2,310 research outputs found

    A model-based multithreshold method for subgroup identification

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    Thresholding variable plays a crucial role in subgroup identification for personalizedmedicine. Most existing partitioning methods split the sample basedon one predictor variable. In this paper, we consider setting the splitting rulefrom a combination of multivariate predictors, such as the latent factors, principlecomponents, and weighted sum of predictors. Such a subgrouping methodmay lead to more meaningful partitioning of the population than using a singlevariable. In addition, our method is based on a change point regression modeland thus yields straight forward model-based prediction results. After choosinga particular thresholding variable form, we apply a two-stage multiple changepoint detection method to determine the subgroups and estimate the regressionparameters. We show that our approach can produce two or more subgroupsfrom the multiple change points and identify the true grouping with high probability.In addition, our estimation results enjoy oracle properties. We design asimulation study to compare performances of our proposed and existing methodsand apply them to analyze data sets from a Scleroderma trial and a breastcancer study

    Use Of Chinese Medicine Among Colorectal Cancer Patients: A Nationwide Population-Based Study.

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    Background: Traditional Chinese medicine (CM) appears to be used worldwide, especially by cancer patients. The aim of the present study was to explore CM uses and CM non-users by patients with colorectal cancer (CRC).Materials and methods: A retrospective study was conducted using registration and claims data sets for 2007 from the National Health Insurance Research Database. Patients with colorectal cancer were identified from the Registry for Catastrophic illness Patients. Binary logistic regression was used to estimate odds ratios as the measure of association with the use of CM.Results: A total of 61,211 CRC patients diagnosed in 2007 were analysis. Most CM users preferred to visit private clinics (46.9%) with 306,599 visits. In contrast, the majority of CM non-users preferred to visit private hospitals (42.2%) with 538,769 visits. Among all 176,707 cancer-specific CM visit, there were 66.6% visits to CM outpatient department (OPD) of private hospitals, while in 477,612 non-cancer-specific CM visits, 62.0% was for private clinics. The proportion of expenses for diagnostic fees for CM user in CM visits was much less than that for WM visits and CM non-users (US4.6vs.29.3vs.33.5).TheaveragecostforCMuserinCMwaslessthanthatforWMvisitsandCMnonusers(US4.6 vs. 29.3 vs. 33.5). The average cost for CM user in CM was less than that for WM visits and CM non-users (US6.3 vs. 25.9 vs. 30.3). Female patients, younger age, and patients not living in the northern region, with higher EC or more comorbidities were more likely to receive CM treatment.Conclusion: The prevalence and costs of insurance-covered CM among CRC patients were low. Further longer longitudinal study is needed to follow up this trend.Key words: Chinese Medicine, Digestive System Neoplasms, Health Insuranc

    Experiential Persona: Towards Supporting Richer and Unfinalized Representations of People

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    The Persona, as a 2D poster, is a commonly created and used tool in user-centred design activities. Whilst popular, many in HCI have critiqued its depictions of g€the user' as reductive, shallow, and static. Yet, there are not many alternatives. In this late-breaking work, we present our efforts to imagine and create an alternative to this 2D persona - one that consists of a carefully curated, staged collection of artifacts. We call this an Experiential Persona because it allows designers to interact with and explore the artifacts, individually and as a collection, to imagine and experience the world of g€the user'. This more embodied, interactive and open-ended persona can potentially support richer sense making; encouraging a more open, emergent, and unfinalized view of people we design for. This study contributes to extending design tools, and exploring novel use of tangible artifacts to support design, as well as a way to represent design knowledge

    An “Escape Clock” for Estimating the Turnover of SIV DNA in Resting CD4+ T Cells

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    Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most studies suggest that cells with latently integrated HIV decay very slowly under therapy. However, it is much more difficult to study the turnover and persistence of HIV DNA during active infection. We have developed an “escape clock” approach for measuring the turnover of HIV DNA in resting CD4+ T cells. This approach studies the replacement of wild-type (WT) SIV DNA present in early infection by CTL escape mutant (EM) strains during later infection. Using a strain-specific real time PCR assay, we quantified the relative amounts of WT and EM strains in plasma SIV RNA and cellular SIV DNA. Thus we can track the formation and turnover of SIV DNA in sorted resting CD4+ T cells. We studied serial plasma and PBMC samples from 20 SIV-infected Mane-A*10 positive pigtail macaques that have a signature Gag CTL escape mutation. In animals with low viral load, WT virus laid down early in infection is extremely stable, and the decay of this WT species is very slow, consistent with findings in subjects on anti-retroviral medications. However, during active, high level infection, most SIV DNA in resting cells was turning over rapidly, suggesting a large pool of short-lived DNA produced by recent infection events. Our results suggest that, in order to reduce the formation of a stable population of SIV DNA, it will be important either to intervene very early or intervene during active replication

    Male water striders attract predators to intimidate females into copulation

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    Despite recent advances in our understanding of sexual conflict and antagonistic coevolution between sexes, the role of interspecific interactions, such as predation, in these evolutionary processes remains unclear. In this paper, we present a new male mating strategy whereby a male water strider Gerris gracilicornis intimidates a female by directly attracting predators as long as she does not accept the male's coercive copulation attempt. We argue that this male strategy is a counteradaptation to the evolution of the female morphological shield protecting her genitalia from coercive intromission by water strider males. The G. gracilicornis mating system clearly represents an effect expected from models of the coevolutionary arms race between sexes, whereby one sex causes a decrease in the fitness component of the other sex. Moreover, our study demonstrates a crucial role that interspecific interactions such as predation can have in the antagonistic coevolution between sexes

    Case report – ancient schwannoma of the scrotum

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    BACKGROUND: Scrotal schwannoma is a rare neoplasm and poses a diagnostic challenge to urologists. This article describes a rare case of ancient scrotal schwannoma and reviews the current modality of investigation and treatment of this tumour. CASE REPORT: A 28 year old man presented with a 3-month history of an asymptomatic scrotal swelling. Ultrasonography and computer topography revealed an intra-scrotal and extra-testicular mass without local invasion. Surgical excision was undertaken and histology was an ancient schwannoma of the scrotum. CONCLUSION: Schwannoma is a benign encapsulating neoplasm with an overall low incidence, occurring mostly in the head and neck region and seldom in the scrotum. Histology shows two distinctive patterns, Antoni type A and B areas. Variations of schwannoma such as cellular, ancient, glandular and epithelioid are observed based on the appearances. Ancient schwannoma exhibits pleomorphism without mitosis as the result of cellular degeneration, which can lead to an erroneous diagnosis of malignancy. Imaging modalities are non-specific for schwannomas, but can define tumour size, site and extension. The mainstay treatment is complete excision, although local recurrence may occur in large and incompletely excised lesions. Malignant change is exceedingly rare

    Carrier Screening for Spinal Muscular Atrophy (SMA) in 107,611 Pregnant Women during the Period 2005–2009: A Prospective Population-Based Cohort Study

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    BACKGROUND: Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program. METHODS AND FINDINGS: This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968. CONCLUSION: The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling

    Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates

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    The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use
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