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1.
ACS ES T Water ; 4(4): 1483-1497, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38633367

ABSTRACT

Environmental reclamation of Canada's oil sands tailings ponds is among the single largest water treatment challenges globally. The toxicity of oil sands process-affected water (OSPW) has been associated with its dissolved organics, a complex mixture of naphthenic acid fraction components (NAFCs). Here, we evaluated solar treatment with buoyant photocatalysts (BPCs) as a passive advanced oxidation process (P-AOP) for OSPW remediation. Photocatalysis fully degraded naphthenic acids (NAs) and acid extractable organics (AEO) in 3 different OSPW samples. However, classical NAs and AEO, traditionally considered among the principal toxicants in OSPW, were not correlated with OSPW toxicity herein. Instead, nontarget petroleomic analysis revealed that low-polarity organosulfur compounds, composing <10% of the total AEO, apparently accounted for the majority of waters' toxicity to fish, as described by a model of tissue partitioning. These findings have implications for OSPW release, for which a less extensive but more selective treatment may be required than previously expected.

2.
Article in English | MEDLINE | ID: mdl-38124357

ABSTRACT

OBJECTIVE: We tested the ability of chat generative pretrained transformer (ChatGPT), an artificial intelligence chatbot, to answer questions relevant to scenarios covered in 3 clinical guidelines, published by the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), which has published management guidelines: endovascular treatment of stroke, perioperative stroke (Stroke), and care of patients undergoing complex spine surgery (Spine). METHODS: Four neuroanesthesiologists independently assessed whether ChatGPT could apply 52 high-quality recommendations (HQRs) included in the 3 SNACC guidelines. HQRs were deemed present in the ChatGPT responses if noted by at least 3 of the 4 reviewers. Reviewers also identified incorrect references, potentially harmful recommendations, and whether ChatGPT cited the SNACC guidelines. RESULTS: The overall reviewer agreement for the presence of HQRs in the ChatGPT answers ranged from 0% to 100%. Only 4 of 52 (8%) HQRs were deemed present by at least 3 of the 4 reviewers after 5 generic questions, and 23 (44%) HQRs were deemed present after at least 1 additional targeted question. Potentially harmful recommendations were identified for each of the 3 clinical scenarios and ChatGPT failed to cite the SNACC guidelines. CONCLUSIONS: The ChatGPT answers were open to human interpretation regarding whether the responses included the HQRs. Though targeted questions resulted in the inclusion of more HQRs than generic questions, fewer than 50% of HQRs were noted even after targeted questions. This suggests that ChatGPT should not currently be considered a reliable source of information for clinical decision-making. Future iterations of ChatGPT may refine algorithms to improve its reliability as a source of clinical information.

3.
Emerg Med J ; 40(7): 518-524, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37185304

ABSTRACT

BACKGROUND: The COVID-19 pandemic has been linked to a sharp drop in ED attendance, but the exact reasons for this are unclear. The aim of this study was to investigate differences between individuals attending the ED before and during the pandemic and the reasons for their choices. METHODS: Two population-based online surveys were conducted before (2019) and during (2020) the pandemic. Participants were recruited by a survey panel to be representative of the UK population aged 18-45 years. Both surveys asked about the circumstances and reasons for the last ED attendance, with specific pandemic-related questions in the second one. Comparisons of characteristics and symptoms of individuals attending during the pandemic were compared with those attending in prior years using χ2 tests. We determined the proportion of patients who had symptoms during the pandemic but did not attend, and the reasons for that choice. RESULTS: Young and high-income people, those with chronic illnesses and those with influenza-like symptoms were more likely to attend the ED during lockdown than before. 18% of respondents had experienced urgent symptoms during the pandemic; 60% of these individuals chose not to go to the ED. While about 30% of this group stated they believed their symptoms were not serious enough, 85% of these individuals mentioned fear of infection or worry about overburdening the system as a reason for not attending. Individuals attending during the pandemic were more likely to consider their visit unnecessary compared with those attending previously. CONCLUSIONS: The study suggests that the decision to use the ED has a discretionary component. This could potentially contribute to unnecessary visits, and raises concerns that some patients who should present at the ED do not go. More effective communication about who should visit EDs during a pandemic, and the safety of doing so, is needed.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , Pandemics , Emergency Service, Hospital , Communicable Disease Control , United Kingdom/epidemiology
4.
Heliyon ; 7(8): e07876, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34485748

ABSTRACT

This study applies the germane principles of service-dominant logic by investigating how different dimensions of service value impact customers' satisfaction and related behavioral intentions in the surf camps context. An empirical model was developed and tested via survey responses from 300 Portuguese surf camps tourists who profiled their experience. Data were analyzed using Structural Equation Modeling, specifically Partial Least Squares (PLS-PM). Results highlight the respective impact the numerous value dimensions (functional, emotional, social, epistemic, experiential, and contextual) have on the overall level of perceived value as well as its resultant impact on satisfaction and repurchase intentions.

5.
Pediatr Allergy Immunol ; 32(3): 457-464, 2021 04.
Article in English | MEDLINE | ID: mdl-33098584

ABSTRACT

BACKGROUND: Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis. METHODS: In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16 years of age. Methacholine bronchoprovocation was available in 127 and 79 children at 7 and 12 years of age, respectively. Longitudinal changes in FEV1 , FVC, and FEV1 /FVC z-scores and methacholine PC20 were analyzed. RESULTS: 55% of the study cohort (N = 122) were male, and 55% were Caucasian. During follow-up, longitudinal changes in z-scores for pre- and post-bronchodilator FEV1 (P < .0001) FVC (P < .0001) and FEV1 /FVC (P < .0001 for pre- and 0.007 for post-bronchodilator) from age 5 to 10-16 years were observed. Declined lung function in late childhood was significantly associated with gender, physician diagnosis of asthma, and allergic sensitization. PC20 geometric mean increased from 0.28 mg/mL at 7 years to 0.53 mg/mL at 12 years of age, and the frequency of abnormal bronchial hyperreactivity decreased from 96% to 78% (P = .0003). CONCLUSIONS: Following severe RSV bronchiolitis, there appear to be significant longitudinal changes in pre- and post-bronchodilator lung function during childhood. The study has several limitations including significant dropouts and the lack of a control group and post-bronchodilator measurements. Bronchial hyperreactivity is common in children following severe RSV bronchiolitis; however, it appears to decrease as they enter late childhood.


Subject(s)
Bronchial Hyperreactivity , Bronchiolitis, Viral , Bronchiolitis , Respiratory Syncytial Virus Infections , Bronchial Hyperreactivity/diagnosis , Bronchiolitis, Viral/diagnosis , Child , Follow-Up Studies , Humans , Infant , Lung , Male , Prospective Studies , Respiratory Syncytial Virus Infections/complications , Respiratory Syncytial Virus Infections/diagnosis
6.
Immun Inflamm Dis ; 8(1): 30-39, 2020 03.
Article in English | MEDLINE | ID: mdl-31901157

ABSTRACT

BACKGROUND: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life. METHODS: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin-10, interferon-γ, tumor necrosis factor-α (TNF-α), IL-4, and IL-5 production by in vitro anti-CD3/CD28- and anti-CD3/CD46-activated CD4+ T cells, and percentage of peripheral Treg (CD4+CD25hi Foxp3hi ) cells were measured by flow cytometry. Wheezing was assessed every 6 months. Recurrent wheezing was defined as three or more episodes following the initial RSV bronchiolitis. RESULTS: Sixty-seven percent (n = 111) of children had wheezing after their initial RSV infection, with 30% having recurrent wheezing. The percentage of peripheral Treg (CD4+CD25hi Foxp3hi ) cells was not significantly different between the wheezing groups. Decreased TNF-α production from anti-CD3/CD28- and anti-CD3/CD46- activated CD4+ T cells was observed in the recurrent wheezers, compared with nonwheezers (p = .048 and .03, respectively). There were no significant differences in the GZB+ CD4+ T cells and production of other inflammatory cytokines between these groups. CONCLUSIONS: We demonstrated lower TNF-α production by in vitro stimulated CD4+ T cells during severe RSV bronchiolitis in children that subsequently developed recurrent wheezing, compared with children with no subsequent wheeze. These findings support the role of CD4+ T cell immunity in the development of subsequent wheezing in these children.


Subject(s)
Bronchiolitis, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , Respiratory Sounds/etiology , Respiratory Syncytial Virus Infections/immunology , Tumor Necrosis Factor-alpha/metabolism , Cells, Cultured , Cytokines/metabolism , Female , Humans , Infant , Male , Respiratory Syncytial Virus Infections/complications , Respiratory Syncytial Viruses/isolation & purification
7.
BMJ Qual Saf ; 28(5): 382-388, 2019 05.
Article in English | MEDLINE | ID: mdl-30728187

ABSTRACT

BACKGROUND: Risk aversion among junior doctors that manifests as greater intervention (ordering of tests, diagnostic procedures and so on) has been proposed as one of the possible causes for increased pressure in emergency departments (EDs). Here we tested the prediction that doctors with more experience would be more tolerant of uncertainty and therefore less risk-averse in decision making. METHODS: In this cross-sectional, vignette-based study, doctors working in three EDs were asked to complete a questionnaire measuring experience (length of service in EDs), reactions to uncertainty (Gerrity et al, 1995) and risk aversion (responses about the appropriateness of patient management decisions). RESULTS: Data from 90 doctors were analysed. Doctors had worked in the ED for between 5 weeks and 21 years. We found a large association between experience and risk aversion so that more experienced clinicians made less risk-averse decisions (r=0.47, p<0.001). We also found a large association between experience and reactions to uncertainty (r=-0.50, p<0.001), with more experienced doctors being much more at ease with uncertainty. Mediation analyses indicated that tolerance of uncertainty partially mediated the relationship between experience and lower risk aversion, explaining about a quarter of the effect. CONCLUSION: While we might be tempted to conclude from this research that experience and the ability to tolerate uncertainty lead to positive outcomes for patients (less risk-averse management strategies and higher levels of safety netting), what we are unable to conclude from this design is that these less risk-averse strategies improve patient safety.


Subject(s)
Clinical Decision-Making , Decision Support Systems, Clinical/statistics & numerical data , Emergency Service, Hospital , Physicians/psychology , Safety Management/standards , State Medicine , Attitude of Health Personnel , Cross-Sectional Studies , England/epidemiology , Humans , Outcome and Process Assessment, Health Care , Physicians/standards , Risk Assessment , Uncertainty
8.
PLoS One ; 13(10): e0204314, 2018.
Article in English | MEDLINE | ID: mdl-30325919

ABSTRACT

Spindly Leg Syndrome (SLS) is a persistent animal welfare issue associated with the rearing of amphibians in captivity. We conducted two experiments to investigate the effects of diet, water composition and overfeeding on prevalence of SLS in newly metamorphosed harlequin frogs (Atelopus spp.). In our first experiment, we offered 400 full-sibling tadpoles of Atelopus certus isocaloric diets in treatments of 31%, 37%, 42% and 48% crude protein respectively. Tadpoles fed higher protein diets metamorphosed faster, but the incidence of SLS exceeded 80% in all treatments leading to the conclusion that variation in dietary protein was not responsible for causing SLS. We used 720 full-sibling Atelopus glyphus tadpoles in a second experiment to examine the effects of diet type, water composition and diet ration on SLS. We found that an overall incidence of 58% spindly leg in tadpoles reared in tap water, but reduced to about 10% in water treated by reverse osmosis and then reconstituted. It is possible that the reverse osmosis treatment removed some factor that caused the SLS, or that the reconstitution may have added a mineral lacking in the original tap water. Within tap water treatments, overfeeding tadpoles in tanks increased the incidence of SLS. We recommend further experimental research into this condition to identify the causative factors in the water. Additional research into the nutritional composition of food available to wild tadpoles would be useful in formulating captive diets, that have to date been solely based on surrogate species.


Subject(s)
Animal Feed/analysis , Animal Welfare/statistics & numerical data , Bufonidae/growth & development , Water/analysis , Animal Feed/adverse effects , Animal Nutritional Physiological Phenomena , Animals , Dietary Proteins/adverse effects , Incidence , Metamorphosis, Biological
10.
J Immunol Methods ; 431: 63-5, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26859243

ABSTRACT

BACKGROUND: Studies evaluating circulating dendritic cells (DCs) and natural and induced regulatory T cells (nTregs, iTregs) are often obtained at a single time point and difficult to interpret without understanding their intrinsic day-to-day biologic variability. METHODS: We investigated the day-to-day variability in quantifying DCs, nTregs (FoxP3(+)CD25(+)CD4(+)) and cytokine production by iTregs (granzyme B-GZB, Th1/2 cytokines following CD3 plus CD46 in vitro activation) from peripheral blood mononuclear cells (PBMCs) collected on three consecutive days in healthy adults. Intraclass correlation coefficients (ICCs) were used to evaluate intra-individual variability. RESULTS: In 10 healthy adults, the %PBMCs of plasmacytoid (pDC) and myeloid (mDC1 and mDC2) were 0.27 ± 0.12, 0.22 ± 0.10, and 0.02 ± 0.02, with ICC 0.91, 0.90, and 0.17 respectively. Natural Tregs (3.27 ± 1.27% CD4(+) cells) had an ICC of 0.86. Inducible Tregs (GZB-positive, 35.3 ± 17.7% CD4(+) cells) had an ICC of 0.77. The ICCs for IL-10, TNF-α, IFN-γ, IL-4, and IL-5 production by iTregs were 0.49, 0.63, 0.68, 0.74, and 0.82, respectively. There were no significant changes in ICC (<0.1) after adjusting for age, gender and atopy except for IL-4. Substantial variability for iTregs was determined for the control condition (PBS with IL-2). CONCLUSIONS: No meaningful day-to-day biologic variability was observed for the quantification of nTregs, pDC and mDC1 in normal adults; however, there was substantial variability in measuring mDC2 proportions and iTreg production of IL-10. These results suggest obtaining an average of several measurements over time to determine the most representative value of these biologic measures.


Subject(s)
Dendritic Cells/immunology , Leukocytes, Mononuclear/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Blood Cell Count , Cytokines/biosynthesis , Cytokines/immunology , Female , Health , Healthy Volunteers , Humans , Leukocytes, Mononuclear/cytology , Male , Time Factors
11.
R Soc Open Sci ; 2(10): 150287, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26587243

ABSTRACT

The 2014 Research Excellence Framework (REF2014) was conducted to assess the quality of research carried out at higher education institutions in the UK over a 6 year period. However, the process was criticized for being expensive and bureaucratic, and it was argued that similar information could be obtained more simply from various existing metrics. We were interested in whether a prediction market on the outcome of REF2014 for 33 chemistry departments in the UK would provide information similar to that obtained during the REF2014 process. Prediction markets have become increasingly popular as a means of capturing what is colloquially known as the 'wisdom of crowds', and enable individuals to trade 'bets' on whether a specific outcome will occur or not. These have been shown to be successful at predicting various outcomes in a number of domains (e.g. sport, entertainment and politics), but have rarely been tested against outcomes based on expert judgements such as those that formed the basis of REF2014.

12.
Proc Natl Acad Sci U S A ; 112(50): 15343-7, 2015 Dec 15.
Article in English | MEDLINE | ID: mdl-26553988

ABSTRACT

Concerns about a lack of reproducibility of statistically significant results have recently been raised in many fields, and it has been argued that this lack comes at substantial economic costs. We here report the results from prediction markets set up to quantify the reproducibility of 44 studies published in prominent psychology journals and replicated in the Reproducibility Project: Psychology. The prediction markets predict the outcomes of the replications well and outperform a survey of market participants' individual forecasts. This shows that prediction markets are a promising tool for assessing the reproducibility of published scientific results. The prediction markets also allow us to estimate probabilities for the hypotheses being true at different testing stages, which provides valuable information regarding the temporal dynamics of scientific discovery. We find that the hypotheses being tested in psychology typically have low prior probabilities of being true (median, 9%) and that a "statistically significant" finding needs to be confirmed in a well-powered replication to have a high probability of being true. We argue that prediction markets could be used to obtain speedy information about reproducibility at low cost and could potentially even be used to determine which studies to replicate to optimally allocate limited resources into replications.


Subject(s)
Forecasting , Research , Science , Commerce , Probability , Reproducibility of Results , Surveys and Questionnaires
13.
J Pediatric Infect Dis Soc ; 4(3): 182-8, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26336601

ABSTRACT

BACKGROUND: Vitamin D deficiency at birth has been reported as a risk factor for respiratory syncytial virus (RSV) lower respiratory tract infection during the first year of life. Limited data are available on whether an infant's vitamin D status is associated with the severity of acute RSV bronchiolitis. METHODS: Infants < 1 year of age and hospitalized with their first episode of RSV bronchiolitis were enrolled into the RSV Bronchiolitis in Early Life II cohort. We investigated the relationships between vitamin D status at enrollment and the following indicators of bronchiolitis severity: duration of hospitalization, lowest oxygen saturation measured during hospitalization, and bronchiolitis severity score. RESULTS: Among the 145 enrolled infants, the median (quartile 1 [Q1], Q3) serum 25-OH-VitD level was 36.8 (29.8, 42.3) ng/mL, with 14 infants (9.7%) having deficient serum vitamin D levels (25-OH-VitD <20 ng/mL). Vitamin D-deficient infants were younger than infants with 25-OH-VitD ≥ 20 ng/mL (2.8 vs 4.5 months, respectively; P = .04) and were less likely to consume infant's formula (42.9% vs 87.0%, respectively; P < .01). The following indicators of acute bronchiolitis severity did not differ between infants who were vitamin D-deficient and nondeficient: duration of hospitalization (P = .53), lowest oxygen saturation (P = .45), and bronchiolitis severity score (P = .97), even after adjusting for age, and for infant's formula consumption. CONCLUSIONS: Among this cohort of infants that were hospitalized for RSV bronchiolitis, vitamin D status at the time of bronchiolitis was not associated with indicators of acute bronchiolitis severity.


Subject(s)
Bronchiolitis, Viral/physiopathology , Respiratory Syncytial Virus Infections/physiopathology , Respiratory Syncytial Virus, Human , Vitamin D/blood , Bronchiolitis, Viral/complications , Cohort Studies , Female , Humans , Immunologic Factors/blood , Infant , Male , Prospective Studies , Respiratory Syncytial Virus Infections/complications , Severity of Illness Index , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications , Vitamin D Deficiency/physiopathology
14.
J Comput Assist Tomogr ; 39(4): 584-90, 2015.
Article in English | MEDLINE | ID: mdl-25938213

ABSTRACT

OBJECTIVE: We reduced the computed tomography (CT)-reconstructed field of view (FOV), increasing pixel density across airway structures and reducing partial volume effects, to determine whether this would improve accuracy of airway wall thickness quantification. METHODS: We performed CT imaging on a lung phantom and 29 participants. Images were reconstructed at 30-, 15-, and 10-cm FOV using a medium-smooth kernel. Cross-sectional airway dimensions were compared at each FOV with repeated-measures analysis of variance. RESULTS: Phantom measurements were more accurate when FOV decreased from 30 to 15 cm (P < 0.05). Decreasing FOV further to 10 cm did not significantly improve accuracy. Human airway measurements similarly decreased by decreasing FOV (P < 0.001). Percent changes in all measurements when reducing FOV from 30 to 15 cm were less than 3%. CONCLUSIONS: Airway measurements at 30-cm FOV are near the limits of CT resolution using a medium-smooth kernel. Reducing reconstructed FOV would minimally increase sensitivity to detect differences in airway dimensions.


Subject(s)
Asthma/diagnostic imaging , Asthma/physiopathology , Image Processing, Computer-Assisted/methods , Lung/diagnostic imaging , Lung/physiopathology , Multidetector Computed Tomography , Adult , Analysis of Variance , Body Weights and Measures/methods , Female , Humans , Male , Middle Aged , Phantoms, Imaging , Reproducibility of Results , Sensitivity and Specificity , Young Adult
15.
Zoo Biol ; 33(6): 485-501, 2014.
Article in English | MEDLINE | ID: mdl-25296396

ABSTRACT

Amphibian biology is intricate, and there are many inter-related factors that need to be understood before establishing successful Conservation Breeding Programs (CBPs). Nutritional needs of amphibians are highly integrated with disease and their husbandry needs, and the diversity of developmental stages, natural habitats, and feeding strategies result in many different recommendations for proper care and feeding. This review identifies several areas where there is substantial room for improvement in maintaining healthy ex situ amphibian populations specifically in the areas of obtaining and utilizing natural history data for both amphibians and their dietary items, achieving more appropriate environmental parameters, understanding stress and hormone production, and promoting better physical and population health. Using a scientific or research framework to answer questions about disease, nutrition, husbandry, genetics, and endocrinology of ex situ amphibians will improve specialists' understanding of the needs of these species. In general, there is a lack of baseline data and comparative information for most basic aspects of amphibian biology as well as standardized laboratory approaches. Instituting a formalized research approach in multiple scientific disciplines will be beneficial not only to the management of current ex situ populations, but also in moving forward with future conservation and reintroduction projects. This overview of gaps in knowledge concerning ex situ amphibian care should serve as a foundation for much needed future research in these areas.


Subject(s)
Amphibians/physiology , Animal Husbandry/methods , Animal Husbandry/standards , Animal Nutritional Physiological Phenomena , Animals, Zoo , Conservation of Natural Resources/methods , Life Cycle Stages/physiology , Amphibians/metabolism , Animals , Bone Diseases, Metabolic/prevention & control , Bone Diseases, Metabolic/veterinary , Breeding/methods , Stress, Physiological/physiology , Vitamin A Deficiency/prevention & control , Vitamin A Deficiency/veterinary
16.
Zoo Biol ; 33(6): 516-26, 2014.
Article in English | MEDLINE | ID: mdl-25255888

ABSTRACT

The success of ex situ survival assurance populations as tools for amphibian conservation depends on the health and reproductive success of founder populations. Necropsy examination and histopathology of animals that die in assurance populations are useful for the identification of population-limiting disease problems and can help to direct applied research efforts in areas such as amphibian husbandry and nutrition. This study reviewed postmortem findings in 167 frogs from 13 species that died in a large Panamanian rescue and survival assurance population between 2006 and 2011. Common problems identified in long-term captive animals, especially in Atelopus species, were epithelial squamous metaplasia suggestive of vitamin A deficiency and a polycystic nephropathy resembling lesions seen in laboratory animals with electrolyte imbalances. Metabolic bone disease was a significant contributor to morbidity in captive-bred juvenile frogs of Gastrotheca cornuta, Hemiphractus fasciatus, and Hylomantis lemur. Findings common to multiple species included poor overall nutritional condition that was sometimes attributable to maladaptation to captive husbandry and epidermal hyperplasia and hyperkeratosis possibly reflecting environmental skin irritation. Infectious diseases and endoparasitism were most common in recently captured animals and included chytridiomycosis and Rhabdias sp. lungworms. Applied research efforts to improve sustainability of survival assurance populations should focus on elucidating optimal husbandry practices for diverse species, improving methods for nutritional supplementation of cultured insects and examination of the role of water composition in disease development.


Subject(s)
Animals, Zoo , Anura , Bone Diseases, Metabolic/veterinary , Conservation of Natural Resources/methods , Metaplasia/veterinary , Mortality , Polycystic Kidney Diseases/veterinary , Animal Nutritional Physiological Phenomena/physiology , Animals , Bone Diseases, Metabolic/epidemiology , Bone Diseases, Metabolic/pathology , Conservation of Natural Resources/statistics & numerical data , Metaplasia/epidemiology , Metaplasia/pathology , Panama/epidemiology , Polycystic Kidney Diseases/epidemiology , Polycystic Kidney Diseases/pathology , Species Specificity
17.
Acad Radiol ; 21(8): 986-93, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25018070

ABSTRACT

RATIONALE AND OBJECTIVES: Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aimed to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma. MATERIALS AND METHODS: Phenotypic characterization and quantitative multidetector-row computed tomography (MDCT) of the chest were performed at baseline and ∼2.6 years later in 38 participants with asthma (severe n = 24 and mild-to-moderate n = 14) and nine normal controls from the Severe Asthma Research Program. RESULTS: Subjects with severe asthma had a significant decline in postbronchodilator forced expiratory volume in 1 second percent (FEV1%) predicted over time (P < .001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent [WA%]: P < .05) and normals (P < .05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness percent (WT%) in all subjects (P = .030 and .009, respectively) with no change in emphysema-like lung or air trapping. Baseline prebronchodilator FEV1% inversely correlated with WA% and WT% (both P < .05). In a multivariable regression model, baseline WA%, race, and health care utilization were predictors of subsequent airway remodeling. CONCLUSIONS: Severe asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling.


Subject(s)
Airway Remodeling , Asthma/diagnostic imaging , Bronchial Diseases/diagnostic imaging , Lung/diagnostic imaging , Lung/physiopathology , Multidetector Computed Tomography/methods , Adult , Asthma/complications , Bronchial Diseases/complications , Female , Humans , Longitudinal Studies , Male , Reproducibility of Results , Sensitivity and Specificity
18.
Cardiovasc Res ; 103(1): 17-27, 2014 Jul 01.
Article in English | MEDLINE | ID: mdl-24667851

ABSTRACT

AIMS: Understanding the novel signalling pathways involved in the pathogenesis of hypertension is vital for the development of effective therapeutic strategies. Recent evidence suggests a role for Toll-like receptor (TLR) 4 in the development of cardiovascular diseases. Although brain has been implicated in the pathogenesis of hypertension, the role of brain TLR4 in hypertension is largely unexplored. Therefore, we investigated the role of brain TLR4 in angiotensin (Ang) II-induced hypertension and whether central TLR4 blockade has cardioprotective effects in hypertension. METHODS AND RESULTS: Hypertension was induced in male Sprague-Dawley rats by delivering AngII for 14 days. The rats were administered either specific TLR4 blocker, viral inhibitory peptide (VIPER), or control peptide, intracerebroventricularly. Blood pressure, and cardiac hypertrophy and function, was evaluated by radiotelemetry and echocardiography, respectively. Blood and paraventricular nucleus were collected for measurement of plasma norepinephrine (NE), tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and TLR4 expression, respectively. Heart was analysed for TNF-α, IL-1ß, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NFκB), and renin-angiotensin system (RAS) components. Hypertensive rats had dramatically increased TLR4 expression compared with normotensive rats. Central blockade of TLR4 delayed progression of hypertension and improved cardiac hypertrophy and function in hypertensive rats. TLR4 blockade significantly reduced myocardial TNF-α, IL-1ß, iNOS levels, NFκB activity, and altered RAS components in hypertensive rats. These results were associated with reduced circulating NE levels in VIPER-treated hypertensive rats. CONCLUSION: These results provide mechanistic evidence that AngII-induced hypertensive effects are mediated, at least in part, by brain TLR4, and that brain TLR4 blockade attenuates AngII-induced hypertensive response, possibly via down-regulation of myocardial inflammatory molecules and sympathetic activity.


Subject(s)
Brain/physiopathology , Hypertension/physiopathology , Myocarditis/physiopathology , Toll-Like Receptor 4/antagonists & inhibitors , Angiotensin II/physiology , Animals , Blood Pressure , Cardiomegaly/etiology , Cardiomegaly/physiopathology , Cardiomegaly/therapy , Hypertension/etiology , Hypertension/therapy , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , Myocarditis/etiology , Myocarditis/therapy , NF-kappa B/metabolism , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Paraventricular Hypothalamic Nucleus/physiopathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Renin-Angiotensin System , Signal Transduction , Toll-Like Receptor 4/physiology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
19.
JAMA Ophthalmol ; 131(12): 1554-62, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24263699

ABSTRACT

IMPORTANCE: Patients often report greater visual difficulties at home than expected from vision testing in the clinic. Such discordance may be owing to worse vision in the home than measured in clinic. OBJECTIVE: To compare vision measured between the clinic and home and evaluate factors, including lighting, associated with these differences. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study conducted from 2005-2009 involved 126 patients with glaucoma and 49 without glaucoma recruited from the Glaucoma and Comprehensive Eye Clinics at Washington University, St Louis, Missouri. Patients underwent clinic and home visits, were aged 55 to 90 years, were consecutively recruited, and met inclusion criteria for this study. A total of 166 eligible patients refused participation. EXPOSURE: Participants underwent clinic and home visits randomized to order of completion. At each visit, masked and certified examiners measured binocular distance visual acuity (DVA) with a nonbacklit chart, near visual acuity (NVA), contrast sensitivity (CS), CS with glare, and lighting. MAIN OUTCOMES AND MEASURES: Differences in vision between the clinic and home. RESULTS: The mean scores for all vision tests were significantly better in the clinic than home for participants with and without glaucoma (P < .05, matched-pair t tests). For DVA, 29% of participants with glaucoma read 2 or more lines better in the clinic than home and 39% with advanced glaucoma read 3 or more lines better. For the entire sample, 21% of participants read 2 or more lines better in the clinic than home for NVA and 49% read 2 or more triplets better in the clinic for CS with glare. Lighting was the most significant factor associated with differences in vision between the clinic and home for DVA, NVA, and CS with glare testing (P < .05, multiple regression model). Median home lighting was 4.3 times and 2.8 times lower than clinic lighting in areas tested for DVA and NVA, respectively. Home lighting was below that recommended in 85% or greater of participants. CONCLUSIONS AND RELEVANCE: Vision measured in the clinic is generally better than vision measured at home, with differences mainly owing to poor home lighting. Knowledge that vision discrepancies between patient report and clinical testing may be owing to home lighting may initiate clinician-patient discussions to optimize home lighting and improve the vision of older adults in their homes.


Subject(s)
Glaucoma/physiopathology , House Calls , Lighting , Outpatient Clinics, Hospital , Vision Disorders/physiopathology , Vision, Binocular/physiology , Visual Acuity/physiology , Aged , Aged, 80 and over , Contrast Sensitivity/physiology , Cross-Sectional Studies , Female , Glare , Humans , Light , Male , Middle Aged , Pilot Projects , Quality of Life , Surveys and Questionnaires , Vision, Ocular , Visual Fields/physiology
20.
PLoS One ; 8(8): e71183, 2013.
Article in English | MEDLINE | ID: mdl-23940713

ABSTRACT

BACKGROUND: Advancements in knowledge of obesity aetiology and mobile phone technology have created the opportunity to develop an electronic tool to predict an infant's risk of childhood obesity. The study aims were to develop and validate equations for the prediction of childhood obesity and integrate them into a mobile phone application (App). METHODS AND FINDINGS: Anthropometry and childhood obesity risk data were obtained for 1868 UK-born White or South Asian infants in the Born in Bradford cohort. Logistic regression was used to develop prediction equations (at 6 ± 1.5, 9 ± 1.5 and 12 ± 1.5 months) for risk of childhood obesity (BMI at 2 years >91(st) centile and weight gain from 0-2 years >1 centile band) incorporating sex, birth weight, and weight gain as predictors. The discrimination accuracy of the equations was assessed by the area under the curve (AUC); internal validity by comparing area under the curve to those obtained in bootstrapped samples; and external validity by applying the equations to an external sample. An App was built to incorporate six final equations (two at each age, one of which included maternal BMI). The equations had good discrimination (AUCs 86-91%), with the addition of maternal BMI marginally improving prediction. The AUCs in the bootstrapped and external validation samples were similar to those obtained in the development sample. The App is user-friendly, requires a minimum amount of information, and provides a risk assessment of low, medium, or high accompanied by advice and website links to government recommendations. CONCLUSIONS: Prediction equations for risk of childhood obesity have been developed and incorporated into a novel App, thereby providing proof of concept that childhood obesity prediction research can be integrated with advancements in technology.


Subject(s)
Cell Phone , Pediatric Obesity/diagnosis , Software , Algorithms , Birth Weight , Body Mass Index , Child, Preschool , England , Female , Humans , Infant, Newborn , Logistic Models , Male , Models, Biological , Multivariate Analysis , National Health Programs , Risk Assessment
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