Tunneling into Nonequilibrium Luttinger Liquid with Impurity

We evaluate tunneling rates into/from a voltage biased quantum wire containing weak backscattering defect. Interacting electrons in such a wire form a true nonequilibrium state of the Luttinger liquid (LL). This state is created due to inelastic electron backscattering leading to the emission of nonequilibrium plasmons with typical frequency $\hbar \omega \leq U$. The tunneling rates are split into two edges. The tunneling exponent at the Fermi edge is positive and equals that of the equilibrium LL, while the exponent at the side edge $E_F-U$ is negative if Coulomb interaction is not too strong.Comment: 4+ pages, 5 figure

Safety, Quality, and Acceptability of Contraceptive Subdermal Implant Provision by Community Health Extension Workers Versus Nurses and Midwives in Nigeria: Protocol for a Quasi-Experimental, Noninferiority Study.

BACKGROUND: As part of its Family Planning 2020 commitment, the Nigerian government is aiming for a contraceptive prevalence rate of 36% by 2018, and in 2014, approved a policy to allow community health extension workers (CHEWs), in addition to doctors, nurses, and midwives, to provide contraceptive subdermal implants. There is a lack of rigorous evidence on the safety of long-acting reversible contraceptive provision, such as implants, among lower cadres of health providers. OBJECTIVE: This study aimed to compare implant provision by CHEWs versus nurses and midwives up to 14 days post insertion. METHODS: The quasi-experimental, noninferiority study will take place in public sector facilities in Kaduna and Ondo States. In each state, we will select 60 facilities, and from these, we will select a total of 30 nurses and midwives and 30 CHEWs to participate. Selected providers will be trained to provide implant services. Once trained, providers will recruit a minimum of 8125 women aged between 18 and 49 years who request and are eligible for an implant, following comprehensive family planning counseling. During implant insertion, providers will record data about the process and any adverse events, and 14 days post insertion, providers will ask 4410 clients about adverse events arising from the implant. Supervisors will observe 792 implant insertions to assess service provision quality and ask clients about their satisfaction with the procedure. We will conclude noninferiority if the CI for the difference in the proportion of adverse events between CHEWs and nurses and midwives on the day of insertion or 14 days post insertion lies to the right of -2%. RESULTS: In September and October 2015, we trained 60 CHEWs and a total of 60 nurses and midwives from 12 local government areas (LGAs) in Kaduna and 23 LGAs in Ondo. Recruitment took place between November 2015 and December 2016. Data analysis is being finalized, and results are expected in March 2018. CONCLUSIONS: The strength of this study is having a standard care (nurse and midwife provision) group with which CHEW provision can be compared. The intervention builds on existing training and supervision procedures, which increases the sustainability and scalability of CHEW implant provision. Important limitations include the lack of randomization due to nurses and midwives in Nigeria working in separate types of health care facilities compared with CHEWs, and that providers self-assess their own practices. It is unfeasible to observe all procedures independently, and observation may change practice. Although providers will be trained to conduct implant removals, the study time will be too short to reach the sample size required to make noninferiority comparisons for removals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03088722; https://clinicaltrials.gov/ct2/show/NCT03088722 (Archived by WebCite at http://www.webcitation.org/6xIHImWvu)

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.This work was supported by the following grants: NHGRIU54HG003273 to R.A.G; EU Marie Curie ITN #215781 “Evonet” to M.A.; a Wellcome Trust Value in People (VIP) award to C.B. and Wellcome Trust graduate studentship WT089615MA to J.E.G; Marine rhythms of Life” of the University of Vienna, an FWF (http://www.fwf.ac.at/) START award (#AY0041321) and HFSP (http://www.hfsp.org/) research grant (#RGY0082/2010) to KT-­‐R; MFPL Vienna International PostDoctoral Program for Molecular Life Sciences (funded by Austrian Ministry of Science and Research and City of Vienna, Cultural Department -­‐Science and Research to T.K; Direct Grant (4053034) of the Chinese University of Hong Kong to J.H.L.H.; NHGRI HG004164 to G.M.; Danish Research Agency (FNU), Carlsberg Foundation, and Lundbeck Foundation to C.J.P.G.; U.S. National Institutes of Health R01AI55624 to J.H.W.; Royal Society University Research fellowship to F.M.J.; P.D.E. was supported by the BBSRC via the Babraham Institute;This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pbio.100200

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Complete genome characterization of two wild-type measles viruses from Vietnamese infants during the 2014 outbreak

A large measles virus outbreak occurred across Vietnam in 2014. We identified and obtained complete measles virus genomes in stool samples collected from two diarrheal pediatric patients in Dong Thap Province. These are the first complete genome sequences of circulating measles viruses in Vietnam during the 2014 measles outbreak

Genome sequences of a novel Vietnamese bat bunyavirus

To document the viral zoonotic risks in Vietnam, fecal samples were systematically collected from a number of mammals in southern Vietnam and subjected to agnostic deep sequencing. We describe here novel Vietnamese bunyavirus sequences detected in bat feces. The complete L and S segments from 14 viruses were determined

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke