Nevin Manimala

Stat Med. 2021 Jul 15. doi: 10.1002/sim.9144. Online ahead of print.

ABSTRACT

In biomedical studies, the causal mediation effect might be heterogeneous across individuals in the study population due to each study subject’s unique characteristics. While individuals’ mediation effects may differ from each other, it is often reasonable and more interpretable to assume that individuals belong to several distinct latent subgroups with similar attributes. In this article, we first show that the subgroup-specific mediation effect can be identified under the group-specific sequential ignorability assumptions. Then, we propose a simple mixture modeling approach to account for the latent subgroup structure where each mixture component corresponds to one latent subgroup in the linear structural equation model framework. Model parameters can be estimated using the standard expectation-maximization (EM) algorithm. Each individual’s subgroup membership can be inferred based on the posterior probability. We propose to use the singular Bayesian information criterion to consistently select the number of latent subgroups by recognizing that the Fisher information matrix for mixture models might be singular. We then propose to use nonparametric bootstrap method to compute standard errors and confidence intervals. We conducted simulation studies to evaluate the empirical performance of our proposed method named iMed. Finally, we reanalyzed a DNA methylation data set from the Normative Aging Study and found that the mediation effects of two well-documented DNA methylation CpG sites are heterogeneous across two latent subgroups in the causal pathway from smoking behavior to lung function. We also developed an R package iMed for public use.

PMID:34263963 | DOI:10.1002/sim.9144

Biometrics. 2021 Jul 15. doi: 10.1111/biom.13530. Online ahead of print.

ABSTRACT

When to initiate treatment on patients is an important problem in many medical studies such as AIDS and cancer. In this article, we formulate the treatment initiation time problem for time-to-event data and propose an optimal individualized regime that determines the best treatment initiation time for individual patients based on their characteristics. Different from existing optimal treatment regimes where treatments are undertaken at a pre-specified time, here new challenges arise from the complicated missing mechanisms in treatment initiation time data and the continuous treatment rule in terms of initiation time. To tackle these challenges, we propose to use restricted mean residual lifetime as a value function to evaluate the performance of different treatment initiation regimes, and develop a nonparametric estimator for the value function, which is consistent even when treatment initiation times are not completely observable and their distribution is unknown. We also establish the asymptotic properties of the resulting estimator in the decision rule and its associated value function estimator. In particular, the asymptotic distribution of the estimated value function is nonstandard, which follows a weighted chi-squared distribution. The finite-sample performance of the proposed method is evaluated by simulation studies and is further illustrated with an application to a breast cancer data. This article is protected by copyright. All rights reserved.

PMID:34263933 | DOI:10.1111/biom.13530

Transfusion. 2021 Jul 15. doi: 10.1111/trf.16587. Online ahead of print.

ABSTRACT

BACKGROUND: Prophylactic platelet transfusions prevent bleeding in hemato-oncology patients, but it is unclear how any benefit varies between patients. Our aim was to assess if patients with different baseline risks for bleeding benefit differently from a prophylactic platelet transfusion strategy.

STUDY DESIGN AND METHODS: Using the data from the randomized controlled TOPPS trial (Trial of Platelet Prophylaxis), we developed a prediction model for World Health Organization grades 2, 3, and 4 bleeding risk (defined as at least one bleeding episode in a 30 days period) and grouped patients in four risk-quartiles based on this predicted baseline risk. Predictors in the model were baseline platelet count, age, diagnosis, disease modifying treatment, disease status, previous stem cell transplantation, and the randomization arm.

RESULTS: The model had a c-statistic of 0.58 (95% confidence interval [CI] 0.54-0.64). There was little variation in predicted risks (quartiles 46%, 47%, and 51%), but prophylactic platelet transfusions gave a risk reduction in all risk quartiles. The absolute risk difference (ARD) was 3.4% (CI -12.2 to 18.9) in the lowest risk quartile (quartile 1), 7.4% (95% CI -8.4 to 23.3) in quartile 2, 6.8% (95% CI -9.1 to 22.9) in quartile 3, and 12.8% (CI -3.1 to 28.7) in the highest risk quartile (quartile 4).

CONCLUSION: In our study, generally accepted bleeding risk predictors had limited predictive power (expressed by the low c-statistic), and, given the wide confidence intervals of predicted ARD, could not aid in identifying subgroups of patients who might benefit more (or less) from prophylactic platelet transfusion.

PMID:34263930 | DOI:10.1111/trf.16587

Ginekol Pol. 2021 Jul 15. doi: 10.5603/GP.a2021.0115. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this randomised study was to investigate whether early or late clamping of the cord influences the status of micro-elements and thyroid hormone levels in newborns.

MATERIAL AND METHODS: The study participants were randomised into two groups: Group 1, in which cord clamping was performed within 10 s (n = 32) and Group 2, in which clamping was performed at the 60th second (n = 28). Sociodemographic parameters were recorded; maternal and neonatal levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulant hormone (TSH), urinary iodine concentration levels (UIC) folate and vitamin B12 were measured.

RESULTS: Of the maternal and neonatal thyroid hormone values examined, a significant difference was determined between the groups only in respect of the FT4 and FT3 values of the newborns in the first 24 hours (p = 0.037, p = 0.009, respectively). The FT4 values in the first 24 hours were determined to be lower than normal in 15.6% (n: 5) of the newborns in Group 1 and in 0% of Group 2. The FT3 values in the first 24 hours were determined to be lower than normal in 62.5% (n: 20) of the newborns in Group 1 and in 28.5% of Group 2. Vitamin B12 values below the normal limit were determined at a significantly higher rate in Group 1 (p = 0.009). A statistically significant positive correlation was observed between the maternal and neonatal vitamin B12 levels (r: 0.334, p = 0.009).

CONCLUSIONS: Late clamping of the umbilical cord may contribute to erythrocyte synthesis by allowing passage of vitamins such as B12 and folic acid to the newborn.

PMID:34263919 | DOI:10.5603/GP.a2021.0115

Ginekol Pol. 2021 Jul 15. doi: 10.5603/GP.a2021.0064. Online ahead of print.

ABSTRACT

OBJECTIVES: Concentrations of soluble ICAM-2, -3, -4 and syndecan-1 and -4 have not yet been marked in the peritoneal fluid of women with endometriosis. The aim of the study was to determine whether these molecules can participate in formation and development of endometriosis.

MATERIAL AND METHODS: The study comprised of 80 women at the proliferative phase of the menstrual cycle, aged 21 to 49 years (mean age 31. 3 ± 6. 7 years) undergoing laparoscopy, to determine the causes of primary infertility and to confirm or exclude endometriosis. The study group consisted of 60 women with endometriosis in the pelvis as confirmed by laparoscopy and histopathology. The reference group consisted of 20 women in whom no endometriosis. Concentrations of selected sICAM and syndecans in the peritoneal fluid were determined with the use of ELISA method.

RESULTS: Decreased concentrations of sICAM-2 and increased concentrations of sICAM-3, sICAM-4 and syndnecan-1 and -4 were observed in the peritoneal fluid of women with endometriosis and compared with concentrations of this parameter in the reference group (p < 0.0001). Additionally, negative correlation was found between the concentrations of sICAM-3 and sICAM-2 among women with endometriosis. There was no statistically significant correlation between the concentration of sICAM-2 and sICAM-4, sICAM-3 and sICAM-4 and syndecan-1 and syndecan-4 in the examined women.

CONCLUSIONS: Changes in concentrations of all the evaluated molecules were observed in the peritoneal fluid in women suffering from endometriosis. Since they have a role in regulation of the immune response, in angiogenesis and apoptosis of the endometrial cells.

PMID:34263915 | DOI:10.5603/GP.a2021.0064

Appl Opt. 2021 Jul 1;60(19):5517-5522. doi: 10.1364/AO.424362.

ABSTRACT

In inertial confinement fusion (ICF) systems, a continuous phase plate is often used to generate a speckle pattern in order to reduce the growth of parametric instabilities. An analytic model based on the vector diffraction theory is proposed in order to analyze the characteristics of the speckle field generated under sharper focusing conditions. The statistical and spatial autocorrelation function of the speckle field are deduced and calculated. Results show that more accurate results can be achieved by vector theory than by scalar theory. Furthermore, since light-field components in different directions are involved in the vector diffraction integral, more comprehensive information on statistical characteristics of the speckle field can be discovered. Additionally, the impact of the speckle field on three waves plasma parametric instabilities are discussed. Results show that speckle field generated under sharp focusing conditions can efficiently increase the phase mismatch among the three waves and then limit the growth of the instability.

PMID:34263839 | DOI:10.1364/AO.424362

J Opt Soc Am A Opt Image Sci Vis. 2021 Jul 1;38(7):908-923. doi: 10.1364/JOSAA.413772.

ABSTRACT

It is well known that natural images possess statistical regularities that can be captured by bandpass decomposition and divisive normalization processes that approximate early neural processing in the human visual system. We expand on these studies and present new findings on the properties of space-time natural statistics that are inherent in motion pictures. Our model relies on the concept of temporal bandpass (e.g., lag) filtering in lateral geniculate nucleus (LGN) and area V1, which is similar to smoothed frame differencing of video frames. Specifically, we model the statistics of the differences between adjacent or neighboring video frames that have been slightly spatially displaced relative to one another. We find that when these space-time differences are further subjected to locally pooled divisive normalization, statistical regularities (or lack thereof) arise that depend on the local motion trajectory. We find that bandpass and divisively normalized frame differences that are displaced along the motion direction exhibit stronger statistical regularities than for other displacements. Conversely, the direction-dependent regularities of displaced frame differences can be used to estimate the image motion (optical flow) by finding the space-time displacement paths that best preserve statistical regularity.

PMID:34263746 | DOI:10.1364/JOSAA.413772

Dis Aquat Organ. 2021 Jul 15;145:165-172. doi: 10.3354/dao03606.

ABSTRACT

Meagre Argyrosomus regius is a potential candidate for Mediterranean aquaculture diversification, although several health issues still represent important bottlenecks for its sustainable production, including systemic granulomatosis (SG). To evaluate the SG progression in meagre during a 10 mo period of cage ongrowing, a histopathological investigation was carried out on 108 meagre fed 3 different diets (commercial pellets, hydrated commercial pellets and defrosted sardines). Histological sections of the gills and visceral organs were examined and lesions referable to SG scored from 1-3 according to the severity of the granulomatosis. The kidney and liver were the most affected organs, showing the highest percentage of positivity for granulomas and severity of lesions along the whole observation period. Using a statistical mixed model (GLMM) followed by odds ratio analysis, an effect of diet and temperature was found: the severity of liver and digestive tract SG scores decreased in the Cage 3 group (defrosted sardines) and with increasing temperature (p < 0.05, negative estimates, odds ratio <1). These observations, in accordance with the literature, suggest that SG in meagre could be related to nutritional-metabolic factors with the possible influence of environmental factors such as temperature.

PMID:34263731 | DOI:10.3354/dao03606

Subst Use Misuse. 2021 Jul 15:1-4. doi: 10.1080/10826084.2021.1949615. Online ahead of print.

ABSTRACT

BACKGROUND: The effects of cannabis use in vulnerable persons with schizophrenia or schizoaffective disorder, continues to be elucidated.

METHODS: We compared 55 cannabis-only users (Group 1) with 462 non-substance users (Group 2) on measures of length of stay and number of psychiatric hospitalizations with a primary discharge diagnosis of schizophrenia or schizoaffective disorder using the Wilcoxon-Mann-Whitney non-parametric test for non-normal distributions, analysis of variance (ANOVA), and Poisson regression analysis.

RESULTS: Group 1 had a mean length of stay of 6.15 days (sd = 5.32 days) and Group 2 had a mean length of stay of 8.66 days (sd = 11.14 days) (i.e. Wilcoxon-Mann-Whitney, p = .0347; log-transformed ANOVA, p = .0203). This difference was no longer statistically significant when controlling for three covariates (p = .1543). Poisson regressions for the mean number of admissions (1.84) were not statistically significant.

CONCLUSIONS: Cannabis use may not be a good predictor of length of stay, once covariates are considered, and mean number of hospitalizations in hospitalized patients with schizophrenia or schizoaffective disorder.

PMID:34263706 | DOI:10.1080/10826084.2021.1949615

J Orthod. 2021 Jul 15:14653125211028862. doi: 10.1177/14653125211028862. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the degree to which the anteroposterior (AP) skeletal jaw relation can accurately be determined from a silhouetted clinical profile photograph and whether the level of agreement is influenced by patient vertical proportions.

DESIGN: Cross-sectional study.

SETTING: University Dental Hospital of Manchester, United Kingdom.

PARTICIPANTS: Specialist orthodontists.

METHOD: Eight specialist orthodontists assessed 37 silhouetted profile photographs of individuals aged 11-19 years and determined the class and severity of AP skeletal pattern. These assessments were compared to corresponding lateral cephalometric radiographs, where ANB values, supplemented by an Eastman Correction and a Wits Appraisal, where appropriate, were used for sagittal skeletal classification.

RESULTS: The agreement between silhouette and cephalometric AP determination yielded a weighted kappa score of 0.207 (95% confidence interval [CI] 0.135-0.278), which indicates only a fair level of agreement. The silhouetted sagittal skeletal pattern classification, along with severity, agreed with the lateral cephalometric radiograph in 29% of instances. Class III individuals were identified correctly 19.2% of the time. There was a statistically significant difference in kappa scores between the high angle (K= 0.439; 95% CI 0.310-0.568) and low angle (K = 0.068; 95% CI 0.007-0.130) patients (P < 0.001), as well as the high and average angle (K= 0.151; 95% CI 0.031-0.270) patients (P < 0.05).

CONCLUSION: AP skeletal pattern, as determined from a lateral cephalometric radiograph, has only a fair level of agreement to that from a silhouetted profile photograph. Vertical proportions were shown to have a significant effect on the determination of the sagittal skeletal pattern and class III skeletal patterns were shown to be the most difficult to identify from profile silhouettes.

PMID:34263691 | DOI:10.1177/14653125211028862