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3.  Coronary Revascularization in Lung Transplant Recipients With Concomitant Coronary Artery Disease 
Coronary artery disease (CAD) is not uncommon among lung transplant candidates. Several small, single-center series have suggested that short-term outcomes are acceptable in selected patients who undergo coronary revascularization prior to, or concomitant with, lung transplantation. Our objective was to evaluate perioperative and intermediate-term outcomes in this patient population at our institution. We performed a retrospective, observational cohort analysis of 898 lung transplant recipients between 1997 and 2010. Pediatric, multivisceral, lobar or repeat transplantations were excluded, resulting in 791 patients for comparative analysis, of which 49 (median age 62, 79.6% bilateral transplant) underwent concurrent coronary artery bypass and 38 (median age 64, 63.2% bilateral transplant) received preoperative percutaneous coronary intervention (PCI). Perioperative mortality, overall unadjusted survival and adjusted hazard ratio for cumulative risk of death were similar among both revascularization groups as well as controls. The rate of postoperative major adverse cardiac events was also similar among groups; however, concurrent coronary artery bypass was associated with longer postoperative length of stay, more time in the intensive care unit and more postoperative days requiring ventilator support. These results suggest that patients with CAD need not be excluded from lung transplantation. Preferential consideration should be given to preoperative PCI when feasible.
doi:10.1111/ajt.12435
PMCID: PMC4332513  PMID: 24102830
Cardiac disease in transplant; coronary artery disease; lung transplant; revascularization; surgery—heart; lung; transplant
4.  Molecular cloning, characterisation and mRNA expression of the ryanodine receptor from the peach-potato aphid, Myzus persicae 
Gene  2015;556(2):106-112.
The peach potato aphid, Myzus persicae, is one of the most important agricultural pests of temperate climates. It is mainly controlled through the judicious application of insecticides; however, over time, aphids have developed resistance to many insecticidal classes. The recent introduction of synthetic diamide insecticides, with a novel mode of action, potentially offers new tools to control aphid populations. These diamides act on the ryanodine receptor (RyR), a large endoplasmic calcium release channel. In this study we have cloned cDNAs encoding the complete open reading frame of the RyR from M. persicae. The open reading frame is 15,306 base pairs long and encodes a protein of 5101 amino acids. The aphid RyR shares many of the features of other insect and vertebrate RyRs, including a highly conserved transmembrane region. However, unlike the other RyRs characterised to date, the M. persicae channel does not display alternative splicing at any stage of its developmental cycle, so it cannot generate functional variants of the channel.
Highlights
•We obtained the full-length cDNA sequence of the M. persicae RyR.•The ORF is 15,306 bp long and encodes a protein of 5101 amino acids.•The aphid RyR shares many common features with other insect and vertebrate RyRs.•The aphid channel does not display alternative splicing at any developmental stage.•Aphids cannot generate variants of the RyR channel, unlike other insects.
doi:10.1016/j.gene.2014.11.035
PMCID: PMC4309888  PMID: 25447916
Ryanodine receptor; Insect; Diamide insecticides; Alternative splicing; Aphid
5.  The effects of amount of home meditation practice in Mindfulness Based Cognitive Therapy on hazard of relapse to depression in the Staying Well after Depression Trial 
Few empirical studies have explored the associations between formal and informal mindfulness home practice and outcome in Mindfulness-based Cognitive Therapy (MBCT). In this study ninety-nine participants randomised to MBCT in a multi-centre randomised controlled trial completed self-reported ratings of home practice over 7 treatment weeks. Recurrence of Major Depression was assessed immediately after treatment, and at 3, 6, 9, and 12-months post-treatment. Results identified a significant association between mean daily duration of formal home practice and outcome and additionally indicated that participants who reported that they engaged in formal home practice on at least 3 days a week during the treatment phase were almost half as likely to relapse as those who reported fewer days of formal practice. These associations were independent of the potentially confounding variable of participant-rated treatment plausibility. The current study identified no significant association between informal home practice and outcome, although this may relate to the inherent difficulties in quantifying informal home mindfulness practice. These findings have important implications for clinicians discussing mindfulness-based interventions with their participants, in particular in relation to MBCT, where the amount of participant engagement in home practice appears to have a significant positive impact on outcome.
Highlights
•We examine the relation between home practice and outcome in people receiving MBCT.•Formal home practice is negatively associated with hazard of relapse to depression.•Those who engage in such practice at least three days/week approximately halve hazard of relapse.•Informal home practice was unrelated to risk of relapse to major depression.•Effects of formal home practice on outcome are not confounded with treatment plausibility.
doi:10.1016/j.brat.2014.08.015
PMCID: PMC4271738  PMID: 25261599
Mindfulness Based Cognitive Therapy; Depression; Recurrence; Home practice
6.  Childhood traumatic events and adolescent overgeneral autobiographical memory: Findings in a UK cohort 
Background
Overgeneral autobiographical memory has repeatedly been identified as a risk factor for adolescent and adult psychopathology but the factors that cause such over-generality remain unclear. This study examined the association between childhood exposure to traumatic events and early adolescent overgeneral autobiographical memory in a large population sample.
Methods
Thirteen-year-olds, n = 5,792, participating in an ongoing longitudinal cohort study (ALSPAC) completed a written version of the Autobiographical Memory Test. Performance on this task was examined in relation to experience of traumatic events, using data recorded by caregivers close to the time of exposure.
Results
Results indicated that experiencing a severe event in middle childhood increased the likelihood of an adolescent falling into the lowest quartile for autobiographical memory specificity (retrieving 0 or 1 specific memory) at age 13 by approximately 60%. The association persisted after controlling for a range of potential socio-demographic confounders.
Limitations
Data on the traumatic event exposures was limited by the relatively restricted range of traumas examined, and the lack of contextual details surrounding both the traumatic event exposures themselves and the severity of children's post-traumatic stress reactions.
Conclusions
This is the largest study to date of the association between childhood trauma exposure and overgeneral autobiographical memory in adolescence. Findings suggest a modest association between exposure to traumatic events and later overgeneral autobiographical memory, a psychological variable that has been linked to vulnerability to clinical depression.
Highlights
•Overgeneral autobiographical memory has been linked to trauma in childhood.•We examined associations between low AMT score and trauma exposure at age 13.•A severe middle childhood life event increased likelihood of low AMT by 60%.•This association was not appreciably attenuated after adjustment for confounders.
doi:10.1016/j.jbtep.2014.02.004
PMCID: PMC4053588  PMID: 24657714
Memory; Adolescence; Trauma; Depression; ALSPAC
7.  Who mixes with whom among men who have sex with men? Implications for modelling the HIV epidemic in southern India 
Journal of Theoretical Biology  2014;355(100):140-150.
In India, the identity of men who have sex with men (MSM) is closely related to the role taken in anal sex (insertive, receptive or both), but little is known about sexual mixing between identity groups. Both role segregation (taking only the insertive or receptive role) and the extent of assortative (within-group) mixing are known to affect HIV epidemic size in other settings and populations. This study explores how different possible mixing scenarios, consistent with behavioural data collected in Bangalore, south India, affect both the HIV epidemic, and the impact of a targeted intervention. Deterministic models describing HIV transmission between three MSM identity groups (mostly insertive Panthis/Bisexuals, mostly receptive Kothis/Hijras and versatile Double Deckers), were parameterised with behavioural data from Bangalore. We extended previous models of MSM role segregation to allow each of the identity groups to have both insertive and receptive acts, in differing ratios, in line with field data. The models were used to explore four different mixing scenarios ranging from assortative (maximising within-group mixing) to disassortative (minimising within-group mixing). A simple model was used to obtain insights into the relationship between the degree of within-group mixing, R0 and equilibrium HIV prevalence under different mixing scenarios. A more complex, extended version of the model was used to compare the predicted HIV prevalence trends and impact of an HIV intervention when fitted to data from Bangalore. With the simple model, mixing scenarios with increased amounts of assortative (within-group) mixing tended to give rise to a higher R0 and increased the likelihood that an epidemic would occur. When the complex model was fit to HIV prevalence data, large differences in the level of assortative mixing were seen between the fits identified using different mixing scenarios, but little difference was projected in future HIV prevalence trends. An oral pre-exposure prophylaxis (PrEP) intervention was modelled, targeted at the different identity groups. For intervention strategies targeting the receptive or receptive and versatile MSM together, the overall impact was very similar for different mixing patterns. However, for PrEP scenarios targeting insertive or versatile MSM alone, the overall impact varied considerably for different mixing scenarios; more impact was achieved with greater levels of disassortative mixing.
Highlights
•Different mixing scenarios are explored for 3 groups of role-segregated MSM.•Models show that the mixing scenario affects both R0 and endemic HIV prevalence.•When models are fit to data, predicted HIV trends are unaffected by mixing.•Impact of targeted (but not non-targeted) interventions can be affected by mixing.
doi:10.1016/j.jtbi.2014.04.005
PMCID: PMC4064301  PMID: 24727187
Mathematical model; Mixing matrix; Sexually transmitted infection; Disassortative mixing; Pre-exposure prophylaxis
8.  Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma 
Purpose
Sunitinib is a first-line advanced renal cell carcinoma (RCC) standard of care. In a randomized phase II trial comparing sunitinib treatment schedules, separate exploratory biomarker analyses investigated the correlations of efficacy with selected serum, germ line single-nucleotide polymorphism (SNP), or tumor markers.
Methods
Advanced RCC patients received first-line sunitinib 50 mg/day on the approved 4-week-on-2-week-off schedule (n = 146) or 37.5 mg/day continuous dosing (n = 146). The following correlation analyses were performed: (1) response evaluation criteria in solid tumors-defined tumor response with serum soluble protein levels via two distinct multiplex (n < 1,000) platforms; (2) response and time-to-event outcomes with germ line SNPs in vascular endothelial growth factor (VEGF)-A and VEGF receptor (VEGFR)3 genes; and (3) response and time-to-event outcomes with tumor immunohistochemistry status for hypoxia-inducible factor 1-alpha (HIF-1α) and carbonic anhydrase-IX or tumor Von Hippel–Lindau (VHL) gene inactivation status.
Results
Lower baseline angiopoietin-2 (Ang-2) and higher baseline matrix metalloproteinase-2 (MMP-2) levels were identified by both platforms as statistically significantly associated with tumor response. There were no significant correlations between VEGF-A or VEGFR3 SNPs and outcomes. Progression-free survival was longer for HIF-1α percent of tumor expression groups 0–2 (HIF-1α low) versus 3–4 (HIF-1α high; p = 0.034). There were no significant correlations between outcomes and each VHL inactivation mechanism [mutation (86 % of VHL-inactive patients), methylation (14 %), and large deletion (7 %)] or mechanisms combined.
Conclusions
Serum Ang-2 and MMP-2 and tumor HIF-1α were identified as relevant baseline biomarkers of sunitinib activity in advanced RCC, warranting further research into their prognostic versus predictive value.
Electronic supplementary material
The online version of this article (doi:10.1007/s00280-014-2539-0) contains supplementary material, which is available to authorized users.
doi:10.1007/s00280-014-2539-0
PMCID: PMC4175044  PMID: 25100134
Sunitinib; Renal cell carcinoma; Serum marker; Germ line polymorphism marker; Tumor marker
9.  An Evaluation of the Effectiveness of Recruitment Methods: The Staying Well after Depression Randomized Controlled Trial 
Clinical trials (London, England)  2014;11(2):141-149.
Background
Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited and trials often fail to report sufficient details about the recruitment sources and resources utilised.
Purpose
We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression.
Methods
We describe eight recruitment methods utilised and two further sources not initiated by the research team and examine their efficacy in terms of (i) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial, (ii) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants, and (iii) comparison of sociodemographic characteristics of individuals recruited from different sources.
Results
Poster advertising, web-based advertising and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important.
Limitations
It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations.
Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated.
Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed.
Conclusions
Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs.
doi:10.1177/1740774514521905
PMCID: PMC4110646  PMID: 24686105
Recruitment; randomized controlled trial; RCT; methodology; cost effectiveness
10.  Gene Therapy Prolongs Survival and Restores Function in Murine and Canine Models of Myotubular Myopathy 
Science translational medicine  2014;6(220):220ra10.
Loss-of-function mutations in the myotubularin gene (MTM1) cause X-linked myotubular myopathy (XLMTM), a fatal, congenital pediatric disease that affects the entire skeletal musculature. Systemic administration of a single dose of a recombinant serotype-8 adeno-associated virus (AAV8) vector expressing murine myotubularin to Mtm1-deficient knockout mice at the onset or at late stages of the disease resulted in robust improvement in motor activity and contractile force, corrected muscle pathology and prolonged survival throughout a 6-month study. Similarly, single-dose intravascular delivery of a canine AAV8-MTM1 vector in XLMTM dogs markedly improved severe muscle weakness and respiratory impairment, and prolonged lifespan to more than one year in the absence of toxicity, humoral and cell-mediated immune response. These results demonstrate the therapeutic efficacy of AAV-mediated gene therapy for myotubular myopathy in small and large animal models, and provide proof of concept for future clinical trials in XLMTM patients.
doi:10.1126/scitranslmed.3007523
PMCID: PMC4105197  PMID: 24452262
11.  Trait Mindfulness as a Limiting Factor for Residual Depressive Symptoms: An Explorative Study Using Quantile Regression 
PLoS ONE  2014;9(7):e100022.
Mindfulness has been suggested to be an important protective factor for emotional health. However, this effect might vary with regard to context. This study applied a novel statistical approach, quantile regression, in order to investigate the relation between trait mindfulness and residual depressive symptoms in individuals with a history of recurrent depression, while taking into account symptom severity and number of episodes as contextual factors. Rather than fitting to a single indicator of central tendency, quantile regression allows exploration of relations across the entire range of the response variable. Analysis of self-report data from 274 participants with a history of three or more previous episodes of depression showed that relatively higher levels of mindfulness were associated with relatively lower levels of residual depressive symptoms. This relationship was most pronounced near the upper end of the response distribution and moderated by the number of previous episodes of depression at the higher quantiles. The findings suggest that with lower levels of mindfulness, residual symptoms are less constrained and more likely to be influenced by other factors. Further, the limiting effect of mindfulness on residual symptoms is most salient in those with higher numbers of episodes.
doi:10.1371/journal.pone.0100022
PMCID: PMC4079585  PMID: 24988072
12.  Association of aberrant neural synchrony and altered GAD67 expression following exposure to maternal immune activation, a risk factor for schizophrenia 
Translational Psychiatry  2014;4(7):e418-.
A failure of integrative processes within the brain, mediated via altered GABAergic inhibition, may underlie several features of schizophrenia. The present study examined, therefore, whether maternal immune activation (MIA), a risk factor for schizophrenia, altered inhibitory markers in the hippocampus and medial prefrontal cortex (mPFC), while also altering electroencephalogram (EEG) coherence between these regions. Pregnant rats were treated with saline or polyinosinic:polycytidylic acid mid-gestation. EEG depth recordings were made from the dorsal and ventral hippocampus and mPFC of male adult offspring. Glutamic decarboxylase (GAD67) levels were separately assayed in these regions using western blot. GAD67 expression was also assessed within parvalbumin-positive cells in the dorsal and ventral hippocampus using immunofluorescence alongside stereological analysis of parvalbumin-positive cell numbers. EEG coherence was reduced between the dorsal hippocampus and mPFC, but not the ventral hippocampus and mPFC, in MIA animals. Western blot and immunofluorescence analyses revealed that GAD67 expression within parvalbumin-positive cells was also reduced in the dorsal hippocampus relative to ventral hippocampus in MIA animals when compared with controls. This reduction was observed in the absence of parvalbumin-positive neuronal loss. Overall, MIA produced a selective reduction in EEG coherence between the dorsal hippocampus and mPFC that was paralleled by a similarly specific reduction in GAD67 within parvalbumin-positive cells of the dorsal hippocampus. These results suggest a link between altered inhibitory mechanisms and synchrony and, therefore point to potential mechanisms via which a disruption in neurodevelopmental processes might lead to pathophysiology associated with schizophrenia.
doi:10.1038/tp.2014.64
PMCID: PMC4119228  PMID: 25072323
13.  Evaluation of a modified Fitts law BCI target acquisition task in able and motor disabled individuals 
Journal of neural engineering  2009;6(5):056002.
A brain-computer interface (BCI) is a communication system that takes recorded brain signals and translates them into real-time actions, in this case movement of a cursor on a computer screen. This work applied Fitts’ law to the evaluation of performance on a target acquisition task during sensorimotor rhythm-based BCI training. Fitts’ law, which has been used as a predictor of movement time in studies of human movement, was used here to determine the information transfer rate, which was based on target acquisition time and target difficulty. The information transfer rate was used to make comparisons between control modalities and subject groups on the same task. Data were analyzed from eight able-bodied and five motor disabled participants who wore an electrode cap that recorded and translated their electroencephalogram (EEG) signals into computer cursor movements. Direct comparisons were made between able-bodied and disabled subjects and between EEG and joystick cursor control in able-bodied subjects. Fitts’ law aptly described the relationship between movement time and index of difficulty for each task movement direction when evaluated separately and averaged together. This study showed that Fitts’ law can be successfully applied to computer cursor movement controlled by neural signals.
doi:10.1088/1741-2560/6/5/056002
PMCID: PMC4075430  PMID: 19700814
14.  Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism 
The Journal of Physiology  2013;591(Pt 11):2911-2923.
Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses–fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is ‘sensed’ have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-13C2]Leu and [2H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A–V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70%vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling ≤90 min vs. ≤30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; −57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu.
doi:10.1113/jphysiol.2013.253203
PMCID: PMC3690694  PMID: 23551944
15.  Executive dysfunction and autobiographical memory retrieval in recovered depressed women☆ 
Background and objectives
Depressed individuals have difficulty remembering specific autobiographical events. These deficits often persist after recovery of mood symptoms, but the mechanisms underlying impaired memory specificity in recovered depressed individuals remain unclear. Here, we sought to examine whether performance on two cognitive measures might be related to deficits in autobiographical memory retrieval in individuals with a history of depression.
Methods
Twenty-four recovered depressed women (12 with more than one previous episode) and 24 never depressed women completed two cognitive measures (Digit Span and a Number Generation Task) and tests of autobiographical memory recall.
Results
Overall, the recovered depressed women did not show deficits in autobiographical retrieval. However, those with more than one previous episode had impaired retrieval of categorical autobiographical memories. Moreover, depression history moderated the relationship between Digit Span and retrieval of categoric autobiographical memories such that within the whole recovered depressed group (but not the never depressed group), those with lower Digit Span also had poorer retrieval of categorical autobiographical memories.
Limitations
Our sample size was small and included only women. Moreover, order effects may have been a significant factor.
Conclusions
These findings support the notion that working memory is an important factor in impairing autobiographical memory in those who have recovered from depression, but suggest a complex relationship with autobiographical recall.
Highlights
•Recovered depressed women had no autobiographical memory (ABM) specificity deficits.•Women with more than 1 past episode had categorical ABM deficits.•In recovered depressed women, low categorical ABM correlated with worse Digit Span.•The findings suggest a complex relationship between working memory and ABM.
doi:10.1016/j.jbtep.2013.12.001
PMCID: PMC3989034  PMID: 24374578
Depression; Recovered depressed; Autobiographical memory; Executive dysfunction; Female
16.  Mindfulness-Based Cognitive Therapy for Preventing Relapse in Recurrent Depression: A Randomized Dismantling Trial 
Objective: We compared mindfulness-based cognitive therapy (MBCT) with both cognitive psychological education (CPE) and treatment as usual (TAU) in preventing relapse to major depressive disorder (MDD) in people currently in remission following at least 3 previous episodes. Method: A randomized controlled trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus TAU, CPE plus TAU, and TAU alone, and data were analyzed for the 255 (93%; MBCT = 99, CPE = 103, TAU = 53) retained to follow-up. MBCT was delivered in accordance with its published manual, modified to address suicidal cognitions; CPE was modeled on MBCT, but without training in meditation. Both treatments were delivered through 8 weekly classes. Results: Allocated treatment had no significant effect on risk of relapse to MDD over 12 months follow-up, hazard ratio for MBCT vs. CPE = 0.88, 95% CI [0.58, 1.35]; for MBCT vs. TAU = 0.69, 95% CI [0.42, 1.12]. However, severity of childhood trauma affected relapse, hazard ratio for increase of 1 standard deviation = 1.26 (95% CI [1.05, 1.50]), and significantly interacted with allocated treatment. Among participants above median severity, the hazard ratio was 0.61, 95% CI [0.34, 1.09], for MBCT vs. CPE, and 0.43, 95% CI [0.22, 0.87], for MBCT vs. TAU. For those below median severity, there were no such differences between treatment groups. Conclusion: MBCT provided significant protection against relapse for participants with increased vulnerability due to history of childhood trauma, but showed no significant advantage in comparison to an active control treatment and usual care over the whole group of patients with recurrent depression.
doi:10.1037/a0035036
PMCID: PMC3964149  PMID: 24294837
mindfulness-based cognitive therapy; major depression; relapse prevention; suicidality; childhood trauma
17.  Psychological Processes and Repeat Suicidal Behavior: A Four-Year Prospective Study 
Objective: Although suicidal behavior is a major public health concern, understanding of individually sensitive suicide risk mechanisms is limited. In this study, the authors investigated, for the first time, the utility of defeat and entrapment in predicting repeat suicidal behavior in a sample of suicide attempters. Method: Seventy patients hospitalized after a suicide attempt completed a range of clinical and psychological measures (depression, hopelessness, suicidal ideation, defeat, and entrapment) while in hospital. Four years later, a nationally linked database was used to determine who had been hospitalized again after a suicide attempt. Results: Over 4 years, 24.6% of linked participants were readmitted to hospital after a suicidal attempt. In univariate logistic regression analyses, defeat and entrapment as well as depression, hopelessness, past suicide attempts, and suicidal ideation all predicted suicidal behavior over this interval. However, in the multivariate analysis, entrapment and past frequency of suicide attempts were the only significant predictors of suicidal behavior. Conclusions: This longitudinal study supports the utility of a new theoretical model in the prediction of suicidal behavior. Individually sensitive suicide risk processes like entrapment could usefully be targeted in treatment interventions to reduce the risk of repeat suicidal behavior in those who have been previously hospitalized after a suicide attempt.
doi:10.1037/a0033751
PMCID: PMC3933214  PMID: 23855989
suicidal; longitudinal; cognition; defeat; entrapment
18.  Effects of Mindfulness on Meta-Awareness and Specificity of Describing Prodromal Symptoms in Suicidal Depression 
Emotion (Washington, D.C.)  2010;10(1):34-42.
The authors examined the effects of mindfulness training on 2 aspects of mode of processing in depressed participants: degree of meta-awareness and specificity of memory. Each of these has been suggested as a maladaptive aspect of a mode of processing linked to persistence and recurrence of symptoms. Twenty-seven depressed participants, all of whom had experienced suicidal crises, described warning signs for their last crisis. These descriptions were blind-rated independently for meta-awareness and specificity. Participants were then randomly allocated to receive mindfulness-based cognitive therapy (MBCT) plus treatment as usual (TAU) or TAU alone, and retested after 3 months. Results showed that, although comparable at baseline, patients randomized to MBCT displayed significant posttreatment differences in meta-awareness and specificity compared with TAU patients. These results suggest that mindfulness training may enable patients to reflect on memories of previous crises in a detailed and decentered way, allowing them to relate to such experiences in a way that is likely to be helpful in preventing future relapses.
doi:10.1037/a0016825
PMCID: PMC3933215  PMID: 20141300
suicidality; depression; relapse; meta-awareness; memory specificity; mindfulness
19.  Obesity prevention in defined (high school) populations 
Background
A challenge for the widespread dissemination of Internet-based programs designed to produce weight maintenance/loss in defined (high school) populations is to adapt them to local needs and interests, whereas demonstrating effectiveness and salience for both universal and targeted populations.
Objective
The objective of this study is to examine the feasibility of providing an inexpensive, Internet-based universal (healthy weight regulation) and targeted (weight maintenance/loss) health program to all ninth-grade students in a high school serving a lower socioecnomic status, diverse population.
Design
A total of 118 normal-weight and 64 overweight/obese students in the same ninth-grade class completed a baseline screen and were allocated to a healthy weight regulation program or a weight-loss maintenance program. Both groups simultaneously received a 10-week Internet-based intervention. Program implementation required minimal teacher time. Measurement included self-reported fruit, vegetable and high-fat/-calorie food consumption, self-reported change in body mass index (BMI), weight and shape concerns, as well as program engagement.
Results
The program was successfully implemented in nine classes, with minimal help from the investigators. There was a significant increase in self-reported consumption of fruits and vegetables (P=0.001). There was a significant reduction in self-reported BMI in the overweight/obese group (P=0.001). Students found the program helpful and engaging. There was a significant reduction in weight and shape concerns in the high-risk female students, consistent with a reduced risk for the development of an eating disorder. Providing a universal and targeted online healthy weight regulation program to ninth-grade students is feasible and inexpensive. The results suggest the program can serve as ‘core’ for future studies using adaptive, continuous quality-improvement designs.
doi:10.1038/ijosup.2012.8
PMCID: PMC3932060  PMID: 24567839
20.  A Sense of Embodiment Is Reflected in People's Signature Size 
PLoS ONE  2014;9(2):e88438.
Background
The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined.
Methods/Results
We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations.
Conclusions
Together, these findings suggest that a person's sense of embodiment is reflected in their signature size.
doi:10.1371/journal.pone.0088438
PMCID: PMC3922804  PMID: 24533088
21.  Monoamine Oxidase is a Major Determinant of Redox Balance in Human Atrial Myocardium and is Associated With Postoperative Atrial Fibrillation 
Background
Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high‐risk patients, remains elusive.
Methods and Results
Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH‐peroxidase (GPx) and GSH‐reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10‐fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk.
Conclusions
Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis.
doi:10.1161/JAHA.113.000713
PMCID: PMC3959694  PMID: 24572256
biomarkers; cardiopulmonary bypass; catecholamines; oxidative stress; post‐operative atrial fibrillation; redox; tachyarrhythmias
22.  Comfort from suicidal cognition in recurrently depressed patients☆ 
Journal of Affective Disorders  2014;155(100):241-246.
Background
Previous research has suggested that some individuals may obtain comfort from their suicidal cognitions.
Method
This study explored clinical variables associated with comfort from suicidal cognition using a newly developed 5 item measure in 217 patients with a history of recurrent depression and suicidality, of whom 98 were followed up to at least one relapse to depression and reported data on suicidal ideation during the follow-up phase.
Results
Results indicated that a minority of patients, around 15%, reported experiencing comfort from suicidal cognitions and that comfort was associated with several markers of a more severe clinical profile including both worst ever prior suicidal ideation and worst suicidal ideation over a 12 month follow-up period.
Limitations
Few patients self-harmed during the follow-up period preventing an examination of associations between comfort and repetition of self-harm.
Conclusions
These results, although preliminary, suggest that future theoretical and clinical research would benefit from further consideration of the concept of comfort from suicidal thinking.
doi:10.1016/j.jad.2013.11.006
PMCID: PMC3972436  PMID: 24289891
Suicidality; Depression; Cognition; Comfort
23.  Genetic Modification of Primate Amniotic Fluid-derived Stem Cells Produces Pancreatic Progenitor Cells in vitro 
Cells, tissues, organs  2013;197(4):269-282.
Insulin therapy for Type 1 diabetes (T1D) does not prevent serious long-term complications including vascular disease, neuropathy, retinopathy and renal failure. Stem cells, including amniotic fluid-derived stem (AFS) cells--highly expansive, multipotent, and non-tumorigenic cells--could serve as an appropriate stem cell source for β-cell differentiation. In the current study we tested whether nonhuman primate (nhp) AFS cells ectopically expressing key pancreatic transcription factors were capable of differentiating into a beta-like cell phenotype in vitro. NHPAFS cells were obtained from Cynomolgus monkey amniotic fluid by immunomagnetic selection for a CD117 (c-kit) positive population. RT-PCR for endodermal and pancreatic lineage-specific markers was performed on AFS cells after adenovirally transduced expression of PDX1, NGN3 and MAFA. Expression of MAFA was sufficient to induce insulin mRNA expression in nhpAFS cell lines, whereas a combination of MAFA, PDX1 and NGN3further induced insulin expression, as well as induced the expression of other important endocrine cell genes such as glucagon, NEUROD1, NKX2.2, ISL1 and PCSK2. Higher induction of these and other important pancreatic genes was achieved by growing the triply infected AFS cells in media supplemented with a combination of B27, betacellulin and nicotinamide, as well as culturing the cells on extra-cellular matrix coated plates. The expression of pancreatic genes such as NEUROD1, glucagon and insulin progressively decreased with the decline of adenovirally-expressed PDX1, NGN3 and MAFA. Together, these experiments suggest that forced expression of pancreatic transcription factors in primate AFS cells induces them towards the pancreatic lineage.
doi:10.1159/000345816
PMCID: PMC3725583  PMID: 23306211
amniotic fluid stem cells; differentiation; diabetes; pancreas; beta-cells; cell therapy; nonhuman primates
24.  A comparison of vulnerability factors in patients with persistent and remitting lifetime symptom course of depression☆ 
Journal of Affective Disorders  2014;152-154(100):155-161.
Background
Research has suggested fundamental differences between patients with persistent and those with remitting courses of depression. This study investigated whether patients with different lifetime symptom course configurations differ in early risk and cognitive vulnerability factors.
Methods
Patients with at least three previous episodes who were currently in remission were categorized based on visual timelines of their lifetime symptom course and compared with regard to a number of different indicators of vulnerability including questionnaire measures of childhood trauma and experiential avoidance.
Results
Of the N=127 patients, n=47 showed a persistent course of the disorder with unstable remissions and symptoms most of the time, and n=59 showed a course with more stable, lasting remissions. Group comparisons indicated that patients with a more persistent course were significantly more likely to have suffered from childhood emotional abuse, and reported higher levels of experiential avoidance as well as related core beliefs. Experiential avoidance partially mediated the effect of childhood emotional abuse on persistence of symptoms.
Limitations
The study is cross-sectional and does not allow conclusions with regard to whether differentiating variables are causally related to chronicity. Self-report measures may be subject to reporting biases.
Conclusions
The results highlight the detrimental effects of childhood adversity and suggest that experiential avoidance may play an important role in mediating such effects.
doi:10.1016/j.jad.2013.09.001
PMCID: PMC3878770  PMID: 24183488
Depression; Lifetime course; Chronicity; Experiental avoidance; Childhood adversity
25.  Diagnostic yield of colonoscopy to evaluate melena after a nondiagnostic EGD 
Gastrointestinal endoscopy  2012;75(4):10.1016/j.gie.2011.11.041.
Background
Melena can be caused by bleeding from lower GI sources. Colonoscopy is frequently used to investigate melena after a nondiagnostic EGD.
Objective
To determine the diagnostic yield and rate of therapeutic intervention during colonoscopy in patients with melena and a nondiagnostic EGD.
Design
Retrospective case-control study.
Setting
Community and academic centers over a diverse geographic area in the United States.
Patients
This study involved patients in the Clinical Outcomes Research Initiative database with a colonoscopy performed to investigate melena within 30 days of a nondiagnostic EGD for the same indication. A control group had colonoscopies performed for average-risk screening.
Main Outcome Measurements
The endoscopic finding of a suspected bleeding source defined as right-sided arteriovenous malformation, colitis, polyp 20 mm, tumor, or ulcer. Rate of therapeutic intervention during colonoscopy.
Results
Colonoscopy found a suspected bleeding source in 4.8% of patients with melena, more frequently than in the control group (odds ratio [OR] 2.17; 95% confidence interval [CI], 1.65–2.86; P .0001). The rate of therapeutic intervention during melena-related colonoscopy was 1.7%. Patients with melena were more likely to have a colon tumor (OR 2.87; 95% CI, 1.82–5.51; P .0001) than were control patients.
Limitations
Retrospective design, conclusions being dependent on the accuracy of database input, and lack of pertinent clinical data (eg, hemoglobin).
Conclusion
The diagnostic yield of colonoscopy to investigate melena after nondiagnostic EGD is low. The need for therapeutic intervention during colonoscopy for this indication is very low. This population should undergo colonoscopy because they are at increased risk of colorectal cancer. Colonoscopy can potentially be performed electively in stable patients without continued bleeding.
doi:10.1016/j.gie.2011.11.041
PMCID: PMC3864591  PMID: 22301339

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