fMRI activation maps based on the NN-ARx model

The most significant progresses in the understanding of human brain functions have been possible due to the use of functional magnetic resonance imaging (fMRI), which when used in combination with other standard neuroimaging techniques (i.e., EEG) provides researchers with a potential tool to elucidate many biophysical principles, established previously by animal comparative studies. However, to date, most of the methods proposed in the literature seeking fMRI signs have been limited to the use of a top-down data analysis approach, thus ignoring a pool of physiological facts. In spite of the important contributions achieved by applying these methods to actual data, there is a disproportionate gap between theoretical models and data-analysis strategies while trying to focus on several new prospects, like for example fMRI/EEG data fusion, causality/connectivity patterns, and nonlinear BOLD signal dynamics. In this paper, we propose a new approach which will allow many of the abovementioned hot topics to be addressed in the near future with an underlying interpretability based on bottom-up modeling. In particular, the theta-MAP presented in the paper to test brain activation corresponds very well with the standardized t test of the SPM99 toolbox. Additionally, a new Impulse Response Function (IRF) has been formulated, directly related to the well-established concept of the hemodynamics response function (HRF). The model uses not only the information contained in the signal but also that in the structure of the background noise to simultaneously estimate the IRF and the autocorrelation function (ACF) by using an autoregressive (AR) model with a filtered Poisson process driving the dynamics. The short-range contributions of voxels within the near-neighborhood are also included, and the potential drift was characterized by a polynomial series. Since our model originated from an immediate extension of the hemodynamics approach [Friston, K.J., Mechelli, A., Turner, R., Price C.J. (2000a). Nonlinear responses in fMRI: the balloon model, volterra kernels, and other hemodynamics. NeuroImage 12, 466-477.], a natural interpretability of the results is feasible.     

应用行为分析法治疗儿童孤独症

目的:观察应用行为分析法对孤独症患儿的干预效果。方法:选择2003-01/2005-12在天津市孤独症康复训练中心进行应用行为分析疗法训练的孤独症患儿85例,年龄2岁2个月～6岁1个月,患儿监护人均知情同意。运用应用行为分析疗法进行训练,设计个体化的治疗方案,内容包括:语言、模仿、自理能力、社交技能、大运动、精细动作和认知能力7个方面。每周训练30～40h,3个月为1个疗程,患儿训练3～12个月不等。分别于训练前、后应用Gesell发育量表(包括5个能区,计算每个能区的发育商及平均发育商,发育正常儿童的平均发育商≥85)、孤独症行为评定量表(分5大因素57条项目,按其在量表中的负荷大小分别记4,3,2,1分,相加计算总分,分数的高低表明孤独症行为严重程度的高低)、孤独症评定量表(共设14项行为表现,每项根据表现的程度及频率记0,1,2分,相加计算总分,分数的高低表明疾病程度的高低)对患儿进行评估。于治疗后3个月对完成训练后能联络到的患儿进行随访观察。结果:85例孤独症患儿全部进入结果分析,无脱落。①孤独症患儿训练后Gesell发育检查各能区发育商及平均发育商均高于训练前(P<0.01);训练后孤独症行为评定量表各因子分及总分均低于训练前(P<0.01);训练后孤独症评定量表评分低于训练前(13.96±3.81,20.96±3.48,t=-11.18,P<0.01)。②训练完成后3个月对能联系到的48例当地患儿进行随访发现,有43例仍继续进步,其中29例入正常幼儿园或小学。结论:应用行为分析疗法是治疗儿童孤独症的一种非常有效的方法。     

Acute oral, pulmonary and intravenous toxicity/pathogenicity testing of a new formulation of Bacillus thuringiensis var israelensis SH-14 in rats

During the last decades, efforts are being made to develop microbial insecticides as biological control agents. Bacillus thuringiensis has been one of the most consistent and significant biopesticides for using on crops as an insecticidal spray. The aim of this study was to assess and to compare the pathogenicity of a new formulation of B.thuringiensis var israelensis SH-14 in rats through oral, intranasal and intravenous single dosing. Through 21 days after administration, clinical examinations were performed daily, and body weight gain was evaluated. Clearance was estimated by means of collection of feces or examination of lungs and blood, and infectivity was evaluated enumerating microorganisms from organs of Bti SH-14 treated animals sacrificed at intervals. Gross necropsy of animals was performed at interim or final sacrifice. There were no treatment-related mortalities, and no evidence of pathogenicity or treatment related toxicity, although in the intravenous study, the microorganism was capable of achieving persistence in organs after administration, and the Bti SH-14 treated animals developed skin ulcerations and hemorrhages at the injection site. It could be concluded that the tested microorganism was not toxic or pathogenic to rats via oral or intranasal route, although it was capable of achieving persistence in organs after intravenous administration, eliciting local effects at the injection site.     

Combination of antidepressants in the treatment of major depressive disorder: a systematic review and meta-analysis

The objective was to perform a systematic review and meta-analysis of studies that assessed the effect of the combination of antidepressants from the beginning of the treatment of major depressive disorder. Studies were retrieved from PubMed (1966 to August 2010), Cochrane Library (August 2010), Embase (1980 to August 2010), PsycINFO (1980 to August 2010), Lilacs (1982 to August 2010), clinical trials registry, thesis database (www.capes.gov.br), and secondary references. All randomized controlled trials that compared a combination of antidepressants with a single antidepressant from the beginning of the treatment of major depressive disorder in adults were included. Data analysis was performed using the Review Manager 5.0. Of 3492 studies retrieved, five satisfied the inclusion criteria. In one study, only data about dropouts were included. Antidepressant combination was shown to be better than a single antidepressant considering remission (relative risk [RR], 2.71; 95% confidence interval [CI], 1.69-4.35) and response (RR, 1.55; 95% CI, 1.21-1.97). Mirtazapine plus selective serotonin reuptake inhibitor (SSRI) was superior to an isolated SSRI for remission (RR, 1.88; 95% CI, 1.06-3.33). Tricyclic antidepressant plus SSRI was superior to SSRI for remission and response (RR, 8.58; 95% CI, 1.70-43.32 and RR, 1.78; 95% CI, 1.07-2.93, respectively). There was no difference between combined and monotherapy groups in dropouts owing to adverse effects. The results suggest that antidepressant combination is more efficient than a single antidepressant without a significant decrease in tolerability. However, the small number of clinical trials and methodological problems precludes definitive conclusions.     

The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals

Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p < 0.05), with a predominant impact on polymorphonuclear over mononuclear cells, especially after 12 hours of the medication. The montelukast/indometacine combination showed an additive effect. Our data show that montelukast has an anti-inflammatory effect in the model of gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.     

Wide dispersion of ST175 clone despite high genetic diversity of carbapenem-nonsusceptible Pseudomonas aeruginosa clinical strains in 16 Spanish hospitals

During the COMParative Activity of Carbapenems Testing (COMPACT) surveillance study, 448 Pseudomonas aeruginosa clinical isolates were obtained from 16 Spanish hospitals. Nonsusceptibility (EUCAST breakpoints) to imipenem (35%), meropenem (33%), and/or doripenem (33%) was observed with 175 isolates (39%). Simultaneous resistance to these three drugs was observed with 126 of the 175 isolates (72%). Except for colistin, high resistance rates were observed among noncarbapenem antibiotics. Clonal relatedness was investigated by pulsed-field gel electrophoresis (PFGE) with SpeI, discriminating 68 patterns. Multilocus sequence typing (MLST) was performed on 84 isolates representing different PFGE types and all participating hospitals. Thirty-nine sequence types (STs) could be distinguished, and of these, ST175 (48 isolates, 10 hospitals), ST646 (16 isolates, 4 hospitals), ST532 (13 isolates, 3 hospitals), and ST111 (13 isolates, 7 hospitals) were the most frequently encountered. Minimum-spanning tree analysis confirmed a wide dissemination of different clones among participant hospitals, particularly ST175. PFGE pattern comparison within the four most frequent STs revealed that ST175 isolates were relatively uniform, while ST646, ST532, and ST111 isolates were highly diverse, with almost every isolate belonging to a unique pulsotype, even when originating from the same center. The population of carbapenem-nonsusceptible P. aeruginosa isolates from 16 hospitals is highly diverse, with one ST (ST175) representing a highly conserved clone disseminated in 10 of the 16 participant hospitals. This ST175 clone should be added to the list of P. aeruginosa clones at high risk for epidemic spread, such as the Liverpool, Manchester, and Melbourne clones previously found in cystic fibrosis patients and ST235 in the nosocomial setting.     

从美国刑事法律沿革思考我国司法精神病鉴定模式的转变

2008年4月3-6日笔者有幸参加了美国司法精神病学院在旧金山举行的第26届学术论坛.来自司法精神病学、犯罪心理学、法学界等领域的100余名代表参加了会议,32名专家、学者在会上做了丰富多彩的专题演讲.     

A cohort study of guselkumab in the treatment of psoriasis refractory to previous biologic therapies: effectiveness,safety and adherence

International Journal of Clinical Pharmacy - Background Guselkumab is indicated for moderate-to-severe plaque psoriasis. Data from real-life clinical practice regarding its use are scarce,...