Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes

Background - Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5–10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. Methods - We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. Results - We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. Conclusions - A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits.

A cross-sectional study assessing the association between online ratings and structural and quality of care measures : results from two German physician rating websites

BACKGROUND: Even though physician rating websites (PRWs) have been gaining in importance in both practice and research, little evidence is available on the association of patients' online ratings with the quality of care of physicians. It thus remains unclear whether patients should rely on these ratings when selecting a physician. The objective of this study was to measure the association between online ratings and structural and quality of care measures for 65 physician practices from the German Integrated Health Care Network "Quality and Efficiency" (QuE). METHODS: Online reviews from two German PRWs were included which covered a three-year period (2011 to 2013) and included 1179 and 991 ratings, respectively. Information for 65 QuE practices was obtained for the year 2012 and included 21 measures related to structural information (N = 6), process quality (N = 10), intermediate outcomes (N = 2), patient satisfaction (N = 1), and costs (N = 2). The Spearman rank coefficient of correlation was applied to measure the association between ratings and practice-related information. RESULTS: Patient satisfaction results from offline surveys and the patients per doctor ratio in a practice were shown to be significantly associated with online ratings on both PRWs. For one PRW, additional significant associations could be shown between online ratings and cost-related measures for medication, preventative examinations, and one diabetes type 2-related intermediate outcome measure. There again, results from the second PRW showed significant associations with the age of the physicians and the number of patients per practice, four process-related quality measures for diabetes type 2 and asthma, and one cost-related measure for medication. CONCLUSIONS: Several significant associations were found which varied between the PRWs. Patients interested in the satisfaction of other patients with a physician might select a physician on the basis of online ratings. Even though our results indicate associations with some diabetes and asthma measures, but not with coronary heart disease measures, there is still insufficient evidence to draw strong conclusions. The limited number of practices in our study may have weakened our findings.

Predictors of future falls in Parkinson disease

Background: Falls are a major health and injury problem for people with Parkinson disease (PD). Despite the severe consequences of falls, a major unresolved issue is the identification of factors that predict the risk of falls in individual patients with PD. The primary aim of this study was to prospectively determine an optimal combination of functional and disease-specific tests to predict falls in individuals with PD. ----- ----- Methods: A total of 101 people with early-stage PD undertook a battery of neurologic and functional tests in their optimally medicated state. The tests included Tinetti, Berg, Timed Up and Go, Functional Reach, and the Physiological Profile Assessment of Falls Risk; the latter assessment includes physiologic tests of visual function, proprioception, strength, cutaneous sensitivity, reaction time, and postural sway. Falls were recorded prospectively over 6 months. ----- ----- Results: Forty-eight percent of participants reported a fall and 24% more than 1 fall. In the multivariate model, a combination of the Unified Parkinson's Disease Rating Scale (UPDRS) total score, total freezing of gait score, occurrence of symptomatic postural orthostasis, Tinetti total score, and extent of postural sway in the anterior-posterior direction produced the best sensitivity (78%) and specificity (84%) for predicting falls. From the UPDRS items, only the rapid alternating task category was an independent predictor of falls. Reduced peripheral sensation and knee extension strength in fallers contributed to increased postural instability. ----- ----- Conclusions: Falls are a significant problem in optimally medicated early-stage PD. A combination of both disease-specific and balance- and mobility-related measures can accurately predict falls in individuals with PD.

Enlightening, balancing and transcending entrepreneurial orientation : the 4th annual EO3 research PDW

Entrepreneurial Orientation (EO) has a 30 year history as one of the most used concepts in entrepreneurship research. “Recent attention in formal sessions at the Academy of Management conference programs confirm Entrepreneurial Orientation as a primary construct with a majority of Entrepreneurship Division sponsored sessions devoted to studies using EO related measures”, as reported by the 2010 division program chair, Per Davidson (Roberts, 2010: 9). However, questions continue to be raised concerning over-dependence on parts of one strategic scale, possible inappropriate or under-theorized adaptations, and the lack of theoretical development on application and performance variance in emergent, organizational, and socioeconomic settings. One recent area of investigation in analysis, methods, theory and application concerns an “EO gestalt”, focusing on the family of EO-related measures and theory, rather than on one or more dimensions, in order to explore the theory and process of the Entrepreneurial Orientation phenomenon. The goals of the 4th Annual EO3 PDW are to enlighten researchers on the development of Entrepreneurial Orientation theory and related scales, balance the use of Entrepreneurial Orientation current knowledge with new research frontiers suggested by EO3 scholars’ questions, and transcend boundaries in the discoveries undertaken in the shared interdisciplinary and cross-cultural research agenda currently developing for Entrepreneurial Orientation concepts. Going into its forth year, the EO3 PDW has been pivotal in formalizing discussion, pushing research forward, and gaining insights from experienced and cutting edge scholars, as it provides a point of reference for coalescing research questions and findings surrounding this important concept.

Dimensions of neuroticism : relationships with gender and personality traits

Reports results of 2 studies into sex-related neuroticism. Measures included sex-free and sex-related neuroticism scales (L. Francis, see record 1994-00056-001), the Psychoticism, Extraversion, and Lie scales of the Eysenck Personality Questionnaire (EPQ), and the Beck Depression Inventory. In Study 1 with 69 male and 75 female undergraduates, no support for the validity of sex-free and sex-related measures of neuroticism was found. Although scores on both neuroticism measures were significantly related to depression scores, sex-free neuroticism was also associated with extraversion, psychoticism, and social desirability but only among males. Women tended to have significantly higher neuroticism scores than did men. In Study 2 involving 56 male and 129 female undergraduates, no significant differences in total scale scores were observed between the sexes when a natural language measure of neuroticism was used.

Validation of a parent-proxy quality of life questionnaire for paediatric chronic cough (PC-QOL)

Background Quality of life (QOL) measures are an important patient-relevant outcome measure for clinical studies. Currently there is no fully validated cough-specific QOL measure for paediatrics. The objective of this study was to validate a cough-specific QOL questionnaire for paediatric use. Method 43 children (28 males, 15 females; median age 29 months, IQR 20–41 months) newly referred for chronic cough participated. One parent of each child completed the 27-item Parent Cough-Specific QOL questionnaire (PC-QOL), and the generic child (Pediatric QOL Inventory 4.0 (PedsQL)) and parent QOL questionnaires (SF-12) and two cough-related measures (visual analogue score and verbal category descriptive score) on two occasions separated by 2–3 weeks. Cough counts were also objectively measured on both occasions. Results Internal consistency for both the domains and total PC-QOL at both test times was excellent (Cronbach alpha range 0.70–0.97). Evidence for repeatability and criterion validity was established, with significant correlations over time and significant relationships with the cough measures. The PC-QOL was sensitive to change across the test times and these changes were significantly related to changes in cough measures (PC-QOL with: verbal category descriptive score, rs=−0.37, p=0.016; visual analogue score, rs=−0.47, p=0.003). Significant correlations of the difference scores for the social domain of the PC-QOL and the domain and total scores of the PedsQL were also noted (rs=0.46, p=0.034). Conclusion The PC-QOL is a reliable and valid outcome measure that assesses QOL related to childhood cough at a given time point and measures changes in cough-specific QOL over time.

Relating urban airborne particle concentrations to shipping using carbon based elemental emission ratios

This study demonstrates a novel method for testing the hypothesis that variations in primary and secondary particle number concentration (PNC) in urban air are related to residual fuel oil combustion at a coastal port lying 30 km upwind, by examining the correlation between PNC and airborne particle composition signatures chosen for their sensitivity to the elemental contaminants present in residual fuel oil. Residual fuel oil combustion indicators were chosen by comparing the sensitivity of a range of concentration ratios to airborne emissions originating from the port. The most responsive were combinations of vanadium and sulfur concentration ([S], [V]) expressed as ratios with respect to black carbon concentration ([BC]). These correlated significantly with ship activity at the port and with the fraction of time during which the wind blew from the port. The average [V] when the wind was predominantly from the port was 0.52 ng.m-3 (87%) higher than the average for all wind directions and 0.83 ng.m-3 (280%) higher than that for the lowest vanadium yielding wind direction considered to approximate the natural background. Shipping was found to be the main source of V impacting urban air quality in Brisbane. However, contrary to the stated hypothesis, increases in PNC related measures did not correlate with ship emission indicators or ship traffic. Hence at this site ship emissions were not found to be a major contributor to PNC compared to other fossil fuel combustion sources such as road traffic, airport and refinery emissions.

Pilot study evaluating the effect of massage therapy on stress, anxiety and aggression in a young adult psychiatric inpatient unit

Objective: The aim of the present pilot study was to examine the effectiveness of a relaxation massage therapy programme in reducing stress, anxiety and aggression on a young adult psychiatric inpatient unit. Method: This was a prospective, non-randomized intervention study comparing treatment as usual (TAU) with TAU plus massage therapy intervention (MT) over consecutive 7 week blocks (May–August 2006). MT consisted of a 20 min massage therapy session offered daily to patients during their period of hospitalization. The Kennedy Nurses’ Observational Scale for Inpatient Evaluation (NOSIE), the Symptom Checklist-90–Revised (SCL-90-R), the State–Trait Anxiety Inventory (STAI) and stress hormone (saliva cortisol) levels were used to measure patient outcomes at admission and discharge from the unit. The Staff Observation Aggression Scale–Revised (SOAS-R) was used to monitor the frequency and severity of aggressive incidents on the unit. Results: There was a significant reduction in self-reported anxiety (p < 0.001), resting heart rate (p < 0.05) and cortisol levels (p < 0.05) immediately following the initial and final massage therapy sessions. Significant improvements in hostility (p = 0.007) and depression scores (p < 0.001) on the SCL-90-R were observed in both treatment groups. There was no group×time interaction on any of the measures. Poor reliability of staff-reported incidents on the SOAS-R limited the validity of results in this domain. Conclusions: Massage therapy had immediate beneficial effects on anxiety-related measures and may be a useful de-escalating tool for reducing stress and anxiety in acutely hospitalized psychiatric patients. Study limitations preclude any definite conclusions on the effect of massage therapy on aggressive incidents in an acute psychiatric setting. Randomized controlled trials are warranted.

Bivariate genome-wide association study of genetically correlated neuroimaging phenotypes from DTI and MRI through a seemingly unrelated regression model

Large multisite efforts (e.g., the ENIGMA Consortium), have shown that neuroimaging traits including tract integrity (from DTI fractional anisotropy, FA) and subcortical volumes (from T1-weighted scans) are highly heritable and promising phenotypes for discovering genetic variants associated with brain structure. However, genetic correlations (rg) among measures from these different modalities for mapping the human genome to the brain remain unknown. Discovering these correlations can help map genetic and neuroanatomical pathways implicated in development and inherited risk for disease. We use structural equation models and a twin design to find rg between pairs of phenotypes extracted from DTI and MRI scans. When controlling for intracranial volume, the caudate as well as related measures from the limbic system - hippocampal volume - showed high rg with the cingulum FA. Using an unrelated sample and a Seemingly Unrelated Regression model for bivariate analysis of this connection, we show that a multivariate GWAS approach may be more promising for genetic discovery than a univariate approach applied to each trait separately.

黄土高原半干旱区农田干旱防御与抗旱措施

系统分析农田抗旱管理与相应措施对黄土高原半干旱区社会和经济的协调健康发展以及粮食安全具有重要意义。黄土高原半干旱区干旱发生的特点决定了农田抗旱管理的复杂性和艰巨性。论文阐述了农田抗旱管理中防、抗与避三种措施的主要内容,并就农田抗旱管理系统进行了介绍。认为通过建立完善的农业技术推广服务体系和针对地区特点的抗旱管理措施,是半干旱区农业可持续发展一项重要而积极的对策,不仅需要从资金和政策上给予扶持和倾斜,更需要在管理机制上予以重视。

高含水油藏复合驱剩油分布研究-以羊三木油田馆陶组油藏复合驱为例

Based on the study of the combined flooding test block of Guantao formation in Third faulted block of Yangsanmu oil field, this paper carries out the integration of reservoir precise characterization for very high water cut reservoir, establishes precise 3D geologic model for high water cut development period and states the changing law of the reservoir architecture dtiring development by combined flooding. Then, by subdivided the thick oil reservoir, the study of remaining oil saturation monitoring in fiber glass cased well and tracer monitoring is developed. According the study of multiple constrained combined flooding reservoir numerical simulation, remaining oil distribution are predicted, the methods architecture of predicting remaining oil distribution are established for fluvial facies reservoir at late development stage, develops plan is designed and adjustment associating technologies for enhancing oil recovery. On these base, related measures for tapping the potential are given, it is verified and optimized through the field former test and the good economic effect is achieved . The major achievements of this paper are as follows. The changing law of the reservoir architecture and it's property parameters is revealed, The result indicates that the temperature-pressure of the injecting material and the interaction effect of the injecting material and reservoir petrography are the main factors of the dynamic changes of the reservoir architecture. The quantitative reservoir geologic model, which is tallied with dynamic reservoir parameters of the study area, is established. Subdivided the thick oil reservoir is very important for the study of the remaining oil distribution within the thick oil reservoir. Subdivided the thick oil reservoir technology, which consists of six technologies as follow: micro-cyclic divided, flow unit method, architectural element method, high resolution log technology, high resolution-process technology for normal logging data and using the production data is presented. 3. It is established dynamic monitoring system of remaining oil saturation quantitative research which are inner and interlayer remaining oil saturation from time-lapse logging in fiber glass cased well, inter-well remaining oil saturation from the technology of isotopic tracer monitoring technology, and 4d remaining oil saturation distribution from combined flooding numerical modeling integrated by production datao The forming mechanism of remaining oil for polymer flooding and alkali/polymer combined flooding is clarified, and the plane and vertical distribution law of remaining oil after combined flooding is revealed. Predicting methods and technologies for the combined flooding reservoir of fluvial facies is developed. Combined flooding has been achieved good displacement result in the pilot of Third fault block in Yangsanmu oil field, and accumulated types of important parameters and optimum plans, this technology of combined flooding is expected to increase recovery ratio by 4.77%.

On the Relationship Between File Sizes, Transport Protocols, and Self-Similar Network Traffic

Recent measurements of local-area and wide-area traffic have shown that network traffic exhibits variability at a wide range of scales self-similarity. In this paper, we examine a mechanism that gives rise to self-similar network traffic and present some of its performance implications. The mechanism we study is the transfer of files or messages whose size is drawn from a heavy-tailed distribution. We examine its effects through detailed transport-level simulations of multiple TCP streams in an internetwork. First, we show that in a "realistic" client/server network environment i.e., one with bounded resources and coupling among traffic sources competing for resources the degree to which file sizes are heavy-tailed can directly determine the degree of traffic self-similarity at the link level. We show that this causal relationship is not significantly affected by changes in network resources (bottleneck bandwidth and buffer capacity), network topology, the influence of cross-traffic, or the distribution of interarrival times. Second, we show that properties of the transport layer play an important role in preserving and modulating this relationship. In particular, the reliable transmission and flow control mechanisms of TCP (Reno, Tahoe, or Vegas) serve to maintain the long-range dependency structure induced by heavy-tailed file size distributions. In contrast, if a non-flow-controlled and unreliable (UDP-based) transport protocol is used, the resulting traffic shows little self-similar characteristics: although still bursty at short time scales, it has little long-range dependence. If flow-controlled, unreliable transport is employed, the degree of traffic self-similarity is positively correlated with the degree of throttling at the source. Third, in exploring the relationship between file sizes, transport protocols, and self-similarity, we are also able to show some of the performance implications of self-similarity. We present data on the relationship between traffic self-similarity and network performance as captured by performance measures including packet loss rate, retransmission rate, and queueing delay. Increased self-similarity, as expected, results in degradation of performance. Queueing delay, in particular, exhibits a drastic increase with increasing self-similarity. Throughput-related measures such as packet loss and retransmission rate, however, increase only gradually with increasing traffic self-similarity as long as reliable, flow-controlled transport protocol is used.

Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.

Impact of Kidney Function on Effects of the Dietary Approaches to Stop Hypertension (Dash) Diet.

OBJECTIVES: Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure in adults with hypertension, how kidney function impacts this effect is not known. We evaluated whether Estimated Glomerular Filtration Rate (eGFR) modifies the effect of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function. METHODS: Secondary analysis of the DASH-Sodium trial, a multicenter, randomized, controlled human feeding study that evaluated the blood pressure lowering effect of the DASH diet at three levels of sodium intake. Data from 92 participants with pre-hypertension or stage 1 hypertension during the 3450 mg /day sodium diet assignment contributed to this analysis. Stored frozen plasma and urine specimens were used to measure kidney related laboratory outcomes. RESULTS: Effects of the DASH diet on blood pressure, phosphorus, intact parathyroid hormone, creatinine, and albuminuria were not modified by baseline eGFR (mean 84.5 ± 18.0 ml/min/1.73 m(2), range 44.1 to 138.6 ml/min/1.73 m(2)) or the presence of chronic kidney disease (N=13%). CONCLUSIONS: The impact of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function does not appear to be modified by eGFR in this small subset of DASH-Sodium trial participants with relatively preserved kidney function. Whether greater reduction in eGFR modifies the effects of DASH on kidney related measures is yet to be determined. A larger study in individuals with more advanced kidney disease is needed to establish the efficacy and safety of the DASH diet in this patient population.