Category: Statistics

Forensic Sci Int Genet. 2021 Aug 8;55:102568. doi: 10.1016/j.fsigen.2021.102568. Online ahead of print.

ABSTRACT

Short tandem repeats of the nuclear genome have been the preferred markers for analyzing forensic DNA mixtures. However, when nuclear DNA in a sample is degraded or limited, mitochondrial DNA (mtDNA) markers provide a powerful alternative. Though historically considered challenging, the interpretation and analysis of mtDNA mixtures have recently seen renewed interest with the advent of massively parallel sequencing. However, there are only a few software tools available for mtDNA mixture interpretation. To address this gap, the Mitochondrial Mixture Deconvolution and Interpretation Tool (MMDIT) was developed. MMDIT is an interactive application complete with a graphical user interface that allows users to deconvolve mtDNA (whole or partial genomes) mixtures into constituent donor haplotypes and estimate random match probabilities on these resultant haplotypes. In cases where deconvolution might not be feasible, the software allows mixture analysis directly within a binary framework (i.e. qualitatively, only using data on allele presence/absence). This paper explains the functionality of MMDIT, using an example of an in vitro two-person mtDNA mixture with a ratio of 1:4. The uniqueness of MMDIT lies in its ability to resolve mixtures into complete donor haplotypes using a statistical phasing framework before mixture analysis and evaluating statistical weights employing a novel graph algorithm approach. MMDIT is the first available open-source software that can automate mtDNA mixture deconvolution and analysis. The MMDIT web application can be accessed online at https://www.unthsc.edu/mmdit/. The source code is available at https://github.com/SammedMandape/MMDIT_UI and archived on zenodo (https://doi.org/10.5281/zenodo.4770184).

PMID:34416654 | DOI:10.1016/j.fsigen.2021.102568

Semin Arthritis Rheum. 2021 Aug 2;51(5):1045-1056. doi: 10.1016/j.semarthrit.2021.07.020. Online ahead of print.

ABSTRACT

BACKGROUND: Kawasaki disease (KD) is a form of self-limiting vasculitis that causes coronary artery abnormalities in children. Although clinical trials of monoclonal antibodies and anti-cytokine biologics that block cytokine cascades have been conducted, the studies have revealed contradictory results. To examine the effectiveness of treatment with monoclonal antibodies and anti-cytokine biologics for KD patients, we conducted this systematic review and meta-analysis.

METHODS: Relevant randomized controlled trials (RCTs) and observational studies (e.g., cohort studies, case-control studies, case-series, and case-reports) were included to summarize available evidence, both qualitatively and quantitatively. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ICUSHI were used for systematic research. Meta-analysis of the included studies was conducted using fixed-effect or random-effects models, depending on the degree of between-study heterogeneity. We assessed coronary artery and treatment outcomes of the interventions. The certainty of evidence and risk of bias were assessed using the GRADE and Cochrane risk of bias tool. The protocol of this review is registered with PROSPERO (CRD42016033079).

RESULTS: Results: Of all searched studies, 183 studies were qualitatively analyzed. We finally included four randomized controlled trials with 456 patients in quantitative syntheses. Monoclonal antibodies and anti-cytokine biologics did not reduce the frequency of CAA (risk ratio [RR], 0.93; 95% confidence interval [95%CI], 0.65 to 1.32, low certainty of evidence), compared with the conventional treatment with IVIG. However, the frequency of treatment resistance (RR, 0.60; 95%CI, 0.38 to 0.95, moderate certainty of evidence) was reduced by the antibodies. We found no statistical differences in either “any adverse event” (RR, 0.92; 95%CI, 0.80 to 1.06, low certainty of evidence) or “adverse events attributable to the administration of the medication” (RR, 1.10; 95%CI, 0.72 to 1.69, low certainty of evidence) between the two groups.

CONCLUSION: Conclusions: Although monoclonal antibodies and anti-cytokine biologics were not effective in reducing the frequency of CAA in KD patients, the frequency of treatment resistance might be reduced by those agents compared with conventional IVIG therapy alone.

PMID:34416626 | DOI:10.1016/j.semarthrit.2021.07.020

Chemosphere. 2021 Aug 13;286(Pt 3):131859. doi: 10.1016/j.chemosphere.2021.131859. Online ahead of print.

ABSTRACT

Three different innovative mathematical models were established to assess the volumetric nitrogen conversion rates of a lab-scale ANAMMOX upflow anaerobic sludge blanket reactor. Despite the vast technological and economical advantages of ANAMMOX, major challenges in process implementation call for mathematic simulations of the process, optimization of operating conditions, and kinetic/statistical analysis of the entire process. In this study, all developed mathematical models implemented via BioWin®, were calibrated and validated, with adequate representations of a bench-scale micro-granular ANAMMOX process, to understand the potential setbacks of ANAMMOX process start-up and stabilization. Fundamental calculations of the kinetic and stoichiometric constants were integrated in the BioWin® software, and the adjusted parameters based on experimental analysis were applied for the assessments. Based on the results from the statistical approach, one of the models (Model III) exhibited a precise prognosis of the effluent data for the entire operational phases with a mean relative error (MRE) of approximately 1.96, 4.36 and 2.54% for nitrogen removal efficiency, removal rate and loading rate, respectively. Evaluating alkalinity and pH during the operation, led to identifying an acceptable fit between the experiment and Model III results, with a MRE of -7.19 and -0.35%, correspondingly. This study confirms the reliability of ANAMMOX-based process modeling and high predictive ability with BioWin®. The presented simulation constants and modeling outline, can be further employed in full-scale applications design and development.

PMID:34416583 | DOI:10.1016/j.chemosphere.2021.131859

Accid Anal Prev. 2021 Aug 17;161:106346. doi: 10.1016/j.aap.2021.106346. Online ahead of print.

ABSTRACT

This study aims to explore the associations between near-crash events and road geometry and trip features by investigating a naturalistic driving dataset and a corresponding roadway inventory dataset using an association rule mining method – the Apriori algorithm. To provide more insights into near-crash behavior, this study classified near-crash events into two severity levels: trivial near-crash events (-7.5 g ≤ deceleration rate ≤ -4.5 g) and non-trivial near-crash events (≤-7.5 g). From the perspective of descriptive statistics, the frequency of the itemsets, a set of categories of various variables, generated by the Apriori algorithm suggests that near-crash events are highly associated with several factors, including roadways without access control, driving during non-peak hours, roadways without a shoulder or a median, roadways with the minor arterial functional class, and roadways with a speed limit between 30 and 60 mph. By comparing the frequency of the occurrence of the itemset during trivial and non-trivial near-crash events, the results indicate that the length of the trip is a strong indicator of the near-crash event type. The results show that non-trivial near-crash events are more likely to occur if the trip is longer than 2 h. After applying the association rule mining algorithm, more interesting patterns for the two near-crash events were generated through the rules. The main findings include: 1) trivial near-crash events are more likely to occur on roadways without a median and shoulder that have a relatively lower functional class; 2) relatively higher functional roadways with relatively wide medians and shoulders could be an intriguing combination for non-trivial near-crash events; 3) non-trivial near-crash events often occur on long trips (more than 2 h); 4) congestion on roadways that have a lower functional class is a dominant rule associating with the high frequency of non-trivial near-crash events. This study associates near-crash events and the corresponding road geometry and trip features to provide a unique understanding of near-crash events.

PMID:34416576 | DOI:10.1016/j.aap.2021.106346

Eur J Obstet Gynecol Reprod Biol. 2021 Aug 8;265:7-17. doi: 10.1016/j.ejogrb.2021.08.001. Online ahead of print.

ABSTRACT

OBJECTIVE: In the absence of an effective screening test, women with a high genetic predisposition for ovarian cancer are recommended to undergo risk-reducing bilateral salpingo-oophorectomy (RRBSO) once childbearing is complete. This reduces the risk of ovarian cancer by up to 96%, but can result in undesirable side effects, including menopausal symptoms and sexual dysfunction. We have performed a systematic review and meta-analysis to investigate the effect of RRBSO on sexual function in women at high risk of breast/and or ovarian cancer.

METHODS: A literature search of the AMED (Allied and complementary medicine), Embase and Medline databases was performed, using search terms including sexual function, risk reducing and oophorectomy. Results were filtered according to the PRISMA protocol. Quality assessment of studies was performed using the Newcastle-Ottawa scale. Data were pooled in meta-analysis.

RESULTS: There were 21 eligible studies, 10 of which reported sufficient data for meta-analysis. Most studies were retrospective cohort or observational studies. Fifteen of the 21 studies (71%) reported a negative impact of RRBSO on sexual function. Participant numbers ranged from 37 to 1522. Meta-analysis was performed with studies including 3201 patients. This demonstrated that RRBSO has a statistically significant negative impact on sexual function (SMD -0.63, [-0.82, -0.44], p = 0.03). There was a trend towards reduced sexual pleasure and increased discomfort but this did not reach statistical significance. There was minimal change in the frequency of sex. There was a significant increase in vaginal dryness post-RRBSO (SMD 9.25, [3.66, 14.83], p < 0.00001). There was no significant difference in sexual function between pre-menopausal and post-menopausal RRBSO. Hormone replacement therapy (HRT) did not abolish this negative impact.

CONCLUSION: Sexual function declines post RRBSO, independent of menopausal status. Comprehensive pre-operative counselling regarding anticipated menopausal and sexual symptoms is key to setting realistic patient expectations and minimising post-operative distress. Information and support regarding management of these side effects should be available to all patients.

PMID:34416580 | DOI:10.1016/j.ejogrb.2021.08.001

Comput Biol Med. 2021 Aug 13;136:104760. doi: 10.1016/j.compbiomed.2021.104760. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: In binary classification problems with a rare class of interest, there is relatively little information available for the rare class to build a model. On the other hand, the number of useful variables to develop a model for classification can be high-dimensional. For example, in drug discovery, there are usually a very few bioactive compounds in a large chemical library, whereas thousands of potentially useful explanatory variables characterize a compound’s chemical structure. The sparsity of information for the rare class of interest makes it difficult for the standard classification models to exploit the richness of the useful feature variables. Thus, the objective of this paper is to develop an R package which clusters the feature variables into diverse subsets to be aggregated into a powerful ensemble for the detection of a rare class object.

METHODS: The ensemble of phalanxes (EPX) builds a classifier by exploiting the richness of feature variables using several diverse subsets of variables, called phalanxes, and outperforms many competitive state-of-the-art classification methods in terms of predictive ranking of the rare class of interest.

RESULTS: We present an R package EPX which implements the algorithm to form the ensemble of phalanxes as well as its associated functions. We further show how the ensemble of phalanxes can be constructed using parallel computing to lower the computational burden given high-dimensional data.

CONCLUSIONS: The R package EPX shows a flexible way of clustering feature variable space into smaller and diverse subsets of variables to develop an ensemble of phalanxes which better ranks a rare class object in a highly unbalanced two class classification problem. The ensemble EPX will be useful to detect the rare drug-like active biomolecules for development in drug discovery (Tomal et al., Mar. 2016) [1] and homologous proteins using similarity scores of amino acid sequences in protein homology (Tomal et al., 2019) [2]. The package EPX is freely available to download from CRAN (https://CRAN.R-project.org/package=EPX).

PMID:34416572 | DOI:10.1016/j.compbiomed.2021.104760

Public Health. 2021 Aug 17;198:118-122. doi: 10.1016/j.puhe.2021.07.009. Online ahead of print.

ABSTRACT

OBJECTIVES: In 2015, the South African government implemented the national health promotion policy (NHPP), intending to reduce stillbirth and maternal mortality. This study was designed to quantify the impact of the NHPP on stillbirth and maternal mortality in both the South African population and immigrant citizens.

STUDY DESIGN: This was a panel analysis using secondary data issued by Statistic South Africa-Vital Statistics.

METHODS: The author exploited the changes in smoking status that the NHPP exerted between 2015 and 2017. The author then builds credible control and treatment groups based on smoking status for both groups. Women who quitted smoking post-NHPP implementation were considered as the treatment group. Women who persisted with smoking post-NHPP implementation were classified as the control group. The author then used a Two-stage Least Squared Model to quantify the impact of the NHPP on stillbirth and maternal mortality in both the South African and immigrant populations.

RESULTS: The model shows that NHPP averts stillbirths by 8.36% in the South African population residing in the urban areas and by 2.84% in the rural segments of the country. NHPP averts South African maternal mortalities by 20.88% in urban areas and by 15.60% in the rural segments of the country.Regarding the immigrant population, the model shows that NHPP averts immigrant’s stillbirths by 7.61% in the urban areas and by 2.79% in the rural segments of the country. In addition, NHPP averts immigrant maternal mortalities by 19.22% in the urban areas and by 13.04% in the rural segments of the country.

CONCLUSIONS: NHPP reduces stillbirth and maternal mortality outcomes slightly biased toward the South African population. These inequalities reflect immigrant’s lack of response to the NHPP framework and inadequate access to the South African health system.

PMID:34416574 | DOI:10.1016/j.puhe.2021.07.009

Musculoskelet Sci Pract. 2021 Aug 14;56:102448. doi: 10.1016/j.msksp.2021.102448. Online ahead of print.

ABSTRACT

BACKGROUND: Educational standards of advanced musculoskeletal physiotherapy include mentored clinical practice. Whilst traditionally delivered face-to-face, telehealth e-mentoring affords a distinctive andragogy to facilitate mentee development.

OBJECTIVE: To understand the experiences and outcomes of stakeholders participating in musculoskeletal physiotherapy telehealth e-mentoring.

DESIGN: A case study design with sequential mixed methods (quantitative patient outcome data and qualitative interviews and a focus group) of a 20-week e-mentored telehealth physiotherapy service.

METHODS: Data collection comprised 1) Patient experiences and measures of musculoskeletal health 2) Mentee semi-structured interviews 3) Mentor focus group. Data analysis included descriptive statistics (median and IQR) and the Framework Method for qualitative and quantitative data respectively. An exploratory bidirectional approach supported data integration across all participants.

RESULTS: Participants included patients (n = 90), mentees (n = 10) and mentors (n = 6). Patients reported improvements (>MCID) in MSK-HQ and Patient Specific Functional Scale, with high scores for Consultation and Relational Empathy and Patient Enablement Instruments. Main themes were a) social learning b) advanced professional practice c) learner experience and d) limitations of telehealth for mentees, and for mentors a) preparedness b) journey of development and c) challenges. Participant data integration resulted in 4 main themes 1) energising/positive experience 2) communications skills valued 3) perceptions of telehealth 4) upskilling required.

CONCLUSIONS: Telehealth e-mentoring is a valuable alternative to face-to-face mentored physiotherapy practice to support development in advanced musculoskeletal physiotherapy practice. Findings indicate that technical and professional skills are required, high levels of communication skills were valued, there is a need for reconceptualisation of musculoskeletal physiotherapeutic interventions.

PMID:34416558 | DOI:10.1016/j.msksp.2021.102448

PLoS One. 2021 Aug 20;16(8):e0256493. doi: 10.1371/journal.pone.0256493. eCollection 2021.

ABSTRACT

In order to eliminate COVID-19, many countries provided vaccinations. However, success depends on peoples’ knowledge levels and rates of acceptance. But, previous research on this topic is currently lacking in Bangladesh. This cross-sectional study aimed at to investigate Bangladeshi peoples’ knowledge, acceptance, and perception of challenges regarding COVID-19 vaccines. Quantitative data were collected using an online survey (n = 1975) and face-to-face interviews (n = 2200) with a pre-tested structured questionnaire. In addition, seven open-ended interviews were conducted with health experts regarding challenges of vaccination. Binary logistic regression analyses were conducted to assess the association between explanatory and dependent variables. Effect size was estimated to understand the magnitude of relationship between two variables. Of 4175 respondents, 92.6% knew about COVID-19 vaccines, while only 37.4% believed vaccines to be effective in controlling COVID-19. Nearly 46% of respondents believed that COVID-19 vaccines have side-effects, and 16.4% of respondents believed that side-effects could be life-threatening. Only 60.5% of respondents indicated that they would receive the COVID-19 vaccine. Out of 1650 respondents (39.5%) who did not intend to receive the vaccine, 948 (57.4%) believed that they would be naturally protected. Regressions results indicated that men had higher rates of knowledge regarding the vaccine. In addition, rural respondents demonstrated lower knowledge regarding the vaccine. Furthermore, education had a significant association with knowledge of COVID-19 vaccines. Respondents with university education had more knowledge regarding the vaccine (Odds ratio, OR = 29.99; 95% confidence interval, CI 11.40-78.90, effect size 1.88; p = 0.01) and correct dosage (OR 27.34; 95% CI 15.25-49.00, effect size 1.83; p = 0.01). However, women (OR 1.16; 95% CI 0.96-1.40, effect size 0.08) and rural (OR 1.24; 95% CI 1.07-1.44, effect size 0.12; p = 0.01) respondents were more enthusiastic regarding receiving the COVID-19 vaccine. Higher educated respondents showed higher probability of receiving the vaccine. Those who believed in the effectiveness of the COVID-19 vaccine were 11.57 times more interested (OR 11.57; 95% CI 8.92-15.01, effect size 1.35; p = 0.01) in receiving the vaccine. Open-ended interviews identified several challenges toward successful COVID-19 vaccination. Mass awareness creation, uninterrupted supply, equitable distribution, and sectoral coordination were suggested to achieve at least 70% immunization across the country.

PMID:34415969 | DOI:10.1371/journal.pone.0256493

Cochrane Database Syst Rev. 2021 Aug 20;8:CD014641. doi: 10.1002/14651858.CD014641.

ABSTRACT

BACKGROUND: Tuberculosis is the primary cause of hospital admission in people living with HIV, and the likelihood of death in the hospital is unacceptably high. The Alere Determine TB LAM Ag test (AlereLAM) is a point-of-care test and the only lateral flow lipoarabinomannan assay (LF-LAM) assay currently commercially available and recommended by the World Health Organization (WHO). A 2019 Cochrane Review summarised the diagnostic accuracy of LF-LAM for tuberculosis in people living with HIV. This systematic review assesses the impact of the use of LF-LAM (AlereLAM) on mortality and other patient-important outcomes.

OBJECTIVES: To assess the impact of the use of LF-LAM (AlereLAM) on mortality in adults living with HIV in inpatient and outpatient settings. To assess the impact of the use of LF-LAM (AlereLAM) on other patient-important outcomes in adults living with HIV, including time to diagnosis of tuberculosis, and time to initiation of tuberculosis treatment.

SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded (Web of Science), BIOSIS Previews, Scopus, LILACS; ProQuest Dissertations and Theses; ClinicalTrials.gov; and the WHO ICTRP up to 12 March 2021.

SELECTION CRITERIA: Randomized controlled trials that compared a diagnostic intervention including LF-LAM with diagnostic strategies that used smear microscopy, mycobacterial culture, a nucleic acid amplification test such as Xpert MTB/RIF, or a combination of these tests. We included adults (≥ 15 years) living with HIV.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility, extracted data, and analysed risk of bias using the Cochrane tool for assessing risk of bias in randomized studies. We contacted study authors for clarification as needed. We used risk ratio (RR) with 95% confidence intervals (CI). We used a fixed-effect model except in the presence of clinical or statistical heterogeneity, in which case we used a random-effects model. We assessed the certainty of the evidence using GRADE.

MAIN RESULTS: We included three trials, two in inpatient settings and one in outpatient settings. All trials were conducted in sub-Saharan Africa and assessed the impact of diagnostic strategies that included LF-LAM on mortality when the test was used in conjunction with other tuberculosis diagnostic tests or clinical assessment for clinical decision-making in adults living with HIV. Inpatient settings In inpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy likely reduces mortality in people living with HIV at eight weeks compared to routine tuberculosis diagnostic testing without LF-LAM (pooled RR 0.85, 95% CI 0.76 to 0.94; 5102 participants, 2 trials; moderate-certainty evidence). That is, people living with HIV who received LF-LAM had 15% lower risk of mortality. The absolute effect was 34 fewer deaths per 1000 (from 14 fewer to 55 fewer). In inpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy probably results in a slight increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF-LAM (pooled RR 1.26, 95% CI 0.94 to 1.69; 5102 participants, 2 trials; moderate-certainty evidence). Outpatient settings In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality in people living with HIV at six months compared to routine tuberculosis diagnostic testing without LF-LAM (RR 0.89, 95% CI 0.71 to 1.11; 2972 participants, 1 trial; low-certainty evidence). Although this trial did not detect a difference in mortality, the direction of effect was towards a mortality reduction, and the effect size was similar to that in inpatient settings. In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may result in a large increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF-LAM (RR 5.44, 95% CI 4.70 to 6.29, 3022 participants, 1 trial; low-certainty evidence). Other patient-important outcomes Assessment of other patient-important and implementation outcomes in the trials varied. The included trials demonstrated that a higher proportion of people living with HIV were able to produce urine compared to sputum for tuberculosis diagnostic testing; a higher proportion of people living with HIV were diagnosed with tuberculosis in the group that received LF-LAM; and the incremental diagnostic yield was higher for LF-LAM than for urine or sputum Xpert MTB/RIF.

AUTHORS’ CONCLUSIONS: In inpatient settings, the use of LF-LAM as part of a tuberculosis diagnostic testing strategy likely reduces mortality and probably results in a slight increase in tuberculosis treatment initiation in people living with HIV. The reduction in mortality may be due to earlier diagnosis, which facilitates prompt treatment initiation. In outpatient settings, the use of LF-LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality and may result in a large increase in tuberculosis treatment initiation in people living with HIV. Our results support the implementation of LF-LAM to be used in conjunction with other WHO-recommended tuberculosis diagnostic tests to assist in the rapid diagnosis of tuberculosis in people living with HIV.

PMID:34416013 | DOI:10.1002/14651858.CD014641