P2P情境下基于用户兴趣的个人数字图书馆资源定位

根据个人数字图书馆的分散性特征,将P2P（Peer to Peer）技术应用于个人数字图书馆系统,提出一种基于P2P技术的个人数字图书馆共享模型－MIPDLM,以提高个人数字图书馆共享水平。在该模型中,个人数字图书馆可根据兴趣分簇,探讨拓扑重构的过程,其基于多兴趣的搜索机制,可将搜索消息不断向兴趣相似度较高的个人数字图书馆转发,因此能大大缩小搜索范围。仿真结果表明,与随机漫步（Random Walk）机制相比,MIPDLM模型可在一定程度上提高个人数字图书馆搜索成功率,减少平均路径长度,提高资源定位效率。     

The Effect of Food on the Pharmacokinetics of Sildenafil after Single Administration of a Sublingual Testosterone and Oral Sildenafil Combination Tablet in Healthy Female Subjects

IntroductionFemale sexual interest/arousal disorder (FSIAD) affects many women worldwide, but pharmacological treatment options are scarce. A new medicine being developed for FSIAD is an on-demand, dual-route, dual-release drug combination product containing 0.5 mg testosterone (T) and 50 mg sildenafil (S), referred to here as T+S.AimThe aim of this study was to compare the effect of a fed and a fasted state on the pharmacokinetics of sildenafil following administration of T+S.MethodsEighteen healthy women were administered T+S under fed and fasted conditions during 2 separate overnight visits in this randomized, open-label, balanced, 2-period, 2-treatment, 2-sequence crossover study.Main Outcome MeasuresThe pharmacokinetics of sildenafil and its active metabolite N-desmethyl sildenafil were determined over a 24-hour period. Total testosterone was assessed only at a limited number of time points for quality purposes, as sublingual uptake is not expected to be affected by food intake.ResultsThe observed geometric mean ratios (GMRs) and 90% confidence intervals of sildenafil were not all contained within the prespecified bounds (0.80, 1.25). The GMR (90% CI) for plasma AUC_0–last was 1.2753 (0.9706–1.6755); for AUC_0–14h, it was 1.7521 (1.0819–2.8374); and for C_max, it was 1.5591 (0.8634–2.8153). Only lower limits of the CIs fell within the bounds. For N-desmethyl sildenafil, the GMR (90% CI) for AUC_0–last was 0.8437 (0.6738–1.0564); for AUC_0–10h, it was 1.0847 (0.7648–1.5383); and for C_max, it was 1.0083 (0.6638–1.5318). Only the GMRs were contained within bounds. No differences were observed between plasma testosterone C_max and T_max under fed and fasted conditions, which is in line with expectations for a sublingual administration.Clinical ImplicationsThe T+S combination tablet ruptures too late when taken in a fasted state and should therefore not be taken on an empty stomach.Strengths & LimitationsThis is a well-controlled study that provides important insights into the performance characteristics of the delayed-release coating of the combination tablet. The higher variability of the pharmacokinetic parameters in the fasted state was caused by severely delayed rupture in one-third of the women. A reason for this is proposed but the present data do not explain this phenomenon.ConclusionThe pharmacokinetics of sildenafil from this modified-release tablet are more robust under fed conditions as compared to the artificial fasted condition where no food is consumed 10 hours prior to and 4 hours after dosing. The dosing situation under the tested fasting condition does not represent the expected common use of this product. Patients should, however, be instructed not to take the tablet on an empty stomach.Bloemers J, Gerritsen J, van Rooij K, et al. The Effect of Food on the Pharmacokinetics of Sildenafil After Single Administration of a Sublingual Testosterone and Oral Sildenafil Combination Tablet in Healthy Female Subjects. J Sex Med 2019; 19:1433–1443.     

Partners Experience Consequences,Too: A Comparison of the Sexual,Relational, and Psychological Adjustment of Women with Sexual Interest/Arousal Disorder and Their Partners to Control Couples

Introduction

Women diagnosed with female sexual interest/arousal disorder (FSIAD) report lower health-related quality of life, more depressive symptoms, and lower sexual and relationship satisfaction compared with healthy control subjects. Despite the impact of FSIAD on women’s sexuality and the inherently interpersonal nature of the sexual problem, it remains unclear whether the partners of women with FSIAD also face negative consequences, as seen in other sexual dysfunctions.

Evaluation of optimised 3D turbo spin echo and gradient echo MR pulse sequences of the knee at 3T and 1.5T

IntroductionTo investigate the impact of parameter optimisation for novel three-dimensional 3D sequences at 1.5T and 3T on resultant image quality.MethodsFollowing institutional review board approval and acquisition of informed consent, MR phantom and knee joint imaging on healthy volunteers (n = 16) was performed with 1.5 and 3T MRI scanners, respectively incorporating 8- and 15-channel phased array knee radiofrequency coils. The MR phantom and healthy volunteers were prospectively scanned over a six-week period. Acquired sequences included standard two-dimensional (2D) turbo spin echo (TSE) and novel three-dimensional (3D) TSE PDW (SPACE) both with and without fat-suppression, and T21W gradient echo (TrueFISP) sequences. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured for knee anatomical structures. Two musculoskeletal radiologists evaluated anatomical structure visualisation and image quality. Quantitative and qualitative findings were investigated for differences using Friedman tests. Inter- and intra-observer agreements were determined with κ statistics.ResultsPhantom and healthy volunteer images revealed higher SNR for sequences acquired at 3T (p-value <0.05). Generally, the qualitative findings ranked images acquired at 3T higher than corresponding images acquired at 1.5T (p < 0.05). 3D image data sets demonstrated less sensitivity to partial volume averaging artefact (PVA) compared to 2D sequences. Inter- and intra-observer agreements for evaluation across all sequences ranged from 0.61 to 0.79 and 0.71 to 0.92, respectively.ConclusionBoth 2D and 3D images demonstrated higher image quality at 3T than at 1.5T. Optimised 3D sequences performed better than the standard 2D PDW TSE sequence for contrast resolution between cartilage and joint fluid, with reduced PVA artefact.Implications for practiceWith rapid advances in MRI scanner technology, including hardware and software, the optimisation of 3D MR pulse sequences to reduce scan time while maintaining image quality, will improve diagnostic accuracy and patient management in musculoskeletal MRI.     

Feasibility of extracellular volume quantification using dual-energy CT

ObjectiveTo assess the feasibility of dual energy CT (DECT) to derive myocardial extracellular volume (ECV) and detect myocardial ECV differences without a non-contrast acquisition, compared to single energy CT (SECT).MethodsSubjects (n = 35) with focal fibrosis (n = 17), diffuse fibrosis (n = 10), and controls (n = 9) underwent non-contrast and delayed acquisitions to calculate SECT-ECV. DECT-ECV was calculated using the delayed acquisition and the derived virtual non-contrast images. In the control and diffuse fibrotic groups, the entire myocardium of the left ventricle was used to calculate ECV. Two ROIs were placed in the focal fibrotic group, one in normal and one in fibrotic myocardium.ResultsMedian ECV was 33.4% (IQR, 30.1–37.4) using SECT and 34.9% (IQR, 31.2–39.2) using DECT (p = 0.401). For both techniques, focal and diffuse fibrosis had significantly higher ECV values (all p < 0.021) than normal myocardium. There was no systematic bias between DECT and SECT (p = 0.348). SECT had a higher radiation dose (1.1 mSv difference) than DECT (p < 0.001).ConclusionECV can be measured using a DECT approach with only a delayed acquisition. The DECT approach provides similar results at a lower radiation dose compared to SECT.     

Efficacy and Safety of Tofacitinib in Ulcerative Colitis Based on Prior Tumor Necrosis Factor Inhibitor Failure Status

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An audit of orthopaedic referrals via Multi-Professional Triage Teams

INTRODUCTION

Multi-Professional Triage Teams (MPTTs) were created to reduce the caseload of hospital orthopaedic clinics and this prospective study evaluated referrals made to a district general hospital orthopaedic department from a lower limb MPTT clinic.

PATIENTS AND METHODS

Over 9 months, 277 referrals to a lower limb hospital orthopaedic clinic were assessed. The temporal delay to hospital clinic review between patients seen at the MPTT clinic and those referred directly by their general practitioner (GP) was analysed using an ANOVA test. A qualitative assessment of diagnoses given to patients reviewed at the MPTT clinic was performed.

RESULTS

The 132 patients initially reviewed at the MPTT clinic and subsequently referred to a hospital consultant waited significantly longer (140 days compared to 62 days by direct GP referral; P < 0.05) to see an orthopaedic consultant. Over three-quarters of this patient cohort incorrectly identified the healthcare professional conducting their consultation at the MPTT clinic. One-third of cases (31%) had no diagnosis made and 22% were assessed as having an incorrect diagnosis.

CONCLUSIONS

Time delays, patient confusion regarding professional roles and diagnostic indecision are significant problems for patients referred to hospital orthopaedic clinics from MPTT clinics. This risks sub-optimal patient care and may lead to future medicolegal implications.