Modelling asset correlations: A nonparametric approach

This article proposes a time-varying nonparametric estimator and a time-varying semiparametric estimator of the correlation matrix. We discuss representation, estimation based on kernel smoothing and inference. An extensive Monte Carlo simulation study is performed to compare the semiparametric and nonparametric models with the DCC speci fication. Our bivariate simulation results show that the semiparametric and nonparametric models are best in DGPs with gradual changes or structural breaks in correlations. However, in DGPs with rapid changes or constancy in correlations the DCC delivers the best outcome. Moreover, in multivariate simulations the semiparametric and nonparametric models fare the best in DGPs with substantial time-variability in correlations, while when allowing for little variability in the correlations the DCC is the dominant speci fication. The methodologies are illustrated by estimating the correlations for two interesting portfolios. The rst portfolio consists of the equity sectors SPDRs and the S&P 500 composite, while the second one contains major currencies that are actively traded in the foreign exchange market. Portfolio evaluation results show that the nonparametric estimator generally dominates its competitors, with a statistically significant lower portfolio variance

Tamoxifen for the treatment of polycystic liver disease:A case report

RATIONALE: Polycystic liver disease is a rare disease characterized by the growth of numerous cysts in the liver. The liver function remains well preserved, but liver volumes can grow very large, and some patients ultimately need a liver transplantation. Other treatment options are limited and there is an unmet need for new therapeutic options. PATIENT CONCERNS: We describe a 59-year-old patient with pain in the abdomen, especially when bending forward. Five years ago, she was diagnosed with breast cancer and as an incidental finding a couple of large liver cysts were diagnosed, explaining her abdominal pain. DIAGNOSIS: Polycystic liver disease with several large liver cysts. INTERVENTIONS: The patient was treated with tamoxifen, an estrogen receptor modulator, as treatment for her hormone receptor positive breast cancer. One of the liver cysts was aspirated. OUTCOMES: In the 4.6 years after the start of tamoxifen treatment, 20 mg once daily, the volume of her liver cysts decreased remarkably. There was a reduction of combined cyst volume from 311 mL to 22 mL without percutaneous drainage. LESSONS: Epidemiological as well as experimental evidence supports a pivotal role for estrogens as a driver for growth of polycystic livers. Estrogen antagonism has often been proposed as a therapeutic target, but supporting evidence is lacking in the literature. We hypothesize that the decrease in cyst size in this patient was caused by tamoxifen therapy, suggesting an in vivo antagonistic effect on cystic cholangiocytes. This is an important finding because tamoxifen could be a promising new treatment option for polycystic liver disease

Конференции

Background Polypharmacy poses threats to patients’ health. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) is a drug optimization process for conducting medication reviews in primary care. To effectively and efficiently incorporate this method into daily practice, the STRIP Assistant—a decision support system that aims to assist physicians with the pharmacotherapeutic analysis of patients’ medical records—has been developed. It generates context-specific advice based on clinical guidelines. Objective The aim of this study was to validate the STRIP Assistant’s usability as a tool for physicians to optimize medical records for polypharmacy patients. Methods In an online experiment, 42 physicians were asked to optimize medical records for two comparable polypharmacy patients, one in their usual manner and one using the STRIP Assistant. Changes in effectiveness were measured by comparing respondents’ optimized medicine prescriptions with medication prepared by an expert panel of two geriatrician-pharmacologists. Efficiency was operationalized by recording the time the respondents took to optimize the two cases. User satisfaction was measured with the System Usability Scale (SUS). Independent and paired t tests were used for analysis. Results Medication optimization significantly improved with the STRIP Assistant. Appropriate decisions increased from 58 % without the STRIP Assistant to 76 % with it (p < 0.0001). Inappropriate decisions decreased from 42 % without the STRIP Assistant to 24 % with it (p < 0.0001). Participants spent significantly more time optimizing medication with the STRIP Assistant (24 min) than without it (13 min; p < 0.0001). They assigned it a below-average SUS score of 63.25. Conclusion The STRIP Assistant improves the effectiveness of medication reviews for polypharmacy patients

Episodic abdominal pain characteristics are not associated with clinically relevant improvement of health status after cholecystectomy

BACKGROUND: Cholecystectomy is the therapy of first choice in patients with uncomplicated symptomatic cholecystolithiasis, but it remains unclear which patients truly benefit in terms of health status improvement. Patients generally present with episodic abdominal pain of varying frequency, duration, and intensity. We assessed whether characteristics of abdominal pain episodes are determinants of clinically relevant improvement of health status after cholecystectomy. METHODS: In a post hoc analysis of a prospective multicenter cohort study, patients of ≥18 years of age with uncomplicated symptomatic cholecystolithiasis subjected to cholecystectomy were included. Preoperatively, patients received a structured interview and a questionnaire consisting of the visual analogue scale (VAS; range 0–100) and gastrointestinal quality of life index (GIQLI). At 12 weeks after cholecystectomy, the GIQLI was again administered. Logistic regression analyses were performed to determine significant associations. RESULTS: Questionnaires were sent to 261 and returned by 166 (63.6 %) patients (128 females, mean age at surgery 49.5 ± 13.8). A total of 131 (78.9 %) patients reported a clinically relevant improvement of health status. The median (interquartile range) frequency, duration, and intensity of abdominal pain episodes were 0.38 (0.18–0.75) a week, 4.00 (2.00–8.00) hours, and 92 (77–99), respectively. None of the characteristics was associated with a clinically relevant improvement of health status at 12 weeks after cholecystectomy. CONCLUSIONS: Characteristics of abdominal pain episodes cannot be used to inform patients with symptomatic cholecystolithiasis who are skeptic about the timing of cholecystectomy for optimal benefit. Timing of cholecystectomy should therefore be based on other characteristics and preferences

Safe use of medication in patients with cirrhosis:pharmacokinetic and pharmacodynamic considerations

Contains fulltext : 218240.pdf (Publisher’s version ) (Open Access)Introduction: The global burden of cirrhosis is rising, and clinicians increasingly face the challenge of safely prescribing medicines for complications of hepatic disease and comorbidities. Prescribing in patients with cirrhosis is complicated by alterations that can occur in the pharmacology of medicines.Areas covered: This paper provides an overview of current knowledge on the pharmacokinetics and pharmacodynamics of medicines in patients with cirrhosis. We describe the pathophysiological changes that occur and their consequences on pharmacokinetic parameters. We explain that the influence of cirrhosis on the pharmacokinetics depends on several drug and patient characteristics. Patients with cirrhosis also have an increased susceptibility to some toxicological effects of medicines, such as renal impairment and hematological toxicity, which we describe in detail. In addition, we discuss approaches to apply this knowledge in practice and improve safe medication use in patients with cirrhosis.Expert opinion: Tailored pharmacotherapy is needed to ensure safe and appropriate use of medicines in patients with cirrhosis. Clinicians are supported by freely available recommendations on safe drug use in cirrhosis published on a website. In addition, a regular evaluation of medication use in patients with cirrhosis could resolve and prevent medication-related problems

Short mucin 6 alleles are associated with H pylori infection

Contains fulltext : 49314.pdf (publisher's version ) (Open Access)AIM: To investigate the relationship between mucin 6 (MUC6) VNTR length and H pylori infection. METHODS: Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme (Pvu II) and the length of the allele fragments was determined by Southern blotting. H pylori infection was diagnosed by (14)C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long (> 13.5 kbp) or short (< or = 13.5 kbp) and patients were classified according to genotype [long-long (LL), long-short (LS), short-short (SS)]. RESULTS: 160 patients were studied (mean age 43 years, 36% were males, 58% H pylori positive). MUC6 Pvu II-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6 genotype, 43% (24/56), 57% (25/58) and 76% (11/46) were infected with H pylori, respectively (P = 0.003). CONCLUSION: Short MUC6 alleles are associated with H pylori infection

Abuse in the caregiving relationship between older people with memory disorders and family caregivers: A systematic review

Aim To synthesize what is known about elder abuse and relationship factors associated with abuse between caregivers and older people with memory disorders at home. Background Concerns about abuse in the caring relationship between older people with memory disorders and family caregivers have increased. Abuse is associated with negative outcomes on older people's health, quality of life, and zest for life. Abuse in the caring relationship manifests in financial exploitation, neglect, mistreatment, and physical issues. Design Systematic review. Data Sources Databases including Scopus, PubMed/Medline, SveMed+, Cinalh, SonINDEX, and ProQuest were searched using keywords about abuse in the caring relationship between older people with memory disorders and family caregivers at home. Articles published between 2005–2019 were retrieved and underwent data analysis and knowledge synthesis. Review Methods The review was presented under the categories of the dyadic approach of elder abuse in connection with the role of caregiver (risk) and care recipient (vulnerability) by Fulmer et al. (2005). Results The search process led to 12 quantitative studies, including an intervention, a prospective, nine surveys, and a cross‐sectional structural interview. Findings were synthesized and presented under ‘personal’, ‘physical and psychological’, and ‘social’ domains indicating the bilateral roles of caregiver and care recipient leading to abuse. Conclusion This review depicted factors influencing abuse in the caring relationship between older people with memory disorders and their family caregivers at home. They included family caregivers’ psychological issues, knowledge of memory disorders and modifications, previous caring relationship, social support, number of care recipients, and care recipients’ functional level. Impact This review identifies what influences elder abuse by family caregivers using the dyadic approach and explains how abuse can be prevented through suggested strategies. The review findings are relevant to multidisciplinary healthcare providers and can guide the provision of support, screening and assessment, educational programs, and legislative initiatives

Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex

The rough endoplasmic reticulum (ER) of nucleated human cells has crucial functions in protein biogenesis, calcium (Ca2+) homeostasis, and signal transduction. Among the roughly one hundred components, which are involved in protein import and protein folding or assembly, two components stand out: The Sec61 complex and BiP. The Sec61 complex in the ER membrane represents the major entry point for precursor polypeptides into the membrane or lumen of the ER and provides a conduit for Ca2+ ions from the ER lumen to the cytosol. The second component, the Hsp70-type molecular chaperone immunoglobulin heavy chain binding protein, short BiP, plays central roles in protein folding and assembly (hence its name), protein import, cellular Ca2+ homeostasis, and various intracellular signal transduction pathways. For the purpose of this review, we focus on these two components, their relevant allosteric effectors and on the question of how their respective functional cycles are linked in order to reconcile the apparently contradictory features of the ER membrane, selective permeability for precursor polypeptides, and impermeability for Ca2+. The key issues are that the Sec61 complex exists in two conformations: An open and a closed state that are in a dynamic equilibrium with each other, and that BiP contributes to its gating in both directions in cooperation with different co-chaperones. While the open Sec61 complex forms an aqueous polypeptide-conducting- and transiently Ca2+-permeable channel, the closed complex is impermeable even to Ca2+. Therefore, we discuss the human hereditary and tumor diseases that are linked to Sec61 channel gating, termed Sec61-channelopathies, as disturbances of selective polypeptide-impermeability and/or aberrant Ca2+-permeability

Postgraduate Research Studies handbook

2001 handbook for Postgraduate Research Studie

Familial Mediterranean Fever and Hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features

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