Category: Statistics

PLoS One. 2021 Aug 17;16(8):e0255223. doi: 10.1371/journal.pone.0255223. eCollection 2021.

ABSTRACT

Large-scale excavations conducted by Smithsonian Institution archaeologists and avocational archaeologists during the 1960s and 1970s at three sites in Seaside, Oregon, resulted in the recovery of a diverse range of material culture curated by multiple institutions. One site, known as Palmrose (35CLT47), provides compelling evidence for the presence of one of the earliest examples of a rectangular plank house along the Oregon Coast. Previous research suggests habitation of the Palmrose site occurred between 2340 cal BC to cal AD 640. However, recent research highlights significant chronometric hygiene concerns of previously reported radiocarbon dates for the Seaside area, calling into question broader regional chronologies. This paper presents a revised chronology for the Palmrose site based on 12 new accelerator mass spectrometry (AMS) radiocarbon dates of ancient cervid bones. I evaluate these new dates and previously reported radiocarbon dates from the site, applying chronometric hygiene assessments and Bayesian statistics to build a refined chronology for the Palmrose site. Calibration of the 12 AMS radiocarbon dates suggests an initial occupation range from 345-55 cal BC and a terminal occupation range from cal AD 225-340-. Bayesian modeling of the Palmrose sequence suggests initial occupation may have spanned from 195-50 cal BC and the terminal occupation from cal AD 210-255. Modeling suggests the maximum range of occupation may span from 580-55 cal BC to cal AD 210-300 based on the start and end boundary calculations. Bayesian modeling of radiocarbon dates directly associated with the plank house deposits suggests the plank house’s occupation may have spanned from 160-1 cal BC to cal AD 170-320. The new radiocarbon dates significantly constrain the Palmrose habitation and alter regional chronologies.

PMID:34403411 | DOI:10.1371/journal.pone.0255223

PLoS Negl Trop Dis. 2021 Aug 17;15(8):e0009670. doi: 10.1371/journal.pntd.0009670. Online ahead of print.

ABSTRACT

BACKGROUND: Fever with jaundice is a common symptom of some infectious diseases. In public health surveillance within the Democratic Republic of the Congo (DRC), yellow fever is the only recognized cause of fever with jaundice. However, only 5% of the surveillance cases are positive for yellow fever and thus indicate the involvement of other pathogens. Leptospira spp. are the causative agents of leptospirosis, a widespread bacterial zoonosis, a known cause of fever with jaundice. This study aimed to determine the seropositivity of anti-Leptospira antibodies among suspected yellow fever cases and map the geographical distribution of possible leptospirosis in the DRC.

METHODS: We conducted a retrospective study using 1,300 samples from yellow fever surveillance in the DRC from January 2017 to December 2018. Serum samples were screened for the presence of IgM against Leptospira spp. by a whole cell-based IgM ELISA (Patoc-IgM ELISA) at the Institut National de Recherche Biomedicale in Kinshasa (INRB) according to World Health Organization (WHO) guidance. Exploratory univariable and multivariable logistic regression analyses were undertaken to assess associations between socio-demographic factors and the presence of Leptospira IgM.

RESULTS: Of the 1,300 serum samples screened, 88 (7%) showed evidence of IgM against Leptospira spp. Most positive cases (34%) were young adult males in the 20-29-year group. There were statistically significant associations between having Leptospira IgM antibodies, age, sex, and living area. Observed positive cases were mostly located in urban settings, and the majority lived in the province of Kinshasa. There was a statistically significant association between seasonality and IgM Leptospira spp. positivity amongst those living in Kinshasa, where most of the positive cases occurred during the rainy season.

CONCLUSIONS: This study showed that leptospirosis is likely an overlooked cause of unexplained cases of fever with jaundice in the DRC and highlights the need to consider leptospirosis in the differential diagnosis of fever with jaundice, particularly in young adult males. Further studies are needed to identify animal reservoirs, associated risk factors, and the burden of human leptospirosis in the DRC.

PMID:34403427 | DOI:10.1371/journal.pntd.0009670

PLoS One. 2021 Aug 17;16(8):e0256307. doi: 10.1371/journal.pone.0256307. eCollection 2021.

ABSTRACT

To assess trends in life expectancy and the contribution of specific causes of death to Native American-White longevity gaps in the Four Corners states, we used death records from the National Center for Health Statistics and population estimates from the U.S. Census Bureau from 1999-2017 to generate period life tables and decompose racial gaps in life expectancy. Native American-White life expectancy gaps narrowed between 2001 and 2012 but widened thereafter, reaching 4.92 years among males and 2.06 years among females in 2015. The life expectancy disadvantage among Native American males was primarily attributable to motor vehicle accidents (0.96 years), liver disease (1.22 years), and diabetes (0.78 years). These causes of deaths were also primary contributors to the gap among females, forming three successive waves of mortality that occurred in young adulthood, midlife, and late adulthood, respectively, among Native American males and females. Interventions to reduce motor vehicle accidents in early adulthood, alcohol-related mortality in midlife, and diabetes complications at older ages could reduce Native American-White longevity disparities in the Four Corners states.

PMID:34403430 | DOI:10.1371/journal.pone.0256307

Eur J Endocrinol. 2021 Aug 1:EJE-21-0552.R1. doi: 10.1530/EJE-21-0552. Online ahead of print.

ABSTRACT

OBJECTIVE: Polycystic ovary syndrome is diagnosed based on clinical signs, but its presentation is heterogeneous and potentially confounded by concurrent conditions, as obesity and insulin-resistance. MicroRNAs have recently emerged as putative pathophysiological and diagnostic factors in PCOS. However, no reliable miRNA-based method for molecular diagnosis of PCOS has been reported. The aim of this study was to develop a tool for accurate diagnosis of PCOS by targeted miRNA profiling of plasma samples, defined on the basis of unbiased biomarker-finding analyses and biostatistical-tools.

METHODS: A case-control PCOS cohort was cross-sectionally studied, including 170 women classified into four groups: non-PCOS/lean; non-PCOS/obese; PCOS/lean; and PCOS/obese women. High-throughput miRNA analyses were performed in plasma, using NanoString technology and a 800-human-miRNA panel, followed by targeted-qPCR validation. Statistics were applied to define optimal normalization methods, identify deregulated biomarker miRNAs and build classification algorithms, considering PCOS and obesity as major categories.

RESULTS: The geometric mean of circulating hsa-miR-103a-3p, hsa-miR-125a-5p and hsa-miR-1976, selected among 125 unchanged miRNAs, was defined as optimal reference for internal normalization (named mR3-method). Ten miRNAs were identified and validated after mR3-normalization as differentially expressed across the groups. Multinomial LASSO-Regression and decision-tree models were built to reliably discriminate PCOS vs. non-PCOS, either in obese or non-obese women, using subsets of these miRNAs as performers.

CONCLUSIONS: We define herein a robust method for molecular classification of PCOS, based on unbiased identification of miRNA biomarkers and decision-tree protocols. This method allows not only reliable diagnosis of non-obese women with PCOS, but also discrimination between PCOS and obesity.

PMID:34403358 | DOI:10.1530/EJE-21-0552

PLoS Genet. 2021 Aug 17;17(8):e1009728. doi: 10.1371/journal.pgen.1009728. Online ahead of print.

ABSTRACT

Dosage compensation equalizes X-linked expression between XY males and XX females. In male fruit flies, expression levels of the X-chromosome are increased approximately two-fold to compensate for their single X chromosome. In testis, dosage compensation is thought to cease during meiosis; however, the timing and degree of the resulting transcriptional suppression is difficult to separate from global meiotic downregulation of each chromosome. To address this, we analyzed testis single-cell RNA-sequencing (scRNA-seq) data from two Drosophila melanogaster strains. We found evidence that the X chromosome is equally transcriptionally active as autosomes in somatic and pre-meiotic cells, and less transcriptionally active than autosomes in meiotic and post-meiotic cells. In cells experiencing dosage compensation, close proximity to MSL (male-specific lethal) chromatin entry sites (CES) correlates with increased X chromosome transcription. We found low or undetectable levels of germline expression of most msl genes, mle, roX1 and roX2 via scRNA-seq and RNA-FISH, and no evidence of germline nuclear roX1/2 localization. Our results suggest that, although dosage compensation occurs in somatic and pre-meiotic germ cells in Drosophila testis, there might be non-canonical factors involved in the dosage compensation mechanism. The single-cell expression patterns and enrichment statistics of detected genes can be explored interactively in our database: https://zhao.labapps.rockefeller.edu/gene-expr/.

PMID:34403408 | DOI:10.1371/journal.pgen.1009728

Eur J Endocrinol. 2021 Aug 1:EJE-21-0475.R2. doi: 10.1530/EJE-21-0475. Online ahead of print.

ABSTRACT

OBJECTIVE: The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because IGF-1 or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature.

DESIGN: Boys and girls, n=429, (0.7 – 16 years old) that attended our department for short stature, participated in this study. They were followed up for an average period of 9 years (4-15). At the end of follow up, a definitive diagnosis was assigned to each individual, and all the components of ternary complex (IGF-1, IGFBP-3, ALS and IGF-1/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis.

RESULTS: All components of ternary complex were tightly correlated with each other and positively related to age. IGF-1, IGFBP-3, ALS, and IGF-1/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-1 and ALS levels were lower in GHD compared to children with familial short stature, while IGF-1 and IGF-1/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-1 and IGF-1/IGFBP-3 Receiver Operating Curves (ROC) cutoff points were unable to discriminate between GHD and normal or between GHD and CDGP groups.

CONCLUSION: Despite the tight correlation among all components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-1, ALS and IGF-1/IGFBP-3 ratio in the distinction between GHD and CDGP or GHD and normal groups but without usable discriminating power, making thus auxology the primary criterion of establishing the diagnosis.

PMID:34403357 | DOI:10.1530/EJE-21-0475

J Biopharm Stat. 2021 Aug 17:1-21. doi: 10.1080/10543406.2021.1918140. Online ahead of print.

ABSTRACT

The use of real-world data became more and more popular in the pharmaceutical industry. The impact of real-world evidence is now well emphasized by the regulatory authorities. Indeed, the analysis of this type of data can play a key role for treatment efficacy and safety. The aim of this work is to assess various methods and give guidance on the comparisons of drugs, mostly with respect to time-to-event data, in non-randomized studies with potentially confounding variables. For that purpose, several statistical methodologies are compared based on simulation studies. These methodologies belong to family classes of methods that are widely used for this type of problem: regression, matching, weighting and subclassification methods. The evaluation criteria used to compare methods performances are the relative bias, the mean square error, the coverage probability and the width of the confidence interval. In this paper, we consider different scenarios of dataset features in order to study the effect of the sample size, the number of covariates and the magnitude of the treatment effect on the statistical methodologies performances. These statistical analyses are conducted within a proportional hazard model framework. Furthermore, we highlight the advantage of using techniques to identify relevant covariates for time-to-event outcomes by comparing two variable selection methods under a frequentist and a Bayesian inference. Based on simulation results, recommendations on each of the family of methods are provided to guide decision making.

PMID:34403296 | DOI:10.1080/10543406.2021.1918140

Acta Oncol. 2021 Aug 17:1-10. doi: 10.1080/0284186X.2021.1962972. Online ahead of print.

ABSTRACT

BACKGROUND: With increased survival among patients with metastatic melanoma and limited time with health care providers, patients are expected to assume a more active role in managing their treatment and care. Activated patients have the knowledge, skills, and confidence to make effective solutions to self-manage health. The use of patient-reported outcomes (PRO) could have the potential to enhance patient activation. However, PRO-based interventions that facilitate an activation in patients with metastatic melanoma are lacking and warranted.

MATERIAL AND METHODS: In this prospective non-randomized controlled, clinical trial, patients with metastatic melanoma were assigned to either the intervention (systematic feedback and discussion of PRO during consultation) given at one hospital or the control group (treatment as usual) if they received treatment from two other hospitals in Denmark. The primary outcome was the patient activation measure (PAM), which reflects self-management. Secondary outcomes were health-related quality of life (HRQoL), self-efficacy, and Patient-Physician interaction. Outcomes were measured at baseline, and after 3, 6, and 12 months. The analysis of the effect from baseline to 12 months employed mixed-effects modeling.

RESULTS: Between 2017 and 2019, patients were allocated to either the intervention group (n = 137) or the control group (n = 142). We found no significant difference in the course of patient activation between the two groups over time. The course of HRQoL was statistically significantly improved by the intervention compared to the control group. Especially, females in the intervention group performed better than males. The other secondary outcomes were not improved by the intervention.

CONCLUSION: The intervention did not improve knowledge, skills, and confidence for self-management for patients with metastatic melanoma. Neither did it improve coping self-efficacy nor perceived efficacy in Patient-Physician interaction. However, the results suggest that the intervention can have a significant impact on HRQoL and in particular social and emotional well-being among the females.

PMID:34403293 | DOI:10.1080/0284186X.2021.1962972

Metabolomics. 2021 Aug 16;17(9):74. doi: 10.1007/s11306-021-01822-2.

ABSTRACT

INTRODUCTION: To study metabolic signatures can be used to identify predictive biomarkers for a patient’s therapeutic response.

OBJECTIVES: We hypothesized that the characterization of a patients’ metabolic profile, utilizing one-dimensional nuclear magnetic resonance (¹H-NMR), may predict a response to tocilizumab in patients with rheumatoid arthritis (RA).

METHODS: 40 active RA patients meeting the 2010 ACR/EULAR classification criteria initiating treatment with tocilizumab were recruited. Clinical outcomes were determined at baseline, and after six and twelve months of treatment. EULAR response criteria at 6 and 12 months to categorize patients as responders and non-responders. Blood was collected at baseline and after six months of tocilizumab therapy. ¹H-NMR was used to acquire a spectra of plasma samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification. SPSS v.27 and MetaboAnalyst 4.0 were used for statistical and pathway analysis.

RESULTS: Isobutyrate, 3-hydroxybutyrate, lysine, phenylalanine, sn-glycero-3-phosphocholine, tryptophan and tyrosine were significantly elevated in responders at the baseline. OPLS-DA at baseline partially discriminated between RA responders and non-responders. A multivariate diagnostic model showed that concentrations of 3-hydroxybutyrate and phenylalanine improved the ability to specifically predict responders classifying 77.1% of the patients correctly. At 6 months, levels of methylamine, sn-glycero-3-phosphocholine and tryptophan tended to still be low in non-responders.

CONCLUSION: The relationship between plasma metabolic profiles and the clinical response to tocilizumab suggests that ¹H-NMR may be a promising tool for RA therapy optimization. More studies are needed to determine if metabolic profiling can predict the response to biological therapies in RA patients.

PMID:34402961 | DOI:10.1007/s11306-021-01822-2

Graefes Arch Clin Exp Ophthalmol. 2021 Aug 17. doi: 10.1007/s00417-021-05340-8. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the clinical profile and visual outcomes of infectious endophthalmitis in children at a single tertiary hospital in France, and propose an evidence-based protocol for management.

METHODS: This is a retrospective monocentric study that involved children with a history of endophthalmitis between January 2008 and January 2020. The clinical characteristics, etiology, microbiological spectrum from aqueous/vitreous tab, anatomical and visual outcomes, and management were analyzed. The Fischer and chi-square tests were used in the statistical evaluation.

RESULTS: Twenty-six children were eligible for inclusion. The mean patients age at presentation was 4.2 years (range, 8 days-14.3 years). With regard to etiology, patients were divided into posttraumatic group (n = 7 (26.9%)), postoperative group (n = 15 (57.7%)), endogenous group (n = 3 (11.5%)), and infectious corneal ulcer group (n = 1 (3.9%)). Time-to-onset of symptoms was highest in children ≤ 3 years old and in the postoperative subgroup who had at least one glaucoma procedure. Microbiology results showed growth in 12/26 (46.2%). The most common microorganism identified was Streptococcus pneumoniae (5/12 (41.7%)). The antibiotic regimen varied depending on age, organism, and sensitivities. The final visual outcomes were 20/200 or better in 11/26 (42.3%) eyes, and 13/26 (50.0%) eyes had no light perception. Twelve of twenty-six (46.2%) eyes ended up with phthisis bulbi.

CONCLUSION: Pediatric endophthalmitis is a rare but devastating condition with poor visual prognosis, requiring prompt recognition and treatment. Despite aggressive management with antibiotics and vitrectomy, the visual prognosis is generally poor. A protocol for management with an adapted systemic antibiotic therapy is proposed in order to improve outcomes.

PMID:34402964 | DOI:10.1007/s00417-021-05340-8