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Nevin Manimala Statistics

Predominantly inverse modulation of gene expression in genomically unbalanced disomic haploid maize

Plant Cell. 2021 Feb 2:koab029. doi: 10.1093/plcell/koab029. Online ahead of print.

ABSTRACT

The phenotypic consequences of the addition or subtraction of part of a chromosome is more severe than changing the dosage of the whole genome. By crossing diploid trisomies to a haploid inducer, we identified 17 distal segmental haploid disomies that cover ∼80% of the maize genome. Disomic haploids provide a level of genomic imbalance that is not ordinarily achievable in multicellular eukaryotes, allowing the impact to be stronger and more easily studied. Transcriptome size estimates revealed that a few disomies inversely modulate most of the transcriptome. Based on RNA sequencing, the expression levels of genes located on the varied chromosome arms (cis) in disomies ranged from being proportional to chromosomal dosage (dosage effect) to showing dosage compensation with no expression change with dosage. For genes not located on the varied chromosome arm (trans), an obvious trans-acting effect can be observed, with the majority showing a decreased modulation (inverse effect). The extent of dosage compensation of varied cis genes correlates with the extent of trans inverse effects across the 17 genomic regions studied. The results also have implications for the role of stoichiometry in gene expression, the control of quantitative traits, and the evolution of dosage-sensitive genes.

PMID:33656551 | DOI:10.1093/plcell/koab029

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Nevin Manimala Statistics

Using Population Pharmacokinetic Modeling to Estimate Exposure to Δ9-tetrahydrocannabinol in an Observational Study of Cannabis Smokers in Colorado

Ther Drug Monit. 2021 Feb 25. doi: 10.1097/FTD.0000000000000882. Online ahead of print.

ABSTRACT

BACKGROUND: Self-report questionnaires, weighing products consumed, and Δ9-tetrahydrocannabinol (THC) biomarkers are established techniques for estimating cannabis exposure. Population pharmacokinetic modeling of plasma THC and metabolite concentrations by incorporating self-reported and weighed products as covariates could improve estimates of THC exposure in regular cannabis users.

METHODS: In this naturalistic study, blood samples were obtained from 36 regular smokers of cannabis for analysis of THC and its two metabolites at four time points: recruitment and during an experimental mobile laboratory assessment that included three time points: before, immediately after, and one hour after ad libitum legal market flower use. These data were analyzed using an established model of population pharmacokinetics developed from laboratory-controlled cannabis administration data. Elimination and metabolite production clearances were estimated for each subject as well as their daily THC doses and the dose consumed during the ad libitum event.

RESULTS: A statistically significant correlation existed between the daily THC dose estimated by self-report questionnaire and population pharmacokinetic modeling (correlation coefficient = 0.79, p<0.05) between the weighed cannabis smoked ad libitum and that estimated by population pharmacokinetic modeling (correlation coefficient = 0.71, p<0.05).

CONCLUSION: Inclusion of self-reported questionnaire data of THC consumption improved pharmacokinetic model-derived estimates based on measured THC and metabolite concentrations. Additionally, the pharmacokinetic-derived dose estimates for the ad libitum smoking event underestimated the THC consumption compared to the weighed amount smoked. Thus, the subjects in this study, who smoked ad libitum, and used cannabis products with high concentrations of THC were less efficient (lower bioavailability) compared to computer-paced smokers of low potency, NIDA cannabis in a laboratory setting.

PMID:33656464 | DOI:10.1097/FTD.0000000000000882

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Nevin Manimala Statistics

Vestibular, Oculomotor, and Balance Functions in Children With and Without Concussion

J Head Trauma Rehabil. 2021 Feb 22. doi: 10.1097/HTR.0000000000000651. Online ahead of print.

ABSTRACT

OBJECTIVE: The main objective of this study was to assess whether objective vestibular, oculomotor, and balance functions were impaired in children with a current diagnosis of concussion with vestibular and/or ocular symptoms.

SETTING: Data were collected in a vestibular/ocular clinical laboratory. Patient participants were recruited from a concussion clinic in a children’s hospital.

PARTICIPANTS: Thirty-three children aged 8 to 17 years with a current diagnosis of concussion and vestibular and/or ocular symptoms and 30 children without concussion.

DESIGN: Cross-sectional single-visit study.

MAIN OUTCOME MEASURES: Eye-tracking rotary chair oculomotor and vestibular measures, vestibular evoked potentials, and static posturography.

RESULTS: There were no statistically significant differences on any clinical measure between children with concussion and children without concussion. Younger children without concussion performed significantly worse on several rotary chair and balance measures compared with older children without concussion.

CONCLUSIONS: No vestibular, oculomotor, or balance measures were significantly different between children with concussion and children without concussion, suggesting these measures may not be useful in the evaluation of a child with concussion and vestibular and/or oculomotor symptoms. Future research should investigate age effects and other vestibular and oculomotor tests to identify objective findings that better relate to vestibular and/or ocular symptoms in children with concussion.

PMID:33656474 | DOI:10.1097/HTR.0000000000000651

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Nevin Manimala Statistics

Race/Ethnicity and Community Participation Among Veterans and Service Members With Traumatic Brain Injury: A VA Traumatic Brain Injury Model Systems Study

J Head Trauma Rehabil. 2021 Feb 22. doi: 10.1097/HTR.0000000000000657. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine racial/ethnic disparities in community participation among veterans and active duty service members with traumatic brain injury (TBI).

SETTING: Five Department of Veterans Affairs (VA) TBI Model Systems (TBIMS) Polytrauma Rehabilitation Centers (PRCs). Participants: Three hundred forty-two community-dwelling adults (251 White, 34 Black, and 57 Hispanic) with TBI enrolled in the VA TBIMS National Database who completed a 1-year follow-up interview. Mean age was 38.6 years (range, 19-84 years).

DESIGN: Cross-sectional analysis of a prospective observational cohort study. Main Measures: Community participation at 1 year postinjury assessed by 3 domains of the Participation Assessment with Recombined Tools-Objective (PART-O): Out & About, Productivity, and Social Relations.

RESULTS: Significant differences were observed among race/ethnicity groups in PART-O Productivity and Out & About domains without controlling for relevant participant characteristics; Productivity scores were significantly higher for non-Hispanic Black than for non-Hispanic White participants (t = 2.40, P = .0169). Out & About scores were significantly higher for Hispanic than for non-Hispanic White participants (t = 2.79, P = .0056). However, after controlling for demographic, injury severity, and 1-year follow-up characteristics, only differences in the Out & About domain remained statistically significant (t = 2.62, P = .0094), with scores being significantly higher for Hispanics than for non-Hispanic Whites.

CONCLUSIONS: The results, which differ from findings from studies conducted in non-VA healthcare settings where there are greater racial/ethnic disparities in participation outcomes, could reflect differences between military and civilian samples that may reduce disparities.

PMID:33656479 | DOI:10.1097/HTR.0000000000000657

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Nevin Manimala Statistics

Availability of diagnostic services and essential medicines for non-communicable respiratory diseases in African countries

Int J Tuberc Lung Dis. 2021 Feb 1;25(2):120-125. doi: 10.5588/ijtld.20.0762.

ABSTRACT

BACKGROUND: The global burden of disease due to asthma and chronic obstructive pulmonary disease (COPD) is substantial and particularly great in low- and middle-income countries, including many African countries. Management is affected by availability of diagnostic tests and essential medicines. The study aimed to explore the availability of spirometry services and essential medicines for asthma and COPD in African countries.METHOD: Questionnaires were delivered to healthcare workers at the annual meeting of the Pan African Thoracic Society Methods in Epidemiology and Clinical Research (PATS MECOR) and International Multidisciplinary Programme to Address Lung Health and TB in Africa (IMPALA). Data were analysed using simple descriptive statistics.RESULTS: A total of 37 questionnaires representing 13 African countries were returned. Spirometry availability was 73.0%. The most common reasons for non-availability were lack of knowledge of the utility of the test. Within the study sample, 33.3% faced sporadic availability due to maintenance issues. Essential medicines availability ranged from 37.8% for inhaled corticosteroid-long-acting beta-agonist inhalers to 100% for prednisolone 5 mg tablets, mainly due to supply chain problems.CONCLUSION: There is varied availability of spirometry and WHO essential medicines for COPD and asthma in African countries. Strategies are needed to improve access to basic effective care for people with non-communicable lung disease in Africa.

PMID:33656423 | DOI:10.5588/ijtld.20.0762

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Nevin Manimala Statistics

TB management in the European Union/European Economic Area: a multi-centre survey

Int J Tuberc Lung Dis. 2021 Feb 1;25(2):126-133. doi: 10.5588/ijtld.20.0849.

ABSTRACT

BACKGROUND: Essential TB care in the European Union/European Economic Area (EU/EEA) comprises 21 standards for the diagnosis, treatment and prevention of TB that constitute the European Union Standards for Tuberculosis Care (ESTC).METHODS: In 2017, we conducted an audit on TB management and infection control measures against the ESTC standards. TB reference centres in five EU/EEA countries were purposely selected to represent the heterogeneous European TB burden and examine geographic variability.RESULTS: Data from 122 patients, diagnosed between 2012 and 2015 with multidrug-resistant TB (n = 49), extensively drug-resistant TB (XDR-TB) (n = 11), pre-XDR-TB (n = 29) and drug-susceptible TB (n = 33), showed that TB diagnosis and treatment practices were in general in agreement with the ESTC.CONCLUSION: Overall, TB management and infection control practices were in agreement with the ESTC in the selected EU/EEA reference centres. Areas for improvement include strengthening of integrated care services and further implementation of patient-centred approaches.

PMID:33656424 | DOI:10.5588/ijtld.20.0849

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Nevin Manimala Statistics

Digital Technology Interventions for Risk Factor Modification in Patients With Cardiovascular Disease: Systematic Review and Meta-analysis

JMIR Mhealth Uhealth. 2021 Mar 3;9(3):e21061. doi: 10.2196/21061.

ABSTRACT

BACKGROUND: Approximately 50% of cardiovascular disease (CVD) cases are attributable to lifestyle risk factors. Despite widespread education, personal knowledge, and efficacy, many individuals fail to adequately modify these risk factors, even after a cardiovascular event. Digital technology interventions have been suggested as a viable equivalent and potential alternative to conventional cardiac rehabilitation care centers. However, little is known about the clinical effectiveness of these technologies in bringing about behavioral changes in patients with CVD at an individual level.

OBJECTIVE: The aim of this study is to identify and measure the effectiveness of digital technology (eg, mobile phones, the internet, software applications, wearables, etc) interventions in randomized controlled trials (RCTs) and determine which behavior change constructs are effective at achieving risk factor modification in patients with CVD.

METHODS: This study is a systematic review and meta-analysis of RCTs designed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) statement standard. Mixed data from studies extracted from selected research databases and filtered for RCTs only were analyzed using quantitative methods. Outcome hypothesis testing was set at 95% CI and P=.05 for statistical significance.

RESULTS: Digital interventions were delivered using devices such as cell phones, smartphones, personal computers, and wearables coupled with technologies such as the internet, SMS, software applications, and mobile sensors. Behavioral change constructs such as cognition, follow-up, goal setting, record keeping, perceived benefit, persuasion, socialization, personalization, rewards and incentives, support, and self-management were used. The meta-analyzed effect estimates (mean difference [MD]; standard mean difference [SMD]; and risk ratio [RR]) calculated for outcomes showed benefits in total cholesterol SMD at -0.29 [-0.44, -0.15], P<.001; high-density lipoprotein SMD at -0.09 [-0.19, 0.00], P=.05; low-density lipoprotein SMD at -0.18 [-0.33, -0.04], P=.01; physical activity (PA) SMD at 0.23 [0.11, 0.36], P<.001; physical inactivity (sedentary) RR at 0.54 [0.39, 0.75], P<.001; and diet (food intake) RR at 0.79 [0.66, 0.94], P=.007. Initial effect estimates showed no significant benefit in body mass index (BMI) MD at -0.37 [-1.20, 0.46], P=.38; diastolic blood pressure (BP) SMD at -0.06 [-0.20, 0.08], P=.43; systolic BP SMD at -0.03 [-0.18, 0.13], P=.74; Hemoglobin A1C blood sugar (HbA1c) RR at 1.04 [0.40, 2.70], P=.94; alcohol intake SMD at -0.16 [-1.43, 1.10], P=.80; smoking RR at 0.87 [0.67, 1.13], P=.30; and medication adherence RR at 1.10 [1.00, 1.22], P=.06.

CONCLUSIONS: Digital interventions may improve healthy behavioral factors (PA, healthy diet, and medication adherence) and are even more potent when used to treat multiple behavioral outcomes (eg, medication adherence plus). However, they did not appear to reduce unhealthy behavioral factors (smoking, alcohol intake, and unhealthy diet) and clinical outcomes (BMI, triglycerides, diastolic and systolic BP, and HbA1c).

PMID:33656444 | DOI:10.2196/21061

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Nevin Manimala Statistics

Estimating the Incidence of Conjunctivitis by Comparing the Frequency of Google Search Terms With Clinical Data: Retrospective Study

JMIR Public Health Surveill. 2021 Mar 3;7(3):e22645. doi: 10.2196/22645.

ABSTRACT

BACKGROUND: Infectious conjunctivitis is contagious and may lead to an outbreak. Prevention systems can help to avoid an outbreak.

OBJECTIVE: We aimed to evaluate if Google search data on conjunctivitis and associated terms can be used to estimate the incidence and if the data can provide an estimation for outbreaks.

METHODS: We obtained Google search data over 4 years for the German term for conjunctivitis (“Bindehautentzündung”) and 714 associated terms in 12 selected German cities and Germany as a whole using the Google AdWords Keyword Planner. The search volume from Freiburg was correlated with clinical data from the Freiburg emergency practice (Eye Center University of Freiburg).

RESULTS: The search volume for the German term for conjunctivitis in Germany as a whole and in the 12 German cities showed a highly uniform seasonal pattern. Cross-correlation between the temporal search frequencies in Germany as a whole and the 12 selected cities was high without any lag. Cross-correlation of the search volume in Freiburg with the frequency of conjunctivitis (International Statistical Classification of Diseases and Related Health Problems [ICD] code group “H10.-“) from the centralized ophthalmologic emergency practice in Freiburg revealed a considerable temporal association, with the emergency practice lagging behind the frequency. Additionally, Pearson correlation between the count of patients per month and the count of searches per month in Freiburg was statistically significant (P=.04).

CONCLUSIONS: We observed a close correlation between the Google search volume for the signs and symptoms of conjunctivitis and the frequency of patients with a congruent diagnosis in the Freiburg region. Regional deviations from the nationwide average search volume may therefore indicate a regional outbreak of infectious conjunctivitis.

PMID:33656450 | DOI:10.2196/22645

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Nevin Manimala Statistics

Clinical Evaluation of a Three-Dimensional Internal Dosimetry Technique for Liver Radioembolization with 90Y Microspheres Using Dose Voxel Kernels

Cancer Biother Radiopharm. 2021 Mar 2. doi: 10.1089/cbr.2020.4554. Online ahead of print.

ABSTRACT

Background: The purpose of this study was to develop a rapid, reliable, and efficient tool for three-dimensional (3D) dosimetry treatment planning and post-treatment evaluation of liver radioembolization with 90Y microspheres, using tissue-specific dose voxel kernels (DVKs) that can be used in everyday clinical practice. Materials and Methods: Two tissue-specific DVKs for 90Y were calculated through Monte Carlo (MC) simulations. DVKs for the liver and lungs were generated, and the dose distribution was compared with direct MC simulations. A method was developed to produce a 3D dose map by convolving the calculated DVKs with the activity biodistribution derived from clinical single-photon emission computed tomography (SPECT) or positron emission tomography (PET) images. Image registration for the SPECT or PET images with the corresponding computed tomography scans was performed before dosimetry calculation. The authors first compared the DVK convolution dosimetry with a direct full MC simulation on an XCAT anthropomorphic phantom. They then tested it in 25 individual clinical cases of patients who underwent 90Y therapy. All MC simulations were carried out using the GATE MC toolkit. Results: Comparison of the measured absorbed dose using tissue-specific DVKs and direct MC simulation on 25 patients revealed a mean difference of 1.07% ± 1.43% for the liver and 1.03% ± 1.21% for the tumor tissue, respectively. The largest difference between DVK convolution and full MC dosimetry was observed for the lung tissue (10.16% ± 1.20%). The DVK statistical uncertainty was <0.75% for both media. Conclusions: This semiautomatic algorithm is capable of performing rapid, accurate, and efficient 3D dosimetry. The proposed method considers tissue and activity heterogeneity using tissue-specific DVKs. Furthermore, this method provides results in <1 min, making it suitable for everyday clinical practice.

PMID:33656372 | DOI:10.1089/cbr.2020.4554

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Nevin Manimala Statistics

Recognition Receiver Operating Characteristic Curves: The Complex Influence of Input Statistics, Memory, and Decision-making

J Cogn Neurosci. 2021 Mar 3:1-24. doi: 10.1162/jocn_a_01697. Online ahead of print.

ABSTRACT

Receiver operating characteristic (ROC) analysis is the standard tool for studying recognition memory. In particular, the curvilinearity and the y-offset of recognition ROC curves have been interpreted as indicative of either memory strength (single-process models) or different memory processes (dual-process model). The distinction between familiarity and recollection has been widely studied in cognitive neuroscience in a variety of conditions, including lesions of different brain regions. We develop a computational model that explicitly shows how performance in recognition memory is affected by a complex and, as yet, underappreciated interplay of various factors, such as stimulus statistics, memory processing, and decision-making. We demonstrate that (1) the factors in the model affect recognition ROC curves in unexpected ways, (2) fitting R and F parameters according to the dual-process model is not particularly useful for understanding the underlying processes, and (3) the variability of recognition ROC curves and the controversies they have caused might be due to the uncontrolled variability in the contributing factors. Although our model is abstract, its functional components can be mapped onto brain regions, which are involved in corresponding functions. This enables us to reproduce and interpret in a coherent framework the diverse effects on recognition memory that have been reported in patients with frontal and hippocampal lesions. To conclude, our work highlights the importance of the rich interplay of a variety of factors in driving recognition memory performance, which has to be taken into account when interpreting recognition ROC curves.

PMID:33656399 | DOI:10.1162/jocn_a_01697