Interventions to reduce inequalities for pregnant women living with disadvantage in high-income countries: an umbrella review protocol.

BACKGROUND: Women who live with disadvantages such as socioeconomic deprivation, substance misuse, poor mental health, or domestic abuse face inequalities in health before, during, and after pregnancy and for their infants through to childhood. Women do not experience these factors alone; they accumulate and interact. Therefore, there is a need for an overview of interventions that work across health and social care and target women at risk of inequalities in maternal or child health. METHODS: Systematic review methodology will be used to identify systematic reviews from high-income countries that describe interventions aiming to reduce inequalities for women who experience social disadvantage during pregnancy. We will describe the range of interventions and their effectiveness in reducing inequalities in maternal or child health. Any individual, hospital, or community-level activity specific to women during the pre-conception, antenatal, or postpartum period up to 1 year after birth will be included, regardless of the setting in which they are delivered. We will search eight electronic databases with the pre-determined search strategy and supplement them with extensive grey literature searches. We will present a narrative synthesis, taking into account the quality assessment and coverage of included studies. DISCUSSION: Inequalities in maternal and child health are a key priority area for national policymakers. Understanding the range and effectiveness of interventions across the perinatal period will inform policy and practice. Identifying gaps in the evidence will inform future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023455502.

Saline and hydrocarbon-bearing fluids detected in shallow aquifers of southern New Brunswick, Canada: Natural occurrence, or deep migration along faults and industrial wellbores?

Unconventional hydrocarbon production has sparked public concerns for several years, especially regarding potential potable groundwater contamination by hydrocarbons, brines, and various chemicals related to hydraulic fracturing operations. One possible contamination mechanism is upward migration of deep-seated contaminants over large vertical distances, through preferential pathways such as leaky well casings or permeable geological faults. In New Brunswick (Canada), thermogenic hydrocarbons and brackish water were previously reported in shallow water wells, some of them located close to unconventional gas wells or to major faults, but the exact origin of these fluids remained uncertain. The objective of this paper is to determine whether the presence of these fluids is the result of migration from the deep (>1 km) hydrocarbon bearing units (via natural or anthropogenic migration pathways), or whether they rather originate within the shallow aquifer (<100 m) or from intermediate zone. Tracking fluid origin was achieved by fingerprinting compositional and isotopic values of three indicators: 1) water isotopic signature (including tritium (3H), radiocarbon (14CDIC), δ18OH2O, δ2HH2O), 2) salinity (including Na, Ca, K, SO4, Cl, Br, 87Sr/86Sr), and 3) hydrocarbons (compositional data and δ13CCH4). These various analyses were conducted, when relevant, on samples of different matrices composing the hydrogeological system, namely shallow groundwater (12-90 m depth), shallow bedrock gas (8-131 m), and intermediate zone evaporitic rocks (173-332 m); they were compared with previously published values for deep basin brines and gases (1940-3168 m) from the hydrocarbon bearing Carboniferous Albert Formation. This unique suite of indicators, analytes and matrices allowed drawing the conclusion that thermogenic gas and high salinities present in the sampled wells were naturally occurring and originating from shallow and intermediate-zone bedrock units. Results obtained through this approach did not provide any evidence that hydrocarbon wells in this area have acted as preferential migration pathways for deep-seated fluids towards shallow aquifers.

Value transfer in ecosystem accounting applications.

Ecosystem accounting is a statistical framework that aims to track the state of ecosystems and ecosystem services, with periodic updates. This framework follows the statistical standard of the System of Environmental Economic Accounting Ecosystem Accounting (SEEA EA). SEEA EA is composed of physical ecosystem extent, condition and ecosystem service supply-use accounts and monetary ecosystem service and asset accounts. This paper focuses on the potential use of the "Value Transfer" (VT) valuation method to produce the monetary ecosystem service accounts, taking advantage of experience with rigorous benefit transfer methods that have been developed and tested over many years in environmental economics. Although benefit transfer methods have been developed primarily for welfare analysis, the underlying techniques and advantages are directly applicable to monetary exchange values required for ecosystem accounting. The compilation of regular accounts is about to become a key area of work for the National Statistical Offices worldwide as well as for the EU Member States in particular, due to the anticipated amendment to regulation on European environmental economic accounts introducing ecosystem accounts. On this basis, accounting practitioners have voiced their concerns in a global consultation during SEEA EA revision, about three issues in particular: the lack of resources, the need for guidelines and the challenge of periodically updating the accounts. We argue that VT can facilitate empirical applications that assess ecosystem services in monetary terms, especially at national scales and in situations with limited expertise and resources available. VT is a low-cost valuation approach in line with SEEA EA requirements able to provide periodic, rigorous and consistent estimates for use in accounts. While some methodological challenges remain, it is likely that VT can help to implement SEEA EA at scale and in time to respond to the pressing need to incorporate nature into mainstream decision-making processes.

Elasmobranchs from Indonesian Waters: Feeding Ecology and Trypanorhynch Cestode Fauna Composition to Support Efforts in Shark and Ray Conservation.

PURPOSE: The stomachs and spiral valves of sharks and rays were examined for their trypanorhynch (Cestoda) parasite fauna and dietary items to infer feeding ecology. In Indonesia, sharks and rays have been experiencing increasing awareness and conservation in the recent years due to high fisheries activities and to avoid future species extinction. METHODS: The samples were collected in 2009 from two different sampling sites at the southern coasts of Java and Bali in Indonesia. The parasite fauna was studied for 41 elasmobranch fishes. Amongst these, three shark species, Carcharhinus sorrah, Carcharhinus sp. I and Squalus megalops and seven ray species, Brevitrygon heterura, B. cf. heterura, Gymnura zonura, Maculabatis gerrardi, Mobula kuhlii, Neotrygon cauruleopuncatata and Rhinobatos penggali were studied. Four additional specimens, belonging to the shark species Carcharhinus sp. II and Mustelus cf. manazo and the ray species Maculabatis gerrardi were studied from the waters of South Bali. RESULTS: Analyses of the feeding ecology of the ray M. gerrardi revealed distinct differences between both sampling sites, indicating the presence of ecological differences between the geographically independent regions. A total of 11 different trypanorhynch species/taxa belonging to the five families Eutetrarhynchidae (5), Gilquiniidae (1), Lacistorhynchidae (1), Pterobothriidae (1) and Tentaculariidae (3) were found. Ten trypanorhynch species from Penyu Bay and four species from South Bali could be identified. Two taxa that might represent new species were collected: Dollfusiella sp. from Brevitrygon heterura and Prochristianella sp. from Maculabatis gerrardi. CONCLUSIONS: The present paper gives insights in using the trypanorhynch cestode community in combination with feeding ecology analyses to support conservation of elasmobranchs in Indonesian waters.

Nematodes from the Tasmanian devil (Sarcophilus harrisii (Boitard)), with the description of Sarcophiloxyuris longus n. gen. and n. sp. (Oxyuridae).

The Tasmanian devil (Sarcophilus harrisii (Boitard)) is an endangered carnivorous marsupial, limited to the islands of Tasmania in southern Australia. The parasites of the Tasmanian devil are understudied. This study aimed to increase the knowledge of the nematode fauna of Tasmanian devils. Ten Tasmanian devils were examined for parasites from northern and southern Tasmania. Nematodes that were collected were morphologically characterized as two separate species. Molecular sequencing was undertaken to verify the identity of these species. A new genus and species of oxyurid nematode was collected from a single Tasmanian devil from the northern part of Tasmania. The nematode is differentiated from oxyurids described from other Australian amphibians, reptiles and marsupials by the characters of the male posterior end - that is, in having three pairs of caudal papillae, two pairs peri-cloacal, one large pair post-cloacal, a long tapering tail, a stout spicule and a gubernaculum and accessory piece, as well as its much larger overall size. Molecular sequencing was unsuccessful. The remaining nematodes collected from the Tasmanian devil in this study were all identified as Baylisascaris tasmaniensis Sprent, 1970, through morphology and molecular sequencing. This paper presents the first description of a new genus and species of oxyurid nematode from the Tasmanian devil, Sarcophiloxyuris longus n. gen., n. sp. The need to undertake more sampling of the parasites of endangered hosts, such as the Tasmanian devil, to assist with a better understanding of their conservation management, is discussed.

The impact of the Covid-19 pandemic on care of women with ectopic pregnancy in a tertiary London hospital.

BACKGROUND: In response to the COVID-19 pandemic, a central London tertiary referral hospital's nurse-led Early Pregnancy & Acute Gynaecology Unit (EPAGU) suspended its walk-in service in favour of a telephone triage system with scheduled appointments. OBJECTIVE: To assess if the pandemic and this adaptation to clinical services had an impact on the presentation, management and complication rate of ectopic pregnancies. MATERIALS AND METHODS: A retrospective review was performed of ectopic pregnancies diagnosed in the EPAGU between 5th of March 2020 - 15th of July 2020 (pandemic) and 5th of March 2019 - 15th of July 2019 (pre-pandemic). MAIN OUTCOME MEASURES: Ultrasound findings, patient demographics, serum hCG concentrations, operative findings and complications. RESULTS: There was a 36% reduction in attendances to the unit during the pandemic. Allowing for this, there was no significant difference in the diagnosis rate between the two periods. There was no significant difference in the gestation at diagnosis, serum hCG concentration or volume of mass at presentation. There was also no significant difference in rate of surgical intervention or complications including rupture of fallopian tube, haemoperitoneum or need for blood transfusion. CONCLUSION: This study suggests this is a safe means of caring for women with ectopic pregnancies which does not limit management options nor lead to higher complication rates. WHAT IS NEW: Other EPAGUs may choose to adopt a telephone triage system with reassurance of its safety.

Wild fallow deer (Dama dama) as definitive hosts of Fasciola hepatica (liver fluke) in alpine New South Wales.

To determine the extent to which wild deer are contributing in the transmission of Fasciola hepatica (liver fluke) livers from deer shot by hunters, farmers undertaking population control on their farms and vertebrate pest controllers were collected and frozen. The livers were later thawed, sliced and examined for the presence of adult flukes or evidence of past infection. Livers from 19 deer were examined (18 fallow [Dama dama] and one sambar [Rusa unicolor]). Seventeen of the fallow deer were animals collected on farms near Jindabyne, New South Wales. The remaining fallow deer was collected in the Australian Capital Territory and one sambar deer was collected in north-eastern Victoria. Nine of the 17 deer (53%) from the Jindabyne area were either infected with Fasciola hepatica (liver fluke) or had thickened bile ducts indicating past infection. Infection levels in the infected animals varied widely from 3 liver fluke to over 50 per liver. No sign of infection was present in the deer from the Australian Capital Territory or Victoria. Fallow deer are wide-spread in the Jindabyne area and their population is increasing. It is likely their contribution to the maintenance and distribution of F. hepatica to livestock in the Jindabyne area, and in other livestock rearing areas of south-eastern Australia, is important and increasing.

Development of Peritoneal Carcinoma in women diagnosed with Serous Tubal Intraepithelial Carcinoma (STIC) following Risk-Reducing Salpingo-Oophorectomy (RRSO).

INTRODUCTION: The management of Serous Tubal Intraepithelial Carcinoma (STIC) found at the time of Risk-Reducing Salpingo-Oophorectomy (RRSO) remains unclear. We set out to analyse the incidence of peritoneal carcinomas developed after prophylactic surgery and to formulate further guidance for these patients. METHODS: This is a retrospective study of 300 consecutive RRSO performed at the Royal Marsden Hospital between January 2008 and January 2017. RESULTS: The median age at RRSO was 47.8 years (range 34 to 60 years) and median BMI was 26.2 kg/m2 (range 16 to 51 kg/m2). A total of 273 patients (91%) were tested for BRCA mutations. Of these, 124 (45.4%) had a BRCA 1 mutation, 118 (43.2%) had a BRCA 2 mutation, 2 (0.7%) had both a BRCA 1 and a BRCA 2 mutation and 29 (10.6%) had no BRCA mutation detected. Isolated STIC lesions were identified in 7 cases (2.3%) and p53 signatures in 75 cases (25%). There were five (1.6%) incidental tubal carcinomas and one (0.3%) ovarian carcinoma at the time of surgery. Two (28.6%) of the 7 patients with STIC identified following RRSO had high grade serous peritoneal carcinoma diagnosed at 53 and 75 months. One (0.3%) patient from the other 287 patients from our series with no STIC diagnosis or incidental carcinomas at RRSO developed high grade serous carcinoma of peritoneal origin after 92 months. CONCLUSION: This study demonstrates that when a STIC lesion is identified following RRSO there is a significantly higher risk of a subsequent peritoneal cancer. Although there is no published consensus in literature, we recommend that consideration should be given for long term follow-up if a STIC lesion is identified at RRSO.

Sertoli-Leydig Cell Tumour and DICER1 Mutation: A Case Report and Review of the Literature.

Sertoli-Leydig cell tumours of the ovary (SLCT) are rare tumours predominantly caused by mutations in the DICER1 gene. We present a patient with a unilateral SLCT who had an underlying germline DICER1 gene mutation. We discuss the underlying pathology, risks, and screening opportunities available to those with a mutation in this gene as SLCT is only one of a multitude of other tumours encompassing DICER1 syndrome. The condition is inherited in an autosomal dominant fashion. As such, genetic counselling is a key component of the management of women with SLCT.

Strengthening Non-Communicable Disease Research Capacity in Thailand: Leveraging PhD Nurses and other Health Professionals.

The mounting burden of non-communicable disease (NCD) in lower-to-middle income countries (LMIC) was recognized two decades ago by the World Health Organization (WHO). In 2012, the WHO reported that NCDs were responsible for 71% of total deaths in Thailand. Thus, the goal of our ongoing NIH D43 training grant is to increase the quantity and quality of NCD research in Thailand by producing nurse scientists with the capacity to design, implement, guide, and evaluate cutting-edge research projects. The three components of the program are 1) a long-term component to train 10 Thai postdoctoral scholars that includes one year of intensive mentored research training in the US and one year implementing a research project back in Thailand; 2) a short-term component that provides an opportunity for Thai scientists, teachers, administrators and policy makers to take classes in areas relevant to NCD; 3) a yearly two-day NCD workshop to be held in different regions of Thailand. To date, 8 long-term trainees have completed various stages of their training. Eleven short-term trainees have taken courses at the University of Michigan. Two NCD workshops have been held so far under the auspices of the grant with a third planned for 2018. The ability to participate in the in-depth activities provided by the grant have not only expanded knowledge around NCD's, but also has enabled US and Thai investigators to grow in the area of culturally informed research.

Force appropriation of nonlinear structures.

Nonlinear normal modes (NNMs) are widely used as a tool for developing mathematical models of nonlinear structures and understanding their dynamics. NNMs can be identified experimentally through a phase quadrature condition between the system response and the applied excitation. This paper demonstrates that this commonly used quadrature condition can give results that are significantly different from the true NNM, in particular, when the excitation applied to the system is limited to one input force, as is frequently used in practice. The system studied is a clamped-clamped cross-beam with two closely spaced modes. This paper shows that the regions where the quadrature condition is (in)accurate can be qualitatively captured by analysing transfer of energy between the modes of the system, leading to a discussion of the appropriate number of input forces and their locations across the structure.

nab-Paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial.

Background: Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and aggressive clinical course. tnAcity evaluated the efficacy and safety of first-line nab-paclitaxel plus carboplatin (nab-P/C), nab-paclitaxel plus gemcitabine (nab-P/G), and gemcitabine plus carboplatin (G/C) in patients with mTNBC. Patients and methods: Patients with pathologically confirmed mTNBC and no prior chemotherapy for metastatic BC received (1 : 1 : 1) nab-P 125 mg/m2 plus C AUC 2, nab-P 125 mg/m2 plus G 1000 mg/m2, or G 1000 mg/m2 plus C AUC 2, all on days 1, 8 q3w. Phase II primary end point: investigator-assessed progression-free survival (PFS); secondary end points included overall response rate (ORR), overall survival (OS), percentage of patients initiating cycle 6 with doublet therapy, and safety. Results: In total, 191 patients were enrolled (nab-P/C, n = 64; nab-P/G, n = 61; G/C, n = 66). PFS was significantly longer with nab-P/C versus nab-P/G [median, 8.3 versus 5.5 months; hazard ratio (HR), 0.59 [95% CI, 0.38-0.92]; P = 0.02] or G/C (median, 8.3 versus 6.0 months; HR, 0.58 [95% CI, 0.37-0.90]; P = 0.02). OS was numerically longer with nab-P/C versus nab-P/G (median, 16.8 versus 12.1 months; HR, 0.73 [95% CI, 0.47-1.13]; P = 0.16) or G/C (median, 16.8 versus 12.6 months; HR, 0.80 [95% CI, 0.52-1.22]; P = 0.29). ORR was 73%, 39%, and 44%, respectively. In the nab-P/C, nab-P/G, and G/C groups, 64%, 56%, and 50% of patients initiated cycle 6 with a doublet. Grade ≥3 adverse events were mainly hematologic. Conclusions: First-line nab-P/C was active in mTNBC and resulted in a significantly longer PFS and improved risk/benefit profile versus nab-P/G or G/C.

Identifying the significance of nonlinear normal modes.

Nonlinear normal modes (NNMs) are widely used as a tool for understanding the forced responses of nonlinear systems. However, the contemporary definition of an NNM also encompasses a large number of dynamic behaviours which are not observed when a system is forced and damped. As such, only a few NNMs are required to understand the forced dynamics. This paper firstly demonstrates the complexity that may arise from the NNMs of a simple nonlinear system-highlighting the need for a method for identifying the significance of NNMs. An analytical investigation is used, alongside energy arguments, to develop an understanding of the mechanisms that relate the NNMs to the forced responses. This provides insight into which NNMs are pertinent to understanding the forced dynamics, and which may be disregarded. The NNMs are compared with simulated forced responses to verify these findings.

A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism.

Norepinephrine released from sympathetic nerves is removed from the neuroeffector junction via the action of the norepinephrine transporter (NET). NET impairment is evident in several clinically important conditions including major depressive disorder (MDD), panic disorder (PD), essential hypertension and the postural orthostatic tachycardia syndrome (POTS). We aimed to determine whether a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the NET gene is associated with NET impairment and to elucidate the mechanisms involved. The analyses were carried out in two cohorts of European ancestry, which included healthy controls and MDD, PD, hypertensive and POTS patients. Compared with controls, cases had significantly higher prevalence of the T allele of rs7194256 (C/T), arterial norepinephrine, depression and anxiety scores, larger left ventricular mass index, higher systolic and diastolic blood pressures, and heart rate. Bioinformatic analysis identified that the microRNA miR-19a-3p could bind preferentially to the sequence created by the presence of the T allele. This was supported by results of luciferase assays. Compared with controls, cases had significantly lower circulating miR-19a-3p, which was associated with pathways related to blood pressure and regulation of neurotransmission. In vitro norepinephrine downregulated miR-19a-3p. In conclusion, the T allele of the rs7194256 SNP in the 3'UTR of the NET gene is more prevalent in diseases where NET impairment is evident. This might be explained by the creation of a binding site for the microRNA miR-19a-3p. A defect in NET function may potentiate the sympathetic neurochemical signal, predisposing individuals with affective diseases to increased risk of cardiovascular disease development.

Age Adjusted D-Dimer for exclusion of Pulmonary Embolism: a retrospective cohort study.

D-Dimer (DD) will increase with age and recent studies have shown the upper limit of normal can be raised in those who are low risk and over 50. We studied age adjusted D-dimer (AADD) levels to assess whether pulmonary embolism (PE) could be safely excluded. This study analysed the Emergency Department (ED) Computed Tomographic Pulmonary Angiography (CTPA) requests. There were 756 requests. The parameters studied were; age, DD value, calculated AADD, CT result and Simplified Geneva Score (SGS). The primary outcome was the diagnostic performance of AADD. One hundred and eighty-five patients were included in the final cohort. Twenty-one patients had a negative DD after age adjustment. Of these one had a PE, corresponding to a failure rate of 4.76% (1 in 22). The sensitivity of AADD was 0.96 (95% CI 0.76 to 0.99) and its specificity was 0.12 (95% CI 0.08- 0.19). AADD demonstrated a reduction in false positives with one false negative, giving rise to a failure rate higher than that of other larger studies. Further study is indicated to accurately define the diagnostic characteristics for the Irish context.

REpeated AutoLogous Infusions of STem cells In Cirrhosis (REALISTIC): a multicentre, phase II, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony-stimulating factor (GCSF) mobilised CD133+ bone marrow stem cells in patients with cirrhosis. A study protocol for a randomised controlled trial.

INTRODUCTION: Liver disease mortality and morbidity are rapidly rising and liver transplantation is limited by organ availability. Small scale human studies have shown that stem cell therapy is safe and feasible and has suggested clinical benefit. No published studies have yet examined the effect of stem cell therapy in a randomised controlled trial and evaluated the effect of repeated therapy. METHODS AND ANALYSIS: Patients with liver cirrhosis will be randomised to one of three trial groups: group 1: Control group, Standard conservative management; group 2 treatment: granulocyte colony-stimulating factor (G-CSF; lenograstim) 15 µg/kg body weight daily on days 1-5; group 3 treatment: G-CSF 15 µg/kg body weight daily on days 1-5 followed by leukapheresis, isolation and aliquoting of CD133+ cells. Patients will receive an infusion of freshly isolated CD133+ cells immediately and frozen doses at days 30 and 60 via peripheral vein (0.2×10(6) cells/kg for each of the three doses). Primary objective is to demonstrate an improvement in the severity of liver disease over 3 months using either G-CSF alone or G-CSF followed by repeated infusions of haematopoietic stem cells compared with standard conservative management. The trial is powered to answer two hypotheses of each treatment compared to control but not powered to detect smaller expected differences between the two treatment groups. As such, the overall α=0.05 for the trial is split equally between the two hypotheses. Conventionally, to detect a relevant standardised effect size of 0.8 point reduction in Model for End-stage Liver Disease score using two-sided α=0.05(overall α=0.1 split equally between the two hypotheses) and 80% power requires 27 participants to be randomised per group (81 participants in total). ETHICS AND DISSEMINATION: The trial is registered at Current Controlled Trials on 18 November 2009 (ISRCTN number 91288089, EuDRACT number 2009-010335-41). The findings of this trial will be disseminated to patients and through peer-reviewed publications and international presentations.

After 20 years, industry critics bury skeptics, despite empirical vacuum.

After more than 20 years, the conflict of interest (COI) movement has failed to substantiate its central claim that interactions between physicians, researchers and the medical products industry cause physicians to make clinical decisions that are adverse to the best interests of their patients. The COI movement's instigators have produced no solid evidence of harm commensurate with their extravagant allegations. At the same time, they have diverted resources away from more worthwhile pursuits, such as basic and applied medical research, clinical care and medical education towards onerous compliance exercises and obtrusive laws. Perhaps worst of all, they have made it respectable to ignore the epistemological foundations of medical science, diverting attention away from the scientific merit of the information presented and focusing it instead on the identity and motives of those who present the information.