Cardiotoxicity and cardiovascular disease risk assessment for patients receiving breast cancer treatment

Background: Cardiotoxicity from anticancer therapy affects heart function and structure. Cardiotoxicity can also lead to accelerated development of chronic diseases, especially in the presence of risk factors. Methods: This study aimed to develop and pilot a combined cardiovascular disease and cardiotoxicity risk assessment questionnaire to quantify the potential extent of risk factors in breast cancer patients prior to treatment. The questionnaire underwent content and face validity evaluation by an expert panel followed by pilot testing in a sample of breast cancer patients (n = 36). Questionnaires were self-administered while attending chemotherapy clinic, in the presence of a research assistant. Results: Mean age of participants was 54.8 years (range 36–72 years). Participants reported CVD risk factors including diabetes 2.8%, hypertension 19.8%, hypercholesterolaemia 11% and sleep apnoea 5%. Lifestyle risk factors, included not eating the recommended serves of vegetables (100%) or fruit (78%) per day; smoking (13%) and regularly consuming alcohol (75%). Twenty five percent reported being physically inactive, 61%, overweight or obese, 24%, little or no social support and 30% recorded high to very high psychological distress. Participants were highly (75%) reluctant to undertake lifestyle changes; i.e. changing alcohol consumption; dietary habits; good emotional/mental health strategies; improving physical activity; quitting smoking; learning about heart-health and weight loss. Conclusion: This study is an important step towards prevention and management of treatment-associated cardiotoxicity after breast cancer diagnosis. We recommend that our questionnaire is providing important data that should be included in cancer registries so that researchers can establish the relationship between CVD risk profile and cardiotoxicity outcomes and that this study revealed important teaching opportunities that could be used to examine the impact on health literacy and help patients better understand the consequences of cancer treatment

Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells

This is a non-final version of an article published in final form in J Urol. 2019 Aug 7:101097JU0000000000000475. doi: 10.1097/JU.0000000000000475

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio

Increased temporal sensitivity for threat: A Bayesian generalized linear mixed modeling approach.

People overestimate the duration of threat-related facial expressions, and this effect increases with self-reported fearfulness (Tipples in Emotion, 8, 127-131, 2008, Emotion, 11, 74-80, 2011). One explanation (Cheng, Tipples, Narayanan, & Meck in Timing and Time Perception, 4, 99-122, 2016) for this effect is that emotion increases the rate at which temporal information accumulates. Here I tested whether increased overestimation for threat-related facial expressions in high fearfulness generalizes to pictures of threatening animals. A further goal was to illustrate the use of Bayesian generalized linear mixed modeling (GLMM) to gain more accurate estimates of temporal performance, including estimates of temporal sensitivity. Participants (N = 53) completed a temporal bisection task in which they judged the presentation duration for pictures of threatening animals (poised to attack) and nonthreatening animals. People overestimated the duration of threatening animals, and the effect increased with self-reported fearfulness. In support of increased accumulation of pacemaker ticks due to threat, temporal sensitivity was higher for threat than for nonthreat images. Analyses indicated that temporal sensitivity effects may have been absent in previous research because of the method used to calculate the index of temporal sensitivity. The benefits of using Bayesian GLMM are highlighted, and researchers are encouraged to use this method as the first option for analyzing temporal bisection data

The developmental trajectory of attentional orienting to socio-biological cues.

It has been proposed that the orienting of attention in the same direction as another’s point of gaze relies on innate brain mechanisms which are present from birth, but direct evidence relating to the influence of eye gaze cues on attentional orienting in young children is limited. In two experiments, 137 children aged 3–10 years old performed an adapted pro-saccade task with centrally presented uninformative eye gaze, finger pointing and arrow pre-cues which were either congruent or incongruent with the direction of target presentations. When the central cue overlapped with presentation of the peripheral target (Experiment 1), children up to 5 years old had difficulty disengaging fixation from central fixation in order to saccade to the target. This effect was found to be particularly marked for eye gaze cues. When central cues were extinguished simultaneously with peripheral target onset (Experiment 2), this effect was greatly reduced. In both experiments finger pointing cues (image of pointing index finger presented at fixation) exerted a strong influence on saccade reaction time to the peripheral stimulus for the youngest group of children (<5 years). Overall the results suggest that although young children are strongly engaged by centrally presented eye gaze cues, the directional influence of such cues on overt attentional orienting is only present in older children, meaning that the effect is unlikely to be dependent upon an innate brain module. Instead, the results are consistent with the existence of stimulus–response associations which develop with age and environmental experience

Recognising and reacting to angry and happy facial expressions: a diffusion model analysis.

Researchers have reported two biases in how people recognise and respond to angry and happy facial expressions: (1) a gender-expression bias (Becker et al. in J Pers Soc Psychol, 92(2):179-190, https://doi.org/10.1037/0022-3514.92.2.179 , 2007)-faster identification of male faces as angry and female faces as happy and (2) an approach-avoidance bias-faster avoidance of people who appear angry and faster approach responses people who appear happy (Heuer et al. in Behav Res The, 45(12):2990-3001, https://doi.org/10.1016/j.brat.2007.08.010 2007; Marsh et al. in Emotion, 5(1), 119-124, https://doi.org/10.1037/1528-3542.5.1.119 , 2005; Rotteveel and Phaf in Emotion 4(2):156-172, https://doi.org/10.1037/1528-3542.4.2.156 , 2004). The aim of the current research is to gain insight into the nature of such biases by applying the drift diffusion model to the results of an approach-avoidance task. Sixty-five participants (33 female) identified faces as either happy or angry by pushing and pulling a joystick. In agreement with the original study of this effect (Solarz 1960) there were clear participant gender differences-both the approach avoidance and gender-expression biases were larger in magnitude for female compared to male participants. The diffusion model results extend recent research (Krypotos et al. in Cogn Emot 29(8):1424-1444, https://doi.org/10.1080/02699931.2014.985635 , 2015) by indicating that the gender-expression and approach-avoidance biases are mediated by separate cognitive processes

The Chlamydia psittaci Genome: A Comparative Analysis of Intracellular Pathogens

Chlamydiaceae are a family of obligate intracellular pathogens causing a wide range of diseases in animals and humans, and facing unique evolutionary constraints not encountered by free-living prokaryotes. To investigate genomic aspects of infection, virulence and host preference we have sequenced Chlamydia psittaci, the pathogenic agent of ornithosis.A comparison of the genome of the avian Chlamydia psittaci isolate 6BC with the genomes of other chlamydial species, C. trachomatis, C. muridarum, C. pneumoniae, C. abortus, C. felis and C. caviae, revealed a high level of sequence conservation and synteny across taxa, with the major exception of the human pathogen C. trachomatis. Important differences manifest in the polymorphic membrane protein family specific for the Chlamydiae and in the highly variable chlamydial plasticity zone. We identified a number of psittaci-specific polymorphic membrane proteins of the G family that may be related to differences in host-range and/or virulence as compared to closely related Chlamydiaceae. We calculated non-synonymous to synonymous substitution rate ratios for pairs of orthologous genes to identify putative targets of adaptive evolution and predicted type III secreted effector proteins.This study is the first detailed analysis of the Chlamydia psittaci genome sequence. It provides insights in the genome architecture of C. psittaci and proposes a number of novel candidate genes mostly of yet unknown function that may be important for pathogen-host interactions

The potential of using circulating tumour cells and their gene expression to predict docetaxel response in metastatic prostate cancer

Background: Docetaxel improves overall survival (OS) in castration-resistant prostate cancer (PCa) (CRPC) and metastatic hormone-sensitive PCa (mHSPC). However, not all patients respond due to inherent and/or acquired resistance. There remains an unmet clinical need for a robust predictive test to stratify patients for treatment. Liquid biopsy of circulating tumour cell (CTCs) is minimally invasive, can provide real-time information of the heterogeneous tumour and therefore may be a potentially ideal docetaxel response prediction biomarker. Objective: In this study we investigate the potential of using CTCs and their gene expression to predict post-docetaxel tumour response, OS and progression free survival (PFS). Methods: Peripheral blood was sampled from 18 mCRPC and 43 mHSPC patients, pre-docetaxel treatment, for CTC investigation. CTCs were isolated using the epitope independent Parsortix® system and gene expression was determined by multiplex RT-qPCR. We evaluated CTC measurements for post-docetaxel outcome prediction using receiver operating characteristics and Kaplan Meier analysis. Results: Detection of CTCs pre-docetaxel was associated with poor patient outcome post-docetaxel treatment. Combining total-CTC number with PSA and ALP predicted lack of partial response (PR) with an AUC of 0.90, p= 0.037 in mCRPC. A significantly shorter median OS was seen in mCRPC patients with positive CTC-score (12.80 vs. 37.33 months, HR= 5.08, p= 0.0005), ≥3 total-CTCs/7.5mL (12.80 vs. 37.33 months, HR= 3.84, p= 0.0053), ≥1 epithelial-CTCs/7.5mL (14.30 vs. 37.33 months, HR= 3.89, p= 0.0041) or epithelial to mesenchymal transitioning (EMTing)-CTCs/7.5mL (11.32 vs. 32.37 months, HR= 6.73, p= 0.0001). Significantly shorter PFS was observed in patients with ≥2 epithelial-CTCs/7.5mL (7.52 vs. 18.83 months, HR= 3.93, p= 0.0058). mHSPC patients with ≥5 CTCs/7.5mL had significantly shorter median OS (24.57 vs undefined months, HR= 4.14, p= 0.0097). In mHSPC patients, expression of KLK2, KLK4, ADAMTS1, ZEB1 and SNAI1 was significantly associated with shorter OS and/or PFS. Importantly, combining CTC measurements with clinical biomarkers increased sensitivity and specificity for prediction of patient outcome. Conclusion: While it is clear that CTC numbers and gene expression were prognostic for PCa post-docetaxel treatment, and CTC subtype analysis may have additional value, their potential predictive value for docetaxel chemotherapy response needs to be further investigated in large patient cohorts

Visual attention and action: How cueing, direct mapping, and social interactions drive orienting

Despite considerable interest in both action perception and social attention over the last 2 decades, there has been surprisingly little investigation concerning how the manual actions of other humans orient visual attention. The present review draws together studies that have measured the orienting of attention, following observation of another’s goal-directed action. Our review proposes that, in line with the literature on eye gaze, action is a particularly strong orienting cue for the visual system. However, we additionally suggest that action may orient visual attention using mechanisms, which gaze direction does not (i.e., neural direct mapping and corepresentation). Finally, we review the implications of these gaze-independent mechanisms for the study of attention to action. We suggest that our understanding of attention to action may benefit from being studied in the context of joint action paradigms, where the role of higher level action goals and social factors can be investigated