Pathway to biomarker discovery in psoriatic arthritis

ABSTRACT

Introduction

Biomarkers may help influence long-term outcomes of psoriatic disease by improving the objective assessment of the presence and severity of psoriatic arthritis (PsA) and by guiding treatment selection. However, there are no validated biomarkers for PsA.     

Prediction of resting cardiovascular functioning in youth with family histories of essential hypertension: A 5-year follow-up

Two hundred forty-six children (96 Whites, of whom 51 were mates; 150 African- Americans, of whom 69 were males) with a familial history of essential hypertension (EH) were re-evaluated 5 years after an initial evaluation. During the initial visit, anthropometric, demographic, and resting cardiovascular (CV) parameters (designated initial baseline levels) were assessed. These CV parameters (systolic and diastolic blood pressure [BP], heart rate, cardiac output index [CI], and total peripheral resistance index [TPRI]) were also measured during postural challenge, a video game challenge, and a cold pressor task. At follow-up, resting CV parameters were again evaluated, and designated as follow-up resting levels. Moderate temporal stability (r range = .43-.56) was observed for all resting CV parameters. Mean stress responses for each CV parameter for all 3 stressors during the initial visit were positively related to the respective CV follow-up resting level. BP stress responses to postural change and video game challenge were found to be significant independent predictors of future resting BP after controlling for standard EH risk factors. Follow-up resting CI was not predicted by any stress responses, whereas follow-up resting TPRI was predicted by TPRI responses to the video game after controlling for standard EH risk Factors. These results contrast with those from an earlier 1-year follow-up. where stress responses for neither CI nor TPRI predicted follow-up resting levels. It appears that, as children get older. TPRI stress responses play a stronger role in vasoconstrictive function. This research was supported by National Institutes of Health Grant HL41781.     

Scaling of smooth anticipatory eye velocity in response to sequences of discrete target movements in humans

We investigated the ability to generate anticipatory smooth pursuit to sequences of constant velocity (ramp) stimuli of increasing complexity. Previously, it was shown that repeated presentation of sequences composed of four ramps with two speeds in two directions, evoked anticipatory smooth pursuit after only one or two presentations. Here, sequences of four or six ramps, each having a choice of four speeds and either one or two directions (uni- or bi-directional) were examined. The components of each sequence were presented as discrete ramps (duration: 400 ms; randomised velocity: 10–40°/s), each starting from the centre with 1,200 ms periods of central fixation between ramps, allowing anticipatory activity to be segregated from prior eye movement. Auditory warning cues occurred 600 ms prior to each target presentation. Anticipatory smooth eye velocity was assessed by calculating eye velocity 50 ms after target onset (V ₅₀), prior to the availability of visual feedback. Despite being required to re-fixate centre during inter-ramp gaps, subjects could still generate anticipatory smooth pursuit with V ₅₀ comparable to single speed control sequences, but with less accuracy. In the steady state V ₅₀ was appropriately scaled in proportion to upcoming target velocity for each ramp component and thus truly predictive. Only one to two repetitions were required to attain a steady-state for unidirectional sequences (four or six ramps), but three or four repeats were required for bi-directional sequences. Results suggest working memory can be used to acquire multiple levels of velocity information for prediction, but its use in rapid prediction is compromised when direction as well as speed must be retained.     

Early life markers of atopy and asthma

Since early intervention could modulate the natural course of atopic disease, the availability of predictive markers is of considerable interest. As long as specific genetic markers are not available, early IgE-responses (hen's egg) together with a positive family history of atopy can be proposed as highly specific and predictive markers, which could define subgroups as potential candidates for secondary prevention.     

基于EEG模糊相似性的癫痫发作预测

本研究提出基于EEG序列模糊相似性指数方法预测癫痫发作.首先,结合复自相关法和Cao法对EEG序列进行了相空间重构;然后,计算相关积分时用Gaussian函数代替Heavyside函数,克服了Heavyside函数的刚性边界问题,使得计算相似性指数更加准确和可靠;最后,分析大鼠癫痫EEG信号,检测癫痫发作前期状态.分析结果表明模糊相似性指数方法能够比动态相似性指数方法获得更长的预测时间和更低的错误预测率.     

中西医结合治疗腰椎管狭窄208例

目的探讨腰椎管狭窄临床治疗的方法。方法230例腰椎管狭窄病人，采用中两医结合治疗，治疗时间10～30天，平均20天，回顾性分析其治疗效果。结果经1～3年随访(平均20个月)，按照中华骨科学会脊柱外科的评定标准优62例(29．8％)，良127例(61％)，差19例(9．2％)，优良率90．8％。结论对于腰椎管狭窄症采用卧床休息，适当运动，合理锻炼，骶管疗法，中药的辨证施治等措施，结果表明，本方法为治疗腰椎管狭窄症的一种好方法。     

Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study

The Scandinavian Simvastatin Survival Study (4S) was a double-blind. randomized placebo-controlled multi-centre clinical trial of long-term Simvastatin therapy in patients with coronary heart disease who had total cholesterol levels between 5.5 and 8.0 mmol/1, comprising 4444 patients, equally distributed to a Simvastatin and a placebo group. Patients achieved a significant 30% relative reduction in overall mortality with Simvastatin therapy through a 42% relative reduction in coronary heart disease mortality. Lp(a) lipoprotein levels in Scandinavian coronary heart disease patients were strikingly higher than in healthy controls. Numbers of deaths in the Simvastatin group differed significantly between quartiles of Lp(a) lipoprotein levels, the reduction in deaths being most pronounced in the second (next to lowest) quartile. Subjects with major coronary events had significantly higher Lp(a) lipoprotein levels than subjects without such events, in all groups. The relationship between Lp(a) lipoprotein level and total mortality as well as between Lp(a) lipoprotein level and major coronary events was significantly different from zero, in logistic regression analyses. The findings show that Lp(a) lipoprotein predicts major coronary events as well as death in secondary prevention with Simvastatin. This prospective study provides independent confirmation that a high Lp(a) lipoprotein level is a significant coronary heart disease risk factor.     

基因功能预测问题中的样本不平衡处理

应用机器学习进行分类是基因功能预测的一种重要手段。但是许多预测集中的阳性样本过少，会降低功能预测的效果。针对此问题，本研究对结合支持向量机（SVM）算法的几种常用非平衡数据分类方法进行实验比较，包括投票整合分类器和移动分类面等。在此基础上提出通过加权修正投票的整合策略，以提高预测效果。实验结果显示，结合多数类样本限数取样及整合思想的投票整合法预测效果优于移动分类面法，而在投票整合法基础上的加权修正整合方法在所有方法中获得更好更稳定的结果。     

Establishment of predictive variables associated with testicular sperm retrieval in men with non-obstructive azoospermia

Although testicular biopsy for sperm extraction is a procedure with a potential for complications, sperm retrieval is successful in 30-70% of patients with non-obstructive azoospermia. In order to predict the probability of retrieving at least one testicular spermatozoon we conducted a prospective study of a set of variables in 40 patients with non-obstructive azoospermia. Using the receiver operating characteristic curves, we determined the probability estimates of testicular volume, plasma follicle stimulating hormone (FSH) concentration, Johnsen score and visualization of testicular spermatids in discriminating between patients with successful and failed testicular sperm extraction. Visualization of testicular spermatids provided the best estimate of success of testicular sperm extraction. Of the factors studied using logistic-regression analysis (age, maternal and paternal age at birth, body mass index, luteinizing hormone, testosterone, FSH, testicular volume, the presence of testicular spermatids and Johnsen score), only the presence of spermatids and Johnsen score were independent variables able to predict the success of testicular sperm extraction. The visualization of the presence of spermatids gave a correct prediction of 77% and Johnsen score of 71%. The diagnostic model derived from these independent predictors when validated in 40 patients using the Jackknife technique gave a correct overall prediction of 87%. The probability of successful testicular sperm extraction in patients with non-obstructive azoospermia could be objectively predicted on the basis of simple histopathological criteria represented by the visualization of testicular spermatids and Johnsen score.     

Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome

Total ovarian volumes were measured before the administrationof HCG in 42 women undergoing treatment for infertility by in-vitrofertilization (IVF) and embryo transfer and considered to havean exaggerated response to stimulation (>20 follicles). Sevenwomen who subsequently developed moderate or severe ovarianhyperstimulation syndrome (OHSS) (n = 7; group 1) were comparedwith 35 matched controls (five matched controls per case; n= 35; group 2) of similar age, number of follicles and durationof infertility who underwent follicular stimulation, oocyterecovery, in-vitro fertilization and embryo transfer duringthe same period but did not develop moderate or severe OHSS.The mean age, duration of infertility and total number of follicleswere similar but the mean total ovarian volume was significantlyhigher in the group of women who developed moderate or severeOHSS compared with controls (271.00 ± 87.00 versus 157.30± 54.20 ml; P < 0.01). We conclude that total ovarianvolume measured before HCG administration is higher in womenwho develop moderate or severe OHSS compared with controls andmay therefore be used as an additional parameter in the preventativestrategy for the ovarian hyperstimulation syndrome.