Outcome of patients with acute coronary syndrome in hospitals of different sizes. A report from the AMIS Plus Registry.

To assess the impact of admission to different hospital types on early and 1-year outcomes in patients with acute coronary syndrome (ACS). Between 1997 and 2009, 31 010 ACS patients from 76 Swiss hospitals were enrolled in the AMIS Plus registry. Large tertiary institutions with continuous (24 hour/7 day) cardiac catheterisation facilities were classified as type A hospitals, and all others as type B. For 1-year outcomes, a subgroup of patients admitted after 2005 were studied. Eleven type A hospitals admitted 15987 (52%) patients and 65 type B hospitals 15023 (48%) patients. Patients admitted into B hospitals were older, more frequently female, diabetic, hypertensive, had more severe comorbidities and more frequent non-ST segment elevation (NSTE)-ACS/unstable angina (UA). STE-ACS patients admitted into B hospitals received more thrombolysis, but less percutaneous coronary intervention (PCI). Crude in-hospital mortality and major adverse cardiac events (MACE) were higher in patients from B hospitals. Crude 1-year mortality of 3747 ACS patients followed up was higher in patients admitted into B hospitals, but no differences were found for MACE. After adjustment for age, risk factors, type of ACS and comorbidities, hospital type was not an independent predictor of in-hospital mortality, in-hospital MACE, 1-year MACE or mortality. Admission indicated a crude outcome in favour of hospitalisation during duty-hours while 1-year outcome could not document a significant effect. ACS patients admitted to smaller regional Swiss hospitals were older, had more severe comorbidities, more NSTE-ACS and received less intensive treatment compared with the patients initially admitted to large tertiary institutions. However, hospital type was not an independent predictor of early and mid-term outcomes in these patients. Furthermore, our data suggest that Swiss hospitals have been functioning as an efficient network for the past 12 years.

Swain: Stata module to correct the SEM chi-square overidentification test in small sample sizes or complex models. Statistical Software Components S457617, Boston College Department of Economics.

Swain corrects the chi-square overidentification test (i.e., likelihood ratio test of fit) for structural equation models whethr with or without latent variables. The chi-square statistic is asymptotically correct; however, it does not behave as expected in small samples and/or when the model is complex (cf. Herzog, Boomsma, & Reinecke, 2007). Thus, particularly in situations where the ratio of sample size (n) to the number of parameters estimated (p) is relatively small (i.e., the p to n ratio is large), the chi-square test will tend to overreject correctly specified models. To obtain a closer approximation to the distribution of the chi-square statistic, Swain (1975) developed a correction; this scaling factor, which converges to 1 asymptotically, is multiplied with the chi-square statistic. The correction better approximates the chi-square distribution resulting in more appropriate Type 1 reject error rates (see Herzog & Boomsma, 2009; Herzog, et al., 2007).

Quantitative analysis of crystal/grain sizes and their distributions in 2D and 3D

We review methods to estimate the average crystal (grain) size and the crystal (grain) size distribution in solid rocks. Average grain sizes often provide the base for stress estimates or rheological calculations requiring the quantification of grain sizes in a rock's microstructure. The primary data for grain size data are either 1D (i.e. line intercept methods), 2D (area analysis) or 3D (e.g., computed tomography, serial sectioning). These data have been used for different data treatments over the years, whereas several studies assume a certain probability function (e.g., logarithm, square root) to calculate statistical parameters as the mean, median, mode or the skewness of a crystal size distribution. The finally calculated average grain sizes have to be compatible between the different grain size estimation approaches in order to be properly applied, for example, in paleo-piezometers or grain size sensitive flow laws. Such compatibility is tested for different data treatments using one- and two-dimensional measurements. We propose an empirical conversion matrix for different datasets. These conversion factors provide the option to make different datasets compatible with each other, although the primary calculations were obtained in different ways. In order to present an average grain size, we propose to use the area-weighted and volume-weighted mean in the case of unimodal grain size distributions, respectively, for 2D and 3D measurements. The shape of the crystal size distribution is important for studies of nucleation and growth of minerals. The shape of the crystal size distribution of garnet populations is compared between different 2D and 3D measurements, which are serial sectioning and computed tomography. The comparison of different direct measured 3D data; stereological data and direct presented 20 data show the problems of the quality of the smallest grain sizes and the overestimation of small grain sizes in stereological tools, depending on the type of CSD. (C) 2011 Published by Elsevier Ltd.

Skeletal muscle mitochondrial and lipid droplet content assessed with standardized grid sizes for stereology.

Skeletal muscle mitochondrial (Mito) and lipid droplet (Lipid) content are often measured in human translational studies. Stereological point counting allows computing Mito and Lipid volume density (Vd) from micrographs taken with transmission electron microscopes. Former studies are not specific as to the size of individual squares that make up the grids, making reproducibility difficult, particularly when different magnifications are used. Our objective was to determine which size grid would be best at predicting fractional volume efficiently without sacrificing reliability and to test a novel method to reduce sampling bias. Methods: ten subjects underwent vastus lateralis biopsies. Samples were fixed, embedded, and cut longitudinally in ultrathin sections of 60 nm. Twenty micrographs from the intramyofibrillar region were taken per subject at Ã-33,000 magnification. Different grid sizes were superimposed on each micrograph: 1,000 Ã- 1,000 nm, 500 Ã- 500 nm, and 250 Ã- 250 nm. Results: mean Mito and Lipid Vd were not statistically different across grids. Variability was greater when going from 1,000 Ã- 1,000 to 500 Ã- 500 nm grid than from 500 Ã- 500 to 250 Ã- 250 nm grid. Discussion: this study is the first to attempt to standardize grid size while keeping with the conventional stereology principles. This is all in hopes of producing replicable assessments that can be obtained universally across different studies looking at human skeletal muscle mitochondrial and lipid droplet content.

Outcome of patients with acute coronary syndrome in hospitals of different sizes in Switzerland

Objective: To assess the impact of patient admission in different hospital types in Switzerland on early in-hospital and 1-year outcomes in patients with acute coronary syndrome (ACS).Methods: From 1997 to 2009, 31,010 ACS patients from 76 Swiss hospitals were enrolled in the AMIS Plus registry. Large tertiary teaching institutions with 24 hour/7 day cardiac catheterization facilities were classified as type A hospitals, all others as type B. One-year outcome was studied in a subgroup of patients admitted after 2005. Multivariate logistic regression models were used to calculate the odds ratios (OR with 95%CI) for independent predictors of mortality and major adverse cardiac events (MACE).Results: There were 11 type A hospitals with admissions of 15,987 (52%) patients and 65 type B hospitals with 15,023 (48%) patients. Patients initially admitted into B hospitals were older, more frequently female, hypertensive and diabetic, had more severe comorbidities and more frequently NSTE-ACS/UA. They were less likely to receive aspirin, clopidogrel and GPIIb/IIIa antagonists. STE-ACS patients initially admitted into B hospitals received more thrombolysis than those admitted into A hospitals, but less percutaneous coronary intervention (PCI). From the patients admitted to B hospitals, 5271 (35%) were transferred for intervention. Crude in-hospital mortality and MACE were higher in patients from B hospitals. Crude 1-year mortality of 3747 ACS patients followed up was higher in patients initially admitted into B hospitals, but no differences were found for MACE. Hospital type, after adjustment for age, risk factors, type of ACS and co-morbidities, was not an independent predictor of in-hospital mortality (OR 0.94; 0.76-1.16), in-hospital MACE (0.98; 0.82-1.17), 1-year mortality or 1-year MACE (1.06; 0.85-1.33). Analysis of the time of admission indicated a crude outcome in favor of hospitalization during duty-hours but no significant effect could be documented for 1-year outcome.Conclusion: ACS patients admitted to type B hospitals were older, had more severe co-morbidities, more NSTEACS and received less intensive treatment. However, after correcting for baseline inequalities, early and mid-term outcomes were similar regardless of hospital type. Ultimate patient outcome thus does not appear to be influenced by the type of hospital where the initial admission takes place. Appropriate early referral of selected patients probably partly explains this finding.

Sexual dimorphism in resource acquisition and deployment: both size and timing matter.

Background and Aims The males and females of many dioecious plant species differ from one another in important life-history traits, such as their size. If male and female reproductive functions draw on different resources, for example, one should expect males and females to display different allocation strategies as they grow. Importantly, these strategies may differ not only between the two sexes, but also between plants of different age and therefore size. Results are presented from an experiment that asks whether males and females of Mercurialis annua, an annual plant with indeterminate growth, differ over time in their allocation of two potentially limiting resources (carbon and nitrogen) to vegetative (below-and above-ground) and reproductive tissues.Methods Comparisons were made of the temporal patterns of biomass allocation to shoots, roots and reproduction and the nitrogen content in the leaves between the sexes of M. annua by harvesting plants of each sex after growth over different periods of time.Key Results and Conclusions Males and females differed in their temporal patterns of allocation. Males allocated more to reproduction than females at early stages, but this trend was reversed at later stages. Importantly, males allocated proportionally more of their biomass towards roots at later stages, but the roots of females were larger in absolute terms. The study points to the important role played by both the timing of resource deployment and the relative versus absolute sizes of the sinks and sources in sexual dimorphism of an annual plant.

The Teggiolo zone: a key to the Helvetic-Penninic connection (stratigraphy and tectonics in the Val Bavona, Ticino, Central Alps)

The Teggiolo zone is the sedimentary cover of the Antigorio nappe, one of the lowest tectonic units of the Penninic Central Alps. Detailed mapping, stratigraphic and structural analyses, and comparisons with less metamorphic series in several well-studied domains of the Alps, provide a new stratigraphic interpretation. The Teggiolo zone is comprised of several sedimentary cycles, separated by erosive surfaces and large stratigraphic gaps, which cover the time span from Triassic to Eocene. At Mid-Jurassic times it appears as an uplifted, partially emergent block, marking the southern limit of the main Helvetic basin (the Limiting South-Helvetic Rise LSHR). The main mass of the Teggiolo calcschists, whose base truncates the Triassic-Jurassic cycles and can erode the Antigorio basement, consists of fine-grained clastic sediments analogous to the deep-water flyschoid deposits of Late Cretaceous to Eocene age in the North-Penninic (or Valais s.l.) basins. Thus the Antigorio-Teggiolo domain occupies a crucial paleogeographic position, on the boundary between the Helvetic and Penninic realms: from Triassic to Early Cretaceous its affinity is with the Helvetic; at the end of Cretaceous it is incorporated into the North-Penninic basins. An unexpected result is the discovery of the important role played by complex formations of wildflysch type at the top of the Teggiolo zone. They contain blocks of various sizes. According to their nature, three different associations are distinguished that have specific vertical and lateral distributions. These blocks give clues to the existence of territories that have disappeared from the present-day level of observation and impose constraints on the kinematics of early folding and embryonic nappe emplacement. Tectonics produced several phases of superimposed folds and schistosities, more in the metasediments than in the gneissic basement. Older deformations that predate the amplification of the frontal hinge of the nappe generated the dominant schistosity and the km-wide Vanzèla isoclinal fold.

Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity.

The limited ability of common variants to account for the genetic contribution to complex disease has prompted searches for rare variants of large effect, to partly explain the 'missing heritability'. Analyses of genome-wide genotyping data have identified genomic structural variants (GSVs) as a source of such rare causal variants. Recent studies have reported multiple GSV loci associated with risk of obesity. We attempted to replicate these associations by similar analysis of two familial-obesity case-control cohorts and a population cohort, and detected GSVs at 11 out of 18 loci, at frequencies similar to those previously reported. Based on their reported frequencies and effect sizes (OR≥25), we had sufficient statistical power to detect the large majority (80%) of genuine associations at these loci. However, only one obesity association was replicated. Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population frequency of 2×10(-4) (95% confidence interval [9.6×10(-5)-3.1×10(-4)]); accounts overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8×10(-10); odds ratio = 25.0 [9.9-60.6]); and results in a mean body mass index (BMI) increase of 5.8 kg.m(-2) [1.8-10.3] in adults from the general population. We also attempted replication using BMI as a quantitative trait in our population cohort; associations with BMI at or near nominal significance were detected at two further loci near KIF2B and within FOXP2, but these did not survive correction for multiple testing. These findings emphasise several issues of importance when conducting rare GSV association, including the need for careful cohort selection and replication strategy, accurate GSV identification, and appropriate correction for multiple testing and/or control of false discovery rate. Moreover, they highlight the potential difficulty in replicating rare CNV associations across different populations. Nevertheless, we show that such studies are potentially valuable for the identification of variants making an appreciable contribution to complex disease.

EEG-based functional brain networks: does the network size matter?

Functional connectivity in human brain can be represented as a network using electroencephalography (EEG) signals. These networks--whose nodes can vary from tens to hundreds--are characterized by neurobiologically meaningful graph theory metrics. This study investigates the degree to which various graph metrics depend upon the network size. To this end, EEGs from 32 normal subjects were recorded and functional networks of three different sizes were extracted. A state-space based method was used to calculate cross-correlation matrices between different brain regions. These correlation matrices were used to construct binary adjacency connectomes, which were assessed with regards to a number of graph metrics such as clustering coefficient, modularity, efficiency, economic efficiency, and assortativity. We showed that the estimates of these metrics significantly differ depending on the network size. Larger networks had higher efficiency, higher assortativity and lower modularity compared to those with smaller size and the same density. These findings indicate that the network size should be considered in any comparison of networks across studies.

Skeletal Muscle Mitochondrial and Lipid Droplet Volume Density: Validity of Electron Microscopy Point-counting Measurements

Mitochondrial (M) and lipid droplet (L) volume density (vd) are often used in exercise research. Vd is the volume of muscle occupied by M and L. The means of calculating these percents are accomplished by applying a grid to a 2D image taken with transmission electron microscopy; however, it is not known which grid best predicts these values. PURPOSE: To determine the grid with the least variability of Mvd and Lvd in human skeletal muscle. METHODS: Muscle biopsies were taken from vastus lateralis of 10 healthy adults, trained (N=6) and untrained (N=4). Samples of 5-10mg were fixed in 2.5% glutaraldehyde and embedded in EPON. Longitudinal sections of 60 nm were cut and 20 images were taken at random at 33,000x magnification. Vd was calculated as the number of times M or L touched two intersecting grid lines (called a point) divided by the total number of points using 3 different sizes of grids with squares of 1000x1000nm sides (corresponding to 1µm2), 500x500nm (0.25µm2) and 250x250nm (0.0625µm2). Statistics included coefficient of variation (CV), 1 way-BS ANOVA and spearman correlations. RESULTS: Mean age was 67 ± 4 yo, mean VO2peak 2.29 ± 0.70 L/min and mean BMI 25.1 ± 3.7 kg/m2. Mean Mvd was 6.39% ± 0.71 for the 1000nm squares, 6.01% ± 0.70 for the 500nm and 6.37% ± 0.80 for the 250nm. Lvd was 1.28% ± 0.03 for the 1000nm, 1.41% ± 0.02 for the 500nm and 1.38% ± 0.02 for the 250nm. The mean CV of the three grids was 6.65% ±1.15 for Mvd with no significant differences between grids (P>0.05). Mean CV for Lvd was 13.83% ± 3.51, with a significant difference between the 1000nm squares and the two other grids (P<0.05). The 500nm squares grid showed the least variability between subjects. Mvd showed a positive correlation with VO2peak (r = 0.89, p < 0.05) but not with weight, height, or age. No correlations were found with Lvd. CONCLUSION: Different size grids have different variability in assessing skeletal muscle Mvd and Lvd. The grid size of 500x500nm (240 points) was more reliable than 1000x1000nm (56 points). 250x250nm (1023 points) did not show better reliability compared with the 500x500nm, but was more time consuming. Thus, choosing a grid with square size of 500x500nm seems the best option. This is particularly relevant as most grids used in the literature are either 100 points or 400 points without clear information on their square size.

Species identification in mammals from mixed biological samples based on mitochondrial DNA control region length polymorphism.

The ability to identify the species origin of an unknown biological sample is relevant in the fields of human and wildlife forensics. However, the detection of several species mixed in the same sample still remains a challenge. We developed and tested a new approach for mammal DNA identification in mixtures of two or three species, based on the analysis of mitochondrial DNA control region interspecific length polymorphism followed by direct sequencing. Contrary to other published methods dealing with species mixtures, our protocol requires a single universal primer pair and is not based on a pre-defined panel of species. Amplicons can be separated either on agarose gels or using CE. The advantages and limitations of the assay are discussed under different conditions, such as variable template concentration, amplicon sizes and size difference among the amplicons present in the mixture. For the first time, this protocol provides a simple, reliable and flexible method for simultaneous identification of multiple mammalian species from mixtures, without any prior knowledge of the species involved.

The effectiveness of brief alcohol interventions in primary care settings: a systematic review.

Issues. Numerous studies have reported that brief interventions delivered in primary care are effective in reducing excessive drinking. However, much of this work has been criticised for being clinically unrepresentative. This review aimed to assess the effectiveness of brief interventions in primary care and determine if outcomes differ between efficacy and effectiveness trials. Approach. A pre-specified search strategy was used to search all relevant electronic databases up to 2006. We also hand-searched the reference lists of key articles and reviews. We included randomised controlled trials (RCT) involving patients in primary care who were not seeking alcohol treatment and who received brief intervention. Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, subgroup and sensitivity analyses and meta-regression were conducted. Key Findings. The primary meta-analysis included 22 RCT and evaluated outcomes in over 5800 patients. At 1 year follow up, patients receiving brief intervention had a significant reduction in alcohol consumption compared with controls [mean difference: -38 g week(-1), 95%CI (confidence interval): -54 to -23], although there was substantial heterogeneity between trials (I(2) = 57%). Subgroup analysis confirmed the benefit of brief intervention in men but not in women. Extended intervention was associated with a non-significantly increased reduction in alcohol consumption compared with brief intervention. There was no significant difference in effect sizes for efficacy and effectiveness trials. Conclusions. Brief interventions can reduce alcohol consumption in men, with benefit at a year after intervention, but they are unproven in women for whom there is insufficient research data. Longer counselling has little additional effect over brief intervention. The lack of differences in outcomes between efficacy and effectiveness trials suggests that the current literature is relevant to routine primary care.

Minimal clinically meaningful differences for the eortc QLQ-C30 and eortc QLQ-Bn20 scales in brain cancer patients

Objective: The aim of this study was to determine the smallest changes in health-related quality of life (HRQOL) scores in the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the EORTC Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. Methods: World Health Organization (WHO) performance status (PS) and the Mini Mental State Examination (MMSE) were used as clinical anchors to determine minimal clinically important differences (MCID) in HRQOL change scores (range 0 - 100) in the EORTC QLQ-C30 and QLQ-BN20. Anchor-based MCID estimates less than 0.2SD (small effect) were not recommended for interpretation. Other selected distribution-based methods were also used for comparison purposes. Results: Based on WHO PS, our findings support the following whole number estimates of the MCID for improvement and deterioration respectively: physical functioning (6, 9), role functioning (14, 12), cognitive functioning (8, 8), global health status (7, 4*), fatigue (12, 9) and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and those for communication deficit were (9, 7). The estimates with asterisks were less that the set 0.2 SD threshold and are therefore not recommended for interpretation. Our MCID estimates therefore range from 5-14. Conclusion: These estimates can help clinicians to evaluate changes in HRQOL over time and, in conjunction with other measures of efficacy, help to assess the value of a health care intervention or to compare treatments. Furthermore, the estimates can be useful in determining sample sizes in the design of future clinical trials.