bluuebunny/crossref_metadata_2025 huggingface dataset:
The moral content of psychiatric treatment
Authors: Pearce Steve , Pickard Hanna
Published: September 2009

Psychiatric treatment can enhance human morality. It can promote the emergence of moral motives and intentions, aid in the acquisition of skills essential to moral action, and help to develop the ability to apply moral understanding and skills in particular circumstances. Good psychiatric practice demands an honest appraisal of its moral dimension.
Pharmacogenomic perspectives on the management of mood disorders
Authors: Alarcón Renato D.
Published: September 2009

Psychiatric pharmacogenomics is a relatively young field of clinical practice, focused on the identification of genetic profiles determining varieties of metabolic patterns that, in turn, assist in the choice of appropriate medications and their corresponding doses. In psychiatry, the mood disorders area has been the most active in trying to advance knowledge and expertise in pharmacogenomics. the cytochrome P450 system (particularly 2D6 and 2C19 enzymes and their respective codifying genes) and, more recently, serotonin transporter and receptor gene tests are among the most utilised and promising. In spite of encouraging findings, however, there are still many questions related to preciseness, scope, ethnic variations, diagnostic implications, ‘non-biological’ factors, and ethic considerations. the need of algorithms, follow-up studies, and assessment of financial impact, all listed here, require continuous and systematic research. It will not only add to the excitement of pharmacogenomics, but also to the creation of cogent evidence of its benefits.
Characteristics of patients seen by a community perinatal mental health service
Authors: Durrani Amanullah , Cantwell Roch
Published: September 2009

Aims and Method

Recent guidelines on perinatal mental health highlight the need to predict, detect and prevent mental illness in childbearing women, but there are a limited number of studies in this field. This study describes the characteristics of 277 service users newly referred to a specialist community perinatal mental health service over 1 year, and discusses the implications for effective management of mental illness related to childbearing.

Results

The most common diagnosis was affective disorder (51%), of which 8% had bipolar affective disorder. Almost three in five women had previous non-pregnancy-related psychiatric contact and a fourth had previous ante/postnatal psychiatric contact. More than half were on medication at conception, most commonly antidepressants (43%).

Clinical Implications

This study highlights the opportunities for identifying women at high risk of postnatal mental illness and the need for adequate pregnancy planning advice for women taking psychotropic medication.
Junior doctors' knowledge and practice of electrocardiographic monitoring for high-risk patients receiving antipsychotic medications
Authors: Darwiche Fai-Žaza , Ugradar Shoaib Tyi , Turner Trevor
Published: September 2009

Aims and Method

The risk of developing fatal tachyarrhythmias can increase in patients receiving antipsychotic medication. Two surveys were conducted, one to evaluate junior doctors' knowledge of the QTc interval and the second to investigate the experience of electrocardiographic (ECG) monitoring among patients on four acute psychiatric wards.

Results

The first survey revealed that junior doctors were lacking in knowledge regarding the QTc interval. the second revealed that ECG monitoring of high-risk patients was inadequate. Half of the high-risk patients who required an ECG were not given one, whereas 6% who did not require one still received this investigation.

Clinical Implications

There is a need to increase knowledge about the cardiac risk of antipsychotic medication on psychiatric wards. Following simple recommendations could improve clinical practice.
A Novel Loss-of-Function Mutation, Gln459Arg, of the Calcium-Sensing Receptor Gene Associated with Apparent Autosomal Recessive Inheritance of Familial Hypocalciuric Hypercalcemia
Authors: Lietman Steven A. , Tenenbaum-Rakover Yardena , Jap Tjin Shing , Yi-Chi Wu , De-Ming Yang , Ding Changlin , Kussiny Najat , Levine Michael A.
Published: September 2009

Context: Mutations that inactivate one allele of the gene encoding the calcium sensing receptor (CaSR) cause autosomal dominant familial hypocalciuric hypercalcemia (FHH), whereas homozygous mutations cause neonatal severe hyperparathyroidism.

Objective: We describe the identification and biochemical characterization of a novel CASR gene mutation that caused apparent autosomal recessive FHH in an extended consanguineous kindred.

Design: The study design involved direct sequence analysis of the CaSR gene, clinical and biochemical analyses of patients, and in vitro immunobiochemical studies of the mutant CaSR.

Results: A novel inactivating mutation (Q459R) was identified in exon 4 of both alleles of the CASR in the proband, who presented with asymptomatic hypercalcemia and hypocalciuria at age 2 yr. The proband’s parents were heterozygous for the Q459R mutation consistent with autosomal recessive inheritance of FHH. Among 13 family members that were studied, eight subjects were heterozygous for the Q459R mutation and five had normal genotypes. All heterozygous subjects were asymptomatic and normocalcemic apart from one subject who was mildly hypercalcemic. The Q459R mutant CaSR was normally expressed at the cell membrane but retained only 30–50% of the calcium-dependent activity of the wild-type CaSR.

Conclusion: We identified a novel loss-of-function Q459R mutation in the CASR gene that exhibits mildly reduced sensitivity to calcium and that is associated with apparent autosomal recessive transmission of FHH. This study demonstrates the importance of genetic testing in FHH to distinguish between de novo and inherited mutations of the CASR gene and assist in management decisions.

An extended kindred with familial hypocalciuric hypercalcemia possessed a novel inactivating mutation of the CaSR with highly variable biochemical phenotypes and apparent autosomal recessive inheritance.
Persistence and the First-Person Perspective
Authors: Ninan Dilip
Published: September 2009

When one considers one's own persistence over time from the first-person perspective, it seems as if facts about one's persistence are “further facts,” over and above facts about physical and psychological continuity. But the idea that facts about one's persistence are further facts is objectionable on independent theoretical grounds: it conflicts with physicalism and requires us to posit hidden facts about our persistence. This essay shows how to resolve this conflict using the idea that imagining from the first-person point of view is a guide to centered possibility, a type of possibility analyzed in terms of centered worlds.
Noumenal Affection
Authors: Hogan Desmond
Published: September 2009

A central doctrine of Kant's Critique of Pure Reason holds that the content of human experience is rooted in an affection of sensibility by unknowable things in themselves. This famous and puzzling affection doctrine raises two seemingly intractable old problems, which can be termed the Indispensability and the Consistency Problems. By what right does Kant present affection by supersensible entities as an indispensable requirement of experience? And how could any argument for such indispensability avoid violating the Critique's doctrine of noumenal ignorance? This essay develops a new solution to both problems, setting out from the continuity between Kant's early and mature views on sensibility and mind-world relations. Kant's early writings subscribe to an interactionist cosmology opposed to both Leibniz's preestablished harmony and Malebranche's occasionalism. The modern debate on mind-world relations shaping Kant's early cosmology points us to a widely recognized motivation for interactionism, turning on a constraint on agency within certain noninteractionist cosmologies. In particular, Kant's early conversion to a libertarian theory of freedom, together with his rejection of occasionalism, provides the basis for a compelling argument for the indispensability of world-mind affection relations. Extended to the transcendental idealist framework, the same argument reveals noumenal affection as an indispensable presupposition of some knowledge claims consistently upheld by Kant. This leads in turn to a satisfying solution to the Consistency Problem, showing that the doctrine of noumenal affection is not merely consistent with, but is partly motivated by, Kant's commitment to noumenal ignorance.
Finite Element Analysis to Determine Stress Concentration Factors of Dragline Tubular Joints
Authors: Pang N.L. , Zhao X.L.
Published: September 2009

This paper presents a finite element analysis (FEA), by using ANSYS 10.0 (SAS IP Inc 2005), to determine the stress concentration factor (SCF) of the dragline tubular joints. Different load cases, element types, weld sizes and shapes are considered in the analysis. The predicted SCF are compared with the experimental values based on full-size laboratory testing. Finite element (FE) model for the dragline tubular joint consists of the main chord and bracing members with all the attachments like, end plates, load cells, nuts and rods, with concave weld shape and equal weld leg length has been selected to determine SCF. Two layers of 10-node tetrahedral element (SOLID187) and 2 layers of 20-node hexahedral element (SOLID186) have been used in the FE model. The FEA results for all the laboratory test specimens are particularly good when loaded under load case 1 (LC1) and reasonable when loaded under load case 2 (LC2).
Experimental Research on Biaxial Compressive Strength of Grouted Concrete Block Masonry
Authors: Liu Lipeng , Wang Zonglin , Zhai Changhai , Zhai Ximei
Published: September 2009

Grouted concrete block masonry (GCBM) exhibits distinct directional properties. In total, 66 tests on 5 kinds of macro-elements were conducted for different principal stress ratios under biaxial compression. The surface of peak strength has been obtained in terms of heterogeneity index and stress ratio. The surface can express the anisotropic nature of GCMB. Comparisons of 5 kinds of macro-element failure curves were made and it has been found that the biaxial compressive strength when the applied stress direction and the material axis coincide is much greater than that of applied stress inclined to material axis. On term of heterogeneity index and stress ratio, the law of strength varying with orientation has been obtained. It shows that the degree of anisotropy is affected by the stress state. Strong behaviour occurs only when one principal stress predominates, that is, the stress ratio value is low, and gradually becomes weaken as the difference between the two principal compression stresses decreases, namely the stress ratio is increasing. Under equal biaxial compression, the different macro-element strengths are nearly equivalent and the masonry seems to be isotropic. The work conducted in this paper provides a basis for further theoretical study on the behaviour of GCBM under biaxial compressive stress.
A systematic characterization of Cwc21, the yeast ortholog of the human spliceosomal protein SRm300
Authors: Khanna May , Van Bakel Harm , Tang Xinyi , Calarco John A. , Babak Tomas , Guo Grace , Emili Andrew , Greenblatt Jack F. , Hughes Timothy R. , Krogan Nevan J. , Blencowe Benjamin J.
Published: September 2009

Cwc21 (complexed with Cef1 protein 21) is a 135 amino acid yeast protein that shares homology with the N-terminal domain of human SRm300/SRRM2, a large serine/arginine-repeat protein shown previously to associate with the splicing coactivator and 3′-end processing stimulatory factor, SRm160. Proteomic analysis of spliceosomal complexes has suggested a role for Cwc21 and SRm300 at the core of the spliceosome. However, specific functions for these proteins have remained elusive. In this report, we employ quantitative genetic interaction mapping, mass spectrometry of tandem affinity-purified complexes, and microarray profiling to investigate genetic, physical, and functional interactions involving Cwc21. Combined data from these assays support multiple roles for Cwc21 in the formation and function of splicing complexes. Consistent with a role for Cwc21 at the core of the spliceosome, we observe strong genetic, physical, and functional interactions with Isy1, a protein previously implicated in the first catalytic step of splicing and splicing fidelity. Together, the results suggest multiple functions for Cwc21/SRm300 in the splicing process, including an important role in the activation of splicing in association with Isy1.
The early results of joint-sparing proximal tibial replacement for primary bone tumours, using extracortical plate fixation
Authors: Spiegelberg B. G. I. , Sewell M. D. , Aston W. J. S. , Blunn G. W. , Pollock R. , Cannon S. R. , Briggs T. W. R.
Published: September 2009

This paper describes the preliminary results of a proximal tibial endoprosthesis which spares the knee joint and enables retention of the natural articulation by replacing part of the tibial metaphysis and diaphysis. In eight patients who had a primary malignant bone tumour of the proximal tibia, the distal stem, which had a hydroxyapatite-coated collar to improve fixation, was cemented into the medullary canal. The proximal end had hydroxyapatite-coated extracortical plates which were secured to the remaining proximal tibial metaphysis using cortical screws. The mean age of the patients at operation was 28.9 years (8 to 43) and the mean follow-up was for 35 months (4 to 48). The mean Musculoskeletal Tumour Society score was 79% (57% to 90%), the mean Oxford Knee score was 40 points of 48 (36 to 46) and the mean knee flexion was 112° (100° to 120°). In one patient, revision to a below-knee amputation through the prosthesis was required because of recurrence of the tumour. Another patient sustained a periprosthetic fracture which healed with a painful malunion. This was revised to a further endoprosthesis which replaced the knee.

In the remaining six patients the prosthesis allowed preservation of the knee joint with good function and no early evidence of loosening. Further follow-up is required to assess the longevity of these prostheses.
Non-invasive extendible endoprostheses for limb reconstruction in skeletally-mature patients
Authors: Sewell M. D. , Spiegelberg B. G. I. , Hanna S. A. , Aston W. J. S. , Meswania J. M. , Blunn G. W. , Henry C. , Cannon S. R. , Briggs T. W. R.
Published: September 2009

We describe the application of a non-invasive extendible endoprosthetic replacement in skeletally-mature patients undergoing revision for failed joint replacement with resultant limb-length inequality after malignant or non-malignant disease. This prosthesis was developed for tumour surgery in skeletally-immature patients but has now been adapted for use in revision procedures to reconstruct the joint or facilitate an arthrodesis, replace bony defects and allow limb length to be restored gradually in the post-operative period.

We record the short-term results in nine patients who have had this procedure after multiple previous reconstructive operations. In six, the initial reconstruction had been performed with either allograft or endoprosthetic replacement for neoplastic disease and in three for non-neoplastic disease. The essential components of the prosthesis are a magnetic disc, a gearbox and a drive screw which allows painless lengthening of the prosthesis using the principle of electromagnetic induction. The mean age of the patients was 37 years (18 to 68) with a mean follow-up of 34 months (12 to 62). They had previously undergone a mean of six (2 to 14) open procedures on the affected limb before revision with the non-invasive extendible endoprosthesis.

The mean length gained was 56 mm (19 to 107) requiring a mean of nine (3 to 20) lengthening episodes performed in the outpatient department. There was one case of recurrent infection after revision of a previously infected implant and one fracture of the prosthesis after a fall. No amputations were performed. Planned exchange of the prosthesis was required in three patients after attainment of the maximum lengthening capacity of the implant. There was no failure of the lengthening mechanism. The Mean Musculoskeletal Tumour Society rating score was 22 of 30 available points (18 to 28).

The use of a non-invasive extendible endoprosthesis in this manner provided patients with good functional results and restoration of leg-length equality, without the need for multiple open lengthening procedures.
The management of Charcot joint disease affecting the ankle and foot by arthrodesis controlled by an Ilizarov frame
Authors: El-Gafary K. A. M. , Mostafa K. M. , Al-adly W. Y.
Published: September 2009

Charcot osteoarthropathy of the foot is a chronic and progressive disease of bone and joint associated with a risk of amputation. The main problems encountered in this process are osteopenia, fragmentation of the bones of the foot and ankle, joint subluxation or even dislocation, ulceration of the skin and the development of deep sepsis. We report our experience of a series of 20 patients with Charcot osteoarthropathy of the foot and ankle treated with an Ilizarov external fixator. The mean age of the group was 30 years (21 to 50). Diabetes mellitus was the underlying cause in 18 patients. Five had chronic ulcers involving the foot and ankle. Each patient had an open lengthening of the tendo Achillis with excision of all necrotic and loose bone from the ankle, subtalar and midtarsal joints when needed. The resulting defect was packed with corticocancellous bone graft harvested from the iliac crest and an Ilizarov external fixator was applied. Arthrodesis was achieved after a mean of 18 weeks (15 to 20), with healing of the skin ulcers. Pin track infection was not uncommon, but no frame had to be removed before the arthrodesis was sound.

Every patient was able to resume wearing regular shoes after a mean of 26.5 weeks (20 to 45).
The effect of obesity on the mid-term survival and clinical outcome of cementless total hip replacement
Authors: Jackson M. P. , Sexton S. A. , Yeung E. , Walter W. L. , Walter W. K. , Zicat B. A.
Published: September 2009

The outcome of total hip replacement (THR) is potentially affected by the body mass index (BMI) of the patient. We studied the outcome of 2026 consecutive primary cementless THRs performed for osteoarthritis. The mean follow-up was 6.3 years (0 to 11.71) and no patient was lost to follow-up for survival analysis. The patients were divided into two groups according to their BMI as follows: non-obese (BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2).

The obese patient undergoing surgery was found to be significantly younger (p < 0.001). The log-rank test for equality of survival showed no difference in the mid-term survival (p = 0.552) with an estimated survival at 11 years of 95.2% (95% CI 92.5 to 98.0) in the non-obese and 96.7% (95% CI 94.9 to 98.5) in the obese groups. The clinical and radiological outcome was determined in a case-matched study performed on 134 obese individuals closely matched with 134 non-obese controls. The non-obese group was found to have a significantly higher post-operative Harris hip score (p < 0.001) and an increased range of movement, but overall satisfaction with surgery was comparable with that of the obese patients. Radiological analysis of the acetabular and femoral components showed no significant differences with regard to radiolucent lines, osteolysis, ingrowth of the femoral component, the acetabular inclination angle or alignment of the femoral component. Our results suggest that the survival of cementless THR is not adversely affected by obesity. Obese patients can therefore be counselled that despite a lower clinical score, they should expect to be satisfied with the result of their THR with a mid-term survival rate equivalent to that of non-obese patients.
Wrong-site surgery in orthopaedics
Authors: Robinson P. M. , Muir L. T.
Published: September 2009

Procedures performed at the incorrect anatomical site are commonly perceived as being relatively rare. However, they can be a devastating event for patients and doctors. Evidence from the United Kingdom and North America suggests that wrong-site, wrong-procedure and wrong-patient events occur more commonly than we think. Furthermore, their incidence may be increasing as NHS Trusts increase the volume and complexity of procedures undertaken in order to cope with increasing demands on the system. In previous studies from North America orthopaedic surgery has been found to be the worst-offending specialty.

In this paper we review the existing literature on wrong-site surgery and analyse data from the National Patient Safety Agency and NHS Litigation Authority on 292 cases of wrong-site surgery in England and Wales. Orthopaedic surgery accounted for 87 (29.8%) of these cases. In the year 2006 to 2007, the rate of wrong-site surgery in England and Wales was highest in orthopaedic surgery, in which the estimated rate was 1:105 712 cases.
Two simple approximations to the distributions of quadratic forms
Authors: Yuan Ke‐Hai , Bentler Peter M.
Published: September 2009

Many test statistics are asymptotically equivalent to quadratic forms of normal variables, which are further equivalent to with zi being independent and following N(0,1). Two approximations to the distribution of T have been implemented in popular software and are widely used in evaluating various models. It is important to know how accurate these approximations are when compared to each other and to the exact distribution of T. The paper systematically studies the quality of the two approximations and examines the effect of the λi and the degrees of freedom d by analysis and Monte Carlo. The results imply that the adjusted distribution for T can be as good as knowing its exact distribution. When the coefficient of variation of the λi is small, the rescaled statistic is also adequate for practical model inference. But comparing TR against will inflate type I errors when substantial differences exist among the λi, especially, when d is also large.
‘You didn't take Lucy's skirt off’: The effect of misleading information on omissions and commissions in children's memory reports
Authors: Otgaar Henry , Candel Ingrid , Smeets Tom , Merckelbach Harald
Published: September 2009

Purpose. The current study explored how misleading information affects children's omissions and commissions over time.

Method. Fifty‐nine younger (Mage = 4.16) and fifty‐nine older (Mage = 9.44) children were instructed to remove three pieces of clothing from a puppet. Half of them were provided with false evidence that they had removed only two items, while the other half were provided with false evidence that they had removed a fourth piece of clothing. In three neutral interviews separated by 1‐week intervals, children had to report which pieces of clothing they had removed.

Results. Overall, omission and commission errors significantly decreased over time, although this pattern was more pronounced for omission errors. Younger and older children were equally likely to make omission errors, whereas commission errors were more typical for younger than for older children. Also, we found that commission errors more readily occur than omission errors.

Conclusion. Even when children's memory reports pertain to an event in which they actively participated, misleading information may elicit omission and commission errors, with especially the latter category being very persistent over time.
Assessing trait memory distrust: Psychometric properties of the Squire Subjective Memory Questionnaire
Authors: van Bergen Saskia , Brands Ineke , Jelicic Marko , Merckelbach Harald
Published: September 2009

Purpose. When people suffer from memory distrust, they evaluate their memory in negative terms. Memory distrust plays an important role in police interrogations because it may underlie false confessions. The Squire Subjective Memory Questionnaire (SSMQ) intends to be a simple measure of trait memory distrust. To our knowledge, no data have been published about the psychometric properties of the SSMQ.

Methods. Relying on five samples (Ns = 70–819) of healthy individuals and patients, we studied the psychometric characteristics of the SSMQ. Participants were recruited at the university, a neuropsychological unit or through advertisements in newspapers. They were asked to complete the SSMQ and several other tests. In this way, reliability and validity parameters could be assessed.

Results. Principle component analysis showed that the SSMQ has a one‐dimensional structure referring to subjective memory evaluation. The SSMQ was found to have adequate reliability and good construct validity. Furthermore, it appears to correlate in a theoretically meaningful way with age and cognitive failures.

Conclusions. All together, the SSMQ is a psychometrically sound screening tool that can be helpful in assessing subjective memory evaluations in the legal domain. In this way, vulnerable suspects can be identified in an early stage.
Examination of the stability and consistency of investigative interviewer performance across similar mock interview contexts
Authors: Powell Martine B. , Hughes‐Scholes Carolyn H. , Cavezza Cristina , Stoové Mark A.
Published: September 2009

Purpose. Three studies examined the degree to which investigative interviewers' adherence to best‐practice guidelines is consistent across similar mock interviews.

Method. In each study, two interviews were administered within a period of several hours. Further, group and individual stability of interviewer performance was analysed, and performance was measured by calculating the proportion of open‐ended and leading questions as well as the presence of predetermined problem behaviours. The studies varied depending on the type of interview paradigm employed. Interviewer performance in Study 1was measured in a group context where participants rotated between the role of interviewer, child respondent, and observer. In Study 2, an adult played the role of a child recalling abuse but this occurred in isolation (participants did not observe others or play the child). Study 3 was similar to Study 2 except that in each interview an unfamiliar child aged 5–7 years recalled an innocuous event.

Results. Interviewer performance was relatively stable across tasks, although the strength of the relationship between measures varied across analyses. Improvement in open‐ended question usage occurred in Study 1 but not Studies 2 and 3. Irrespective of the assessment context, the dichotomous rating scale yielded greater consistency than when questions were tallied. Further, group stability overestimated individual stability. The practical implications of these findings for trainers and researchers are discussed.
Proxy Healthcare Decision-Making for Persons With Intellectual Disability: Perspectives of Residential-Agency Directors
Authors: Fisher Kathleen M. , Orkin Fredrick K. , Green Michael J. , Chinchilli Vernon M. , Bhattacharya Anand
Published: September 2009

Directors of residential agencies for persons with intellectual disability in one U.S. state completed a self-administered, mailed survey to assess relative importance of information sources and decision factors in proxy healthcare decision-making. The most important sources were physician recommendations and input from the person; family input, care staff recommendations, and medical records were less valued. The person's wishes and best interests and recommendations of medical experts were the most important decision factors. Less important were benefits and risks of the intervention, family wishes, and health status; little emphasis was accorded to religious affiliation and extra cost to agency. More research is needed on how best to elicit the wishes and determine what constitutes the “best interests” of these vulnerable individuals.
Limitations in Life Participation and Independence Due to Secondary Conditions
Authors: Koritsas Stella , Iacono Teresa
Published: September 2009

The effects of secondary conditions across adults with autism, Down syndrome, and cerebral palsy were explored in terms of overall limitation in life participation and independence, changes over time, and the degree and nature of limitation in specific secondary conditions. Information was obtained for 35 adults with autism, 49 with Down syndrome, and 29 with cerebral palsy (N  =  113). Caregivers completed a questionnaire exploring secondary conditions on two occasions. Participants with cerebral palsy experienced the greatest overall limitations of the three groups. This finding is due to several secondary conditions. There were no changes in limitation scores over time. Implications related to health care for these groups are discussed.
Pequeño glosario de tiburones
Authors: Haensch Günther
Published: September 2009

Hay varios centenares de especies de tiburones o escualos. A continuación ofrecemos un glosario de los nombres de tiburones que con más frecuencia aparecen en la prensa y en los libros. Se indican también los nombres científicos de las distintas especies. Como éstos varían a veces de un autor a otro, damos los nombres más usuales en la bibliografía reciente.
The Distillation of “VISCI”: Towards a Better Identification of Suicidal Inmates
Authors: Frottier Patrick , Koenig Franz , Seyringer Michaela , Matschnig Teresa , Fruehwald Stefan
Published: September 2009

The “Viennese Instrument for Suicidality in Correctional Institutions” (VISCI) presented here is based on the results of a large case‐control study and on research on literature examining suicide prevention in general and in the prison population in particular. The aim of this study was to validate the properties of the VISCI to differentiate between suicides and nonsuicides. The sensitivity and specificity of the VISCI was tested in the files of 55 correctional suicides, and 110 controls. VISCI differentiated well between suicides and nonsuicides. The routine administration of the VISCI may help to direct the existing professional attention to inmates with the highest need.
Beyond Randomized Controlled Trials in Attempted Suicide Research
Authors: Hatcher Simon , Sharon Cynthia , Coggan Carol
Published: September 2009

There is a lack of evidence about what is the best treatment for people who present to hospital after self harm. Most treatment trials have been small and involved unrepresentative groups of patients which result in inconclusive findings. Here we note some of the characteristics of attempted suicide which make it a difficult subject to study. We describe the problems of doing randomized controlled trials in attempted suicide and outline the advantages and difficulties of randomized controlled trials, Zelen designs, patient preference designs, and cluster randomized trials in attempted suicide intervention trials. Researchers and consumers should consider other research designs when asking what is effective after self harm.
Evaluation of the Heterogeneous Reactivity of the Syntaxin Molecules on the Inner Leaflet of the Plasma Membrane
Authors: Bar-On Dana , Gutman Menachem , Mezer Aviv , Ashery Uri , Lang Thorsten , Nachliel Esther
Published: September 2009

The solubleN-ethylmaleimide-sensitive fusion (NSF) attachment protein (SNAP) receptor (SNARE) protein syntaxin 1A forms nano-sized clusters (membrane rafts) on the plasma membrane (PM) that are in equilibrium with freely diffusing syntaxin molecules. SNARE-complex formation between syntaxin 1A and SNAP-25 (synaptosome-associated protein of 25 kDa) on the PM and synaptobrevin 2 on the vesicles (trans-SNAREs) is crucial for vesicle priming and fusion. This process might be impeded by the spontaneous accumulation of non-fusogeniccis-SNARE complexes formed when all three SNARE proteins reside on the PM. We investigated the kinetics ofcis-SNARE complex assembly and disassembly and both exhibited biphasic behavior. The experimental measurements were analyzed through integration of differential rate equations pertinent to the reaction mechanism and through the application of a heuristic search for time constants and concentrations using a genetic algorithm. Reconstruction of the measurements necessitated the partitioning of syntaxin into two phases that might represent the syntaxin clusters and free syntaxin outside the clusters. The analysis suggests that most of the syntaxin in the clusters is concentrated in a nonreactive form. Consequently,cis-SNARE complex assembly in the clusters is substantially slower than outside the rafts. Interestingly, the clusters also mediate efficient disassembly ofcis-SNARE complexes possibly attributable to the high local concentration of complexes in the clusters area that allows efficient disassembly by the enzymatic reaction of NSF.
Control of NMDA Receptor Function by the NR2 Subunit Amino-Terminal Domain
Authors: Yuan Hongjie , Hansen Kasper B. , Vance Katie M. , Ogden Kevin K. , Traynelis Stephen F.
Published: September 2009

NMDA receptors comprised of different NR2 subunits exhibit strikingly unique biophysical and pharmacological properties. Here, we report that the extracellular amino-terminal domain (ATD) of the NR2 subunit controls pharmacological and kinetic properties of recombinant NMDA receptors, such as agonist potency, deactivation time course, open probability (POPEN), and mean open/shut duration. Using ATD deletion mutants of NR2A, NR2B, NR2C, NR2D, and chimeras of NR2A and NR2D with interchanged ATD [NR2A-(2D-ATD) and NR2D-(2A-ATD)], we show that the ATD contributes to the low glutamate potency of NR2A-containing NMDA receptors and the high glutamate potency of NR2D-containing receptors. The ATD influences the deactivation time courses of NMDA receptors, as removal of the ATD from NR2A slows the deactivation rate, while removal of the ATD from NR2B, NR2C and NR2D accelerates the deactivation rate. Open probability also is influenced by the ATD. Removal of the ATD from NR2A or replacement of the NR2A-ATD with that of NR2D decreasesPOPENin single-channel recordings from outside-out patches of HEK 293 cells. In contrast, deletion of the ATD from NR2D or replacement of the NR2D ATD with that of NR2A increasesPOPENand mean open duration. These data demonstrate the modular nature of NMDA receptors, and show that the ATD of the different NR2 subunits plays an important role in fine-tuning the functional properties of the individual NMDA receptor subtypes.
Functional and Anatomical Reorganization of the Sensory-Motor Cortex after Incomplete Spinal Cord Injury in Adult Rats
Authors: Ghosh Arko , Sydekum Esther , Haiss Florent , Peduzzi Stefano , Zörner Björn , Schneider Regula , Baltes Christof , Rudin Markus , Weber Bruno , Schwab Martin E.
Published: September 2009

A lateral hemisection injury of the cervical spinal cord results in Brown-Séquard syndrome in humans and rats. The hands/forelimbs on the injured side are rendered permanently impaired, but the legs/hindlimbs recover locomotor functions. This is accompanied by increased use of the forelimb on the uninjured side. Nothing is known about the cortical circuits that correspond to these behavioral adaptations. In this study, on adult rats with cervical spinal cord lateral hemisection lesions (at segment C3/4), we explored the sensory representation and corticospinal projection of the intact (ipsilesional) cortex. Using blood oxygenation level-dependent functional magnetic resonance imaging and voltage-sensitive dye (VSD) imaging, we found that the cortex develops an enhanced representation of the unimpaired forepaw by 12 weeks after injury. VSD imaging also revealed the cortical spatio-temporal dynamics in response to electrical stimulation of the ipsilateral forepaw or hindpaw. Interestingly, stimulation of the ipsilesional hindpaw at 12 weeks showed a distinct activation of the hindlimb area in the intact, ipsilateral cortex, probably via the injury-spared spinothalamic pathway. Anterograde tracing of corticospinal axons from the intact cortex showed sprouting to recross the midline, innervating the spinal segments below the injury in both cervical and lumbar segments. Retrograde tracing of these midline-crossing axons from the cervical spinal cord (at segment C6/7) revealed the formation of a new ipsilateral forelimb representation in the cortex. Our results demonstrate profound reorganizations of the intact sensory-motor cortex after unilateral spinal cord injury. These changes may contribute to the behavioral adaptations, notably for the recovery of the ipsilesional hindlimb.
Color-Related Signals in the Primate Superior Colliculus
Authors: White Brian J. , Boehnke Susan E. , Marino Robert A. , Itti Laurent , Munoz Douglas P.
Published: September 2009

Color is important for segmenting objects from backgrounds, which can in turn facilitate visual search in complex scenes. However, brain areas involved in orienting the eyes toward colored stimuli in our environment are not believed to have access to color information. Here, we show that neurons in the intermediate layers of the monkey superior colliculus (SC), a critical structure for the production of saccadic eye movements, can respond to isoluminant color stimuli with the same magnitude as a maximum contrast luminance stimulus. In contrast, neurons from the superficial SC layers showed little color-related activity. Crucially, visual onset latencies were 30–35 ms longer for color, implying that luminance and chrominance information reach the SC through distinct pathways and that the observed color-related activity is not the result of residual luminance signals. Furthermore, these differences in visual onset latency translated directly into differences in saccadic reaction time. The results demonstrate that the saccadic system can signal the presence of chromatic stimuli only one stage from the brainstem premotor circuitry that drives the eyes.
Evidence for a Common Representation of Decision Values for Dissimilar Goods in Human Ventromedial Prefrontal Cortex
Authors: Chib Vikram S. , Rangel Antonio , Shimojo Shinsuke , O'Doherty John P.
Published: September 2009

To make economic choices between goods, the brain needs to compute representations of their values. A great deal of research has been performed to determine the neural correlates of value representations in the human brain. However, it is still unknown whether there exists a region of the brain that commonly encodes decision values for different types of goods, or if, in contrast, the values of different types of goods are represented in distinct brain regions. We addressed this question by scanning subjects with functional magnetic resonance imaging while they made real purchasing decisions among different categories of goods (food, nonfood consumables, and monetary gambles). We found activity in a key brain region previously implicated in encoding goal-values: the ventromedial prefrontal cortex (vmPFC) was correlated with the subjects' value for each category of good. Moreover, we found a single area in vmPFC to be correlated with the subjects' valuations for all categories of goods. Our results provide evidence that the brain encodes a “common currency” that allows for a shared valuation for different categories of goods.
Visually Induced Analgesia: Seeing the Body Reduces Pain
Authors: Longo Matthew R. , Betti Viviana , Aglioti Salvatore M. , Haggard Patrick
Published: September 2009

Given previous reports of strong interactions between vision and somatic senses, we investigated whether vision of the body modulates pain perception. Participants looked into a mirror aligned with their body midline at either the reflection of their own left hand (creating the illusion that they were looking directly at their own right hand) or the reflection of a neutral object. We induced pain using an infrared laser and recorded nociceptive laser-evoked potentials (LEPs). We also collected subjective ratings of pain intensity and unpleasantness. Vision of the body produced clear analgesic effects on both subjective ratings of pain and the N2/P2 complex of LEPs. Similar results were found during direct vision of the hand, without the mirror. Furthermore, these effects were specific to vision of one's own hand and were absent when viewing another person's hand. These results demonstrate a novel analgesic effect of non-informative vision of the body.
Chemical Manipulation of Hsp70 ATPase Activity Regulates Tau Stability
Authors: Jinwal Umesh K. , Miyata Yoshinari , Koren John , Jones Jeffrey R. , Trotter Justin H. , Chang Lyra , O'Leary John , Morgan David , Lee Daniel C. , Shults Cody L. , Rousaki Aikaterini , Weeber Edwin J. , Zuiderweg Erik R. P. , Gestwicki Jason E. , Dickey Chad A.
Published: September 2009

Alzheimer's disease and other tauopathies have recently been clustered with a group of nervous system disorders termed protein misfolding diseases. The common element established between these disorders is their requirement for processing by the chaperone complex. It is now clear that the individual components of the chaperone system, such as Hsp70 and Hsp90, exist in an intricate signaling network that exerts pleiotropic effects on a host of substrates. Therefore, we have endeavored to identify new compounds that can specifically regulate individual components of the chaperone family. Here, we hypothesized that chemical manipulation of Hsp70 ATPase activity, a target that has not previously been pursued, could illuminate a new pathway toward chaperone-based therapies. Using a newly developed high-throughput screening system, we identified inhibitors and activators of Hsp70 enzymatic activity. Inhibitors led to rapid proteasome-dependent tau degradation in a cell-based model. Conversely, Hsp70 activators preserved tau levels in the same system. Hsp70 inhibition did not result in general protein degradation, nor did it induce a heat shock response. We also found that inhibiting Hsp70 ATPase activity after increasing its expression levels facilitated tau degradation at lower doses, suggesting that we can combine genetic and pharmacologic manipulation of Hsp70 to control the fate of bound substrates. Disease relevance of this strategy was further established when tau levels were rapidly and substantially reduced in brain tissue from tau transgenic mice. These findings reveal an entirely novel path toward therapeutic intervention of tauopathies by inhibition of the previously untargeted ATPase activity of Hsp70.
Turnover of Newborn Olfactory Bulb Neurons Optimizes Olfaction
Authors: Mouret Aurélie , Lepousez Gabriel , Gras Julien , Gabellec Marie-Madeleine , Lledo Pierre-Marie
Published: September 2009

Postdevelopmental neurogenesis occurs in the olfactory bulb (OB), to which new interneurons are continuously recruited. However, only a subset of the adult-generated interneurons survives, as many undergo programmed cell death. As part of homeostatic processes, the removal of new neurons is required alongside the addition of new ones, to ensure a stable neuron number. In addition to a critical role in tissue maintenance, it is still unclear whether this neuronal elimination affects the functioning of adult circuits. Using focal drug delivery restricted to the OB, we investigated the significance of programmed cell death in the adult OB circuits. Cell death was effectively blocked by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD). The zVAD effect differed with newborn interneuron location, either in the superficial (periglomerular cells) or in the deep (granule cells) OB layers. Furthermore, whereas sensory experience potentiated the effect of zVAD on the survival of new granule cells, it had no additional effect on the survival of new periglomerular cells. Thus, distinct mechanisms control the survival/elimination decision of newborn interneuron subtypes. However, zVAD had no effect on the olfactory sensory neurons projecting to the bulb. Remarkably, psychophysical analyzes revealed that a normal rate of new neuron elimination was essential for optimal odorant exploration and discrimination. This study highlights the importance of cell elimination for adjusting olfactory performance. We conclude that adult-generated OB interneurons are continually turned over, rather than simply added, and the precise balance between new and mature interneurons, set through active selection/elimination processes, is essential for optimizing olfaction.
Mitochondrial Ca2+Cycling Facilitates Activation of the Transcription Factor NFAT in Sensory Neurons
Authors: Kim Man-Su , Usachev Yuriy M.
Published: September 2009

Ca2+-dependent gene regulation controls many aspects of neuronal plasticity. Significant progress has been made toward understanding the roles of voltage- and ligand-gated Ca2+channels in triggering specific transcriptional responses. In contrast, the functional importance of Ca2+buffers and Ca2+transporters in neuronal gene regulation is less clear despite their critical contribution to the spatiotemporal control of Ca2+signals. Here we examined the role of mitochondrial Ca2+uptake and release in regulating the Ca2+-dependent transcription factor NFAT (nuclear factor of activated T-cells), which has been implicated in synaptic plasticity, axonal growth, and neuronal survival. Intense stimulation of sensory neurons by action potentials or TRPV1 agonists induced rapid activation and nuclear import of NFAT. Nuclear translocation of NFAT was associated with a characteristic prolonged [Ca2+]ielevation (plateau) that resulted from Ca2+uptake by, and its subsequent release from, mitochondria. Measurements using a mitochondrial Ca2+indicator, mtPericam, showed that this process recruited mitochondria throughout the cell body, including the perinuclear region. [Ca2+]ilevels attained during the plateau phase were similar to or higher than those required for NFAT activation (200–300 nm). The elimination of the [Ca2+]iplateau by blocking either mitochondrial Ca2+uptake via the uniporter or Ca2+release via the mitochondrial Na+/Ca2+exchanger strongly reduced nuclear import of NFAT. Furthermore, preventing Ca2+mobilization via the mitochondrial Na+/Ca2+exchanger diminished NFAT-mediated transcription. Collectively, these data implicate activity-induced Ca2+uptake and prolonged release from mitochondria as a novel regulatory mechanism in neuronal excitation–transcription coupling.
Perceptual Training Narrows the Temporal Window of Multisensory Binding
Authors: Powers Albert R. , Hillock Andrea R. , Wallace Mark T.
Published: September 2009

The brain's ability to bind incoming auditory and visual stimuli depends critically on the temporal structure of this information. Specifically, there exists a temporal window of audiovisual integration within which stimuli are highly likely to be bound together and perceived as part of the same environmental event. Several studies have described the temporal bounds of this window, but few have investigated its malleability. Here, the plasticity in the size of this temporal window was investigated using a perceptual learning paradigm in which participants were given feedback during a two-alternative forced choice (2-AFC) audiovisual simultaneity judgment task. Training resulted in a marked (i.e., ∼40%) narrowing in the size of the window. To rule out the possibility that this narrowing was the result of changes in cognitive biases, a second experiment using a two-interval forced choice (2-IFC) paradigm was undertaken during which participants were instructed to identify a simultaneously presented audiovisual pair presented within one of two intervals. The 2-IFC paradigm resulted in a narrowing that was similar in both degree and dynamics to that using the 2-AFC approach. Together, these results illustrate that different methods of multisensory perceptual training can result in substantial alterations in the circuits underlying the perception of audiovisual simultaneity. These findings suggest a high degree of flexibility in multisensory temporal processing and have important implications for interventional strategies that may be used to ameliorate clinical conditions (e.g., autism, dyslexia) in which multisensory temporal function may be impaired.