Publications by authors named "Paul C Johnson"

101 Publications

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Nat Commun 2021 01 5;12(1):24. Epub 2021 Jan 5.

Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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http://dx.doi.org/10.1038/s41467-020-19366-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785747PMC
January 2021

Classification and characterisation of livestock production systems in northern Tanzania.

PLoS One 2020 30;15(12):e0229478. Epub 2020 Dec 30.

Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Livestock keepers in sub-Saharan Africa face a range of pressures, including climate change, land loss, restrictive policies, and population increase. Widespread adaptation in response can lead to the emergence of new, non-traditional typologies of livestock production. We sought to characterise livestock production systems in two administrative regions in northern Tanzania, an area undergoing rapid social, economic, and environmental change. Questionnaire and spatial data were collected from 404 livestock-keeping households in 21 villages in Arusha and Manyara Regions in 2016. Multiple factor analysis and hierarchical cluster analysis were used to classify households into livestock production systems based on household-level characteristics. Adversity-based indicators of vulnerability, including reports of hunger, illness, and livestock, land and crop losses were compared between production systems. Three distinct clusters emerged through this process. The ethnic, environmental and livestock management characteristics of households in each cluster broadly mapped onto traditional definitions of 'pastoral', 'agro-pastoral' and 'smallholder' livestock production in the study area, suggesting that this quantitative classification system is complementary to more qualitative classification methods. Our approach allowed us to demonstrate a diversity in typologies of livestock production at small spatial scales, with almost half of study villages comprising more than one production system. We also found indicators of change within livestock production systems, most notably the adoption of crop agriculture in the majority of pastoral households. System-level heterogeneities in vulnerability were evident, with agro-pastoral households most likely to report hunger and pastoral households most likely to report illness in people and livestock, and livestock losses. We demonstrate that livestock production systems can provide context for assessing household vulnerability in northern Tanzania. Policy initiatives to improve household and community well-being should recognise the continuing diversity of traditional livestock production systems in northern Tanzania, including the diversity that can exist at small spatial scales.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773236PMC
January 2021

Towards the elimination of dog-mediated rabies: development and application of an evidence-based management tool.

BMC Infect Dis 2020 Oct 20;20(1):778. Epub 2020 Oct 20.

University of Glasgow, Institute of Biodiversity, Animal Health and Comparative Medicine, Graham Kerr building, MVLS, Glasgow, G12 8QQ, UK.

Background: International organizations advocate for the elimination of dog-mediated rabies, but there is only limited guidance on interpreting surveillance data for managing elimination programmes. With the regional programme in Latin America approaching elimination of dog-mediated rabies, we aimed to develop a tool to evaluate the programme's performance and generate locally-tailored rabies control programme management guidance to overcome remaining obstacles.

Methods: We developed and validated a robust algorithm to classify progress towards rabies elimination within sub-national administrative units, which we applied to surveillance data from Brazil and Mexico. The method combines criteria that are easy to understand, including logistic regression analysis of case detection time series, assessment of rabies virus variants, and of incursion risk. Subjecting the algorithm to robustness testing, we further employed simulated data sub-sampled at differing levels of case detection to assess the algorithm's performance and sensitivity to surveillance quality.

Results: Our tool demonstrated clear epidemiological transitions in Mexico and Brazil: most states progressed rapidly towards elimination, but a few regressed due to incursions and control lapses. In 2015, dog-mediated rabies continued to circulate in the poorest states, with foci remaining in only 1 of 32 states in Mexico, and 2 of 27 in Brazil, posing incursion risks to the wider region. The classification tool was robust in determining epidemiological status irrespective of most levels of surveillance quality. In endemic settings, surveillance would need to detect less than 2.5% of all circulating cases to result in misclassification, whereas in settings where incursions become the main source of cases the threshold detection level for correct classification should not be less than 5%.

Conclusion: Our tool provides guidance on how to progress effectively towards elimination targets and tailor strategies to local epidemiological situations, while revealing insights into rabies dynamics. Post-campaign assessments of dog vaccination coverage in endemic states, and enhanced surveillance to verify and maintain freedom in states threatened by incursions were identified as priorities to catalyze progress towards elimination. Our finding suggests genomic surveillance should become increasingly valuable during the endgame for discriminating circulating variants and pinpointing sources of incursions.
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http://dx.doi.org/10.1186/s12879-020-05457-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574347PMC
October 2020

Development and Validation of a Controlled Pressure Method Test Protocol for Vapor Intrusion Pathway Assessment.

Environ Sci Technol 2020 06 29;54(12):7117-7125. Epub 2020 May 29.

Department of Civil and Environmental Engineering, Colorado School of Mines, Golden, Colorado 80401, United States.

Controlled pressure method (CPM) testing is a building-specific diagnostic tool for vapor intrusion (VI) pathway assessment which offers advantages over traditional pathway assessment approaches. By manipulating the building pressure conditions, the CPM creates the worst-case VI impact and provides rapid insight into the type of vapor source(s). The primary barrier to general acceptance and use of this tool is the need for definitive guidance on test design parameters, such as the indoor-outdoor pressure difference (or exhaust fan flow rate), CPM test duration, exhaust fan location, and air sampling location(s) and conditions. This study focused on a systematic evaluation of each of these factors, which then led to the formulation of proposed CPM testing guidelines. The results suggest that CPM tests should be conducted with both negative and positive pressure indoor-outdoor differentials of about 10-15 Pa, and the tests should last for at least nine indoor air exchanges for negative pressure difference testing and four indoor air exchanges for positive pressure difference testing. Although exhaust fan intake sampling is sufficient to provide critical information to assess impacts during negative pressure testing, adding room-specific indoor air sampling to both negative and positive pressure difference testing can provide insight into vapor entry locations and indoor source contributions.
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http://dx.doi.org/10.1021/acs.est.0c00811DOI Listing
June 2020

Virus-virus interactions impact the population dynamics of influenza and the common cold.

Proc Natl Acad Sci U S A 2019 Dec 16. Epub 2019 Dec 16.

MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, G61 1QH Glasgow, United Kingdom;

The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus-virus interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions.
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http://dx.doi.org/10.1073/pnas.1911083116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936719PMC
December 2019

Estimating the Size of Dog Populations in Tanzania to Inform Rabies Control.

Vet Sci 2018 Sep 7;5(3). Epub 2018 Sep 7.

Boyd Orr Centre for Population and Ecosystem Health, Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow G12 8QQ, UK.

Estimates of dog population sizes are a prerequisite for delivering effective canine rabies control. However, dog population sizes are generally unknown in most rabies-endemic areas. Several approaches have been used to estimate dog populations but without rigorous evaluation. We compare post-vaccination transects, household surveys, and school-based surveys to determine which most precisely estimates dog population sizes. These methods were implemented across 28 districts in southeast Tanzania, in conjunction with mass dog vaccinations, covering a range of settings, livelihoods, and religious backgrounds. Transects were the most precise method, revealing highly variable patterns of dog ownership, with human/dog ratios ranging from 12.4:1 to 181.3:1 across districts. Both household and school-based surveys generated imprecise and, sometimes, inaccurate estimates, due to small sample sizes in relation to the heterogeneity in patterns of dog ownership. Transect data were subsequently used to develop a predictive model for estimating dog populations in districts lacking transect data. We predicted a dog population of 2,316,000 (95% CI 1,573,000⁻3,122,000) in Tanzania and an average human/dog ratio of 20.7:1. Our modelling approach has the potential to be applied to predicting dog population sizes in other areas where mass dog vaccinations are planned, given census and livelihood data. Furthermore, we recommend post-vaccination transects as a rapid and effective method to refine dog population estimates across large geographic areas and to guide dog vaccination programmes in settings with mostly free roaming dog populations.
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http://dx.doi.org/10.3390/vetsci5030077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164483PMC
September 2018

Creation of a Sub-slab Soil Gas Cloud by an Indoor Air Source and Its Dissipation Following Source Removal.

Environ Sci Technol 2018 09 29;52(18):10637-10646. Epub 2018 Aug 29.

School of Sustainable Engineering and the Built Environment, Ira A. Fulton Schools of Engineering , Arizona State University , Tempe , Arizona 85287 , United States.

It is accepted that indoor sources of volatile organic compounds can confound vapor intrusion (VI) pathway assessment. When they are discovered during pre-sampling inspection, indoor sources are removed and air sampling is delayed, with the assumption that a few hours to a few days are sufficient for indoor source impacts to dissipate. This assumption was tested through the controlled release of SF and its monitoring in indoor air and soil gas at a study house over 2 years. Results show that indoor sources generate subsurface soil gas clouds as a result of fluctuating direction in the exchange between soil gas and indoor air and that it may take days to weeks under natural conditions for a soil gas cloud beneath a building to dissipate following indoor source removal. The data also reveal temporal variability in indoor air and soil gas concentrations, long-term seasonal patterns, and dissipation of soil gas clouds over days to weeks following source removal. Preliminary modeling results for similar conditions are consistent field observations. If representative of other sites, these results suggest that a typical 1-3 day waiting period following indoor source removal may not be sufficient to avoid confounding data and erroneous conclusions regarding VI occurrence.
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http://dx.doi.org/10.1021/acs.est.8b01188DOI Listing
September 2018

Implications Enzymatic Degradation of the Endothelial Glycocalyx on the Microvascular Hemodynamics and the Arteriolar Red Cell Free Layer of the Rat Cremaster Muscle.

Front Physiol 2018 16;9:168. Epub 2018 Mar 16.

Department of Bioengineering, University of California, San Diego, San Diego, La Jolla, CA, United States.

The endothelial glycocalyx is a complex network of glycoproteins, proteoglycans, and glycosaminoglycans; it lines the vascular endothelial cells facing the lumen of blood vessels forming the endothelial glycocalyx layer (EGL). This study aims to investigate the microvascular hemodynamics implications of the EGL by quantifying changes in blood flow hydrodynamics post-enzymatic degradation of the glycocalyx layer. High-speed intravital microscopy videos of small arteries (around 35 μm) of the rat cremaster muscle were recorded at various time points after enzymatic degradation of the EGL. The thickness of the cell free layer (CFL), blood flow velocity profiles, and volumetric flow rates were quantified. Hydrodynamic effects of the presence of the EGL were observed in the differences between the thickness of CFL in microvessels with an intact EGL and glass tubes of similar diameters. Maximal changes in the thickness of CFL were observed 40 min post-enzymatic degradation of the EGL. Analysis of the frequency distribution of the thickness of CFL allows for estimation of the thickness of the endothelial surface layer (ESL), the plasma layer, and the glycocalyx. Peak flow, maximum velocity, and mean velocity were found to statistically increase by 24, 27, and 25%, respectively, after enzymatic degradation of the glycocalyx. The change in peak-to-peak maximum velocity and mean velocity were found to statistically increase by 39 and 32%, respectively, after 40 min post-enzymatic degradation of the EGL. The bluntness of blood flow velocity profiles was found to be reduced post-degradation of the EGL, as the exclusion volume occupied by the EGL increased the effective volume impermeable to RBCs in microvessels. This study presents the effects of the EGL on microvascular hemodynamics. Enzymatic degradation of the EGL resulted in a decrease in the thickness of CFL, an increase in blood velocity, blood flow, and decrease of the bluntness of the blood flow velocity profile in small arterioles. In summary, the EGL functions as a molecular sieve to solute transport and as a lubrication layer to protect the endothelium from red blood cell (RBC) motion near the vessel wall, determining wall shear stress.
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http://dx.doi.org/10.3389/fphys.2018.00168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864934PMC
March 2018

The coefficient of determination and intra-class correlation coefficient from generalized linear mixed-effects models revisited and expanded.

J R Soc Interface 2017 09 13;14(134). Epub 2017 Sep 13.

Population Ecology Group, Institute of Ecology, Friedrich Schiller University Jena, Dornburger Strasse 159, 07743 Jena, Germany

The coefficient of determination quantifies the proportion of variance explained by a statistical model and is an important summary statistic of biological interest. However, estimating for generalized linear mixed models (GLMMs) remains challenging. We have previously introduced a version of that we called [Formula: see text] for Poisson and binomial GLMMs, but not for other distributional families. Similarly, we earlier discussed how to estimate intra-class correlation coefficients (ICCs) using Poisson and binomial GLMMs. In this paper, we generalize our methods to all other non-Gaussian distributions, in particular to negative binomial and gamma distributions that are commonly used for modelling biological data. While expanding our approach, we highlight two useful concepts for biologists, Jensen's inequality and the delta method, both of which help us in understanding the properties of GLMMs. Jensen's inequality has important implications for biologically meaningful interpretation of GLMMs, whereas the delta method allows a general derivation of variance associated with non-Gaussian distributions. We also discuss some special considerations for binomial GLMMs with binary or proportion data. We illustrate the implementation of our extension by worked examples from the field of ecology and evolution in the environment. However, our method can be used across disciplines and regardless of statistical environments.
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http://dx.doi.org/10.1098/rsif.2017.0213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636267PMC
September 2017

Comparing Methods of Assessing Dog Rabies Vaccination Coverage in Rural and Urban Communities in Tanzania.

Front Vet Sci 2017 14;4:33. Epub 2017 Mar 14.

Environmental Health and Ecological Sciences Thematic Group, Ifakara Health Institute, Ifakara, Tanzania; Boyd Orr Centre for Population and Ecosystem Health, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Rabies can be eliminated by achieving comprehensive coverage of 70% of domestic dogs during annual mass vaccination campaigns. Estimates of vaccination coverage are, therefore, required to evaluate and manage mass dog vaccination programs; however, there is no specific guidance for the most accurate and efficient methods for estimating coverage in different settings. Here, we compare post-vaccination transects, school-based surveys, and household surveys across 28 districts in southeast Tanzania and Pemba island covering rural, urban, coastal and inland settings, and a range of different livelihoods and religious backgrounds. These approaches were explored in detail in a single district in northwest Tanzania (Serengeti), where their performance was compared with a complete dog population census that also recorded dog vaccination status. Post-vaccination transects involved counting marked (vaccinated) and unmarked (unvaccinated) dogs immediately after campaigns in 2,155 villages (24,721 dogs counted). School-based surveys were administered to 8,587 primary school pupils each representing a unique household, in 119 randomly selected schools approximately 2 months after campaigns. Household surveys were conducted in 160 randomly selected villages (4,488 households) in July/August 2011. Costs to implement these coverage assessments were $12.01, $66.12, and $155.70 per village for post-vaccination transects, school-based, and household surveys, respectively. Simulations were performed to assess the effect of sampling on the precision of coverage estimation. The sampling effort required to obtain reasonably precise estimates of coverage from household surveys is generally very high and probably prohibitively expensive for routine monitoring across large areas, particularly in communities with high human to dog ratios. School-based surveys partially overcame sampling constraints, however, were also costly to obtain reasonably precise estimates of coverage. Post-vaccination transects provided precise and timely estimates of community-level coverage that could be used to troubleshoot the performance of campaigns across large areas. However, transects typically overestimated coverage by around 10%, which therefore needs consideration when evaluating the impacts of campaigns. We discuss the advantages and disadvantages of these different methods and make recommendations for how vaccination campaigns can be better monitored and managed at different stages of rabies control and elimination programs.
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http://dx.doi.org/10.3389/fvets.2017.00033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348529PMC
March 2017

Erratum to: Development and evaluation of mosquito-electrocuting traps as alternatives to the human landing catch technique for sampling host-seeking malaria vectors.

Malar J 2016 15;15:558. Epub 2016 Nov 15.

Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Graham Kerr Building, Glasgow, G12 8QQ UK.

[This corrects the article DOI: 10.1186/s12936-015-1025-4.].
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http://dx.doi.org/10.1186/s12936-016-1562-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111336PMC
November 2016

An improved mosquito electrocuting trap that safely reproduces epidemiologically relevant metrics of mosquito human-feeding behaviours as determined by human landing catch.

Malar J 2016 Sep 13;15:465. Epub 2016 Sep 13.

Environmental Health and Ecological Sciences Thematic Group, Coordination Office, Ifakara Health Institute, PO Box 78373, Kiko Avenue, Mikocheni, Dar es Salaam, United Republic of Tanzania.

Background: Reliable quantification of mosquito host-seeking behaviours is required to determine the efficacy of vector control methods. For malaria, the gold standard approach remains the risky human landing catch (HLC). Here compare the performance of an improved prototype of the mosquito electrocuting grid trap (MET) as a safer alternative with HLC for measuring malaria vector behaviour in Dar es Salaam, Tanzania.

Methods: Mosquito trapping was conducted at three sites within Dar es Salaam representing a range of urbanicity over a 7-month period (December 2012-July 2013, 168 sampling nights). At each site, sampling was conducted in a block of four houses, with two houses being allocated to HLC and the other to MET on each night of study. Sampling was conducted both indoors and outdoors (from 19:00 to 06:00 each night) at all houses, with trapping method (HLC and MET) being exchanged between pairs of houses at each site using a crossover design.

Results: The MET caught significantly more Anopheles gambiae sensu lato than the HLC, both indoors (RR [95 % confidence interval (CI)]) = 1.47 [1.23-1.76], P < 0.0001 and outdoors = 1.38 [1.14-1.67], P < 0.0001). The sensitivity of MET compared with HLC did not detectably change over the course of night for either An. gambiae s.l. (OR [CI]) = 1.01 [0.94-1.02], P = 0.27) or Culex spp. (OR [CI]) = 0.99 [0.99-1.0], P = 0.17) indoors and declined only slightly outdoors: An. gambiae s.l. (OR [CI]) = 0.92 [0.86-0.99], P = 0.04), and Culex spp. (OR [CI]) = 0.99 [0.98-0.99], P = 0.03). MET-based estimates of the proportions of mosquitoes caught indoors (P i ) or during sleeping hours (P fl ), as well as the proportion of human exposure to bites that would otherwise occurs indoors (π i ), were statistically indistinguishable from those based on HLC for An. gambiae s.l. (P = 0.43, 0.07 and 0.48, respectively) and Culex spp. (P = 0.76, 0.24 and 0.55, respectively).

Conclusions: This improved MET prototype is highly sensitive tool that accurately quantifies epidemiologically-relevant metrics of mosquito biting densities, behaviours and human exposure distribution.
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http://dx.doi.org/10.1186/s12936-016-1513-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020444PMC
September 2016

Evolution of drug-tolerant nematode populations in response to density reduction.

Evol Appl 2016 Jun 29;9(5):726-38. Epub 2016 Mar 29.

Institute of Biodiversity, Animal Health and Comparative Medicine College of Medical, Veterinary and Life Sciences University of Glasgow Glasgow UK.

Resistance to xenobiotics remains a pressing issue in parasite treatment and global agriculture. Multiple factors may affect the evolution of resistance, including interactions between life-history traits and the strength of selection imposed by different drug doses. We experimentally created replicate selection lines of free-living Caenorhabditis remanei exposed to Ivermectin at high and low doses to assess whether survivorship of lines selected in drug-treated environments increased, and if this varied with dose. Additionally, we maintained lines where mortality was imposed randomly to control for differences in density between drug treatments and to distinguish between the evolutionary consequences of drug-treatment versus ecological processes due to changes in density-dependent feedback. After 10 generations, we exposed all of the selected lines to high-dose, low-dose and drug-free environments to evaluate evolutionary changes in survivorship as well as any costs to adaptation. Both adult and juvenile survival were measured to explore relationships between life-history stage, selection regime and survival. Intriguingly, both drug-selected and random-mortality lines showed an increase in survivorship when challenged with Ivermectin; the magnitude of this increase varied with the intensity of selection and life-history stage. Our results suggest that interactions between density-dependent processes and life history may mediate evolved changes in susceptibility to control measures.
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http://dx.doi.org/10.1111/eva.12376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869413PMC
June 2016

Problem behaviours and symptom dimensions of psychiatric disorders in adults with intellectual disabilities: An exploratory and confirmatory factor analysis.

Res Dev Disabil 2016 Aug 25;55:1-13. Epub 2016 Mar 25.

University of Glasgow, Institute of Health and Wellbeing, Academic Centre, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow G12 0XH, Scotland, UK. Electronic address:

Background: The limited evidence on the relationship between problem behaviours and symptoms of psychiatric disorders experienced by adults with intellectual disabilities leads to conflict about diagnostic criteria and confused treatment. This study examined the relationship between problem behaviours and other psychopathology, and compared the predictive validity of dimensional and categorical models experienced by adults with intellectual disabilities.

Methods: Exploratory and confirmatory factor analyses appropriate for non-continuous data were used to derive, and validate, symptom dimensions using two clinical datasets (n=457; n=274). Categorical diagnoses were derived using DC-LD. Severity and 5-year longitudinal outcome was measured using a battery of instruments.

Results: Five factors/dimensions were identified and confirmed. Problem behaviours were included in an emotion dysregulation-problem behaviour dimension that was distinct from the depressive, anxiety, organic and psychosis dimensions. The dimensional model had better predictive validity than categorical diagnosis.

Conclusions: International classification systems should not include problem behaviours as behavioural equivalents in diagnostic criteria for depression or other psychiatric disorders. Investigating the relevance of emotional regulation to psychopathology may provide an important pathway for development of improved interventions.

What This Paper Adds: There is uncertainty whether new onset problem behaviours or a change in longstanding problem behaviours should be considered as symptoms of depression or other types of psychiatric disorders in adults with intellectual disabilities. The validity of previous studies was limited by the use of pre-defined, categorical diagnoses or unreliable statistical methods. This study used robust statistical modelling to examine problem behaviours within a dimensional model of symptoms. We found that problem behaviours were included in an emotional dysregulation dimension and not in the dimension that included symptoms that are typical of depression. The dimensional model of symptoms had greater predictive validity than categorical diagnoses of psychiatric disorders. Our findings suggest that problem behaviours are a final common pathway for emotional distress in adults with intellectual disabilities so clinicians should not use a change in problem behaviours as a diagnostic criterion for depression, or other psychiatric disorders.
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http://dx.doi.org/10.1016/j.ridd.2016.03.007DOI Listing
August 2016

High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort.

PLoS One 2016 16;11(3):e0151587. Epub 2016 Mar 16.

Dept. of Gastroenterology, Gartnavel General Hospital, Glasgow, United Kingdom.

Background & Aims: Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.

Methods: The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.

Results: Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4-2.6]. High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2-12.7] for HDA, 1.4 [0.9-2.0] for LDA and 1.5 [1.0-2.2] for HDS.

Conclusions: The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151587PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794178PMC
July 2016

Development and evaluation of mosquito-electrocuting traps as alternatives to the human landing catch technique for sampling host-seeking malaria vectors.

Malar J 2015 Dec 15;14:502. Epub 2015 Dec 15.

Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Graham Kerr Building, Glasgow, G12 8QQ, UK.

Background: The human landing catch (HLC) is the gold standard method for sampling host-seeking malaria vectors. However, the HLC is ethically questionable because it requires exposure of humans to potentially infectious mosquito bites.

Methods: Two exposure-free methods for sampling host-seeking mosquitoes were evaluated using electrocuting surfaces as potential replacements for HLC: (1) a previously evaluated, commercially available electrocuting grid (CA-EG) designed for killing flies, and (2) a custom-made mosquito electrocuting trap (MET) designed to kill African malaria vectors. The MET and the CA-EG were evaluated relative to the HLC in a Latin Square experiment conducted in the Kilombero Valley, Tanzania. The sampling consistency of the traps across the night and at varying mosquito densities was investigated. Estimates of the proportion of mosquitoes caught indoors (P(i)), proportion of human exposure occurring indoors (π(i)), and proportion of mosquitoes caught when most people are likely to be indoors (P(fl)) were compared for all traps.

Results: Whereas the CA-EG performed poorly (<10% of catch of HLC), sampling efficiency of the MET for sampling Anopheles funestus s.l. was indistinguishable from HLC indoors and outdoors. For Anopheles gambiae s.l., sampling sensitivity of MET was 20.9% (95% CI 10.3-42.2) indoors and 58.5% (95% CI 32.2-106.2) outdoors relative to HLC. There was no evidence of density-dependent sampling by the MET or CA-EG. Similar estimates of P(i) were obtained for An. gambiae s.l. and An. funestus s.l. from all trapping methods. The proportion of mosquitoes caught when people are usually indoors (P(fl)) was underestimated by the CA-EG and MET for An. gambiae s.l., but similar to the HLC for An. funestus. Estimates of the proportion of human exposure occurring indoors (π(i)) obtained from the CA-EG and MET were similar to the HLC for An. gambiae s.l., but overestimated for An. funestus.

Conclusions: The MET showed promise as an outdoor sampling tool for malaria vectors where it achieved >50% sampling sensitivity relative to the HLC. The CA-EG had poor sampling sensitivity outdoors and inside. With further modification, the MET could provide an efficient and safer alternative to the HLC for the surveillance of mosquito vectors outdoors.
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http://dx.doi.org/10.1186/s12936-015-1025-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681165PMC
December 2015

Identification of Alternative Vapor Intrusion Pathways Using Controlled Pressure Testing, Soil Gas Monitoring, and Screening Model Calculations.

Environ Sci Technol 2015 Nov 5;49(22):13472-82. Epub 2015 Nov 5.

School of Sustainable Engineering and the Built Environment, Ira A Fulton Schools of Engineering, Arizona State University , Tempe, Arizona 85287, United States.

Vapor intrusion (VI) pathway assessment and data interpretation have been guided by an historical conceptual model in which vapors originating from contaminated soil or groundwater diffuse upward through soil and are swept into a building by soil gas flow induced by building underpressurization. Recent studies reveal that alternative VI pathways involving neighborhood sewers, land drains, and other major underground piping can also be significant VI contributors, even to buildings beyond the delineated footprint of soil and groundwater contamination. This work illustrates how controlled-pressure-method testing (CPM), soil gas sampling, and screening-level emissions calculations can be used to identify significant alternative VI pathways that might go undetected by conventional sampling under natural conditions at some sites. The combined utility of these tools is shown through data collected at a long-term study house, where a significant alternative VI pathway was discovered and altered so that it could be manipulated to be on or off. Data collected during periods of natural and CPM conditions show that the alternative pathway was significant, but its presence was not identifiable under natural conditions; it was identified under CPM conditions when measured emission rates were 2 orders of magnitude greater than screening-model estimates and subfoundation vertical soil gas profiles changed and were no longer consistent with the conventional VI conceptual model.
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http://dx.doi.org/10.1021/acs.est.5b03564DOI Listing
November 2015

Perfusion pressure and blood flow determine microvascular apparent viscosity.

Exp Physiol 2015 Aug 28;100(8):977-87. Epub 2015 Jun 28.

Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093-0412, USA.

New Findings: What is the central question of this study? The aim was to evaluate the effect of perfusion pressure on blood flow in small arterioles. The hypothesis was that blood flow regulates the thickness of the red-cell-free layer and, therefore, blood flow determines blood apparent viscosity and local vascular resistance in vascular networks with limited myogenic or metabolic regulation of blood flow. What is the main finding and its importance? Reduced perfusion pressures lowered volumetric flow rates and increased local vascular resistance, due to increased blood apparent viscosity. Thus, the local vascular resistance of small arterioles with limited myogenic or metabolic regulation of blood flow, appeared to be determined by changes in blood rheology rather than blood vessel diameter. The study of blood flow regulation is important to understand and resolve pathological conditions. As blood is a complex non-Newtonian multiphase system, the foundations of blood rheological properties have been obtained mostly in viscometers. However, blood rheological behaviour in vivo depends on the concentration of red blood cells (RBCs), their mechanical properties and the RBC hydrodynamics, including RBC migration away from the vessel wall in shear flow. This migration promotes the formation of a RBC-depleted zone, or cell-free layer (CFL), which reduces the apparent viscosity of blood. We hypothesize that perfusion pressure determines blood apparent viscosity in microvessels, as shear rate affects axial migration of RBCs by influencing the CFL thickness. In this study, we analysed the effects of perfusion pressure on blood flow in individual arterioles within the rat cremaster muscle preparation. Perfusion pressures to this microvascular bed were controlled by occlusions of the iliac artery using a pressure cuff. Blood flow measurements were obtained from direct measurements of blood flow velocity profile, as well as determination of CFL thickness using intravital microscopy. Our results indicate that perfusion pressure determines shear rates and the CFL thickness and its variations. In addition, blood flow reduction increased local vascular resistance by augmenting blood apparent viscosity rather than vascular hindrance. In conclusion, blood rheology could act as an intrinsic mechanism to further limit blood flow to tissue with limited myogenic and metabolic responses at low perfusion pressures.
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http://dx.doi.org/10.1113/EP085101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361618PMC
August 2015

Risk factors for bloodstream infection caused by extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: A focus on antimicrobials including cefepime.

Am J Infect Control 2015 Jul 29;43(7):719-23. Epub 2015 Apr 29.

Wayne State University, Detroit, MI.

Background: Extended-spectrum β-lactamase (ESBL)-producing pathogens represent increasing challenges to physicians because of rising prevalence, high mortality, and challenging treatment. Identifying high risks and early appropriate therapy is critical to favorable outcomes.

Methods: This is a 5-year retrospective case-case-control study performed at the Detroit Medical Center on adult patients with bloodstream infection (BSI) caused by ESBL-producing and non-ESBL-producing Escherichia coli or Klebsiella pneumoniae, each compared with uninfected controls. Data were collected from December 2004-August 2009. Multivariate analysis was performed using logistic regression.

Results: Participants included 103 patients with BSI caused by ESBL-producing pathogens and 79 patients with BSI caused by pathogens that did not produce ESBLs. The mean age of patients in the ESBL group was 67 years; of the patients, 51% were men, 77% were black, and 38% (n = 39) died in hospital. The mean age of patients in the non-ESBL group was 58 years; of the patients, 51% were men, 92% were black, and 22% (n = 17) died in hospital. On multivariate analysis, predictors of BSI caused by ESBL-producing pathogens included central venous catheter (odds ratio [OR], 29.4; 95% confidence interval [CI], 3.0-288.3), prior β-lactam-/β-lactamase-inhibitor therapy (OR, 28.1; 95% CI, 1.99-396.5), and prior cefepime therapy (OR, 22.7; 95% CI, 2.7-192.4). The only risk factor for BSI caused by non-ESBL-producing pathogens was urinary catheter insertion (OR, 18.2; 95% CI, 3.3-100.3).

Conclusion: Prior antimicrobial therapy, particularly with β-lactam, was the strongest unique risk factor for BSI caused by ESBL-producing E coli or K pneumoniae.
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http://dx.doi.org/10.1016/j.ajic.2015.02.030DOI Listing
July 2015

Power analysis for generalized linear mixed models in ecology and evolution.

Methods Ecol Evol 2015 Feb 6;6(2):133-142. Epub 2014 Dec 6.

Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute Socinstrasse 57, PO Box, Basel, CH-4002, Switzerland ; University of Basel Petersplatz 1, Basel, CH-4003, Switzerland.

'Will my study answer my research question?' is the most fundamental question a researcher can ask when designing a study, yet when phrased in statistical terms - 'What is the power of my study?' or 'How precise will my parameter estimate be?' - few researchers in ecology and evolution (EE) try to answer it, despite the detrimental consequences of performing under- or over-powered research. We suggest that this reluctance is due in large part to the unsuitability of simple methods of power analysis (broadly defined as any attempt to quantify prospectively the 'informativeness' of a study) for the complex models commonly used in EE research. With the aim of encouraging the use of power analysis, we present simulation from generalized linear mixed models (GLMMs) as a flexible and accessible approach to power analysis that can account for random effects, overdispersion and diverse response distributions.We illustrate the benefits of simulation-based power analysis in two research scenarios: estimating the precision of a survey to estimate tick burdens on grouse chicks and estimating the power of a trial to compare the efficacy of insecticide-treated nets in malaria mosquito control. We provide a freely available function, , for simulating from GLMMs.Analysis of simulated data revealed that the effects of accounting for realistic levels of random effects and overdispersion on power and precision estimates were substantial, with correspondingly severe implications for study design in the form of up to fivefold increases in sampling effort. We also show the utility of simulations for identifying scenarios where GLMM-fitting methods can perform poorly.These results illustrate the inadequacy of standard analytical power analysis methods and the flexibility of simulation-based power analysis for GLMMs. The wider use of these methods should contribute to improving the quality of study design in EE.
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http://dx.doi.org/10.1111/2041-210X.12306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394709PMC
February 2015

Modeling HLA associations with EBV-positive and -negative Hodgkin lymphoma suggests distinct mechanisms in disease pathogenesis.

Int J Cancer 2015 Sep 20;137(5):1066-75. Epub 2015 Feb 20.

MRC - University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

HLA genotyping and genome wide association studies provide strong evidence for associations between Human Leukocyte Antigen (HLA) alleles and classical Hodgkin lymphoma (cHL). Analysis of these associations is complicated by the extensive linkage disequilibrium within the major histocompatibility region and recent data suggesting that associations with EBV-positive and EBV-negative cHL are largely distinct. To distinguish independent and therefore potentially causal associations from associations confounded by linkage disequilibrium, we applied a variable selection regression modeling procedure to directly typed HLA class I and II genes and selected SNPs from EBV-stratified patient subgroups. In final models, HLA-A*01:01 and B*37:01 were associated with an increased risk of EBV-positive cHL whereas DRB1*15:01 and DPB1*01:01 were associated with decreased risk. Effects were independent of a prior history of infectious mononucleosis. For EBV-negative cHL the class II SNP rs6903608 remained the strongest predictor of disease risk after adjusting for the effects of common HLA alleles. Associations with "all cHL" and differences by case EBV status reflected the subgroup analysis. In conclusion, this study extends previous findings by identifying novel HLA associations with EBV-stratified subgroups of cHL, highlighting those alleles likely to be biologically relevant and strengthening evidence implicating genetic variation associated with the SNP rs6903608.
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http://dx.doi.org/10.1002/ijc.29467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737225PMC
September 2015

Long-term evaluation of the controlled pressure method for assessment of the vapor intrusion pathway.

Environ Sci Technol 2015 Feb 29;49(4):2091-8. Epub 2015 Jan 29.

School of Sustainable Engineering and the Built Environment, Ira A. Fulton Schools of Engineering, Arizona State University , Tempe, Arizona 85287, United States.

Vapor intrusion (VI) investigations often require sampling of indoor air for evaluating occupant risks, but can be confounded by temporal variability and the presence of indoor sources. Controlled pressure methods (CPM) have been proposed as an alternative, but temporal variability of CPM results and whether they are indicative of impacts under natural conditions have not been rigorously investigated. This study is the first involving a long-term CPM test at a house having a multiyear high temporal resolution indoor air data set under natural conditions. Key observations include (a) CPM results exhibited low temporal variability, (b) false-negative results were not obtained, (c) the indoor air concentrations were similar to the maximum concentrations under natural conditions, and (d) results exceeded long-term average concentrations and emission rates under natural conditions by 1-2 orders of magnitude. Thus, the CPM results were a reliable indicator of VI occurrence and worst-case exposure regardless of day or time of year of the CPM test.
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http://dx.doi.org/10.1021/es5052342DOI Listing
February 2015

Long-term trends in Anopheles gambiae insecticide resistance in Côte d'Ivoire.

Parasit Vectors 2014 Nov 28;7:500. Epub 2014 Nov 28.

Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.

Background: Malaria control is heavily dependent on the use of insecticides that target adult mosquito vectors via insecticide treated nets (ITNs) or indoor residual spraying (IRS). Four classes of insecticide are approved for IRS but only pyrethroids are available for ITNs. The rapid rise in insecticide resistance in African malaria vectors has raised alarms about the sustainability of existing malaria control activities. This problem might be particularly acute in Côte d'Ivoire where resistance to all four insecticide classes has recently been recorded. Here we investigate temporal trends in insecticide resistance across the ecological zones of Côte d'Ivoire to determine whether apparent pan-African patterns of increasing resistance are detectable and consistent across insecticides and areas.

Methods: We combined data on insecticide resistance from a literature review, and bioassays conducted on field-caught Anopheles gambiae mosquitoes for the four WHO-approved insecticide classes for ITN/IRS. The data were then mapped using Geographical Information Systems (GIS) and the IR mapper tool to provide spatial and temporal distribution data on insecticide resistance in An. gambiae sensu lato from Côte d'Ivoire between 1993 and 2014.

Results: Bioassay mortality decreased over time for all insecticide classes, though with significant spatiotemporal variation, such that stronger declines were observed in the southern ecological zone for DDT and pyrethroids than in the central zone, but with an apparently opposite effect for the carbamate and organophosphate. Variation in relative abundance of the molecular forms, coupled with dramatic increase in kdr 1014F frequency in M forms (An. coluzzii) seems likely to be a contributory factor to these patterns. Although records of resistance across insecticide classes have become more common, the number of classes tested in studies has also increased, precluding a conclusion that multiple resistance has also increased.

Conclusion: Our analyses attempted synthesis of 22 years of bioassay data from Côte d'Ivoire, and despite a number of caveats and potentially confounding variables, suggest significant but spatially-variable temporal trends in insecticide resistance. In the light of such spatio-temporal dynamics, regular, systematic and spatially-expanded monitoring is warranted to provide accurate information on insecticide resistance for control programme management.
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http://dx.doi.org/10.1186/s13071-014-0500-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269959PMC
November 2014

Reduction of diffusive contaminant emissions from a dissolved source in a lower permeability layer by sodium persulfate treatment.

Environ Sci Technol 2014 Dec 26;48(24):14582-9. Epub 2014 Nov 26.

School of Sustainable Engineering and the Built Environment, Ira A Fulton Schools of Engineering, Arizona State University , Tempe, Arizona 85287, United States.

Residual contamination contained in lower permeability zones is difficult to remediate and can, through diffusive emissions to adjacent higher permeability zones, result in long-term impacts to groundwater. This work investigated the effectiveness of oxidant delivery for reducing diffusive emissions from lower permeability zones. The experiment was conducted in a 1.2 m tall × 1.2 m wide × 6 cm thick tank containing two soil layers having 3 orders of magnitude contrast in hydraulic conductivity. The lower permeability layer initially contained dissolved methyl tert-butyl ether (MTBE) and benzene, toluene, ethylbenzene, and p-xylenes (BTEX). The treatment involved delivery of 10% w/w nonactivated sodium persulfate (Na2S2O8) solution to the high permeability layer for 14 days. The subsequent diffusion into the lower permeability layer and contaminant emission response were monitored for about 240 days. The S2O8(2-) diffused about 14 cm at 1% w/w into the lower permeability layer during the 14 day delivery and continued diffusing deeper into the layer as well as back toward the higher-lower permeability interface after delivery ceased. Over 209 days, the S2O8(2-) diffused 60 cm into the lower permeability layer, the BTEX mass and emission rate were reduced by 95-99%, and the MTBE emission rate was reduced by 63%. The overall treatment efficiency was about 60-110 g-S2O8(2-)delivered/g-hydrocarbon oxidized, with a significant fraction of the oxidant delivered likely lost by back-diffusion and not involved in hydrocarbon destruction.
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http://dx.doi.org/10.1021/es5040443DOI Listing
December 2014

Predictors of positive and negative parenting behaviours: evidence from the ALSPAC cohort.

BMC Pediatr 2014 Oct 3;14:247. Epub 2014 Oct 3.

Centre for Rural Health, The Centre for Health Science, University of Aberdeen, Old Perth Road, Inverness IV2 3JH, Scotland.

Background: This study aimed to establish the predictors of positive and negative parenting behaviours in a United Kingdom population. The majority of previous research has focused on specific risk factors and has used a variety of outcome measures. This study used a single assessment of parenting behaviours and started with a wide range of potential pre- and post-natal variables; such an approach might be used to identify families who might benefit from parenting interventions.

Methods: Using a case-control subsample of 160 subjects from the Avon Longitudinal Study of Parents and Children (ALSPAC), regression analysis was undertaken to model parenting behaviours at 12 months as measured by the Mellow Parenting Observational System.

Results: Positive parenting increased with maternal age at delivery, levels of education and with prenatal anxiety. More negative interactions were observed among younger mothers, mothers with male infants, with prenatal non-smokers and among mothers who perceived they had a poor support structure.

Conclusions: This study indicates two factors which may be important in identifying families most at risk of negative parenting: younger maternal age at delivery and lack of social support during pregnancy. Such factors could be taken into account when planning provision of services such as parenting interventions. We also established that male children were significantly more likely to be negatively parented, a novel finding which may suggest an area for future research. However the findings have to be accepted cautiously and have to be replicated, as the measures used do not have established psychometric validity and reliability data.
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http://dx.doi.org/10.1186/1471-2431-14-247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287514PMC
October 2014

HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.

Lancet 2015 Jan 24;385(9965):351-61. Epub 2014 Sep 24.

National Institute for Public Health and the Environment, Bilthoven, Netherlands.

Background: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.

Methods: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.

Findings: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials).

Interpretation: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.

Funding: The funding sources are cited at the end of the paper.
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http://dx.doi.org/10.1016/S0140-6736(14)61183-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322187PMC
January 2015

Association between parent-infant interactions in infancy and disruptive behaviour disorders at age seven: a nested, case-control ALSPAC study.

BMC Pediatr 2014 Sep 6;14:223. Epub 2014 Sep 6.

Robertson Centre for Biostatistics, University of Glasgow, Boyd Orr Building, Glasgow, Scotland G12 8QQ, UK.

Background: Effective early intervention to prevent oppositional/conduct disorders requires early identification of children at risk. Patterns of parent-child interaction may predict oppositional/conduct disorders but large community-based prospective studies are needed to evaluate this possibility.

Methods: We sought to examine whether the Mellow Parenting Observational System (MPOS) used to assess parent-infant interactions at one year was associated with psychopathology at age 7. The MPOS assesses positive and negative interactions between parent and child. It examines six dimensions: anticipation of child's needs, responsiveness, autonomy, cooperation, containment of child distress, and control/conflict; these are summed to produce measures of total positive and negative interactions. We examined videos from the Avon Longitudinal Study of Parents and Children (ALSPAC) sub-cohort who attended the 'Children in Focus' clinic at one year of age. Our sample comprised 180 videos of parent-infant interaction: 60 from infants who received a psychiatric diagnostic categorisation at seven years and 120 randomly selected controls who were group-matched on sex.

Results: A negative association between positive interactions and oppositional/conduct disorders was found. With the exception of pervasive developmental disorders (autism), an increase of one positive interaction per minute predicted a 15% (95% CI: 4% to 26%) reduction in the odds of the infant being case diagnosed. There was no statistically significant relationship between negative parenting interactions and oppositional/conduct disorders, although negative interactions were rarely observed in this setting.

Conclusions: The Mellow Parenting Observation System, specifically low scores for positive parenting interactions (such as Responsiveness which encompasses parental warmth towards the infant), predicted later psychiatric diagnostic categorisation of oppositional/conduct disorders.
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http://dx.doi.org/10.1186/1471-2431-14-223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177234PMC
September 2014