An adaptive space-time phase field formulation for dynamic fracture of brittle shells based on LR NURBS

We present an adaptive space-time phase field formulation for dynamic fracture of brittle shells. Their deformation is characterized by the Kirchhoff–Love thin shell theory using a curvilinear surface description. All kinematical objects are defined on the shell’s mid-plane. The evolution equation for the phase field is determined by the minimization of an energy functional based on Griffith’s theory of brittle fracture. Membrane and bending contributions to the fracture process are modeled separately and a thickness integration is established for the latter. The coupled system consists of two nonlinear fourth-order PDEs and all quantities are defined on an evolving two-dimensional manifold. Since the weak form requires C1-continuity, isogeometric shape functions are used. The mesh is adaptively refined based on the phase field using Locally Refinable (LR) NURBS. Time is discretized based on a generalized-α method using adaptive time-stepping, and the discretized coupled system is solved with a monolithic Newton–Raphson scheme. The interaction between surface deformation and crack evolution is demonstrated by several numerical examples showing dynamic crack propagation and branching

Early Pregnancy-Associated Plasma Protein A Concentrations are Associated with Third Trimester Insulin Sensitivity

Context: First or early second trimester pregnancy-associated plasma protein-A (PAPP-A) concentrations have previously been shown to be lower in women who subsequently develop gestational diabetes (GDM) and gestational hypertension. Objective: We therefore sought to investigate why circulating PAPP-A concentrations are related to the subsequent risk of GDM and gestational hypertension. Patients, Design and Setting: We measured serum PAPP-A concentrations around week 15 of pregnancy and related these to indices derived from week 28 oral glucose tolerance tests (OGTT) and blood pressures across pregnancy in the Cambridge Baby Growth Study cohort. Results: Increased PAPP-A concentrations were associated with reduced GDM risk (odds ratio 0.623 (0.453, 0.856), P=3.5 x 10$^{-3}$, n=777) and reduced mean arterial blood pressures (β=-0.202– -0.177, P=1.7–6.9 x 10$^{-3}$, n=347–355). They were also negatively associated with week 28 fasting (β=-0.149, P=6.6 x 10$^{-4}$, n=777) and 60 minute (β=-0.188, P=1.5 x 10-5, n=777) OGTT glucose concentrations. These associations were underpinned by the strong associations between increased week 15 PAPP-A concentrations and decreased week 28 insulin resistance (HOMA IR: β=-0.319, P=1.7 x 10$^{-13}$, n=768), and increased insulin secretion relative to insulin sensitivity (insulin disposition index: β=0.202, P=6.5 x 10$^{-6}$, n=731). Conclusions: These results suggest that links between PAPP-A concentrations in early pregnancy and subsequent glucose concentrations and blood pressures may be mediated by changes in insulin sensitivity (and secretion).Most of the endocrine measurements described in this study were funded by the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, U.K.) (RG1644). Core funding for the Cambridge Baby Growth Study has come from the Medical Research Council (7500001180); European Union Framework 5 (QLK4-1999-01422); the Mothercare Charitable Foundation (RG54608); Newlife Foundation for Disabled Children (07/20) and the World Cancer Research Fund International (2004/03). In addition, there has been support from National Institute for Health Research Cambridge Biomedical Research Centre

RepSeq-A database of amino acid repeats present in lower eukaryotic pathogens

BACKGROUND Amino acid repeat-containing proteins have a broad range of functions and their identification is of relevance to many experimental biologists. In human-infective protozoan parasites (such as the Kinetoplastid and Plasmodium species), they are implicated in immune evasion and have been shown to influence virulence and pathogenicity. RepSeq http://repseq.gugbe.com is a new database of amino acid repeat-containing proteins found in lower eukaryotic pathogens. The RepSeq database is accessed via a web-based application which also provides links to related online tools and databases for further analyses. RESULTS The RepSeq algorithm typically identifies more than 98% of repeat-containing proteins and is capable of identifying both perfect and mismatch repeats. The proportion of proteins that contain repeat elements varies greatly between different families and even species (3 - 35% of the total protein content). The most common motif type is the Sequence Repeat Region (SRR) - a repeated motif containing multiple different amino acid types. Proteins containing Single Amino Acid Repeats (SAARs) and Di-Peptide Repeats (DPRs) typically account for 0.5 - 1.0% of the total protein number. Notable exceptions are P. falciparum and D. discoideum, in which 33.67% and 34.28% respectively of the predicted proteomes consist of repeat-containing proteins. These numbers are due to large insertions of low complexity single and multi-codon repeat regions. CONCLUSION The RepSeq database provides a repository for repeat-containing proteins found in parasitic protozoa. The database allows for both individual and cross-species proteome analyses and also allows users to upload sequences of interest for analysis by the RepSeq algorithm. Identification of repeat-containing proteins provides researchers with a defined subset of proteins which can be analysed by expression profiling and functional characterisation, thereby facilitating study of pathogenicity and virulence factors in the parasitic protozoa. While primarily designed for kinetoplastid work, the RepSeq algorithm and database retain full functionality when used to analyse other species

Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants.

STUDY QUESTION: What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8-14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW? SUMMARY ANSWER: Intrauterine paracetamol exposure during 8-14 weeks of gestation is associated with shorter AGD from birth to 24 months of age. WHAT IS ALREADY KNOWN: The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism. STUDY DESIGN, SIZE, DURATION: Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHOD: Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8-14 weeks. AGD measurements were available for 434 male infants. MAIN RESULTS AND THE ROLE OF CHANCE: Paracetamol exposure during 8-14 weeks of gestation, but not any other period, was associated with shorter AGD (by 0.27 SD, 95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was independent of body size. Paracetamol exposure was not related to penile length or testicular descent. LIMITATIONS, REASONS FOR CAUTION: Confounding by other drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not fully representative of pregnant women in the UK, particularly in terms of maternal ethnicity and smoking prevalence. There is likely to have been misclassification of paracetamol exposure due to recall error. WIDER IMPLICATIONS OF THE FINDINGS: Our observational findings support experimental evidence that intrauterine paracetamol exposure during the MPW may adversely affect male reproductive development. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation for Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead Johnson Nutrition, and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. The authors declare no conflict of interest.European Union (Framework V programme), World Cancer Research Fund International, Medical Research Council (UK), Newlife Foundation for Disabled Children, Evelyn Trust, Mothercare Group Foundation, Mead Johnson Nutrition, National Institute for Health Research Cambridge Comprehensive Biomedical Research CentreThis is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Oxford University Press

Comparative study of nonlinear properties of EEG signals of a normal person and an epileptic patient

Background: Investigation of the functioning of the brain in living systems has been a major effort amongst scientists and medical practitioners. Amongst the various disorder of the brain, epilepsy has drawn the most attention because this disorder can affect the quality of life of a person. In this paper we have reinvestigated the EEGs for normal and epileptic patients using surrogate analysis, probability distribution function and Hurst exponent. Results: Using random shuffled surrogate analysis, we have obtained some of the nonlinear features that was obtained by Andrzejak \textit{et al.} [Phys Rev E 2001, 64:061907], for the epileptic patients during seizure. Probability distribution function shows that the activity of an epileptic brain is nongaussian in nature. Hurst exponent has been shown to be useful to characterize a normal and an epileptic brain and it shows that the epileptic brain is long term anticorrelated whereas, the normal brain is more or less stochastic. Among all the techniques, used here, Hurst exponent is found very useful for characterization different cases. Conclusions: In this article, differences in characteristics for normal subjects with eyes open and closed, epileptic subjects during seizure and seizure free intervals have been shown mainly using Hurst exponent. The H shows that the brain activity of a normal man is uncorrelated in nature whereas, epileptic brain activity shows long range anticorrelation.Comment: Keywords:EEG, epilepsy, Correlation dimension, Surrogate analysis, Hurst exponent. 9 page

Percutaneous coronary intervention in asians- are there differences in clinical outcome?

<p>Abstract</p> <p>Background</p> <p>Ethnic differences in clinical outcome after percutaneous coronary intervention (PCI) have been reported. Data within different Asian subpopulations is scarce. We aim to explore the differences in clinical profile and outcome between Chinese, Malay and Indian Asian patients who undergo PCI for coronary artery disease (CAD).</p> <p>Methods</p> <p>A prospective registry of consecutive patients undergoing PCI from January 2002 to December 2007 at a tertiary care center was analyzed. Primary endpoint was major adverse cardiovascular events (MACE) of myocardial infarction (MI), repeat revascularization and all-cause death at six months.</p> <p>Results</p> <p>7889 patients underwent PCI; 7544 (96%) patients completed follow-up and were included in the analysis (79% males with mean age of 59 years ± 11). There were 5130 (68%) Chinese, 1056 (14%) Malays and 1001 (13.3%) Indian patients. The remaining 357 (4.7%) patients from other minority ethnic groups were excluded from the analysis. The primary end-point occurred in 684 (9.1%) patients at six months. Indians had the highest rates of six month MACE compared to Chinese and Malays (Indians 12% vs. Chinese 8.2% vs. Malays 10.7%; OR 1.55 95%CI 1.24-1.93, p < 0.001). This was contributed by increased rates of MI (Indians 1.9% vs. Chinese 0.9% vs. Malays 1.3%; OR 4.49 95%CI 1.91-10.56 p = 0.001), repeat revascularization (Indians 6.5% vs. Chinese 4.1% vs. Malays 5.1%; OR 1.64 95%CI 1.22-2.21 p = 0.0012) and death (Indians 11.4% vs. Chinese 7.6% vs. Malays 9.9%; OR 1.65 95%CI 1.23-2.20 p = 0.001) amongst Indian patients.</p> <p>Conclusion</p> <p>These data indicate that ethnic variations in clinical outcome exist following PCI. In particular, Indian patients have higher six month event rates compared to Chinese and Malays. Future studies are warranted to elucidate the underlying mechanisms behind these variations.</p

Melody, an ENU mutation in Caspase 3, alters the catalytic cysteine residue and causes sensorineural hearing loss in mice

Progeny from the Harwell N-ethyl-N-nitrosourea (ENU) recessive mutagenesis screen were assessed for auditory defects. A pedigree was identified with multiple progeny lacking response to a clickbox test. Auditory brainstem response (ABR) analysis showed that homozygous mutant mice were profoundly deaf and the line was named melody. We subsequently mapped this mutation to a 6-Mb region on chromosome 8 and identified a point mutation in melody that results in a C163S substitution in the catalytic site of Caspase 3, a cysteine protease involved in apoptosis. Melody fails to complement a null Caspase-3 mutant. Scanning electron microscopy (SEM) has revealed disorganised sensory hair cells and hair cell loss. Histological analysis of melody has shown degeneration of spiral ganglion cells in homozygote mice, with a gradient of severity from apical to basal turns. Melody heterozygotes also show evidence of loss of spiral ganglion neurons, suggesting that the C163S mutation may show dominant negative effects by binding and sequestering proteins at the active site. The melody line provides a new model for studying the role of Caspase 3 in deafness and a number of other pathways and systems

Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

$\textbf{Aim}$ We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy. $\textbf{Methods}$ In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios). $\textbf{Results}$ Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10$^{-4}$) and INS rs2585 (P-value = 7 × 10$^{-4}$), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10$^{-3}$) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10$^{-3}$), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10$^{-6}$, n = 981, r$^{2}$ = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10$^{-3}$, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10$^{-8}$, rs2585, P-value = 3.6 × 10$^{-5}$) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10$^{-8}$), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2). $\textbf{Conclusion}$ This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.This work was supported by the Evelyn Trust (grant number EW9035322); Diabetes UK (grant number 11/0004241); the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (grant number RG1644); the Medical Research Council (grant number 7500001180); European Union Framework 5 (grant number QLK4-1999-01422); the Mothercare Charitable Foundation (grant number RG54608); Newlife Foundation for Disabled Children (grant number 07/20); the World Cancer Research Fund International (grant number 2004/03); and the National Institute for Health Research Cambridge Biomedical Research Centre. The HAPO Study work was supported by the National Institutes of Health (grant numbers HD-34242, HD-34243, HG-004415, and CA-141688); the Institutes of Health Research–INMD (grant number 110791); and by the American Diabetes Association