Moving beyond the 'CAP' of the Iceberg: Intrinsic connectivity networks in fMRI are continuously engaging and overlapping.

Resting-state functional magnetic resonance imaging is currently the mainstay of functional neuroimaging and has allowed researchers to identify intrinsic connectivity networks (aka functional networks) at different spatial scales. However, little is known about the temporal profiles of these networks and whether it is best to model them as continuous phenomena in both space and time or, rather, as a set of temporally discrete events. Both categories have been supported by series of studies with promising findings. However, a critical question is whether focusing only on time points presumed to contain isolated neural events and disregarding the rest of the data is missing important information, potentially leading to misleading conclusions. In this work, we argue that brain networks identified within the spontaneous blood oxygenation level-dependent (BOLD) signal are not limited to temporally sparse burst moments and that these event present time points (EPTs) contain valuable but incomplete information about the underlying functional patterns. We focus on the default mode and show evidence that is consistent with its continuous presence in the BOLD signal, including during the event absent time points (EATs), i.e., time points that exhibit minimum activity and are the least likely to contain an event. Moreover, our findings suggest that EPTs may not contain all the available information about their corresponding networks. We observe distinct default mode connectivity patterns obtained from all time points (AllTPs), EPTs, and EATs. We show evidence of robust relationships with schizophrenia symptoms that are both common and unique to each of the sets of time points (AllTPs, EPTs, EATs), likely related to transient patterns of connectivity. Together, these findings indicate the importance of leveraging the full temporal data in functional studies, including those using event-detection approaches.

Monitoring telehealth vomiting calls as a potential public health early warning system for seasonal norovirus activity in Ontario, Canada.

Norovirus is a predominant cause of infectious gastroenteritis in countries worldwide [1-5]. It accounts for approximately 50% of acute gastroenteritis (AGE) and >90% of viral gastroenteritis outbreaks [6, 7]. The incubation period ranges between 10 and 48 h and illness duration is generally 1-3 days with self-limiting symptoms; however, this duration is often longer (e.g. 4-6 days) in vulnerable populations such as hospital patients or young children [2, 8]. Symptomatic infection of norovirus presents as acute vomiting, diarrhoea, abdominal cramps and nausea, with severe vomiting and diarrhoea (non-bloody) being most common [2, 5, 9].

Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms.

BACKGROUND: Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities. METHOD: Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined. RESULTS: HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior. CONCLUSIONS: Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

Development and pre-testing of a rehabilitation planning consultation for head-and-neck cancer.

BACKGROUND: In contrast with other major chronic conditions such as heart disease and stroke, cancer care does not routinely integrate evidence-based rehabilitation services within the standard continuum. The objectives of the present project were to develop a rehabilitation planning consultation (rpc) for survivors of head-and-neck (hn) cancer, to test its feasibility, and to make refinements. METHODS: Using intervention mapping, the rpc-alpha was developed by examining potential theoretical methods and practical applications relative to the program objectives. During feasibility testing, a single case series was conducted with survivors of hn cancer who had completed their cancer treatment within the preceding 11 months; iterative refinements were made after each case. RESULTS: The rpc-alpha was led by a rehabilitation professional and was based on self-management principles. The initial consultation included instruction in a global cognitive strategy, goal-setting, introduction to available resources, action planning, and coping planning. A follow-up consultation was conducted a few weeks later. Of 9 participants recruited, 5 completed post-intervention assessments. Participants reported that the rpc helped them to make rehabilitation plans. CONCLUSIONS: The rpc was feasible to use and satisfactory to a small group of hn cancer survivors. A pilot test of the refined version is in process.

Scoping review to identify potential non-antimicrobial interventions to mitigate antimicrobial resistance in commensal enteric bacteria in North American cattle production systems.

A scoping review was conducted to identify modifiable non-antimicrobial factors to reduce the occurrence of antimicrobial resistance in cattle populations. Searches were developed to retrieve peer-reviewed published studies in animal, human and in vitro microbial populations. Citations were retained when modifiable non-antimicrobial factors or interventions potentially associated with antimicrobial resistance were described. Studies described resistance in five bacterial genera, species or types, and 40 antimicrobials. Modifiable non-antimicrobial factors or interventions ranged widely in type, and the depth of evidence in animal populations was shallow. Specific associations between a factor or intervention with antimicrobial resistance in a population (e.g. associations between organic systems and tetracycline susceptibility in E. coli from cattle) were reported in a maximum of three studies. The identified non-antimicrobial factors or interventions were classified into 16 themes. Most reported associations between the non-antimicrobial modifiable factors or interventions and antimicrobial resistance were not statistically significant (P > 0·05 and a confidence interval including 1), but when significant, the results were not consistent in direction (increase or decrease in antimicrobial resistance) or magnitude. Research is needed to better understand the impacts of promising modifiable factors or interventions on the occurrence of antimicrobial resistance before any recommendations can be offered or adopted.

Estimated hospitalizations attributed to norovirus and rotavirus infection in Canada, 2006-2010.

Enteric viruses including norovirus and rotavirus are leading causes of gastroenteritis in Canada. However, only a small number of clinical cases are actually tested for these pathogens leading to systematic underestimation of attributed hospitalizations in administrative databases. The objective of this analysis was to estimate the number of hospitalizations due to norovirus and rotavirus in Canada. Hospitalization records for acute gastroenteritis-associated discharges at all acute-care hospitals in Canada between 2006 and 2011 were analysed. Cause-unspecified gastroenteritis hospitalizations were modelled using age-specific negative binomial models with cause-specified gastroenteritis admissions as predictors. The coefficients from the models were used to estimate the number of norovirus and rotavirus admissions. The total annual hospitalizations for rotavirus were estimated to be between 4500 and 10 000. Total annual hospitalizations for norovirus were estimated to be between 4000 and 11 000. The mean total annual cost associated with these hospitalizations was estimated to be at least $16 million for rotavirus and $21 million for norovirus (all figures in Canadian dollars). This study is the first comprehensive analysis of norovirus and rotavirus hospitalizations in Canada. These estimates provide a more complete assessment of the burden and economic costs of these pathogens to the Canadian healthcare system.

The zoonotic potential of Mycobacterium avium ssp. paratuberculosis: a systematic review and meta-analyses of the evidence.

This systematic review-meta-analysis appraises and summarizes all the available research (128 papers) on the zoonotic potential of Mycobacterium avium ssp. paratuberculosis. The latter has been debated for a century due to pathogenic and clinical similarities between Johne's disease in ruminants and Crohn's disease (108 studies) in humans and recently for involvement in other human diseases; human immunodeficiency virus (HIV) infection (2), sarcoidosis (3), diabetes mellitus type 1 (T1DM) (7) and type 2 (3), multiple sclerosis (5) and Hashimoto's thyroiditis (2). Meta-analytical results indicated a significant positive association, consistently across different laboratory methods for Crohn's disease [odds ratio (OR) range 4·26-8·44], T1DM (OR range 2·91-9·95) and multiple sclerosis (OR range 6·5-7·99). The latter two and the thyroiditis hypothesis require further investigation to confirm the association. Meta-regression of Crohn's disease studies using DNA detection methods indicated that choice of primers and sampling frame (e.g. general population vs. hospital-based sample) explained a significant proportion of heterogeneity. Other epidemiological studies demonstrated a lack of association between high-risk occupations and development of Crohn's disease. Due to knowledge gaps in understanding the role of M. paratuberculosis in the development or progression of human disease, the evidence at present is not strong enough to inform the potential public health impact of M. paratuberculosis exposure.

Stool submission data to help inform population-level incidence rates of enteric disease in a Canadian community.

Laboratory-based surveillance data is essential for monitoring trends in the incidence of enteric disease. Current Canadian human enteric surveillance systems report only confirmed cases of human enteric disease and are often unable to capture the number of negative test results. Data from 9116 hospital stool specimens from the Waterloo Region in Canada, with a mixed urban and rural population of about 500 000 were analysed to investigate the use of stool submission data and its role in reporting bias when determining the incidence of enteric disease. The proportion of stool specimens positive for Campylobacter spp. was highest in the 15-29 years age group, and in the 5-14 years age group for Salmonella spp. and E. coli O157:H7. By contrast, the age-specific incidence rates were highest for all three pathogens in the 0-4 years age group which also had the highest stool submission rate. This suggests that variations in age-specific stool submission rates are influencing current interpretation of surveillance data.

Acute gastrointestinal illness in two Inuit communities: burden of illness in Rigolet and Iqaluit, Canada.

Food- and waterborne disease is thought to be high in some Canadian Indigenous communities; however, the burden of acute gastrointestinal illness (AGI) is not well understood due to limited availability and quality of surveillance data. This study estimated the burden of community-level self-reported AGI in the Inuit communities of Rigolet, Nunatsiavut, and Iqaluit, Nunavut, Canada. Cross-sectional retrospective surveys captured information on AGI and potential environmental risk factors. Multivariable logistic regression models identified potential AGI risk factors. The annual incidence of AGI ranged from 2·9-3·9 cases/person per year in Rigolet and Iqaluit. In Rigolet, increased spending on obtaining country foods, a homeless person in the house, not visiting a cabin recently, exposure to puppies, and alternative sources of drinking water were associated with increased odds of AGI. In Iqaluit, eating country fish often, exposure to cats, employment status of the person responsible for food preparation, not washing the countertop with soap after preparing meat, a homeless person in the house, and overcrowding were associated with increased odds of AGI. The results highlight the need for systematic data collection to better understand and support previously anecdotal indications of high AGI incidence, as well as insights into unique AGI environmental risk factors in Indigenous populations.

Resting-state connectivity deficits associated with impaired inhibitory control in non-treatment-seeking adolescents with psychotic symptoms.

OBJECTIVE: Psychotic symptoms are common in the population and index risk for a range of severe psychopathological outcomes. We wished to investigate functional connectivity in a community sample of adolescents who reported psychotic symptoms (the extended psychosis phenotype). METHOD: This study investigated intrinsic functional connectivity (iFC) during resting-state functional magnetic resonance imaging (fMRI; rs-fMRI). Following screening in schools, 11 non-treatment seeking, youth with psychotic symptoms (aged 11-13) and 14 community controls participated in the study. Seed regions of interest comprised brain regions previously shown to exhibit aberrant activation during inhibitory control in adolescents with psychotic symptoms. RESULTS: Relative to controls, adolescents with psychotic symptoms exhibited reduced iFC between regions supporting inhibitory control. Specifically, they showed weaker iFC between the right inferior frontal gyrus (IFG) and the cingulate, IFG and the striatum, anterior cingulate and claustrum, and precuneus and supramarginal gyrus. Conversely, the psychotic symptoms group exhibited stronger iFC between the superior frontal gyrus and claustrum and IFG and lingual gyrus. CONCLUSION: The present findings are the first to reveal aberrant functional connectivity in resting-state networks in a community sample of adolescents with psychotic symptoms and suggest that disruption in integration between distributed neural networks (particularly between prefrontal, cingulate and striatal brain regions) may be a key neurobiological feature of the extended psychosis phenotype.

A longitudinal study of feed contamination by European starling excreta in Ohio dairy farms (2007-2008).

The objectives of this study were to understand the temporal pattern of contamination of cattle feed by starling excrement on dairy farms and to evaluate the temporal pattern in recovering Escherichia coli O157:H7 or Salmonella in relation to the absolute mass of excrement recovered. A longitudinal study was conducted on 15 dairy farms in Ohio from July 2007 to October 2008. One open-topped tray filled with bird feed was placed near a cattle feeding site; bird excrement from the tray was weighed monthly for 12 consecutive months. Linear regression models with a random intercept for farm were computed to examine the association between the absolute weight of excrement recovered each month or the farm-specific standard score for weight of excrement, and month or season. Exact logistic regression was used to determine whether an association between recovering E. coli O157:H7 or Salmonella was present and the amount of excrement recovered and season. A spatial scan statistic was used to test for evidence of space-time clustering of excrement, based on the standard score for the weight of the excrement, among our study farms. A total of 5 of 179 excrement samples (2.79%) were positive for E. coli O157:H7 and 2 (1.12%) were positive for Salmonella. A significantly higher level of contamination with excrement was observed during the winter. The odds of recovering a pathogen increased with the amount of excrement recovered and decreased if the excrement was collected in the winter. A spatio-temporal cluster of contamination with excrement was detected. These findings provide basic information for future quantitative microbial risk assessments concerning the role of starlings in spreading enteric pathogens on dairy farms.

Burden of illness and factors associated with duration of illness in clinical campylobacteriosis.

A population-based study investigated the burden of illness, including the duration of illness associated with laboratory-confirmed cases of campylobacteriosis in two health unit areas. Questionnaire data were collected for 250 cases. The median duration of illness was 8 days and 66% of cases reported symptoms of moderate severity or greater. A Cox proportional hazards model identified antimicrobial use factors associated with a significantly increased rate of symptom resolution (shorter duration of illness): macrolides for less than the recommended number of days, ciprofloxacin for at least 3 days, and antimicrobials not recommended for campylobacteriosis. The impact of antimicrobial use was consistent regardless of when, during the course of illness, the antimicrobial use began. The effectiveness of ciprofloxacin in these results may be due to the low prevalence of resistance to ciprofloxacin in isolates from this study. The effect of antimicrobials not recommended for campylobacteriosis should be further investigated.

A combined exercise and cognitive training intervention induces fronto-cingulate cortical plasticity in first-episode psychosis patients.

OBJECTIVE: Schizophrenia (SZ) is characterized by neurobiological and associated cognitive and functional deficits, including pronounced cortical thinning, that lead to acute and long-term functional impairment. Research with older adults supports the role of non-pharmacological interventions, such as exercise (E) and cognitive training (CT), for cognitive impairments. This literature influenced the development of combined CT&E treatments for individuals with SZ. However, the impact of longer combined treatment duration (6 months) on neuroanatomy has yet to be explored in patients in the early course of the illness. The impact of adding exercise to cognitive training for key brain regions associated with higher-order cognition was examined here using magnetic resonance imaging (MRI) in first-episode psychosis (FEP) patients. METHODS: UCLA Aftercare Research Program patients with a recent first episode of schizophrenia were randomly assigned to either combined cognitive and exercise training (CT&E) (N = 20) or cognitive training alone (CT) (N = 17) intervention. Cortical thickness was measured longitudinally and analyzed for two regions of interest using FreeSurfer. RESULTS: Compared to patients in the CT group, those in the CT&E group demonstrated an increase in cortical thickness within the left anterior cingulate cortex over the six-month treatment period (ACC: F(1, 35) = 4.666, P < .04). Directional tendencies were similar in the left dorsolateral prefrontal cortex (DLPFC: F(1,35) = 4.132, P < .05). CONCLUSIONS: These findings suggest that exercise and cognitive training may synergistically increase fronto-cingulate cortical thickness to mitigate progressive neural atrophy in the early course of SZ. This combined intervention appears to be a valuable adjunct to standard pharmacologic treatment in FEP patients.

Evaluating interventions against Salmonella in broiler chickens: applying synthesis research in support of quantitative exposure assessment.

A scoping study and systematic review-meta-analyses (SR-MAs) were conducted to evaluate the effectiveness of various interventions for Salmonella in broiler chicken, from grow-out farm to secondary processing. The resulting information was used to inform a quantitative exposure assessment (QEA) comparing various control options within the context of broiler chicken production in Ontario, Canada. Multiple scenarios, including use of two separate on-farm interventions (CF3 competitive exclusion culture and a 2% lactose water additive), a package of processing interventions (a sodium hydroxide scald water disinfectant, a chlorinated post-evisceration spray, a trisodium phosphate pre-chill spray and chlorinated immersion chilling) a package consisting of these farm and processing interventions and a hypothetical scenario (reductions in between-flock prevalence and post-transport concentration), were simulated and compared to a baseline scenario. The package of on-farm and processing interventions was the most effective in achieving relative reductions (compared to baseline with no interventions) in the concentration and prevalence of Salmonella by the end of chilling ranging from 89·94% to 99·87% and 43·88% to 87·78%, respectively. Contaminated carcasses entering defeathering, reductions in concentration due to scalding and post-evisceration washing, and the potential for cross-contamination during chilling had the largest influence on the model outcomes under the current assumptions. Scoping study provided a transparent process for mapping out and selecting promising interventions, while SR-MA was useful for generating more precise and robust intervention effect estimates for QEA. Realization of the full potential of these methods was hampered by low methodological soundness and reporting of primary research in this area.

The role of drinking water in the transmission of antimicrobial-resistant E. coli.

To determine whether drinking water contaminated with antimicrobial-resistant E. coli is associated with the carriage of resistant E. coli, selected households sending water samples to Ontario and Alberta laboratories in 2005-2006 were asked to participate in a cross-sectional study. Household members aged ≥12 years were asked to complete a questionnaire and to submit a rectal swab. In 878 individuals, 41% carried a resistant strain of E. coli and 28% carried a multidrug-resistant strain. The risk of carriage of resistant E. coli was 1·26 times higher for users of water contaminated with resistant E. coli. Other risk factors included international travel [prevalence ratio (PR) 1·33], having a child in nappies (PR 1·33), being male (PR 1·33), and frequent handling of raw red meats (PR 1·10). Protecting private water sources (e.g. by improving systems to test and treat them) may help slow the emergence of antimicrobial resistance in E. coli.

Drinking water consumption patterns in Canadian communities (2001-2007).

A pooled analysis of seven cross-sectional studies from Newfoundland and Labrador, Waterloo and Hamilton Regions, Ontario and Vancouver, East Kootenay and Northern Interior Regions, British Columbia (2001 to 2007) was performed to investigate the drinking water consumption patterns of Canadians and to identify factors associated with the volume of tap water consumed. The mean volume of tap water consumed was 1.2 L/day, with a large range (0.03 to 9.0 L/day). In-home water treatment and interactions between age and gender and age and bottled water use were significantly associated with the volume of tap water consumed in multivariable analyses. Approximately 25% (2,221/8,916) of participants were classified as bottled water users, meaning that 75% or more of their total daily drinking water intake was bottled. Approximately 48.6% (4,307/8,799) of participants used an in-home treatment method to treat their tap water for drinking purposes. This study provides a broader geographic perspective and more current estimates of Canadian water consumption patterns than previous studies. The identified factors associated with daily water consumption could be beneficial for risk assessors to identify individuals who may be at greater risk of waterborne illness.

Considering the risk of infection by cryptosporidium via consumption of municipally treated drinking water from a surface water source in a Southwestern Ontario community.

Through the use of case-control analyses and quantitative microbial risk assessment (QMRA), relative risks of transmission of cryptosporidiosis have been evaluated (recreational water exposure vs. drinking water consumption) for a Canadian community with higher than national rates of cryptosporidiosis. A QMRA was developed to assess the risk of Cryptosporidium infection through the consumption of municipally treated drinking water. Simulations were based on site-specific surface water contamination levels and drinking water treatment log10 reduction capacity for Cryptosporidium. Results suggested that the risk of Cryptosporidium infection via drinking water in the study community, assuming routine operation of the water treatment plant, was negligible (6 infections per 10¹³ persons per day--5th percentile: 2 infections per 10¹5 persons per day; 95th percentile: 3 infections per 10¹² persons per day). The risk is essentially nonexistent during optimized, routine treatment operations. The study community achieves between 7 and 9 log10 Cryptosporidium oocyst reduction through routine water treatment processes. Although these results do not preclude the need for constant vigilance by both water treatment and public health professionals in this community, they suggest that the cause of higher rates of cryptosporidiosis are more likely due to recreational water contact, or perhaps direct animal contact. QMRA can be successfully applied at the community level to identify data gaps, rank relative public health risks, and forecast future risk scenarios. It is most useful when performed in a collaborative way with local stakeholders, from beginning to end of the risk analysis paradigm.

Quantitative human health risk assessments of antimicrobial use in animals and selection of resistance: a review of publicly available reports.

Quantitative risk assessments have been conducted to estimate the probability and magnitude of adverse human health effects from antimicrobial use in food animals through selection for antimicrobial resistance in bacteria. The majority focused on licensed antimicrobials under regulatory scrutiny, including growth promoters and agents of critical importance to human health. Most used models to attribute fractions of surveillance-derived estimates of antimicrobial-resistant infections in humans to antimicrobial use in animals. Risk estimates ranged from a few additional illnesses per million at risk, to many thousands. Although useful, published quantitative risk assessments have been unable to comprehensively address important aspects of antimicrobial resistance, including multiple exposure pathways, interrelationships among bacteria, co-selection, and cumulative effects of antimicrobial use in multiple species and countries. However, quantitative risk assessment shows promise for synthesis and analysis of scientific data. Work is required to develop methodology and train more risk analysts. An international forum is needed to pool expertise, review existing risk assessments and disseminate the results to risk managers throughout the world.

Burden of acute gastrointestinal illness in the Metropolitan region, Chile, 2008.

The purpose of this study was to determine the magnitude and distribution of acute gastrointestinal illness (GI) in the Chilean population, describe its burden and presentation, identify risk factors associated with GI and assess the differences between a 7-day, 15-day and a 30-day recall period in the population-based burden of illness study design. Face-to-face surveys were conducted on 6047 randomly selected residents in the Metropolitan region, Chile (average response rate 75·8%) in 2008. The age-adjusted monthly prevalence of GI was 9·2%. The 7-day recall period provided annual incidence rate estimates about 2·2 times those of the 30-day recall period. Age, occupation, healthcare system, sewer system, antibiotic use and cat ownership were all found to be significant predictors for being a case. This study expands on the discussion of recall bias in retrospective population studies and reports the first population-based burden and distribution of GI estimates in Chile.

Improving Aboriginal health data capture: evidence from a health registry evaluation.

The lack of high-quality health information for accurately estimating burdens of disease in some Aboriginal populations is a challenge for developing effective and relevant public health programmes and for health research. We evaluated data from a health registry system that captured patient consultations, provided by Labrador Grenfell Health (Labrador, Canada). The goal was to evaluate the registry's utility and attributes using modified CDC guidelines for evaluating surveillance systems. Infectious gastrointestinal illness data were used as a reference syndrome to determine various aspects of data collection and quality. Key-informant interviews were conducted to provide information about system utility. The study uncovered limitations in data quality and accessibility, resulting in region-specific recommendations including conversion to an electronic system. More generally, this study emphasized how a systematic and standardized evaluation of health registry systems can help address challenges to obtaining quality health data in often remote areas where many Aboriginal communities are found.