Correcting forensic DNA errors

DNA mixture interpretation can produce opposing conclusions by qualified forensic analysts, even within the same laboratory. The long-delayed publication of the National Institutes of Standards and Technology (NIST) study of 109 North American crime laboratories in this journal demonstrates this most clearly. This latest study supports earlier work that shows common methods such as the Combined Probability of Inclusion (CPI) have wrongly included innocent people as contributors to DNA mixtures. The 2016 President's Council of Advisors on Science and Technology report concluded, “In summary, the interpretation of complex DNA mixtures with the CPI statistic has been an inadequately specified—and thus inappropriately subjective—method. As such, the method is clearly not foundationally valid” [7]. The adoption of probabilistic genotyping by many laboratories will certainly prevent some of these errors from occurring in the future, but the same laboratories that produced past errors can also now review old cases with their new software—without additional bench work. It is critical that laboratories adopt procedures and policies to do this.     

病例组合指数的内涵及应用探讨

国内普遍认为病例组合指数(CMI)属于医疗服务能力维度,体现收治疾病的疑难复杂程度和医疗服务的整体技术难度。通过结构方程模型分析发现,CMI与时间消耗指数、费用消耗指数等服务效率维度指标联系更紧密,与DRG组数、入组病例数及总权重等服务能力维度指标联系相对较弱,故应归属医疗服务效率维度。CMI的直接应用主要是对平均住院费用的预测控制及对科室绩效的评价;CMI的间接应用主要是对管理指标的调整/校正。医院管理者应准确把握CMI内涵,恰当应用CMI对不同层级及不同类别住院费用进行预测、评价与控制,并对其他管理指标进行调整后再评价。     

基于混合正态模型的糖尿病住院病人医疗保险设计

目的提出一种基于混合正态模型来拟合糖尿病住院病人风险损失规律的精算方法.方法采用EM算法对混合正态风险模型进行参数估计;采用Kolmogorov-Smirnov检验对混合正态风险模型的拟合优度进行检验;采用随机抽样模拟和t检验法比较随机样本指标与模型参数之间的差异;采用逐步判别分析方法,对随机保单进行分类与甄别;设计保险条款,作为保险双方有约束力的合同.结果由训练样本拟合得到四元混合正态模型;模型的拟合精度很高（P=0.99701）;按μi＋1.645σi可得到4种保险等级下的总保费;样本指标与模型参数之间的差异无统计学意义.结论 本文设计的面向糖尿病住院病人的医疗保险,可根据投保人因糖尿病住院风险损失额划分成4种类型保单持有者,并由此厘定出4种不同等级的保险费,因而体现了高风险损失应承担高额保险费的保险原则,有利于投保人根据自身情况选择保单类别.     

Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats

Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action.Pregnant rat dams were exposed during gestation and lactation to mixtures of environmentally relevant EDCs with estrogenic, anti-androgenic or dissimilar modes of action (TotalMix) of 100-, 200- or 450-fold high end human intake estimates. Mammary glands of prepubertal and adult female and male offspring were examined.Oestrogens increased mammary outgrowth in prepubertal females and the mRNA level of matrix metalloproteinase-3, which may be a potential biomarker for increased outgrowth. Mixtures of EDCs gave rise to ductal hyperplasia in adult males. Adult female mammary glands of the TotalMix group showed morphological changes possibly reflecting increased prolactin levels. In conclusion both estrogenic and anti-androgenic chemicals given during foetal life and lactation affected mammary glands in the offspring.     

优泌乐50治疗初诊2型糖尿病的临床体会

目的探讨优泌乐50治疗初诊2型糖尿病的临床疗效。方法选取初诊2型糖尿病患者80例,使用优泌乐50治疗12周,比较治疗前后空腹血糖、餐后2h血糖、糖化血红蛋白、空腹胰岛素、胰岛素分泌指数、胰岛素抵抗指数的变化。结果治疗后空腹血糖、餐后2h血糖、糖化血红蛋白、胰岛素抵抗指数较治疗前明显下降（P〈0．05）;空腹胰岛素、胰岛素分泌指数明显升高（P〈0．01）。结论应用优泌乐50治疗能显著降低初诊2型糖尿病患者血糖和改善胰岛功能。     

The DURABLE Trial Study Design: Comparing the Safety, Efficacy, and Durability of Insulin Glargine to Insulin Lispro Mix 75/25 Added to Oral Antihyperglycemic Agents in Patients with Type 2 Diabetes

Background

While studies have compared the safety and efficacy of starter insulin regimens in type 2 diabetes, none have evaluated regimen durability (length of time a patient can maintain glycemic control) or the safety and efficacy of subsequent intensification regimens in a large, multinational cohort.

Methods

The DURABLE (Assessing the DURAbility of Basal vs Lispro Mix 75/25 Insulin Efficacy) trial will compare the ability of glargine once daily vs lispro mix 75/25 (75% insulin lispro protamine suspension, 25% lispro) twice daily added to oral antihyperglycemic agents to achieve and maintain hemoglobin A1c (HbA1c) goals. This randomized, open label, parallel study will enroll over 2000 insulin-naïve patients with type 2 diabetes from 11 countries, ages 30 to 80, with HbA1c >7.0% on at least two oral antihyperglycemic agents. At the completion of the 6-month initiation phase, safety and efficacy of the two regimens will be compared. Patients who achieve an HbA1c ≤7.0% at 6 months will continue into the 24-month maintenance phase to evaluate durability.In a substudy, patients not achieving HbA1c ≤7.0% at 6 months may be randomized to one of two intensification comparisons: patients previously on glargine will receive lispro mix 75/25 twice daily or basal/bolus therapy (glargine + thrice-daily mealtime lispro) and patients previously on lispro mix 75/25 will receive lispro mix 50/50 (50% insulin lispro protamine suspension, 50% lispro) thrice daily or basal/bolus therapy.

Results

Upon completion, this trial will provide new information about starter insulin durability, defined as the length of time patients can maintain HbA1c control (HbA1c ≤7.0%, or >7.0% but with an increase of <0.4% from the most recent HbA1c ≤7.0%). Additionally, the study will provide comparative data on HbA1c, blood glucose profiles, 1,5-anhydroglucitol, hypoglycemic episodes, weight change, and insulin dose for starter insulin regimens following 6 and 24 months of treatment, as well as intensified insulin via the 6-month substudy.

Conclusion

This trial aims to broaden clinicians'' understanding of the ability of starter insulin and insulin intensification regimens to achieve and maintain glycemic control in patients with type 2 diabetes.     

Addition of biphasic insulin aspart 30 to optimized metformin and pioglitazone treatment of type 2 diabetes mellitus: The ACTION Study (Achieving Control Through Insulin plus Oral ageNts)

Aim: Efficacy and safety of biphasic insulin aspart (BIAsp 30, 30% short‐acting and 70% intermediate‐acting insulin aspart) added to an optimized treatment of metformin and pioglitazone (met/pio) were compared with treatment with optimized met/pio in type 2 diabetes patients. Methods: This randomized, 34‐week, parallel‐group study enrolled insulin‐naive, type 2 diabetes patients (HbA_1c 7.5–12.0%) previously using two oral antidiabetic (OAD) agents. During an 8‐week run‐in period, treatment was changed to met/pio and doses were adjusted up to 2500 mg/day and 30 or 45 mg/day respectively. Subjects either continued met/pio alone or added BIAsp 30 initiated at 6 units twice daily and titrated to target plasma glucose (PG) (4.4–6.1 mmol/l). Results: At end‐of‐study, subjects treated with BIAsp 30+met/pio (n = 93) had a mean (±s.d.) HbA_1c reduction significantly greater than treatment with met/pio (n = 88) (1.5% ± 1.1 vs. 0.2% ± 0.9, p < 0.0001 between groups). Subjects treated with BIAsp 30+met/pio were more likely to reach The American Association of Clinical Endocrinologists and European Association for the Study of Diabetes/American Diabetes Association HbA_1c targets of ≤6.5 and <7.0%, respectively, than with met/pio only (HbA_1c≤6.5%: 59 vs. 12%; HbA_1c <7.0%: 76 vs. 24%). At end‐of‐study, self‐monitored glucose profile values at all eight daily time points were significantly less for the BIAsp 30+met/pio group compared with the met/pio group, and minor hypoglycaemia (defined as PG < 3.1 mmol/l) was more frequent (8.3 vs. 0.1 events/year, p < 0.001). Both groups gained weight during treatment (BIAsp 30+met/pio, 4.6 ± 4.3 kg; met/pio, 0.8 ± 3.2 kg; p < 0.001). Conclusion: Addition of insulin in type 2 patients treated with met/pio is an effective way to achieve glycaemic targets. Treatment with BIAsp 30+met/pio achieved significantly greater reduction in HbA_1c, as compared with met/pio alone. In patients with type 2 diabetes poorly controlled by 2 OADs, more achieved glycaemic targets using BIAsp 30+met/pio than using met/pio alone.     

Efficacy and safety of biphasic insulin aspart 70/30 in type 2 diabetes patients of different race or ethnicity (INITIATEplus trial)

Abstract

Objective:

To determine if self-titration using biphasic insulin aspart 70/30 (BIAsp 30) had a different impact on efficacy and safety across different racial/ethnic subgroups.