Transmission disequilibrium of small CNVs in simplex autism.

We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference from Exome Reads). Compared to high-density SNP microarrays, our approach yielded ∼2× more smaller genic rare CNVs. We found that affected probands inherited more CNVs than did their siblings (453 versus 394, p = 0.004; odds ratio [OR] = 1.19) and that the probands' CNVs affected more genes (921 versus 726, p = 0.02; OR = 1.30). These smaller CNVs (median size 18 kb) were transmitted preferentially from the mother (136 maternal versus 100 paternal, p = 0.02), although this bias occurred irrespective of affected status. The excess burden of inherited CNVs among probands was driven primarily by sibling pairs with discordant social-behavior phenotypes (p < 0.0002, measured by Social Responsiveness Scale [SRS] score), which contrasts with families where the phenotypes were more closely matched or less extreme (p > 0.5). Finally, we found enrichment of brain-expressed genes unique to probands, especially in the SRS-discordant group (p = 0.0035). In a combined model, our inherited CNVs, de novo CNVs, and de novo single-nucleotide variants all independently contributed to the risk of autism (p < 0.05). Taken together, these results suggest that small transmitted rare CNVs play a role in the etiology of simplex autism. Importantly, the small size of these variants aids in the identification of specific genes as additional risk factors associated with ASD.

Poor value of pulsed-field gel electrophoresis to investigate long-term scale epidemiology of methicillin-resistant Staphylococcus aureus.

Pulsed-field gel electrophoresis (PFGE) is widely used for epidemic investigations of methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we evaluated its use in a long-term epidemiological setting (years to few decades, country to continent level). The clustering obtained from PFGE patterns after SmaI digestion of the DNA of 20 strains was compared to that obtained using a phylogenetic typing method (multiprimer RAPD). The results showed that the analysis of small PFGE bands (10-85kb) correlates better with multiprimer RAPD than the analysis of large PFGE bands (>85-700kb), suggesting that the analysis of small bands would be more suitable for the investigation of long-term epidemiological setting. However, given the technical difficulties to obtain a good resolution of these bands and the putative presence of plasmids among them, PFGE does not appear to be a method of choice for the long-term epidemiology analysis of MRSA.

High-resolution numerical modelling of flow-vegetation interactions

In this paper, we present and apply a new three-dimensional model for the prediction of canopy-flow and turbulence dynamics in open-channel flow. The approach uses a dynamic immersed boundary technique that is coupled in a sequentially staggered manner to a large eddy simulation. Two different biomechanical models are developed depending on whether the vegetation is dominated by bending or tensile forces. For bending plants, a model structured on the Euler-Bernoulli beam equation has been developed, whilst for tensile plants, an N-pendula model has been developed. Validation against flume data shows good agreement and demonstrates that for a given stem density, the models are able to simulate the extraction of energy from the mean flow at the stem-scale which leads to the drag discontinuity and associated mixing layer.

Italy's urban waste metabolism

The problem of waste management is causing growing concern due to increasing generation rates, the emissions into soil, water and air, the social conflicts derived from the election of disposal sites and the loss of resources and energy among others. In this work, an innovative methodology is used to enable a better understanding of the waste generation and management system in Italy. Two new waste indicators are built to complement the conventional indicators used by official statistics. Then a multi-scale analysis of the Density of Waste Disposed (DWD) is carried out to highlight the territorial diversity of waste performances and test its contribution to detect plausible risky areas. Starting from Italian regions, the scale down goes on to the provincial level and, only for the region of Campania, the municipal one. First, the analysis shows that the DWD is able to complement the information provided by the conventional waste indicators. Second, the analysis shows the limitations of using a unique institutional solution to waste management problems. In this sense the multi-scale analysis provides with a more realistic picture of Italian waste system than using a single scale.

Revisiting the size-R&D productivity relation: introducing the mediating role of decision-making style on the scale and quality of innovative output

We develop a mediation model in which firm size is proposed to affect the scale and quality of innovative output through the adoption of different decision styles during the R&D process. The aim of this study is to understand how the internal changes that firms undergo as they evolve from small to larger organizations affect R&D productivity. In so doing, we illuminate the underlying theoretical mechanism affecting two different dimensions of R&D productivity, namely the scale and quality of innovative output which have not received much attention in previous literature. Using longitudinal data of Spanish manufacturing firms we explore the validity of this mediation model. Our results show that as firms evolve in size, they increasingly emphasize analytical decision making, and consequently, large-sized firms aim for higher-quality innovations while small firms aim for a larger scale of innovative output.

Gaussian estimates for the density of the non-linear stochastic heat equation in any space dimension

In this paper, we establish lower and upper Gaussian bounds for the probability density of the mild solution to the stochastic heat equation with multiplicative noise and in any space dimension. The driving perturbation is a Gaussian noise which is white in time with some spatially homogeneous covariance. These estimates are obtained using tools of the Malliavin calculus. The most challenging part is the lower bound, which is obtained by adapting a general method developed by Kohatsu-Higa to the underlying spatially homogeneous Gaussian setting. Both lower and upper estimates have the same form: a Gaussian density with a variance which is equal to that of the mild solution of the corresponding linear equation with additive noise.

Density-dependent pollen limitation and reproductive assurance in a wind-pollinated herb with contrasting sexual systems

1. Wind pollination is thought to have evolved in response to selection for mechanisms to promote pollination success, when animal pollinators become scarce or unreliable. We might thus expect wind-pollinated plants to be less prone to pollen limitation than their insect-pollinated counterparts. Yet, if pollen loads on stigmas of wind-pollinated species decline with distance from pollen donors, seed set might nevertheless be pollen-limited in populations of plants that cannot self-fertilize their progeny, but not in self-compatible hermaphroditic populations.2. Here, we test this hypothesis by comparing pollen limitation between dioecious and hermaphroditic (monoecious) populations of the wind-pollinated herb Mercurialis annua.3. In natural populations, seed set was pollen-limited in low-density patches of dioecious, but not hermaphroditic, M. annua, a finding consistent with patterns of distance-dependent seed set by females in an experimental array. Nevertheless, seed set was incomplete in both dioecious and hermaphroditic populations, even at high local densities. Further, both factors limited the seed set of females and hermaphrodites, after we manipulated pollen and resource availability in a common garden experiment.4. Synthesis. Our results are consistent with the idea that pollen limitation plays a role in the evolution of combined vs. separate sexes in M. annua. Taken together, they point to the potential importance of pollen transfer between flowers on the same plant (geitonogamy) by wind as a mechanism of reproductive assurance and to the dual roles played by pollen and resource availability in limiting seed set. Thus, seed set can be pollen-limited in sparse populations of a wind-pollinated species, where mates are rare or absent, having potentially important demographic and evolutionary implications.

Human mercury exposure associated with small-scale gold mining in Burkina Faso.

PURPOSE: In Burkina Faso, gold ore is one of the main sources of income for an important part of the active population. Artisan gold miners use mercury in the extraction, a toxic metal whose human health risks are well known. The aim of the present study was to assess mercury exposure as well as to understand the exposure determinants of gold miners in Burkinabe small-scale mines.METHODS: The examined gold miners' population on the different selected gold mining sites was composed by persons who were directly and indirectly related to gold mining activities. But measurement of urinary mercury was performed on workers most susceptible to be exposed to mercury. Thus, occupational exposure to mercury was evaluated among ninety-three workers belonging to eight different gold mining sites spread in six regions of Burkina Faso. Among others, work-related exposure determinants were taken into account for each person during urine sampling as for example amalgamating or heating mercury. All participants were medically examined by a local medical team in order to identify possible symptoms related to the toxic effect of mercury.RESULTS: Mercury levels were high, showing that 69% of the measurements exceeded the ACGIH (American Conference of Industrial Hygienists) biological exposure indice (BEI) of 35 µg per g of creatinine (µg/g-Cr) (prior to shift) while 16% even exceeded 350 µg/g-Cr. Basically, unspecific but also specific symptoms related to mercury toxicity could be underlined among the persons who were directly related to gold mining activities. Only one-third among the studied subpopulation reported about less than three symptoms possibly associated to mercury exposure and nearly half of them suffered from at least five of these symptoms. Ore washers were more involved in the direct handling of mercury while gold dealers in the final gold recovery activities. These differences may explain the overexposure observed in gold dealers and indicate that the refining process is the major source of exposure.CONCLUSIONS: This study attests that mercury exposure still is an issue of concern. North-South collaborations should encourage knowledge exchange between developing and developed countries, for a cleaner artisanal gold mining process and thus for reducing human health and environmental hazards due to mercury use.

The Swiss Early Psychosis Project SWEPP: a national network.

Aim: The study aims to describe the activities of the Swiss Early Psychosis Project (SWEPP) which was founded in 1999 as a national network to further and disseminate knowledge on early psychosis (EP) and to enhance collaboration between healthcare groups. Methods: The present paper is a detailed account of the initiation and the development of the Swiss network. We describe all activities such as the several educational campaigns that were addressed to primary and secondary care groups since the early days. We also provide an overview of the current status of EP services throughout the country. Results: Today, most regions in Switzerland provide specialized EP inpatient and/or outpatient services with a clinical or combined clinical research approach that targets at-risk and/or first-episode populations. Some more recently initiated EP services have been launched as collaborative models between several local or regional psychiatric services. Conclusions: The increasing number of EP services and experts in Switzerland may mirror the catalyzing contribution of the Swiss Early Psychosis Project in this important field of health care. The country's small size and the increasing density of specialized services provide excellent bases for larger-scale networking activities in the future, both in clinical and research areas.

The effects of nutrition, puberty and dancing on bone density in adolescent ballet dancers.

Ballet dancers have on average a low bone mineral content (BMC), with elevated fracture-risk, low body mass index (BMI) for age (body mass index, kg/m2), low energy intake, and delayed puberty. This study aims at a better understanding of the interactions of these factors, especially with regard to nutrition. During a competition for pre-professional dancers we examined 127 female participants (60 Asians, 67 Caucasians). They averaged 16.7 years of age, started dancing at 5.8 years, and danced 22 hours/week. Assessments were made for BMI, BMC (DXA), and bone mineral apparent density (BMAD) at the lumbar spine and femoral neck, pubertal stage (Tanner score), and nutritional status (EAT-40 questionnaire and a qualitative three-day dietary record). BMI for age was found to be normal in only 42.5% of the dancers, while 15.7% had a more or less severe degree of thinness (12.6% Grade2 and 3.1% Grade 3 thinness). Menarche was late (13.9 years, range 11 to 16.8 years). Food intake, evaluated by number of consumed food portions, was below the recommendations for a normally active population in all food groups except animal proteins, where the intake was more than twice the recommended amount. In this population, with low BMI and intense exercise, BMC was low and associated with nutritional factors; dairy products had a positive and non-dairy proteins a negative influence. A positive correlation between BMAD and years since menarche confirmed the importance of exposure to estrogens and the negative impact of delayed puberty. Because of this and the probable negative influence of a high intake of non-dairy proteins, such as meat, fish, and eggs, and the positive association with a high dairy intake, ballet schools should promote balanced diets and normal weight and should recognize and help dancers avoid eating disorders and delayed puberty caused by extensive dancing and inadequate nutrition.

Prognostic ability of practitioners of traditional arabic medicine: comparison with Western methods through a relative patient progress scale.

The ancient Greek medical theory based on balance or imbalance of humors disappeared in the western world, but does survive elsewhere. Is this survival related to a certain degree of health care efficiency? We explored this hypothesis through a study of classical Greco-Arab medicine in Mauritania. Modern general practitioners evaluated the safety and effectiveness of classical Arabic medicine in a Mauritanian traditional clinic, with a prognosis/follow-up method allowing the following comparisons: (i) actual patient progress (clinical outcome) compared with what the traditional 'tabib' had anticipated (= prognostic ability) and (ii) patient progress compared with what could be hoped for if the patient were treated by a modern physician in the same neighborhood. The practice appeared fairly safe and, on average, clinical outcome was similar to what could be expected with modern medicine. In some cases, patient progress was better than expected. The ability to correctly predict an individual's clinical outcome did not seem to be better along modern or Greco-Arab theories. Weekly joint meetings (modern and traditional practitioners) were spontaneously organized with a modern health centre in the neighborhood. Practitioners of a different medical system can predict patient progress. For the patient, avoiding false expectations with health care and ensuring appropriate referral may be the most important. Prognosis and outcome studies such as the one presented here may help to develop institutions where patients find support in making their choices, not only among several treatment options, but also among several medical systems.

Knowledge of Glasgow coma scale by air-rescue physicians.

OBJECTIVE: To assess the theoretical and practical knowledge of the Glasgow Coma Scale (GCS) by trained Air-rescue physicians in Switzerland. METHODS: Prospective anonymous observational study with a specially designed questionnaire. General knowledge of the GCS and its use in a clinical case were assessed. RESULTS: From 130 questionnaires send out, 103 were returned (response rate of 79.2%) and analyzed. Theoretical knowledge of the GCS was consistent for registrars, fellows, consultants and private practitioners active in physician-staffed helicopters. The clinical case was wrongly scored by 38 participants (36.9%). Wrong evaluation of the motor component occurred in 28 questionnaires (27.2%), and 19 errors were made for the verbal score (18.5%). Errors were made most frequently by registrars (47.5%, p = 0.09), followed by fellows (31.6%, p = 0.67) and private practitioners (18.4%, p = 1.00). Consultants made significantly less errors than the rest of the participating physicians (0%, p < 0.05). No statistically significant differences were shown between anesthetists, general practitioners, internal medicine trainees or others. CONCLUSION: Although the theoretical knowledge of the GCS by out-of-hospital physicians is correct, significant errors were made in scoring a clinical case. Less experienced physicians had a higher rate of errors. Further emphasis on teaching the GCS is mandatory.

Ascertaining late-life depressive symptoms in Europe: an evaluation of the survey version of the EURO-D scale in 10 nations. The SHARE project.

The reported prevalence of late-life depressive symptoms varies widely between studies, a finding that might be attributed to cultural as well as methodological factors. The EURO-D scale was developed to allow valid comparison of prevalence and risk associations between European countries. This study used Confirmatory Factor Analysis (CFA) and Rasch models to assess whether the goal of measurement invariance had been achieved; using EURO-D scale data collected in 10 European countries as part of the Survey of Health, Ageing and Retirement in Europe (SHARE) (n = 22,777). The results suggested a two-factor solution (Affective Suffering and Motivation) after Principal Component Analysis (PCA) in 9 of the 10 countries. With CFA, in all countries, the two-factor solution had better overall goodness-of-fit than the one-factor solution. However, only the Affective Suffering subscale was equivalent across countries, while the Motivation subscale was not. The Rasch model indicated that the EURO-D was a hierarchical scale. While the calibration pattern was similar across countries, between countries agreement in item calibrations was stronger for the items loading on the affective suffering than the motivation factor. In conclusion, there is evidence to support the EURO-D as either a uni-dimensional or bi-dimensional scale measure of depressive symptoms in late-life across European countries. The Affective Suffering sub-component had more robust cross-cultural validity than the Motivation sub-component.

Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: The manitoba study.

The measurement of BMD by dual-energy X-ray absorptiometry (DXA) is the "gold standard" for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel gray-level texture measurement that can be extracted from DXA images, correlates with 3D parameters of bone microarchitecture. Our aim was to evaluate the ability of lumbar spine TBS to predict future clinical osteoporotic fractures. A total of 29,407 women 50 years of age or older at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Health service records were assessed for the incidence of nontraumatic osteoporotic fracture codes subsequent to BMD testing (mean follow-up 4.7 years). Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Osteoporotic fractures were identified in 1668 (5.7%) women, including 439 (1.5%) spine and 293 (1.0%) hip fractures. Significantly lower spine TBS and BMD were identified in women with major osteoporotic, spine, and hip fractures (all p < 0.0001). Spine TBS and BMD predicted fractures equally well, and the combination was superior to either measurement alone (p < 0.001). Spine TBS predicts osteoporotic fractures and provides information that is independent of spine and hip BMD. Combining the TBS trabecular texture index with BMD incrementally improves fracture prediction in postmenopausal women. © 2011 American Society for Bone and Mineral Research.