Category: Statistics

Mov Disord. 2021 Oct 6. doi: 10.1002/mds.28808. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson’s disease (PD) is a highly age-related disorder, where common genetic risk variants affect both disease risk and age at onset. A statistical approach that integrates these effects across all common variants may be clinically useful for individual risk stratification. A polygenic hazard score methodology, leveraging a time-to-event framework, has recently been successfully applied in other age-related disorders.

OBJECTIVES: We aimed to develop and validate a polygenic hazard score model in sporadic PD.

METHODS: Using a Cox regression framework, we modeled the polygenic hazard score in a training data set of 11,693 PD patients and 9841 controls. The score was then validated in an independent test data set of 5112 PD patients and 5372 controls and a small single-study sample of 360 patients and 160 controls.

RESULTS: A polygenic hazard score predicts the onset of PD with a hazard ratio of 3.78 (95% confidence interval 3.49-4.10) when comparing the highest to the lowest risk decile. Combined with epidemiological data on incidence rate, we apply the score to estimate genetically stratified instantaneous PD risk across age groups.

CONCLUSIONS: We demonstrate the feasibility of a polygenic hazard approach in PD, integrating the genetic effects on disease risk and age at onset in a single model. In combination with other predictive biomarkers, the approach may hold promise for risk stratification in future clinical trials of disease-modifying therapies, which aim at postponing the onset of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:34612543 | DOI:10.1002/mds.28808

Hum Brain Mapp. 2021 Oct 6. doi: 10.1002/hbm.25672. Online ahead of print.

ABSTRACT

This Special Issue of Human Brain Mapping is dedicated to a 10-year anniversary of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium. It reports updates from a broad range of international neuroimaging projects that pool data from around the world to answer fundamental questions in neuroscience. Since ENIGMA was formed in December 2009, the initiative grew into a worldwide effort with over 2,000 participating scientists from 45 countries, and over 50 working groups leading large-scale studies of human brain disorders. Over the last decade, many lessons were learned on how best to pool brain data from diverse sources. Working groups were created to develop methods to analyze worldwide data from anatomical and diffusion magnetic resonance imaging (MRI), resting state and task-based functional MRI, electroencephalography (EEG), magnetoencephalography (MEG), and magnetic resonance spectroscopy (MRS). The quest to understand genetic effects on human brain development and disease also led to analyses of brain scans on an unprecedented scale. Genetic roadmaps of the human cortex were created by researchers worldwide who collaborated to perform statistically well-powered analyses of common and rare genetic variants on brain measures and rates of brain development and aging. Here, we summarize the 31 papers in this Special Issue, covering: (a) technical approaches to harmonize analysis of different types of brain imaging data, (b) reviews of the last decade of work by several of ENIGMA’s clinical and technical working groups, and (c) new empirical papers reporting large-scale international brain mapping analyses in patients with substance use disorders, schizophrenia, bipolar disorders, major depression, posttraumatic stress disorder, obsessive compulsive disorder, epilepsy, and stroke.

PMID:34612558 | DOI:10.1002/hbm.25672

Health Serv Res. 2021 Oct 6. doi: 10.1111/1475-6773.13880. Online ahead of print.

ABSTRACT

OBJECTIVE: To understand whether the Comprehensive Care for Joint Replacement (CJR) program induces participating hospitals to (1) preferentially select lower risk patients, (2) reduce 90-day episode-of-care costs, (3) improve quality of care, and (4) achieve greater cost reduction during its second year, when downside financial risk was applied.

DATA SOURCES: We identified beneficiaries of age 65 years or older undergoing hip or knee joint replacement in the 100% sample of Medicare fee-for-service inpatient (Part A) claims from January 1, 2013 to August 31, 2017. Cases were linked to subsequent outpatient, Part B, home health agency, and skilled nursing facility claims, as well as publicly available participation status for CJR.

STUDY DESIGN: We estimated the effect of CJR for hospitals in the 67 metropolitan statistical areas (MSA) selected to participate in CJR (785 hospitals), compared to those in 104 non-CJR MSAs (962 hospitals; maintaining fee-for-service). A difference-in-differences approach was used to detect patient selection, as well as to compare 90-day episode-of-care costs and quality of care between CJR and non-CJR hospitals over the first two performance years.

DATA COLLECTION: We excluded 172 hospitals from our analysis due to their preexisting BPCI participation. We focused on elective admissions in the main analysis.

PRINCIPAL FINDINGS: While reductions in 90-day episode-of-care costs were greater among CJR hospitals (-$902, 95% CI: -$1305, -$499), largely driven by a 16.8% (p < 0.01) decline in 90-day spending in skilled nursing facilities, CJR hospitals significantly reduced the 90-day readmission rate (-3.9%; p < 0.05) and preferentially avoided patients aged 85 years or older (-5.9%; p < 0.01) and Black (-7.0%; p < 0.01). Cost reduction was greater in 2017 than in 2016, corresponding to the start of downside risk.

CONCLUSIONS: Participation in CJR was associated with a modest cost reduction and a reduction in 90-day readmission rates; however, we also observed evidence of preferential avoidance of older patients perceived as being higher risk among CJR hospitals.

PMID:34612519 | DOI:10.1111/1475-6773.13880

Phys Chem Chem Phys. 2021 Sep 14;23(34):18268-18282. doi: 10.1039/d1cp02654b. Epub 2021 Aug 24.

ABSTRACT

This perspective article provides a comprehensive but organized tutorial introduction of the kinetics related to photon upconversion (UC) by triplet-triplet annihilation (TTA) (TTA-UC). The field of TTA-UC is multi-disciplinary and rapidly growing with the involvement of researchers from diverse backgrounds. TTA-UC consists of a series of tangled photophysical processes, so a solid understanding of the kinetic features and consequences is important to develop and evaluate materials for TTA-UC. This tutorial starts with an introduction of the standard model of TTA-UC along with the assumptions used in the model. The essential concept of the spin statistics for TTA and how this concept is related to the singlet branching ratio, which directly affects the efficiency of UC, are then explained through step-by-step analyses. Using these foundations, solutions for the steady-state behaviors are derived, featuring the universal curve that describes the excitation intensity dependence of the UC quantum yield for any sample type. Various useful functions for analyzing experimental data are also introduced and summarized. The transient behaviors of TTA-UC are then discussed along with their equations, and the usefulness for analyzing transient experimental data is explained using examples. In this article, self-consistent derivations and relevant references are provided for an easy understanding of the advanced discussion and analyses.

PMID:34612372 | DOI:10.1039/d1cp02654b

Phys Chem Chem Phys. 2021 Sep 14;23(34):18506-18516. doi: 10.1039/d1cp02812j. Epub 2021 Aug 19.

ABSTRACT

The reaction of the D1-silylidyne radical (SiD; X²Π) with phosphine (PH₃; X¹A₁) was conducted in a crossed molecular beams machine under single collision conditions. Merging of the experimental results with ab initio electronic structure and statistical Rice-Ramsperger-Kassel-Marcus (RRKM) calculations indicates that the reaction is initiated by the barrierless formation of a van der Waals complex (i0) as well as intermediate (i1) formed via the barrierless addition of the SiD radical with its silicon atom to the non-bonding electron pair of phosphorus of the phosphine. Hydrogen shifts from the phosphorous atom to the adjacent silicon atom yield intermediates i2a, i2b, i3; unimolecular decomposition of these intermediates leads eventually to the formation of trans/cis-phosphinidenesilyl (HSiPH, p2/p4) and phosphinosilylidyne (SiPH₂, p3) via hydrogen deuteride (HD) loss (experiment: 80 ± 11%, RRKM: 68.7%) and d-trans/cis-phosphinidenesilyl (DSiPH, p2’/p4′) plus molecular hydrogen (H₂) (experiment: 20 ± 7%, RRKM: 31.3%) through indirect scattering dynamics via tight exit transition states. Overall, the study reveals branching ratios of p2/p4/p2’/p4′ (trans/cis HSiPH/DSiPH) to p3 (SiPH₂) of close to 4 : 1. The present study sheds light on the complex reaction dynamics of the silicon and phosphorous systems involving multiple atomic hydrogen migrations and tight exit transition states, thus opening up a versatile path to access the previously elusive phosphinidenesilyl and phosphinosilylidyne doublet radicals, which represent potential targets of future astronomical searches toward cold molecular clouds (TMC-1), star forming regions (Sgr(B2)), and circumstellar envelopes of carbon rich stars (IRC + 10216).

PMID:34612389 | DOI:10.1039/d1cp02812j

Prep Biochem Biotechnol. 2021 Oct 6:1-11. doi: 10.1080/10826068.2021.1955710. Online ahead of print.

ABSTRACT

This study describes the hyaluronic acid (HA) production by S. zooepidemicus ATCC 43079, and the effect of the hyaluronidase enzyme on HA levels. The hyaluronidase production, glucose consumption, and lactate formation were recorded during fermentation. The HA production, and productivity at different amounts of glucose, yeast extract and pH were evaluated by response surface statistical approach in presence of 6-O-palmytoil-l-ascorbic acid as a chemical inhibitor for biocatalyst hyaluronidase. Under optimum conditions, HA production was increased two-fold from 190 ± 17 mg L^-1 in basal medium to 384.6 ± 7.5 mg L^-1 in the optimized medium containing enzyme inhibitor. Furthermore, the results indicated that the chemical inhibitor could suppress the biocatalyst activity and prevent the HA loss at the end of the exponential phase of S. zooepidemicus ATCC 43079.

PMID:34612172 | DOI:10.1080/10826068.2021.1955710

J Int Neuropsychol Soc. 2021 Oct 6:1-8. doi: 10.1017/S1355617721001089. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the properties of the cognitive battery used in the MIND Diet Intervention to Prevent Alzheimer’s Disease. The MIND Diet Intervention is a randomized control trial to determine the relative effectiveness of the MIND diet in slowing cognitive decline and reducing brain atrophy in older adults at risk for Alzheimer’s dementia.

METHODS: The MIND cognitive function battery was administered at baseline to 604 participants of an average age of 70 years, who agreed to participate in the diet intervention study, and was designed to measure change over time. The battery included 12 cognitive tests, measuring the 4 cognitive domains of executive function, perceptual speed, episodic memory, and semantic memory. We conducted a principal component analysis to examine the consistency between our theoretical domains and the statistical performance of participants in each domain. To further establish the validity of each domain, we regressed the domain scores against a late-life cognitive activity score, controlling for age, race, sex, and years of education.

RESULTS: Four factors emerged in the principal component analyses that were similar to the theoretical domains. In regression equations, we found the expected associations with age, education, and late-life cognitive activity with each of the four cognitive domains.

CONCLUSIONS: These results indicate that the MIND cognitive battery is a comprehensive and valid battery of four separate domains of cognitive function that can be used in diet intervention trials for older adults.

PMID:34612190 | DOI:10.1017/S1355617721001089

Expert Rev Vaccines. 2021 Oct 6. doi: 10.1080/14760584.2021.1990045. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 pandemic has disrupted health services, including vaccination demand. We describe the impact of the COVID-19 pandemic on routine pediatric vaccination in Brazil.

METHODS: We conducted a retrospective analysis of all vaccine doses provided to children aged 0-6 years from January 2019 to December 2020. We obtained data stratified by age group (0 to 2 years and >2 to 6 years) and Brazilian region. Difference-in-difference (DiD) analyses were performed to compare vaccine uptake in the pre-pandemic (January-February), stay-at-home (March-June), and reopening (July-December) periods.

RESULTS: The number of vaccine doses administered declined in the stay-at-home period. For children aged 0 to 2 years, the highest reductions were recorded in the North (-25.3%), Northeast (-16.8%) and Central-West (-10.2%) regions. For children aged >2 to 6 years, the highest decline was observed in the North (DiD = -27.2%) and South (DiD = -14.0%) regions. The number of vaccine doses administered in the reopening period has slightly increased in all regions.

CONCLUSIONS: Vaccination decreased during the COVID-19 pandemic. Although the number of doses recovered in part during the reopening phase, additional strategies, such as increased public awareness and vaccination booster campaigns are required.

PMID:34612135 | DOI:10.1080/14760584.2021.1990045

Int J Inj Contr Saf Promot. 2021 Oct 6:1-10. doi: 10.1080/17457300.2021.1983844. Online ahead of print.

ABSTRACT

Crash hot spot identification and prediction using spatial statistics and random forest methods on the interstate of Michigan are evaluated. The Getis-Ord statistics are adopted to identify hot spots using location, frequency, and equivalent property damage only weights computed from the cost and severity of crashes. In the random forest approach, data patterns between 2010 and 2017 are determined to predict hot spots of crashes in 2018. Accordingly, the results indicate that: (i) interstate routes have witnessed 13,089 crashes on significant hot spots, 7,413 on cold spots, and the rest in other locations; (ii) random forest shows 76.7% and 74% accuracy for validation and prediction, respectively. The performance of the model is further affirmed with precision, recall, and F-scores of 75%, 74%, and 70%, respectively; and (iii) clustering of the crashes exhibits spatial dependence of high and low equivalent property damage only crashes. The practical significance of the approach is highlighted in the identification and prediction of hot spots.

PMID:34612168 | DOI:10.1080/17457300.2021.1983844

Connect Tissue Res. 2021 Oct 6:1-13. doi: 10.1080/03008207.2021.1982915. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to investigate the effectiveness of docosahexaenoic acid (DHA) as a treatment for Achilles tendinopathy (AT) induced with type-I collagenase in rats and compare it with collagen.

METHODS: The AT model was induced with type I collagenase, and animals were randomly assigned to groups. Group 1:AT, Group 2: Collagen (7.2 mg/kg/day), Group 3:DHA (300 mg/kg/day), and Group 4:DHA (100 mg/kg/day). Right tendons of Group1 were used as a healthy control (HC). Oral treatments were applied for eight weeks. Serum tumor necrosis factor-alpha(TNF-α), matrix metalloproteinase-13 (MMP-13), and interleukin-1 beta(IL-1β) concentrations were determined by ELISA. Tendon samples were taken for histopathological evaluation and examined immunohistochemically with antibodies specific for Col1A1, TNF-α, MMP-13, IL-1β, and nitric oxide synthase-2(NOS-2). The ultimate tensile force (UTF) yield force(YF) and stiffness were measured by biomechanical assessments.

RESULTS: UTF,YF and stiffness values were increased in all treatment groups compared to the AT control, a significant increase was found in Group 2 (p < 0.05). There was severe degeneration of tendon cells in the AT control. The tendon cells in samples from Groups 2-3 were less degraded, and this was statistically significant (p < 0.05). TNF-α, MMP-13, IL-1β, and NOS-2 expressions were significantly higher in the AT control compared to the HC. In all treatment groups, their concentrations were lower than in the AT control. Serum TNF-α, MMP-13, and IL-1β levels were lower in all treatment groups (Especially in Group3 (p < 0.001)) compared to Group1.

CONCLUSION: The efficacy of high-dose DHA as a treatment for AT was investigated from biochemical, histopathological, and biomechanical perspectives. The results showed that DHA could be an alternative treatment compound to collagen.

PMID:34612118 | DOI:10.1080/03008207.2021.1982915