CellCircuits: a database of protein network models

CellCircuits () is an open-access database of molecular network models, designed to bridge the gap between databases of individual pairwise molecular interactions and databases of validated pathways. CellCircuits captures the output from an increasing number of approaches that screen molecular interaction networks to identify functional subnetworks, based on their correspondence with expression or phenotypic data, their internal structure or their conservation across species. This initial release catalogs 2019 computationally derived models drawn from 11 journal articles and spanning five organisms (yeast, worm, fly, Plasmodium falciparum and human). Models are available either as images or in machine-readable formats and can be queried by the names of proteins they contain or by their enriched biological functions. We envision CellCircuits as a clearinghouse in which theorists may distribute or revise models in need of validation and experimentalists may search for models or specific hypotheses relevant to their interests. We demonstrate how such a repository of network models is a novel systems biology resource by performing several meta-analyses not currently possible with existing databases

Improving the organisation of maternal health service delivery and optimising childbirth by increasing vaginal birth after caesarean section through enhanced women-centred care (OptiBIRTH trial): study protocol for a randomised controlled trial (ISRCTN10612254)

Open Access JournalBackground The proportion of pregnant women who have a caesarean section shows a wide variation across Europe, and concern exists that these proportions are increasing. Much of the increase in caesarean sections in recent years is due to a cascade effect in which a woman who has had one caesarean section is much more likely to have one again if she has another baby. In some places, it has become common practice for a woman who has had a caesarean section to have this procedure again as a matter of routine. The alternative, vaginal birth after caesarean (VBAC), which has been widely recommended, results in fewer undesired results or complications and is the preferred option for most women. However, VBAC rates in some countries are much lower than in other countries. Methods/Design The OptiBIRTH trial uses a cluster randomised design to test a specially developed approach to try to improve the VBAC rate. It will attempt to increase VBAC rates from 25 % to 40 % through increased women-centred care and women’s involvement in their care. Sixteen hospitals in Germany, Ireland and Italy agreed to join the study, and each hospital was randomly allocated to be either an intervention or a control site. Discussion If the OptiBIRTH intervention succeeds in increasing VBAC rates, its application across Europe might avoid the 160,000 unnecessary caesarean sections that occur every year at an extra direct annual cost of more than €150 million

Longitudinal flow evolution and turbulence structure of dynamically similar, sustained, saline density and turbidity currents

Experimental results are presented concerning flow evolution and turbulence structure of sustained saline and turbidity flows generated on 0°, 3°, 6°, and 9° sloping ramps that terminate abruptly onto a horizontal floor. Two-component velocity and current density were measured with an ultrasonic Doppler velocity profiler and siphon sampler on the slope, just beyond the slope break and downstream on the horizontal floor. Three main factors influence longitudinal flow evolution and turbulence structure: sediment transport and sedimentation, slope angle, and the presence of a slope break. These controls interact differently depending on flow type. Sediment transport is accompanied by an inertial fluid reaction that enhances Reynolds stresses in turbidity flows. Thus turbidity flows mix more vigorously than equivalent saline density flows. For saline flows, turbulent kinetic energy is dependent on slope, and rapid deceleration occurs on the horizontal floor. For turbidity flows, normalized turbulent kinetic energy increases downstream, and mean streamwise deceleration is reduced compared with saline flows. The slope break causes mean bed-normal velocity of turbidity flows to become negative and have a gentler gradient compared with other locations. A reduction of peak Reynolds normal stress in the bed-normal direction is accompanied by an increase in turbulent accelerations across the rest of the flow thickness. Thus the presence of particles acts to increase Reynolds normal stresses independently of gradients of mean velocity, and sediment transport increases across the break in slope. The experiments illustrate that saline density currents may not be good dynamic analogues for natural turbidity currents

SDC-Net final meeting: Decisions, decisions, decisions – survey commissioning in a multi-source, multi-mode world

This video is a recording of the final meeting of the Survey Data Collection Network, which took place online on 22 March 2023. The event began with presentations from a panel of experts, who then answered questions from the audience. The panel members were: Mike Daly (Department for Work and Pensions); Michael Dale (Department for Education); Ally McAlpine (Scottish Government); Martina Portanti (Office for National Statistics); Andrew Spiers (Sport England). The speakers discussed how survey commissioners need to consider various trade-offs with regard to cost, accuracy, timeliness, inclusivity, granularity and other issues when deciding on the design of a survey, but also the use of ‘new’ technologies and alternative data sources alongside or instead of surveys. Panel members also explored what information survey commissioners need from suppliers, researchers and/or methodologists to be able to make informed decisions about the commissioning and design of surveys. The panel discussion was chaired by Gerry Nicolaas, Director of the National Centre for Social Research (NatCen)

Process evaluation for OptiBIRTH, a randomised controlled trial of a complex intervention designed to increase rates of vaginal birth after caesarean section

Complex interventions encompassing several interconnecting and interacting components can be challenging to evaluate. Examining the underlying trial processes while an intervention is being tested can assist in explaining why an intervention was effective (or not). This paper describes a process evaluation of a pan-European cluster randomised controlled trial, OptiBIRTH (undertaken in Ireland, Italy and Germany), that successfully used both quantitative and qualitative methods to enhance understanding of the underlying trial mechanisms and their effect on the trial outcome

Accidental consumption of aspartame in phenylketonuria: patient experiences

Aspartame is a phenylalanine containing sweetener, added to foods and drinks, which is avoided in phenylketonuria (PKU). However, the amount of phenylalanine provided by aspartame is unidentifiable from food and drinks labels. We performed a cross-sectional online survey aiming to examine the accidental aspartame consumption in PKU. 206 questionnaires (58% female) were completed. 55% of respondents (n = 114) were adults with PKU or their parent/carers and 45% (n = 92) were parents/carers of children with PKU. 74% (n = 152/206) had consumed food/drinks containing aspartame. Repeated accidental aspartame consumption was common and more frequent in children (p 0.0001). The aspartame containing food/drinks accidentally consumed were fizzy drinks (68%, n = 103/152), fruit squash (40%, n = 61/152), chewing gum (30%, n = 46/152), flavoured water (25%, n = 38/152), ready to drink fruit squash cartons (23%, n = 35/152) and sports drinks (21%, n = 32/152). The main reasons described for accidental consumption, were manufacturers’ changing recipes (81%, n = 123/152), inability to check the ingredients in pubs/restaurants/vending machines (59%, n = 89/152) or forgetting to check the label (32%, n = 49/152). 23% (n= 48/206) had been prescribed medicines containing aspartame and 75% (n = 36/48) said that medicines were not checked by medics when prescribed. 85% (n = 164/192) considered the sugar tax made accidental aspartame consumption more likely. Some of the difficulties for patients were aspartame identification in drinks consumed in restaurants, pubs, vending machines (77%, n = 158/206); similarities in appearance of aspartame and non-aspartame products (62%, n = 127/206); time consuming shopping/checking labels (56%, n = 115/206); and unclear labelling (55%, n = 114/206). These issues caused anxiety for the person with PKU (52%, n = 106/206), anxiety for parent/caregivers (46%, n = 95/206), guilt for parent/carers (42%, n = 87/206) and social isolation (42%, n = 87/206). It is important to understand the impact of aspartame and legislation such as the sugar tax on people with PKU. Policy makers and industry should ensure that the quality of life of people with rare conditions such as PKU is not compromised through their action

Biological Oxidant and Life Detection (BOLD) mission: an outline for a new mission to Mars

The Viking mission was the only mission to date that conducted life detection experiments. It revealed ambiguous and still controversial results. New findings and hypotheses urge a re-evaluation of the Viking results and a re-evaluation of the evidence for the possible presence of life on Mars in general. Recent findings of abundant water ice on Mars, the presence of liquid contemporary water on the Martian surface, and the detection of methane in the Martian atmosphere further support this possibility. Current missions to be launched focus on habitability considerations (e.g., NASA Phoenix, NASA Mars Science Laboratory), but shy away from directly testing for life on Mars, with the potential exception of the ESA ExoMars mission. If these currently planned missions collect positive evidence toward habitability and the possible existence of extraterrestrial (microbial) life on Mars, it would be timely to propose a new mission to Mars with a strong life detection component. We propose such a mission called BOLD: Biological Oxidant and Life Detection Mission. The BOLD mission objective would be to quantify the amount of hydrogen peroxide existing in the Martian soil and to test for processes typically associated with life. Six landing packages are projected to land on Mars that include a limited power supply, a set of oxidant and life detection experiments, and a transmitter, which is able to transmit information via an existing Mars orbiter back to Earth

Biological Oxidant and Life Detection (BOLD) mission: an outline for a new mission to Mars

The Viking mission was the only mission to date that conducted life detection experiments. It revealed ambiguous and still controversial results. New findings and hypotheses urge a re-evaluation of the Viking results and a re-evaluation of the evidence for the possible presence of life on Mars in general. Recent findings of abundant water ice on Mars, the presence of liquid contemporary water on the Martian surface, and the detection of methane in the Martian atmosphere further support this possibility. Current missions to be launched focus on habitability considerations (e.g., NASA Phoenix, NASA Mars Science Laboratory), but shy away from directly testing for life on Mars, with the potential exception of the ESA ExoMars mission. If these currently planned missions collect positive evidence toward habitability and the possible existence of extraterrestrial (microbial) life on Mars, it would be timely to propose a new mission to Mars with a strong life detection component. We propose such a mission called BOLD: Biological Oxidant and Life Detection Mission. The BOLD mission objective would be to quantify the amount of hydrogen peroxide existing in the Martian soil and to test for processes typically associated with life. Six landing packages are projected to land on Mars that include a limited power supply, a set of oxidant and life detection experiments, and a transmitter, which is able to transmit information via an existing Mars orbiter back to Earth

Provision and supervision of food and protein substitute in school for children with PKU: parent experiences

Children spend a substantial part of their childhood in school, so provision of dietary care and inclusion of children with phenylketonuria (PKU) in this setting is essential. There are no reports describing the dietary support children with PKU receive whilst at school. The aim of this cross-sectional study was to explore the experiences of the dietary management of children with PKU in schools across the UK. Data was collected using an online survey completed by parents/caregivers of children with PKU. Of 159 questionnaire responses, 92% (n = 146) of children attended state school, 6% (n = 10) private school and 2% (n = 3) other. Fourteen per cent (n = 21/154) were at nursery/preschool, 51% (n = 79/154) primary and 35% (n = 54/154) secondary school. Sixty-one per cent (n = 97/159) said their child did not have school meals, with some catering services refusing to provide suitable food and some parents distrusting the school meals service. Sixty-one per cent of children had an individual health care plan (IHCP) (n = 95/155). Children were commonly unsupervised at lunchtime (40%, n = 63/159), with snacks (46%, n = 71/155) and protein substitute (30%, n = 47/157), with significantly less supervision in secondary than primary school (p 0.001). An IHCP was significantly associated with improved supervision of food and protein substitute administration (p 0.01), and better communication between parents/ caregivers and the school team (p 0.05). Children commonly accessed non-permitted foods in school. Therefore, parents/caregivers described important issues concerning the school provision of low phenylalanine food and protein substitute. Every child should have an IHCP which details their dietary needs and how these will be met safely and discreetly. It is imperative that children with PKU are supported in school

Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel

Light transmission aggregometry (LTA) is used worldwide for the investigation of heritable platelet function disorders (PFDs), but interpretation of results is complicated by the feedback effects of ADP and thromboxane A(2) (TxA(2)) and by the overlap with the response of healthy volunteers. Over 5 years, we have performed lumi-aggregometry on 9 platelet agonists in 111 unrelated research participants with suspected PFDs and in 70 healthy volunteers. Abnormal LTA or ATP secretion test results were identified in 58% of participants. In 84% of these, the patterns of response were consistent with defects in Gi receptor signaling, the TxA(2) pathway, and dense granule secretion. Participants with defects in signaling to Gq-coupled receptor agonists and to collagen were also identified. Targeted genotyping identified 3 participants with function-disrupting mutations in the P2Y(12) ADP and TxA(2) receptors. The results of the present study illustrate that detailed phenotypic analysis using LTA and ATP secretion is a powerful tool for the diagnosis of PFDs. Our data also enable subdivision at the level of platelet-signaling pathways and in some cases to individual receptors. We further demonstrate that most PFDs can be reliably diagnosed using a streamlined panel of key platelet agonists and specified concentrations suitable for testing in most clinical diagnostic laboratories