What checkers actually check:an eye tracking study of inhibitory control and working memory

Background - Not only is compulsive checking the most common symptom in Obsessive Compulsive Disorder (OCD) with an estimated prevalence of 50–80% in patients, but approximately ~15% of the general population reveal subclinical checking tendencies that impact negatively on their performance in daily activities. Therefore, it is critical to understand how checking affects attention and memory in clinical as well as subclinical checkers. Eye fixations are commonly used as indicators for the distribution of attention but research in OCD has revealed mixed results at best. Methodology/Principal Finding - Here we report atypical eye movement patterns in subclinical checkers during an ecologically valid working memory (WM) manipulation. Our key manipulation was to present an intermediate probe during the delay period of the memory task, explicitly asking for the location of a letter, which, however, had not been part of the encoding set (i.e., misleading participants). Using eye movement measures we now provide evidence that high checkers’ inhibitory impairments for misleading information results in them checking the contents of WM in an atypical manner. Checkers fixate more often and for longer when misleading information is presented than non-checkers. Specifically, checkers spend more time checking stimulus locations as well as locations that had actually been empty during encoding. Conclusions/Significance - We conclude that these atypical eye movement patterns directly reflect internal checking of memory contents and we discuss the implications of our findings for the interpretation of behavioural and neuropsychological data. In addition our results highlight the importance of ecologically valid methodology for revealing the impact of detrimental attention and memory checking on eye movement patterns.

Single dose flucloxacillin in the treatment of wounds

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Patient education in the treatment of asthma:a controlled evaluation of providing information for "new" asthmatics

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Risk and benefit assessment for Tolcapone in the treatment of Parkinson's disease

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A systematic review of the adverse events of imatinib mesylate in the treatment of chronic myeloid leukemia.

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The effectiveness of leflunomide etanercept and infliximab in the treatment of rheumatoid arthritis:a systematic review

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Tissue Transglutaminase (TG2) is a potential therapeutic target in the treatment of chemoresistant breast cancer

Tissue transglutaminase (TG2) has been suggested to be a key player in the progression and metastasis of chemoresistant breast cancer. One of the foremost survival signalling pathways implicated in causing drug resistance in breast cancer is the constitutive activation of NFκB (Nuclear Factor -kappa B) induced by TG2. This study provides a mechanism by which TG2 constitutively activates NFκB which in turn confers chemoresistance to breast cancer cells against doxorubicin. Breast cancer cell lines with varying expression levels of TG2 as well as TG2 null breast cancer cells transfected with TG2 were used as the major cell models for this study. This study made use of cell permeable and impermeable TG2 inhibitors, specific TG2 and Rel A/ p65 targeting siRNA, TG2 functional blocking antibodies, IKK inhibitors and a specific targeting peptide against Rel A/p65 to investigate the pathway of activation involved in the constitutive activation of NFκB by TG2 leading to drug resistance. Crucial to the activation of Rel A/p65 and drug resistance in the breast cancer cells is the interaction between the complex of IκBα and Rel A/p65 with TG2 which results in the dimerization of Rel A/p65 and polymerization of IκBα. The association of TG2 with the IκBα-NFκB complex was determined to be independent of IKKα/β function. The polymerized IκBα is degraded in the cytoplasm by the μ-calpain pathway which allows the cross linked Rel A/ p65 dimers to translocate into the nucleus. Using R283 and ZDON (cell permeable TG2 activity inhibitors) and specific TG2 targeting siRNA, the Rel A/ p65 dimer formation could be inhibited. Co-immunoprecipitation studies confirmed that the phosphorylation of the Rel A/p65 dimers at the Ser536 residue by IKKε took place in the cell nucleus. Importantly, this study also investigated the transcriptional regulation of the TGM2 gene by the pSer536 Rel A/ p65 dimer and the importance of this TG2-NFκB feedback loop in conferring drug resistance to breast cancer cells. This data provides evidence that TG2 could be a key therapeutic target in the treatment of chemoresistant breast cancer.

A safety evaluation of ranibizumab in the treatment of age-related macular degeneration

Introduction: The use of intravitreal ranibizumab has transformed the outcomes for thousands of patients with wet age related macular degeneration (AMD), which is the leading cause of blindness in developed countries. Prior to its introduction, most patients with wet AMD would rapidly lose central vision. The use of intravitreal ranibizumab has been shown to reduce certifiable visual loss by about a half. Current treatment regimens with ranibizumab in wet AMD require multiple injections over several years and so it is highly relevant to review the safety record of this important drug.Areas covered: This review considers the important ocular and systemic adverse events (AE) that have been reported in the literature, particularly in the context of the pivotal clinical trials that have been performed. It also reviews the safety of other anti-VEGF drugs that are used in wet AMD, namely bevacizumab and aflibercept, and compares these drugs with ranibizumab.Expert opinion: Overall, intravitreal ranibizumab can be considered a safe and highly effective drug for patients with wet AMD. However recent concerns about retinal thinning following ranibizumab therapy, possible systemic AE associated with all anti-VEGF drugs and the occurrence of complications relating to drug preparation and delivery must be considered. © 2014 Informa UK, Ltd.

The use of antidepressants to treat attention deficit hyperactivity disorder in adults

There is increasing evidence that children continue to experience attention deficit hyperactivity disorder (ADHD) symptoms into adult life. The two main treatments for ADHD are antidepressants and stimulants. Here, the effectiveness data relating to the use of antidepressants in adults with ADHD are reviewed. Four controlled and six open studies were identified. Although, there is only limited data currently available, antidepressants may offer an effective therapy for adult ADHD. Controlled trials have studied desipramine, atomoxetine and bupropion, with most evidence supporting the efficacy of desipramine. The initial data indicate that atomoxetine is less effective than desipramine. The efficacy of bupropion is unclear. Initial published open data suggest a response rate of 50-78% with venlafaxine. Controlled studies are required to confirm this efficacy. Most of the present data are short-term, therefore long-term effectiveness data are required.

DSM-5 Autism Spectrum Disorder:in search of essential behaviours for diagnosis

Background: Despite initial concerns about the sensitivity of the proposed diagnostic criteria for DSM-5 Autism Spectrum Disorder (ASD; e.g. Gibbs et al., 2012; McPartland et al., 2012), evidence is growing that the DSM-5 criteria provides an inclusive description with both good sensitivity and specificity (e.g. Frazier et al., 2012; Kent, Carrington et al., 2013). The capacity of the criteria to provide high levels of sensitivity and specificity comparable with DSM-IV-TR however relies on careful measurement to ensure that appropriate items from diagnostic instruments map onto the new DSM-5 descriptions.Objectives: To use an existing DSM-5 diagnostic algorithm (Kent, Carrington et .al., 2013) to identify a set of ‘essential’ behaviors sufficient to make a reliable and accurate diagnosis of DSM-5 Autism Spectrum Disorder (ASD) across age and ability level. Methods: Specific behaviors were identified and tested from the recently published DSM-5 algorithm for the Diagnostic Interview for Social and Communication Disorders (DISCO). Analyses were run on existing DISCO datasets, with a total participant sample size of 335. Three studies provided step-by-step development towards identification of a minimum set of items. Study 1 identified the most highly discriminating items (p<.0001). Study 2 used a lower selection threshold than in Study 1 (p<.05) to facilitate better representation of the full DSM-5 ASD profile. Study 3 included additional items previously reported as significantly more frequent in individuals with higher ability. The discriminant validity of all three item sets was tested using Receiver Operating Characteristic curves. Finally, sensitivity across age and ability was investigated in a subset of individuals with ASD (n=190).Results: Study 1 identified an item set (14 items) with good discriminant validity, but which predominantly measured social-communication behaviors (11/14). The Study 2 item set (48 items) better represented the DSM-5 ASD and had good discriminant validity, but the item set lacked sensitivity for individuals with higher ability. The final Study 3 adjusted item set (54 items) improved sensitivity for individuals with higher ability and performance and was comparable to the published DISCO DSM-5 algorithm.Conclusions: This work represents a first attempt to derive a reduced set of behaviors for DSM-5 directly from an existing standardized ASD developmental history interview. Further work involving existing ASD diagnostic tools with community-based and well characterized research samples will be required to replicate these findings and exploit their potential to contribute to a more efficient and focused ASD diagnostic process.

Muscle motion and EMG activity in vibration treatment

The aim of this study is to highlight the relationship between muscle motion, generated by whole body vibration, and the correspondent electromyographic (EMG) activity and to suggest a new method to customize the stimulation frequency. Simultaneous recordings of EMG and tri-axial accelerations of quadriceps rectus femoris from fifteen subjects undergoing vibration treatments were collected. Vibrations were delivered via a sinusoidal oscillating platform at different frequencies (10-45 Hz). Muscle motion was estimated by processing the accelerometer data. Large EMG motion artifacts were removed using sharp notch filters centred at the vibration frequency and its superior harmonics. EMG-RMS values were computed and analyzed before and after artifact suppression to assess muscular activity. Muscles acceleration amplitude increased with frequency. Muscle displacements revealed a mechanical resonant-like behaviour of the muscle. Resonance frequencies and dumping factors depended on subject. Moreover, RMS of artifact-free EMG was found well correlated (R 2 = 0.82) to the actual muscle displacement, while the maximum of the EMG response was found related to the mechanical resonance frequency of muscle. Results showed that maximum muscular activity was found in correspondence to the mechanical resonance of the muscle itself. Assuming the hypothesis that muscle activation is proportional to muscle displacement, treatment optimization (i.e. to choose the best stimulation frequency) could be obtained by simply monitoring local acceleration (resonance), leading to a more effective muscle stimulation. Motion artifact produced an overestimation of muscle activity, therefore its removal was essential. © 2009 IPEM.

DSM-5 Autism Spectrum Disorder:in search of essential behaviours for diagnosis

The objective of this study was to identify a set of 'essential' behaviours sufficient for diagnosis of DSM-5 Autism Spectrum Disorder (ASD). Highly discriminating, 'essential' behaviours were identified from the published DSM-5 algorithm developed for the Diagnostic Interview for Social and Communication Disorders (DISCO). Study 1 identified a reduced item set (48 items) with good predictive validity (as measured using receiver operating characteristic curves) that represented all symptom sub-domains described in the DSM-5 ASD criteria but lacked sensitivity for individuals with higher ability. An adjusted essential item set (54 items; Study 2) had good sensitivity when applied to individuals with higher ability and performance was comparable to the published full DISCO DSM-5 algorithm. Investigation at the item level revealed that the most highly discriminating items predominantly measured social-communication behaviours. This work represents a first attempt to derive a reduced set of behaviours for DSM-5 directly from an existing standardised ASD developmental history interview and has implications for the use of DSM-5 criteria for clinical and research practice. © 2014 The Authors.

Personality profile of male adolescents with Tourette syndrome:a controlled study

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and commonly associated with behavioral problems, especially obsessive-compulsive disorder and attention-deficit hyperactivity disorder (ADHD). The presence of specific personality traits has been documented in adult clinical populations with Tourette syndrome but has been underresearched in younger patients. We assessed the personality profiles of 17 male adolescents with Tourette syndrome and 51 age- and gender-matched healthy controls using the Minnesota Multiphasic Personality Inventory-Adolescent version, along with a standardized psychometric battery. All participants scored within the normal range across all Minnesota Multiphasic Personality Inventory-Adolescent version scales. Patients with Tourette syndrome scored significantly higher than healthy controls on the Obsessiveness Content Scale only (P = .046). Our findings indicate that younger male patients with Tourette syndrome do not report abnormal personality traits and have similar personality profiles to healthy peers, with the exception of obsessionality traits, which are likely to be related to the presence of comorbid obsessive compulsive symptoms rather than tics.

Developmental dissociation of analytical and holistic object recognition in adolescence

Previous research (e.g., Jüttner et al, 2013, Developmental Psychology, 49, 161-176) has shown that object recognition may develop well into late childhood and adolescence. The present study extends that research and reveals novel di erences in holistic and analytic recognition performance in 7-11 year olds compared to that seen in adults. We interpret our data within Hummel’s hybrid model of object recognition (Hummel, 2001, Visual Cognition, 8, 489-517) that proposes two parallel routes for recognition (analytic vs. holistic) modulated by attention. Using a repetition-priming paradigm, we found in Experiment 1 that children showed no holistic priming, but only analytic priming. Given that holistic priming might be thought to be more ‘primitive’, we confirmed in Experiment 2 that our surprising finding was not because children’s analytic recognition was merely a result of name repetition. Our results suggest a developmental primacy of analytic object recognition. By contrast, holistic object recognition skills appear to emerge with a much more protracted trajectory extending into late adolescence

Developmental commonalities between object and face recognition in adolescence

In the visual perception literature, the recognition of faces has often been contrasted with that of non-face objects, in terms of differences with regard to the role of parts, part relations and holistic processing. However, recent evidence from developmental studies has begun to blur this sharp distinction. We review evidence for a protracted development of object recognition that is reminiscent of the well-documented slow maturation observed for faces. The prolonged development manifests itself in a retarded processing of metric part relations as opposed to that of individual parts and offers surprising parallels to developmental accounts of face recognition, even though the interpretation of the data is less clear with regard to holistic processing. We conclude that such results might indicate functional commonalities between the mechanisms underlying the recognition of faces and non-face objects, which are modulated by different task requirements in the two stimulus domains.