Distance Properties of Short LDPC Codes and their Impact on the BP, ML and Near-ML Decoding Performance

Parameters of LDPC codes, such as minimum distance, stopping distance, stopping redundancy, girth of the Tanner graph, and their influence on the frame error rate performance of the BP, ML and near-ML decoding over a BEC and an AWGN channel are studied. Both random and structured LDPC codes are considered. In particular, the BP decoding is applied to the code parity-check matrices with an increasing number of redundant rows, and the convergence of the performance to that of the ML decoding is analyzed. A comparison of the simulated BP, ML, and near-ML performance with the improved theoretical bounds on the error probability based on the exact weight spectrum coefficients and the exact stopping size spectrum coefficients is presented. It is observed that decoding performance very close to the ML decoding performance can be achieved with a relatively small number of redundant rows for some codes, for both the BEC and the AWGN channels

Comparative efficacy of ultrasound-guided and stimulating popliteal-sciatic perineural catheters for postoperative analgesia

Perineural catheter insertion using ultrasound guidance alone is a relatively new approach. Previous studies have shown that ultrasound-guided catheters take less time to place with high placement success rates, but the analgesic efficacy compared with the established stimulating catheter technique remains unknown. We tested the hypothesis that popliteal-sciatic perineural catheter insertion relying exclusively on ultrasound guidance results in superior postoperative analgesia compared with stimulating catheters. Preoperatively, subjects receiving a popliteal-sciatic perineural catheter for foot or ankle surgery were assigned randomly to either ultrasound guidance (bolus via needle with non-stimulating catheter insertion) or electrical stimulation (bolus via catheter). We used 1.5% mepivacaine 40 mL for the primary surgical nerve block and 0.2% ropivacaine (basal 8 mL·hr−1; bolus 4 mL; 30 min lockout) was infused postoperatively. The primary outcome was average surgical pain on postoperative day one. Forty of the 80 subjects enrolled were randomized to each treatment group. One of 40 subjects (2.5%) in the ultrasound group failed catheter placement per protocol vs nine of 40 (22.5%) in the stimulating catheter group (P = 0.014). The difference in procedural duration (mean [95% confidence interval (CI)]) was −6.48 (−9.90 - −3.05) min, with ultrasound requiring 7.0 (4.0-14.1) min vs stimulation requiring 11.0 (5.0-30.0) min (P < 0.001). The average pain scores of subjects who provided data on postoperative day one were somewhat higher for the 33 ultrasound subjects than for the 26 stimulation subjects (5.0 [1.0-7.8] vs 3.0 [0.0-6.5], respectively; P = 0.032), a difference (mean [95%CI]) of 1.37 (0.03-2.71). For popliteal-sciatic perineural catheters, ultrasound guidance takes less time and results in fewer placement failures compared with stimulating catheters. However, analgesia may be mildly improved with successfully placed stimulating catheters. Clinical trial registration number NCT00876681

Professionalism and Evolving Concepts of Quality

For much of the twentieth century, quality of care was defined specifically in terms of physician characteristics and behaviors. High-quality physicians were well trained, knowledgeable, skillful, and compassionate. More recently, quality of care has been defined in terms of systems of care. High-quality organizations develop and adopt practices to reduce adverse events and optimize outcomes. This essay discusses this transformation from physician-based to organization-based concepts of quality and the consequences for patient care and medical professionalism

Investigation into the annotation of protocol sequencing steps in the sequence read archive

BACKGROUND: The workflow for the production of high-throughput sequencing data from nucleic acid samples is complex. There are a series of protocol steps to be followed in the preparation of samples for next-generation sequencing. The quantification of bias in a number of protocol steps, namely DNA fractionation, blunting, phosphorylation, adapter ligation and library enrichment, remains to be determined. RESULTS: We examined the experimental metadata of the public repository Sequence Read Archive (SRA) in order to ascertain the level of annotation of important sequencing steps in submissions to the database. Using SQL relational database queries (using the SRAdb SQLite database generated by the Bioconductor consortium) to search for keywords commonly occurring in key preparatory protocol steps partitioned over studies, we found that 7.10%, 5.84% and 7.57% of all records (fragmentation, ligation and enrichment, respectively), had at least one keyword corresponding to one of the three protocol steps. Only 4.06% of all records, partitioned over studies, had keywords for all three steps in the protocol (5.58% of all SRA records). CONCLUSIONS: The current level of annotation in the SRA inhibits systematic studies of bias due to these protocol steps. Downstream from this, meta-analyses and comparative studies based on these data will have a source of bias that cannot be quantified at present

Body odor quality predicts behavioral attractiveness in humans

Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits

From gene-discovery to gene-tailored clinical management: 25 years of research in channelopathies and cardiomyopathies.

In the early nineties, few years before the birth of Europace, the clinical and scientific world of familial arrhythmogenic conditions was revolutionized by the identification of the first disease-causing genes. The explosion of genetic studies over a 15-year period led to the discovery of major disease-causing genes in practically all channelopathies and cardiomyopathies, bringing insight into the pathophysiological mechanisms of these conditions. The birth of next generation sequencing allowed a further step forward and other significant genes, as CALM1-3 in channelopathies and FLN C and TTN in cardiomyopathies were identified. Genotype-phenotype studies allowed the implementation of the genetic results in diagnosis, risk stratification, and therapeutic management with a different level of evidence in different arrhythmogenic conditions. The influence of common genetic variants, i.e. SNPs, on disease manifestation was proved in mid-twenties, and in the last 10 years with the advent of genome-wide association studies performed in familial arrhythmogenic diseases, the concept of polygenic risk score has been consolidated. Now, we are at the start of another amazing phase, i.e. the initiation of first gene therapy clinical trials

Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse

High Incidence of Unplanned Pregnancy after Antiretroviral Therapy Initiation: Findings from a Prospective Cohort Study in South Africa

Increased fertility rates in HIV-infected women receiving antiretroviral therapy (ART) have been attributed to improved immunological function; it is unknown to what extent the rise in pregnancy rates is due to unintended pregnancies.Non-pregnant women ages 18-35 from four public-sector ART clinics in Johannesburg, South Africa, were enrolled into a prospective cohort and followed from August 2009-March 2011. Fertility intentions, contraception and pregnancy status were measured longitudinally at participants' routine ART clinic visits.Of the 850 women enrolled, 822 (97%) had at least one follow-up visit and contributed 745.2 person-years (PY) at-risk for incident pregnancy. Overall, 170 pregnancies were detected in 161 women (incidence rate [IR]: 21.6/100 PY [95% confidence interval (CI): 18.5-25.2]). Of the 170 pregnancies, 105 (62%) were unplanned. Unmet need for contraception was 50% higher in women initiating ART in the past year as compared to women on ART>1 year (prevalence ratio 1.5 [95% CI: 1.1-2.0]); by two years post-ART initiation, nearly one quarter of women had at least one unplanned pregnancy. Cumulative incidence of pregnancy was equally high among recent ART initiators and ART experienced participants: 23.9% [95% CI: 16.4-34.1], 15.9% [12.0-20.8], and 21.0% [16.8-26.1] for women on ART 0-1 yr, >1 yr-2 yrs, and >2 yrs respectively (log-rank, p = 0.54). Eight hormonal contraceptive failures were detected [IR: 4.4 [95% CI: 2.2-8.9], 7/8 among women using injectable methods. Overall 47% (80/170) of pregnancies were not carried to term.Rates of unintended pregnancies among women on ART are high, including women recently initiating ART with lower CD4 counts and higher viral loads. A substantial burden of pregnancy loss was observed. Integration of contraceptive services and counselling into ART care is necessary to reduce maternal and child health risks related to mistimed and unwanted pregnancies. Further research into injectable contraceptive failures on ART is warranted

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome