Health services research in the public healthcare system in Hong Kong: An analysis of over 1 million antihypertensive prescriptions between 2004-2007 as an example of the potential and pitfalls of using routinely collected electronic patient data

<b>Objectives</b> Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example.<p></p> <b>Methods</b> Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients’ demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes). <p></p> <b>Results</b> 1,096,282 visit episodes were accessed, representing 93,450 patients. Patients’ demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age > 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32-0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39). <p></p> In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension. <p></p> <b>Conclusion</b> The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant on ICPC codes some caution is warranted. In the case of uncomplicated hypertension, future research on pharmaco-epidemiology (such as prescription patterns) and clinical issues (such as side-effects of medications on metabolic parameters) seems feasible given the large size of the data set and the comparability of coded and non-coded patients

Protein-coding and non-coding gene expression analysis in differentiating human keratinocytes using a three-dimensional epidermal equivalent

The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and corniWed layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, diVerentiation, and cell death. To determine genes responsible for initiating and maintaining a corniWed epidermis, organotypic cultures comprised entirely of stratiWed KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array proWle of submerged cultures containing KCs predominantly in a proliferative (relatively undiVerentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct proWle of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, diVerentiation, and cell death. Next, diVerentially expressed microRNAs (miRNAs) and long noncoding (lncRNA) RNAs were identiWed in EEs. Several diVerentially expressed miRNAs were validated by qRT-PCR and Northern blots. miRNAs 203, 205 and Let-7b were up-regulated at early time points (6, 18 and 24 h) but downregulated by 120 h. To study the lncRNA regulation in EEs, we proWled lncRNA expression by microarray and validated the results by qRT-PCR. Although the diVerential expression of several lncRNAs is suggestive of a role in epidermal diVerentiation, their biological functions remain to be elucidated. The current studies lay the foundation for relevant model systems to address such fundamentally important biological aspects of epidermal structure and function in normal and diseased human skin

Pacific island regional preparedness for El Niño

The El Niño Southern Oscillation (ENSO) cycle is often blamed for disasters in Pacific island communities. From a disaster risk reduction (DRR) perspective, the challenges with the El Niño part of the ENSO cycle, in particular, are more related to inadequate vulnerability reduction within development than to ENSO-induced hazard influences. This paper analyses this situation, filling in a conceptual and geographic gap in El Niño-related research, by reviewing El Niño-related preparedness (the conceptual gap) for Pacific islands (the geographic gap). Through exploring El Niño impacts on Pacific island communities alongside their vulnerabilities, resiliences, and preparedness with respect to El Niño, El Niño is seen as a constructed discourse rather than as a damaging phenomenon, leading to suggestions for El Niño preparedness as DRR as part of development. Yet the attention which El Niño garners might bring resources to the Pacific region and its development needs, albeit in the short term while El Niño lasts. Conversely, the attention given to El Niño could shift blame from underlying causes of vulnerability to a hazard-centric viewpoint. Instead of focusing on one hazard-influencing phenomenon, opportunities should be created for the Pacific region to tackle wider DRR and development concerns

A transcriptomic analysis of Echinococcus granulosus larval stages:implications for parasite biology and host adaptation

The cestode Echinococcus granulosus--the agent of cystic echinococcosis, a zoonosis affecting humans and domestic animals worldwide--is an excellent model for the study of host-parasite cross-talk that interfaces with two mammalian hosts. To develop the molecular analysis of these interactions, we carried out an EST survey of E. granulosus larval stages. We report the salient features of this study with a focus on genes reflecting physiological adaptations of different parasite stages.We generated ~10,000 ESTs from two sets of full-length enriched libraries (derived from oligo-capped and trans-spliced cDNAs) prepared with three parasite materials: hydatid cyst wall, larval worms (protoscoleces), and pepsin/H(+)-activated protoscoleces. The ESTs were clustered into 2700 distinct gene products. In the context of the biology of E. granulosus, our analyses reveal: (i) a diverse group of abundant long non-protein coding transcripts showing homology to a middle repetitive element (EgBRep) that could either be active molecular species or represent precursors of small RNAs (like piRNAs); (ii) an up-regulation of fermentative pathways in the tissue of the cyst wall; (iii) highly expressed thiol- and selenol-dependent antioxidant enzyme targets of thioredoxin glutathione reductase, the functional hub of redox metabolism in parasitic flatworms; (iv) candidate apomucins for the external layer of the tissue-dwelling hydatid cyst, a mucin-rich structure that is critical for survival in the intermediate host; (v) a set of tetraspanins, a protein family that appears to have expanded in the cestode lineage; and (vi) a set of platyhelminth-specific gene products that may offer targets for novel pan-platyhelminth drug development.This survey has greatly increased the quality and the quantity of the molecular information on E. granulosus and constitutes a valuable resource for gene prediction on the parasite genome and for further genomic and proteomic analyses focused on cestodes and platyhelminths

Moonlighting Proteins Hal3 and Vhs3 Form a Heteromeric PPCDC with Ykl088w in Yeast CoA Biosynthesis

Premi a l'excel·lència investigadora. 2010Unlike most other organisms, the essential five-step Coenzyme A biosynthetic pathway has not been fully resolved in yeast. Specifically, the gene(s) encoding the phosphopantothenoylcysteine decarboxylase (PPCDC) activity still remains unidentified. Sequence homology analyses suggest three candidates, namely Ykl088w, Hal3 and Vhs3, as putative PPCDC enzymes in Saccharomyces cerevisiae. Interestingly, Hal3 and Vhs3 have been characterized as negative regulatory subunits of the Ppz1 protein phosphatase. Here we show that YKL088w does not encode a third Ppz1 regulatory subunit, and that the essential roles of Ykl088w and the Hal3/Vhs3 pair are complementary, cannot be interchanged and can be attributed to PPCDC-related functions. We demonstrate that while known eukaryotic PPCDCs are homotrimers, the active yeast enzyme is a heterotrimer which consists of Ykl088w and Hal3/Vhs3 monomers that separately provides two essential catalytic residues. Our results unveil Hal3/Vhs3 as moonlighting proteins, involved in both CoA biosynthesis and protein phosphatase regulation

Genome-wide identification of potato long intergenic noncoding RNAs responsive to <i>Pectobacterium carotovorum</i> subspecies <i>brasiliense</i> infection

BACKGROUND: Long noncoding RNAs (lncRNAs) represent a class of RNA molecules that are implicated in regulation of gene expression in both mammals and plants. While much progress has been made in determining the biological functions of lncRNAs in mammals, the functional roles of lncRNAs in plants are still poorly understood. Specifically, the roles of long intergenic nocoding RNAs (lincRNAs) in plant defence responses are yet to be fully explored. RESULTS: In this study, we used strand-specific RNA sequencing to identify 1113 lincRNAs in potato (Solanum tuberosum) from stem tissues. The lincRNAs are expressed from all 12 potato chromosomes and generally smaller in size compared to protein-coding genes. Like in other plants, most potato lincRNAs possess single exons. A time-course RNA-seq analysis between a tolerant and a susceptible potato cultivar showed that 559 lincRNAs are responsive to Pectobacterium carotovorum subsp. brasiliense challenge compared to mock-inoculated controls. Moreover, coexpression analysis revealed that 17 of these lincRNAs are highly associated with 12 potato defence-related genes. CONCLUSIONS: Together, these results suggest that lincRNAs have potential functional roles in potato defence responses. Furthermore, this work provides the first library of potato lincRNAs and a set of novel lincRNAs implicated in potato defences against P. carotovorum subsp. brasiliense, a member of the soft rot Enterobacteriaceae phytopathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2967-9) contains supplementary material, which is available to authorized users

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and Broadband Follow-Up of the Gravitational-Wave Transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser InterferometerGravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimatesof the time, significance, and sky location of the event were shared with 63 teams of observers covering radio,optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter wedescribe the low-latency analysis of the GW data and present the sky localization of the first observed compactbinary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-rayCoordinates Network circulars, giving an overview of the participating facilities, the GW sky localizationcoverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger,there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadbandcampaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broadcapabilities of the transient astronomy community and the observing strategies that have been developed to pursueneutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-upcampaign are being disseminated in papers by the individual teams

New models of health and social care for people in later life: mapping of innovation in services in two regions of the United Kingdom using a mixed method approach

\ua9 The Author(s) 2024.Background: Innovation for reforming health and social care is high on the policy agenda in the United Kingdom in response to the growing needs of an ageing population. However, information about new innovations of care being implemented is sparse. Methods: We mapped innovations for people in later life in two regions, North East England and South East Scotland. Data collection included discussions with stakeholders (n = 51), semi-structured interviews (n = 14) and website searches that focused on technology, evaluation and health inequalities. We analysed qualitative data using framework and thematic analyses. Quantitative data were analysed descriptively. Results: One hundred eleven innovations were identified across the two regions. Interviewees reported a wide range of technologies that had been rapidly introduced during the COVID-19 pandemic and many remained in use. Digital exclusion of certain groups of older people was an ongoing concern. Innovations fell into two groups; system-level ones that aimed to alleviate systems pressures such as preventing hospital (re)admissions, and patient-level ones which sought to enhance health and wellbeing directly. Interviewees were aware of the importance of health inequalities but lacked data to monitor the impact of innovations on these, and evaluation was challenging due to lack of time, training, and support. Quantitative findings revealed that two thirds of innovations (n = 74, 67%) primarily focused on the system level, whilst a third (n = 37, 33%) primarily focused on the patient-level. Overall, over half (n = 65, 59%) of innovations involved technologies although relatively few (n = 12, 11%) utilised advanced technologies. Very few (n = 16, 14%) focused on reducing health inequalities, and only a minority of innovations (n = 43, 39%) had undergone evaluation (most of which were conducted by the service providers themselves). Conclusions: We found a wide range of innovative care services being developed for people in later life, yet alignment with key policy priorities, such as addressing health inequalities, was limited. There was a strong focus on technology, with little consideration for the potential to widen the health inequality gap. The absence of robust evaluation was also a concern as most innovations were implemented without support to monitor effectiveness and/or without plans for sustainability and spread

Long non-coding RNAs and cancer: a new frontier of translational research?

Author manuscriptTiling array and novel sequencing technologies have made available the transcription profile of the entire human genome. However, the extent of transcription and the function of genetic elements that occur outside of protein-coding genes, particularly those involved in disease, are still a matter of debate. In this review, we focus on long non-coding RNAs (lncRNAs) that are involved in cancer. We define lncRNAs and present a cancer-oriented list of lncRNAs, list some tools (for example, public databases) that classify lncRNAs or that scan genome spans of interest to find whether known lncRNAs reside there, and describe some of the functions of lncRNAs and the possible genetic mechanisms that underlie lncRNA expression changes in cancer, as well as current and potential future applications of lncRNA research in the treatment of cancer.RS is supported as a fellow of the TALENTS Programme (7th R&D Framework Programme, Specific Programme: PEOPLE—Marie Curie Actions—COFUND). MIA is supported as a PhD fellow of the FCT (Fundação para a Ciência e Tecnologia), Portugal. GAC is supported as a fellow by The University of Texas MD Anderson Cancer Center Research Trust, as a research scholar by The University of Texas System Regents, and by the Chronic Lymphocytic Leukemia Global Research Foundation. Work in GAC’s laboratory is supported in part by the NIH/ NCI (CA135444); a Department of Defense Breast Cancer Idea Award; Developmental Research Awards from the Breast Cancer, Ovarian Cancer, Brain Cancer, Multiple Myeloma and Leukemia Specialized Programs of Research Excellence (SPORE) grants from the National Institutes of Health; a 2009 Seena Magowitz–Pancreatic Cancer Action Network AACR Pilot Grant; the Laura and John Arnold Foundation and the RGK Foundation