Estos forman un conjunto cada vez más estandarizado y riguroso y, junto con el trabajo estadístico y formal, han contribuido a mejorar de forma acumulativa el entendimiento de la política mundial. El artículo analiza y revisa ejemplos de criterios de selección de casos (incluyendo los menos probables, menos y más similares y los casos desviados); la innovación conceptual; teorías tipológicas, tipologías explicativas, el análisis comparativo cualitativo y el análisis de conjuntos difusos; el proceso de rastreo, y la integración de múltiples métodos

El tratamiento de los estudios de caso como herramienta de investigación : Su aporte en el subcampo de las Relaciones Internacionales

Este artículo revisa el papel clave que los métodos de estudio de casos han jugado en el estudio de las relaciones internacionales, especialmente en los estudios de Estados Unidos. Los estudios de caso en el subcampo de Relaciones Internacionales no son los estudios inconexos, a-teóricos e ideográficos que sus críticos censuran. Estos forman un conjunto cada vez más estandarizado y riguroso y, junto con el trabajo estadístico y formal, han contribuido a mejorar de forma acumulativa el entendimiento de la política mundial. El artículo analiza y revisa ejemplos de criterios de selección de casos (incluyendo los menos probables, menos y más similares y los casos desviados); la innovación conceptual; teorías tipológicas, tipologías explicativas, el análisis comparativo cualitativo y el análisis de conjuntos difusos; el proceso de rastreo, y la integración de múltiples métodos

Synthesis, Modification, and Application of Siloxane Materials for Environmental Sensing

As human populations and resource consumption increase, it is increasingly important to monitor the quality of our environment. While laboratory instruments offer useful information, portable, easy to use sensors would allow environmental analysis to occur on-site, at lower cost, and with minimal operator training. We explore the synthesis, modification, and applications of modified polysiloxane in environmental sensing. Multiple methods of producing modified siloxanes were investigated. Oligomers were formed by using functionalized monomers, producing siloxane materials containing silicon hydride, methyl, and phenyl side chains. Silicon hydride-functionalized oligomers were further modified by hydrosilylation to incorporate methyl ester and naphthyl side chains. Modifications to the siloxane materials were also carried out using post-curing treatments. Methyl ester-functionalized siloxane was incorporated into the surface of a cured poly(dimethylsiloxane) film by siloxane equilibration. The materials containing methyl esters were hydrolyzed to reveal carboxylic acids, which could later be used for covalent protein immobilization. Finally, the siloxane surfaces were modified to incorporate antibodies by covalent, affinity, and adsorption-based attachment. These modifications were characterized by a variety of methods, including contact angle, attenuated total reflectance Fourier transform infrared spectroscopy, dye labels, and 1H nuclear magnetic resonance spectroscopy. The modified siloxane materials were employed in a variety of sensing schemes. Volatile organic compounds were detected using methyl, phenyl, and naphthyl-functionalized materials on a Fabry-Perot interferometer and a refractometer. The Fabry-Perot interferometer was found to detect the analytes upon siloxane extraction by deformation of the Bragg reflectors. The refractometer was used to determine that naphthyl-functionalized siloxanes had elevated refractive indices, rendering these materials more sensitive to some analytes. Antibody-modified siloxanes were used to detect biological analytes through a solid phase microextraction-mediated enzyme linked immunosorbent assay (SPME ELISA). The SPME ELISA was found to have higher analyte sensitivity compared to a conventional ELISA system. The detection scheme was used to detect Escherichia coli at 8500 CFU/mL. These results demonstrate the variety of methods that can be used to modify siloxanes and the wide range of applications of modified siloxanes has been demonstrated through chemical and biological sensing schemes.

Changing Banking Supervision in the Eurozone: the ECB as a Policy Entrepreneur. Bruges Political Research Paper No. 38, December 2014

In 2012, the European Union adopted a transformational change to its banking policy for the Eurozone. It dropped the model of decentralized supervision and regulatory competition between countries, and replaced it with a single supervisor and harmonization. Transferring banking supervision to the ECB also alters the existing constitutional order. The policy process leading to this transformational change was rapid and highly political, which was different compared to earlier incremental changes to banking policy. Kingdon's model, whereby policy entrepreneurs seize opportunities at times when the independent streams of solutions, problems and politics converge, partly explains this transformation. The study of EU banking policy suggests, however, that the multiple streams framework should pay more attention to the way in which entrepreneurs engineer fluctuations within the streams and thereby contribute to creating opportunities for change. This paper identifies the ECB as an effective entrepreneur which also played an active role in political bargaining.

Victim-perpetrator differences in reports of hurtful events

This research project addressed limitations identified in previous studies of role differences (victim vs. perpetrator) in evaluations of hurtful events. The study employed multiple methods (open-ended and structured retrospective reports and experience-sampling diary records), and involved a community sample of both dating and married couples. Retrospective reports indicated that the extent and direction of role-related differences varied markedly across dependent measures. Further, role differences were moderated by forgiveness, but not relationship status, relationship satisfaction, or event severity. Diary records pointed to the ambiguity inherent in many communication acts as contributing to differing perceptions of hurtful events. Results are discussed in terms of theories of interdependence and self-presentation and in terms of the complex and often ambiguous nature of couples' communication processes.

Evaluating the properties of a stage-specific self-efficacy scale for physical activity using classical test theory, confirmatory factor analysis and item response modeling

The purpose of this paper was to evaluate the psychometric properties of a stage-specific selfefficacy scale for physical activity with classical test theory (CTT), confirmatory factor analysis (CFA) and item response modeling (IRM). Women who enrolled in the Women On The Move study completed a 20-item stage-specific self-efficacy scale developed for this study [n = 226, 51.1% African-American and 48.9% Hispanic women, mean age = 49.2 (67.0) years, mean body mass index = 29.7 (66.4)]. Three analyses were conducted: (i) a CTT item analysis, (ii) a CFA to validate the factor structure and (iii) an IRM analysis. The CTT item analysis and the CFA results showed that the scale had high internal consistency (ranging from 0.76 to 0.93) and a strong factor structure. Results also showed that the scale could be improved by modifying or eliminating some of the existing items without significantly altering the content of the scale. The IRM results also showed that the scale had few items that targeted high self-efficacy and the stage-specific assumption underlying the scale was rejected. In addition, the IRM analyses found that the five-point response format functioned more like a four-point response format. Overall, employing multiple methods to assess the psychometric properties of the stage-specific self-efficacy scale demonstrated the complimentary nature of these methods and it highlighted the strengths and weaknesses of this scale.