Predicting high-level visual areas in the absence of task fMRI.

The ventral visual stream is organized into units, or functional regions of interest (fROIs), specialized for processing high-level visual categories. Task-based fMRI scans ("localizers") are typically used to identify each individual's nuanced set of fROIs. The unique landscape of an individual's functional activation may rely in large part on their specialized connectivity patterns; recent studies corroborate this by showing that connectivity can predict individual differences in neural responses. We focus on the ventral visual stream and ask: how well can an individual's resting state functional connectivity localize their fROIs for face, body, scene, and object perception? And are the neural processors for any particular visual category better predicted by connectivity than others, suggesting a tighter mechanistic relationship between connectivity and function? We found, among 18 fROIs predicted from connectivity for each subject, all but one were selective for their preferred visual category. Defining an individual's fROIs based on their connectivity patterns yielded regions that were more selective than regions identified from previous studies or atlases in nearly all cases. Overall, we found that in the absence of a domain-specific localizer task, a 10-min resting state scan can be reliably used for defining these fROIs.

Immunogenic cell death in colorectal cancer: a review of mechanisms and clinical utility.

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide. Despite several clinical advances the survival of patients with advanced colorectal cancer remains limited, demanding newer approaches. The immune system plays a central role in cancer development, propagation, and treatment response. Within the bowel, the colorectal mucosa is a key barrier and site of immune regulation that is generally immunosuppressive. Nonetheless, within this tumour microenvironment, it is evident that anti-neoplastic treatments which cause direct cytotoxic and cytostatic effects may also induce immunogenic cell death (ICD), a form of regulated cell death that leads to an anti-tumour immune response. Therefore, novel ICD inducers and molecular biomarkers of ICD action are urgently needed to advance treatment options for advanced CRC. This article reviews our knowledge of ICD in CRC.

Socioeconomic resources in youth are linked to divergent patterns of network integration and segregation across the brain's transmodal axis.

Socioeconomic resources (SER) calibrate the developing brain to the current context, which can confer or attenuate risk for psychopathology across the lifespan. Recent multivariate work indicates that SER levels powerfully influence intrinsic functional connectivity patterns across the entire brain. Nevertheless, the neurobiological meaning of these widespread alterations remains poorly understood, despite its translational promise for early risk identification, targeted intervention, and policy reform. In the present study, we leverage the resources of graph theory to precisely characterize multivariate and univariate associations between household SER and the functional integration and segregation (i.e., participation coefficient, within-module degree) of brain regions across major cognitive, affective, and sensorimotor systems during the resting state in 5,821 youth (ages 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) Study. First, we establish that decomposing the brain into profiles of integration and segregation captures more than half of the multivariate association between SER and functional connectivity with greater parsimony (100-fold reduction in number of features) and interpretability. Second, we show that the topological effects of SER are not uniform across the brain; rather, higher SER levels are related to greater integration of somatomotor and subcortical systems, but greater segregation of default mode, orbitofrontal, and cerebellar systems. Finally, we demonstrate that the effects of SER are spatially patterned along the unimodal-transmodal gradient of brain organization. These findings provide critical interpretive context for the established and widespread effects of SER on brain organization, indicating that SER levels differentially configure the intrinsic functional architecture of developing unimodal and transmodal systems. This study highlights both sensorimotor and higher-order networks that may serve as neural markers of environmental stress and opportunity, and which may guide efforts to scaffold healthy neurobehavioral development among disadvantaged communities of youth.

A personalized cortical atlas for functional regions of interest.

Advances in functional MRI (fMRI) allow mapping an individual's brain function in vivo. Task fMRI can localize domain-specific regions of cognitive processing or functional regions of interest (fROIs) within an individual. Moreover, data from resting state (no task) fMRI can be used to define an individual's connectome, which can characterize that individual's functional organization via connectivity-based parcellations. However, can connectivity-based parcellations alone predict an individual's fROIs? Here, we describe an approach to compute individualized rs-fROIs (i.e., regions that correspond to given fROI constructed using only resting state data) for motor control, working memory, high-level vision, and language comprehension. The rs-fROIs were computed and validated using a large sample of young adults (n = 1,018) with resting state and task fMRI from the Human Connectome Project. First, resting state parcellations were defined across a sequence of resolutions from broadscale to fine-grained networks in a training group of 500 individuals. Second, 21 rs-fROIs were defined from the training group by identifying the rs network that most closely matched task-defined fROIs across all individuals. Third, the selectivity of rs-fROIs was investigated in a training set of the remaining 518 individuals. All computed rs-fROIs were indeed selective for their preferred category. Critically, the rs-fROIs had higher selectivity than probabilistic atlas parcels for nearly all fROIs. In conclusion, we present a potential approach to define selective fROIs on an individual-level circumventing the need for multiple task-based localizers.NEW & NOTEWORTHY We compute individualized resting state parcels that identify an individual's own functional regions of interest (fROIs) for high-level vision, language comprehension, motor control, and working memory, using only their functional connectome. This approach demonstrates a rapid and powerful alternative for finding a large set of fROIs in an individual, using only their unique connectivity pattern, which does not require the costly acquisition of multiple fMRI localizer tasks.

Effect of Extremely Preterm Birth on Adolescent Brain Network Organization.

Introduction: Extremely preterm (EPT) birth, defined as birth at a gestational age (GA) <28 weeks, can have a lasting impact on cognition throughout the life span. Previous investigations reveal differences in brain structure and connectivity between infants born preterm and full-term (FT), but how does preterm birth impact the adolescent connectome? Methods: In this study, we investigate how EPT birth can alter broadscale network organization later in life by comparing resting-state functional magnetic resonance imaging connectome-based parcellations of the entire cortex in adolescents born EPT (N = 22) to age-matched adolescents born FT (GA ≥37 weeks, N = 28). We compare these parcellations to adult parcellations from previous studies and explore the relationship between an individual's network organization and behavior. Results: Primary (occipital and sensorimotor) and frontoparietal networks were observed in both groups. However, there existed notable differences in the limbic and insular networks. Surprisingly, the connectivity profile of the limbic network of EPT adolescents was more adultlike than the same network in FT adolescents. Finally, we found a relationship between adolescents' overall cognition score and their limbic network maturity. Discussion: Overall, preterm birth may contribute to the atypical development of broadscale network organization in adolescence and may partially explain the observed cognitive deficits.

Individual variability in functional organization of the neonatal brain.

The adult brain is organized into distinct functional networks, forming the basis of information processing and determining individual differences in behavior. Is this network organization genetically determined and present at birth? And what is the individual variability in this organization in neonates? Here, we use unsupervised learning to uncover intrinsic functional brain organization using resting-state connectivity from a large cohort of neonates (Developing Human Connectome Project). We identified a set of symmetric, hierarchical, and replicable networks: sensorimotor, visual, default mode, ventral attention, and high-level vision. We quantified individual variability across neonates, and found the most individual variability in the ventral attention networks. Crucially, the variability of these networks was not driven by SNR differences or differences from adult networks (Yeo et al., 2011). Finally, differential gene expression provided a potential explanation for the emergence of these distinct networks and identified potential genes of interest for future developmental and individual variability research. Overall, we found neonatal connectomes (even at the voxel-level) can reveal broad individual-specific information processing units. The presence of individual differences in neonates and the framework for personalized parcellations demonstrated here has the potential to improve prediction of behavior and future outcomes from neonatal and infant brain data.

Hierarchies improve individual assessment of temporal discounting behavior.

Delay discounting behavior has proven useful in assessing impulsivity across a wide range of populations. As such, accurate estimation of the shape of each individual's temporal discounting profile is paramount when drawing conclusions about how impulsivity relates to clinical and health outcomes such as gambling, addiction, and obesity. Here, we identify an estimation problem with current methods of assessing temporal discounting behavior, and propose a simple solution. First, through a simulation study we identify types of temporal discounting profiles that cannot reliably be estimated. Second, we show how imposing constraints through hierarchical modeling ameliorates these recovery problems. Finally, we apply our solution to a large data set from a temporal discounting task, and illustrate the importance of reliable estimation within patient populations. We conclude with a brief discussion on how hierarchical Bayesian methods can aid in model estimation, compensate for small samples, and improve predictions of externalizing psychopathology.

Individual Differences in the Neural Dynamics of Response Inhibition.

Response inhibition is a widely studied aspect of cognitive control that is particularly interesting because of its applications to clinical populations. Although individual differences are integral to cognitive control, so too is our ability to aggregate information across a group of individuals, so that we can powerfully generalize and characterize the group's behavior. Hence, an examination of response inhibition would ideally involve an accurate estimation of both group- and individual-level effects. Hierarchical Bayesian analyses account for individual differences by simultaneously estimating group and individual factors and compensate for sparse data by pooling information across participants. Hierarchical Bayesian models are thus an ideal tool for studying response inhibition, especially when analyzing neural data. We construct hierarchical Bayesian models of the fMRI neural time series, models assuming hierarchies across conditions, participants, and ROIs. Here, we demonstrate the advantages of our models over a conventional generalized linear model in accurately separating signal from noise. We then apply our models to go/no-go and stop signal data from 11 participants. We find strong evidence for individual differences in neural responses to going, not going, and stopping and in functional connectivity across the two tasks and demonstrate how hierarchical Bayesian models can effectively compensate for these individual differences while providing group-level summarizations. Finally, we validated the reliability of our findings using a larger go/no-go data set consisting of 179 participants. In conclusion, hierarchical Bayesian models not only account for individual differences but allow us to better understand the cognitive dynamics of response inhibition.

On the Neural and Mechanistic Bases of Self-Control.

Intertemporal choice requires a dynamic interaction between valuation and deliberation processes. While evidence identifying candidate brain areas for each of these processes is well established, the precise mechanistic role carried out by each brain region is still debated. In this article, we present a computational model that clarifies the unique contribution of frontoparietal cortex regions to intertemporal decision making. The model we develop samples reward and delay information stochastically on a moment-by-moment basis. As preference for the choice alternatives evolves, dynamic inhibitory processes are executed by way of asymmetric lateral inhibition. We find that it is these lateral inhibition processes that best explain the contribution of frontoparietal regions to intertemporal decision making exhibited in our data.

Telehealth and telenursing using simulation for pre-licensure USA students.

An innovative simulation was used to teach pre-licensure USA nursing students about telenursing for screening, assessment, and patient education during a home visit. The students used telepresence technology to deliver nursing care to a homebound geriatric patient. After the simulation, students (N = 73) felt increased confidence with the skills needed to deliver telenursing care and in using telepresence technology. Students reported that they modified and improved their communication in order to adapt to perceived barriers posed by the new technology. As telenursing becomes more prevalent for managing patient care at a distance, nursing programs will need to incorporate educational strategies to reflect this change.

Antimicrobial-resistant Faecal Organisms in Algae Products Marketed as Health Supplements.

Dietary supplements are increasingly popular in Irish society. One of these is blue-green algae which is used with a variety health benefits in mind. A batch of Chlorella powder was found to be contaminated with Salmonella species in Ireland in 2015. This prompted additional testing of a total of 8 samples of three different products (Chlorella, Spirulina and Super Greens), for other faecal flora and antimicrobial resistance in any bacteria isolated. All 8 samples cultured enteric flora such as Enterococci, Enterobacteriaceae and Clostridium species. Antimicrobial susceptibility testing revealed one isolate with extended-spectrum ?-lactamase (ESBL) activity and one with carbapenemase activity. Clinicians caring for vulnerable patients should be aware of the potential risk of exposure to antimicrobial resistant bacteria associated with these products.

The effect of exercise interventions on inflammatory biomarkers in healthy, physically inactive subjects: a systematic review.

BACKGROUND: Increases in physical activity ameliorate low-grade systemic inflammation in disease populations such as type 2 diabetes mellitus and coronary artery disease. The effects of aerobic and resistance training (RT) on inflammatory biomarker profiles in non-disease, physically inactive individuals are unknown. METHODS: A systematic review of randomized controlled trials measuring the effect of aerobic and resistance exercise on pro-inflammatory biomarkers in healthy, inactive adult populations was conducted. The available peer-reviewed literature was searched from January 1990 to June 2016 using the electronic databases PubMed and Scopus. A narrative synthesis of review findings was constructed with discussion of the impact of aerobic, resistance and combined training on C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8, interleukin-1ß and tumour necrosis factor-α. RESULTS: The initial search revealed 1596 potentially relevant studies. Application of the study eligibility criteria led to the full-text review of 54 articles with 11 studies deemed suitable for inclusion. Review of related articles and the reference lists of the 54 full-text articles led to the inclusion of 2 additional studies. The review revealed inconsistent findings relating to the effect of aerobic training and RT on CRP and IL-6. Studies of older-aged adults (>65 years old) demonstrated the greatest and most consistent reduction in inflammatory biomarkers post-training intervention. CONCLUSIONS: A paucity of evidence exists relating to the effect of exercise training on inflammatory markers in non-disease, physically inactive adults. The available evidence suggests potential for the greatest benefit to be seen in older populations and with higher intensity aerobic exercise.

Application of a Sub-set of Skinfold Sites for Ultrasound Measurement of Subcutaneous Adiposity and Percentage Body Fat Estimation in Athletes.

Body composition assessment is an integral feature of elite sport as optimization facilitates successful performance. This study aims to refine the use of B-mode ultrasound in the assessment of athlete body composition by determining suitable sites for measurement. 67 elite athletes recruited from the Human Performance Laboratory, University College Cork, Ireland, underwent dual measurement of body composition. Subcutaneous adipose tissue thickness at 7 anatomical sites were measured using ultrasound and compared to percentage body fat values determined using Dual-Energy X-ray Absorptiometry. Multiple linear regressions were performed and an equation to predict percentage body fat was derived. The present study found subcutaneous adipose tissue depths at the triceps, biceps, anterior thigh and supraspinale sites correlated significantly with percentage body fat by X-ray absorptiometry (all p<0.05). Summation of the depths at these locations correlated strongly with percentage body fat by Dual-Energy X-ray Absorptiometry (R²=0.879). The triceps, biceps, anterior thigh and supraspinale sites are suitable anatomical landmarks for the estimation of %BF using B-mode ultrasound. Use of B-mode ultrasound in the assessment of athlete body composition confers many benefits including lack of ionising radiation and its potential to be used as a portable field tool.

High risk HPV testing following treatment for cervical intraepithelial neoplasia.

AIM: To determine the results of combined cytology and high-risk human papilloma virus (HR HPV) tests at 6 and 18 months postcolposcopy treatment at one Irish colposcopy centre. METHODS: All women who attended the centre's colposcopy smear clinic for a co-test 6 months (initial test) posttreatment were included in the audit (n = 251). RESULTS: The results revealed negative HR HPV for 79 % (n = 198) of women tested 6 months after treatment and positive results for 21 % (n = 53). HR HPV testing was more sensitive than cytology and led to early detection of residual disease. No women with negative HR HPV had high-grade cytology. CONCLUSION: HR HPV is more sensitive than cytology for detection of persistent CIN. However, 19 women with positive HR HPV had normal colposcopy with no persistent CIN detected. A national cost-benefit analysis is recommended to determine the value of the second co-test.

Concussion in rugby: knowledge and attitudes of players.

BACKGROUND: Concussion is a traumatic brain injury, resulting in the alteration of mental status with or without loss of consciousness. There is increasing awareness that recurrent concussion may contribute to long-term neurological complication. AIMS: To determine player knowledge and attitudes regarding concussion. To identify sources of information and medical care, and to estimate the incidence of concussion in this group. To determine if player gender and grade of competition are associated with differences in knowledge, attitudes, medical care, and incidence. METHODS: Five rugby teams were recruited and players invited to complete a paper-based questionnaire. The questionnaire sought information on player demographics, knowledge level, attitudes and concussion experience. RESULTS: 90.8 % of players knew they should not continue playing when concussed. 75 % of players would continue an important game even if concussed. Of those concussed, 39.1 % have tried to influence medical assessment with 78.2 % stating it is possible or quite easy to do so. Males are less likely to worry about long-term effects of concussion (χ (2) = 9.23, p = 0.026). Club players are less likely to have medical care at training (χ (2) = 28.2, p < 0.001) or matches (χ (2) = 19.47 p < 0.001). CONCLUSION: Despite good knowledge of concussion complications, management players engage in unsafe behaviour with little difference between gender and competition grades. Information regarding symptoms and management should be available to all players, coaches, and parents. Provision of medical care should be mandatory at every level of competition.

Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer.

BACKGROUND: Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. METHODS: PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. RESULTS: PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1ß, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002). CONCLUSIONS: In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.

Overexpression of protein S100A4 is independently associated with overall survival in stage C colonic cancer but only in cytoplasm at the advancing tumour front.

PURPOSE: S100A4, a multifunctional protein, has been linked to the invasive growth and metastases of several human cancers. This study investigated the association between S100A4 and overall survival and other clinicopathological features in patients with stage C colonic cancer. METHODS: Clinical and pathological data were obtained from a prospective hospital registry of 409 patients who had a resection for stage C colonic cancer. Tissue microarrays for immunohistochemistry were constructed from archived tissue. S100A4 staining intensity and percentage of stained cells were assessed in nuclei and cytoplasm for both the central part of the tumour and at the advancing front. Overall survival was analysed by the Kaplan-Meier method and Cox regression. RESULTS: Only a high percentage of cells with S100A4 cytoplasmic staining in frontal tissue was associated with poor survival (hazard ratio, 1.6; 95 % CI 1.1-2.2; p = 0.008) after adjustment for other prognostic variables. There was no association between frontal cytoplasmic S100A4 expression and any of 13 other clinicopathological variables. CONCLUSIONS: High expression of S100A4 in cytoplasm at the advancing front of stage C colonic tumours indicates a poor prognosis. Whether S100A4 can predict response to adjuvant chemotherapy remains to be investigated in a randomised clinical trial.

Further evidence of validity of the Gait Deviation Index.

In this paper, the relationship of the Gait Deviation Index (GDI) to gross motor function and its ability to distinguish between different Gross Motor Function Classification System (GMFCS) levels was determined. A representative sample of 184 ambulant children with CP in GMFCS levels I (n=57), II (n=91), III (n=22) and IV (n=14) were recruited as part of a population-based study. Representative gait cycles were selected following a 3D gait analysis and gross motor function was assessed using the Gross Motor Function Measure (GMFM). GDI scores were calculated in Matlab. Valid 3D kinematic data were obtained for 173 participants and both kinematic and GMFM data were obtained for 150 participants. A substantial relationship between mean GDI and GMFM-66 scores was demonstrated (r=0.70; p<0.001) with significant differences in mean GDI scores between GMFCS levels (p<0.001) indicating increasing levels of gait deviation in subjects less functionally able. The relationship between the GDI, GMFM and GMFCS in a representative sample of ambulators, lends further weight to the validity of the GDI scoring system. Furthermore it suggests that the subtleties of gait may not be wholly accounted for by gross motor function evaluation alone. Gait specific tools such as the GDI more likely capture both the functional and aesthetic components of walking.

Sport and recreation-related injuries and fracture occurrence among emergency department attendees: implications for exercise prescription and injury prevention.

OBJECTIVE: To investigate the epidemiology of sports and recreation-related injury (SRI) among emergency department (ED) attendees. DESIGN: Descriptive epidemiology study. SETTING: An Irish university hospital ED. PARTICIPANTS: All patients aged over 4 years attending a large regional ED, during a 6-month period, for the treatment of SRI were prospectively surveyed. ASSESSMENT OF RISK FACTORS: In all cases identified as SRI the attending physician completed a specifically designed questionnaire. It was postulated that recreation-related injury is a significant proportion of reported SRI. RESULTS: Fracture rate was highest in the 4-9-year age group (44%). On multivariate logistic regression the adjusted odds ratio (OR; 95% CI) of fracture was higher for children (vs adults) at 1.21 (1.0 to 1.45). The adjusted OR was higher for upper-limb 5.8 (4.5 to 7.6) and lower-limb injuries 1.87 (1.4 to 2.5) versus axial site of injury and for falls 2.2 (1.6 to 2.9) and external force 1.59 (1.2 to 2.1) versus an overextension mechanism of injury. In the same model, "play" was independently associated with fracture risk, adjusted OR 1.98 (1.2 to 3.0; p = 0.001) versus low-risk ball sports 1.0 (reference); an effect size similar to that seen for combat sports 1.96 (1.2 to 3.3; p = 0.01) and greater than that seen for presumed high-risk field sports 1.4 (0.9 to 2.0) CONCLUSION: Fall and subsequent upper-limb injury was the commonest mechanism underlying SRI fracture. Domestic "play" in all age groups at the time of injury accorded a higher fracture risk than field sports. Patient education regarding the dangers of unsupervised play and recreation represents a means of reducing the burden of SRI.