Suicide risk and suicide method in patients with personality disorders

ObjectiveThe influence of psychopathology on suicide method has revealed different distributions among different psychiatric disorders. However, evidence is still scarce. We hypothesized that having a diagnosis of personality disorder (PD) affect the suicide method, and that different PD clusters would influence the suicide method in different ways. In addition, we hypothesized that the presence of psychiatric and somatic co-morbidity also affects the suicide method.MethodWe examined 25,217 individuals aged 15–64 who had been hospitalized in Sweden with a main diagnosis of PD the years 1987–2013 (N = 25,217). The patients were followed from the date of first discharge until death or until the end of the follow-up period, i.e. December 31, 2013, for a total of 323,508.8 person-years, with a mean follow up time of 11.7 years. The SMR, i.e. the ratio between the observed number of suicides and the expected number of suicides, was used as a measure of risk.ResultsOverall PD, different PD-clusters, and comorbidity influenced the suicide method. Hanging evidenced highest SMR in female PD patients (SMR 34.2 (95% CI: 29.3–39.8)), as compared to non-PD patients and jumping among male PD patients (SMR 24.8 (95% CI: 18.3–33.6)), as compared to non PD-patients. Furthermore, the elevated suicide risk was related to both psychiatric and somatic comorbidity.ConclusionThe increased suicide risk was unevenly distributed with respect to suicide method and type of PD. However, these differences were only moderate and greatly overshadowed by the overall excess suicide risk in having PD. Any attempt from society to decrease the suicide rate in persons with PD must take these characteristics into account.     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

B cell and B cell-related pathways for novel cancer treatments

B cells are recognized as the main effector cells of humoral immunity which suppress tumor progression by secreting immunoglobulins, promoting T cell response, and killing cancer cells directly. Given these properties, their anti-tumor immune response in the tumor micro-environment (TME) is of great interest. Although T cell-related immune responses have become a therapeutic target with the introduction of immune checkpoint inhibitors, not all patients benefit from these treatments. B cell and B cell-related pathways (CCL19, −21/CCR7 axis and CXCL13/CXCR5 axis) play key roles in activating immune response through humoral immunity and local immune activation via tertiary lymphoid structure (TLS) formation. However they have some protumorigenic works in the TME. Thus, a better understanding of B cell and B cell-related pathways is necessary to develop effective cancer control. In this review, we summarize recent evidences regarding the roles of B cell and B cell-related pathways in the TME and immune response and discuss their potential roles for novel cancer treatment strategies.     

Oscillating gradient diffusion kurtosis imaging of normal and injured mouse brains

Recent advances in diffusion MRI employ multiple diffusion encoding schemes with varying diffusion direction, weighting, and diffusion time to investigate specific microstructural properties in biological tissues. In this study, we examined time‐dependent diffusion kurtosis contrast in adult mouse brains and in neonatal mouse brains after hypoxic–ischemic (HI) injury. In vivo diffusion kurtosis maps were acquired with a short diffusion time using an oscillating gradient spin echo (OGSE) sequence at 100 Hz and with a relatively long diffusion time (20 ms) using a pulsed gradient spin echo (PGSE) sequence. In the adult mouse brain, we found that the cortex and hippocampus showed larger differences between OGSE kurtosis and PGSE kurtosis than major white matter tracts. In neonatal mouse brains with unilateral HI injury, the OGSE kurtosis map overall provided stronger edema contrast than the PGSE kurtosis map, and the differences between OGSE and PGSE kurtosis measurements in the edema region reflected heterogeneity of injury. This is the first in vivo study that has demonstrated multi‐direction OGSE kurtosis contrasts in the mouse brain. Comparing PGSE and OGSE kurtosis measures may provide additional information on microstructural changes after ischemic stroke.     

Biomechanical effect of the configuration of screw hole style on locking plate fixation in proximal humerus fracture with a simulated gap: A finite element analysis

BackgroundLocking plate fixation for proximal humeral fractures is a commonly used device. Recently, plate breakages were continuously reported that the implants all have a mixture of holes allowing placement of both locking and non-locking screws (so-called combi plates). In commercialized proximal humeral plates, there still are two screw hole styles included “locking and dynamic holes separated” and “locking hole only” configurations. It is important to understand the biomechanical effect of different screw hole style on the stress distribution in bone plate.MethodsFinite element method was employed to conduct a computational investigation. Three proximal humeral plate models with different screw hole configurations were reconstructed depended upon an identical commercialized implant. A three-dimensional model of a humerus was created using process of thresholding based on the grayscale values of the CT scanning of an intact humerus. A “virtual” subcapital osteotomy was performed. Simulations were performed under an increasing axial load. The von Mises stresses around the screw holes of the plate shaft, the construct stiffness and the directional displacement within the fracture gap were calculated for comparison.ResultsThe mean value of the peak von Mises stresses around the screw holes in the plate shaft was the highest for combi hole design while it was smallest for the locking and dynamic holes separated design. The stiffness of the plate-bone construct was 15% higher in the locking screw only design (132.6 N/mm) compared with the combi design (115.0 N/mm), and it was 4% higher than the combi design for the locking and dynamic holes separated design (119.5 N/mm). The displacement within the fracture gap was greatest in the combi hole design, whereas it was smallest for the locking hole only design.ConclusionsThe computed results provide a possible explanation for the breakages of combi plates revealed in clinical reports. The locking and dynamic holes separated design may be a better configuration to reduce the risk of plate fracture.     

褪黑素时间序列中缺失值的填补方法研究

目的模拟同一时间点数据完全缺失和部分缺失2种情况,通过填补值和实际值的对比,比较各填补方法对褪黑素(MT)时间序列的填补效果。方法同一时间点完全缺失时,比较实际值与SPSS 5种填补方法填补结果;部分缺失时,除完全缺失的填补方法外,增加拟合时间序列模型填充。结果完全缺失时,临近点的中位数和线性插值法的填补结果和两因素析因设计资料方差分析结果更接近于实际。实际值波动幅度较小的时候,插值法拟合效果好;在实际值波动较大时,临近中位数拟合效果好。部分缺失时,拟合模型填充效果好。结论完全缺失时,如排除缺失值大幅波动,可以运用临近中位数和插值法对缺失值进行填充。在临近值波动幅度较小时,选用插值法填充值;在临近值波动幅度较大时,选用临近中位数填充值。部分缺失时,选用时间序列拟合模型填充。     

Do regions of interest location and type influence liver stiffness measurement using magnetic resonance elastography?

PurposeTo assess the variability of liver stiffness measurements using magnetic resonance elastography (MRE) at 1.5 T, depending on different approaches of regions of interest (ROIs) drawing.Material and methodsFifty consecutive patients with successful liver MRE were included. There were 32 men and 18 women with a mean age of 52 ± 14 (SD) years (range: 20–85 years). MRE was acquired using a gradient recalled-echo MRE sequence. At the level of the portal bifurcation, one observer drawn in the right liver first 3 elliptical ROI and then one free-hand ROI, as large as possible based on the confidence map and the anatomy. Three additional elliptical ROIs were further drawn on the slice above and 3 other on the slice below, for a total of 9 elliptical ROIs. The average value of liver stiffness in the 3 elliptical ROIs of the central slice and the one from the 9 elliptical ROIs were computed. Three liver stiffness values were obtained for each patient from the 3 measurement methods (one free-hand ROI, 3 elliptical ROIs and 9 elliptical ROIs). Inter-method variability was assessed using the intra-class correlation coefficient (ICC) and Bland-Altman analysis.ResultsThe variability between the 3 methods was excellent with ICC > 0.978 (P < 0.0001). The Bland-Altman analysis revealed high agreement between the 3 methods with bias < 0.45 kPa and limits of agreement < ±1.13 kPa. The variability was lower when comparing a large free-hand ROI and the 3-elliptical ROIs, than when comparing the 9-elliptical ROIs to one of the other methods.ConclusionOur results show that the variability between the 3 methods of ROI drawing and placement is very low.     

Hcy与IMA在AMI诊断中的应用价值

目的探讨血清同型半胱氨酸(Hcy)、缺血修饰清蛋白(IMA)联合检测在急性心肌梗死(AMI)诊断中的意义。方法对80例AMI患者、60例不定型心绞痛患者和40例健康体检者(对照组)的血清Hcy、IMA进行检测,并对结果进行统计分析。结果 AMI患者Hcy、IMA水平显著高于对照组,差异有统计学意义(P0.05);Hcy、IMA联合诊断的灵敏度较单一项目诊断高;Hcy与IMA呈正相关(P0.05)。结论联合检测血清Hcy、IMA水平对AMI早期诊断、监测疗效效果较好,值得推广使用。     

Characterization of odor-active compounds in cooked meat of farmed obscure puffer (Takifugu obscurus) using gas chromatography–mass spectrometry–olfactometry

The volatile and odor-active compounds in cooked meat of farmed obscure puffer (Takifugu obscurus) were analyzed by gas chromatography–mass spectrometry–olfactometry (GC–MS–O). The volatile compounds were extracted by the simultaneous distillation–extraction (SDE) method, then separated and identified by GC–MS. Odor-active compounds in the SDE extract were characterized by GC–MS–O. A total of 68 volatile compounds were found, including 23 aldehydes, 10 alcohols, nine ketones, 17 N- or S-containing compounds and aromatics, three acids, three alkanes, and three esters. Of these, 31 odor-active compounds were detected and identified. Trimethylamine (fishy), octanal (grassy, leafy, green), (E)-2-octenal (roast, fatty), 1-octen-3-ol (fishy, fatty, mushroom, grassy), 2-ethyl-1-hexanethiol (cooked fish), (E,E)-2,4-octadienal (cooked meat, sweet), 2-acetylthiazole (meaty, roast, nutty, sulfur), 2-acetylpyrrole (nutty, walnut, bread) were identified as the key odorants in the cooked meat of farmed obscure puffer based on posterior intensity and time-intensity methods.