Correlated many-body treatment of Breit interaction with application to cesium atomic properties and parity violation

Corrections from Breit interaction to basic properties of atomic 133Cs are determined in the framework of third-order relativistic many-body perturbation theory. The corrections to energies, hyperfine-structure constants, off-diagonal hyperfine 6S-7S amplitude, and electric-dipole matrix elements are tabulated. It is demonstrated that the Breit corrections to correlations are comparable to the Breit corrections at the Dirac-Hartree-Fock level. Modification of the parity-nonconserving (PNC) 6S-7S amplitude due to Breit interaction is also evaluated; the resulting weak charge of $^{133}$Cs shows no significant deviation from the prediction of the standard model of elementary particles. The neutron skin correction to the PNC amplitude is also estimated to be -0.2% with an error bound of 30% based on the analysis of recent experiments with antiprotonic atoms. The present work supplements publication [A. Derevianko, Phys. Rev. Lett. 85, 1618 (2000)] with a discussion of the formalism and provides additional numerical results and updated discussion of parity violation.Comment: 16 pages; 5 figs; submitted to Phys. Rev.

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

Digital image analysis using video microscopy of human-derived prostate cancer vs normal prostate organoids to assess migratory behavior on extracellular matrix proteins

The advent of perpetuating living organoids derived from patient tissue is a promising avenue for cancer research but is limited by difficulties with precise characterization. In this brief communication, we demonstrate via time-lapse imaging distinct phenotypes of prostate organoids derived from patient material– without confirmation of cellular identity. We show that organoids derived from histologically normal tissue more readily spread on a physiologic extracellular matrix (ECM) than on pathologic ECM (p<0.0001), while tumor-derived organoids spread equally on either substrate (p=0.2406). This study is an important proof-of-concept to defer precise characterization of organoids and still glean information into disease pathology

The Association between Mental Health and Violence among a Nationally Representative Sample of College Students from the United States

Objectives Recent violent attacks on college campuses in the United States have sparked discussions regarding the prevalence of psychiatric disorders and the perpetration of violence among college students. While previous studies have examined the potential association between mental health problems and violent behavior, the overall pattern of findings flowing from this literature remain mixed and no previous studies have examined such associations among college students. Methods The current study makes use of a nationally representative sample of 3,929 college students from the National Epidemiologic Study on Alcohol and Related Conditions (NESARC) to examine the prevalence of seven violent behaviors and 19 psychiatric disorder diagnoses tapping mood, anxiety, personality, and substance use disorders. Associations between individual and composite psychiatric disorder diagnoses and violent behaviors were also examined. Additional analyses were adjusted for the comorbidity of multiple psychiatric diagnoses. Results The results revealed that college students were less likely to have engaged in violent behavior relative to the non-student sample, but a substantial portion of college students had engaged in violent behavior. Age- and sex-standardized prevalence rates indicated that more than 21% of college students reported at least one violent act. In addition, more than 36% of college students had at least one diagnosable psychiatric disorder. Finally, the prevalence of one or more psychiatric disorders significantly increased the odds of violent behavior within the college student sample. Conclusions These findings indicate that violence and psychiatric disorders are prevalent on college campuses in the United States, though perhaps less so than in the general population. In addition, college students who have diagnosable psychiatric disorders are significantly more likely to engage in various forms of violent behavior

BioPhysConnectoR: Connecting Sequence Information and Biophysical Models

<p>Abstract</p> <p>Background</p> <p>One of the most challenging aspects of biomolecular systems is the understanding of the coevolution in and among the molecule(s).</p> <p>A complete, theoretical picture of the selective advantage, and thus a functional annotation, of (co-)mutations is still lacking. Using sequence-based and information theoretical inspired methods we can identify coevolving residues in proteins without understanding the underlying biophysical properties giving rise to such coevolutionary dynamics. Detailed (atomistic) simulations are prohibitively expensive. At the same time reduced molecular models are an efficient way to determine the reduced dynamics around the native state. The combination of sequence based approaches with such reduced models is therefore a promising approach to annotate evolutionary sequence changes.</p> <p>Results</p> <p>With the <monospace>R</monospace> package <monospace>BioPhysConnectoR</monospace> we provide a framework to connect the information theoretical domain of biomolecular sequences to biophysical properties of the encoded molecules - derived from reduced molecular models. To this end we have integrated several fragmented ideas into one single package ready to be used in connection with additional statistical routines in <monospace>R</monospace>. Additionally, the package leverages the power of modern multi-core architectures to reduce turn-around times in evolutionary and biomolecular design studies. Our package is a first step to achieve the above mentioned annotation of coevolution by reduced dynamics around the native state of proteins.</p> <p>Conclusions</p> <p><monospace>BioPhysConnectoR</monospace> is implemented as an <monospace>R</monospace> package and distributed under GPL 2 license. It allows for efficient and perfectly parallelized functional annotation of coevolution found at the sequence level.</p

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

We All Know How, Don’t We? On the Role of Scrum in IT-Offshoring

Part 2: Creating Value through Software DevelopmentInternational audienceOffshoring in the IT-industry involves dual interactions between a mother company and an external supplier, often viewed with an implicit perspective from the mother company. This article review general off shoring and IT offshoring literature, focusing on the proliferation of a globally available set of routines; Scrum and Agile. Two cases are studied; a small company and short process and a large mother company with a long process. The interactions of the set ups shows that global concepts like Scrum and Agile are far from a common platform. The “well known” concepts are locally shaped and the enterprises have mixed experiences

Impact of Atomic Parity Violation Measurements on Precision Electroweak Physics

The impact of atomic parity violation experiments on determination of the weak mixing parameter $\sin^2 \theta$ and the Peskin-Takeuchi parameters $S$ and $T$ is reassessed in the light of recent electroweak measurements at LEP, SLAC, and Fermilab. Since the weak charge $Q_W$ provides unique information on $S$, its determination with a factor of four better accuracy than present levels can have a noticeable effect on global fits. However, the measurement of $\Delta Q_W / Q_W$ for two different isotopes provides primarily information on $\sin^2 \theta$. To specify this quantity to an accuracy of $\pm 0.0004$, comparable to that now provided by other electroweak experiments, one would have to determine $\Delta Q_W/Q_W$ in cesium to about 0.1\% of its value, with comparable demands for other nuclei. The relative merits of absolute measurements of $Q_W$ and isotope ratios for discovering effects of new gauge bosons are noted briefly.Comment: 11 pages, latex, 1 uuencoded figure sent separatel