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Ordinal response is commonly found in medicine, biology, and other fields. In many situations, the predictors for this ordinal response are compositional, which means that the sum of predictors for each sample is fixed. Examples of compositional data include the relative abundance of species in microbiome data and the relative frequency of nutrition concentrations. Moreover, the predictors that are strongly correlated tend to have similar influence on the response outcome. Conventional cumulative logistic regression models for ordinal responses ignore the fixed-sum constraint on predictors and their associated interrelationships, and thus are not appropriate for analyzing compositional predictors.To solve this problem, we proposed Bayesian Compositional Models for Ordinal Response to analyze the relationship between compositional data and an ordinal response with a structured regularized horseshoe prior for the compositional coefficients and a soft sum-to-zero restriction on coefficients through the prior distribution. The method was implemented with R package rstan using efficient Hamiltonian Monte Carlo algorithm. We performed simulations to compare the proposed approach and existing methods for ordinal responses. Results revealed that our proposed method outperformed the existing methods in terms of parameter estimation and prediction. We also applied the proposed method to a microbiome study HMP2Data, to find microorganisms linked to ordinal inflammatory bowel disease levels. To make this work reproducible, the code and data used in this paper are available at https://github.com/Li-Zhang28/BCO., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Spike-and-slab prior distributions are used to impose variable selection in Bayesian regression-style problems with many possible predictors. These priors are a mixture of two zero-centered distributions with differing variances, resulting in different shrinkage levels on parameter estimates based on whether they are relevant to the outcome. The spike-and-slab lasso assigns mixtures of double exponential distributions as priors for the parameters. This framework was initially developed for linear models, later developed for generalized linear models, and shown to perform well in scenarios requiring sparse solutions. Standard formulations of generalized linear models cannot immediately accommodate categorical outcomes with > 2 categories, i.e. multinomial outcomes, and require modifications to model specification and parameter estimation. Such modifications are relatively straightforward in a Classical setting but require additional theoretical and computational considerations in Bayesian settings, which can depend on the choice of prior distributions for the parameters of interest. While previous developments of the spike-and-slab lasso focused on continuous, count, and/or binary outcomes, we generalize the spike-and-slab lasso to accommodate multinomial outcomes, developing both the theoretical basis for the model and an expectation-maximization algorithm to fit the model. To our knowledge, this is the first generalization of the spike-and-slab lasso to allow for multinomial outcomes., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 Informa UK Limited, trading as Taylor & Francis Group.)

Background: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown., Objective: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg)., Study Design: We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferred treatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit., Results: Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3 and 6.3±2.1 weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models., Conclusion: In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To estimate the association between state-level abortion legislation and all-cause mortality among all females of reproductive age and maternal, fetal, and infant mortality., Methods: We conducted a retrospective cohort study using the Centers for Disease Control and Prevention's WONDER (Wide-ranging ONline Data for Epidemiologic Research) database. Generalized estimating equations were used to estimate the association between supportive, moderate, and restrictive state abortion regulations and all-cause mortality in reproductive-aged females. Secondary outcomes included maternal, fetal, and infant mortality. The association of the number and type of laws on mortality were estimated., Results: Moderate and supportive states were not associated with a significant decrease in all-cause mortality compared with restrictive states. Maternal mortality (per 100,000 live births) was significantly lower in moderate (-5.79, 95% CI -9.88 to -1.70) compared with restrictive states, but not supportive states (-2.51, 95% CI -6.75 to 1.72). Infant mortality (per 1,000 live births) was significantly lower in both moderate (-0.56, 95% CI -1.09 to -0.04) and supportive (-1.10, 95% CI -1.56 to -0.64) states. Fetal mortality was lower in moderate states (-0.69, 95% CI -1.18 to -0.20) but not in supportive states (-0.64, 95% CI -1.14 to 0.13). Each additional abortion regulation was associated with an increase in maternal mortality (1.09/100,000 live births, 95% CI 0.36-1.82) and infant mortality (0.20/1,000 live births, 95% CI 0.12-0.26)., Conclusion: Moderate state abortion legislation was associated with lower rates of maternal, fetal, and infant mortality but not lower all-cause mortality in reproductive-aged females compared with restrictive laws. An increasing number of laws restricting abortion was associated with increased maternal and infant mortality., Competing Interests: Financial Disclosure Torri D. Metz served on a medical advisory board and was a site PI for a Pfizer SARS-CoV-2 vaccination in pregnancy trial, and is the site PI for a Pfizer RSV vaccination in pregnancy trial. She was the site PI for a Gestvision trial of a point-of-care test for preeclampsia. She receives royalties from UpToDate for two topics related to trial of labor after cesarean. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction/aims: We studied the progression of myasthenia gravis (MG) disease burden and medication adjustment among MG Patient Registry participants., Methods: Participants diagnosed with MG (age ≥18 years), registered between July 1, 2013 and July 31, 2018 and completing both 6- and 12-month follow-up surveys, were included in this investigation. Participants were grouped into high-burden (Myasthenia Gravis Activity of Daily Living scale [MG-ADL] score ≥6) and low-burden (MG-ADL <6) groups based on MG-ADL scores at enrollment. Demographics and disease history were compared between groups. MG-ADL score change and medication changes (escalation, no change, de-escalation) between enrollment and 12-month follow-up were compared between groups. Minimal symptom expression (MSE, MG-ADL <2) at 12 months was compared between groups. Logistic regression analysis was performed to study factors associated with MSE at 12 months., Results: In total, 520 participants (56% female) were included in high-burden (n = 248) and low-burden (n = 272) groups. Those in the high-burden group were more likely to be younger, female, and have shorter disease duration. At 12 months, MSE was achieved in 6% of the high-burden group and newly achieved (42 of 201, 21%) or maintained (52 of 71, 73%) in the low-burden group. In the multivariable analysis, being in the high-burden group and use of pyridostigmine were associated with less likelihood of MSE, whereas MG-ADL score improvement (>2 or >20%) at 6 months significantly increased the likelihood of achieving MSE at 12 months (P = .0004)., Discussion: In both groups, but more so in the high-burden group, patients infrequently achieved MSE after 1 year of MG treatment. Baseline low disease burden, improvement at 6 months and no pyridostigmine use were associated with a higher likelihood of MSE at 12 months., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Background: The Symbol Digit Modalities Test (SDMT) is a common screen of cognitive function for people with Multiple Sclerosis (pwMS) but growing acknowledgement that people with cognitive impairment are a heterogeneous population suggests that a single screen may provide limited information., Objective: To assess the adequacy of the SDMT in capturing impairment across specific cognitive domains as measured by a multi-domain cognitive assessment battery (CAB, NeuroTrax)., Methods: 113 pwMS were assessed with SDMT and the CAB. Cognitive impairment in each CAB domain was defined as ≥1.5 SD below the normalized mean. Logistic regression models were fit for each CAB domain with domain-specific cognitive impairment as the outcome and SDMT as the predictor, and a classifier created by selecting cutpoints using the Youden Index. Model performance was assessed by predicting domain-specific cognitive impairment in an independent data set consisting of 81 pwMS., Results: SDMT was a significant predictor of cognitive impairment in all outcomes considered (Odds Ratio: 0.885-0.950), but prediction metrics such as area under the receiver operating curve (AUC) were modest (0.623-0.778), and the alignment between observed/predicted impairment was less than optimal., Conclusion: The SDMT is not sufficient to differentiate between impaired and non-impaired pwMS across several cognitive domains., (Copyright © 2022. Published by Elsevier B.V.)

Spike-and-slab priors model predictors as arising from a mixture of distributions: those that should (slab) or should not (spike) remain in the model. The spike-and-slab lasso (SSL) is a mixture of double exponentials, extending the single lasso penalty by imposing different penalties on parameters based on their inclusion probabilities. The SSL was extended to Generalized Linear Models (GLM) for application in genetics/genomics, and can handle many highly correlated predictors of a scalar outcome, but does not incorporate these relationships into variable selection. When images/spatial data are used to model a scalar outcome, relevant parameters tend to cluster spatially, and model performance may benefit from incorporating spatial structure into variable selection. We propose to incorporate spatial information by assigning intrinsic autoregressive priors to the logit prior probabilities of inclusion, which results in more similar shrinkage penalties among spatially adjacent parameters. Using MCMC to fit Bayesian models can be computationally prohibitive for large-scale data, but we fit the model by adapting a computationally efficient coordinate-descent-based EM algorithm. A simulation study and an application to Alzheimer's Disease imaging data show that incorporating spatial information can improve model fitness.

Alzheimer's disease (AD) is the leading cause of dementia and has received considerable research attention, including using neuroimaging biomarkers to classify patients and/or predict disease progression. Generalized linear models, e.g., logistic regression, can be used as classifiers, but since the spatial measurements are correlated and often outnumber subjects, penalized and/or Bayesian models will be identifiable, while classical models often will not. Many useful models, e.g., the elastic net and spike-and-slab lasso, perform automatic variable selection, which removes extraneous predictors and reduces model variance, but neither model exploits spatial information in selecting variables. Spatial information can be incorporated into variable selection by placing intrinsic autoregressive priors on the logit probabilities of inclusion within a spike-and-slab elastic net framework. We demonstrate the ability of this framework to improve classification performance by using cortical thickness and tau-PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to classify subjects as cognitively normal or having dementia, and by using a simulation study to examine model performance using finer resolution images., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Justin M. Leach, Lloyd J. Edwards, Rajesh Kana, Kristina Visscher, and Nengjun Yi have no conflicts to declare. Inmaculada Aban has received funding and lists the following as possible conflicts of interests: Myasthenia Gravis Foundation of America (MGFA), Ra Pharmaceutical through MGFA, Alexion through MGFA, Argenx through MGFA, Catalyst through MGFA, Verona Pharmaceutical. No patents, products in development or marketed products associated with this research need to be declared. No information here alters our adherence to policies on sharing data and materials.

Background: Sickle cell anemia may be associated with cognitive dysfunction, and some complications of sickle cell anemia might affect those with sickle cell trait (SCT), so we hypothesized that SCT is a risk factor for cognitive impairment., Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a national cohort of 30,239 white and black Americans from 2003 to 7, who are followed every 6 months. Baseline and annual global cognitive function testing used the Six-Item Screener (SIS), a validated instrument (scores range 0-6; ≤ 4 indicates cognitive impairment). Participants with baseline cognitive impairment and whites were excluded. Logistic regression was used to calculate the association of SCT with incident cognitive impairment, adjusted for risk factors. Linear mixed models assessed multivariable-adjusted change in test scores on a biennially administered 3-test battery measuring learning, memory, and semantic and phonemic fluency., Findings: Among 7743 participants followed for a median of 7·1 years, 85 of 583 participants with SCT (14·6%) developed incident cognitive impairment compared to 902 of 7160 (12·6%) without SCT. In univariate analysis, the odds ratio (OR) of incident cognitive impairment was 1·18 (95% CI: 0·93, 1·51) for those with SCT vs. those without. Adjustment did not impact the OR. There was no difference in change on 3-test battery scores by SCT status (all p  > 0·11)., Interpretation: In this prospective cohort study of black Americans, SCT was not associated with incident cognitive impairment or decline in test scores of learning, memory and executive function., Funding: National Institutes of Health, American Society of Hematology.

Introduction : Increased variability in motor function has been observed during the initial stages of cognitive decline. However, the natural variability of postural control, as well as its association with cognitive status and decline, remains unknown. The objective of this pilot study was to characterize the day-to-day variability in postural sway in non-demented older adults. We hypothesized that older adults with a lower cognitive status would have higher day-to-day variability in postural sway. Materials and Methods : A Nintendo Wii balance board (WBB) was used to quantify postural sway in the home twice daily for 30 days in 20 non-demented, community-dwelling older adults: once under a single-task condition and once under a dual-task condition (using a daily word search task administered via a Nook tablet). Mean sway distance, velocity, area, centroidal frequency and frequency dispersion were derived from the center of pressure data acquired from the WBB. Results : Linear relationships were observed between the day-to-day variability in postural sway and cognitive status (indexed by cognitive global z-scores). More variability in time-domain postural sway (sway distance and area) and less variability in frequency-domain postural sway (centroidal sway frequency) were associated with a lower cognitive status under both the single- and dual-task conditions. Additionally, lower cognitive performance rates on the daily word search task were related to a lower cognitive status. Discussion : This small pilot study conducted on a short time scale motivates large-scale implementations over more extended time periods. Tracking longitudinal changes in postural sway may further our understanding of early-stage postural decline and its association with cognitive decline and, in turn, may aid in the early detection of dementia during preclinical stages when the utility of disease-modifying therapies would be greatest.

Although turning has been reported as one of the leading activities performed during a fall, and falls during turning result in 8-times more hip fractures than falls during linear gait, the quantity and quality of turns resulting in falls remain unknown since turns are rarely assessed during activities of daily living. 160 community-dwelling older adults were monitored for one week using smartphone technology. Turn measures and activity rates were quantified. Fall incidence within 12 months from continuous monitoring defined fall status, with 7/153 prospective fallers/non-fallers. Based on the analysis of 718,582 turns, prospective fallers turned less frequently, took longer to turn, and were less consistent in turn angle (p = 0.007, 0.025, and 0.038, respectively). Prospective fallers also walked slower and spent less time walking and turning and more time engaged in sedentary behavior (p = 0.043, 0.012, and 0.015, respectively). Individuals experiencing decline in the control of gait and/or turning may attempt to reduce their risk of falling by limiting their exposure and implementing cautionary movement strategies while turning. Since there was no difference in the overall active rate between prospective fallers and non-fallers, impaired gait and turning ability, specifically, may attribute to elevated fall risk within this cohort.

Expansion of novel therapeutics to all patients with cystic fibrosis (CF) requires personalized CFTR modulator therapy. We have developed nasospheroids, a primary cell culture-based model derived from individual CF patients and healthy subjects by a minimally invasive nasal biopsy. Confocal microscopy was utilized to measure CFTR activity by analyzing changes in cross-sectional area over time that resulted from CFTR-mediated ion and fluid movement. Both the rate of change over time and AUC were calculated. Non-CF nasospheroids with active CFTR-mediated ion and fluid movement showed a reduction in cross-sectional area, whereas no changes were observed in CF spheroids. Non-CF spheroids treated with CFTR inhibitor lost responsiveness for CFTR activation. However, nasospheroids from F508del CF homozygotes that were treated with lumacaftor and ivacaftor showed a significant reduction in cross-sectional area, indicating pharmacologic rescue of CFTR function. This model employs a simple measurement of size corresponding to changes in CFTR activity and is applicable for detection of small changes in CFTR activity from individual patients in vitro. Advancements of this technique will provide a robust model for individualized prediction of CFTR modulator efficacy.

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

The Nintendo Wii balance board (WBB) has generated significant interest in its application as a postural control measurement device in both the clinical and (basic, clinical, and rehabilitation) research domains. Although the WBB has been proposed as an alternative to the "gold standard" laboratory-grade force plate, additional research is necessary before the WBB can be considered a valid and reliable center of pressure (CoP) measurement device. In this study, we used the WBB and a laboratory-grade AMTI force plate (AFP) to simultaneously measure the CoP displacement of a controlled dynamic load, which has not been done before. A one-dimensional inverted pendulum was displaced at several different displacement angles and load heights to simulate a variety of postural sway amplitudes and frequencies (<1 Hz). Twelve WBBs were tested to address the issue of inter-device variability. There was a significant effect of sway amplitude, frequency, and direction on the WBB's CoP measurement error, with an increase in error as both sway amplitude and frequency increased and a significantly greater error in the mediolateral (ML) (compared to the anteroposterior (AP)) sway direction. There was no difference in error across the 12 WBB's, supporting low inter-device variability. A linear calibration procedure was then implemented to correct the WBB's CoP signals and reduce measurement error. There was a significant effect of calibration on the WBB's CoP signal accuracy, with a significant reduction in CoP measurement error (quantified by root-mean-squared error) from 2-6 mm (before calibration) to 0.5-2 mm (after calibration). WBB-based CoP signal calibration also significantly reduced the percent error in derived (time-domain) CoP sway measures, from -10.5% (before calibration) to -0.05% (after calibration) (percent errors averaged across all sway measures and in both sway directions). In this study, we characterized the WBB's CoP measurement error under controlled, dynamic conditions and implemented a linear calibration procedure for WBB CoP signals that is recommended to reduce CoP measurement error and provide more reliable estimates of time-domain CoP measures. Despite our promising results, additional work is necessary to understand how our findings translate to the clinical and rehabilitation research domains. Once the WBB's CoP measurement error is fully characterized in human postural sway (which differs from our simulated postural sway in both amplitude and frequency content), it may be used to measure CoP displacement in situations where lower accuracy and precision is acceptable.

PURPOSE: The prime purpose of the study was to investigate whether focus groups were a practical way of seeking the views of dying people and whether the information collected added to that collected by more established methods. DESIGN: A sample frame of Macmillan nurse patients was collated from which three cluster samples were randomly selected to participate in focus groups. The focus groups were structured with an experienced facilitator and recorder to answer three key questions. SETTING AND PARTICIPANTS: Patients of Macmillan nurses in three NHS Trusts in West Yorkshire who were living at home with incurable cancer. They were aware of their condition and were willing to participate. MAIN VARIABLES STUDIED: The three key questions were; what kind of help are you currently receiving? What sort of help do you want? Of the kind of help you are receiving what kind is most important to you? RESULTS: 17 patients participated in three focus groups. Participants were generally fairly able and living with spouses or relatives. They were of varying age with different types and duration of cancer. They were receiving a range of health and social services of varying importance to them. More help was particularly wanted with support for daily living, support from specialist cancer nurses, help getting out and with housework. Macmillan nurses and general practice services were highly rated in some but not all three trust areas. CONCLUSIONS: We propose that focus groups are a practical way of collecting information about dying patients that can complement other sources of information in planning and auditing the provision of care.

A simplified computer method for recording postmortem and histopathological findings is described. The method allows a major reduction in the workload of the pathologist and provides a convient means of selection and comparison of experimental results.

A new latex agglutination test system (ANTIGEX-TM) for the detection of Hepatitis B Antigen (HBAg) is described. It can be used to detect HBAg in either serum or plasma with a sensitivity comparable to that of complement fixation and about four times greater than counterimmunoelectrophoresis. The sensitivity and specificity of the system is illustrated by the test results obtained on the F.D.A. Bureau of Biologics Sera Panel No. 2 and on sera and plasma specimens from normal blood donors in the U.K. and the USA. Further applications of the technique, in the detection of HBAg in finger-prick blood samples, and in the rapid determination of antigen subtype ('ad' or 'ay'), are also described.

Hepatitis associated antigen may be detected quickly and reliably by the latex agglutination test, using antiserum from guinea pigs immunized with the antigen. The latex test has a sensitivity comparable to the counter current immunoelectrophoresis technique.