NIHRDataInsights/HRCSData huggingface dataset:
Title: Over two years to study microneedle-enhanced neonatal therapeutic drug monitoring
Funder: Action Medical Research

Abstract: Background Around one in nine babies born in the UK will spend at least a few days in a neonatal unit. This may be for the treatment of an infection, breathing difficulties, jaundice or other complications and these units specialise in looking after preterm, small and sick babies. Advances in treatment mean that more premature babies now survive. Many of these babies will require treatment with multiple medicines and monitoring of drug levels in premature and newborn babies is especially important since their liver and kidney functions can vary. It is vital to establish whether a medicine is building up in the body or being removed effectively. Unfortunately, taking blood samples can cause severe bruising or scarring and babies also have very limited blood volumes, which prevents frequent sampling. There is a need for new techniques which would be more suitable for babies and permit rapid and frequent monitoring of drug levels without drawing of blood. This would allow detection of dangerously high or low medicine levels and therefore improve disease control. The research project In this project, the researchers will carry out laboratory studies to further develop novel technology based on tiny needles (microneedles) that puncture the outer layer of skin without causing any pain or bleeding - the sensation is said to feel like a cat's tongue. These needles then swell, turning into a jelly-like material that keeps the holes in the skin open and allows collection of skin fluid. As the medicine levels in the fluid in people's skin are very similar to those in their blood, the team hopes that once fully developed, their microneedles, in combination with a sophisticated measurement technique will enable accurate, pain-free monitoring of blood levels of medicines in babies. In the longer term, this technique could be of benefit to patients worldwide.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Investigation of how best to prevent preterm delivery in twins
Funder: SPARKS

Abstract: More than half of all women pregnant with twins will deliver prematurely. Such births are the largest cause of death and disability in children – and twins contribute disproportionately. Recent evidence suggests that drugs that work to help prevent preterm birth in single baby pregnancies do not work for twins. We therefore want to determine what are the best drug combinations to use in twins, and how they work. The data obtained will provide the basis for a subsequent clinical trial with the aim of reducing pre-term birth in twins.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Can chemicals detected in the urine or blood be used to predict risk of premature birth?
Funder: SPARKS

Abstract: Early preterm labour, causing birth before 32 weeks, is the major cause of neonatal death and neurodevelopmental handicap. The onset of preterm labour itself is preceded by changes which are seen in the cervix several weeks before the onset of contractions. We hypothesise that these changes are themselves preceded by changes in metabolic markers in urine or blood and that these markers are likely to be detected as early as 13 weeks in pregnancy. In this study we will assess blood and urine from pregnant woman at high risk of preterm birth at 13, 16 and 20 weeks using metabonomic to identify metabolic markers which predict cervical change and preterm birth. The markers will be validated in a second independent population.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Combined Preclinical xenon safety study and a Phase II clinical study of xenon and cooling in term newborns with moderate or severe perinatal asphyxia
Funder: SPARKS

Abstract: Aims: Validate 1)whether 72h of combined xenon-cooling treatment is safe using a newborn global pig-hypoxic-ischemic-model; 2)whether early tests (<14day-old) predict BayleyIII outcome at 18months in a small Phase-II-trial. Adding 50%xenon to cooling doubled neuroprotection compared to cooling alone in our newborn brain-injury rat and pig models (3,4,6,14). Safety-data for 18h of xenon in infants (13) is published; however 72h xenon in combination with standard 72h-cooling has not been studied. Xenon interacts with a number of receptors, cellular messengers and genetic factors. Xenon is and NMDA antagonist (15,16). Long-lasting NMDA-blockade by other substances has adversely affected the brain. Xenon is heavier (x4) than air and breathing a heavy gas for 72hrs may harm the lungs (17,18). Sixty-two newborn pigs, with-or-without 72h xenon at normothermia or hypothermia after a global insult and appropriate sham controls, will be ventilated for 72hrs and brain and organs examined after 4d survival. This application also studies a small(n=52) phase-II randomised trial comparing cooling alone with cooling+18h xenon for term asphyxiated infants. Our recent randomised pilot trial (n=32), showed it was feasible to recruit infants within 5h to deliver xenon after developing a xenon-ambulance-delivery system. Early outcome examinations: our modified “Dubowitch-score” for this population on day 7, continuous aEEG for 4 days, ultrasound scans and MRI/MRS on day2 and 7 will be undertaken as well as corrected Bayley III(19) follow-up at 18months. (Lay summary also provided)


Research activity codes: 5.7 PHYSICAL;6.7 PHYSICAL
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Development of vascular homing peptides as a drug delivery system in pregnancy
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The future in tailored healthcare is to direct systemically administered pharmaceuticals to their target organs. As the endothelial lining of blood vessels of each organ expresses a unique array of molecules, phage display will be used to identify 'homing peptides' that bind exclusively to particular vascular beds. In this system, a phage library engineered to express random peptides on their surface proteins is injected into a host animal. Non-specific peptide sequences are diluted within the host, whereas peptides that bind specifically to one site are enriched in that location. Peptides that bind exclusively to the placenta or the uterine spiral arteries of pregnant mice will be identified, as both locations express a unique complement of antigens, making the materno-fetal interface a good model system in which to develop targeted drug delivery strategies. Specific peptides will be enriched in rounds of selection, then incorporated into liposomes and used as molecular couriers to deliver insulin-like growth factor-I (IGF-I) or IGF-II exclusively to the placenta, or interferon-gamma or interleukin-15 (IL-15) to the spiral arteries. These molecules promote placental growth and vascular remodelling in the mouse, thus a successful drug delivery strategy will be reflected by enhanced fetal and placental development, in the absence of any maternal or fetal pathology. Once validated, this method will be used to manipulate pregnancy outcome in mouse models that exhibit impaired placental growth and reduced arterial remodelling. The affinity of the isolated peptides for human placenta and spiral arteries will also be assessed; high affinity peptides will be incorporated into liposomes and used to deliver IGFs to manipulate cell turnover in placental explants, or deliver interferon-gamma/interleukin-15 to excised spiral arteries to promote receptivity to remodelling. This will provide the basis for a targeted drug delivery system suitable for use in human pregnancy.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Maternal mechanisms induced by diet regulating embryo developmental plasticity affecting life-long health
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The worldwide increase in cardiovascular and metabolic diseases has been shown in epidemiological studies to derive mainly from prenatal causes associated with poor maternal nutrition and adverse developmental programming. Our past work using rodent models has shown that maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to induce adult cardiovascular, metabolic and behavioural disease. Thus, embryos make compensatory responses to poor diet (developmental plasticity) that act to stimulate nutrient retrieval during later gestation to promote survival and growth but which associate with adult disease. An increased risk of cardiovascular and metabolic disorders has recently been shown in IVF children. This proposal will investigate two mechanisms induced by maternal Emb-LPD within the mother that contribute to embryo responses. The first concerns the molecular nature of the communication pathway within the maternal tract that induces embryo responses. Our substantial preliminary data implicate specific amino acid composition potentially coupled with insulin signalling as the inductive components. We will use an in vitro culture model to modulate this communication pathway and monitor outcomes at embryo, fetal and adult stages following embryo transfer as necessary. This will provide precise molecular information on the induction mechanism for adverse developmental plasticity leading to adult disease and will allow us to modulate diet in a precise way in an attempt to prevent adult disease. The second mechanism concerns our recent discovery of maternal upregulation of uterine angiogenesis at the time of implantation induced by Emb-LPD. This mechanism will be characterised in molecular terms, how it is induced, and its relative contribution to developmental programming determined in quantitative terms


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Glucocorticoid programming of placental nutrient transport capacity
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Many epidemiological and experimental studies have shown that environmental conditions during pregnancy produce a specific offspring epigenome with phenotypical consequences long after the original insult. Glucocorticoids (GCs) have an important role in this process of developmental programming but little is known about the epigenetic regulation of placental phenotype, despite the placenta's importance in supplying nutrients for fetal growth. Thus, the aim of the project is to establish the role of GCs in programming the placental nutrient transport capacity. Using chronically catheterised sheep, the study will determine whether maternal and fetal GCs alter the placental nutrient transport capacity differentially and the extent to which these effects persist after treatment and are sex-linked. In vivo measurements of placental clearance, consumption and net transfer of nutrients will be made in male and females fetuses during and after treatment of the mother and/or fetus with cortisol for 5 days during late gestation at doses known to impair fetal growth. These measurements will be compared to saline infused controls and related to in vitro analyses of placental morphology and expression for growth regulatory, GC bioavailability and nutrient supply genes quantified using stereological and molecular biology techniques. The study, therefore, provides a comprehensive integrated assessment of placental nutrient transfer by simple and faciltated diffusion and active transport. The results will establish whether the placental epigenome provides a mechanism of transmitting memories of early events to fetuses later in development and the importance of placental phenotype as an index of conditions experienced during prenatal development. This has implications for the outcome of pregnancies treated clinically with glucocoticoids or compromised by maternal or fetal stress. The long term goal is to identify novel placental biomarkers of the offspring's future health.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Stress and timing of puberty: is the amygdala the key?
Funder: Biotechnology and Biological Sciences Research Council

Abstract: This project will address the neural mechanisms by which the amygdala controls the timing of puberty in response to environmental perturbations. We will test the hypothesis that variable effects of stress on the timing of puberty, both delay and advance, are critically dependent on levels of corticotrophin-releasing factor (CRF) activity in the amygdala. Our multidisciplinary approach will involve a combination of pharmacological, neuroanatomical and molecular biological techniques applied to well established early life stress and metabolic models. The project will focus on (i) determining the functional relationship between amygdala CRF and CRF receptor systems, and hypothalamic kisspeptin-gonadotrophin releasing hormone (GnRH) neuronal signalling that underlie stress-induced delay or advancement of puberty, (ii) establish the differential role of the medial (MeA) and central (CeA) amygdala in early life stress, maternal care or high caloric diet induced regulation of pubertal timing and (iii) determine whether advanced puberty is due to modulatory impact of food-related stimuli on amygdala CRF tone or direct metabolic change. This project will not only provide novel insight of key neural mechanisms integrating limbic brain stress and reward-emotional eating centres with hypothalamic reproductive kisspeptin-GnRH systems that regulate the impact of common diverse environmental factors on the timing of puberty, but may help future development of more effective treatments for stress-related disorders of puberty.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Understanding and assessing impact of hyaluronidases in supporting preimplantation embryo development
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Low fertility is a problem in domestic animals and human, impose major economic loss for farmers and social discomfort and costs to couples and expenses to the NHS. To date, efficiency of embryos production in the lab is much less than of those grown in the body, indicating a need for further research to improve formulation of embryo culture media. With BBSRC support, we have identified an enzyme (Hyal-2) which chops embryos' and oviductal hyaluronan (HA) to improve embryo development and quality when added to cow or sheep embryo culture or infused into the sheep oviduct. Similar enzymes are released by sperm at fertilisation in the oviduct. These enzymes could improve efficiency of embryo culture media, but before commercialization, further knowledge of their actions is needed. Our study will test Hyals and HA on sheep embryos in our laboratory. We will place treated embryos in ewes to measure pregnancy rates. We will also begin studies on human embryos, with ethical approval.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The impact of sexual dimorphism on reproduction and health
Funder: Biotechnology and Biological Sciences Research Council

Abstract: In all livestock systems, one sex is more productive: male animals are often more suited for meat production, while female animals may be used for breeding stock, eggs and milk. In each case, the more productive sex is required in greater numbers. This is well illustrated by the poultry industry, where chicks of egg-laying strains are sexed on the day of hatch and only the females retained while poultry meat producers are forced to accept the relative inefficiency of raising an equal number of slower growing females (males outweigh females by as much as 35% at age of sale). Obviously, the capability to manipulate the sex-ratio of birds raised would be a major benefit to the poultry industry and significantly increase food production. For all livestock species, an ability to carry out sex selection and/or mitigate the impact of gender on productivity would substantially increase reproductive efficiency, reduce waste and alleviate welfare concerns associated with culling the less useful gender. This project aims to address these issues by applying our understanding of the mechanisms underlying sexual development to devise means of manipulating sex ratios, and to increase reproductive efficiency by improving follicle selection. Understanding of the processes controlling the generation of healthy sperm and oocytes lies at the core of fertility and we will determine key features of germ cell development to facilitate in vitro production of gametes.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The Barkantine Birth Centre (BaBC): an ethnographic study of the philosophy, culture and practice in a freestanding urban midwife-led unit.
Funder: Department of Health (England)

Abstract: Objective: To explore the culture, philosophy and practice within a freestanding midwifery-led birth centre. Research Design: Ethnographic study.Expected Outcomes: Evaluation of the impact of the BaBC on service users, families and staff. To explore issues such as: risk, safety, decision making and choice. Shed light on the transfer system and the relationship between the BaBC and the Acute Trust.Anticipated Benefits: It will contribute to the development of midwifery practice and theory. Service users’ choices and experiences will be explored. Health and safety will be enhanced by looking at the accessibility and delivery of care as well as shed light on the system for transferring women, who develop obstetric complications during labour, to the acute unit.In addition commisioners and managers of maternity services will benefit from understanding this new model of care.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: A Feasibility and Acceptability Study and a Qualitative Process Evaluation of a Coping Intervention for Women with Recurrent Miscarriage
Funder: Department of Health (England)

Abstract: Some women experience the pain of miscarriage on numerous occasions. Studies show that these women experience feelings of anxiety and distress during the early stages of a new pregnancy as they worry another miscarriage will occur. This study will investigate whether a coping strategy, developed for a similar group of women, would be acceptable and useful to women suffering recurrent miscarriage, and reduce the anxiety and worry they experience. A secondary aim of the study is to develop a deeper understanding of the experiences and feelings of women in the early stages of a new pregnancy, following multiple miscarriages.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Fear of normal birth and its consequences: A mixed methods study
Funder: Department of Health (England)

Abstract: The recent NICE Caesarean section guidelines (2011) made a controversial recommendation stating that, for women with anxiety about childbirth, a planned caesarean section can be offered. This recommendation stems from the acknowledgement that anxiety, stemming from fear of childbirth, is associated with poor pregnancy outcomes for mother (postnatal depression) and baby (preterm birth, low birth weight and delayed infant development). However, there is little understanding of the complexities of this phenomenon, or the effectiveness of supportive antenatal interventions to reduce caesarean births and/or improve outcomes. The overall aim of this exploratory study is to gain understanding of the phenomenon of childbirth fear and the associated impact on health professional practice, clinical outcomes and women's experiences


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The effect of Birth after Anal Sphincter Injury on bowel symptoms and Quality of life: The BASIQ Study
Funder: Department of Health (England)

Abstract: In the UK, >18,000 women a year sustain a tear that extends into the anal muscle during childbirth (OASIS). Bowel symptoms associated with these tears are widely recognized. However, the impact of future births on these women is not. The BASIQ-study is designed to explore the effects of subsequent births for women with previous OASIS on bowel symptoms and quality of life. Data will be collected by questionnaires and anal scan at 34-weeks of pregnancy and 6-months following birth. This study will provide essential information that will enable women and clinicians to choose the mode of birth most appropriate to them.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Long term health of women diagnosed with endometriosis: a Scottish record linkage study
Funder: Chief Scientist Office (Scotland)

Abstract: Endometriosis is a common condition affecting 10% of women with a significant impact on quality of life. The natural history of the condition is not known but it tends to recur following treatment such that multiple surgical procedures are necessary. Women with endometriosis may also be at increased risk of adverse reproductive outcomes and cancer. We propose to undertake a longitudinal study using routinely collected Scottish national data to determine the risk of future gynaecological, cancer and reproductive outcomes in a cohort of women diagnosed with endometriosis over a 30 year period between 1981 and 2010. The results of this study will provide much needed information about the long term health of women diagnosed with this condition. The findings from this study have the potential to improve the way women with endometriosis are counselled and inform the development of better pathways of clinical care.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH