Effects of Partial and Complete Ablation of the Slow Pathway on Fast Pathway Properties in Patients with Atrioventricular Nodal Reentrant Tachycardia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73520/1/j.1540-8167.1994.tb01187.x.pd

Temporal perception deficits in schizophrenia: integration is the problem, not deployment of attentions

Patients with schizophrenia are known to have impairments in sensory processing. In order to understand the specific temporal perception deficits of schizophrenia, we investigated and determined to what extent impairments in temporal integration can be dissociated from attention deployment using Attentional Blink (AB). Our findings showed that there was no evident deficit in the deployment of attention in patients with schizophrenia. However, patients showed an increased temporal integration deficit within a hundred-millisecond timescale. The degree of such integration dysfunction was correlated with the clinical manifestations of schizophrenia. There was no difference between individuals with/without schizotypal personality disorder in temporal integration. Differently from previous studies using the AB, we did not find a significant impairment in deployment of attention in schizophrenia. Instead, we used both theoretical and empirical approaches to show that previous findings (using the suppression ratio to correct for the baseline difference) produced a systematic exaggeration of the attention deficits. Instead, we modulated the perceptual difficulty of the task to bring the baseline levels of target detection between the groups into closer alignment. We found that the integration dysfunction rather than deployment of attention is clinically relevant, and thus should be an additional focus of research in schizophrenia

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al

Update in the management of chronic lymphocytic leukemia

Advances in the treatment of chronic lymphocytic leukemia (CLL) have improved initial overall response (OR) rates, complete response (CR) rates and progression free survival (PFS). Despite these advances, CLL remains incurable with standard therapies. Thus, there remains a need for more effective therapies in both the upfront and relapsed setting, particularly for patients with high-risk cytogenetic abnormalities such as del(11q22) and del(17p13). The 2008 American Society of Hematology (ASH) Annual Meeting featured several presentations which highlighted the ongoing clinical advances in CLL. The benefit of adding rituximab to purine analog therapy in the upfront setting was demonstrated by a large randomized study which showed that the addition of rituximab to fludarabine and cyclophosphamide (FCR) significantly improved OR, CR and PFS. The improvement in PFS directly resulted from an improved ability to eliminate minimal residual disease (MRD) in the peripheral blood, highlighting the importance of MRD eradication. However, a multi-center study suggested that the high CR rates to chemoimmunotherapy regimens such as FCR obtained in academic centers may not be reproducible when the same regimens are given in the community setting. The immunomodulatory drug lenalidomide is active in relapsed high-risk CLL, but two studies of lenalidomide in previously untreated CLL patients failed to achieve a CR and were associated with significant tumor lysis, tumor flare and hematologic toxicity. In the relapsed setting, a combination study of the bifunctional alkylator bendamustine and rituximab (BR) demonstrated a high OR rate in patients with del(11q22) and del(17p13), indicating that further studies to define's bendamustine activity are warranted in high-risk CLL. Similarly, the CDK inhibitor flavopiridol demonstrated significant clinical activity and durable remissions in heavily treated, refractory CLL patients with high-risk cytogenetic features and bulky lymphadenopathy. The monoclonal anti-CD20 antibody ofatumumab appeared to be superior to rituximab in relapsed CLL patients with bulky nodal disease or high-risk cytogenetic features. Ongoing studies of these agents and other novel therapeutic agents in clinical development hold forth the promise that treatment options for CLL patients will continue to expand and improve

Study protocol: a randomized controlled trial of a computer-based depression and substance abuse intervention for people attending residential substance abuse treatment

Background: A large proportion of people attending residential alcohol and other substance abuse treatment have a co-occurring mental illness. Empirical evidence suggests that it is important to treat both the substance abuse problem and co-occurring mental illness concurrently and in an integrated fashion. However, the majority of residential alcohol and other substance abuse services do not address mental illness in a systematic way. It is likely that computer delivered interventions could improve the ability of substance abuse services to address co-occurring mental illness. This protocol describes a study in which we will assess the effectiveness of adding a computer delivered depression and substance abuse intervention for people who are attending residential alcohol and other substance abuse treatment. Methods/Design. Participants will be recruited from residential rehabilitation programs operated by the Australian Salvation Army. All participants who satisfy the diagnostic criteria for an alcohol or other substance dependence disorder will be asked to participate in the study. After completion of a baseline assessment, participants will be randomly assigned to either a computer delivered substance abuse and depression intervention (treatment condition) or to a computer-delivered typing tutorial (active control condition). All participants will continue to complete The Salvation Army residential program, a predominantly 12-step based treatment facility. Randomisation will be stratified by gender (Male, Female), length of time the participant has been in the program at the commencement of the study (4 weeks or less, 4 weeks or more), and use of anti-depressant medication (currently prescribed medication, not prescribed medication). Participants in both conditions will complete computer sessions twice per week, over a five-week period. Research staff blind to treatment allocation will complete the assessments at baseline, and then 3, 6, 9, and 12 months post intervention. Participants will also complete weekly self-report measures during the treatment period. Discussion. This study will provide comprehensive data on the effect of introducing a computer delivered, cognitive behavioral therapy based co-morbidity treatment program within a residential substance abuse setting. If shown to be effective, this intervention can be disseminated within other residential substance abuse programs. Trial registration. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000618954

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

The clubfoot assessment protocol (CAP); description and reliability of a structured multi-level instrument for follow-up

BACKGROUND: In most clubfoot studies, the outcome instruments used are designed to evaluate classification or long-term cross-sectional results. Variables deal mainly with factors on body function/structure level. Wide scorings intervals and total sum scores increase the risk that important changes and information are not detected. Studies of the reliability, validity and responsiveness of these instruments are sparse. The lack of an instrument for longitudinal follow-up led the investigators to develop the Clubfoot Assessment Protocol (CAP). The aim of this article is to introduce and describe the CAP and evaluate the items inter- and intra reliability in relation to patient age. METHODS: The CAP was created from 22 items divided between body function/structure (three subgroups) and activity (one subgroup) levels according to the International Classification of Function, Disability and Health (ICF). The focus is on item and subgroup development. Two experienced examiners assessed 69 clubfeet in 48 children who had a median age of 2.1 years (range, 0 to 6.7 years). Both treated and untreated feet with different grades of severity were included. Three age groups were constructed for studying the influence of age on reliability. The intra- rater study included 32 feet in 20 children who had a median age of 2.5 years (range, 4 months to 6.8 years). The Unweighted Kappa statistics, percentage observer agreement, and amount of categories defined how reliability was to be interpreted. RESULTS: The inter-rater reliability was assessed as moderate to good for all but one item. Eighteen items had kappa values > 0.40. Three items varied from 0.35 to 0.38. The mean percentage observed agreement was 82% (range, 62 to 95%). Different age groups showed sufficient agreement. Intra- rater; all items had kappa values > 0.40 [range, 0.54 to 1.00] and a mean percentage agreement of 89.5%. Categories varied from 3 to 5. CONCLUSION: The CAP contains more detailed information than previous protocols. It is a multi-dimensional observer administered standardized measurement instrument with the focus on item and subgroup level. It can be used with sufficient reliability, independent of age, during the first seven years of childhood by examiners with good clinical experience. A few items showed low reliability, partly dependent on the child's age and /or varying professional backgrounds between the examiners. These items should be interpreted with caution, until further studies have confirmed the validity and sensitivity of the instrument

Confirmation bias in the utilization of others' opinion strength

Humans tend to discount information that undermines past choices and judgments. This confirmation bias has significant impact on domains ranging from politics to science and education. Little is known about the mechanisms underlying this fundamental characteristic of belief formation. Here we report a mechanism underlying the confirmation bias. Specifically, we provide evidence for a failure to use the strength of others' disconfirming opinions to alter confidence in judgments, but adequate use when opinions are confirmatory. This bias is related to reduced neural sensitivity to the strength of others' opinions in the posterior medial prefrontal cortex when opinions are disconfirming. Our results demonstrate that existing judgments alter the neural representation of information strength, leaving the individual less likely to alter opinions in the face of disagreement