The incidence of schizophrenia: A systematic review

There has been a debate on whether or not the incidence of schizophrenia varies across time and place. In order to optimise the evidence upon which this debate is based, we have undertaken a systematicsystematic review of the literature. In this paper we provide an overview of the methods of the review and a preliminary analysis of the studies identified to date. Electronic databases (Medline, Psychlnfo, Embase, LILAC) were systematically searched for articles published between January 1965 and December 2001. The search terms were: (schizo* OR psycho*)AND (incidence OR prevalence). References were also identified from review articles, reference list and by writing to authors. To date we have identified 137 papers drawn from 33 nations. 37 papers in language other than English await translation. The currently included papers have generated 1413 different items of rate information data. In order to analyze these data we have undertaken several sequential filters in order to identify (a) non-overlapping data, (b) birth cohort study versus noncohort studies, (c) overall and sex-specific rates, (d) diagnostic criteria, (e) age ranges, (f) epoch of study, and (g) data on migrant or other special interest groups. In addition, we will examine the impact of urbanicity of site, age and/or sex standardization, and quality score on the incidence rates. The various discrete incidence rates will be presented graphically and the impact of various filters on these rates will be inspected using meta-analytic techniques. The use of meta-analysis may help elucidate the epidemiological landscape with respect to the incidence of schizophrenia and aid in the generation of new hypothesis. Acknowledgements: The Stanley Medical Research Institute supported project

The preparation and readiness for voluntary movement: a high-field event-related fMRI study of the Bereitschafts-BOLD response

Activity within motor areas of the cortex begins to increase 1 to 2 s prior to voluntary self-initiated movement (termed the Bereitschaftspotential or readiness potential). There has been much speculation and debate over the precise source of this early premovement activity as it is important for understanding the roles of higher order motor areas in the preparation and readiness for voluntary movement. In this study, we use high-field (3-T) event-related fMRI with high temporal sampling (partial brain volumes every 250 ms) to specifically examine hemodynamic response time courses during the preparation, readiness, and execution of purely self-initiated voluntary movement. Five right-handed healthy volunteers performed a rapid sequential finger-to-thumb movement performed at self-determined times (12-15 trials). Functional images for each trial were temporally aligned and the averaged time series for each subject was iteratively correlated with a canonical hemodynamic response function progressively shifted in time. This analysis method identified areas of activation without constraining hemodynamic response timing. All subjects showed activation within frontal mesial areas, including supplementary motor area (SMA) and cingulate motor areas, as well as activation in left primary sensorimotor areas. The time courses of hemodynamic responses showed a great deal of variability in shape and timing between subjects; however, four subjects clearly showed earlier relative hemodynamic responses within SMA/cingulate motor areas compared with left primary motor areas. These results provide further evidence that the SMA and cingulate motor areas are major contributors to early stage premovement activity and play an important role in the preparation and readiness for voluntary movement. (C) 2003 Elsevier Inc. All rights reserved.

Brazilian Adaptation of the Woodcock-Johnson III Cognitive Tests

An adaptation of the standard battery of Woodcock-Johnson III Tests of Cognitive Abilities (WJ-III) for Brazilian children and youth was investigated. The sample was composed of 1094 students (54 percent girls), ages 7-17, living in Sao Paulo state (91 percent). Items from Brazilian school books as well as from the WJ-III Spanish version (Bateria-R) were added to comprehension-knowledge tests. Brazilian words were adapted to the auditory tests according to syllabic division and stressed syllables. Items were examined through IRT and age differences through analysis of variance. Results indicated the need to remove items from all WJ-III subtests with the exception of the visual learning test. Analysis of Variance indicated significant age differences (p <= 0.001) for all tests. Thus, the importance of a Brazilian adaptation for the WJ-III was confirmed.

Auction price anomalies: Evidence from wool auctions in Australia

Using detailed Australian wool auction data we test for further evidence of pricing anomalies at sequential auctions. We find that an anomaly frequently exists and order is frequently endogenously determined. Moreover, prices increase through some sales and decrease through others. We examine whether it is possible to explain the variation in the anomaly across sales and conclude that there is no systematic relationship between the direction of the price anomaly and the characteristics of the wool or the auction. We do, however, find evidence that an anomaly, is more likely in longer sales.

Investment prioritization based on broadscale spatial budgeting to meet downstream targets for suspended sediment loads

On the basis of a spatially distributed sediment budget across a large basin, costs of achieving certain sediment reduction targets in rivers were estimated. A range of investment prioritization scenarios were tested to identify the most cost-effective strategy to control suspended sediment loads. The scenarios were based on successively introducing more information from the sediment budget. The relationship between spatial heterogeneity of contributing sediment sources on cost effectiveness of prioritization was investigated. Cost effectiveness was shown to increase with sequential introduction of sediment budget terms. The solution which most decreased cost was achieved by including spatial information linking sediment sources to the downstream target location. This solution produced cost curves similar to those derived using a genetic algorithm formulation. Appropriate investment prioritization can offer large cost savings because the magnitude of the costs can vary by several times depending on what type of erosion source or sediment delivery mechanism is targeted. Target settings which only consider the erosion source rates can potentially result in spending more money than random management intervention for achieving downstream targets. Coherent spatial patterns of contributing sediment emerge from the budget model and its many inputs. The heterogeneity in these patterns can be summarized in a succinct form. This summary was shown to be consistent with the cost difference between local and regional prioritization for three of four test catchments. To explain the effect for the fourth catchment, the detail of the individual sediment sources needed to be taken into account.

Auctions with synergies and asymmetric buyers

In this paper we consider sequential auctions with synergies where one player wants two objects and the remaining players want one object each. We show that expected prices may not necessarily decrease as predicted by Branco [Econ. Lett. 54 (1997) 159]. Indeed we show that expected prices can actually increase. (C) 2004 Elsevier B.V All rights reserved.

Operational regimes for a simplified one-step artificial chaperone refolding method

The artificial chaperone method for protein refolding developed by Rozema et al. (Rozema, D.; Gellman, S. H. J. Am. Chem. Soc. 1995, 117 (8), 2373-2374) involves the sequential dilution of denatured protein into a buffer containing detergent (cetyltrimethylammonium bromide, CTAB) and then into a refolding buffer containing cyclodextrin WD). In this paper a simplified one-step artificial chaperone method is reported, whereby CTAB is added directly to the denatured solution, which is then diluted directly into a refolding buffer containing P-cyclodextrin (P-CD). This new method can be applied at high protein concentrations, resulting in smaller processing volumes and a more concentrated protein solution following refolding. The increase in achievable protein concentration results from the enhanced solubility of CTAB at elevated temperatures in concentrated denaturant. The refolding yields obtained for the new method were significantly higher than for control experiments lacking additives and were comparable to the yields obtained with the classical two-step approach. A study of the effect of beta-CD and CTAB concentrations on refolding yield suggested two operational regimes: slow stripping ( beta-CDXTABsimilar to1), most suited for higher protein concentrations, and fast stripping (beta-CD/CTABsimilar to2.7), best suited for lower protein concentrations. An increased chaotrope concentration resulted in higher refolding yields and an enlarged operational regime.

Acidity and photolability of ruthenium salen nitrosyl and aquo complexes in aqueous solutions

The photochemical behavior of nitrosyl complexes Ru(salen)(NO)(OH(2))(+) and Ru(salen)(NO) Cl (salen = N, N`-ethylenebis-(salicylideneiminato) dianion) in aqueous solution is described. Irradiation with light in the 350-450 nm range resulted in nitric oxide (NO) release from both. For Ru(salen)(NO) Cl secondary photoreactions also resulted in chloride aquation. Thus, in both cases the final photoproduct is the diaquo cation Ru(III) (salen) (OH(2))(2)(+), for which pK(a)`s of 5.9 and 9.1 were determined for the coordinated waters. The pK(a) of the Ru(salen)(NO)(OH(2))+ cation was also determined as 4.5 +/- 0.1, and the relative acidities of these ruthenium aquo units are discussed in the context of the bonding interactions between Ru(III) and NO. (C) 2007 Elsevier B.V. All rights reserved.

The crystal structure of free human hypoxanthineguanine phosphoribosyltransferase reveals extensive conformational plasticity throughout the catalytic cycle

Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the synthesis of the purine nucleoside monophosphates, IMP and GMP, by the addition of a 6-oxopurine base, either hypoxanthine or guanine, to the 1-beta-position of 5-phospho-U-D-ribosyl-1-pyrophosphate (PRib-PP). The mechanism is sequential, with PRib-PP binding to the free enzyme prior to the base. After the covalent reaction, pyrophosphate is released followed by the nucleoside monophosphate. A number of snapshots of the structure of this enzyme along the reaction pathway have been captured. These include the structure in the presence of the inactive purine base analogue, 7-hydroxy [4,3-d] pyrazolo pyrimidine (HPP) and PRib-PP. Mg2+, and in complex with IMP or GMP. The third structure is that of the immucillinHP.Mg2+.PPi complex, a transition-state analogue. Here, the first crystal structure of free human HGPRT is reported to 1.9 angstrom resolution, showing that significant conformational changes have to occur for the substrate(s) to bind and for catalysis to proceed. Included in these changes are relative movement of subunits within the tetramer, rotation and extension of an active-site alpha-helix (D137-D153), reorientation of key active-site residues K68, D137 and K165, and the rearrangement of three active-site loops (100-128, 165-173 and 186-196). Toxoplasina gondii HGXPRT is the only other 6-oxopurine phosphoribosyltransferase structure solved in the absence of ligands. Comparison of this structure with human HGPRT reveals significant differences in the two active sites, including the structure of the flexible loop containing K68 (human) or K79 (T gondii). (c) 2005 Elsevier Ltd. All rights reserved.

Spatial bias and temporal lag in tactile space perception

Constructing a veridical spatial map by touch poses at least two problems for a perceptual system. First, as the hand is moved through space, the locations of features may be displaced if there is an uncorrected lag between the moment the hand encounters a feature and the time that feature is encoded on a spatial map. Second, due to the sequential nature of the process, some form of memory, which itself may be subject to spatial distortions, is required for integration of spatial samples. We investigated these issues using a task involving active haptic exploration with a stylus swept back and forth in the horizontal plane at the wrist. Remembered locations of tactile targets were shifted towards the medial axis of the forearm, suggesting a central tendency in haptic spatial memory, while evidence for a displacement of perceived locations in the direction of sweep motion was consistent with processing delays.

Cognitive deficits, length of illness and symptom severity in schizophrenia

Background Research using neuropsychological testing has demonstrated that patients with schizophrenia show deficits in multiple neurocognitive domains. The aim of this study is to identify cognitive deficits that correlate with length of illness and symptom severity. Method Twenty clinically stable outpatients with chronic schizophrenia (18M : 2F) and 14 healthy controls (13M : 1F), matched on age, gender and parental education, were administered a neuropsychological battery consisting of the Hayling Sentence Completion Test (HSCT), WMS-III Verbal Paired Associates & Letter Number Sequencing, Modified Card Sort Test (MCST), Pyramids & Palm Trees Test, National Adult Reading Test (NART), Controlled Oral Word Association Test (COWAT), and WAIS-III. Severity of symptoms was rated with the Structured Clinical Interview – Positive and Negative Syndromes Scale (SCI-PANSS). Results In comparison to controls, patients showed significant deficits on all of the neuropsychological tasks except for the COWAT. MCST total categories, NART, Verbal IQ and arithmetic, similarities & digit symbol of the WAIS-III had the largest effect size between the groups. The longer the illness duration, the poorer the performance on WAISIII block design and the lower the performance IQ score. The poorer the performance on WMS-III letter number sequencing, the greater the positive symptoms, negative symptoms and general psychopathology. Conclusion Compared to controls, patients showed large effect sizes on measures of executive functioning, intelligence, working memory, verbal comprehension and speed of processing. The findings suggest that impairment in executive functioning and performance IQ is associated with length of illness, while impairment in working memory is associated with heightened symptom severity.

Synchronization of estrus and ovulation and associated endocrine changes in Bos indicus cows

The effects of 4 estrus synchronization treatments on intervals to and synchrony of estrus and ovulation, on timing of the preovulatory LH surge and associated changes in plasma progesterone, LH, FSH, and 17 beta-estradiol (E(2)) were investigated in 48 Bos indicus cows. Treatment 1 consisted of 2 injections of PGF(2 alpha) 14 d apart (n = 12); Treatment 2 of a subcutaneous 3-mg norgestomet implant and an intramuscular injection of 3 mg of norgestomet and 5 mg estradiol valerate, with the implant removed 10 d later (n = 12; norgestomet-estradiol); Treatment 3 of norgestomet-estradiol, with a subcutaneous injection of PMSG given at time of implant removal (Day 10; n = 12); and Treatment 4 of norgestomet implant (as for Treatments 2 and 3) inserted for 10 d, with an intramuscular injection of PGF(2 alpha) given at the time of implant removal (n = 12). The experiment was conducted in 2 replicates (24 cows/replicate, 6 cows/group). Estrus, ovulation and timing of the preovulatory surge of LH varied less in cows treated with norgestomet-estradiol and PMSG than in cows in Treatments 1 and 4 (P < 0.008). Treatment with PMSG;educed variation in ovulation times and timing of the LH surge in cows treated with norgestomet-estradiol (P < 0.02). Concentrations of E(2) were higher in cows in Treatments 2 and 3 on the final day of treatment and at about 6 h post ovulation compared with cows in Treatments 1 and 4 (P < 0.05). Different methods for synchronizing estrus did not alter sequential endocrine and behavioral changes in relation to the timing of the LH peak, and the results were consistent with current recommendations for insemination times in Bos taurus cattle. (C) 1997 by Elsevier Science Inc.

Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial - SELECT TDCS: Design, rationale and objectives

Background: Despite significant advancements in psychopharmacology, treating major depressive disorder (MDD) is still a challenge considering the efficacy, tolerability, safety, and economical costs of most antidepressant drugs. One approach that has been increasingly investigated is modulation of cortical activity with tools of non-invasive brain stimulation - such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS). Due to its profile, tDCS seems to be a safe and affordable approach. Methods and design: The SELECT TDCS trial aims to compare sertraline vs. tDCS in a double-blinded, randomized, factorial trial enrolling 120 participants to be allocated to four groups to receive sertraline + tDCS, sertraline, tDCS or placebo. Eligibility criteria are moderate-to-severe unipolar depression (Hamilton Depression Rating Scale >17) not currently on sertraline treatment. Treatment will last 6 weeks and the primary outcome is depression change in the Montgomery-Asberg Depression Rating Score (MADRS). Potential biological markers that mediate response, such as BDNF serum levels, Val66Met BDNF polymorphism, and heart rate variability will also be examined. A neuropsychological battery with a focus on executive functioning will be administered. Discussion: With this design we will be able to investigate whether tDCS is more effective than placebo in a sample of patients free of antidepressants and in addition, we will be able to secondarily compare the effect sizes of sertraline vs. tDCS and also the comparison between tDCS and combination of tDCS and sertraline. (C) 2010 Elsevier Inc. All rights reserved.

Functional asymmetries in the movement kinematics of patients with Tourette's syndrome

Objectives-This study adopted a concurrent task design and aimed to quantify the efficiency and smoothness of voluntary movement in Tourette's syndrome via the use of a graphics tablet which permits analysis of movement profiles. In particular, the aim was to ascertain whether a concurrent task (digit span) would affect the kinematics of goal directed movements, and whether patients with Tourette's syndrome would exhibit abnormal functional asymmetries compared with their matched controls. Methods-Twelve patients with Tourette's syndrome and their matched controls performed 12 vertical zig zag movements, with both left and right hands (with and without the concurrent task), to large or small targets over long or short extents. Results-With short strokes, controls showed the predicted right hand superiority in movement time more strongly than patients with Tourette's syndrome, who instead showed greater hand symmetry with short strokes. The right hand of controls was less force efficient with long strokes and more force efficient with short strokes, whereas either hand of patients with Tourette's syndrome was equally force efficient, irrespective of stroke length, with an overall performance profile similar to but better than that of the controls' left hand. The concurrent task, however, increased the force efficiency of the right hand in patients with Tourette's syndrome and the left hand in controls. Conclusions-Patients with Tourette's syndrome, compared with controls, were not impaired in the performance of fast, goal directed movements such as aiming at targets; they performed in certain respects better than controls. The findings clearly add to the growing literature on anomalous lateralisation in Tourette's syndrome, which may be explained by the recently reported loss of normal basal ganglia asymmetries in that disorder.

Movement-related potentials in Parkinson's disease - Motor imagery and movement preparation

Movement-related potentials (MRPs) associated with voluntary movements reflect cortical activity associated with processes Of movement preparation and movement execution. Early-stage pre-movement activity is reduced in amplitude in Parkinson's disease. However it is unclear whether this neurophysiological deficit relates to preparatory or execution-related activity, since previous studies have not been able to separate different functional components of MRPs. Motor imagery is thought to involve mainly processes of movement preparation, with reduced involvement of end-stage movement execution-related processes. Therefore, MRP components relating to movement preparation and execution may be examined separately by comparing MRPs associated with imagined and actual movements. In this study, MRPs were recorded from 14 subjects with Parkinson's disease and 10 age-matched control subjects while they performed a sequential button-pressing task, and while they imagined performance of the same task. Early-stage pre-movement activity was present in both Parkinson's disease patients and control subjects when they imagined movement, but was reduced in amplitude compared with that for actual movement. Movement execution-related components, arising predominantly from the primary motor cortex, were relatively unaffected in Parkinson's disease subjects. However motor preparatory processes, probably involving the supplementary motor area, were reduced in amplitude overall and abnormally prolonged, Indicating impaired termination following the motor response. Further this impaired termination of preparatory-phase activity was observed only in patients with more severe parkinsonian symptoms, and not in early-stage Parkinson's disease.