A count in the dark

The Census of Marine Life has succeeded in raising awareness about marine biodiversity, and contributed much to our understanding of what lives where. But the project has fallen short of its goal to estimate species abundance

Iridum-catalysed C–H Borylation of β-aryl-aminopropionic acids

Iridium-catalysed catalytic, regioselective C–H borylation of β-aryl-aminopropionic acid derivatives gives access to 3,5-functionalised protected β-aryl-aminopropionic acid boronates. The synthetic versatility of these new boronates is demonstrated through telescoped functionalisation reaction to give diverse building blocks for medicinal chemistry. The C-H borylation is also effective for dipeptide substrates. We have exemplified this methodology in the synthesis of a pan av integrin antagonist

Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified

Ablation lesions in Koch's triangle assessed by three-dimensional myocardial contrast echocardiography

BACKGROUND: Myocardial contrast echocardiography (MCE) allows visualization of radiofrequency (RF) ablation lesions in the left ventricle in an animal model. Aim: To test whether MCE allows visualization of RF and cryo ablation lesions in the human right atrium using three-dimensional echocardiography. METHODS: 18 patients underwent catheter ablation of a supraventricular tachycardia and were included in this prospective single-blind study. Twelve patients were ablated inside Koch's triangle and 6, who served as controls, outside this area. Three-dimensional echocardiography of Koch's triangle was performed before and after the ablation procedure in all patients, using respiration and ECG gated pullback of a 9 MHz ICE transducer, with and without continuous intravenous echocontrast infusion (SonoVue, Bracco). Two independent observers analyzed the data off-line. RESULTS: MCE identified ablation lesions as a low contrast area within the normal atrial myocardial tissue. Craters on the endocardial surface were seen in 10 (83%) patients after ablation. Lesions were identified in 11 out of 12 patients (92%). None of the control patients were recognized as having been ablated. The confidence score of the independent echo reviewer tended to be higher when the number of applications increased. CONCLUSIONS: 1. MCE allows direct visualization of ablation lesions in the human atrial myocardium. 2. Both RF and cryo energy lesions can be identified using MCE

An Epidemiology of Reported Needlestick Injuries among Health Care Workers in Sabah Health Government Facilities from 1999 – 2008

Introduction: Health care workers (HCWs) are at a high risk of occupational exposure to blood and body fluids of patients, resulting in possible transmission of blood- borne pathogens such as hepatitis B virus, hepatitis C virus and human immunodeficiency virus. The information on epidemiology of needle stick injury among HCWs is useful in recommending safer work practices. Materials and Methods: All cases of NSI reported within the period 1999 to 2008 from public health care facilities to the Sabah State Health Department were identified and analyzed accordingly. NSI is defined as any injury caused by hollow- bore needles or suture needles regardless of whether they are contaminated by blood/ body fluids or not. Health care worker is defined as Ministry of Health staff, trainees and health facilities support service workers. The software used for data analysis was SPSS version 15.0. Results: A total of 378 cases of NSI were notified after considering NSI definition. Majority of HCWs involved in NSI were from the younger age group (20-29 years old, 61.9%), female gender (76.1%), Kadazan Dusun Murut ethnicity (33.5%), nurses (41.1%) and those who had worked for more than one year (66.6%). The place of occurrence was mostly in Kota Kinabalu district (25.3%), hospital setting (90.5%) and in- patient wards (60.8%). Of this in– patient ward, 64.5% was in medical and surgical wards. About 60% of NSI occurred during the morning shift (7am-2pm) and mostly among the nurses (54.0%). The duration of seeking treatment from injury was mostly within 24 hours (83.3%). The mechanism of accident happens while performing disposal activity (35.3%) and followed by any clinical procedure involving needle (31.1%). Other mechanism of accident was recapping (17.6%) and jolted/ accident (16.1%). Of all the reported NSI, 53.1% involved intravenous procedure. The body part involved in injury was mostly the right finger (57.1%). Almost all the needles were contaminated with blood or body fluid (90.0%). Post injury management, 73.5% were given first aid treatment and 99.4% were not awarded any medical leave. Existing control measures for NSI were standard operating procedure (SOP) (47.9%), training (36.9%) and PPE (10.5%). Conclusion: NSI commonly occurred among nurses, those in the younger age group and those working in medical/ surgical ward. Working during morning shift seems to predispose nurses to NSI. Since most NSI occurred during intravenous procedure and disposal activity, safer work practices should be emphasized to minimize these injuries. Further study in hospital and primary health care setting will determine the details of contributing factors of NSI

A Model-based Approach for Fast Vehicle Detection in Continuously Streamed Urban LIDAR Point Clouds

Detection of vehicles in crowded 3-D urban scenes is a challenging problem in many computer vision related research fields, such as robot perception, autonomous driving, self-localization, and mapping. In this paper we present a model-based approach to solve the recognition problem from 3-D range data. In particular, we aim to detect and recognize vehicles from continuously streamed LIDAR point cloud sequences of a rotating multi-beam laser scanner. The end-to-end pipeline of our framework working on the raw streams of 3-D urban laser data consists of three steps 1) producing distinct groups of points which represent different urban objects 2) extracting reliable 3-D shape descriptors specifically designed for vehicles, considering the need for fast processing speed 3) executing binary classification on the extracted descriptors in order to perform vehicle detection. The extraction of our efficient shape descriptors provides a significant speedup with and increased detection accuracy compared to a PCA based 3-D bounding box fitting method used as baseline

The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Quantifying single nucleotide variant detection sensitivity in exome sequencing

BACKGROUND: The targeted capture and sequencing of genomic regions has rapidly demonstrated its utility in genetic studies. Inherent in this technology is considerable heterogeneity of target coverage and this is expected to systematically impact our sensitivity to detect genuine polymorphisms. To fully interpret the polymorphisms identified in a genetic study it is often essential to both detect polymorphisms and to understand where and with what probability real polymorphisms may have been missed. RESULTS: Using down-sampling of 30 deeply sequenced exomes and a set of gold-standard single nucleotide variant (SNV) genotype calls for each sample, we developed an empirical model relating the read depth at a polymorphic site to the probability of calling the correct genotype at that site. We find that measured sensitivity in SNV detection is substantially worse than that predicted from the naive expectation of sampling from a binomial. This calibrated model allows us to produce single nucleotide resolution SNV sensitivity estimates which can be merged to give summary sensitivity measures for any arbitrary partition of the target sequences (nucleotide, exon, gene, pathway, exome). These metrics are directly comparable between platforms and can be combined between samples to give “power estimates” for an entire study. We estimate a local read depth of 13X is required to detect the alleles and genotype of a heterozygous SNV 95% of the time, but only 3X for a homozygous SNV. At a mean on-target read depth of 20X, commonly used for rare disease exome sequencing studies, we predict 5–15% of heterozygous and 1–4% of homozygous SNVs in the targeted regions will be missed. CONCLUSIONS: Non-reference alleles in the heterozygote state have a high chance of being missed when commonly applied read coverage thresholds are used despite the widely held assumption that there is good polymorphism detection at these coverage levels. Such alleles are likely to be of functional importance in population based studies of rare diseases, somatic mutations in cancer and explaining the “missing heritability” of quantitative traits