Methods for the defining mechanisms of anterior vaginal wall descent (DEMAND) study.

INTRODUCTION AND HYPOTHESIS: The protocol and analysis methods for the Defining Mechanisms of Anterior Vaginal Wall Descent (DEMAND) study are presented. DEMAND was designed to identify mechanisms and contributors of prolapse recurrence after two transvaginal apical suspension procedures for uterovaginal prolapse. METHODS: DEMAND is a supplementary cohort study of a clinical trial in which women with uterovaginal prolapse randomized to (1) vaginal hysterectomy with uterosacral ligament suspension or (2) vaginal mesh hysteropexy underwent pelvic magnetic resonance imaging (MRI) at 30-42 months post-surgery. Standardized protocols have been developed to systematize MRI examinations across multiple sites and to improve reliability of MRI measurements. Anatomical failure, based on MRI, is defined as prolapse beyond the hymen. Anatomic measures from co-registered rest, maximal strain, and post-strain rest (recovery) sequences are obtained from the "true mid-sagittal" plane defined by a 3D pelvic coordinate system. The primary outcome is the mechanism of failure (apical descent versus anterior vaginal wall elongation). Secondary outcomes include displacement of the vaginal apex and perineal body and elongation of the anterior wall, posterior wall, perimeter, and introitus of the vagina between (1) rest and strain and (2) rest and recovery. RESULTS: Recruitment and MRI trials of 94 participants were completed by May 2018. CONCLUSIONS: Methods papers which detail studies designed to evaluate anatomic outcomes of prolapse surgeries are few. We describe a systematic, standardized approach to define and quantitatively assess mechanisms of anatomic failure following prolapse repair. This study will provide a better understanding of how apical prolapse repairs fail anatomically.

Evidence based survey of the distribution volume of ethanol: Comparison of empirically determined values with anthropometric measures.

The Widmark equation is commonly used when blood alcohol calculations are required in forensic and legal medicine, such as in road-traffic cases and alcohol-related deaths. An important biological variable in this connection is the volume of distribution (Vd) of ethanol, which is commonly referred to as the rho-factor. Although a person's Vd can be determined empirically through controlled drinking experiments, this approach is not very practical in reality. For this reason, a number of anthropometric equations have been developed that utilize sex, age, height and weight to estimate the person's total body water (TBW) and hence Vd of ethanol. To date, there are not any studies that compare Vd derived from anthropometric data with robust values measured empirically. From the literature we compiled information about the Vd of ethanol from drinking studies with 173 Caucasian males and 63 Caucasian females from Western Europe. These empirically derived values of Vd were then compared with estimates derived from various anthropometric equations. In males the Watson, Watson and Batt regression equation involving age, height and weight gave the most accurate results (bias was 0.00L/kg) and 95% range ±0.13L/kg. The equation derived by Forrest, which took into consideration a person's body mass index (BMI), gave the best estimates of Vd for females; mean bias -0.01L/kg and range ±0.15L/kg.

Concentrations of drugs determined in blood samples collected from suspected drugged drivers in England and Wales.

This communication reports the blood concentrations of alcohol and drugs from 376 cases of alleged driving under the influence of drugs analysed at the Forensic Science Service Chorley and London laboratories between February 2010 and March 2011. The samples were analysed for alcohol, amphetamine, benzodiazepines, cocaine, MDMA, opiates, γ-hydroxybutyrate (GHB), ketamine, methadone and methylmethcathinone (the 4-isomer of which is known as mephedrone). The results were interpreted with respect to the number and type of drugs of abuse detected and the concentrations measured. Alcohol was quantified in 113 cases (30%), and of these a level in excess of the prescribed UK limit for driving of 80 mg% was present in 90 cases. In 80 cases, only the concentration of alcohol was measured, the concentrations of both drugs and alcohol were measured in 33 cases. In the remaining 263 cases, only the concentrations of relevant drugs of abuse were measured. The most common drug of abuse quantified was cocaine which was detected in 92 cases, either as the active drug or as its major metabolite benzoylecgonine, followed by diazepam which was quantified in 76 cases. Concentrations of some new drugs, and drugs rarely reported in driving under the influence cases are also presented.

Model cortical association fields account for the time course and dependence on target complexity of human contour perception.

Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas) distributed among groups of randomly rotated fragments (clutter). The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms), followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least [Formula: see text] ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas.

Epidemiological investigation of bovine ephemeral Fever outbreaks in Israel.

Outbreaks of bovine ephemeral fever (BEF) occurred in Israel in 1990, 1999, and 2004. The main patterns of BEF spread were similar in the 1990 and in 1999 epidemics, and the BEF virus was probably carried in vectors transported by air streams across the Rift Valley and the Red Sea. In the 2004 outbreak, the primary focus of the disease was the southern Mediterranean coastal plain and the disease agent was apparently brought by infected mosquitoes carried from their breeding site in the Nile Delta by the south-western winds. The disease broke out under optimal ecological conditions, among a vulnerable cattle population and spread rapidly; it showed essentially a spring-summer herd incidence and terminated soon after the night average ambient temperature fell below 16 degrees C in late autumn. The herd incidence of the disease reached 78.4%, 97.7%, and 100% in 1990, 1999, and 2004, respectively. The highest herd incidence, morbidity, and case fatality rates were noted in dairy cattle herds in the Jordan Valley, with morbidity of 20%, 38.6%, and 22.2%, and case fatality rate among affected animals of 2%, 8.6%, and 5.4% in 1990, 1999, and 2004, respectively. The average sero-positivity to BEF in 1999 was 39.5%, which matched the morbidity rate. Comparison among the various age groups showed that the lowest morbidity rates were observed in the youngest age group, that is, heifers up to 1 year, with 3.2%, 3.6%, and 4.2% in 1990, 1999, and 2004, respectively. In heifers from 1 year to calving, the morbidity rates were 13.8%, 14.9%, and 28%, respectively, in first calvers 30.8%, 31.6%, and 28.3%, respectively, and in cows 34.3%, 35.7%, and 27.2%, respectively. All affected cattle were over the age of 3 months. It is hypothesized that mosquitoes and not Culicoides spp. are the vectors of the BEF virus in Israel.

Density-dependence of functional development in spiking cortical networks grown in vitro.

During development, the mammalian brain differentiates into specialized regions with distinct functional abilities. While many factors contribute to functional specialization, we explore the effect of neuronal density on the development of neuronal interactions in vitro. Two types of cortical networks, namely, dense and sparse with 50,000 and 12,500 total cells, respectively, are studied. Activation graphs that represent pairwise neuronal interactions are constructed using a competitive first response model. These graphs reveal that, during development in vitro, dense networks form activation connections earlier than sparse networks. Link entropy analysis of dense network activation graphs suggests that the majority of connections between electrodes are reciprocal in nature. Information theoretic measures reveal that early functional information interactions (among three electrodes) are synergetic in both dense and sparse networks. However, during later stages of development, previously synergetic relationships become primarily redundant in dense, but not in sparse networks. Large link entropy values in the activation graph are related to the domination of redundant ensembles in late stages of development in dense networks. Results demonstrate differences between dense and sparse networks in terms of informational groups, pairwise relationships, and activation graphs. These differences suggest that variations in cell density may result in different functional specializations of nervous system tissue in vivo.

Identification of functional information subgraphs in complex networks.

We present a general information theoretic approach for identifying functional subgraphs in complex networks. We show that the uncertainty in a variable can be written as a sum of information quantities, where each term is generated by successively conditioning mutual informations on new measured variables in a way analogous to a discrete differential calculus. The analogy to a Taylor series suggests efficient optimization algorithms for determining the state of a target variable in terms of functional groups of other nodes. We apply this methodology to electrophysiological recordings of cortical neuronal networks grown in vitro. Each cell's firing is generally explained by the activity of a few neurons. We identify these neuronal subgraphs in terms of their redundant or synergetic character and reconstruct neuronal circuits that account for the state of target cells.

Spontaneous coordinated activity in cultured networks: analysis of multiple ignition sites, primary circuits, and burst phase delay distributions.

All higher order central nervous systems exhibit spontaneous neural activity, though the purpose and mechanistic origin of such activity remains poorly understood. We quantitatively analyzed the ignition and spread of collective spontaneous electrophysiological activity in networks of cultured cortical neurons growing on microelectrode arrays. Leader neurons, which form a mono-synaptically connected primary circuit, and initiate a majority of network bursts were found to be a small subset of recorded neurons. Leader/follower firing delay times formed temporally stable positively skewed distributions. Blocking inhibitory synapses usually resulted in shorter delay times with reduced variance. These distributions are characterizations of general aspects of internal network dynamics and provide estimates of pair-wise synaptic distances. The resulting analysis produced specific quantitative constraints and insights into the activation patterns of collective neuronal activity in self-organized cortical networks, which may prove useful for models emulating spontaneously active systems.

Functional structure of cortical neuronal networks grown in vitro.

We apply an information-theoretic treatment of action potential time series measured with microelectrode arrays to estimate the connectivity of mammalian neuronal cell assemblies grown in vitro. We infer connectivity between two neurons via the measurement of the mutual information between their spike trains. In addition we measure higher-point multi-information between any two spike trains, conditional on the activity of a third cell, as a means to identify and distinguish classes of functional connectivity among three neurons. The use of a conditional three-cell measure removes some interpretational shortcomings of the pairwise mutual information and sheds light on the functional connectivity arrangements of any three cells. We analyze the resultant connectivity graphs in light of other complex networks and demonstrate that, despite their ex vivo development, the connectivity maps derived from cultured neural assemblies are similar to other biological networks and display nontrivial structure in clustering coefficient, network diameter, and assortative mixing. Specifically we show that these networks are weakly disassortative small-world graphs, which differ significantly in their structure from randomized graphs with the same degree. We expect our analysis to be useful in identifying the computational motifs of a wide variety of complex networks, derived from time series data.

A study of blood and urine alcohol concentrations in cases of alleged drug-facilitated sexual assault in the United Kingdom over a 3-year period.

This paper details the alcohol concentrations found in a selection of 1,014 cases of claimed drug-facilitated sexual assault analysed at The Forensic Science Service, London Laboratory between January 2000 and December 2002. Where appropriate, either a whole blood sample and/or a urine sample was analysed for alcohol, common drugs of abuse and potentially stupefying drugs. The samples were collected from a complainant within 12 h of an alleged incident in 391 of the 1014 cases analysed. Of these, the majority (81%) contained alcohol. The presence of alcohol itself was not surprising as most of the alleged incidents were associated with social situations such as at a public house, bar, night-club or party, where it is expected that alcohol would have been consumed. However, 233 (60%) of the 391 cases had a high back-calculated figure, where high is defined as greater than 150 milligrams per 100 millilitres (150 mg%). Some of these samples were also found to contain illicit drugs. This is the first paper to our knowledge which discusses in detail the significance of the alcohol concentrations found in cases of this type.

Toxicological findings in cases of alleged drug-facilitated sexual assault in the United Kingdom over a 3-year period.

This paper outlines the toxicology results from 1014 cases of claimed drug-facilitated sexual assault (DFSA) analysed at the Forensic Science Service, London Laboratory between January 2000 and December 2002. Where appropriate, either a whole blood sample and/or a urine sample was analysed for alcohol, common drugs of abuse and potentially stupefying drugs. The results were interpreted with respect to the number of drugs detected and an attempt was made to distinguish between voluntary and involuntary ingestion from information supplied. Alcohol (either alone or with an illicit and/or medicinal drug) was detected in 470 of all cases (46%). Illicit drugs were detected in 344 cases (34%), with cannabis being the most commonly detected (26% of cases), followed by cocaine (11%). In 21 cases (2%), a sedative or disinhibiting drug was detected which had not been admitted and could therefore be an instance of deliberate spiking. This included three cases in which complainants were allegedly given Ecstasy (MDMA) without their knowledge. Other drugs detected included gammahydroxybutyrate (GHB) and the benzodiazepine drugs diazepam and temazepam. Another nine cases (1%) involved the complainant being either given or forced to ingest pharmaceutical tablets or an illicit drug.