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Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function.
The present study sought to fill this gap by examining healthy controls (N = 75), unmedicated (N = 48) and medicated (N = 148) individuals with schizophrenia. Participants were recruited across five sites as part of the CNTRaCS Consortium to complete tasks assessing processing speed, cognitive control, working memory, verbal learning, relational encoding and retrieval, visual integration and reinforcement learning.
Individuals with schizophrenia who were not taking antipsychotic medications, as well as those taking antipsychotic medications, showed pervasive deficits across cognitive domains including reinforcement learning, processing speed, cognitive control, working memory, verbal learning and relational encoding and retrieval. Further, we found that chlorpromazine equivalency rates were significantly related to processing speed and working memory, while there were no significant relationships between anticholinergic load and performance on other tasks.
These findings add to a body of literature suggesting that cognitive deficits are an enduring aspect of schizophrenia, present in those off antipsychotic medications as well as those taking antipsychotic medications.
While solar photovoltaics are projected to grow, major financial barriers exist that impede installation. Soft costs (human-driven costs) can account for over half of total project costs and are often simplified in typical models. We use the National Renewable Energy Laboratory's “Cost of Renewable Energy Spreadsheet Tool” to quantify uncertainty of three soft cost inputs and their influence on the output cost of energy using variance-based sensitivity indices. We then suggest how the development process and model can be redesigned to represent the complexities of this socio-technical system.
Introduction: The number of seniors presenting to emergency departments after a fall is increasing. Head injury concerns in this population often leads to a head CT scan. The CT rate among physicians is variable and the reasons for this are unknown. This study examined the role of patient characteristics and country of practice in the decision to order a CT. Methods: This study used a case-based survey of physicians across multiple countries. Each survey included 9 cases pertaining to an 82-year old man who falls. Each case varied in one aspect compared to a base case (aspirin, warfarin, or rivaroxaban use, occipital hematoma, amnesia, dementia, and fall with no head trauma). For each case, participants indicated how “likely” they were to order a head CT scan, measured on a 100-point scale. A response of 80 or more was defined a priori as ‘likely to order a CT scan’. The survey was piloted among emergency residents for feedback on design and comprehension, and was published in French and English. Recruitment was through the Canadian Association of Emergency Physicians, Twitter and CanadiEM. For each case we compared the proportion of physicians who were ‘likely to scan’ with relative to the base case. We also compared the proportion of participants who were ‘likely to scan’ each case in the USA, UK and Australia, relative to Canada. Results: Data was collected from 484 respondents (Canada-308, USA-64, UK-67, Australia-27, and 18 from other countries). Social media distribution limited our ability to estimate of the response rate. Physicians were most likely to scan in the anticoagulation cases (90% likely to order a scan compared to 36% for the base case (p = <0.001)). Other features associated with increased scans were occipital hematoma (48%), multiple falls (68%), and amnesia (68%) (all p < 0.005). Compared to Canada, US physicians were more likely to order CT scans for all cases (p = <0.05). Compared to Canada, UK physicians were significantly less likely to order CT for patients in every case except in the patient with amnesia. Finally, Australian physicians differed from Canada only for the occipital hematoma case where they were significantly more likely to order CT scan. Conclusion: Anticoagulation, amnesia and a history of multiple falls appear to drive the ordering a head CT scan in elderly patients who had fallen. We observed variations in practice between countries. Future clinical decision rules will likely have variable impact on head CT scan rates depending on baseline practice variation.
Introduction: Although acute gastroenteritis is an extremely common childhood illness, there is a paucity of literature characterizing the associated pain and its management. Our primary objective was to quantify the pain experienced by children with acute gastroenteritis in the 24-hours prior to emergency department (ED) presentation. Secondary objectives included describing maximum pain, analgesic use, discharge recommendations, and factors that influenced analgesic use in the ED. Methods: Study participants were recruited into this prospective cohort study by the Alberta Provincial Pediatric EnTeric Infection TEam between January 2014 and September 2017. This study was conducted at two Canadian pediatric EDs; the Alberta Children's Hospital (Calgary) and the Stollery Children's Hospital (Edmonton). Eligibility criteria included < 18 years of age, acute gastroenteritis (□ 3 episodes of diarrhea or vomiting in the previous 24 hours), and symptom duration □ 7 days. The primary study outcome, caregiver-reported maximum pain in the 24-hours prior to presentation, was assessed using the 11-point Verbal Numerical Rating Scale. Results: We recruited 2136 patients, median age 20.8 months (IQR 10.4, 47.4); 45.8% (979/2136) female. In the 24-hours prior to enrolment, 28.6% (610/2136) of caregivers reported that their child experienced moderate (4-6) and 46.2% (986/2136) severe (7-10) pain in the preceding 24-hours. During the emergency visit, 31.1% (664/2136) described pain as moderate and 26.7% (571/2136) as severe. In the ED, analgesia was provided to 21.2% (452/2131) of children. The most commonly administered analgesics in the ED were ibuprofen (68.1%, 308/452) and acetaminophen (43.4%, 196/452); at home, acetaminophen was most commonly administered (77.7%, 700/901), followed by ibuprofen (37.5%, 338/901). Factors associated with analgesia use in the ED were greater pain scores during the visit, having a primary-care physician, shorter illness duration, fewer diarrheal episodes, presence of fever and hospitalization. Conclusion: Although children presenting to the ED with acute gastroenteritis experience moderate to severe pain, both prior to and during their emergency visit, analgesic use is limited. Future research should focus on appropriate pain management through the development of effective and safe pain treatment plans.
Introduction: Understanding the spatial distribution of opioid abuse at the local level may facilitate community intervention strategies. The purpose of this analysis was to apply spatial analytical methods to determine clustering of opioid-related emergency medical services (EMS) responses in the City of Calgary. Methods: Using opioid-related EMS responses in the City of Calgary between January 1st through October 31st, 2017, we estimated the dissemination area (DA) specific spatial randomness effects by incorporating the spatial autocorrelation using intrinsic Gaussian conditional autoregressive model and generalized linear mixed models (GLMM). Global spatial autocorrelation was evaluated by Morans I index. Both Getis-Ord Gi and the LISA function in Geoda were used to estimate the local spatial autocorrelation. Two models were applied: 1) Poisson regression with DA-specific non-spatial random effects; 2) Poisson regression with DA-specific G-side spatial random effects. A pseudolikelihood approach was used for model comparison. Two types of cluster analysis were used to identify the spatial clustering. Results: There were 1488 opioid-related EMS responses available for analysis. Of the responses, 74% of the individuals were males. The median age was 33 years ( IQR: 26-42 years) with 65% of individuals between 20 and 39 years, and 27% between 40 and 64 years. In 62% of EMS responses, poisoning/overdose was the chief complaint. The global Morans Index implied the presence of global spatial autocorrelation. Comparing the two models applied suggested that the spatial model provided a better fit for the adjusted opioid-related EMS response rate. Calgary Center and East were identified as hot spots by both types of cluster analysis. Conclusion: Spatial modeling has a better predictability to assess potential high risk areas and identify locations for community intervention strategies. The clusters identified in Calgarys Center and East may have implications for future response strategies.
Broadleaf species escape current integrated weed management strategies in strawberry [Fragaria×ananassa (Weston) Duchesne ex Rozier (pro sp.) [chiloensis×virginiana]] production. Clopyralid is a registered POST control option, but current application timings provide suppression of only some species. Earlier clopyralid application timings may increase spray coverage to weeds at the planting hole, but strawberry plant tolerance to applications shortly after transplant is unknown. The objectives of the study were to determine the degree of clopyralid tolerance when applied to mature strawberry plants according to current management strategies, whether clopyralid absorption and translocation were involved in the tolerance response demonstrated by mature strawberry plants, and whether clopyralid could be safely applied to immature strawberry plants shortly after transplant. Clopyralid caused no damage when applied to mature strawberry plants and did not affect crop height, number of crowns, flowers, immature berries, or yield. Maximal strawberry absorption of radiolabeled clopyralid was 82% of the recovered radioactivity and reached peak (90%) absorption at 15 h. Maximal total translocation of radioactivity from the treated leaf was 17% and reached peak translocation at 52 h. Translocation was primarily to the new leaves and reproductive structures. In the early-application experiment, damage induced by clopyralid for all application timings reached 0 by 8 wk after treatment. Across all timings, maximal damage at 140 g ha−1 was 17% when applied 14 d after transplant (DATr) and 56% at 28 g ha−1 when applied at 21 DATr. Clopyralid dose did not affect the number of crowns, aboveground biomass, or yield. There was some stunting in plant height (3%) by the high labeled dose of clopyralid. Labeled dose clopyralid applications appear safe for application timings closer to strawberry transplant, though considerations of leaf cupping should be taken under consideration for label changes.
Strawberry is an important horticultural crop in Florida. The long growing season and escapes from fumigation and PRE herbicides necessitate POST weed management to maximize harvest potential and efficiency. Alternatives to hand-weeding are desirable, but clopyralid is the only broadleaf herbicide registered for use. Weed control may be improved by early-season clopyralid applications, but at risk of high temperature and increased strawberry injury. The effect of temperature on clopyralid safety on strawberry is unknown. We undertook a growth chamber experiment using a completely randomized design to determine crop safety under various temperature conditions across acclimation, herbicide application, and post-application periods. There was no effect of clopyralid on the number of strawberry leaves across all temperatures. Damage to the strawberry manifested as leaf malformations. Acclimation temperatures affected clopyralid-associated injury (p=0.0309), with increased leaf malformations at higher temperatures (27 C) compared to lower (18 C) temperatures. Pre-treatment temperatures did not affect clopyralid injury. Post-application temperature also affected clopyralid injury (p=0.0161), with increased leaf malformations at higher temperatures compared to lower ones. Clopyralid application did not reduce flowering or biomass production in the growth chamber. If leaf malformations are to be avoided, consideration to growing conditions prior to application is advisable, especially if applying clopyralid early in the season.
X-ray micro-computed tomography (μCT) is a technique which can obtain three-dimensional images of a sample, including its internal structure, without the need for destructive sectioning. Here, we review the capability of the technique and examine its potential to provide novel insights into the lifestyles of parasites embedded within host tissue. The current capabilities and limitations of the technology in producing contrast in soft tissues are discussed, as well as the potential solutions for parasitologists looking to apply this technique. We present example images of the mouse whipworm Trichuris muris and discuss the application of μCT to provide unique insights into parasite behaviour and pathology, which are inaccessible to other imaging modalities.
Strawberries, an important Florida crop, are grown on raised beds covered with plastic mulch. The plastic mulch provides good control of many weeds, but some problem species can emerge from the transplant hole during crop establishment. POST herbicide options for broadleaf weed control within the strawberry bed is limited to clopyralid, which only provides suppression. Strawberry canopy shielding may be responsible for the observed incomplete control with clopyralid application for problematic broadleaf weed species such as black medic and Carolina geranium. Two field experiments were established on mature strawberries to evaluate spray penetration through the canopy. The first examined spray penetration through the canopy of multiple strawberry cultivars at various distances from the crown. The second examined the effects of application volumes and nozzle selection on spray penetration. Cultivar selection had no effect on spray penetration through the canopy. In the first study, when applying at 281 L ha−1, the area around the planting hole (0 to 5 cm from the crown) had 8% coverage below the canopy while the area below the canopy edge (10 to 15 cm from the crown) had 27% coverage. In the second study, increasing the application volume from 187 to 375 L ha−1 increased coverage by 81%. Increasing the application volume from 375 to 740 L ha−1 increased coverage 33% with maximal coverage of 53% at 740 L ha−1. Nozzle type (standard even flat spray tip, Drift Guard, or TwinJet nozzles) did not affect coverage or deposition volume below the canopy. Overall, mature strawberry canopies demonstrated similar spray droplet penetration across cultivars with increased penetration with increased distance from the crown. Penetration increased with increasing application volume, but the nozzle types used in this experiment did not affect penetration. Additional research is needed to better define the effect of application volume on herbicide efficacy.
Strawberries are an important horticultural crop in Florida. Black medic is among the most problematic weeds within the production system. To better coordinate control measures, black medic growth and development while in competition with strawberry was studied. Twelve plants were randomly selected at each of four field sites in Hillsborough County, FL, in 2014. Plants were repeatedly measured over the growing season for stem length and number of primary branches, flower buds, flowers, and seed clusters. Growing degree days (GDD) were calculated (Tbase=0 C) starting from the hole-punch application of the plastic mulch (October 8, 2014, to October 10, 2014) from weather station data generated from the Florida Automated Weather Network. Strawberry height and width increased consistently across all sites, but black medic growth and development varied considerably. Strawberry suppressed black medic growth up to 1,805 cumulative GDD at three of four sites where black medic remained beneath the strawberry canopy. After 1,805 GDD, the black medic stems still remained below but experienced exponential growth for total stem length and, in turn, flower buds, inflorescence, and immature seed clusters. Ideal clopyralid spray timing based on susceptible plant size was 890 to 1,152 GDD. Optimal hand-weeding time frames would likely occur as the plant stems expand beyond the strawberry canopy (to improve visibility) and before flower production to prevent seed return to the seedbank. First seed production was observed at 1,200 GDD at the earliest site and between 1,966 to 2,365 GDD across all the other sites. Overall, consistent trends were observed across sites, but between-site variability was observed that could not be accounted for by differences in temperature.
Patients with schizophrenia have shown cognitive improvements following
cognitive remediation, but the neuroplastic changes that support these
processes are not fully understood.
To use a triple-blind, placebo-controlled trial to examine neural
activation before and after cognitive remediation or a computer skills
training (CST) placebo (trial registration: NCT00995553)).
Twenty-seven participants underwent functional magnetic resonance imaging
before and after being randomised to either cognitive remediation
intervention or CST. Participants completed two variants of the N-back
task during scanning and were assessed on measures of cognition,
functional capacity, community functioning and symptoms.
We observed a group × time interaction in the left prefrontal cortex,
wherein the cognitive remediation group showed increased activation.
These changes correlated with improved task accuracy within the cognitive
remediation group, whereas there was no relationship between changes in
activation in untrained cognitive measures. Significant changes were not
observed in other hypothesised areas for the cognitive remediation
We replicated the finding that cognitive remediation increases left
lateral prefrontal activation during a working memory task in patients
with schizophrenia, suggesting this may be an important neural target for
these types of interventions.
Objective: Multiple system atrophy (MSA) is an incurable neurodegenerative illness in which progressive symptoms, including stridor and acute laryngeal obstruction, occur. Advanced care planning and palliative care discussions in people living with MSA are not well defined. The aim of the present study is to evaluate advanced care planning and current practices in palliative care in MSA to identify opportunities for improving quality of care. Methods: The study is a retrospective chart review assessing the focus and timing of palliative care discussions in people living with MSA. Some 22 charts were reviewed. Results: A total of 22 patients were included. The most common symptoms were parkinsonism, orthostatic hypotension, GI/GU dysfunction, ataxia and gait impairment. Six patients had stridor. Of the palliative care discussions that took place, the most common topics were diagnosis, symptoms or symptom management, and prognosis. In the majority of patients who died and who had a do-not-attempt-resuscitation order, discussions surrounding resuscitation and goals of care took place only hours before death. Conclusions: There is no standard approach to advanced care planning and palliative care discussions in people living with MSA. We propose a framework to guide advanced care planning and palliative care discussions in MSA.
Previous neuroimaging studies indicate abnormalities in cortico-limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel-based morphometry to examine the trajectory of these abnormalities during early stages of illness development.
Unaffected individuals (16–25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls (‘low risk’, n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures.
Significant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub-diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline.
These longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures.
Expert judgement has been used since the actuarial profession was founded. In the past, there has often been a lack of transparency regarding the use of expert judgement, even though those judgements could have a very significant impact on the outputs of calculations and the decisions made by organisations. The lack of transparency has a number of dimensions, including the nature of the underlying judgements, as well as the process used to derive those judgements. This paper aims to provide a practical framework regarding expert judgement processes, and how those processes may be validated. It includes a worked example illustrating how the process could be used for setting a particular assumption. It concludes with some suggested tools for use within expert judgement. Although primarily focussed on the insurance sector, the proposed process framework could be applied more widely without the need for significant changes.
Neurocognitive performance deficits have been observed in mood disorder patients and their unaffected relatives and may therefore qualify as endophenotypes. However, the precise time course of neurocognitive deficits has not been studied so that it is unknown whether neurocognitive abnormalities reflect the early effects of familial vulnerability to mood disorders or if they emerge at illness onset.
A neuropsychological test battery was administered at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy controls (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HR-well). Linear mixed-effects models were used to investigate differences and longitudinal changes in the domains of attentional processing, working memory, verbal learning and memory, and cognitive flexibility.
Reduced long delay verbal memory and extradimensional set-shifting performance across both time points were found in the HR-well group relative to controls. The HR-MDD group displayed decreased extradimensional set-shifting abilities across both time points as compared with the HC group only. There were no significant performance differences between the two high-risk groups.
Reduced verbal memory and cognitive flexibility are familial trait markers for vulnerability to mood disorders in individuals with a close family history of bipolar disorder. Both neurocognitive performance deficits appear to be relatively stable over a 2-year time period and do not appear to be linked to the onset of MDD. These findings support their use as stable quantitative endophenotypes for mood disorders.