Category: Nevin Manimala

Mol Biol Evol. 2023 Feb 15:msad027. doi: 10.1093/molbev/msad027. Online ahead of print.

ABSTRACT

Genomic regions under positive selection harbour variation linked for example to adaptation. Most tools for detecting positively selected variants have computational resource requirements rendering them impractical on population genomic datasets with hundreds of thousands of individuals or more. We have developed and implemented an efficient haplotype-based approach able to scan large datasets and accurately detect positive selection. We achieve this by combining a pattern matching approach based on the positional Burrows-Wheeler transform with model-based inference which only requires the evaluation of closed-form expressions. We evaluate our approach with simulations, and find it to be both sensitive and specific. The computational resource requirements quantified using UK Biobank data indicate that our implementation is scalable to population genomic datasets with millions of individuals. Our approach may serve as an algorithmic blueprint for the era of ‘big data’ genomics: a combinatorial core coupled with statistical inference in closed form.

PMID:36790822 | DOI:10.1093/molbev/msad027

Transl Vis Sci Technol. 2023 Feb 1;12(2):23. doi: 10.1167/tvst.12.2.23.

ABSTRACT

PURPOSE: (1) To assess the performance of geometric deep learning in diagnosing glaucoma from a single optical coherence tomography (OCT) scan of the optic nerve head and (2) to compare its performance to that obtained with a three-dimensional (3D) convolutional neural network (CNN), and with a gold-standard parameter, namely, the retinal nerve fiber layer (RNFL) thickness.

METHODS: Scans of the optic nerve head were acquired with OCT for 477 glaucoma and 2296 nonglaucoma subjects. All volumes were automatically segmented using deep learning to identify seven major neural and connective tissues. Each optic nerve head was then represented as a 3D point cloud with approximately 1000 points. Geometric deep learning (PointNet) was then used to provide a glaucoma diagnosis from a single 3D point cloud. The performance of our approach (reported using the area under the curve [AUC]) was compared with that obtained with a 3D CNN, and with the RNFL thickness.

RESULTS: PointNet was able to provide a robust glaucoma diagnosis solely from a 3D point cloud (AUC = 0.95 ± 0.01).The performance of PointNet was superior to that obtained with a 3D CNN (AUC = 0.87 ± 0.02 [raw OCT images] and 0.91 ± 0.02 [segmented OCT images]) and with that obtained from RNFL thickness alone (AUC = 0.80 ± 0.03).

CONCLUSIONS: We provide a proof of principle for the application of geometric deep learning in glaucoma. Our technique requires significantly less information as input to perform better than a 3D CNN, and with an AUC superior to that obtained from RNFL thickness.

TRANSLATIONAL RELEVANCE: Geometric deep learning may help us to improve and simplify diagnosis and prognosis applications in glaucoma.

PMID:36790820 | DOI:10.1167/tvst.12.2.23

JAMA Netw Open. 2023 Feb 1;6(2):e2255986. doi: 10.1001/jamanetworkopen.2022.55986.

ABSTRACT

IMPORTANCE: Screening adolescents in emergency departments (EDs) for suicidal risk is a recommended strategy for suicide prevention. Comparing screening measures on predictive validity could guide ED clinicians in choosing a screening tool.

OBJECTIVE: To compare the Ask Suicide-Screening Questions (ASQ) instrument with the Computerized Adaptive Screen for Suicidal Youth (CASSY) instrument for the prediction of suicidal behavior among adolescents seen in EDs, across demographic and clinical strata.

DESIGN, SETTING, AND PARTICIPANTS: The Emergency Department Study for Teens at Risk for Suicide is a prospective, random-series, multicenter cohort study that recruited adolescents, oversampled for those with psychiatric symptoms, who presented to the ED from July 24, 2017, through October 29, 2018, with a 3-month follow-up to assess the occurrence of suicidal behavior. The study included 14 pediatric ED members of the Pediatric Emergency Care Applied Research Network and 1 Indian Health Service ED. Statistical analysis was performed from May 2021 through January 2023.

MAIN OUTCOMES AND MEASURES: This study used a prediction model to assess outcomes. The primary outcome was suicide attempt (SA), and the secondary outcome was suicide-related visits to the ED or hospital within 3 months of baseline; both were assessed by an interviewer blinded to baseline information. The ASQ is a 4-item questionnaire that surveys suicidal ideation and lifetime SAs. A positive response or nonresponse on any item indicates suicidal risk. The CASSY is a computerized adaptive screening tool that always includes 3 ASQ items and a mean of 8 additional items. The CASSY’s continuous outcome is the predicted probability of an SA.

RESULTS: Of 6513 adolescents available, 4050 were enrolled, 3965 completed baseline assessments, and 2740 (1705 girls [62.2%]; mean [SD] age at enrollment, 15.0 [1.7] years; 469 Black participants [17.1%], 678 Hispanic participants [24.7%], and 1618 White participants [59.1%]) completed both screenings and follow-ups. The ASQ and the CASSY showed a similar sensitivity (0.951 [95% CI, 0.918-0.984] vs 0.945 [95% CI, 0.910-0.980]), specificity (0.588 [95% CI, 0.569-0.607] vs 0.643 [95% CI, 0.625-0.662]), positive predictive value (0.127 [95% CI, 0.109-0.146] vs 0.144 [95% CI, 0.123-0.165]), and negative predictive value (both 0.995 [95% CI, 0.991-0.998], respectively). Area under the receiver operating characteristic curve findings were similar among patients with physical symptoms (ASQ, 0.88 [95% CI, 0.81-0.95] vs CASSY, 0.94 [95% CI, 0.91-0.96]). Among patients with psychiatric symptoms, the CASSY performed better than the ASQ (0.72 [95% CI, 0.68-0.77] vs 0.57 [95% CI, 0.55-0.59], respectively).

CONCLUSIONS AND RELEVANCE: This study suggests that both the ASQ and the CASSY are appropriate for universal screening of patients in pediatric EDs. For the small subset of patients with psychiatric symptoms, the CASSY shows greater predictive validity.

PMID:36790810 | DOI:10.1001/jamanetworkopen.2022.55986

JAMA Netw Open. 2023 Feb 1;6(2):e2255999. doi: 10.1001/jamanetworkopen.2022.55999.

ABSTRACT

IMPORTANCE: Variation in outcomes across hospitals adversely affects surgical patients. The use of high-quality hospitals varies by population, which may contribute to surgical disparities.

OBJECTIVE: To simulate the implications of data-driven hospital selection for social welfare among patients who underwent colorectal cancer surgery.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used the hospital inpatient file from the Florida Agency for Health Care Administration. Surgical outcomes of patients who were treated between January 1, 2016, and December 31, 2018 (training cohort), were used to estimate hospital performance. Costs and benefits of care at alternative hospitals were assessed in patients who were treated between January 1, 2019, and December 31, 2019 (testing cohort). The cohorts comprised patients 18 years or older who underwent elective colorectal resection for benign or malignant neoplasms. Data were analyzed from March to October 2022.

EXPOSURES: Using hierarchical logistic regression, we estimated the implications of hospital selection for in-hospital mortality risk in patients in the training cohort. These estimates were applied to patients in the testing cohort using bayesian simulations to compare outcomes at each patient’s highest-performing and chosen local hospitals. Analyses were stratified by race and ethnicity to evaluate the potential implications for equity.

MAIN OUTCOMES AND MEASURES: The primary outcome was the mean patient-level change in social welfare, a composite measure balancing the value of reduced mortality with associated costs of care at higher-performing hospitals.

RESULTS: A total of 21 098 patients (mean [SD] age, 67.3 [12.0] years; 10 782 males [51.1%]; 2232 Black [10.6%] and 18 866 White [89.4%] individuals) who were treated at 178 hospitals were included. A higher-quality local hospital was identified for 3057 of 5000 patients (61.1%) in the testing cohort. Selecting the highest-performing hospital was associated with a 26.5% (95% CI, 24.5%-29.0%) relative reduction and 0.24% (95% CI, 0.23%-0.25%) absolute reduction in mortality risk. A mean amount of $1953 (95% CI, $1744-$2162) was gained in social welfare per patient treated. Simulated reassignment to a higher-quality local hospital was associated with a 23.5% (95% CI, 19.3%-32.9%) relative reduction and 0.26% (95% CI, 0.21%-0.30%) absolute reduction in mortality risk for Black patients, with $2427 (95% CI, $1697-$3158) gained in social welfare.

CONCLUSIONS AND RELEVANCE: In this economic evaluation, using procedure-specific hospital performance as the primary factor in the selection of a local hospital for colorectal cancer surgery was associated with improved outcomes for both patients and society. Surgical outcomes data can be used to transform care and guide policy in colorectal cancer.

PMID:36790809 | DOI:10.1001/jamanetworkopen.2022.55999

Am J Epidemiol. 2023 Feb 14:kwad036. doi: 10.1093/aje/kwad036. Online ahead of print.

ABSTRACT

Most reported treatment effects in medical research studies are ambiguously defined, which can lead to misinterpretation of study results. This is because most studies do not attempt to describe what the treatment effect represents, and instead require readers to deduce this based on the reported statistical methods. However, this approach is fraught, as many methods provide counterintuitive results. For example, some methods include data from all patients, yet the resulting treatment effect applies only to a subset of patients, whereas other methods will exclude certain patients while results will apply to everyone. Additionally, some analyses provide estimates pertaining to hypothetical settings where patients never die or discontinue treatment. Herein we introduce estimands as a solution to the aforementioned problem. An estimand is a clear description of what the treatment effect represents, thus saving readers the necessity of trying to infer this from study methods and potentially getting it wrong. We provide examples of how estimands can remove ambiguity from reported treatment effects and describe their current use in practice. The crux of our argument is that readers should not have to infer what investigators are estimating; they should be told explicitly.

PMID:36790803 | DOI:10.1093/aje/kwad036

Am J Epidemiol. 2023 Feb 14:kwad030. doi: 10.1093/aje/kwad030. Online ahead of print.

ABSTRACT

Qualitative research methods, while rising in popularity, are still a relatively underutilized tool in public health research. Usually reserved for small samples, qualitative research techniques have the potential to enhance insights gained from large questionnaires and cohort studies, both deepening the interpretation of quantitative data and generating novel hypotheses that might otherwise be missed by standard approaches; this is especially true where exposures and outcomes are new, understudied, or rapidly changing, as in a pandemic. However, methods for the conduct of qualitative research within large samples are underdeveloped. Here, we describe a novel method of applying qualitative research methods to free-text comments collected in a large epidemiologic questionnaire. Specifically, this method includes: 1) a hierarchical system of coding through content analysis; 2) a qualitative data management application; and 3) an adaptation of Cohen’s kappa and percent agreement statistics for use by a team of coders, applying multiple codes per record from a large codebook. The methods outlined in this paper may help direct future applications of qualitative and mixed methods within large cohort studies.

PMID:36790786 | DOI:10.1093/aje/kwad030

JAMA Dermatol. 2023 Feb 15. doi: 10.1001/jamadermatol.2022.6378. Online ahead of print.

ABSTRACT

IMPORTANCE: Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN.

OBJECTIVE: To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide.

DATA SOURCES: The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022.

STUDY SELECTION: Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN.

DATA EXTRACTION AND SYNTHESIS: Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

MAIN OUTCOMES AND MEASURES: Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs.

RESULTS: Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%). There was a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series.

CONCLUSION AND RELEVANCE: In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.

PMID:36790777 | DOI:10.1001/jamadermatol.2022.6378

Am J Biol Anthropol. 2022 Aug;178 Suppl 74:54-114. doi: 10.1002/ajpa.24494. Epub 2022 Mar 22.

ABSTRACT

This article presents outcomes from a Workshop entitled “Bioarchaeology: Taking Stock and Moving Forward,” which was held at Arizona State University (ASU) on March 6-8, 2020. Funded by the National Science Foundation (NSF), the School of Human Evolution and Social Change (ASU), and the Center for Bioarchaeological Research (CBR, ASU), the Workshop’s overall goal was to explore reasons why research proposals submitted by bioarchaeologists, both graduate students and established scholars, fared disproportionately poorly within recent NSF Anthropology Program competitions and to offer advice for increasing success. Therefore, this Workshop comprised 43 international scholars and four advanced graduate students with a history of successful grant acquisition, primarily from the United States. Ultimately, we focused on two related aims: (1) best practices for improving research designs and training and (2) evaluating topics of contemporary significance that reverberate through history and beyond as promising trajectories for bioarchaeological research. Among the former were contextual grounding, research question/hypothesis generation, statistical procedures appropriate for small samples and mixed qualitative/quantitative data, the salience of Bayesian methods, and training program content. Topical foci included ethics, social inequality, identity (including intersectionality), climate change, migration, violence, epidemic disease, adaptability/plasticity, the osteological paradox, and the developmental origins of health and disease. Given the profound changes required globally to address decolonization in the 21st century, this concern also entered many formal and informal discussions.

PMID:36790761 | DOI:10.1002/ajpa.24494

J Phys Chem A. 2023 Feb 15. doi: 10.1021/acs.jpca.2c07476. Online ahead of print.

ABSTRACT

Recent low-temperature infrared-based experimental studies provided information about the effects of aqueous microsolvation on the intramolecular hydrogen bond of protonated glycine and β-alanine [J. Phys. Chem. A 2019, 123, 3355]. Here we address the temperature-dependent entropic effects on the aqueous microsolvation patterns of these protonated amino acids using the AAH⁺(H₂O)_n (n = 1-8) cluster model at 50 K and room temperature with Born-Oppenheimer molecular dynamics using a calibrated hybrid density functional. The C_COOH-O_w, N-O_w, and center-of-mass-O_w radial distribution functions provide accurate structural data and temperature-dependent water coordination numbers vs. solvation degree. The solvation patterns for protonated glycine at 50 K show structural features in agreement with previous static optimizations. However, entropic effects at room temperature play a crucial role in the evolution of the intramolecular HB strength vs. solvation degree for both protonated amino acids. With increasing hydration entropic effects favor the making of solvent hydrogen bond networks over full solvation of protonated glycine. At room temperature four water molecules are needed to build the first solvation shell for protonated glycine while five are required for protonated β-alanine. A new statistical Cumulative Percentage of Structures (CPS) scheme is proposed; when the CPS data are analyzed in light of the empirical formula of Rozenberg et al. [Phys. Chem. Chem. Phys. 2000, 2, 2699] and the hydrogen bond relative strength (HBRS) criteria of Jeffrey [An Introduction to Hydrogen Bonding; Oxford University: 1997] we can provide a detailed molecular mechanism for the weakening of the intramolecular hydrogen bond based on the average dynamical structures, which clearly reveals the temperature dependence of this process. The new CPS-HBRS scheme proposed here can be utilized using any type of molecular dynamics trajectory (classical, BOMD, CPMD, etc.).

PMID:36790739 | DOI:10.1021/acs.jpca.2c07476

Am J Biol Anthropol. 2023 Feb 7. doi: 10.1002/ajpa.24695. Online ahead of print.

ABSTRACT

OBJECTIVES: Recent studies have associated subarticular trabecular bone distribution in the extant hominid first metacarpal (Mc1) with observed thumb use, to infer fossil hominin thumb use. Here, we analyze the entire Mc1 to test for interspecific differences in: (1) the absolute volume of trabecular volume fraction, (2) the distribution of the deeper trabecular network, and (3) the distribution of trabeculae in the medullary cavity, especially beneath the Mc1 disto-radial flange.

MATERIALS AND METHODS: Trabecular bone was imaged using micro-computed tomography in a sample of Homo sapiens (n = 11), Pan paniscus (n = 10), Pan troglodytes (n = 11), Gorilla gorilla (n = 10) and Pongo sp., (n = 7). Using Canonical Holistic Morphometric Analysis (cHMA), we tested for interspecific differences in the trabecular bone volume fraction (BV/TV) and its relative distribution (rBV/TV) throughout the Mc1, including within the head, medullary cavity, and base.

RESULTS: P. paniscus had the highest, and H. sapiens the lowest, BV/TV relative to other species. rBV/TV distribution statistically distinguished the radial concentrations and lack of medullary trabecular bone in the H. sapiens Mc1 from all other hominids. H. sapiens and, to a lesser extent, G. gorilla also had a significantly higher trabecular volume beneath the disto-radial flange relative to other hominids.

DISCUSSION: These results are consistent with differences in observed thumb use in these species and may also reflect systemic differences in bone volume fraction. The trabecular bone extension into the medullary cavity and concentrations beneath the disto-radial flange may represent crucial biomechanical signals that will aid in the inference of fossil hominin thumb use.

PMID:36790736 | DOI:10.1002/ajpa.24695