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Nevin Manimala Statistics

Scalable algorithms for semiparametric accelerated failure time models in high dimensions

Stat Med. 2022 Jan 11. doi: 10.1002/sim.9264. Online ahead of print.

ABSTRACT

Semiparametric accelerated failure time (AFT) models are a useful alternative to Cox proportional hazards models, especially when the assumption of constant hazard ratios is untenable. However, rank-based criteria for fitting AFT models are often nondifferentiable, which poses a computational challenge in high-dimensional settings. In this article, we propose a new alternating direction method of multipliers algorithm for fitting semiparametric AFT models by minimizing a penalized rank-based loss function. Our algorithm scales well in both the number of subjects and number of predictors, and can easily accommodate a wide range of popular penalties. To improve the selection of tuning parameters, we propose a new criterion which avoids some common problems in cross-validation with censored responses. Through extensive simulation studies, we show that our algorithm and software is much faster than existing methods (which can only be applied to special cases), and we show that estimators which minimize a penalized rank-based criterion often outperform alternative estimators which minimize penalized weighted least squares criteria. Application to nine cancer datasets further demonstrates that rank-based estimators of semiparametric AFT models are competitive with estimators assuming proportional hazards in high-dimensional settings, whereas weighted least squares estimators are often not. A software package implementing the algorithm, along with a set of auxiliary functions, is available for download at github.com/ajmolstad/penAFT.

PMID:35014701 | DOI:10.1002/sim.9264

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Nevin Manimala Statistics

Does secondhand smoke exposure increase the risk of acute respiratory infections among children aged 0-59 months in households that use clean cooking fuel? A cross-sectional study based on 601 509 households in India

Indoor Air. 2022 Jan 11. doi: 10.1111/ina.12980. Online ahead of print.

ABSTRACT

This study examines whether exposure to secondhand smoke (SHS) increases the risk of acute respiratory infections (ARI) among children aged 0-59 months. Study utilized nationally representative data from National Family Health Survey (2015-2016), which adopted two-stage stratified random sampling. Four mutually exclusive groups based on the type of cooking fuel usage and SHS exposure were created. Descriptive statistics and multivariate logistics regression analysis were applied. At the national level, 10.5% prevalence of ARI was reported during 2015-2016. About 47.9% (95%CI 47.7-48.2) of households was exposed to SHS and used solid biomass fuel for cooking. Nearly, 20.7% of households with clean fuel usage was exposed to SHS. Regression analysis suggests that the likelihood of ARI among children who were living in households with solid biomass fuel usage and exposed to SHS was 11% (95%CI 1.06-1.17) greater than children living in households with clean fuel usage with no SHS exposure. Moreover, our results further revealed that the odds of ARI among children living in households with clean fuel but exposed to SHS were 19% (95%CI 1.13-1.25) higher than the children living in the household with no SHS exposure and clean fuel use. Children living in households exposed to SHS are at higher risk of ARI.

PMID:35014716 | DOI:10.1111/ina.12980

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Nevin Manimala Statistics

Hindi Translation and Validation of Childhood Asthma Control Test (C-ACT)

Indian Pediatr. 2022 Jan 9:S097475591600400. Online ahead of print.

ABSTRACT

OBJECTIVE: Hindi translation and validation of the Childhood Asthma Control Test (C-ACT).

METHODS: Children from 5-11 years with newly diagnosed asthma were enrolled and followed every 4-weeks for 12 weeks. Asthma control was assessed with C-ACT and Global Initiative for Asthma (GINA) criteria.

RESULTS: A total of 60 children (34 boys, 56%) were enrolled. C-ACT showed a statistically significant correlation with GINA criteria at all visits. Cronbach’s alpha to assess the internal consistency was 0.74, and the intraclass correlation coefficient to measure test-retest reliability was 0.83. The maximum area under the curve (AUC) for C-ACT was 0.95 (95% CI: 0.89-1.0; P<0.001). At a cutoff score of ≥ 20, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of C-ACT were 97.9%, 25%, 88.7%, and 87.5%, respectively.

CONCLUSIONS: Hindi version of the C-ACT score is valid, reliable, and correlates well with the GINA criteria for asthma control in children. It has a high sensitivity at a cutoff score of ≥20, but the specificity was poor in differentiating asthma control.

PMID:35014617

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Nevin Manimala Statistics

Three-Dimensional Melt-Electrowritten Polycaprolactone/Chitosan Scaffolds Enhance Mesenchymal Stem Cell Behavior

ACS Appl Bio Mater. 2021 Feb 15;4(2):1319-1329. doi: 10.1021/acsabm.0c01213. Epub 2021 Jan 13.

ABSTRACT

Melt electrowriting (MEW) is an emerging technique that precisely fabricates microfibrous scaffolds, ideal for tissue engineering, where biomimetic microarchitectural detail is required. Polycaprolactone (PCL), a synthetic polymer, was selected as the scaffold material due to its biocompatibility, biodegradability, mechanical strength, and melt processability. To increase PCL bioactivity, a natural polymer, chitosan, was added to construct MEW fibrous composite scaffolds. To date, this is the first study of its kind detailing the effects of stem cell behavior on PCL containing chitosan MEW scaffolds. The aim of this study was to melt electrowrite a range of PCL/chitosan tissue-engineered constructs (TECs) and assess their suitability to promote the growth of human bone-marrow-derived mesenchymal stem cells (hBMSCs). In vitro physical and biological characterizations of melt-electrowritten TECs were performed. Physical characterization showed that reproducible, layered micron-range scaffolds could be successfully fabricated. As well, cell migration and proliferation were assessed via an assay to monitor cell infiltration throughout the three-dimensional (3D) melt-electrowritten scaffold structure. A statistically significant increase (∼140%) in hBMSC proliferation in 1 wt % chitosan PCL blends in comparison to PCL-only scaffolds was found when monitored over two weeks. Overall, our study demonstrates the fabrication of melt-electrowritten PCL/chitosan composite scaffolds with controlled microarchitecture and their potential use for regenerative, tissue engineering applications.

PMID:35014483 | DOI:10.1021/acsabm.0c01213

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Nevin Manimala Statistics

The Awareness and Empowerment Aspects of the Needlesticks and Other Sharps Injuries and Reporting in Nursing Education: A Cross-Sectional Survey

Workplace Health Saf. 2022 Jan 11:21650799211049810. doi: 10.1177/21650799211049810. Online ahead of print.

ABSTRACT

BACKGROUND: Occurrence and underreporting of needlesticks and other sharps injuries (NSIs) are still immediate concerns among nursing students. This study examined the relationship between occupational health and safety (OHS) awareness and empowerment levels of nursing students and the occurrence and reporting of NSIs.

METHODS: This cross-sectional study was conducted among purposively selected 840 students in a nursing school in 2018-2019. A self-report questionnaire was used to collect data about students’ sociodemographic characteristics, OHS awareness and empowerment levels, and NSIs characteristics. After bivariate analyses, multivariate logistic regression was used.

RESULTS: The number of evaluated questionnaires was 469, for a response rate of 55.8%. Participants, 21.2% (n = 99), had suffered NSIs, and 47.8% had reported their injuries. The NSIs were statistically related to age, academic year, working night shift, OHS awareness level of students, and the number of clinical placements completed by students. The odds of experiencing NSIs was 2.3 (95% confidence interval [CI] = [1.0, 5.3]) times higher in male students, 4.3 (95% CI = [2.4, 7.4]) times higher in those beyond the second academic year, and 2.5 (95% CI = [1.4, 4.4]) times higher in those who had received OHS training for a shorter period than the average duration.

CONCLUSION/APPLICATION TO PRACTICE: The levels of awareness and empowerment were higher in students who received OHS and NSIs prevention training and those who received OHS training for the above-average duration. Increasing awareness and empowerment levels of nursing students through training can reduce the occurrence and the underreporting of NSIs.

PMID:35014570 | DOI:10.1177/21650799211049810

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Nevin Manimala Statistics

Tunable Crosslinking, Reversible Phase Transition, and 3D Printing of Hyaluronic Acid Hydrogels via Dynamic Coordination of Innate Carboxyl Groups and Metallic Ions

ACS Appl Bio Mater. 2021 Mar 15;4(3):2408-2428. doi: 10.1021/acsabm.0c01300. Epub 2021 Feb 15.

ABSTRACT

This article reports tunable crosslinking, reversible phase transition, and three-dimensional printing (3DP) of hyaluronic acid (HyA) hydrogels via dynamic coordination of Fe3+ ions with their innate carboxyl groups for the first time. The concentrations of Fe3+ and H+ ions and the reaction time determine the tunable ratios of mono-, bi-, and tridentate coordination, leading to the low-to-high crosslinking densities and reversible solid-liquid phase transition of HyA hydrogels. At the monodentate-dominant coordination, the liquid hydrogels have low crosslinking densities (HyA_L). At the mixed coordination of mono-, bi-, and tridentate bonding, the solid hydrogels have medium crosslinking densities (HyA_M). At the tridentate-dominant coordination, the solid hydrogels have high crosslinking densities (HyA_H). The reversible solid-liquid phase transitions among HyA_L, HyA_M, and HyA_H were achieved via controlling the concentrations of Fe3+ and H+ ions and reaction time. When the crosslinking densities are between HyA_L and HyA_M, the hydrogels become 3D printable (HyA_P). HyA_P hydrogels were 3D-printed successfully using cold-stage or direct writing methods, and the 3D constructs achieved better structural stability using the latter method. In the direct exposure culture with bone marrow-derived mesenchymal stem cells, the 3D-printed HyA_H (HyA_H_3D) and HyA_H hydrogels showed higher average cell adhesion densities than the HyA_M, HyA_P, and HyA_L hydrogel groups under both direct and indirect contact conditions. For all hydrogel groups, cell adhesion densities under direct contact conditions were statistically lower than the same groups under indirect contact conditions. In this article, we elucidated the mechanisms of dynamic coordination and the relationships among the key parameters in controlling the tunable crosslinking, reversible phase transition, and 3DP of HyA hydrogels without blending with other polymers or adding functional groups. This approach can be potentially adapted to crosslink and 3D print other polymeric hydrogels with carboxyl groups, which is promising for a wide range of applications.

PMID:35014361 | DOI:10.1021/acsabm.0c01300

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Nevin Manimala Statistics

Amphiphilic Graft Copolymers Capable of Mixed-Mode Interaction as Alternative Nonviral Transfection Agents

ACS Appl Bio Mater. 2021 Feb 15;4(2):1268-1282. doi: 10.1021/acsabm.0c01123. Epub 2021 Jan 12.

ABSTRACT

Nonviral gene delivery vectors are attractive candidates compared to viral ones due to their lower cytotoxicity and immunogenicity. However, their efficacy still requires improvement. Major challenges are the effective complexation and protection of the DNA cargo and the intracellular dissociation of the polyplexes at the site of action. It is commonly accepted that polymer architecture and chemistry influence polyplex characteristics and have an impact on the transfection mechanism. We developed a library of biocompatible copolymers based on methoxy poly(ethylene glycol) and a hydrophobic block of poly(ε-caprolactone-co-propargyl carbonate) grafted with a predetermined number of poly(2-(dimethylamino)ethyl methacrylate) segments. Such copolymers could efficiently deliver their cargo even in the presence of serum proteins and to various “difficult to transfect” cells, thereby outperforming the current gold standard 25 kDa linear poly(ethylenimine). Statistical correlation analysis shows that an optimization of the transfection in the case of copolymers combining several interactive functions benefits from treatment as a multiparameter problem.

PMID:35014479 | DOI:10.1021/acsabm.0c01123

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Nevin Manimala Statistics

Synthesis of a High Affinity Complementary Peptide-Polymer Nanoparticle (NP) Pair Using Phage Display

ACS Appl Bio Mater. 2021 Mar 15;4(3):2704-2712. doi: 10.1021/acsabm.0c01631. Epub 2021 Feb 18.

ABSTRACT

Peptide-polymer complementary pairs can provide useful tools for isolating, organizing, and separating biomacromolecules. We describe a procedure for selecting a high affinity complementary peptide-polymer nanoparticle (NP) pair using phage display. A hydrogel copolymer nanoparticle containing a statistical distribution of negatively charged and hydrophobic groups was used to select a peptide sequence from a phage displayed library of >1010 peptides. The NP has low nanomolar affinity for the selected cyclic peptide and exhibited low affinity for a panel of diverse proteins and peptide variants. Affinity arises from the complementary physiochemical properties of both NP and peptide as well as the specific peptide sequence. Comparison of linear and cyclic variants of the peptide established that peptide structure also contributes to affinity. These findings offer a general method for identifying polymer-peptide complementary pairs. Significantly, precise polymer sequences (proteins) are not a requirement, a low information statistical copolymer can be used to select for a specific peptide sequence with affinity and selectivity comparable to that of an antibody. The data also provides evidence for the physiochemical and structural contributions to binding. The results confirm the utility of abiotic, statistical, synthetic copolymers as selective, high affinity peptide affinity reagents.

PMID:35014309 | DOI:10.1021/acsabm.0c01631

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Nevin Manimala Statistics

Systemic Treatments in Pediatric Psoriasis: A Retrospective Single-Center Study

Arch Iran Med. 2021 Dec 1;24(12):903-909. doi: 10.34172/aim.2021.135.

ABSTRACT

BACKGROUND: Systemic therapies commonly used in adult psoriasis are mostly used only off-label in children and little is known about the efficacy and tolerability of these drugs in this population. In this study, we aimed to evaluate the efficacy and safety of systemic treatments in pediatric patients with psoriasis.

METHODS: Data were obtained retrospectively from the Department of Dermatology, Ondokuz Mayis University, School of Medicine between 2010-2019. Our study consisted of 742 pediatric patients (age ≤18 years) with psoriasis. Demographic data, adverse events of systemic treatments and healing periods were considered.

RESULTS: A total of 195 patients received systemic treatment. The mean age of onset of disease and the initiation of systemic therapy were 9.68±4.62 and 11.33±4.38 years, respectively. Patients received methotrexate (n=52, 26.67%), cyclosporine (n=18, 9.24%), acitretin (n=106, 54.35%) and others (biologics and/or one of conventional treatments) (n=19, 9.74%) as systemic therapy. Adverse events occurred in 12 patients (incidence of 6.15%, and its related 95% confidence interval of 2.75%, 9.56%) and nine of them had to discontinue the medication due to those adverse events. Healing periods calculated in the remaining 186 patients were 13.25±5.87, 10.85±5.67, 11.05±7.00, and 9.41±4.16 (mean±SD) weeks for acitretin, methotrexate, cyclosporine, and others, respectively. No statistically significant differences were noted between the treatments regarding the healing periods.

CONCLUSION: All treatments were effective and none of them was superior in terms of the healing period. Systemic treatments used in adults can also be used in pediatric patients with psoriasis with similar efficacy and safety rates as long as routine monitoring is provided.

PMID:35014238 | DOI:10.34172/aim.2021.135

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Nevin Manimala Statistics

Revisiting the annual incidence of Type 1 Diabetes Mellitus in children from the Southeastern Anatolian Region of Turkey: A Regional report

J Clin Res Pediatr Endocrinol. 2022 Jan 11. doi: 10.4274/jcrpe.galenos.2021.2021-10-7. Online ahead of print.

ABSTRACT

OBJECTIVE: Type 1 Diabetes mellitus (T1D) incidence in children has an increasing trend with a variable rate depending on region and ethnicity. Our group had firstly reported T1D incidence in Diyarbakır in the year 2011. The present study aims to evaluate the current incidence rate of pediatric T1D in Diyarbakır, and compare the incidence, clinical and presenting characteristics of the cases with those reported in our first report.

METHODS: Hospital records of the patients under 18 years old and diagnosed with T1D in Diyarbakır city between 1st January 2020 and 31st December 2020 were retrieved, and their medical data was extracted. Demographic population data were obtained from address-based census records of the Turkish Statistical Institution (TSI).

RESULTS: Fifty-seven children and adolescents were diagnosed with T1D. Of those, 34 were female (59.6%), indicating a male/female ratio of 1.47. The mean age of diagnosis was 9.5±3.9 (0.8-17.9). According to the data obtained from TSI, the population between the ages of 0-18 was found to be 709803. T1D incidence was calculated as 9.14/105 in the 0-14 age group and 8.03/105 in the 0-18 age group. The cumulative increase in the incidence of T1D in the 0-14 age group was 26.9% suggesting an increasing rate of 2.7% per year. The frequency of presentation with DKA was 64.9%.

PMID:35014245 | DOI:10.4274/jcrpe.galenos.2021.2021-10-7