Geometry can provide long-range mechanical guidance for embryogenesis

Downstream of gene expression, effectors such as the actomyosin contractile machinery drive embryo morphogenesis. During $\textit{Drosophila}$ embryonic axis extension, actomyosin has a specific planar-polarised organisation, which is responsible for oriented cell intercalation. In addition to these cell rearrangements, cell shape changes also contribute to tissue deformation. While cell-autonomous dynamics are well described, understanding the tissue-scale behaviour challenges us to solve the corresponding mechanical problem at the scale of the whole embryo, since mechanical resistance of all neighbouring epithelia will feedback on individual cells. Here we propose a novel numerical approach to compute the whole-embryo dynamics of the actomyosin-rich apical epithelial surface. We input in the model specific patterns of actomyosin contractility, such as the planar-polarisation of actomyosin in defined ventro-lateral regions of the embryo. Tissue strain rates and displacements are then predicted over the whole embryo surface according to the global balance of stresses and the material behaviour of the epithelium. Epithelia are modelled using a rheological law that relates the rate of deformation to the local stresses and actomyosin anisotropic contractility. Predicted flow patterns are consistent with the cell flows observed when imaging $\textit{Drosophila}$ axis extension $\textit{in toto}$, using light sheet microscopy. The agreement between model and experimental data indicates that the anisotropic contractility of planar-polarised actomyosin in the ventro-lateral germband tissue can directly cause the tissue-scale deformations of the whole embryo. The three-dimensional mechanical balance is dependent on the geometry of the embryo, whose curved surface is taken into account in the simulations. Importantly, we find that to reproduce experimental flows, the model requires the presence of the cephalic furrow, a fold located anteriorly of the extending tissues. The presence of this geometric feature, through the global mechanical balance, guides the flow and orients extension towards the posterior end.All the computations presented in this paper were performed using the Cactus platform of the CIMENT infrastructure (https://ciment.ujf-grenoble.fr), which is supported by Région Rhône-Alpes (GRANT CPER07-13, http://en.rhonealpes.fr/370-the-quality-of-the-research.htm). MD, PS and JE thank Région Rhône-Alpes (CIBLE and IXXI, all authors; CMIRA, JE only), MD thanks Malian government and French embassy in Bamako "Bourse d’Excellences" programme, LIPHY and LJK (CNRS and Univ. Grenoble Alpes) for financial support. MD and JE thank ANR-12-BS09-0020-01 "Transmig" and ANR-11-LABX-0030 "Tec21", and are members of GDR 3570 MecaBio and GDR 3070 CellTiss of CNRS. JE thanks the Isaac Newton Institute for Mathematical Sciences for its hospitality during the programme "Coupling Geometric PDEs with Physics for Cell Morphology, Motility and Pattern Formation" supported by EPSRC Grant Number EP/K032208/1. CML, GBB and BS were supported by Wellcome Trust Investigator Award 099234/Z/12/Z to BS

Optimising intraperitoneal gentamicin dosing in peritoneal dialysis patients with peritonitis (GIPD) study

Background: Antibiotics are preferentially delivered via the peritoneal route to treat peritonitis, a major complication of peritoneal dialysis (PD), so that maximal concentrations are delivered at the site of infection. However, drugs administered intraperitoneally can be absorbed into the systemic circulation. Drugs excreted by the kidneys accumulate in PD patients, increasing the risk of toxicity. The aim of this study is to examine a model of gentamicin pharmacokinetics and to develop an intraperitoneal drug dosing regime that maximises bacterial killing and minimises toxicity

Generating SQL queries from visual specifications

Abstract: Structured Query Language (SQL) is the most widely used declarative language for accessing relational databases, and an essential topic in introductory database courses in higher learning institutions. Despite the intuitiveness of SQL, formulating and comprehending written queries can be confusing, especially for undergraduate students. One major reason for this is that the simple syntax of SQL is often misleading and hard to comprehend. A number of tools have been developed to aid the comprehension of queries and improve the mental models of students concerning the underlying logic of SQL. Some of these tools employed visualisation and animation in their approach to aid the comprehension of SQL. This paper presents an interactive comprehension aid based on visualisation, specifically designed to support the SQL SELECT statement, an area identified in the literature as problematic for students. The visualisation tool uses visual specifications depicting SQL operations to build queries. This is expected to reduce the cognitive load of a student who is learning SQL. We have shown with an online survey that adopting visual specifications in teaching systems assist students in attaining a richer learning experience in introductory database courses

Diabetes with Hypertension as Risk Factors for Adult Dengue Hemorrhagic Fever in a Predominantly Dengue Serotype 2 Epidemic: A Case Control Study

Dengue is a major vector borne disease in the tropical and subtropical regions. An estimated 50 million infections occur per annum in over 100 countries. A severe form of dengue, characterized by bleeding and plasma leakage, known as dengue hemorrhagic fever (DHF) is estimated to occur in 1–5% of hospitalized cases. It can be fatal if unrecognized and not treated in a timely manner. Previous studies had found a number of risk factors for DHF. However, screening and clinical management strategies based on these risk factors may not be applicable to all populations and epidemics of different serotypes. In this study, we found significant association between DHF and diabetes mellitus and diabetes mellitus with hypertension during the epidemic of predominantly serotype 2 (year 2007 and 2008), but not during the epidemic of predominantly serotype 1 (year 2006). Diabetes mellitus and hypertension are prevalent in Singapore and most parts of South-East Asia, where dengue is endemic. Therefore, it is important to address the risk effect of these co-morbidities on the development of DHF so as to reduce morbidity and mortality. Our findings may have impact on screening and clinical management of dengue patients, when confirmed in more studies

The effects of probiotic bacteria on glycaemic control in overweight men and women: a randomised controlled trial

Background/Objectives: Evidence from animal and in vitro models suggest a role of probiotic bacteria in improving glycaemic control and delaying the onset of type 2 diabetes. However, the evidence from controlled trials in humans is limited. The objective was to determine if the probiotic bacteria L. acidophilus La5 and B. animalis subsp lactis Bb12, supplemented in a whole food (yoghurt) or isolated (capsules) form, can improve biomarkers of glycaemic control. Subjects/methods: Following a 3-week washout period, 156 overweight men and women over 55 years (mean age: 67±8 years; mean body mass index (31±4 kg/m2) were randomized to a 6-week double-blinded parallel study. The four intervention groups were: (A) probiotic yoghurt plus probiotic capsules; (B) probiotic yoghurt plus placebo capsules; (C) control milk plus probiotic capsules; and (D) control milk plus placebo capsules. Outcome measurements, including fasting glucose, insulin, glycated haemoglobin and Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR), were performed at baseline and week 6. Results: Relative to the milk-control group, probiotic yoghurt resulted in a significantly higher HOMA-IR (0.32±0.15, P=0.038), but did not have a significant effect on the other three measures of glycaemic control (P>0.05). Relative to placebo capsules, probiotic capsules resulted in a significantly higher fasting glucose (0.15±0.07 mmol/l, P=0.037), with no significant effect on the other three measures of glycaemic control (P>0.05). Further analyses did not identify other variables as contributing to these adverse findings. Conclusions: Data from this study does not support the hypothesis that L. acidophilus La5 and B. animalis subsp lactis Bb12, either in isolated form or as part of a whole food, benefit short-term glycaemic control. Indeed, there is weak data for an adverse effect of these strains on glucose homoeostasis

The Raine study had no evidence of significant perinatal selection bias after two decades of follow up: A longitudinal pregnancy cohort study

Background: Cohort studies may increase or decrease their selection bias as they progress through time. The Western Australian Pregnancy Cohort (Raine) Study has followed 2868 children for over two decades; from fetal into adult life. This paper analyses the cohort over time, assessing potential bias that may come and go with recruitment, retention and loss of participants. Methods: Linked data from all births in Western Australian over the 3 years the Raine Cohort was recruited were obtained to compare perinatal characteristics and subsequent health outcomes between the Western Australian (WA) contemporaneous birth population and the Raine Cohort at five time points. Perinatal exposure-outcome comparisons were employed to assess bias due to non-participation in Raine Study subsets. Results: There were demographic differences between the Raine Study cohort and its source population at recruitment with further changes across the period of follow up. Despite these differences, the pregnancy and infant data of those with continuing participation were not significantly different to the WA contemporaneous birth population. None of the exposure-outcome associations were significantly different to those in the WA general population at recruitment or at any cohort reviews suggesting no substantial recruitment or attrition bias. Conclusions: The Raine Study is valuable for association studies, even after 20 years of cohort reviews with increasing non-participation of cohort members. Non-participation has resulted in greater attrition of socially disadvantaged participants, however, exposure-outcome association analyses suggest that there is no apparent resulting selection bias

Severity of acute hepatitis and its outcome in patients with dengue fever in a tertiary care hospital Karachi, Pakistan (South Asia)

<p>Abstract</p> <p>Background</p> <p>Liver injury due to dengue viral infection is not uncommon. Acute liver injury is a severe complicating factor in dengue, predisposing to life-threatening hemorrhage, Disseminated Intravascular Coagulation (DIC) and encephalopathy. Therefore we sought to determine the frequency of hepatitis in dengue infection and to compare the outcome (length of stay, in hospital mortality, complications) between patients of Dengue who have mild/moderate (ALT 23-300 IU/L) v/s severe acute hepatitis (ALT > 300 IU/L).</p> <p>Methods</p> <p>A Cohort study of inpatients with dengue viral infection done at Aga Khan University Hospital Karachi. All patients (≥ 14 yrs age) admitted with diagnosis of Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS) were included. Chi square test was used to compare categorical variables and fischer exact test where applicable. Survival analysis (Cox regression and log rank) for primary outcome was done. Student t test was used to compare continuous variables. A p value of less than or equal to 0.05 was taken as significant.</p> <p>Results</p> <p>Six hundred and ninety nine patients were enrolled, including 87% (605) patients with DF and 13% (94) patients with DHF or DSS. Liver functions tests showed median ALT of 88.50 IU/L; IQR 43.25-188 IU/L, median AST of 174 IU/L; IQR 87-371.5 IU/L and median T.Bil of 0.8 mg/dl; IQR 0.6-1.3 mg/dl. Seventy one percent (496) had mild to moderate hepatitis and 15% (103) had severe hepatitis. Mean length of stay (LOS) in patients with mild/moderate hepatitis was 3.63 days v.s 4.3 days in those with severe hepatitis (P value 0.002). Overall mortality was 33.3% (n = 6) in mild/moderate hepatitis vs 66.7% (n = 12) in severe hepatitis group (p value < 0.001). Cox regression analysis also showed significantly higher mortality in severe hepatitis group (H.R (4.91; 95% CI 1.74-13.87 and P value 0.003) and in DHF/DSS (5.43; CI 1.86-15.84 and P value 0.002). There was a significant difference for the complications like Bleeding (P value < 0.001), Acute Renal failure (ARF) (P value 0.002), Acalculus cholecystitis (P value 0.04) and encephalopathy (P value 0.02) in mild/moderate and Severe hepatitis groups respectively.</p> <p>Conclusion</p> <p>Severe hepatitis (SGPT>300IU) in Dengue is associated with prolonged LOS, mortality, bleeding and RF.</p

Bringing Back a Healthy Buzz? Invertebrate Parasites and Reintroductions:A Case Study in Bumblebees

Reintroductions can play a key role in the conservation of endangered species. Parasites may impact reintroductions, both positively and negatively, but few case studies of how to manage parasites during reintroductions exist. Bumblebees are in decline at regional and global scales, and reintroductions can be used to re-establish extinct local populations. Here we report on how the risks associated with parasites are being managed in an ongoing reintroduction of the short-haired bumblebee, Bombus subterraneus, to the UK. Disease risk analysis was conducted and disease risk management plans constructed to design a capture-quarantine-release system that minimised the impacts on both the bumblebees and on their natural parasites. Given that bumblebee parasites are (i) generalists, (ii) geographically ubiquitous, and (iii) show evidence of local adaptation, the disease risk management plan was designed to limit the co-introduction of parasites from the source population in Sweden to the destination site in the UK. Results suggest that this process at best eliminated, or at least severely curtailed the co-introduction of parasites, and ongoing updates of the plan enabled minimization of impacts on natural host-parasite dynamics in the Swedish source population. This study suggests that methods designed for reintroductions of vertebrate species can be successfully applied to invertebrates. Future reintroductions of invertebrates where the parasite fauna is less well known should take advantage of next-generation barcoding and multiple survey years prior to the start of reintroductions, to develop comprehensive disease risk management plans