Machine learning identifies unaffected first‐degree relatives with functional network patterns and cognitive impairment similar to those of schizophrenia patients

Schizophrenia (SCZ) patients and their unaffected first‐degree relatives (FDRs) share similar functional neuroanatomy. However, it remains largely unknown to what extent unaffected FDRs with functional neuroanatomy patterns similar to patients can be identified at an individual level. In this study, we used a multivariate pattern classification method to learn informative large‐scale functional networks (FNs) and build classifiers to distinguish 32 patients from 30 healthy controls and to classify 34 FDRs as with or without FNs similar to patients. Four informative FNs—the cerebellum, default mode network (DMN), ventral frontotemporal network, and posterior DMN with parahippocampal gyrus—were identified based on a training cohort and pattern classifiers built upon these FNs achieved a correct classification rate of 83.9% (sensitivity 87.5%, specificity 80.0%, and area under the receiver operating characteristic curve [AUC] 0.914) estimated based on leave‐one‐out cross‐validation for the training cohort and a correct classification rate of 77.5% (sensitivity 72.5%, specificity 82.5%, and AUC 0.811) for an independent validation cohort. The classification scores of the FDRs and patients were negatively correlated with their measures of cognitive function. FDRs identified by the classifiers as having SCZ patterns were similar to the patients, but significantly different from the controls and FDRs with normal patterns in terms of their cognitive measures. These results demonstrate that the pattern classifiers built upon the informative FNs can serve as biomarkers for quantifying brain alterations in SCZ and help to identify FDRs with FN patterns and cognitive impairment similar to those of SCZ patients.     

BRCA mutation testing for first-degree relatives of women with high-grade serous ovarian cancer

BackgroundWomen with high-grade serous ovarian cancer (HGSC) have a 20% chance of carrying a BRCA1 or 2 mutation. Not all undergo genetic testing, and there is a large legacy group of untested patients. Their female first-degree relatives (FDR) may not qualify for testing unless they have specific ethnicity, or personal/family cancer history. We conducted a cost-effectiveness analysis to evaluate risk-reducing strategies for these FDR who are ineligible for testing.MethodsA Markov Monte Carlo simulation model estimated the costs and benefits of 3 strategies for female FDR of HGSC patients whose BRCA status is unknown: (1) no BRCA testing; (2) universal BRCA testing, followed by risk-reducing bilateral salpingo-oophorectomy (RRBSO) for mutation carriers; (3) universal RRBSO, without BRCA testing. Effectiveness was estimated in quality-adjusted life year (QALY) gains over a 50-year time horizon. Sensitivity analyses accounted for uncertainty around various parameters.ResultsUniversal BRCA testing for female FDR of women with HGSC yielded a higher average QALY gain at acceptable cost compared to no BRCA testing, with an incremental cost-effectiveness ratio of $7888 per QALY. Universal BRCA testing was more effective and less costly than universal RRBSO (19.20 QALYs vs. 18.52 QALYs, and $10,135 vs. $14,231, respectively). Results were stable over wide ranges of plausible costs and estimates. Compliance with hormone replacement therapy had to exceed 79.3% for universal RRBSO to be the most effective strategy.ConclusionBRCA mutation testing should be offered to all female first-degree relatives of women with high-grade serous ovarian cancer when BRCA mutation status is unknown.     

抑郁症及其一级亲属脑基础活动的BOLD-fMRI研究

目的 运用功能磁共振成像(fMRI)研究抑郁症(MDD)及其一级亲属静息状态下脑区的低频振幅(ALFF)及低频振幅比率(fALFF)的特点及差异,以了解MDD患者早期的脑功能状态.方法 对10例MDD患者(MDD组)、10例MDD一级亲属(一级亲属组)、10例健康志愿者(对照组)进行3.0T静息状态脑功能磁共振成像 (fMRI),分别计算各组的ALFF、fALFF,进行统计学分析.结果 与一级亲属组相比,MDD组的左侧小脑、左侧楔前叶、左侧内侧前额叶皮质的ALFF、fALFF值均显著性降低(P<0.05);而右侧背侧扣带回皮质、右侧顶上小叶的ALFF值显著减低(P<0.05);与对照组相比,MDD组的左侧小脑、左侧楔前叶、左侧顶上小叶的ALFF、fALFF值均显著性降低(P<0.05),而右侧扣带回皮质、内侧前额叶皮质的ALFF值显著减低(P<0.05);一级亲属组与对照组相比,ALFF值无统计学差异,一级亲属组的左侧顶上小叶的fALFF值显著降低(P<0.05).结论 MDD患者及一级亲属脑区均存在广泛的ALFF、fALFF异常,这些异常的脑区可能与MDD认知网络障碍及情感低落相关.     

Implementation of Screening Colonoscopy amongst First-Degree Relatives of Patients with Colorectal Cancer in Turkey: a Cross-Sectional Questionnaire Based Survey

Objective: To evaluate the implementation of screening colonoscopy amongst first-degree relatives (FDRs)of patients with colorectal cancer (CRC) in Turkey. Materials and Methods: A total of 400 first-degree relatives(mean(SD)age: 42.5(12.7) years, 55.5% were male) of 136 CRC patients were included in this cross-sectionalquestionnaire based survey. Data on demographic characteristics, relationship to patient and family history formalignancy other than the index case were evaluated in the FDRs of patients as were the data on knowledge aboutand characteristics related to the implementation of screening colonoscopy using a standardized questionnaireform. Results: The mean(SD) age at diagnosis of CRC in the index patients was 60.0(14.0) years, while mean(SD)age of first degree relatives was 42.5(12.7) years. Overall 36.3% of relatives were determined to have knowledgeabout colonoscopy. Physicians (66.9%) were the major source of information. Screening colonoscopy wasrecommended to 19.5% (n=78) of patient relatives, while 48.7% (n=38) of individuals participated in colonoscopyprocedures, mostly (57.9%) one year after the index diagnosis. Screening colonoscopy revealed normal findingsin 25 of 38 (65.8%) cases, while precancerous lesions were detected in 26.3% of screened individuals. In 19.0% ofFDRs of patients, there was a detected risk for Lynch syndrome related cancer. Conclusions: In conclusion, ourfindings revealed that less than 20% of FDRs of patients had received a screening colonoscopy recommendation;only 48.7% participated in the procedure with detection of precancerous lesions in 26.3%. Rise of awarenessabout screening colonoscopy amongst patients with CRC and first degree relatives of patients and motivationof physicians for targeted screening would improve the participation rate in screening colonoscopy by FDRs ofpatients with CRC in Turkey.     

Smoking Habits of Relatives of Patients with Cancer: Cancer Diagnosis in the Family is an Important Teachable Moment for Smoking Cessation

Background: In this study we aimed to determine the rate and habitual patterns of smoking, intentions ofcessation, dependence levels and sociodemographic characteristics of relatives of patients with a diagnosis ofcancer. Materials and Methods: This study was designed by the Turkish Oncology Group, Epidemiology andPrevention Subgroup. The relatives of cancer patients were asked to fill a questionnaire and Fagerstrom testof nicotine dependence. Results: The median ages of those with lower and higher Fagerstrom scores were 40years and 42 years, respectively. We found no evidence of variation between the two groups for the remainingsociodemographic variables, including the subject’s medical status, gender, living in the same house with thepatient, their educational status, their family income, closeness to their cancer patients or spending time withthem or getting any help or wanting to get some help. Only 2% of the subjects started smoking after cancer wasdiagnosed in their loved ones and almost 20% of subjects had quit smoking during the previous year. Conclusions:The Fagerstrom score is helpful in determining who would be the most likely to benefit from a cigarette smokingcessation program. Identification of these people with proper screening methods might help us to pinpoint whowould benefit most from these programs.     

Functional capacity after hip arthroplasty: A comparison between evaluation with three standard instruments and a personal interview

The aim of the present study was to compare the information obtained from three standard instruments used in physiotherapy and occupational therapy and with information acquired from an unstructured interview. Ten patients with osteoarthritis of the hip were consecutively picked from the waiting list at an orthopedic clinic. All were examined before and six months after arthroplasty. The study layout is a mixture of quantitative and qualitative evaluation. The three instruments used were SF-36 (self-reported health-related quality of life), FAS (an instrument for evaluation of lower extremity dysfunction), and the COPM (for evaluation of self-experienced activity level). All patients were also interviewed in a free, unstructured interview, and data were analyzed with a phenomenological approach. All methods could describe function and activity status of the patients very well, and they were also responsive to postoperative improvement. Together the three instruments gave such good information that almost no extra information was obtained through the interviews. On the other hand, the interviews served as powerful validation of the three instruments. The information in the three separate instruments is qualitatively different, and one instrument cannot replace another. They cannot be replaced by the interview either, because the instruments provide the therapist with specific and structured information that is important for further treatment planning and follow-up.     

基于红外光谱法的云南重楼及其近缘种的亲缘关系研究

目的傅里叶变换红外光谱(fourier transform infrared spectroscopy,FTIR)结合化学计量学方法分析云南重楼Paris polyphylla var.yunnanensis及其近缘种的亲缘关系,为重楼属药用植物资源的开发利用提供理论依据。方法采集云南重楼、白花重楼Paris polyphylla var.alba、毛重楼Paris mairei、南重楼Paris vietnamensis、五指莲Paris axialis var.axialis共50份样品的红外光谱信息,对光谱数据进行自动基线校正、自动平滑、纵坐标归一化、多元散射校正、二阶求导等预处理,采用主成分分析(principal component analysis,PCA)、偏最小二乘判别分析(partial least squares discriminant analysis,PLS-DA)及系统聚类分析(hierarchical cluster analysis,HCA)分析光谱数据。结果原始红外光谱中,1 653、1 156、1 082、1 021、925、851、759、572、524 cm~(-1)等为重楼属植物的共有峰,主要归属为黄酮、淀粉和糖苷类成分的吸收峰;毛重楼和五指莲分别在1 535和1 369 cm~(-1)附近有特征吸收峰,可与另外3种重楼属植物相区分。以全波段光谱数据进行PLS-DA和PCA,PLS-DA对重楼属植物分类效果优于PCA,能够准确区分5种野生重楼属植物。系统聚类分析(HCA)及向量夹角余弦相关性分析能够反映5个重楼属植物的亲缘关系,云南重楼与白花重楼和南重楼的亲缘关系较近,与毛重楼和五指莲的关系较远。结论 FTIR结合化学计量学方法,能够快速区分不同种类重楼属植物,明确云南重楼及其近缘种之间的亲缘关系,为重楼属植物亲缘关系研究提供一种快速、有效的方法,同时为重楼种质资源开发和利用提供理论基础。