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Objective: The aim of this project is to review the products and recipes contained within popular subscription meal kits to determine if they are suitable for wider use among people who are food insecure. Design: Across the 6-week period, weekly meal kits from both HelloFresh and Markey Spoon were purchased, resulting in thirty-six individual meals that were prepared and assessed. Meals were assessed based on the content included in the meal kit compared with the recipe card and the nutrition panel, the costs of the individual foods if purchased at one of two major supermarkets and the ease of preparation. Setting: Australia. Participants: Households were comprised of two, 2-person households who were provided with 2 meals each week, and two, single-person households who were provided with one meal each week. Results: The findings of this research suggest that while the meal kits are convenient and, in general, the recipes are easy to follow, and the meals would be made again, the high levels of salt and fat may preclude these kits from regular inclusion in a healthy diet. The meal kits were also found to be more costly than the same ingredients if purchased from a major supermarket. However, the convenience of having most of the foods needed to prepare a full meal with little to no wastage may counterbalance this cost. Conclusions: Meal kits may be a useful component of a healthy diet, that can increase meals prepared and consumed in the home, and thanks to the clear instructions and pre-portioned ingredients, may reduce stress related to food preparation. more...

Context Food insecurity is an important determinant of health and should be identified by clinicians during routine reproductive healthcare. The procedures used in reproductive healthcare settings to identify people experiencing food insecurity have not been fully researched. Objective The objective of this study was to synthesize evidence from published studies that describe the procedures implemented by clinicians in healthcare settings to identify food insecurity in pregnant women, or women of reproductive age (15 years–49 years). Data Sources Four databases were searched in April 2022 to identify studies that met the eligibility criteria. Data Extraction Studies that used tools that were both validated or newly developed were considered, as were studies that incorporated food insecurity screening as part of a multidomain screening tool. Two authors completed the screening, data extraction, and quality assessment independently. Data Analysis There were 1075 studies identified; after screening, 7 studies were included in the narrative synthesis, including studies relating to women who were pregnant or in the postpartum period; none of the included studies related to women in the preconception stage. Four screening tools were identified: 2- and 6-item tools specifically focused on food insecurity, a 58-item multidomain tool incorporating 4 food insecurity items, and a modified version of the 2-item tool. Methods of implementing screening varied across studies. Three described subsequent processes that supported food-insecure patients once identified. Conclusion Few published studies have investigated optimal screening tools and their implementation within reproductive healthcare settings to address food insecurity for this priority population group. Further research is required to determine: the optimal tool, preferable screening methods from the perspectives of both patients and clinicians, and potential strategies for implementation in countries outside of the United States. An additional evidence gap remains about referral pathways and appropriate supports for this population once food insecurity is identified. Systematic Review Registration PROSPERO registration no. CRD42022319687. more...

A healthy diet is particularly important during childhood. Research suggests that more than 95% of Australian primary school aged children do not eat a diet consistent with the Australian Dietary Guidelines, putting them at risk of poor health. Interventions to improve the quality of children's lunchboxes may help address this issue. However, there is limited understanding of the factors impacting lunchbox preparation.This study explored the experiences of 10 mothers of Victorian primary school students. Mothers took part in semi-structured interviews exploring their views on lunchbox preparation and food choices. The study used a Constructivist Grounded Theory methodology and data were analysed using an inductive, thematic approach.Analysis of the interviews yielded four main themes. (i) Mothers experienced a range of non-nutritional barriers that impacted the food choices they made for their children. (ii) Children's preferences influenced parental food choices. (iii) Mothers experienced and/or perceived judgement about the food choices they make for their children. And (iv) Mothers identified a lack of support and information from schools about what was appropriate for school lunch.Findings of this study indicate that mothers are concerned with balancing nutrition and child preferences within the broader context of guidelines, perceived or real judgement and income constraints. SO WHAT?: The school environment may be an ideal setting to promote healthy eating but support for parents is needed. This is the first study in Victoria exploring mothers' perspectives on lunchbox preparation and provides initial information on which future research can build. more...

Grassroots-led global social movements have become increasingly prominent on mainstream media and political agendas. In Scotland, several of these have resulted in significant policy change, including the period poverty movement, which addresses inequalities relating to menstruation. This chapter looks to this movement as a case study, showing how several interventions have led the country to be hailed a world leader in policies providing free access to menstrual products. It will analyze the conditions under which this movement first took hold in Scotland in 2016, moving chronologically from the first mention of the term 'period poverty' in legacy media. It will show how the increasing visibility and discursive realization, or crystallization, of the term itself fueled further activism to influence the political agenda. In doing so, it will show the increasingly hybrid and circuitous dynamic of contemporary political communication and how taking a holistic approach to viewing this may give added insight to appraisals of media and political agenda setting. more...

This article explores the mediated representation of gender in the Scottish public sphere during the independence referendum in 2014. In particular, it focuses on a media sample drawn from the Scottish press that centres on two key political figures, Johann Lamont and Nicola Sturgeon, who took part in a televised debate during the campaign. Using critical discourse analysis, it looks at how language is used to construct overlapping discourses of gender in a specific cultural and national context. Findings show representations pivot on expectations that female politicians should embody a specific feminised style; and when gender norms appear to be violated, this is represented in negatively gendered terms. Though there is evidence of contestation of male-dominated politics, discourses still reify traditional gender norms and situate women as outsiders to the political sphere. This study shows how specific discursive frames can contribute to a cross-cultural practice of gendering women in politics. more...

Highlights • We found a high asymptomatic rate in vulnerable people with epilepsy. • Enhanced surveillance allows to quickly contain outbreaks. • We report a low rate of COVID-19 morbidity and mortality in a long-term care facility. • Preventative measures allow reducing resident-to-resident and -to-caregiver transmission. • Children and young adults appear to have lower infection rates., In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March–6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth’s (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes. more...

Background: A primary consequence of illicit drug markets and the absence of regulation is the variable quality or purity of the final product. Analysis of anabolic-androgenic steroid seizures shows that these products can contain adulterated products, product not included on the label, or product of unsatisfactory standard. While the potential negative effects of counterfeit AAS use is a recognised risk associated with use, no study has explored personal experiences associated with use. The aim of the present study was to use online discussion forums to investigate and explore the experiences associated with the purchase and consumption of counterfeit AAS among consumers. Methods: An online search was conducted to identify online forums that discussed counterfeit or contaminated AAS; three were deemed suitable for the study. The primary source of data for this study were the ‘threads’ from these online forums, identified using search terms including ‘counterfeit’, ‘tampered’, and ‘fake’. Threads were thematically analysed for overall content, leading to the identification of themes. Results: Data from 134 threads (2743 posts from 875 unique avatars) was included. Two main themes were identified from the analysis: 1) Experiences with counterfeit product; and 2) Harms and benefits associated with counterfeit product.Conclusions: The use of counterfeit or contaminated substances represents a public health concern. Those who report using PIEDs such as AAS for non-medical purposes report consuming these substances, and experiencing harm as a result. Consumers take steps to limit coming into contact with counterfeit or contaminated product, though recognise that many of these have limitations. The implementation of accessible drug safety checking services may provide an opportunity to provide consumers with information to assist them with making healthier choices. more...

In recent decades, more women have been elected into office, showing the gains which have been made as more take a seat at the political table. In 2008, women occupied 18.3 per cent of parliamentary seats worldwide, growing to 24.3 per cent in 2019 (IPU 2019). While some affix a positive slant to this upward-moving trajectory, others see this slow tread onwards as overwhelmingly unsatisfactory. According to the World Economic Forum, if the same rate of change were to continue as it has done, the global gender gap in politics would take 107 years to close (World Economic Forum 2018). Women’s low numbers in parliaments across the world highlight that, as a category, they are still an underrepresented group, showing this to be a globally systemic issue. In terms of representative democracies, these low figures are significant, as they arguably have implications for both the descriptive and substantive representation of women (Celis and Childs 2008) and also send important signals about who is elected to stand for the “public” in positions of power and included/excluded in political decision-making. This chapter focuses on the gendered mediation—the gendered discursive practices embedded in social norms (Gidengil and Everitt, 2003)—of female politicians and how this may perpetuate entrenched attitudes around gender norms, thus contributing to women’s mis- and underrepresentation in global politics. more...

BACKGROUND Noninvasive prenatal diagnosis (NIPD) for monogenic disorders has a high uptake by families. Since 2013, our accredited public health service laboratory has offered NIPD for monogenic disorders, predominantly for de novo or paternally dominantly inherited mutations. Here we describe the extension of this service to include definitive NIPD for a recessive condition, cystic fibrosis (CF). METHODS Definitive NIPD for CF was developed using next-generation sequencing. Validation was performed on 13 cases from 10 families before implementation. All cases referred for CF NIPD were reviewed to determine turnaround times, genotyping results, and pregnancy outcomes. RESULTS Of 38 referrals, 36 received a result with a mean turnaround of 5.75 days (range, 3–11 days). Nine cases were initially inconclusive, with 3 reported unaffected because the low-risk paternal allele was inherited and 4 cases in which the high-risk paternal allele was inherited, receiving conclusive results following repeat testing. One case was inconclusive owing to a paternal recombination around the mutation site, and one case was uninformative because of no heterozygosity. Before 2016, 3 invasive referrals for CF were received annually compared with 38 for NIPD in the 24 months since offering a definitive NIPD service. CONCLUSIONS Timely and accurate NIPD for definitive prenatal diagnosis of CF is possible in a public health service laboratory. The method detects recombinations, and the service is well-received as evidenced by the significant increase in referrals. The bioinformatic approach is gene agnostic and will be used to expand the range of conditions tested for. more...

The use of massively parallel sequencing of maternal cfDNA for non-invasive prenatal testing (NIPT) of aneuploidy is widely available. Recently, the scope of testing has increased to include selected subchromosomal abnormalities, but the number of samples reported has been small. We developed a calling pipeline based on a segmentation algorithm for the detection of these rearrangements in maternal plasma. The same read depth used in our standard pipeline for aneuploidy NIPT detected 15/18 (83%) samples with pathogenic rearrangements > 6 Mb but only 2/10 samples with rearrangements < 6 Mb, unless they were maternally inherited. There were two false-positive calls in 534 samples with no known subchromosomal abnormalities (specificity 99.6%). Using higher read depths, we detected 29/31 fetal subchromosomal abnormalities, including the three samples with maternally inherited microduplications. We conclude that test sensitivity is a function of the fetal fraction, read depth, and size of the fetal CNV and that at least one of the two false negatives is due to a low fetal fraction. The lack of an independent method for determining fetal fraction, especially for female fetuses, leads to uncertainty in test sensitivity, which currently has implications for this technique’s future as a clinical diagnostic test. Furthermore, to be effective, NIPT must be able to detect chromosomal rearrangements across the whole genome for a very low false-positive rate. Because standard NIPT can only detect the majority of larger (>6 Mb) chromosomal rearrangements and requires knowledge of fetal fraction, we consider that it is not yet ready for routine clinical implementation. more...

Objective Accurate prenatal diagnosis of genetic conditions can be challenging and usually requires invasive testing. Here, we demonstrate the potential of next-generation sequencing (NGS) for the analysis of cell-free DNA in maternal blood to transform prenatal diagnosis of monogenic disorders. Methods Analysis of cell-free DNA using a PCR and restriction enzyme digest (PCR–RED) was compared with a novel NGS assay in pregnancies at risk of achondroplasia and thanatophoric dysplasia. Results PCR–RED was performed in 72 cases and was correct in 88.6%, inconclusive in 7% with one false negative. NGS was performed in 47 cases and was accurate in 96.2% with no inconclusives. Both approaches were used in 27 cases, with NGS giving the correct result in the two cases inconclusive with PCR–RED. Conclusion NGS provides an accurate, flexible approach to non-invasive prenatal diagnosis of de novo and paternally inherited mutations. It is more sensitive than PCR–RED and is ideal when screening a gene with multiple potential pathogenic mutations. These findings highlight the value of NGS in the development of non-invasive prenatal diagnosis for other monogenic disorders. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. What's already known about this topic? Non-invasive prenatal diagnosis (NIPD) using PCR-based methods has been reported for the detection or exclusion of individual paternally inherited or de novo alleles in maternal plasma. What does this study add? NIPD using next generation sequencing provides an accurate, more sensitive approach which can be used to detect multiple mutations in a single assay and so is ideal when screening a gene with multiple potential pathogenic mutations. Next generation sequencing thus provides a flexible approach to non-invasive prenatal diagnosis ideal for use in a busy service laboratory. more...

Our UK National Health Service regional genetics laboratory offers NIPD for autosomal dominant and de novo conditions (achondroplasia, thanataphoric dysplasia, Apert syndrome), paternal mutation exclusion for cystic fibrosis and a range of bespoke tests. NIPD avoids the risks associated with invasive testing, making prenatal diagnosis more accessible to families at high genetic risk. However, the challenge remains in offering definitive diagnosis for autosomal recessive diseases, which is complicated by the predominance of the maternal mutant allele in the cell-free DNA sample and thus requires a variety of different approaches. Validation and diagnostic implementation for NIPD of congenital adrenal hyperplasia (CAH) is further complicated by presence of a pseudogene that requires a different approach. We have used an assay targeting approximately 6700 heterozygous SNPs around the CAH gene (CYP21A2) to construct the high-risk parental haplotypes and tested this approach in five cases, showing that inheritance of the parental alleles can be correctly identified using NIPD. We are evaluating various measures of the fetal fraction to help determine inheritance of parental mutations. We are currently exploring the utility of an NIPD multi-disorder panel for autosomal recessive disease, to make testing more widely applicable to families with a variety of serious genetic conditions. more...

Optimisation of a series of benzazepine sulfonamide hit compounds identified from high throughput screening led to the discovery of a new series of tractable, potent motilin receptor agonists.

Measurement of intracellular calcium release following agonist challenge within cells expressing the relevant membrane protein is a commonly used format to derive structure-activity relationship (SAR) data within a compound profiling assay. The Fluorometric Imaging Plate Reader (FLIPR) has become the gold standard for this purpose. FLIPR traditionally uses cells that are maintained in continuous culture for compound profiling of iterative chemistry campaigns. This supply dictates that assays can only be run on 4 of 5 weekdays, or alternative cell culture machinery is required such that plating can occur remotely at the weekend. The data reported here demonstrate that high-quality compound profiling data can be generated from the use of cryopreserved cells and that these cells can also be plated at various densities to generate equivalent data between 24 and 72 h postplating. Hence, the authors report a method that allows data generation throughout the week and without the requirement of highly automated cell culture or continuous culture. (Journal of Biomolecular Screening XXXX:xx-xx) more...

Our UK National Health Service regional genetics laboratory offers NIPD for autosomal dominant and de novo conditions (achondroplasia, thanataphoric dysplasia, Apert syndrome), paternal mutation exclusion for cystic fibrosis and a range of bespoke tests. NIPD avoids the risks associated with invasive testing, making prenatal diagnosis more accessible to families at high genetic risk. However, the challenge remains in offering definitive diagnosis for autosomal recessive diseases, which is complicated by the predominance of the maternal mutant allele in the cell-free DNA sample and thus requires a variety of different approaches. Validation and diagnostic implementation for NIPD of congenital adrenal hyperplasia (CAH) is further complicated by presence of a pseudogene that requires a different approach. We have used an assay targeting approximately 6700 heterozygous SNPs around the CAH gene (CYP21A2) to construct the high-risk parental haplotypes and tested this approach in five cases, showing that inheritance of the parental alleles can be correctly identified using NIPD. We are evaluating various measures of the fetal fraction to help determine inheritance of parental mutations. We are currently exploring the utility of an NIPD multi-disorder panel for autosomal recessive disease, to make testing more widely applicable to families with a variety of serious genetic conditions. more...

Over the last 50 years, Australian governments have introduced a range of measures that seek to deter asylum seekers. Current practice sees asylum seekers once again detained in offshore detention in neighbouring countries. more...

Objectives We aim to develop non-invasive prenatal diagnosis (NIPD) for cystic fibrosis (CF) and determine costs and implications for implementation. Methods A next-generation sequencing assay was developed to detect ten common CF mutations for exclusion of the paternal mutation in maternal plasma. Using uptake data from a study exploring views on NIPD for CF, total test-related costs were estimated for the current care pathway and compared with those incorporating NIPD. Results The assay reliably predicted mutation status in all control and maternal plasma samples. Of carrier or affected adults with CF (n = 142) surveyed, only 43.5% reported willingness to have invasive testing for CF with 94.4% saying they would have NIPD. Using these potential uptake data, the incremental costs of NIPD over invasive testing per 100 pregnancies at risk of CF are £9025 for paternal mutation exclusion, and £26 510 for direct diagnosis. Conclusions We have developed NIPD for risk stratification in around a third of CF families. There are economic implications due to potential increased test demand to inform postnatal management rather than to inform decisions around termination of an affected pregnancy. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. more...

Background Non-invasive prenatal testing (NIPT) for aneuploidies is now available through commercial companies in many countries, including through private practice in the United Kingdom (UK). Thorough evaluation of service delivery requirements are needed to facilitate NIPT being offered more widely within state funded healthcare systems such as the UK’s National Health Service (NHS). Successful implementation will require the development of laboratory standards, consideration of stakeholder views, an analysis of costs and development of patient and health professional educational materials. Methods/Design NIPT will be offered in an NHS setting as a contingent screening test. Pregnant woman will be recruited through six maternity units in England and Scotland. Women eligible for Down’s syndrome screening (DSS) will be informed about the study at the time of booking. Women that choose routine DSS will be offered NIPT if they have a screening risk ≥1:1000. NIPT results for trisomy 21, 18, 13 will be reported within 7–10 working days. Data on DSS, NIPT and invasive testing uptake, pregnancy outcomes and test efficacy will be collected. Additional data will be gathered though questionnaires to a) determine acceptability to patients and health professionals, b) evaluate patient and health professional education, c) assess informed choice in women accepting or declining testing and d) gauge family expenses. Qualitative interviews will also be conducted with a sub-set of participating women and health professionals. Discussion The results of this study will make a significant contribution to policy decisions around the implementation of NIPT for aneuploidies within the UK NHS. The laboratory standards for testing and reporting, education materials and counselling strategies developed as part of the study are likely to underpin the introduction of NIPT into NHS practice. NIHR Portfolio Number 13865 more...

This article examines the redress processes for victims of human rights violations. It explores the outcomes of human rights law from the point of view of victims of human rights violations and evaluates what outcome may be satisfactory for victims. The analysis reveals that while efforts to redress human rights violations have produced a considerable volume of legal instruments, reports, recommendations and programs, what victims have actually received at the end of the day is less impressive. This article highlights the fact that many victims of human rights violations are not able to access any avenue of redress. It also stressed the need for procedural justice and victim-centred approaches in the reparations processes. more...

Recently, we have witnessed the rapid translation into clinical practice of non-invasive prenatal testing for the common aneuploidies, most notably within the United States and China. This represents a lucrative market with testing being driven by companies developing and offering their services. These tests are currently aimed at women with high/medium-risk pregnancies identified by serum screening and/or ultrasound scanning. Uptake has been impressive, albeit limited to the commercial sector. However, non-invasive prenatal diagnosis (NIPD) for single-gene disorders has attracted less interest, no doubt because this represents a much smaller market opportunity and in the majority of cases has to be provided on a bespoke, patient or disease-specific basis. The methods and workflows are labour-intensive and not readily scalable. Nonetheless, there exists a significant need for NIPD of single-gene disorders, and the continuing advances in technology and data analysis should facilitate the expansion of the NIPD test repertoire. Here, we review the progress that has been made to date, the different methods and platform technologies, the technical challenges, and assess how new developments may be applied to extend testing to a wider range of genetic disorders. more...

Objective To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down’s syndrome into the NHS maternity care pathway. Design Prospective cohort study. Setting Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015. Participants All pregnant women with a current Down’s syndrome risk on screening of at least 1/1000. Main outcome measures Outcomes were uptake of NIPT, number of cases of Down’s syndrome detected, invasive tests performed, and miscarriages avoided. Pregnancy outcomes and costs associated with implementation of NIPT, compared with current screening, were determined using study data on NIPT uptake and invasive testing in combination with national datasets. Results NIPT was prospectively offered to 3175 pregnant women. In 934 women with a Down’s syndrome risk greater than 1/150, 695 (74.4%) chose NIPT, 166 (17.8%) chose invasive testing, and 73 (7.8%) declined further testing. Of 2241 women with risks between 1/151 and 1/1000, 1799 (80.3%) chose NIPT. Of 71 pregnancies with a confirmed diagnosis of Down’s syndrome, 13/42 (31%) with the diagnosis after NIPT and 2/29 (7%) after direct invasive testing continued, resulting in 12 live births. In an annual screening population of 698 500, offering NIPT as a contingent test to women with a Down’s syndrome screening risk of at least 1/150 would increase detection by 195 (95% uncertainty interval −34 to 480) cases with 3368 (2279 to 4027) fewer invasive tests and 17 (7 to 30) fewer procedure related miscarriages, for a non-significant difference in total costs (£−46 000, £−1 802 000 to £2 661 000). The marginal cost of NIPT testing strategies versus current screening is very sensitive to NIPT costs; at a screening threshold of 1/150, NIPT would be cheaper than current screening if it cost less than £256. Lowering the risk threshold increases the number of Down’s syndrome cases detected and overall costs, while maintaining the reduction in invasive tests and procedure related miscarriages. Conclusions Implementation of NIPT as a contingent test within a public sector Down’s syndrome screening programme can improve quality of care, choices for women, and overall performance within the current budget. As some women use NIPT for information only, the Down’s syndrome live birth rate may not change significantly. Future research should consider NIPT uptake and informed decision making outside of a research setting. more...

Average annual fertility rates in industrialised countries have been below two children per woman for the past 3 decades. The reasons behind women's childbearing behaviour are complex. However, a lack of awareness regarding the consequences of delayed childbearing and the inability of reproductive technologies to overcome the 'biological clock' may be contributory factors.A narrative review guided by the research question: What do women need to know about the consequences of delayed childbearing in order to make informed decisions about their fertility?There are three facts that women need to know in order to make informed decisions around their fertility: Some women want to have more children than they are able to have because they postpone childbearing; there can be medical consequences to delaying childbearing and; some women's ideas about their fertility don't match the 'the scientific facts'. General practitioners are well placed to play a strategic role in the provision of timely, relevant information to help women make informed decisions about their fertility. Further research is needed to identify the most appropriate ways for GPs to communicate this information. more...

N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine 12 (GSK962040) is a novel small molecule motilin receptor agonist. It possesses excellent activity at the recombinant human motilin receptor and also at the native rabbit motilin receptor where its agonist activity results in potentiation of the amplitude of neuronal-mediated contractions of isolated gastric antrum tissue. Compound 12 also possesses highly promising pharmacokinetic profiles in both rat and dog, and these results, in combination with further profiling in human native tissue and an in vivo model of gastrointestinal transit in the rabbit, have led to its selection as a candidate for further development. more...

As part of an on-going lead optimisation effort, a cross screening exercise identified an aryl sulphonyl amide hit that was optimised to afford a highly potent series of ghrelin receptor agonists.

High-throughput screening resulted in the identification of a series of novel motilin receptor agonists with relatively low molecular weights. The series originated from an array of biphenyl derivatives designed to target 7-transmembrane (7-TM) receptors. Further investigation of the structure-activity relationship within the series resulted in the identification of compound (22) as a potent and selective agonist at the motilin receptor. more...

A series of small molecule orally bioavailable ghrelin receptor agonists have been identified through systematic optimisation of a high throughput screening hit.

High throughput screening combined with efficient datamining and parallel synthesis led to the discovery of a novel series of indolines showing potent in vitro ghrelin receptor agonist activity and acceleration of gastric emptying in rats. more...

In northern and central Israel are some 70 villages that are not recognized by the state of Israel. At least half of these villages are not connected to the national drinking water networks and lack sufficient quality and quantity of water. Outbreaks of diseases associated with contaminated water supply have occurred, as well as substantial environmental distress. An outbreak of hepatitis A led to the cooperation of a public health physician, a nurse, an environmental engineer, and a human rights lawyer in successfully taking a case to the International Water Tribunal to get access to safe drinking water for these communities. This case study provides a model for cooperation between proponents and practitioners of health and human rights. more...