The gene expression profile and cell of origin of canine peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) refers to a heterogenous group of T-cell neoplasms with poor treatment responses and survival times. Canine PTCL clinically and immunophenotypically resembles the most common human subtype, PTCL-not otherwise specified (PTCL-NOS), leading to interest in this canine disease as a naturally occurring model for human PTCL. Gene expression profiling in human PTCL-NOS has helped characterize this ambiguous diagnosis into distinct subtypes, but similar gene expression profiling in canine PTCL is lacking. METHODS: Bulk RNA-sequencing was performed on tumor samples from 33 dogs with either CD4+ (26/33), CD8+ (4/33), or CD4-CD8- (3/33) PTCL as diagnosed by flow cytometry, and sorted CD4+ and CD8+ lymphocytes from healthy control dogs. Following normalization of RNA-seq data, we performed differential gene expression and unsupervised clustering methods. Gene set enrichment analysis was performed to determine the enrichment of canine CD4+ PTCL for human PTCL-NOS, oncogenic pathways, and various stages of T-cell development gene signatures. We utilized gene set variation analysis to evaluate individual canine CD4+ PTCLs for various human and murine T-cell and thymocyte gene signatures. Cultured canine PTCL cells were treated with a pan-PI3K inhibitor, and cell survival and proliferation were compared to DMSO-treated controls. Expression of GATA3 and phosphorylated AKT was validated by immunohistochemistry. RESULTS: While the canine CD4+ PTCL phenotype exhibited a consistent gene expression profile, the expression profiles of CD8+ and CD4-CD8- canine PTCLs were more heterogeneous. Canine CD4+ PTCL had increased expression of GATA3, upregulation of its target genes, enrichment for PI3K/AKT/mTOR signaling, and downregulation of PTEN, features consistent with the more aggressive GATA3-PTCL subtype of human PTCL-NOS. In vitro assays validated the reliance of canine CD4+ PTCL cells on PI3K/AKT/mTOR signaling for survival and proliferation. Canine CD4+ PTCL was enriched for thymic precursor gene signatures, exhibited increased expression of markers of immaturity (CD34, KIT, DNTT, and CCR9), and downregulated genes associated with the T-cell receptor, MHC class II associated genes (DLA-DQA1, DLA-DRA, HLA-DQB1, and HLA-DQB2), and CD25. CONCLUSIONS: Canine CD4+ PTCL most closely resembled the GATA3-PTCL subtype of PTCL-NOS and may originate from an earlier stage of T-cell development than the more conventionally posited mature T-helper cell origin.

Are we informing our patients correctly? Evaluation of perioperative counselling for paediatric intestinal stoma formation: a national study.

PURPOSE: Adequate preoperative information is known to improve patient outcomes. We aimed to evaluate perioperative education for paediatric patients and families undergoing intestinal stoma formation. METHODS: UK paediatric surgery centres were invited to recruit patients aged 6-16 years with a stoma in situ or reversed within the last 2 years. Patient and parent questionnaires were posted for potential participants. RESULTS: Eighty-three patient/parent dyads returned questionnaires. Median age was 11.5 years (range 4.1-17.8), with 48% (n = 40) formed electively. Parents rated how well-informed they felt perioperatively out of 10 (0 poorly, 10 highly informed). Parents were better informed about surgical issues and stoma care than psychological and social impacts (7.45 vs 6.11; p < 0.0001). 54% reported surgical complications but significantly fewer patients listed these amongst the worst things about having a stoma (24.4%) when compared with psychosocial issues: distress from bag leaks (90.8%; p < 0.0001), self-consciousness (54.1%; p = 0.0001), and restricted activity (40.2%; p = 0.03). CONCLUSION: Parents felt well-informed for medical and practical aspects but less well-informed of psychological and lifestyle impacts of having a stoma. Surgical complications were less important to patients than the impact on daily life. Increased psychosocial information would enable families to be better prepared for life with a stoma.

The virus be damned: Older adults seek romantic relationships during a pandemic.

COVID-19 was concerning for older adults because they faced greater health risks from the virus and generally experience higher rates of isolation and loneliness. Single older adults are of particular concern because they also lack a cohabiting partner for social connection, so they may face greater levels of loneliness. Many older adults have been using technology to develop and maintain social connections, including romantic connections, to mitigate these feelings of loneliness and isolation. This research explores how feelings of loneliness connect to use of online dating sites during a pandemic, how older adults decided to and rationalized dating at a time when meeting in-person and social interactions were discouraged and dangerous, and how experiences differed between men and women. I interviewed 50 men and 50 women, ages 60-83, about their experiences seeking partners and dating during the pandemic. All respondents were single, heterosexual, and recruited from online dating websites, but varied by race, education level, marital experience, employment status, and geographic location. Single older adults relied on feelings of loneliness and isolation, the ubiquity of online dating sites, and particularly for women, adherence to safety measures while on a date as motivation for seeking and meeting romantic partners during a pandemic. Single older adults seeking new romantic interactions during a pandemic, when health risks were greater, illustrates the importance of intimate relationships even into older age and how loneliness and isolation are powerful drivers in seeking romantic relationships.

Revisiting the self-generation effect in proofreading.

The self-generation effect refers to the finding that people's memory for information tends to be better when they generate it themselves. Counterintuitively, when proofreading, this effect may make it more difficult to detect mistakes in one's own writing than in others' writing. We investigated the self-generation effect and sources of individual differences in proofreading performance in two eye-tracking experiments. Experiment 1 failed to reveal a self-generation effect. Experiment 2 used a studying manipulation to induce overfamiliarity for self-generated text, revealing a weak but non-significant self-generation effect. Overall, word errors (i.e., wrong words) were detected less often than non-word errors (i.e., misspellings), and function word errors were detected less often than content word errors. Fluid intelligence predicted proofreading performance, whereas reading comprehension, working memory capacity, processing speed, and indicators of miserly cognitive processing did not. Students who made more text fixations and spent more time proofreading detected more errors.

Hydrocephalus in patients with vestibular schwannoma.

BACKGROUND: Hydrocephalus (HC) is common in patients with vestibular schwannoma (VS). This can be managed with a cerebrospinal fluid (CSF) diversion procedure prior to VS resection or with VS resection, keeping CSF diversion in reserve unless required postoperatively. No clear consensus exists as to which approach is superior. This study identifies factors predictive of the development of HC, and analyses outcomes for those managed with primary CSF resection versus tumour resection. METHODS: Single-centre retrospective cohort study of 204 consecutive adult patients with a unilateral VS from May 2009 to June 2021. Data was collected on patient and tumour demographics, management, and outcome. RESULTS: 204 patients, with a mean age at presentation of 59.5 (21-83), with 50% female, and a mean follow-up of 7.5 years (1.8-13.9) were included. 119 were managed conservatively, 36 with stereotactic radiosurgery only, and 49 with surgery. 30 (15%) patients had radiological HC, of which 23 (77%) were obstructive, and 7 (23%) were communicating. Maximum intracranial tumour diameter and Koos grade were higher in patients with HC. Of the patients with HC the majority (20, 67%) were managed initially with CSF diversion, with 12 patients undergoing subsequent tumour resection, and three patients avoiding primary resection. Nine (30%) were managed with primary surgical resection, of whom three required subsequent CSF diversion. Complication rates and Modified Rankin Scale (MRS) were comparable or lower in the CSF diversion group (8%, MRS ≤2 = 83%), versus the primary resection group (67%, MRS ≤2 = 67%), and the primary surgical resection without HC group (25%, MRS ≤2 = 86%). CONCLUSIONS: CSF diversion prior to tumour resection is a safe and acceptable strategy compared to primary VS resection, with improved outcomes and reduced surgical complications. Randomized studies and national databases are needed to determine the long-term outcomes of patients treated with CSF diversion versus primary resection.

Granular cell tumour of the cavernous sinus: A rare cause of secondary trigeminal neuralgia.

BACKGROUND: Cavernous sinus tumours comprise 0.1-0.2% of all intracranial tumours, and are most commonly meningiomas or schwannomas. Central nervous system and cranial nerve granular cell tumours (GCTs) are extremely rare. We report the tenth case of a GCT arising from a cranial nerve, and the second case reported in a cavernous sinus location, and review the literature. CLINICAL PRESENTATION: A 67-year-old man presented with right sided trigeminal neuralgia. Imaging findings suggested a trigeminal schwannoma and he was treated with CyberKnife radiosurgery. Over a period of 41 months follow up, there was a progression in both symptoms and imaging findings, requiring debulking surgery. Histopathology identified a GCT. CONCLUSIONS: This is the first case of a cranial nerve GCT treated with stereotactic radiosurgery. Trigeminal nerve GCTs are a rare differential in cases of presumed schwannomas.

Laterality indices consensus initiative (LICI): A Delphi expert survey report on recommendations to record, assess, and report asymmetry in human behavioural and brain research.

Laterality indices (LIs) quantify the left-right asymmetry of brain and behavioural variables and provide a measure that is statistically convenient and seemingly easy to interpret. Substantial variability in how structural and functional asymmetries are recorded, calculated, and reported, however, suggest little agreement on the conditions required for its valid assessment. The present study aimed for consensus on general aspects in this context of laterality research, and more specifically within a particular method or technique (i.e., dichotic listening, visual half-field technique, performance asymmetries, preference bias reports, electrophysiological recording, functional MRI, structural MRI, and functional transcranial Doppler sonography). Experts in laterality research were invited to participate in an online Delphi survey to evaluate consensus and stimulate discussion. In Round 0, 106 experts generated 453 statements on what they considered good practice in their field of expertise. Statements were organised into a 295-statement survey that the experts then were asked, in Round 1, to independently assess for importance and support, which further reduced the survey to 241 statements that were presented again to the experts in Round 2. Based on the Round 2 input, we present a set of critically reviewed key recommendations to record, assess, and report laterality research for various methods.

Computer Prompt Software to Reduce Sedentary Behavior and Promote Physical Activity Among Desk-Based Workers: A Systematic Review.

OBJECTIVE: Do computer prompt software programs at the workplace reduce sitting time and/or increase physical activity at work? BACKGROUND: Many products are promoted and being used in the workplace; however, their effectiveness and use are unknown or the evidence base that they work to change behavior is lacking. METHOD: We searched for relevant papers published between 2005 and 2020. The inclusion criteria were computer prompt software programs installed as behavioral change interventions; interventions implemented during work hours and delivered through a work personal computer or laptop; and measures of sedentary behavior and/or physical activity. To minimize risk of bias, three recommended best-evidence synthesis criteria were used: random assignment, sample size, and external validity. Based on these criteria, articles were selected and evaluated. RESULTS: Six publications met the quality threshold for review. Seven articles did not meet the quality threshold. Four of the six included publications found that computer prompt software programs decreased sedentary behavior and/or increased physical activity. Two publications reported inconsistent results. CONCLUSIONS: The promising results from this systematic review indicate that there is potential for computer prompt software programs to improve the health of desk-based workers. For conclusive findings, more high-quality, scientific studies are needed. APPLICATION: The best-evidence publications in this review can serve as a guide in selecting and implementing computer prompt software programs at the workplace to decrease sedentary behavior and increase physical activity.

Surgery for cerebral cavernous malformations: a systematic review and meta-analysis.

BACKGROUND: We sought to quantify the risks of neurosurgical excision of cerebral cavernous malformations (CCMs) in a systematic review of cohort studies. METHODS: We updated our previous systematic review by searching OVID Medline, OVID EMBASE, and the Cochrane Library from 1 January 2013 to 30 April 2019. The primary outcome was a composite of death attributed to CCM or surgery, non-fatal symptomatic intracerebral haemorrhage (ICH), or new or worsened persistent non-haemorrhagic focal neurological deficit (FND). RESULTS: We included 70 cohorts, 67 reporting surgery alone, and three compared surgery to conservative management. A total of 5,089 patients (median age 36 years, 52% female) underwent surgery (total follow-up 19,404 patient-years). The annual rate of the composite outcome was 4.2% (95% CI 2.9 to 5.7; 46 cohorts; I2 = 93%), which was higher in cohorts reporting exclusively brainstem CCM (6.0%, 95% CI 4.1-8.3; 25 cohorts, I2 = 92%) versus predominantly supratentorial CCM (2.4%, 95% CI 1.3-3.8, 21 cohorts, I2 = 86%, phet = 0.001). The annual rate of the composite outcome was higher in cohorts with > 95% presenting with ICH (6.1%, 95% CI 4.2-8.4; 23 cohorts, I2 = 93%) versus others (2.3%, 95% CI 1.2-3.7; 23 cohorts, I2 = 83%, phet = 0.001). The incidence of the composite outcome did not change over time in cohorts of exclusively brainstem CCM (p = 0.7) or predominantly supratentorial CCM (p = 0.5). CONCLUSIONS: The risk of death, ICH, or FND after CCM excision is ~ 4%. This risk is higher for brainstem CCM and CCM that have caused ICH but has not changed over time. TRIAL REGISTRATION: This systematic review was registered (PROSPERO CRD42019131246).

Examining the Role of Psychosocial Influences on Black Maternal Health During the COVID-19 Pandemic.

INTRODUCTION: Due to the disproportionate impact of COVID-19 on communities of color, racial disparities in maternal mortality and morbidity are likely to increase. However, neighborhood and social support factors have yet to be discussed as potential mechanisms by which COVID-19 can exacerbate racial disparities. METHODS: We examined literature on the role of neighborhood factors and social support on maternal health outcomes and provided analytical perspective on the potential impacts of COVID-19 on Black birthing people. RESULTS: Even prior to the pandemic, Black individuals were disproportionately impacted by psychosocial stress. However, the compounding effect of pre-existing and current pandemic psychosocial stressors may be a mechanism by which racial disparities are exacerbated and result in higher rates of maternal mortality and morbidity in Black women. CONCLUSION: We recommend continued monitoring of data related to racial disparities in maternal mortality and morbidity throughout the pandemic. Given that Black women may be disproportionately impacted by psychosocial stress, it is necessary for leadership structures and communities to recognize the potential for worsening disparities and intervene.

The iCanCope pain self-management application for adolescents with juvenile idiopathic arthritis: a pilot randomized controlled trial.

OBJECTIVES: To evaluate the feasibility and preliminary effectiveness of iCanCope with Pain (iCanCope), a smartphone-based pain self-management program, in adolescents with JIA. iCanCope featured symptom tracking, goal-setting, pain coping skills and social support. METHODS: A two-arm pilot randomized controlled trial was used to evaluate the iCanCope app compared with a version with symptom tracking only. Primary (feasibility) outcomes were: participant accrual/attrition rates, success of app deployment, acceptability and adherence. Secondary (preliminary effectiveness) outcomes were: pain intensity, pain-related activity limitations and health-related quality of life. Outcomes were assessed at baseline and 8 weeks. Adherence was defined as the proportion of completed symptom reports: 'low' (≤24%); 'low-moderate' (25-49%); 'high-moderate' (50-75%); or 'high' (76-100%). Linear mixed models were applied for preliminary effectiveness analyses as per intention-to-treat. RESULTS: Adolescents (N = 60) were recruited from three paediatric rheumatology centres. Rates of accrual and attrition were 82 and 13%, respectively. Both apps were deployed with high success (over 85%) and were rated as highly acceptable. Adherence was similar for both groups, with most participants demonstrating moderate-to-high adherence. Both groups exhibited a clinically meaningful reduction in pain intensity (≥1 point) that did not statistically differ between groups. There were no significant changes in activity limitations or health-related quality of life. CONCLUSION: The iCanCope pilot randomized controlled trial was feasible to implement in a paediatric rheumatology setting. Both apps were deployed successfully, with high acceptability, and were associated with moderate-to-high adherence. Preliminary reductions in pain intensity warrant a future trial to evaluate effectiveness of iCanCope in improving health outcomes in adolescents with JIA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02764346.

Diffuse Small B-Cell Lymphoma: A High-Grade Malignancy.

The most common subtype of lymphoma in the dog is diffuse large B-cell lymphoma (DLBCL). The remaining forms of B-cell lymphoma in dogs are categorized as small-to-intermediate in size and include marginal zone, follicular, mantle cell, and small-cell lymphocytic lymphoma. Marginal zone lymphoma and follicular lymphoma have readily identifiable unique histologic features while other forms of small B-cell lymphoma in the dog are poorly described by histopathology. Forty-seven cases of nodal small B-cell lymphoma identified by flow cytometry (small cell size based on forward scatter) with concurrent histopathology were reviewed. These cases fell into 3 histologic subtypes: marginal zone lymphoma, follicular lymphoma, and a diffuse form of small B-cell lymphoma with consistent features. As a descriptive term, we refer to the latter subtype as diffuse small B-cell lymphoma (DSBCL) until it can be further characterized by gene expression profiling and other molecular tools. Clinical presentation of DSBCL was compared to cases of histologically confirmed DLBCL and clinical follow-up was obtained for 22 of the 27 cases of DSBCL. This subset of diffuse small B-cell lymphoma had an overall median survival of 140 days. The expression of CD21, class II MHC and CD25 by flow cytometry did not differ between DSBCL and the other histologic subtypes of small cell B-cell lymphoma making histopathology the only current method of classification.

Stigma in the face of cancer disfigurement: A systematic review and research agenda.

INTRODUCTION: An emerging body of work has reported on the psychological impact of disfigurement on cancer patients; however, the extent of research focusing on stigmatisation in this context is unclear. This review aimed to evaluate how stigma associated with disfigurement impacts on cancer patients. METHODS: A systematic review of literature was conducted using SCOPUS, Web of Science, MEDLINE and PubMed databases. Articles were included if they described a qualitative or quantitative study that investigated the impact of stigma and disfigurement on individuals with cancer and/or their families. Included studies were appraised for methodology and narratively synthesised. RESULTS: Of the 16 studies which met the inclusion criteria, ten were qualitative and six were quantitative. Publication dates ranged from 1994 to 2020. Results highlighted the varying impact of felt and enacted stigma in people with cancer disfigurement. While individuals cope with stigma in different ways and outcomes can sometimes be positive, most articles documented a negative impact to well-being including emotions such as disgust and shame. CONCLUSION: This review identified negative and (sometimes) positive consequences of disfigurement and stigma on cancer patients; however, the main finding is that relevant research is in its infancy. Several areas of future research are warranted.

Venous sinus thrombosis in traumatic brain injury: a major trauma centre experience.

BACKGROUND: This study explores the presentation, management and outcomes of traumatic venous sinus thrombosis (VST) and identifies risk factors associated with poor outcomes. METHODS: This study is a retrospective review of all patients with VST secondary to trauma who presented to a major trauma centre, between April 2015 and January 2020. VST was confirmed by CT venogram and a consultant neuroradiologist. RESULTS: Forty-six patients were identified (38 male), mean age of 43 (range 12-78) and median follow-up 10.2 months (range 0.7-39.1). Fifty-two percent presented as a severe traumatic brain injury, and all had an associated skull fractures overlying the sinus. Ninety-six percent had cerebral contusions, 96% had an intracranial haematoma, 91% had traumatic subarachnoid haemorrhage (tSAH) and 22% had acute cerebral infarction. Thirty-seven percent of the VSTs were occlusive. Fifty-eight percent had sustained, unprovoked intracranial pressure (ICP) spikes (> 20 mmHg). Fifty percent underwent surgical intervention-20% external ventricular drain and 46% craniotomy/craniectomy. Nine percent were treated with anticoagulation and 4% with antiplatelets, at a median of 13.5 days and 9.5 days post-injury, with no additional complications. Age > 60 was associated with poor outcome (GOS of 3-5) (p = 0.0098). On follow-up CT, 52% of the VSTs remained unchanged, 29% re-canalised, 14% improved and 5% worsened, independent of treatment. CONCLUSIONS: This study demonstrated a higher incidence of VST in severe TBI and strong associations with skull fractures, cerebral contusions, tSAH, raised ICP and surgical intervention. Management was inconsistent, with no difference in outcome with or without anticoagulation. Larger, prospective cohort studies are needed to better understand this condition and establish evidence-based guidelines.

Comparison between outcomes of endovascular and surgical treatments of ruptured anterior communicating artery aneurysms.

INTRODUCTION: The natural history and optimal treatment of previously ruptured anterior communicating artery (ACOM) aneurysms that recur is unknown. This study looks at rates of complications and recurrences of ruptured ACOM aneurysms treated endovascularly and surgically. MATERIALS AND METHODS: A retrospective observational study of all patients presenting to a single tertiary neurosurgical centre with the first presentation of subarachnoid haemorrhage (SAH) secondary to a ruptured ACOM aneurysm. Data was collected from November 2012 to September 2018 and included baseline demographics, aneurysm characteristics, management, complications, follow-up imaging, and clinical outcomes. RESULTS: 137 patients were included in the study. 113 aneurysms were coiled and 19 were clipped. Management decisions were taken by the multidisciplinary team based on aneurysm morphology or the presence of a haematoma exerting mass effect. There were 187.5 patient-years of follow-up, with a median of 3 years (range 0-73 months). Rates of vasospasm, infarction, CSF diversion, rebleed, length of stay, and functional outcome were not significantly different in the two cohorts. There was a statistically significant increase in the risk of ACOM recurrence in the coiled group when compared to the clipped group at one year (p = .0433). 15 patients required further treatment at a median time of 16 months. In a subgroup group analysis of coiled aneurysms, there was no statistical differences in rates of rebleeding or the functional outcome in those that had aneurysm recurrence and those that did not. CONCLUSIONS: This study suggests patients with aneurysms treated by endovascular coiling have an increased risk of recurrence versus those treated with clipping. However, the risk of rebleed was not statistically significant. The prevention and impact of recurrence and residual aneurysms remains incompletely understood. Hence, treatment decisions should be taken by patients after they have been given carefully considered recommendations from the multi-disciplinary team.

Fusion rates for conservative and surgical management of type II odontoid fractures and its impact.

BACKGROUND: Type II odontoid fractures are known to have low fusion rates following conservative management with a hard collar. However, most patients are elderly with comorbidities and are not fit for surgery. The present study identified the rates of bony fusion, complications, and clinical outcomes following conservative management of type II odontoid fractures. METHODS: We included consecutive patients referred with a suspected odontoid fracture to a Major Trauma Centre in the UK between March 2015 and December 2017. Data including patient demographics, fracture management, complications and outcomes. Bony fusion was assessed by two neurosurgeons and one neuroradiologists. Results were analysed with simple statistics and chi-squared test. RESULTS: 102 patients were included in the study (mean age = 80.4 ± 15.3). 10 (9.8%) were managed surgically and 92 (90.2%) were managed conservatively with a hard collar, for a mean of 87 days. Patients were followed up for a mean of 28.1 months (range 1-855 days) until discharge. 37% developed collar complications, namely pain, stiffness and non-tolerance. Bony union was achieved in 37.3% of patients treated with a hard collar (versus 80% in the surgical group, p = 0.0096). Increasing age was an independent risk factor for non-union (p < 0.001). Of the patients without bony union, none reported symptoms, and 90% were discharged without a collar. CONCLUSION: The management of type II odontoid fractures are difficult in an elderly, co-morbid population. With conservative management fusion rates are low, and collar complications are not insignificant. However, outcomes are good regardless of union.

Progressive gammopathy and coagulopathy in a young English bulldog.

A restricted polyclonal or biclonal gammopathy resulting in bleeding tendencies was diagnosed in a young, neutered male English bulldog with concurrent splenomegaly, anemia, and severe elevations in IgM and, to a lesser degree, IgA immunoglobulins. There was a positive clinical response to treatment with prednisone and chlorambucil. This case bears similarity to a recently published syndrome of polyclonal gammopathy that is not neoplastic in origin in this breed. Key clinical message: The current case describes the management and clinical course of a recently described syndrome of polyclonal gammopathy in English bulldogs.

Gammapathie et coagulopathie progressives chez un jeune bouledogue Anglais. Une gammapathie polyclonale restreinte ou biclonale résultant en une tendance aux saignements fut diagnostiquée chez un jeune bouledogue Anglais mâle castré, avec une splénomégalie concomitante, de l'anémie et une augmentation sévère des immunoglobulines IgM et, à un degré moindre, des IgA. Une réponse clinique positive au traitement avec de la prednisone et du chlorambucil fut notée. Ce cas comporte des similarités avec un syndrome récemment décrit de gammapathie polyclonale qui ne serait pas d'origine néoplasique chez cette espèce.Message clinique clé :Le présent cas décrit la gestion et l'évolution clinique d'un syndrome récemment décrit de gammapathie polyclonale chez les bouledogues Anglais.(Traduit par Dr Serge Messier).

Influence of Expected Reward on Temporal Order Judgment.

Perceptual decision-making has been shown to be influenced by reward expected from alternative options or actions, but the underlying neural mechanisms are currently unknown. More specifically, it is debated whether reward effects are mediated through changes in sensory processing, later stages of decision-making, or both. To address this question, we conducted two experiments in which human participants made saccades to what they perceived to be either the first or second of two visually identical but asynchronously presented targets while we manipulated expected reward from correct and incorrect responses on each trial. By comparing reward-induced bias in target selection (i.e., reward bias) during the two experiments, we determined whether reward caused changes in sensory or decision-making processes. We found similar reward biases in the two experiments indicating that reward information mainly influenced later stages of decision-making. Moreover, the observed reward biases were independent of the individual's sensitivity to sensory signals. This suggests that reward effects were determined heuristically via modulation of decision-making processes instead of sensory processing. To further explain our findings and uncover plausible neural mechanisms, we simulated our experiments with a cortical network model and tested alternative mechanisms for how reward could exert its influence. We found that our experimental observations are more compatible with reward-dependent input to the output layer of the decision circuit. Together, our results suggest that, during a temporal judgment task, reward exerts its influence via changing later stages of decision-making (i.e., response bias) rather than early sensory processing (i.e., perceptual bias).

Treatment decisions in women of childbearing age on valproate.

INTRODUCTION: There are little data on the understanding and participation of women of childbearing age in decisions about their choice of antiepileptic drugs (AEDs). Valproate carries a risk of major congenital malformations, developmental and behavioural delay. For some, valproate is the only medication to prevent potentially life-threatening seizures. MATERIALS & METHODS: This was a cross-sectional study of two groups of women of childbearing age; 50 taking valproate and 50 controls. Each patient completed a patient questionnaire and structured telephone interview assessing understanding of the risks and benefits of AEDs in relation to pregnancy. Analysis used unpaired two-tailed t test and chi-squared test, with Bonferroni correction. Follow-up at 12 months showed that 8% of the women taking valproate had switched to other medication. RESULTS: Hundred patients participated in the study, 89 on AEDs for epilepsy, 4 for migraine, and 7 for both. 55% of participants stated they were not involved in decision-making. More patients in the valproate group were informed about (64% vs 42%, P < .005), and expressed understanding of (64%vs 32%, P < .001), the risks involved with treatment. 59% of all patients wanted more information. The minority of women surveyed took folic acid (37%) or used contraceptives (29%). Valproate was used following failure of other AEDs to control seizures in 80%. DISCUSSION: This in-depth survey suggests more information is needed for women taking AEDs, using a range of formats. Women taking valproate are better informed than those on levetiracetam or lamotrigine. Information provision on the use of folic acid and contraception needs improvement.

Emotion regulation accounts for associations between mindfulness and depression across and within diagnostic categories.

BACKGROUND: Previous research shows that mindfulness and emotion regulation (ER) are highly related to each other. Preliminary evidence in small clinical populations show that ER may partially account for the relationship between mindfulness and depressive symptoms. The present study aimed to investigate which diagnostic categories were associated with depressive symptoms after controlling for ER in a heterogeneous sample of treatment-seeking patients. METHODS: A large sample of psychiatric outpatients (N = 911) completed the Structured Clinical Interview for DSM-IV (SCID), Five Facet Mindfulness Questionnaire (FFMQ), Difficulties in Emotion Regulation Scale (DERS), and Clinically Useful Depression Outcome Scale (CUDOS). Partial correlations were conducted to evaluate to what degree the relationship between depression scores and facets of mindfulness were accounted for by ER scores. RESULTS: When controlling for baseline mindfulness, the relationship between emotion dysregulation and depression symptoms remained significant for all data points; however, when controlling for baseline emotion dysregulation, the association between mindfulness and depression was not significant in the majority of cases. Nonjudging was most resistant to this result. CONCLUSIONS: Although mindfulness is negatively associated with depressive symptoms, this association may be better accounted for by emotion dysregulation.