Making Study Populations Visible through Knowledge Graphs

Treatment recommendations within Clinical Practice Guidelines (CPGs) are largely based on findings from clinical trials and case studies, referred to here as research studies, that are often based on highly selective clinical populations, referred to here as study cohorts. When medical practitioners apply CPG recommendations, they need to understand how well their patient population matches the characteristics of those in the study cohort, and thus are confronted with the challenges of locating the study cohort information and making an analytic comparison. To address these challenges, we develop an ontology-enabled prototype system, which exposes the population descriptions in research studies in a declarative manner, with the ultimate goal of allowing medical practitioners to better understand the applicability and generalizability of treatment recommendations. We build a Study Cohort Ontology (SCO) to encode the vocabulary of study population descriptions, that are often reported in the first table in the published work, thus they are often referred to as Table 1. We leverage the well-used Semanticscience Integrated Ontology (SIO) for defining property associations between classes. Further, we model the key components of Table 1s, i.e., collections of study subjects, subject characteristics, and statistical measures in RDF knowledge graphs. We design scenarios for medical practitioners to perform population analysis, and generate cohort similarity visualizations to determine the applicability of a study population to the clinical population of interest. Our semantic approach to make study populations visible, by standardized representations of Table 1s, allows users to quickly derive clinically relevant inferences about study populations.Comment: 16 pages, 4 figures, 1 table, accepted to the ISWC 2019 Resources Track (https://iswc2019.semanticweb.org/call-for-resources-track-papers/

Flood risk and climate change: global and regional perspectives

A holistic perspective on changing rainfall-driven flood risk is provided for the late 20th and early 21st centuries. Economic losses from floods have greatly increased, principally driven by the expanding exposure of assets at risk. It has not been possible to attribute rain-generated peak streamflow trends to anthropogenic climate change over the past several decades. Projected increases in the frequency and intensity of heavy rainfall, based on climate models, should contribute to increases in precipitation-generated local flooding (e.g. flash flooding and urban flooding). This article assesses the literature included in the IPCC SREX report and new literature published since, and includes an assessment of changes in flood risk in seven of the regions considered in the recent IPCC SREX report-Africa, Asia, Central and South America, Europe, North America, Oceania and Polar regions. Also considering newer publications, this article is consistent with the recent IPCC SREX assessment finding that the impacts of climate change on flood characteristics are highly sensitive to the detailed nature of those changes and that presently we have only low confidence1 in numerical projections of changes in flood magnitude or frequency resulting from climate change

Managing housing needs in post conflict housing reconstruction in Sri Lanka: gaps versus recommendations

Addressing housing needs in post conflict housing reconstruction leads to successful housing reconstruction. As part of a study of investigating how the housing needs can be effectively addressed in post conflict housing reconstruction, this paper identifies the gaps in managing housing needs in post conflict housing reconstruction within the context of Sri Lanka and presents the recommendations to minimise such gaps. Data was collected through un-structured interviews conducted with 37 participants, comprising policy makers, practitioners, academics and beneficiaries who engaged in post conflict housing reconstruction in Sri Lanka. Gaps were mainly found in conflict sensitivity, measures related to physical housing, performance of implementing agencies, policy and practice issues. On the job training, application of ‘do no harm’ principles, enhanced beneficiary participation, enhanced accountability, effective monitoring, enhanced knowledge sharing, adequate drinking water facilities, irrigation development and initiatives for material manufacturing were suggested as recommendations to minimise these gaps. Identification of gaps in managing housing needs in post conflict housing reconstruction and recommendations to minimise them inform policy makers to address the housing needs effectively through incorporating these aspects into the related policies. This in turn enhances the sustainability in housing development after conflicts

The use of biomedicine, complementary and alternative medicine, and ethnomedicine for the treatment of epilepsy among people of South Asian origin in the UK

Studies have shown that a significant proportion of people with epilepsy use complementary and alternative medicine (CAM). CAM use is known to vary between different ethnic groups and cultural contexts; however, little attention has been devoted to inter-ethnic differences within the UK population. We studied the use of biomedicine, complementary and alternative medicine, and ethnomedicine in a sample of people with epilepsy of South Asian origin living in the north of England. Interviews were conducted with 30 people of South Asian origin and 16 carers drawn from a sampling frame of patients over 18 years old with epilepsy, compiled from epilepsy registers and hospital databases. All interviews were tape-recorded, translated if required and transcribed. A framework approach was adopted to analyse the data. All those interviewed were taking conventional anti-epileptic drugs. Most had also sought help from traditional South Asian practitioners, but only two people had tried conventional CAM. Decisions to consult a traditional healer were taken by families rather than by individuals with epilepsy. Those who made the decision to consult a traditional healer were usually older family members and their motivations and perceptions of safety and efficacy often differed from those of the recipients of the treatment. No-one had discussed the use of traditional therapies with their doctor. The patterns observed in the UK mirrored those reported among people with epilepsy in India and Pakistan. The health care-seeking behaviour of study participants, although mainly confined within the ethnomedicine sector, shared much in common with that of people who use global CAM. The appeal of traditional therapies lay in their religious and moral legitimacy within the South Asian community, especially to the older generation who were disproportionately influential in the determination of treatment choices. As a second generation made up of people of Pakistani origin born in the UK reach the age when they are the influential decision makers in their families, resort to traditional therapies may decline. People had long experience of navigating plural systems of health care and avoided potential conflict by maintaining strict separation between different sectors. Health care practitioners need to approach these issues with sensitivity and to regard traditional healers as potential allies, rather than competitors or quacks

Collection of Millet Germplasm in Sri Lanka and Thailand

雑穀類は, イネ, ムギ等のような多量生産を行う穀類以外を総称していう言葉である。今回の探索収集では, 禾穀類の中の小粒作物 (アワ, キビ, ヒエ等, ミレットと言われる) を中心に, モロコシ, トウモロコシ等も収集した。ミレットは, 古くからユーラシア大陸或はアフリカ大陸において広く栽培され, 受け継がれてきたが, 近年, 生産性や収益性の高い作物に置き代わり, 急速に耕地から姿を消しつつある。今回は, 特にインドを中心としていまなお広く栽培されているシコクビエ, アワ等のミレットを中心に, 数種類の雑穀類をスリランカ及びタイ北部から収集した。収集した系統のほとんどは各地域の農家において古くから栽培されてきた在来種である。本探索により, 48点のシコクビエ (Eleusine coracana), 23点のアワ (Setariaitalica), 6点のキビ (Panicum miliaceum), 8点のモロコシ (Sorghum bicolor), 9点のトウモロコシ (Zea mays) を収集した。また, ミレットとの混作作物或は隣接した畠の作物も一部収集した。全収集数は106点で, そのうち89点はスリランカで, 17点はタイで収集した。中部及び南部スリランカにおいて, 標高Omから約2,000mの地域を延べ1,475kmに渡り探索し, 作物の生育データと共に種子を収集した。スリランカにおいては, 植物遺伝資源センターが独自に探索収集を行っていたので, 同センターの収集リストを照合し, 探索集落に重複を生じないように配慮した。シコクビエは乾燥・半乾燥地帯の焼畑等において広く栽培されていた。収集したサンプルには穂の形や大きさ, 節の色等に変異が認められた。混作が多く, 混作作物にはアワ, ナ類等色々であった。キビの栽培を見かけることは非常に少なく, 主として農家の保存種子の分譲を受けた。豆類等隣接畑から収集したものもあった。シコクビエはいわゆる "うす焼き" あるいはペースト状にして食べるということであった。アワはお粥として食べるのが一般的のようであった。農家は雑穀, 野菜等の作物の種子をよく保存しており, 古くから集落に伝わる在来種が多かった。スリランカには今回を含めても未収集地域が多くあり, 今後とも収集が必要である。北部タイにおいてはミレットの食用としての栽培は急減していた。作期ではないこともあってか, 栽培畑に巡り会うことはなかった。小数部族の集落を訪ね, 農家が保存している穂や乾燥中の穂から種子を収集した。収集物はモロコシ, トウモロコシがほとんどであった。北部タイのミレット収集を計画する場合, 北西部のカレン族, 北東部のリス族等が住む, より深い山岳地帯に足を踏み入れる必要があると考えられた

Postnatal depression across countries and cultures : a qualitative study

Background: Postnatal depression seems to be a universal condition with similar rates in different countries. However, anthropologists question the cross-cultural equivalence of depression, particularly at a life stage so influenced by cultural factors. Aims: To develop a qualitative method to explore whether postnatal depression is universally recognised, attributed and described and to enquire into people’s perceptions of remedies and services for morbid states of unhappiness within the context of local services. Method: The study took place in 15 centres in 11 countries and drew on three groups of informants: focus groups with new mothers, interviews with fathers and grandmothers, and interviews with health professionals.Textual analysis of these three groups was conducted separately in each centre and emergent themes compared across centres. Results: All centres described morbid unhappiness after childbirth comparable to postnatal depression but not all saw this as an illness remediable by health interventions. Conclusions: Although the findings of this study support the universality of a morbid state of unhappiness following childbirth, they also support concerns about the cross-cultural equivalence of postnatal depression as an illness requiring the intervention of health professionals; this has implications for future research

A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development

Cell lineages of the early human gonad commit to one of the two mutually antagonistic organogenetic fates, the testis or the ovary. Some individuals with a 46,XX karyotype develop testes or ovotestes (testicular or ovotesticular disorder of sex development; TDSD/OTDSD), due to the presence of the testis-determining gene, SRY Other rare complex syndromic forms of TDSD/OTDSD are associated with mutations in pro-ovarian genes that repress testis development (e.g. WNT4); however, the genetic cause of the more common non-syndromic forms is unknown. Steroidogenic factor-1 (known as NR5A1) is a key regulator of reproductive development and function. Loss-of-function changes in NR5A1 in 46,XY individuals are associated with a spectrum of phenotypes in humans ranging from a lack of testis formation to male infertility. Mutations in NR5A1 in 46,XX women are associated with primary ovarian insufficiency, which includes a lack of ovary formation, primary and secondary amenorrhoea as well as early menopause. Here, we show that a specific recurrent heterozygous missense mutation (p.Arg92Trp) in the accessory DNA-binding region of NR5A1 is associated with variable degree of testis development in 46,XX children and adults from four unrelated families. Remarkably, in one family a sibling raised as a girl and carrying this NR5A1 mutation was found to have a 46,XY karyotype with partial testicular dysgenesis. These unique findings highlight how a specific variant in a developmental transcription factor can switch organ fate from the ovary to testis in mammals and represents the first missense mutation causing isolated, non-syndromic 46,XX testicular/ovotesticular DSD in humans

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies

Expansion microscopy (ExM) enables imaging of preserved specimens with nanoscale precision on diffraction-limited instead of specialized super-resolution microscopes. ExM works by physically separating fluorescent probes after anchoring them to a swellable gel. The first ExM method did not result in the retention of native proteins in the gel and relied on custom-made reagents that are not widely available. Here we describe protein retention ExM (proExM), a variant of ExM in which proteins are anchored to the swellable gel, allowing the use of conventional fluorescently labeled antibodies and streptavidin, and fluorescent proteins. We validated and demonstrated the utility of proExM for multicolor super-resolution (~70 nm) imaging of cells and mammalian tissues on conventional microscopes.United States. National Institutes of Health (1R01GM104948)United States. National Institutes of Health (1DP1NS087724)United States. National Institutes of Health ( NIH 1R01EY023173)United States. National Institutes of Health (1U01MH106011