Families With Children With Medical Complexity and Self-Management of Care: A Systematic Review of the Literature

This review analyzes the quantitative literature on children with medical complexity (CMC). Using the Pediatric Self-Management Model, evidence is summarized into facilitators and barriers to self-management. Current quantitative research focuses on the caregiver burden in families with CMC. A model for social work with families with CMC was introduced in response to these findings. A re-envisioned model allows the child with medical complexity to be seen as whole rather than focusing on typically deficit-based areas of medical specialty or service provision.     

Matching variables for research involving youth with Down syndrome: Leiter-R versus PPVT-4

Much of what is known about the cognitive profile of Down syndrome (DS) is based on using either receptive vocabulary (e.g., PPTV-4) or nonverbal ability (e.g., Leiter-R) as a baseline to represent cognitive developmental level. In the present study, we examined the relation between these two measures in youth with DS, with non-DS intellectual disability (ID), and with typical development (TD). We also examined the degree to which these two measures produce similar results when used as a group matching variable. In a cross-sectional developmental trajectory analysis, we found that the relation between PPVT-4 and Leiter-R was largely similar across groups. However, when contrasting PPVT-4 and Leiter-R as alternate matching variables, the pattern of results was not always the same. When matched on Leiter-R or PPVT-4, the group with DS performed below that of the groups with ID and TD on receptive grammar and below the group with TD on category learning. When matched on the PPVT-4, the group with ID performed below that of the group with TD on receptive grammar and category learning, but these differences between the groups with ID and TD were not found when matched on the Leiter-R. The results of the study suggest that the PPVT-4 and Leiter-R are interchangeable at least for some outcome measures for comparing youth with DS and TD, but they may produce different results when comparing youth with ID and TD.     

地黄苷D对皮质酮诱导的PC-12细胞损伤的保护作用及机制研究

目的 研究从地黄Rehmannia glutinosa中分离得到的地黄苷D对皮质酮诱导的肾上腺嗜铬细胞瘤细胞（PC-12细胞）的保护作用及机制。方法 以500μmol/L皮质酮处理PC-12细胞24 h建立损伤模型，同时给予氟西汀和地黄苷D进行干预，采用MTT法检测细胞存活率；采用流式细胞术检测细胞凋亡、活性氧（reactive oxygen species,ROS）以及线粒体膜电位水平；采用In-Cell Western法检测细胞内凋亡相关蛋白半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3,Caspase-3)、剪切型Caspase-3(cleaved Caspase-3)、B淋巴细胞瘤2(B-cell lymphoma 2,Bcl-2)和Bcl-2相关X蛋白（Bcl-2 associated X protein,Bax）表达；采用高内涵细胞成像系统检测细胞内脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）蛋白表达。结果 地黄苷D明显提高皮质酮诱导的PC-12细胞存活率（P<0.05、0.01...     

Cyclin-dependent kinase inhibitors for the treatment of lung cancer

ABSTRACT

Introduction

Cyclin-dependent kinases (CDKs) are critical regulators of cell cycle progression in both normal and malignant cells, functioning through complex molecular interactions. Deregulation of CDK-dependent pathways is commonly found in both non-small cell and small cell lung cancer, and these derangements suggest vulnerabilities that can be exploited for clinical benefit.     

基于PTPR排名的基因随机选择算法

面对高维、小样本的基因微阵列数据,有效地提取特征基因成为一项艰巨的任务.在随机特征选择方法的基础上,引入“种子变量”及滚动的排名机制,提出一种基于职业网球选手排名(PTPR)的特征选择算法.用种子变量提高变量搜索过程的选择性,提高搜索效率,同时充分利用历史记录来动态更新种子变量,加快寻优速度.在公共数据库上的测试实验结果表明,PTPR在随机多次独立运行时得到平均50％ ～ 80％的相同基因,而MichalDraminski的方法只能保持相同基因在10％ ～50％左右；收敛性实验表明,PTPR的收敛速度更快且显著；而在5个数据集的独立测试集上的分类率实验表明,PTPR保持较高的分类率,如PTPR得到最高分类率大约为98％、90％、89％、95％、75％,而Michal Draminski方法的最高分类率为96％、89％、85％、95％、70％.同时,与其他典型方法相比,PTPR也得到了较高的分类率.总体上,PTPR算法具有搜索速度快、结果稳定的特点,而且在不同的分类器上都保持了较优的分类率.     

Practical Treatment Strategies and Future Directions After Progression While Receiving CDK4/6 Inhibition and Endocrine Therapy in Advanced HR+/HER2− Breast Cancer

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with backbone endocrine therapy have markedly improved progression-free survival and overall survival over endocrine therapy alone in advanced hormone receptor–positive, HER2-negative (HR⁺/HER2⁻) breast cancer and are the standard of care in the first- or second-line setting. There are few data to drive decision making for subsequent treatment strategies after inevitable disease progression after CDK4/6i. Information about the genomic landscape of CDK4/6i-resistant disease is emerging. Resistance mechanisms appear to be varied, but mutations in PIK3CA and ESR1, which can be acquired while receiving treatment, are frequent. Activating PIK3CA mutations are present in up to 35% of patients and are now the most actionable genomic alteration in HR⁺/HER2⁻ advanced breast cancer with the recent approval of alpelisib and fulvestrant. Everolimus-based combinations and chemotherapy appear to have continued efficacy after progression while receiving CDK4/6i, although historical data on benefit include CDK4/6i-naive patients. Use of selective estrogen down-regulators over aromatase inhibitors is best once the patient has an acquired ESR1 mutation. Tumor biopsy with genomic sequencing and repeat biomarker analysis in patients with CDK4/6i- and endocrine-resistant disease will be integral to guide subsequent treatment strategies and to inform clinical trial eligibility. Promising novel therapeutics in CDK4/6i-resistant disease including oral selective estrogen down-regulators, fibroblast growth factor receptor antagonists, and immunotherapy will be discussed.     

Mother’s mental health after childbirth: Does the delivery method matter?

The dramatic increase in the utilization of caesarean section has raised concerns on its impact on public expenditure and health. While the financial costs associated with this surgical procedure are well recognized, less is known on the intangible health costs borne by mothers and their families. We contribute to the debate by investigating the effect of unplanned caesarean deliveries on mothers’ mental health in the first nine months after the delivery. Differently from previous studies, we account for the unobserved heterogeneity due to the fact that mothers who give birth through an unplanned caesarean delivery may be different than mothers who give birth with a natural delivery. Identification is achieved exploiting exogenous variation in the position of the baby in the womb at the time of delivery while controlling for hospital unobserved factors. We find that mothers having an unplanned caesarean section are at higher risk of developing postnatal depression and this result is robust to alternative specifications.