Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management.

Purpose Unexpected fetal abnormalities occur in 2-5% of pregnancies. While traditional cytogenetic and microarray approaches achieve diagnosis in around 40% of cases, lack of diagnosis in others impedes parental counseling, informed decision making, and pregnancy management. Postnatally exome sequencing yields high diagnostic rates, but relies on careful phenotyping to interpret genotype results. Here we used a multidisciplinary approach to explore the utility of rapid fetal exome sequencing for prenatal diagnosis using skeletal dysplasias as an exemplar. Methods Parents in pregnancies undergoing invasive testing because of sonographic fetal abnormalities, where multidisciplinary review considered skeletal dysplasia a likely etiology, were consented for exome trio sequencing (both parents and fetus). Variant interpretation focused on a virtual panel of 240 genes known to cause skeletal dysplasias. Results Definitive molecular diagnosis was made in 13/16 (81%) cases. In some cases, fetal ultrasound findings alone were of sufficient severity for parents to opt for termination. In others, molecular diagnosis informed accurate prediction of outcome, improved parental counseling, and enabled parents to terminate or continue the pregnancy with certainty. Conclusion Trio sequencing with expert multidisciplinary review for case selection and data interpretation yields timely, high diagnostic rates in fetuses presenting with unexpected skeletal abnormalities. This improves parental counseling and pregnancy management.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.30

How large should whales be?

The evolution and distribution of species body sizes for terrestrial mammals is well-explained by a macroevolutionary tradeoff between short-term selective advantages and long-term extinction risks from increased species body size, unfolding above the 2g minimum size induced by thermoregulation in air. Here, we consider whether this same tradeoff, formalized as a constrained convection-reaction-diffusion system, can also explain the sizes of fully aquatic mammals, which have not previously been considered. By replacing the terrestrial minimum with a pelagic one, at roughly 7000g, the terrestrial mammal tradeoff model accurately predicts, with no tunable parameters, the observed body masses of all extant cetacean species, including the 175,000,000g Blue Whale. This strong agreement between theory and data suggests that a universal macroevolutionary tradeoff governs body size evolution for all mammals, regardless of their habitat. The dramatic sizes of cetaceans can thus be attributed mainly to the increased convective heat loss is water, which shifts the species size distribution upward and pushes its right tail into ranges inaccessible to terrestrial mammals. Under this macroevolutionary tradeoff, the largest expected species occurs where the rate at which smaller-bodied species move up into large-bodied niches approximately equals the rate at which extinction removes them.Comment: 7 pages, 3 figures, 2 data table

Strengthening health systems in low-income countries by enhancing organizational capacities and improving institutions

Background: This paper argues that the global health agenda tends to privilege short-term global interests at the expense of long-term capacity building within national and community health systems. The Health Systems Strengthening (HSS) movement needs to focus on developing the capacity of local organizations and the institutions that influence how such organizations interact with local and international stakeholders. Discussion: While institutions can enable organizations, they too often apply requirements to follow paths that can stifle learning and development. Global health actors have recognized the importance of supporting local organizations in HSS activities. However, this recognition has yet to translate adequately into actual policies to influence funding and practice. While there is not a single approach to HSS that can be uniformly applied to all contexts, several messages emerge from the experience of successful health systems presented in this paper using case studies through a complex adaptive systems lens. Two key messages deserve special attention: the need for donors and recipient organizations to work as equal partners, and the need for strong and diffuse leadership in low-income countries. Summary: An increasingly dynamic and interdependent post-Millennium Development Goals (post-MDG) world requires new ways of working to improve global health, underpinned by a complex adaptive systems lens and approaches that build local organizational capacity

A structured telephone-delivered intervention to reduce problem alcohol use (Ready2Change): study protocol for a parallel group randomised controlled trial

Background: Current population surveys suggest around 20% of Australians meet diagnostic criteria for an alcohol use disorder. However, only a minority seek professional help due to individual and structural barriers, such as low health literacy, stigma, geography, service operating hours and wait lists. Telephone-delivered interventions are readily accessible and ideally placed to overcome these barriers. We will conduct a randomised controlled trial (RCT) to examine the efficacy of a standalone, structured telephone-delivered intervention to reduce alcohol consumption, problem severity and related psychological distress among individuals with problem alcohol use. Methods/design: This is a single site, parallel group, two-arm superiority RCT. We will recruit 344 participants from across Australia with problem alcohol use. After completing a baseline assessment, participants will be randomly allocated to receive either the Ready2Change (R2C) intervention (n = 172, four to six sessions of structured telephone-delivered intervention, R2C self-help resource, guidelines for alcohol consumption and stress management pamphlets) or the control condition (n = 172, four phone check-ins < 5 min, guidelines for alcohol consumption and stress management pamphlets). Telephone follow-up assessments will occur at 4-6 weeks, 3 months, 6 months and 12 months post-baseline. The primary outcome is the Alcohol Use Disorders Identification Test (AUDIT) score administered at 3 months post-baseline. Secondary outcomes include change in AUDIT score (6 and 12 months post-baseline), change in number of past-month heavy drinking days, psychological distress, health and wellbeing, quality of life, client treatment evaluation and cost effectiveness. Discussion: This study will be one of the first RCTs conducted internationally to examine the impact of a standalone, structured telephone-delivered intervention to address problem alcohol use and associated psychological morbidity. The proposed intervention is expected to contribute to the health and wellbeing of individuals who are otherwise unlikely to seek treatment through mainstream service models, to reduce the burden on specialist services and primary care providers and to provide an accessible and proportionate response, with resulting cost savings for the health system and broader community. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000828224. Pre-registered on 16 May 2018

The State Relationship with Religion:defined through disciplinary procedures of accounting and regulation

State regulation of charities is increasing. Nevertheless, although religious entities also pursue charitable objectives, jurisdictions often regulate them differently. In some states (including England until recently), the church (religious charities) are not called to account for their common-good contribution, despite owning significant assets and receiving public and government income. These regulatory and accounting variations emanate from a state’s historically informed positional relationship with religion, which may be discordant against increasing religious pluralism and citizens’ commonly-held beliefs. To open a debate on state–church relationships within the accounting history literature, this article analyses changes in England since 1534. It utilises a state–church framework from Monsma and Soper, combined with an application and extension of Foucauldian governmentality. The longitudinal study shows direct and indirect governmentality tools change with the state–church relationship. Such harmonisation of regulatory approach relies on citizens/entities subverting imposition of state demands which fail to meet their concept of common-good

Herbivore Preference for Native vs. Exotic Plants: Generalist Herbivores from Multiple Continents Prefer Exotic Plants That Are Evolutionarily Naïve

Enemy release and biotic resistance are competing, but not mutually exclusive, hypotheses addressing the success or failure of non-native plants entering a new region. Enemy release predicts that exotic plants become invasive by escaping their co-adapted herbivores and by being unrecognized or unpalatable to native herbivores that have not been selected to consume them. In contrast, biotic resistance predicts that native generalist herbivores will suppress exotic plants that will not have been selected to deter these herbivores. We tested these hypotheses using five generalist herbivores from North or South America and nine confamilial pairs of native and exotic aquatic plants. Four of five herbivores showed 2.4–17.3 fold preferences for exotic over native plants. Three species of South American apple snails (Pomacea sp.) preferred North American over South American macrophytes, while a North American crayfish Procambarus spiculifer preferred South American, Asian, and Australian macrophytes over North American relatives. Apple snails have their center of diversity in South America, but a single species (Pomacea paludosa) occurs in North America. This species, with a South American lineage but a North American distribution, did not differentiate between South American and North American plants. Its preferences correlated with preferences of its South American relatives rather than with preferences of the North American crayfish, consistent with evolutionary inertia due to its South American lineage. Tests of plant traits indicated that the crayfish responded primarily to plant structure, the apple snails primarily to plant chemistry, and that plant protein concentration played no detectable role. Generalist herbivores preferred non-native plants, suggesting that intact guilds of native, generalist herbivores may provide biotic resistance to plant invasions. Past invasions may have been facilitated by removal of native herbivores, introduction of non-native herbivores (which commonly prefer native plants), or both

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Hysterectomy at a Canadian tertiary care facility: results of a one year retrospective review

BACKGROUND: The purpose of this study was to investigate the indications for and approach to hysterectomy at Kingston General Hospital (KGH), a teaching hospital affiliated with Queen's University at Kingston, Ontario. In particular, in light of current literature and government standards suggesting the superiority of vaginal versus abdominal approaches and a high number of concurrent oophorectomies, the aim was to examine the circumstances in which concurrent oophorectomies were performed and to compare abdominal and vaginal hysterectomy outcomes. METHODS: A retrospective chart audit of 372 consecutive hysterectomies performed in 2001 was completed. Data regarding patient characteristics, process of care and outcomes were collected. Data were analyzed using descriptive statistics, t-tests and linear and logistic regression. RESULTS: Average age was 48.5 years, mean body mass index (BMI) was 28.6, the mean length of stay (LOS) was 5.2 days using an abdominal approach and 3.0 days using a vaginal approach without laparoscopy. 14% of hysterectomies were performed vaginally, 5.9% were laparoscopically assisted vaginal hysterectomies and the rest were abdominal hysterectomies. The most common indication was dysfunctional or abnormal uterine bleeding (37%). The average age of those that had an oophorectomy (removal of both ovaries) was 50.8 years versus 44.3 years for those that did not (p < .05). Factors associated with LOS included surgical approach, age and the number of concurrent procedures. CONCLUSIONS: A significant reduction in LOS was found using the vaginal approach. Both the patient and the health care system may benefit from the tendency towards an increased use of vaginal hysterectomies. The audit process demonstrated the usefulness of an on-going review mechanism to examine trends associated with common surgical procedures