Practical and statistical challenges in driving research

Driving is an integral aspect of many modern societies, and motor vehicle safety is an important public health issue. With advances in sensor technology, more and more driving data are being collected by researchers, insurers, and automobile companies, which has increased the need and opportunities for statisticians to be involved in driving research. This report discusses several practical and statistical challenges in driver-level studies, including the process of defining meaningful driving metrics, issues related to “Big Data” aspects of driving research, and the principle of reproducible research.     

Overview of the university-based addiction studies programs in the United States

Background: The field of addiction studies (AS) has grown in the last several decades. However, little is known about the structure and conditions of current academic programs. Only two studies have examined AS programs in the U.S., and both were conducted almost 15 years ago. The current study was designed to identify AS programs existing in the U.S. universities.

Methods: We conducted an Internet search to identify university-based programs according to defined key words. The university program websites were then subjected to content analysis.

Results: A total of 333 U.S. universities were identified that offered 392 different academic programs in AS of which 302 were degree programs. Out of these, 161 (53%) programs were offered at the associate degree level, 48 (15,9%) at the bachelor’s level, 55 (18.2%) at the master’s level, and 5 (1.6%) at the doctorate level. The largest number of programs was in California. Two states in the U.S. had no identifiable programs. Only one university located in the state of New York offered comprehensive academic programs across the educational spectrum. Many of the academic programs offered certificates. The most common phrases used in program titles were “substance abuse”, “addiction studies/counseling”, and “chemical dependency”.

Conclusions: There is a wide range of academic AS programs in the U.S., although their focus is mostly on clinical training rather than on research or drug policy. Future surveys such as this one would benefit from greater attention to issues related to certification, licensing, and academic curricula.     

Synthesis and docking studies of N-(5-(alkylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamide analogues as potential alkaline phosphatase inhibitors

A series of N-(5-(alkylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamides 6a–i were synthesized as alkaline phosphatase inhibitors. The intermediate 5-substituted 1,3,4-oxadiazole-2-thione 4 was synthesized starting with hippuric acid. Hippuric acid in the first step was converted into corresponding methyl ester 2 which upon reaction with hydrazine hydrate furnished the formation of hydrazide 3 . The hippuric acid hydrazide was then cyclized into 5-substituted 1,3,4-oxadiazole-2-thione 4 . The intermediate 4 was then reacted with alkyl or aryl halides 5a–5i to afford the title compounds N-(5-(methylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamides 6a–i . The bioassay results showed that compounds 6a–i exhibited good to excellent alkaline phosphatase inhibitory activity. The most potent activity was exhibited by the compound 6i having IC₅₀ value 0.420 μM, whereas IC₅₀ value of standard (KH₂PO₄) was 2.80 μM. Molecular docking studies was performed against alkaline phosphatase enzyme (PDBID 1EW2) to check binding affinity of the synthesized compounds 6a–i against target protein. The docking results showed that three compounds 6c , 6e , and 6i have maximum binding interactions with binding energy values of −8 kcal/mol. The compound 6i displayed the interactions of oxadiazole ring nitrogen with amino acid His265 having a binding distance 2.13 Ǻ. It was concluded from our results that synthesized compounds, especially compound 6i may serve as lead structure to design more potent inhibitors of human alkaline phosphatase.     

Does Rest Time before Ultrasonography Imaging Affect Quadriceps Femoris Muscle Thickness,Cross-Sectional Area and Echo Intensity Measurements?

In the work described here, our aim was to determine, in an elderly population, changes in muscle thickness (MT), cross-sectional area (CSA) and echo intensity (EI) of the quadriceps muscles at four time points (0, 5, 10 and 15 min; i.e., T0, T5, T10 and T15, respectively) after changing from a standing to supine position. Twenty-one elderly participants (14 men: 68.1 ± 4.6 y; 8 women: 66.8 ± 4.1 y) were evaluated at four time points. Rectus femoris CSA (RF_CSA), MT and EI of the quadriceps femoris (QF) muscles were assessed. EI significantly increased from T0 to T5, T10 and T15 (p < 0.001), whereas no differences were observed between T5 and T15 in the rectus femoris (RF_EI), vastus intermedius (VI_EI) and quadriceps femoris (QF_EI). No differences were observed between any time points in the RF_CSA and MT of QF muscles. In summary, these results suggest that periods >5 min are not necessary to obtain consistent MT and EI measurements of quadriceps femoris muscles in the elderly population.     

Debate: Bipolar disorder: extremely rare before puberty and antipsychotics cause serious harms – a commentary on Van Meter et al. (2019)

‘Paediatric bipolar disorder’ (PBD) remains controversial; because it is based on the hypothesis that bipolar disorder (BD) often begins in childhood with atypical forms of mania. A meta-analysis of 12 epidemiological surveys found a high prevalence of PBD among children and adolescents worldwide (1.8%), however, our study of the measurement issues (Child and Adolescent Mental Health, 23, 2018, 14) found that PBD rates were lower than claimed. Our findings are consistent with the developmental trajectory of BD, as described by most longitudinal studies of high-risk offspring. BD is extremely rare in childhood with nearly all index manic/hypomanic episodes being in midadolescence or later. Treatment for BD should not commence until the first well-defined manic/hypomanic episode, because children and younger adolescents are extremely sensitive to the side effects of second-generation antipsychotics including weight gain, metabolic syndrome, extrapyramidal side effects and the risk of cerebral atrophy, as observed in studies of juvenile animals.     

妊娠早期胎儿颈部透明层厚度与胎儿预后的前瞻性队列研究

目的探讨妊娠早期胎儿颈部透明层(NT)厚度与胎儿预后的关系。方法收集2015年12月至2018年12月于南京大学医学院附属鼓楼医院行妊娠早期胎儿NT厚度测量的单胎孕妇,共4958例建立前瞻性研究队列,进行妊娠早期胎儿结构超声筛查、妊娠早期血清学筛查、妊娠中期超声筛查及对新生儿出生后28 d的体格检查。根据妊娠早期超声筛查的结果,分为胎儿NT增厚(≥3.0 mm)者167例与NT厚度正常者4791例;将胎儿NT增厚的孕妇,分为胎儿单纯NT增厚者86例与NT增厚合并结构异常者81例。分析不同NT厚度胎儿的预后,并重点对单纯NT增厚与NT增厚合并结构异常胎儿的妊娠结局进行分析。妊娠早期超声筛查发现胎儿结构异常或血清学筛查结果为高风险的孕妇,经绒毛穿刺取样术行染色体微阵列分析(CMA)检测以明确产前诊断。结果(1)胎儿NT厚度正常孕妇的妊娠结局:共4791例孕妇,包括胎儿NT厚度正常且无结构异常者4726例,其中妊娠中期及产后新诊断结构异常83例,4688例活产;胎儿NT厚度正常但结构异常的孕妇65例,其中61例孕妇终止妊娠,4例活产。(2)胎儿单纯NT增厚孕妇的妊娠结局:86例孕妇中,66例(76.7%,66/86)行CMA检测,3例胎儿诊断为21三体综合征;除7例孕妇选择终止妊娠外,余79例行妊娠中期超声检查、新生儿出生后28 d体格检查、新生儿电话随访至6~21个月均未发现发育异常。(3)胎儿NT增厚合并结构异常孕妇的妊娠结局:81例孕妇中,73例(90.1%,73/81)行CMA检测,其中32例的胎儿为染色体非整倍体异常。70例选择终止妊娠,2例妊娠中期自然流产,9例活产。(4)NT增厚是否合并结构异常胎儿的产前诊断结果及预后比较:单纯NT增厚的胎儿染色体非整倍体的发生率为3.5%(3/86),合并结构异常者为39.5%(32/81),两者比较,差异有统计学意义(χ2=32.7,P<0.01);胎儿单纯NT增厚孕妇的健康新生儿存活率为91.9%(79/86),合并结构异常者为9.9%(8/81),两者比较,差异有统计学意义(χ2=112.3,P<0.01)。结论妊娠早期,超声筛查胎儿NT及结构,能提高出生缺陷的产前筛查率。单纯NT增厚胎儿的染色体非整倍体的发生率较低,新生儿健康存活率较高。     

The relative risk of noncervical high-risk human papillomavirus-related (pre)malignancies after recurrent cervical intraepithelial neoplasia grade 3: A population-based study

Women with cervical intraepithelial neoplasia grade 3 (CIN3) have a long-lasting increased risk for noncervical high-risk human papillomavirus (hrHPV)-related (pre)malignancies. The aim of our study was to estimate this risk in women with recurrent CIN3 compared to women without a history of CIN3 and women with a single episode of CIN3. Women with a CIN3 diagnosis between 1990 and 2010 were obtained from the Dutch Pathology Registry (PALGA) and matched with a control group of women without CIN3. Analysis has been conducted in a subset of women with recurrent CIN3, defined as reoccurrence minimally 2 years post-treatment. Cases of noncervical hrHPV-related (pre)malignancies of the anus, vulva, vagina and oropharynx were identified until 2015 and incidence rate ratios (IRRs) were estimated. Then, 1,797 women with recurrent CIN3 were included with a median age of 34 years (range 18–76) and 31,594 person-years of follow-up. Women with recurrent CIN3 had an increased risk of developing noncervical hrHPV-related (pre)malignancies compared to women without CIN3 with an IRR of 25.96 (95%CI 6.32–106.58). The IRR was 2.48 (95% CI 1.87–3.30) compared to women with a single episode of CIN3. Studies on posttreatment follow-up and prophylactic hrHPV vaccination are warranted.