临床医生的个案研究设计

个案研究设计适合于提出研究假说，这种假说以后可以通过其他方法得到临床确认，这也适用于先导性临床试验(pilot study)，即在设计正式的临床试验之前，对要研究的药物进行一个初步的评估。其设计类型包括简单的A-B时序设计、经典的A-B-A反转设计、替代治疗设计、多基线设计。该设计应用的前提是治疗在较短时间能表现出最大效应，并且效应是短暂的，一旦治疗停止，则病情可逆，如果不是这种情况，则必须考虑成组设计。个案研究的方法一般依赖于“A”阶段的稳定基线期。该研究方法不适宜对急性或易变的疾病状况进行研究，而适用于对具有稳定病症表现的慢性或复发性疾病的研究。     

A novel technique of Roux-en-Y gastric bypass reversal for postprandial hyperinsulinemic hypoglycaemia: A case report

BackgroundWe describe an evaluation of the effects of partial Roux-en-Y gastric bypass (RYGB) reversal on postprandial hyperinsulinaemic hypoglycaemia, insulin and GLP-1 levels.Case summaryA 37 year old man was admitted with neuroglycopenia (plasma–glucose 1.6 mmol/l) 18 months after RYGB, with normal 72 h fasting test and abdominal CT. Despite dietary modifications and medical treatment, the hypoglycaemic episodes escalated in frequency. Feeding by a gastrostomy tube positioned in the gastric remnant did not prevent severe episodes of hypoglycaemia. A modified reversal of the RYGB was performed. Mixed meal tests were done perorally (PO), through the gastrostomy tube 1 (GT1), 4 weeks (GT2) after placement and 4 weeks after reversal (POr), with assessment of glucose, insulin and GLP-1 levels.ResultsPlasma–glucose increased to a maximum of 9.6, 5.4, 6.5 and 5.8 mmol/l at the PO, GT1, GT2 and POr tests respectively. The corresponding insulin levels were 2939, 731, 725 and 463 pmol/l. A decrease of plasma–glucose followed: 2.2, 3.0, 3.9 and 2.9 mmol/l respectively and insulin levels were suppressed at 150 min: 45, 22, 21 and 14 pmol/l, respectively. GLP-1 levels increased in the PO test (60 min: 122 pmol/l, 21 fold of basal), but was attenuated in the two latter tests (12–23 pmol/l at 60 min).ConclusionsReduction of plasma–glucose, insulin and GLP-1 excursions and symptoms were seen after gastric tube placement and partial RYGB reversal. This attenuation of GLP-1 response to feeding could reflect an adaptation to nutrients.     

Did We Get Sensorimotor Adaptation Wrong? Implicit Adaptation as Direct Policy Updating Rather than Forward-Model-Based Learning

The human motor system can rapidly adapt its motor output in response to errors. The prevailing theory of this process posits that the motor system adapts an internal forward model that predicts the consequences of outgoing motor commands and uses this forward model to plan future movements. However, despite clear evidence that adaptive forward models exist and are used to help track the state of the body, there is no definitive evidence that such models are used in movement planning. An alternative to the forward-model-based theory of adaptation is that movements are generated based on a learned policy that is adjusted over time by movement errors directly (“direct policy learning”). This learning mechanism could act in parallel with, but independent of, any updates to a predictive forward model. Forward-model-based learning and direct policy learning generate very similar predictions about behavior in conventional adaptation paradigms. However, across three experiments with human participants (N = 47, 26 female), we show that these mechanisms can be dissociated based on the properties of implicit adaptation under mirror-reversed visual feedback. Although mirror reversal is an extreme perturbation, it still elicits implicit adaptation; however, this adaptation acts to amplify rather than to reduce errors. We show that the pattern of this adaptation over time and across targets is consistent with direct policy learning but not forward-model-based learning. Our findings suggest that the forward-model-based theory of adaptation needs to be re-examined and that direct policy learning provides a more plausible explanation of implicit adaptation.SIGNIFICANCE STATEMENT The ability of our brain to adapt movements in response to error is one of the most widely studied phenomena in motor learning. Yet, we still do not know the process by which errors eventually result in adaptation. It is known that the brain maintains and updates an internal forward model, which predicts the consequences of motor commands, and the prevailing theory of motor adaptation posits that this updated forward model is responsible for trial-by-trial adaptive changes. Here, we question this view and show instead that adaptation is better explained by a simpler process whereby motor output is directly adjusted by task errors. Our findings cast doubt on long-held beliefs about adaptation.     

联合应用mTI-ASL和IVIM技术在鉴别高级别胶质瘤术后复发与假性进展中的应用价值

目的: 探讨应用多反转时间动脉自旋标记(multiple inversion time-pulsed arterial spin labeling,mTI-ASL)和体素内不相干运动(intravoxel incoherent motion,IVIM)技术在脑胶质瘤术后复发与假性进展中的鉴别价值。方法: 选择2018年01月至2020年01月就诊于我院高级别胶质瘤术后放化疗后首次复查常规MR增强扫描出现异常强化的患者,行mTI-ASL及IVIM序列扫描,将获取图像数据资料进行相关后处理分析,分别手动勾画感兴趣区,测量术后异常强化区各项定量参数,即真性扩散系数(true diffusion coefficient,D)、假性扩散系数(pseudo-diffusion coefficient,D*)及灌注分数(perfusion fraction,f)、脑血流量(cerebral blood flow,CBF)和动脉通过时间(arterial transit time,ATT)。分别采用独立样本t检验比较两组感兴趣区相关参数值,从而评估mTI-ASL和IVIM技术在两者鉴别诊断中的价值。结果: (1)脑胶质瘤术后复发组CBF值(6.413±0.438)、ATT值(0.198±0.033),比假性进展组CBF值(4.654±0.372)、ATT值(0.165±0.208)高,两者比较具有统计学意义(P＜0.01)。(2)脑胶质瘤术后复发组D值(1.118±0.178),比假性进展组D值(1.380±0.236)低,两者比较具有统计学意义(P＜0.01)。(3)脑胶质瘤术后复发组D*值(17.126±4.274)、f值(0.269±0.095),比假性进展组D*值(12.755±3.974)、f值(0.169±0.052)高,两者比较具有统计学意义(P＜0.01)。结论:应用 mTI-ASL和IVIM技术有助于脑胶质瘤术后复发与假性进展的鉴别诊断。     

术中MR液体反转恢复序列在低级别神经胶质瘤切除术中的应用价值

目的探讨术中磁共振成像(intraoperative MRI,iMRI)中的液体反转恢复序列(fluid attenuated inversion recovery,FLAIR)在低级别神经胶质瘤(WHOⅠ~Ⅱ级)切除术中的应用价值,从而对是否存在残留肿瘤的诊断提供帮助。方法选取18例低级别神经胶质瘤(low-grade gliomas,LGGs)患者的术中MRI,查看FLAIR图像中手术腔周围是否存在高信号,并对术前或术后复查过MRI患者的图像进行分析,比较术区周边FLAIR信号的变化情况。结果低级别神经胶质瘤切除术中手术区域边缘iMRI的FLAIR表现:1)没有FLAIR异常信号7例;2)线状FLAIR高信号(linear FLAIR hyperintensity,LFH)7例;3)结节或片状FLAIR高信号(nodular or patchy FLAIR hyperintensity,NPFH)4例。接受iMRI分析的患者的手术切缘上无FLARI异常信号中的4例术后3个月复查MRI术区周围未见异常改变;出现LFH中有4例患者在术后3个月后复查MRI,异常信号强度减低或消失。而2例NPFH随即进行了第二次手术切除,并再次行术中MRI扫描,最终组织病理学为肿瘤残留,1例NPFH未进行二次手术,半年后复查,异常信号范围增大。结论经iMRI分析的手术区域切缘可能出现FLAIR高信号,出现线状FLAIR高信号时不应误认为是残余肿瘤,而出现结节或片状FLAIR高信号时可能是残余肿瘤。iMRI FLAIR在初步判断低级别神经胶质瘤切除术术区边缘是否存在残留肿瘤方面有一定的应用价值。     

Switchable hardening of a ferromagnet at fixed temperature

The intended use of a magnetic material, from information storage to power conversion, depends crucially on its domain structure, traditionally crafted during materials synthesis. By contrast, we show that an external magnetic field, applied transverse to the preferred magnetization of a model disordered uniaxial ferromagnet, is an isothermal regulator of domain pinning. At elevated temperatures, near the transition into the paramagnet, modest transverse fields increase the pinning, stabilize the domain structure, and harden the magnet, until a point where the field induces quantum tunneling of the domain walls and softens the magnet. At low temperatures, tunneling completely dominates the domain dynamics and provides an interpretation of the quantum phase transition in highly disordered magnets as a localization/delocalization transition for domain walls. While the energy scales of the rare earth ferromagnet studied here restrict the effects to cryogenic temperatures, the principles discovered are general and should be applicable to existing classes of highly anisotropic ferromagnets with ordering at room temperature or above.     

Shared Neuropathological Characteristics of Obesity,Type 2 Diabetes and Alzheimer’s Disease: Impacts on Cognitive Decline

In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer’s disease (AD), has increased. While the consumption of diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes.