scholarly journals FST and kinship for arbitrary population structures I: Generalized definitions

2016 ◽  
Author(s):  
Alejandro Ochoa ◽  
John D. Storey
Keyword(s):  
Population Structure ◽  
Ancestral Population ◽  
Link Type ◽  
Special Cases ◽  
Kinship Coefficients ◽  
Population Structures ◽  
Subdivided Populations ◽  
Specific Allele ◽  
Moments Estimators

AbstractFST is a fundamental measure of genetic differentiation and population structure, currently defined for subdivided populations. FST in practice typically assumes independent, non-overlapping subpopulations, which all split simultaneously from their last common ancestral population so that genetic drift in each subpopulation is probabilistically independent of the other subpopulations. We introduce a generalized FST definition for arbitrary population structures, where individuals may be related in arbitrary ways, allowing for arbitrary probabilistic dependence among individuals. Our definitions are built on identity-by-descent (IBD) probabilities that relate individuals through inbreeding and kinship coefficients. We generalize FST as the mean inbreeding coefficient of the individuals’ local populations relative to their last common ancestral population. We show that the generalized definition agrees with Wright’s original and the independent subpopulation definitions as special cases. We define a novel coancestry model based on “individual-specific allele frequencies” and prove that its parameters correspond to probabilistic kinship coefficients. Lastly, we extend the Pritchard-Stephens-Donnelly admixture model in the context of our coancestry model and calculate its FST. To motivate this work, we include a summary of analyses we have carried out in follow-up papers, where our new approach has been applied to simulations and global human data, showcasing the complexity of human population structure, demonstrating our success in estimating kinship and FST, and the shortcomings of existing approaches. The probabilistic framework we introduce here provides a theoretical foundation that extends FST in terms of inbreeding and kinship coefficients to arbitrary population structures, paving the way for new estimators and novel analyses.Note: This article is Part I of two-part manuscripts. We refer to these in the text as Part I and Part II, respectively.Part I: Alejandro Ochoa and John D. Storey. “FST and kinship for arbitrary population structures I: Generalized definitions”. bioRxiv (10.1101/083915) (2019). https://doi.org/10.1101/083915. First published 2016-10-27.Part II: Alejandro Ochoa and John D. Storey. “FST and kinship for arbitrary population structures II: Method of moments estimators”. bioRxiv (10.1101/083923) (2019). https://doi.org/10.1101/083923. First published 2016-10-27.

scholarly journals PyClone-VI: Scalable inference of clonal population structures using whole genome data

2020 ◽  
Author(s):  
Sierra Gillis ◽  
Andrew Roth
Keyword(s):  
Population Structure ◽  
Statistical Method ◽  
Whole Genome ◽  
Computationally Efficient ◽  
Clonal Population ◽  
Link Type ◽  
Genome Data ◽  
Population Structures ◽  
Scalable Inference ◽  
Clonal Population Structure

AbstractWe describe PyClone-VI, a computationally efficient Bayesian statistical method for inferring the clonal population structure of cancers. Our proposed method is 10-100x times faster than existing methods, while providing results which are as accurate. We demonstrate the utility of the method by analyzing data from 1717 patients from PCAWG study and 100 patients from the TRACERx study. Software implementing our method is freely available https://github.com/Roth-Lab/pyclone-vi.

scholarly journals Homeopathy for Covid-19 in Primary Care: A structured summary of a study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ubiratan Cardinalli Adler ◽  
Maristela Schiabel Adler ◽  
Livia Mitchiguian Hotta ◽  
Ana Elisa Madureira Padula ◽  
Amarilys de Toledo Cesar ◽  
...  
Keyword(s):  
Primary Care ◽  
Alternative Hypothesis ◽  
University Hospital ◽  
List Type ◽  
Study Medication ◽  
Link Type ◽  
Care Protocol ◽  
Full Protocol ◽  
Isolation Period

Abstract Objectives To investigate the effectiveness and safety of homeopathic medicine Natrum muriaticum (LM2) for mild cases of COVID-19 in Primary Health Care. Trial design A randomized, two-armed (1:1), parallel, placebo-controlled, double-blind, clinical trial is being performed to test the following hypotheses: H0: homeopathic medicines = placebo (null hypothesis) vs. H1: homeopathic medicines ≠ placebo (alternative hypothesis) for mild cases of COVID-19 in Primary Care. Participants Setting: Primary Care of São Carlos – São Paulo – Brazil. One hundred participants aged 18 years or older, with Influenza-like symptoms and a positive RT-PCR for SARS-CoV-2. Willingness to give informed consent and to comply with the study procedures is also required. Exclusion criterium: severe acute respiratory syndrome. Intervention and comparator Homeopathy: 1 globule of Natrum muriaticum LM2 diluted in 20 mL of alcohol 30% and dispensed in a 30 ml bottle. Placebo: 20 mL of alcohol 30% dispensed in a 30 ml bottle. Posology: one drop taken orally every 4 hours (6 doses/day) while there is fever, cough, tiredness, or pain (headache, sore throat, muscle aches, chest pain, etc.) followed by one drop every 6 hours (4 doses/day) until the fourteenth day of use. The bottle of study medication should be submitted to 10 vigorous shakes (succussions) before each dose. Posology may be changed by telemedicine, with no break in blinding. Study medication should be maintained during home isolation. According to the Primary Care protocol, the home isolation period lasts until the 10th day after the appearance of the first symptom, or up to 72 hours without symptoms. Main outcomes The primary endpoint will be time to recovery, defined as the number of days elapsed before all COVID-19 Influenza-like symptoms are recorded as mild or absent during home isolation period. Secondary measures are recovery time for each COVID-19 symptom; score of the scale created for the study (COVID-Simile Scale); medicines used during follow-up; number of days of follow-up; number of visits to emergency services; number of hospitalizations; other symptoms and Adverse Events during home isolation period. Randomisation The study Statistician generated a block randomization list, using a 1:1 ratio of the two groups (denoted as A and B) and a web-based tool (http://www.random.org/lists). Blinding (masking) The clinical investigators, the statistician, the Primary Care teams, the study collaborators, and the participants will remain blinded from the identity of the two treatment groups until the end of the study. Numbers to be randomised (sample size) One hundred participants are planned to be randomized (1:1) to placebo (50) or homeopathy (50). Trial Status Protocol version/date May 21, 2020. Recruitment is ongoing. First participant was recruited/included on June 29,2020. Due to recruitment adaptations to Primary Care changes, the authors anticipate the trial will finish recruiting on April 10, 2021. Trial registration COVID-Simile Study was registered at the University Hospital Medical Information Network (UMIN - https://www.umin.ac.jp/ctr/index.htm) on June 1st, 2020, and the trial start date was June 15, 2020. Unique ID: UMIN000040602. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Surnames and population structure in the Doctrine of Belén, Altos de Arica, Viceroyalty of Peru (1750–1813)

2021 ◽  
pp. 1-13
Author(s):  
Emma Alfaro ◽  
Xochitl Inostroza ◽  
José E. Dipierri ◽  
Daniela Peña Aguilera ◽  
Jorge Hidalgo ◽  
...  
Keyword(s):  
Population Structure ◽  
Indigenous Population ◽  
Random Mating ◽  
Quantitative Information ◽  
Geographic Space ◽  
Documentary Sources ◽  
Cultural Variables ◽  
The Social ◽  
Population Structures ◽  
And Migration

Abstract The analysis of multiple population structures (biodemographic, genetic and socio-cultural) and their inter-relations contribute to a deeper understanding of population structure and population dynamics. Genetically, the population structure corresponds to the deviation of random mating conditioned by a limited number of ancestors, by restricted migration in the social or geographic space, or by preference for certain consanguineous unions. Through the isonymic method, surname frequency and distribution across the population can supply quantitative information on the structure of a human population, as they constitute universal socio-cultural variables. Using documentary sources to undertake the Doctrine of Belén’s (Altos de Arica, Chile) historical demography reconstruction between 1763 and 1820, this study identified an indigenous population with stable patronymics. The availability of complete marriage, baptism and death records, low rates of migration and the significant percentage of individuals registered and constantly present in this population favoured the application of the isonymic method. The aim of this work was to use given names and surnames recorded in these documentary sources to reconstruct the population structure and migration pattern of the Doctrine of Belén between 1750 and 1813 through the isonymic method. The results of the study were consistent with the ethno-historical data of this ethnic space, where social cohesion was, in multiple ways, related to the regulation of daily life in colonial Andean societies.

scholarly journals Efficacy of two-week therapy with doxycycline-based quadruple regimen versus levofloxacin concomitant regimen for helicobacter pylori infection: a prospective single-center randomized controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marouf Alhalabi ◽  
Mohammed Waleed Alassi ◽  
Kamal Alaa Eddin ◽  
Khaled Cheha
Keyword(s):  
Clinical Trial ◽  
Helicobacter Pylori ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Controlled Trial ◽  
Helicobacter Pylori Infection ◽  
First Line ◽  
Link Type ◽  
Syrian Population

Abstract Background Antibiotic-resistance reduces the efficacy of conventional triple therapy for Helicobacter Pylori infections worldwide, which necessitates using various treatment protocols. We used two protocols, doxycycline-based quadruple regimen and concomitant levofloxacin regimen. The aim was to assess the effectiveness of doxycycline-based quadruple regimen for treating Helicobacter Pylori infections compared with levofloxacin concomitant regimen as empirical first-line therapy based on intention-to-treat (ITT) and per-protocol analyses (PPA) in Syrian population. Settings and design An open-label, randomised, parallel, superiority clinical trial. Methods We randomly assigned 78 naïve patients who tested positive for Helicobacter Pylori gastric infection, with a 1:1 ratio to (D-group) which received (bismuth subsalicylate 524 mg four times daily, doxycycline 100 mg, tinidazole 500 mg, and esomeprazole 20 mg, each twice per day for 2 weeks), or (L-group) which received (levofloxacin 500 mg daily, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each twice per day for two weeks). We confirmed Helicobacter Pylori eradication by stool antigen test 8 weeks after completing the treatment. Results Thirty-nine patients were allocated in each group. In the D-group, 38 patients completed the follow-up, 30 patients were cured. While in the L-group, 39 completed the follow-up, 32patients were cured. According to ITT, the eradication rates were 76.92%, and 82.05%, for the D-group and L-group respectively. Odds ratio with 95% confidence interval was 1.371 [0.454–4.146]. According to PPA, the eradication rates were 78.9%, and 82.05% for the D-group and L-group respectively. The odds ratio with 95% confidence interval was 1.219 [0.394–3.774]. We didn’t report serious adverse effects. Conclusions Levofloxacin concomitant therapy wasn’t superior to doxycycline based quadruple therapy. Further researches are required to identify the optimal first-line treatment for Helicobacter-Pylori Infection in the Syrian population. Trial registration We registered this study as a standard randomized clinical trial (Clinicaltrial.gov, identifier-NCT04348786, date:29-January-2020).

scholarly journals Cohort profile: the Chinese Pregnant Women Cohort Study and Offspring Follow-up (CPWCSaOF)

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e044933
Author(s):  
Tianchen Lyu ◽  
Yunli Chen ◽  
Yongle Zhan ◽  
Yingjie Shi ◽  
Hexin Yue ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pregnant Women ◽  
First Trimester ◽  
Health Problems ◽  
Environmental Data ◽  
Geographical Information ◽  
Obstetric Outcomes ◽  
Factors Affecting ◽  
Link Type

PurposeA multicentre prospective cohort study, known as the Chinese Pregnant Women Cohort Study (CPWCS), was established in 2017 to collect exposure data during pregnancy (except environmental exposure) and analyse the relationship between lifestyle during pregnancy and obstetric outcomes. Data about mothers and their children’s life and health as well as children’s laboratory testing will be collected during the offspring follow-up of CPWCS, which will enable us to further investigate the longitudinal relationship between exposure in different periods (during pregnancy and childhood) and children’s development.Participants9193 pregnant women in 24 hospitals in China who were in their first trimester (5–13 weeks gestational age) from 25 July 2017 to 26 November 2018 were included in CPWCS by convenience sampling. Five hospitals in China which participated in CPWCS with good cooperation will be selected as the sample source for the Chinese Pregnant Women Cohort Study (Offspring Follow-up) (CPWCS-OF).Findings to dateSome factors affecting pregnancy outcomes and health problems during pregnancy have been discovered through data analysis. The details are discussed in the ‘Findings to date’ section.Future plansInfants and children and their mothers who meet the criteria will be enrolled in the study and will be followed up every 2 years. The longitudinal relationship between exposure (questionnaire data, physical examination and biospecimens, medical records, and objective environmental data collected through geographical information system and remote sensing technology) in different periods (during pregnancy and childhood) and children’s health (such as sleeping problem, oral health, bowel health and allergy-related health problems) will be analysed.Trail registration numberCPWCS was registered with ClinicalTrials.gov on 18 January 2018: NCT03403543. CPWCS-OF was registered with ClinicalTrials.gov on 24 June 2020: NCT04444791.

scholarly journals Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Oriol Grau-Rivera ◽  
◽  
Irene Navalpotro-Gomez ◽  
Gonzalo Sánchez-Benavides ◽  
Marc Suárez-Calvet ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Weight Loss ◽  
Cerebrospinal Fluid ◽  
Weight Change ◽  
Emission Tomography ◽  
Link Type ◽  
Preclinical Ad ◽  
Positron Emission ◽  
T Tau

Abstract Background Recognizing clinical manifestations heralding the development of Alzheimer’s disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change with cognitive changes and AD biomarkers in cognitively unimpaired middle-aged adults. Methods This prospective cohort study included data from cognitively unimpaired adults from the ALFA study (n = 2743), a research platform focused on preclinical AD. Cognitive and anthropometric data were collected at baseline between April 2013 and November 2014. Between October 2016 and February 2020, 450 participants were visited in the context of the nested ALFA+ study and underwent cerebrospinal fluid (CSF) extraction and acquisition of positron emission tomography images with [18F]flutemetamol (FTM-PET). From these, 408 (90.1%) were included in the present study. We used data from two visits (average interval 4.1 years) to compute rates of change in weight and cognitive performance. We tested associations between these variables and between weight change and categorical and continuous measures of CSF and neuroimaging AD biomarkers obtained at follow-up. We classified participants with CSF data according to the AT (amyloid, tau) system and assessed between-group differences in weight change. Results Weight loss predicted a higher likelihood of positive FTM-PET visual read (OR 1.27, 95% CI 1.00–1.61, p = 0.049), abnormal CSF p-tau levels (OR 1.50, 95% CI 1.19–1.89, p = 0.001), and an A+T+ profile (OR 1.64, 95% CI 1.25–2.20, p = 0.001) and was greater among participants with an A+T+ profile (p < 0.01) at follow-up. Weight change was positively associated with CSF Aβ42/40 ratio (β = 0.099, p = 0.032) and negatively associated with CSF p-tau (β = − 0.141, p = 0.005), t-tau (β = − 0.147 p = 0.004) and neurogranin levels (β = − 0.158, p = 0.002). In stratified analyses, weight loss was significantly associated with higher t-tau, p-tau, neurofilament light, and neurogranin, as well as faster cognitive decline in A+ participants only. Conclusions Weight loss predicts AD CSF and PET biomarker results and may occur downstream to amyloid-β accumulation in preclinical AD, paralleling cognitive decline. Accordingly, it should be considered as an indicator of increased risk of AD-related cognitive impairment. Trial registration NCT01835717, NCT02485730, NCT02685969.

scholarly journals Optimising medication management in children and young people with ADHD using a computerised test (QbTest): a feasibility randomised controlled trial

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Williams ◽  
Charlotte L. Hall ◽  
Sue Brown ◽  
Boliang Guo ◽  
Marilyn James ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Young People ◽  
Controlled Trial ◽  
Medication Management ◽  
Control Group ◽  
Global Functioning ◽  
Children And Young People ◽  
Link Type ◽  
Randomised Controlled

Abstract Background Medication for attention deficit hyperactivity disorder (ADHD) should be closely monitored to ensure optimisation. There is growing interest in using computerised assessments of ADHD symptoms to support medication monitoring. The aim of this study was to assess the feasibility and acceptability of a randomised controlled trial (RCT) to evaluate the efficacy of one such computerised assessment, the Quantified Behavior (Qb) Test, as part of medication management for ADHD. Methods This feasibility multi-site RCT conducted in child and adolescent mental health and community paediatric settings recruited participants aged 6–15 years diagnosed with ADHD starting stimulant medication. Participants were randomised into one of two arms: experimental (QbTest protocol) where participants completed a QbTest at baseline and two follow-up QbTests on medication (2–4 weeks and 8–10 weeks later) and control where participants received treatment as usual, including at least two follow-up consultations. Measures of parent, teacher, and clinician-rated symptoms and global functioning were completed at each time point. Clinicians recorded treatment decision-making and health economic measures were obtained. Data were analysed using multi-level modelling and participants (children and parents) and clinicians were interviewed about their experiences, resulting data were thematically analysed. Results Forty-four children and young people were randomised. Completion of study outcome measures by care-givers and teachers ranged from 52 to 78% at baseline to 47–65% at follow-up. Participants reported the questionnaires to be useful to complete. SNAP-IV inattention scores showed greater reduction in the intervention than the control group (− 5.85, 95% CI − 10.33, − 1.36,). Engagement with the intervention ranged from 100% at baseline, to 78% follow-up 1 and 57% follow-up 2. However, only 37% of QbTests were conducted in the correct time period. Interview data highlighted that the objectivity of the QbTest was appreciated by clinicians and parents. Clinicians commented that the additional time and resources required meant that it is not feasible to use QbTest for all cases. Conclusion The trial design and protocol appear to be feasible and acceptable but could be improved by modifying QbTest time periods and the method of data collection. With these changes, the protocol may be appropriate for a full trial. Adding QbTest may improve symptom outcome as measured by SNAP-IV. Trial registration ClinicalTrials.gov, NCT03368573, prospectively registered, 11th December 2017, and ISRCTN, ISRCTN69461593, retrospectively registered, 10th April 2018

scholarly journals Patterns of intraspecific morphological variability in soil mites reflect their dispersal ability

2021 ◽  
Vol 83 (2) ◽  
pp. 241-255
Author(s):  
Julia Baumann
Keyword(s):  
Molecular Genetic ◽  
Morphological Variability ◽  
Mite Species ◽  
Molecular Genetic Analysis ◽  
Dispersal Ability ◽  
Geometric Morphometric ◽  
Geographic Population ◽  
Mobile Species ◽  
Population Structures ◽  
Subdivided Populations

AbstractThe ability to disperse is one of the most important factors influencing the biogeography of species and speciation processes. Highly mobile species have been shown to lack geographic population structures, whereas less mobile species show genetically strongly subdivided populations which are expected to also display at least subtle phenotypic differences. Geometric morphometric methods (GMM) were now used to analyze morphological differences between European populations of a presumed non-phoretic, little mobile mite species in comparison to a highly mobile, phoretic species. The non-phoretic species Scutacarus carinthiacus showed a phenotypic population structure, whereas the phoretic species S. acarorum displayed homogeneity. These different patterns most probably can be explained by different levels of gene flow due to different dispersal abilities of the two species. GMM proved to be a sensitive tool that is especially recommendable for the analysis of (old) museum material and/or specimens in microscopic slides, which are not suitable for molecular genetic analysis.

scholarly journals Non-Homogeneous Markov Set Systems

Mathematics ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 471
Author(s):  
P.-C.G. Vassiliou
Keyword(s):  
Asymptotic Behavior ◽  
Population Structure ◽  
Confidence Intervals ◽  
Limit Set ◽  
Stroke Patients ◽  
Relative Population ◽  
Set Systems ◽  
Population Structures ◽  
Basic Parameters ◽  
Initial Distributions

A more realistic way to describe a model is the use of intervals which contain the required values of the parameters. In practice we estimate the parameters from a set of data and it is natural that they will be in confidence intervals. In the present study, we study Non-Homogeneous Markov Systems (NHMS) processes for which the required basic parameters are in intervals. We call such processes Non-Homogeneous Markov Set Systems (NHMSS). First we study the set of the relative expected population structure of memberships and we prove that under certain conditions of convexity of the intervals of the parameters the set is compact and convex. Next, we establish that if the NHMSS starts with two different initial distributions sets and allocation probability sets under certain conditions, asymptotically the two expected relative population structures coincide geometrically fast. We continue proving a series of theorems on the asymptotic behavior of the expected relative population structure of a NHMSS and the properties of their limit set. Finally, we present an application for geriatric and stroke patients in a hospital and through it we solve problems that surface in an application.

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