Tag: statistics

Syst Biol. 2023 May 25:syad012. doi: 10.1093/sysbio/syad012. Online ahead of print.

ABSTRACT

Models based on the Ornstein-Uhlenbeck process have become standard for the comparative study of adaptation. Cooper et al. (2016) have cast doubt on this practice by claiming statistical problems with fitting Ornstein-Uhlenbeck models to comparative data. Specifically, they claim that statistical tests of Brownian motion may have too high Type I error rates and that such error rates are exacerbated by measurement error. In this note, we argue that these results have little relevance to the estimation of adaptation with Ornstein-Uhlenbeck models for three reasons. First, we point out that Cooper et al. (2016) did not consider the detection of distinct optima (e.g. for different environments), and therefore did not evaluate the standard test for adaptation. Second, we show that consideration of parameter estimates, and not just statistical significance, will usually lead to correct inferences about evolutionary dynamics. Third, we show that bias due to measurement error can be corrected for by standard methods. We conclude that Cooper et al. (2016) have not identified any statistical problems specific to Ornstein-Uhlenbeck models, and that their cautions against their use in comparative analyses are unfounded and misleading. [adaptation, Ornstein-Uhlenbeck model, phylogenetic comparative method.].

PMID:37229537 | DOI:10.1093/sysbio/syad012

Anal Chem. 2023 May 25. doi: 10.1021/acs.analchem.3c00918. Online ahead of print.

ABSTRACT

We report methods that improve the quantification of digital bead assays (DBA)─such as the digital enzyme-linked immunosorbent assay (ELISA)─that have found widespread use for high sensitivity measurement of proteins in clinical research and diagnostics. In digital ELISA, proteins are captured on beads, labeled with enzymes, individual beads are interrogated for activity from one or more enzymes, and the average number of enzymes per bead (AEB) is determined based on Poisson statistics. The widespread use of digital ELISA has revealed limitations to the original approaches to quantification that can lead to inaccurate AEB. Here, we have addressed the inaccuracy in AEB due to deviations from Poisson distribution in a digital ELISA for Aβ-40 by changing the AEB calculation from a fixed threshold between digital counting and average normalized intensity to a smooth, continuous combination of digital counting and intensity. We addressed issues with determining the average product fluorescence intensity from single enzymes on beads by allowing outlier, high intensity arrays to be removed from average intensities, and by permitting the use of a wider range of arrays. These approaches improved the accuracy of a digital ELISA for tau protein that was affected by aggregated detection antibodies. We increased the dynamic range of a digital ELISA for IL-17A from AEB ∼25 to ∼130 by combining long and short exposure images at the product emission wavelength to create virtual images. The methods reported will significantly improve the accuracy and robustness of DBA based on imaging─such as single molecule arrays (Simoa)─and flow detection.

PMID:37229528 | DOI:10.1021/acs.analchem.3c00918

Health Educ Res. 2023 May 25:cyad021. doi: 10.1093/her/cyad021. Online ahead of print.

ABSTRACT

Innovative approaches addressing the elevated human immunodeficiency virus (HIV) risk among men who have sex with men (MSM) or transgender women (TGW) migrants in South Africa are urgently needed. We sought to present the acceptability, feasibility and preliminary efficacy of ‘Externalize and Mobilize!’, a multi-session arts- and theatre-based HIV prevention group intervention for MSM and TGW migrants in South Africa. Fourteen participants-MSM (n = 7; 50%), genderqueer/nonbinary persons (n = 4; 29%) and TGW (n = 3; 21%)-in Cape Town were recruited and enrolled in the intervention and administered pre- and post-intervention assessments of HIV knowledge, HIV risk-reduction self-efficacy, stigma and resilience. The intervention, delivered over 4 days, was completed by all 14 participants. Scores on HIV knowledge and HIV risk-reduction self-efficacy were statistically significantly higher at post-intervention compared with pre-intervention. Additionally, participants responded affirmatively (i.e. ‘Agree’ or ‘Strongly agree’) on all items assessing intervention acceptability. Findings demonstrate the high acceptability, feasibility and preliminary efficacy of an arts- and theatre-based intervention for increasing HIV knowledge and HIV risk-reduction self-efficacy among MSM and TGW migrants in South Africa. This study provides further support for the use of creative and innovative interventions to address entrenched HIV disparities in South Africa.

PMID:37229526 | DOI:10.1093/her/cyad021

J Am Assoc Nurse Pract. 2023 May 25. doi: 10.1097/JXX.0000000000000885. Online ahead of print.

ABSTRACT

BACKGROUND: The increased lifespan of individuals having sickle cell disease (SCD) causes an overall increase in hospitalizations and more instances in which pain may not be well controlled.

LOCAL PROBLEM: The mainstay treatment for severe pain is opioids and the underlying cause. Laws affecting opioid prescribing, implicit bias, racial inequity, poor research funding, and lack of knowledge contribute to poor patient outcomes.

METHOD: Data were collected retrospectively using electronic medical record data from before and after the intervention.

INTERVENTION: The individualized pain management plan (IPMP) was initiated in collaboration with the patient, pain nurse practitioner (NP), and hematologist.

RESULT: The mean length of stay for the traditional pain management plan (TPMP) was 7.89 days compared with 5.66 days for the IPMP, with a mean difference of 2.23 days, t = 2.278, p = .024 (p < .05). There was a decrease in the admission of the individuals with the IPMP, with 25% readmitted within 30 days of discharge, versus 59.0% who were readmitted using the TPMP. Chi-square showed statistical significance (χ2 = 61.667, p = .000) in using nonpharmacological interventions with the IPMP group.

CONCLUSION: The IPMP with a patient-centered approach did improve patient outcomes for African American adults living with SCD.

PMID:37229519 | DOI:10.1097/JXX.0000000000000885

Neurobiol Lang (Camb). 2023 Apr 11;4(2):221-256. doi: 10.1162/nol_a_00094. eCollection 2023.

ABSTRACT

Intuitively, strongly constraining contexts should lead to stronger probabilistic representations of sentences in memory. Encountering unexpected words could therefore be expected to trigger costlier shifts in these representations than expected words. However, psycholinguistic measures commonly used to study probabilistic processing, such as the N400 event-related potential (ERP) component, are sensitive to word predictability but not to contextual constraint. Some research suggests that constraint-related processing cost may be measurable via an ERP positivity following the N400, known as the anterior post-N400 positivity (PNP). The PNP is argued to reflect update of a sentence representation and to be distinct from the posterior P600, which reflects conflict detection and reanalysis. However, constraint-related PNP findings are inconsistent. We sought to conceptually replicate Federmeier et al. (2007) and Kuperberg et al. (2020), who observed that the PNP, but not the N400 or the P600, was affected by constraint at unexpected but plausible words. Using a pre-registered design and statistical approach maximising power, we demonstrated a dissociated effect of predictability and constraint: strong evidence for predictability but not constraint in the N400 window, and strong evidence for constraint but not predictability in the later window. However, the constraint effect was consistent with a P600 and not a PNP, suggesting increased conflict between a strong representation and unexpected input rather than greater update of the representation. We conclude that either a simple strong/weak constraint design is not always sufficient to elicit the PNP, or that previous PNP constraint findings could be an artifact of smaller sample size.

PMID:37229506 | PMC:PMC10205153 | DOI:10.1162/nol_a_00094

EClinicalMedicine. 2023 May;59:101936. doi: 10.1016/j.eclinm.2023.101936.

ABSTRACT

BACKGROUND: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019.

METHODS: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input.

FINDINGS: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6-4.3) with a prevalence of 454.6 million cases (417.4-499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4-225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9-3.6) deaths. With 262.4 million (224.1-309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively.

INTERPRETATION: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries.

PMID:37229504 | PMC:PMC7614570 | DOI:10.1016/j.eclinm.2023.101936

Front Nutr. 2023 May 9;10:1186469. doi: 10.3389/fnut.2023.1186469. eCollection 2023.

ABSTRACT

INTRODUCTION: Spray-dried yogurt powder (SDYP) has shelf stability and other functional properties that improve solubility and facilitate the use, processing, packaging, and transportation of other food derivatives, such as bread and pastries on a large scale. The present research was conducted to develop SDYP and further its utilization to prepare functional cookies.

METHODS: Yogurt was spray-dried by employing different outlet air temperatures (OAT) (65°C, 70°C & 75°C) and inlet air temperature (IAT) (150°C, 155°C & 160°C). Spray drying shows that increasing the temperature increases nutritional loss, whereas S. thermophilus culture shows resistance to the intensive heat approaches. On the other hand L. delbrueckii subsp. Bulgaricus culture was found to be significantly affected. A total of 4 treatments, including one control for the functional cookies development.

RESULTS AND DISCUSSION: A directly proportional relation was investigated between the increasing concentration of SDYP and baking characteristics and cookie’s mineral and protein profile. Bioactive parameters like antioxidant activity of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and total phenolic content (TPC) were also affected significantly. The sensory profile shows an incline towards T0 (0% SDYP) to T3 (10% SDYP) in all attributes but starts to decline when the concentration of SDYP reaches 15%. This study suggests that by employing a certain combination of temperatures (OAT: 60°C IAT: 150°C); maximum survival of inoculated culture can be achieved, and this powder can be utilized in the development of functional cookies with enhanced sensory as well as biochemical characteristics significantly (P< 0.05).

PMID:37229469 | PMC:PMC10204867 | DOI:10.3389/fnut.2023.1186469

Front Nutr. 2023 May 9;10:1172613. doi: 10.3389/fnut.2023.1172613. eCollection 2023.

ABSTRACT

INTRODUCTION: Human milk provides nutrients essential for infant growth and health, levels of which are dynamic during lactation.

METHODS: In this study, changes in macronutrients, fatty acids, and plasmin activities over the first six months of lactation in term milk were studied.

RESULTS: There was a significant influence of lactation stage on levels of protein and plasmin activities, but not on levels of fat and carbohydrate in term milk. Concerning fatty acids in term milk, levels of caproic acid and α-linolenic acid increased significantly (p < 0.05), whereas those of arachidonic acid and docosahexaenoic acid decreased, in the six months after birth. Significant impacts of maternal pre-pregnancy BMI and infant gender on fatty acid profiles were also found. Multivariate statistical analysis showed that protein level, plasmin activity, and several fatty acids (α-linolenic acid, lignoceric acid, and docasadienoic acid) contributed strongly to discrimination of milk from different lactational stages.

DISCUSSION: The study demonstrates that not all but some fatty acids were influenced by lactation, whereas protein and protease levels showed clear decreasing trends during lactation, which may help in understanding the nutritional requirements of infants.

PMID:37229467 | PMC:PMC10203173 | DOI:10.3389/fnut.2023.1172613

Tech Innov Patient Support Radiat Oncol. 2023 May 13;26:100211. doi: 10.1016/j.tipsro.2023.100211. eCollection 2023 Jun.

ABSTRACT

INTRODUCTION: Deep learning (DL) models are increasingly developed for auto-segmentation in radiotherapy. Qualitative analysis is of great importance for clinical implementation, next to quantitative. This study evaluates a DL segmentation model for left- and right-sided locally advanced breast cancer both quantitatively and qualitatively.

METHODS: For each side a DL model was trained, including primary breast CTV (CTVp), lymph node levels 1-4, heart, lungs, humeral head, thyroid and esophagus. For evaluation, both automatic segmentation, including correction of contours when needed, and manual delineation was performed and both processes were timed. Quantitative scoring with dice-similarity coefficient (DSC), 95% Hausdorff Distance (95%HD) and surface DSC (sDSC) was used to compare both the automatic (not-corrected) and corrected contours with the manual contours. Qualitative scoring was performed by five radiotherapy technologists and five radiation oncologists using a 3-point Likert scale.

RESULTS: Time reduction was achieved using auto-segmentation in 95% of the cases, including correction. The time reduction (mean ± std) was 42.4% ± 26.5% and 58.5% ± 19.1% for OARs and CTVs, respectively, corresponding to an absolute mean reduction (hh:mm:ss) of 00:08:51 and 00:25:38. Good quantitative results were achieved before correction, e.g. mean DSC for the right-sided CTVp was 0.92 ± 0.06, whereas correction statistically significantly improved this contour by only 0.02 ± 0.05, respectively. In 92% of the cases, auto-contours were scored as clinically acceptable, with or without corrections.

CONCLUSIONS: A DL segmentation model was trained and was shown to be a time-efficient way to generate clinically acceptable contours for locally advanced breast cancer.

PMID:37229460 | PMC:PMC10205480 | DOI:10.1016/j.tipsro.2023.100211

J Med Internet Res. 2023 May 25;25:e45662. doi: 10.2196/45662.

ABSTRACT

Although randomized controlled trials (RCTs) are the gold standard for establishing the efficacy and safety of a medical treatment, real-world evidence (RWE) generated from real-world data has been vital in postapproval monitoring and is being promoted for the regulatory process of experimental therapies. An emerging source of real-world data is electronic health records (EHRs), which contain detailed information on patient care in both structured (eg, diagnosis codes) and unstructured (eg, clinical notes and images) forms. Despite the granularity of the data available in EHRs, the critical variables required to reliably assess the relationship between a treatment and clinical outcome are challenging to extract. To address this fundamental challenge and accelerate the reliable use of EHRs for RWE, we introduce an integrated data curation and modeling pipeline consisting of 4 modules that leverage recent advances in natural language processing, computational phenotyping, and causal modeling techniques with noisy data. Module 1 consists of techniques for data harmonization. We use natural language processing to recognize clinical variables from RCT design documents and map the extracted variables to EHR features with description matching and knowledge networks. Module 2 then develops techniques for cohort construction using advanced phenotyping algorithms to both identify patients with diseases of interest and define the treatment arms. Module 3 introduces methods for variable curation, including a list of existing tools to extract baseline variables from different sources (eg, codified, free text, and medical imaging) and end points of various types (eg, death, binary, temporal, and numerical). Finally, module 4 presents validation and robust modeling methods, and we propose a strategy to create gold-standard labels for EHR variables of interest to validate data curation quality and perform subsequent causal modeling for RWE. In addition to the workflow proposed in our pipeline, we also develop a reporting guideline for RWE that covers the necessary information to facilitate transparent reporting and reproducibility of results. Moreover, our pipeline is highly data driven, enhancing study data with a rich variety of publicly available information and knowledge sources. We also showcase our pipeline and provide guidance on the deployment of relevant tools by revisiting the emulation of the Clinical Outcomes of Surgical Therapy Study Group Trial on laparoscopy-assisted colectomy versus open colectomy in patients with early-stage colon cancer. We also draw on existing literature on EHR emulation of RCTs together with our own studies with the Mass General Brigham EHR.

PMID:37227772 | DOI:10.2196/45662