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1.
Glob Chang Biol ; 30(5): e17336, 2024 May.
Article in English | MEDLINE | ID: mdl-38775780

ABSTRACT

Climate change and land-use change are widely altering freshwater ecosystem functioning and there is an urgent need to understand how these broad stressor categories may interact in future. While much research has focused on mean temperature increases, climate change also involves increasing variability of both water temperature and flow regimes and increasing concentrations of atmospheric CO2, all with potential to alter stream invertebrate communities. Deposited fine sediment is a pervasive land-use stressor with widespread impacts on stream invertebrates. Sedimentation may be managed at the catchment scale; thus, uncovering interactions with these three key climate stressors may assist mitigation of future threats. This is the first experiment to investigate the individual and combined effects of enriched CO2, heatwaves, flow velocity variability, and fine sediment on realistic stream invertebrate communities. Using 128 mesocosms simulating small stony-bottomed streams in a 7-week experiment, we manipulated dissolved CO2 (ambient; enriched), fine sediment (no sediment; 300 g dry sediment), temperature (ambient; two 7-day heatwaves), and flow velocity (constant; variable). All treatments changed community composition. CO2 enrichment reduced abundances of Orthocladiinae and Chironominae and increased Copepoda abundance. Variable flow velocity had only positive effects on invertebrate abundances (7 of 13 common taxa and total abundance), in contrast to previous experiments showing negative impacts of reduced velocity. CO2 was implicated in most stressor interactions found, with CO2 × sediment interactions being most common. Communities forming under enriched CO2 conditions in sediment-impacted mesocosms had ~20% fewer total invertebrates than those with either treatment alone. Copepoda abundances doubled in CO2-enriched mesocosms without sediment, whereas no CO2 effect occurred in mesocosms with sediment. Our findings provide new insights into potential future impacts of climate change and land use in running freshwaters, in particular highlighting the potential for elevated CO2 to interact with fine sediment deposition in unpredictable ways.


Subject(s)
Carbon Dioxide , Climate Change , Geologic Sediments , Invertebrates , Rivers , Animals , Carbon Dioxide/analysis , Geologic Sediments/analysis , Invertebrates/physiology , Hot Temperature , Water Movements , Ecosystem
2.
Radiography (Lond) ; 29 Suppl 1: S103-S111, 2023 05.
Article in English | MEDLINE | ID: mdl-37062673

ABSTRACT

INTRODUCTION: The rapid pace of research in the field of Artificial Intelligence in medicine has associated risks for near-term AI. Ethical considerations of the use of AI in medicine remain a subject of much debate. Concurrently, the Involvement of People living with disease and the Public (PPI) in research is becoming mandatory in the EU and UK. The goal of this research was to elucidate the important values for our relevant stakeholders: People with MS, Radiologists, neurologists, Registered Healthcare Practitioners and Computer Scientists concerning AI in radiology and synthesize these in an ethical matrix. METHODS: An ethical matrix workshop co-designed with a patient expert. The workshop yielded a survey which was disseminated to the professional societies of the relevant stakeholders. Quantitative data were analysed using the Pingouin 0.53 python package. Qualitative data were examined with word frequency analysis and analysed for themes with grounded theory with a patient expert. RESULTS: 184 participants were recruited, (54, 60, 17, 12, 41 respectively). There were significant (p < 0.00001) differences in age, gender and ethnicity between groups. Key themes emerging from our results were the importance fast and accurate results, explanations over model performance and the significance of maintaining personal connections and choice. These themes were used to construct the ethical matrix. CONCLUSION: The ethical matrix is a useful tool for PPI and stakeholder engagement with particular advantages for near-term AI in the pandemic era. IMPLICATIONS FOR PRACTICE: We have produced an ethical matrix that allows for the inclusion of stakeholder opinion in medical AI research design.


Subject(s)
Artificial Intelligence , Radiology , Humans , Radiology/methods , Radiologists , Delivery of Health Care , Stakeholder Participation
3.
J Extracell Biol ; 1(10)2022 Oct.
Article in English | MEDLINE | ID: mdl-36591537

ABSTRACT

Extracellular vesicles (EVs) have potential in disease treatment since they can be loaded with therapeutic molecules and engineered for retention by specific tissues. However, questions remain on optimal dosing, administration, and pharmacokinetics. Previous studies have addressed biodistribution and pharmacokinetics in rodents, but little evidence is available for larger animals. Here, we investigated the pharmacokinetics and biodistribution of Expi293F-derived EVs labelled with a highly sensitive nanoluciferase reporter (palmGRET) in a non-human primate model (Macaca nemestrina), comparing intravenous (IV) and intranasal (IN) administration over a 125-fold dose range. We report that EVs administered IV had longer circulation times in plasma than previously reported in mice and were detectable in cerebrospinal fluid (CSF) after 30-60 minutes. EV association with PBMCs, especially B-cells, was observed as early as one minute post-administration. EVs were detected in liver and spleen within one hour of IV administration. However, IN delivery was minimal, suggesting that pretreatment approaches may be needed in large animals. Furthermore, EV circulation times strongly decreased after repeated IV administration, possibly due to immune responses and with clear implications for xenogeneic EV-based therapeutics. We hope that our findings from this baseline study in macaques will help to inform future research and therapeutic development of EVs.

4.
Water Res ; 191: 116767, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33418487

ABSTRACT

Bioindication has become an indispensable part of water quality monitoring in most countries of the world, with the presence and abundance of bioindicator taxa, mostly multicellular eukaryotes, used for biotic indices. In contrast, microbes (bacteria, archaea and protists) are seldom used as bioindicators in routine assessments, although they have been recognized for their importance in environmental processes. Recently, the use of molecular methods has revealed unexpected diversity within known functional groups and novel metabolic pathways that are particularly important in energy and nutrient cycling. In various habitats, microbial communities respond to eutrophication, metals, and natural or anthropogenic organic pollutants through changes in diversity and function. In this review, we evaluated the common trends in these changes, documenting that they have value as bioindicators and can be used not only for monitoring but also for improving our understanding of the major processes in lotic and lentic environments. Current knowledge provides a solid foundation for exploiting microbial taxa, community structures and diversity, as well as functional genes, in novel monitoring programs. These microbial community measures can also be combined into biotic indices, improving the resolution of individual bioindicators. Here, we assess particular molecular approaches complemented by advanced bioinformatic analysis, as these are the most promising with respect to detailed bioindication value. We conclude that microbial community dynamics are a missing link important for our understanding of rapid changes in the structure and function of aquatic ecosystems, and should be addressed in the future environmental monitoring of freshwater ecosystems.


Subject(s)
Biological Monitoring , Ecosystem , Archaea/genetics , Environmental Biomarkers , Environmental Monitoring , Fresh Water
5.
AIDS ; 33 Suppl 2: S181-S188, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31789817

ABSTRACT

: The current review examines the role of brain macrophages, that is perivascular macrophages and microglia, as a potential viral reservoir in antiretroviral therapy (ART) treated, simian immunodeficiency virus (SIV)-infected macaques. The role, if any, of latent viral reservoirs of HIV and SIV in the central nervous system during ART suppression is an unresolved issue. HIV and SIV infect both CD4 lymphocytes and myeloid cells in blood and tissues during acute and chronic infection. HIV spread to the brain occurs during acute infection by the infiltration of activated CD4 lymphocytes and monocytes from blood and is established in both embryonically derived resident microglia and monocyte-derived perivascular macrophages. ART controls viral replication in peripheral blood and cerebrospinal fluid in HIV-infected individuals but does not directly eliminate infected cells in blood, tissues or brain. Latently infected resting CD4 lymphocytes in blood and lymphoid tissues are a well recognized viral reservoir that can rebound once ART is withdrawn. In contrast, central nervous system resident microglia and perivascular macrophages in brain have not been examined as potential reservoirs for HIV during suppressive ART. Macrophages in tissues are long-lived cells that are HIV and SIV infected in tissues such as gut, lung, spleen, lymph node and brain and contribute to ongoing inflammation in tissues. However, their potential role in viral persistence and latency or their potential to rebound in the absence ART has not been examined. It has been shown that measurement of HIV latency by HIV DNA PCR in CD4 lymphocytes overestimates the size of the latent reservoirs of HIV that contribute to rebound that is cells containing the genomes of replicative viruses. Thus, the quantitative viral outgrowth assay has been used as a reliable measure of the number of latent cells that harbor infectious viral DNA and, may constitute a functional latent reservoir. Using quantitative viral outgrowth assays specifically designed to quantitate latently infected CD4 lymphocytes and myeloid cells in an SIV macaque model, we demonstrated that macrophages in brain harbor SIV genomes that reactivate and produce infectious virus in this assay, demonstrating that these cells have the potential to be a reservoir.


Subject(s)
Brain/virology , Macrophages/virology , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/physiology , Virus Latency , Animals , Anti-Retroviral Agents/therapeutic use , Brain/immunology , CD4-Positive T-Lymphocytes/virology , HIV Infections/drug therapy , Humans , Macaca mulatta , Myeloid Cells/virology , Simian Acquired Immunodeficiency Syndrome/drug therapy , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Immunodeficiency Virus/genetics , Simian Immunodeficiency Virus/immunology , Viral Load , Virus Replication
6.
Fam Pract ; 34(6): 702-707, 2017 11 16.
Article in English | MEDLINE | ID: mdl-28985299

ABSTRACT

Background: GPs can refer obese children living in deprived areas to multidisciplinary programmes for a weight loss intervention, though the effectiveness of these local initiatives targeted to this specific group is unknown. Objective: To evaluate the effectiveness of the Kids4Fit intervention in deprived areas on child's weight status. Methods: Design and setting: cohort study, including a waiting list control period. Subjects: children (N = 154) aged 6-12 years, who signed up for the Kids4Fit intervention programme, led by a dietitian, physiotherapist and child psychologist were included. Measurements of standardized body mass index (BMI-z) and waist circumference were taken at start of the waiting list period, at start and at the end of the intervention and after 52 weeks. Mixed model analyses (random effects models) were used, expressed in effect per week [ß with 95% confidence interval (CI)], compared to the waiting list expectancy over the 52-week study period. Results: Mixed model analyses showed a non-significant trend towards a lower BMI-z up to 52 weeks after start of Kids4Fit (ß: -0.0024; 95% CI: -0.0053; 0.0004), compared to the waiting list expectancy. A significantly lower waist circumference was found over time compared to the waiting list expectancy (ß: -0.0558; 95% CI: -0.0950; -0.0166). No differences were found in lifestyle and health-related quality of life. Conclusion: A local multidisciplinary intervention programme in deprived areas is effective in reducing waist circumference of obese children, compared to a waiting list expectancy, but no significant changes in lifestyle and quality of life were shown.


Subject(s)
Behavior Therapy , Exercise , Pediatric Obesity/therapy , Weight Loss/physiology , Body Mass Index , Child , Cohort Studies , Female , Humans , Male , Netherlands , Poverty , Primary Health Care , Surveys and Questionnaires
7.
Vox Sang ; 112(1): 18-24, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28001309

ABSTRACT

BACKGROUND AND OBJECTIVES: Platelet function shows significant inheritance that is at least partially genetically controlled. There is also evidence that the platelet response is stable over time, but there are few studies that have assessed consistency of platelet function over months and years. We aimed to measure platelet function in platelet donors over time in individuals selected from a cohort of 956 donors whose platelet function had been previously characterised. MATERIALS AND METHODS: Platelet function was assessed by flow cytometry, measuring fibrinogen binding and P-selectin expression after stimulation with either cross-linked collagen-related peptide or adenosine 5'-diphosphate. Eighty-nine donors from the Cambridge Platelet Function Cohort whose platelet responses were initially within the lower or upper decile of reactivity were retested between 4 months and five and a half years later. RESULTS: There was moderate-to-high correlation between the initial and repeat platelet function results for all assays (P ≤ 0·007, r2 0·2961-0·7625); furthermore, the range of results observed in the initial low and high responder groups remained significantly different at the time of the second test (P ≤ 0·0005). CONCLUSION: Platelet function remains consistent over time. This implies that this potential influence on quality of donated platelet concentrates will remain essentially constant for a given donor.


Subject(s)
Blood Platelets/metabolism , Platelet Activation/physiology , Adenosine Diphosphate/analysis , Adult , Blood Donors , Blood Platelets/cytology , Carrier Proteins/metabolism , Cohort Studies , Female , Fibrinogen/chemistry , Fibrinogen/metabolism , Flow Cytometry , Humans , Male , Middle Aged , P-Selectin/metabolism , Peptides/metabolism , Platelet Function Tests , Protein Binding
8.
Obes Res Clin Pract ; 11(5 Suppl 1): 1-51, 2017.
Article in English | MEDLINE | ID: mdl-27108215

ABSTRACT

BACKGROUND: High dropout rates and low compliance to pediatric weight-management programs have been reported. Socioeconomic status (SES) and ethnicity have been suggested as potentially important determinants of dropout and non-compliance. This review aims to assess the association between SES, ethnicity and study- and intervention dropout and non-compliance among participants in pediatric weight-management programs. METHODS: PubMed, Embase, MEDLINE, Scopus, Cochrane, Web-of-Science and Google Scholar were searched for eligible studies up to March 2014. Included were randomised controlled trials (RCT), controlled clinical trials and cohort studies evaluating pediatric weight-management programs. Studies had to report dropout or non-compliance to the study or intervention with regard to ethnicity or SES. Associations between SES and ethnicity and dropout and non-compliance were analysed descriptively. RESULTS: Fourteen RCTs and 16 cohort studies were included, studying 7264 children and adolescents, aged 2-20 years. Twenty-four studies presented data on dropout or non-compliance regarding ethnicity and 26 studies presented data regarding SES. Black participants showed higher dropout rates in weight-management interventions (range 65-67%) than White participants (range 22-27%), and low family income was associated with lower compliance to weight-management interventions. CONCLUSIONS: Black ethnicity and low family income seemed to be associated with higher dropout and lower compliance to pediatric weight-management interventions. Future qualitative studies may be needed to assess underlying reasons for increased dropout and non-compliance in these sub-populations.


Subject(s)
Ethnicity/statistics & numerical data , Patient Compliance/ethnology , Pediatric Obesity/ethnology , Pediatric Obesity/therapy , Social Class , Weight Reduction Programs/statistics & numerical data , Adolescent , Black People/statistics & numerical data , Child , Child, Preschool , Cohort Studies , Female , Hispanic or Latino/statistics & numerical data , Humans , MEDLINE , Male , Minority Groups/statistics & numerical data , Patient Compliance/statistics & numerical data , Patient Dropouts/ethnology , Patient Dropouts/statistics & numerical data , Publication Bias , Randomized Controlled Trials as Topic , White People/statistics & numerical data , Young Adult
9.
Int J Tuberc Lung Dis ; 20(4): 442-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26970151

ABSTRACT

SETTING: An urban out-patient clinic in Durban, South Africa, providing community-based treatment for drug-resistant tuberculosis (TB). OBJECTIVE: To describe concordance between patient report and clinician documentation of adverse drug reactions (ADRs) to treatment for multidrug-resistant TB (MDR-TB). DESIGN: ADRs were documented by interview using an 18-item symptom checklist and medical record data abstraction during a cross-sectional parent study with 121 MDR-TB patients, 75% of whom were co-infected with the human immunodeficiency virus. Concordance was analyzed using Cohen's κ statistic, Gwet's agreement coefficient (AC) 1, and McNemar's test. RESULTS: ADRs were reported much more frequently in patient interviews (µ = 8.6) than in medical records (µ = 1.4). Insomnia was most common (67% vs. 2%), followed by peripheral neuropathy (65% vs. 18%), and confusion (61 vs. 4%). κ scores were very low, with the highest degree of concordance found in hearing loss (κ = 0.23), which was the only ADR not found to be significantly different between the two data sources (P = 0.34). CONCLUSIONS: Our study showed a lack of concordance between patient report and clinician documentation of ADRs. These findings indicate the need for improved documentation of ADRs to better reflect patients' experiences during MDR-TB treatment. These data have important implications for country-level pharmacovigilance programs that rely on clinician documentation of ADRs for MDR-TB policy formation.


Subject(s)
Antitubercular Agents/adverse effects , Tuberculosis, Multidrug-Resistant/drug therapy , Adolescent , Adult , Antitubercular Agents/therapeutic use , Coinfection/drug therapy , Confusion/chemically induced , Confusion/physiopathology , Cross-Sectional Studies , Female , HIV Infections/drug therapy , Humans , Male , Middle Aged , Outpatients , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/physiopathology , Sleep Initiation and Maintenance Disorders/chemically induced , Sleep Initiation and Maintenance Disorders/physiopathology , South Africa , Young Adult
12.
Qual Life Res ; 24(7): 1635-43, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25477229

ABSTRACT

PURPOSE: To assess the effect of multidisciplinary intervention (MI) programs for overweight and obese children on quality of life (QoL). METHODS: Medline, EMBASE, Web of Science and Cochrane databases were searched for relevant studies without date restrictions up to July 2014. Included were randomized controlled trials and controlled clinical trials evaluating an MI aimed to reduce weight in overweight children and reporting QoL. The risk of bias of the included studies was assessed using the Cochrane guidelines. Data were pooled for short- (up to 6 months) and long-term (12-18 months) effects using a random effects model. RESULTS: In total, 11 studies were included, studying a total of 997 children aged 3-18 years. No significant differences were found between MI and control interventions on short-term QoL outcomes [mean difference (MD) 1.73, 95 % confidence interval (CI) -0.26 to 3.73 on a 0-100 scale]. Long-term results showed a nonsignificant trend toward a higher QoL in children following an MI program compared with control interventions (MD 4.40 95 % CI -0.12 to 8.92). CONCLUSION: There is insufficient evidence that MI programs, aimed to reduce weight in overweight and obese children, improve QoL.


Subject(s)
Interdisciplinary Communication , Obesity/complications , Overweight/complications , Quality of Life , Adolescent , Child , Child, Preschool , Female , Humans , Male , Risk Factors
13.
Acta Psychiatr Scand ; 129(2): 134-42, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23621452

ABSTRACT

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.


Subject(s)
Brain/physiopathology , Inhibition, Psychological , Neural Pathways/physiopathology , Psychotic Disorders/physiopathology , Adolescent , Basal Ganglia/physiopathology , Brain Mapping , Case-Control Studies , Child , Female , Frontal Lobe/physiopathology , Functional Neuroimaging , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging , Male , Neostriatum/physiopathology , Psychotic Disorders/psychology
14.
Behav Brain Res ; 245: 96-100, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23439217

ABSTRACT

Exercise and environmental enrichment are behavioural interventions that have been shown to improve learning and increase neurogenesis in rodents, possibly via neurotrophin-mediated mechanisms. However, many enrichment protocols incorporate exercise, which can itself be viewed as a source of cognitive stimulation in animals housed in standard laboratory conditions. In this experiment we investigate the effect of each intervention separately and in combination on object recognition memory, and analyse associated changes in the dentate gyrus: specifically, in BDNF expression and cell division. We show that both exercise and enrichment improve object recognition memory, but that BDNF mRNA expression and cell proliferation in the dentate gyrus of the hippocampus increase only in exercised rats. These results are in general agreement with recent studies suggesting that the exercise component is the major neurogenic and neurotrophic stimulus in environmental enrichment protocols. We add to the expanding literature several novel aspects including the finding that enrichment in the absence of exercise can improve object recognition memory, probably via mechanisms that are independent of BDNF upregulation and neurogenesis in the dentate gyrus.


Subject(s)
Brain-Derived Neurotrophic Factor/biosynthesis , Cell Proliferation , Cognition/physiology , Environment , Motor Activity/physiology , Physical Conditioning, Animal/physiology , Analysis of Variance , Animals , Cell Division/physiology , Dentate Gyrus/physiology , Male , Polymerase Chain Reaction , Psychomotor Performance/physiology , RNA/biosynthesis , RNA/genetics , Rats , Rats, Wistar , Recognition, Psychology/physiology , Running/physiology , Running/psychology
15.
Front Neurosci ; 6: 152, 2012.
Article in English | MEDLINE | ID: mdl-23087608

ABSTRACT

The National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally centered endeavor aimed at creating a large-scale (N > 1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85 years old) with advanced neuroimaging and genetics. These data will be publically shared, openly, and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.

16.
Lupus ; 20(13): 1372-7, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21729977

ABSTRACT

BACKGROUND: Antiphospholipid antibody (aPL) positive patients and patients with purported chronic Lyme disease ('CLD') share many clinical features. After identifying significant aPL in sera of several index patients with 'CLD', we performed aPL tests on all patients referred in whom 'CLD' was suspected, diagnosed or treated. METHODS: All patients with suspected, diagnosed or treated 'CLD' and reportedly 'positive' Lyme assays were studied. aPL testing included anticardiolipin antibodies (aCL), anti-beta-2-glycoprotein-1 antibodies (anti-ß2GP1) and lupus anticoagulant (LAC). Patients were classified into four newly described categories of CLD and data was analyzed. RESULTS: One hundred and six patients were evaluated, of whom 82% had neurologic symptoms and 51% rheumatologic symptoms. Eighty-eight of 106 (83%) patients had positive Lyme serologies (enzyme-linked immunosorbent assay [ELISA] 62/106, 58.4%; western blot [WB] 64/106, 60%), while 18/106 (16.9%) were negative or equivocal. aPL was found in all 'CLD' categories. aCL and/or anti-ß2GP1 were positive in 85/106 (80%), with aCL present in 69/106 (65%) and anti-ß2GP1 present in 69/106 (65%). For all assays, IgM isotypes predominated: WB 55/64 (85%), aCL 63/69 (91%), anti-ß2GP1 52/69 (75%), aCL and/or anti-ß2GP1 74/85 (87%). Anti-ß2GP1 assays occurred in higher titer than aCL: 36/69 (52%) versus 63/69 (91%), p<0.001. Seventeen patients had aPL-related events. Only 12/106 (11.3%) had true post-Lyme syndromes (PLS), category IV, or late Lyme disease (LLD). Most patients had been treated for Lyme: 82/106 (79%). CONCLUSION: aPL occurs frequently in patients with 'CLD'. IgM anti-ß2GP1, IgM aCL and IgM WB were frequently found. Documented PLS or LLD was uncommon. The role of aPL in patients with 'CLD' needs further investigation.


Subject(s)
Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/immunology , Lyme Disease/blood , Lyme Disease/immunology , Adolescent , Adult , Aged , Antiphospholipid Syndrome/complications , Chronic Disease , Diagnosis, Differential , Female , Humans , Lyme Disease/complications , Male , Middle Aged , Paresis/complications , Stroke/etiology
17.
Neuropsychologia ; 49(5): 937-944, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21354189

ABSTRACT

Risk avoidance is a hallmark of psychopathological conditions such as anxiety disorders. Yet few studies have examined its neural basis. The present work sought to identify the neural correlates of risk avoidance. While functional MRI scans were acquired, healthy adults (N=23) played a Wheel of Fortune game during which they chose to bet or pass on each of 104 proposed gamble trials. Participants also completed the Cognitive Appraisal of Risky Events (CARE, Fromme et al., 1997), a self-report measure of "real world" risky behavior. As expected, decision-making was associated with activation, as measured by increased BOLD responses, of the striatum, insula, anterior cingulate cortex, dorsolateral prefrontal cortex, and parietal lobe. Risk avoidance during probabilistic trials (percent of trials passed) was significantly correlated with precuneus and striatal responses to trials with a certain outcome (No-Risk). Similarly, "real world" risk avoidance, as measured by the CARE, was significantly correlated with precuneus activity during No-Risk trials. Collectively, these data suggest that precuneus and striatal responses to decision-making under certainty represent putative neural markers of risk avoidance in the laboratory and in the "real world." Further, they underline the need to extend neuroimaging research on risk avoidance, and associated anxiety disorders, to posterior cortical regions.


Subject(s)
Brain Mapping , Brain/physiology , Decision Making/physiology , Risk-Taking , Adult , Analysis of Variance , Brain/blood supply , Female , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Oxygen/blood , Reaction Time/physiology , Self Report , Young Adult
18.
Intern Med J ; 40(7): 527-30, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20633062

ABSTRACT

Previous studies show that identification and treatment of osteoporosis in patients with minimal trauma fractures treated as outpatients are poor. Our aim was to test two interventions designed to increase rates of identification and treatment. This prospective, action research study, using explicit medical record review and scripted telephone interview, was conducted at emergency departments (ED) of three hospitals from April 2007 to February 2008. Participants were patients aged over 50 years who were treated as outpatients with a minimal trauma wrist fracture. Data collected included demographic and fracture details, bone density testing and osteoporosis-related medication change. There were two interventions staff education in ED and fracture clinic and information provided to patients by telephone by a research nurse. These interventions were applied to all patients sequentially. The outcome measure of interest was the proportion of patients who underwent bone density testing (DEXA scans) in the follow-up period, analysed by intervention (clinic or phone). One hundred and seventeen patients were studied. Eighty-six per cent were female; median age 64 years. Ten per cent (12/117) of the ED/clinic intervention group had undergone testing at follow up. At follow up after the telephone intervention 55% (65/117) had undergone testing (P < 0.001, chi(2)). Patients undergoing testing were significantly more likely to have an osteoporosis-related medication change (relative risk 6.8, 95% CI 2.8-17.9). A brief telephone intervention and provision of information pack significantly improved testing rates for osteoporosis after minimal trauma wrist fracture. An ED/clinic-based intervention resulted in low rates of testing. Treatment of clinical osteoporosis remains suboptimal.


Subject(s)
Emergency Service, Hospital , Osteoporosis/diagnosis , Radius Fractures/therapy , Telephone , Wrist Injuries/therapy , Aged , Diagnostic Tests, Routine/trends , Emergency Service, Hospital/trends , Female , Follow-Up Studies , Fractures, Bone/etiology , Fractures, Bone/therapy , Humans , Male , Middle Aged , Osteoporosis/complications , Prospective Studies , Radius Fractures/etiology , Telephone/trends , Time Factors , Wrist Injuries/etiology
19.
Schizophr Bull ; 36(5): 1020-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-19336392

ABSTRACT

A significant proportion of patients with schizophrenia demonstrate abnormalities in dorsal prefrontal regions including the dorsolateral prefrontal and dorsal anterior cingulate cortices. However, it is less clear to what extent abnormalities are exhibited in ventral prefrontal and limbic regions, despite their involvement in social cognitive dysfunction and aggression, which represent problem domains for patients with schizophrenia. Previously, we found that reduced white matter integrity in right inferior frontal regions was associated with higher levels of aggression. Here, we used resting-state functional magnetic resonance imaging to examine amygdala/ventral prefrontal cortex (vPFC) functional connectivity (FC) and its relation to aggression in schizophrenia. Twenty-one healthy controls and 25 patients with schizophrenia or schizoaffective disorder participated. Aggression was measured using the Buss Perry Aggression Questionnaire. Regions of interest were placed in the amygdala based on previously published work. A voxelwise FC analysis was performed in which the mean time series across voxels for this bilateral amygdala seed was entered as a predictor in a multiple regression model with motion parameters and global, cerebrospinal fluid, and white matter signals as covariates. Patients showed significant reductions in FC between amygdala and vPFC regions. Moreover, in patients, the strength of this connection showed a significant inverse relationship with aggression, such that lower FC was associated with higher levels of self-rated aggression. Similar results were obtained for 2 other measures--Life History of Aggression and total arrests. These results suggest that amygdala/vPFC FC is compromised in schizophrenia and that this compromise is associated with aggression.


Subject(s)
Aggression/physiology , Amygdala/physiopathology , Magnetic Resonance Imaging , Nerve Net/physiopathology , Prefrontal Cortex/physiopathology , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology , Schizophrenic Psychology , Brain Mapping , Humans , Psychotic Disorders/diagnosis , Psychotic Disorders/psychology , Risk Factors , Schizophrenia/diagnosis
20.
Emerg Med J ; 26(12): 861-3, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19934128

ABSTRACT

OBJECTIVE: The aims of this study were to compare the estimated size of primary spontaneous pneumothorax (PSP) calculated on inspiratory and expiratory radiographs using the volumetrically derived Collins method and to determine whether radiograph type influences size classification for treatment according to published guidelines. METHOD: This retrospective cohort study included patients treated for PSP in the emergency departments of two metropolitan teaching hospitals. Data collected included patient demographics and interpleural distances required to calculate pneumothorax size by the Collins method and to classify PSP according to guidelines. The outcomes of interest were the difference in size estimate between radiograph types and agreement in size classification for treatment according to guidelines. Analysis is by bias-plot analysis, kappa analysis and descriptive statistics. RESULTS: A total of 49 pneumothoraces (44 patients) were studied. Median age was 22 years; 66% were men. Median PSP size on inspiratory radiographs was 24% (IQR 14% to 31%, range 5% to 100%). The average size difference between expiratory and inspiratory films was 9%, with size on expiratory radiographs being larger. The 95% limits of agreement were wide (-5% to 23%). For each guideline, size estimation on expiratory rather than inspiratory radiographs would have suggested a change in treatment for an additional seven patients (14%, 95% CI 7% to 27%). CONCLUSIONS: On average, PSP size calculated on expiratory radiographs is 9% higher than that calculated on matched inspiratory radiographs. Applying current management guidelines, the size difference between inspiratory and expiratory x-rays may alter initial treatment recommendation for some patients.


Subject(s)
Exhalation , Inhalation , Pneumothorax/pathology , Adult , Female , Humans , Male , Pneumothorax/diagnostic imaging , Pneumothorax/physiopathology , Radiographic Image Interpretation, Computer-Assisted/methods , Retrospective Studies , Young Adult
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