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Urine levels of the polyglutamine ataxin-3 protein are elevated in patients with spinocerebellar ataxia type 3

Parkinsonism Relat Disord. 2021 Jul 17;89:151-154. doi: 10.1016/j.parkreldis.2021.07.018. Online ahead of print.

ABSTRACT

INTRODUCTION: Accumulation of polyglutamine (polyQ) ataxin-3 (ATXN3) contributes to the pathobiology of spinocerebellar ataxia type 3 (SCA3). Recently, we showed that polyQ ATXN3 is elevated in the plasma and cerebrospinal fluid (CSF) of SCA3 patients, and has the potential to serve as a biological marker for this disease [1]. Based on these findings, we investigated whether polyQ ATXN3 can also be detected in urine samples from SCA3 patients.

METHODS: We analyzed urine samples from 30 SCA3 subjects (including one pre-symptomatic subject), 35 subjects with other forms of ataxia, and 37 healthy controls. To quantify polyQ ATXN3 protein levels, we used our previously developed immunoassay.

RESULTS: PolyQ ATXN3 can be detected in the urine of SCA3 patients, but not in urine samples from healthy controls or other forms of ataxia. There was a significant statistical association between polyQ ATXN3 levels in urine samples and those in plasma. Further, the levels of polyQ ATXN3 urine associated with an earlier age of SCA3 disease onset.

CONCLUSION: As clinical trials for SCA3 advance, urine polyQ ATXN3 protein has potential to be a useful, non-invasive and inexpensive biomarker for SCA3.

PMID:34303201 | DOI:10.1016/j.parkreldis.2021.07.018

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Is there evidence of shifting baseline syndrome in environmental managers? An assessment using perceptions of bird population targets in UK nature reserves

J Environ Manage. 2021 Jul 21;297:113308. doi: 10.1016/j.jenvman.2021.113308. Online ahead of print.

ABSTRACT

Shifting baseline syndrome (SBS) describes changing perceptions of biological conditions due to a loss of historical knowledge. Perceptions of ‘normal’ environmental conditions are continually updated, leading to underestimation of the true magnitude of long-term ecological change and potential setting of unambitious management targets. There has been speculation as to the presence and impacts of SBS within conservation management since Daniel Pauly’s seminal paper in 1995, which outlined the potential effects of SBS on target-setting in fisheries management. Previous case studies have suggested that SBS may not occur in management, despite empirical evidence of SBS in other systems. In this study, 44 professionals and volunteers involved in bird species management, monitoring and target-setting across England were interviewed. Interviews asked for personal perceptions of current, maximum and target abundance, long-term trends, and perceived conservation priority for six bird species. Using paired tests, this study found no significant effect of experience on perceptions of current, maximum or target abundance of all species, despite differences in national abundance and trends, and differences in participant experience. Further power analysis indicated that even if SBS was statistically detectible with a larger sample, the practical implications of the syndrome would be minimal due to small effect sizes. Finally, the effect of experience on individual perceptions of species conservation priority varied between species, with generational amnesia in the form of ‘lifting baselines’ suggested for only one of the six species. This study suggests that shifting baseline syndrome may not be as significant a threat in conservation management as first thought.

PMID:34303198 | DOI:10.1016/j.jenvman.2021.113308

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Continuous-time deconvolutional regression for psycholinguistic modeling

Cognition. 2021 Jul 21;215:104735. doi: 10.1016/j.cognition.2021.104735. Online ahead of print.

ABSTRACT

The influence of stimuli in psycholinguistic experiments diffuses across time because the human response to language is not instantaneous. The linear models typically used to analyze psycholinguistic data are unable to account for this phenomenon due to strong temporal independence assumptions, while existing deconvolutional methods for estimating diffuse temporal structure model time discretely and therefore cannot be directly applied to natural language stimuli where events (words) have variable duration. In light of evidence that continuous-time deconvolutional regression (CDR) can address these issues (Shain & Schuler, 2018), this article motivates the use of CDR for many experimental settings, exposits some of its mathematical properties, and empirically evaluates the influence of various experimental confounds (noise, multicollinearity, and impulse response misspecification), hyperparameter settings, and response types (behavioral and fMRI). Results show that CDR (1) yields highly consistent estimates across a variety of hyperparameter configurations, (2) faithfully recovers the data-generating model on synthetic data, even under adverse training conditions, and (3) outperforms widely-used statistical approaches when applied to naturalistic reading and fMRI data. In addition, procedures for testing scientific hypotheses using CDR are defined and demonstrated, and empirically-motivated best-practices for CDR modeling are proposed. Results support the use of CDR for analyzing psycholinguistic time series, especially in a naturalistic experimental paradigm.

PMID:34303182 | DOI:10.1016/j.cognition.2021.104735

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Temperature, phytoplankton density and bacteria diversity drive the biotransformation of micropollutants in a lake ecosystem

Water Res. 2021 Jul 7;202:117412. doi: 10.1016/j.watres.2021.117412. Online ahead of print.

ABSTRACT

For most micropollutants (MPs) present in surface waters, such as pesticides and pharmaceuticals, the contribution of biotransformation to their overall removal from lake ecosystems is largely unknown. This study aims at empirically determining the biotransformation rate constants for 35 MPs at different periods of the year and depths of a meso-eutrophic lake. We then tested statistically the association of environmental parameters and microbial community composition with the biotransformation rate constants obtained. Biotransformation was observed for 14 out of 35 studied MPs for at least one sampling time. Large variations in biotransformation rate constants were observed over the seasons and between compounds. Overall, the transformation of MPs was mostly influenced by the lake’s temperature, phytoplankton density and bacterial diversity. However, some individual MPs were not following the general trend or association with microorganism biomass. The antidepressant mianserin, for instance, was transformed in all experiments and depths, but did not show any relationship with measured environmental parameters, suggesting the importance of specific microorganisms in its transformation. The results presented here contribute to our understanding of the fate of MPs in surface waters and thus support improved risk assessment of contaminants in the environment.

PMID:34303164 | DOI:10.1016/j.watres.2021.117412

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Perineal ultrasound in infants with anteriorly displaced anus: A new decision-making tool for the surgeon?

Eur J Radiol. 2021 Jul 9;142:109854. doi: 10.1016/j.ejrad.2021.109854. Online ahead of print.

ABSTRACT

BACKGROUND: Anteriorly displaced anus (ADA) is defined as anterior displacement of the anus toward the perineum. Early radiologic characterization is a crucial step in guiding the first-line management.

OBJECTIVE: The objective of this study was to assess the urethra-to-anus distance (UAD) on perineal ultrasound in female infants under the age of 3 months with anteriorly displaced anus and to retrospectively determine a cut-off to guide the indications for surgery.

MATERIALS AND METHODS: Perineal ultrasound was performed prospectively in female infants under the age of 3 months with determination of the UAD, during screening for congenital hip dislocation. Determinations of the UAD on perineal ultrasound and pelvic MRI were performed for anteriorly displaced anus in girls between 2011 and 2018.

RESULTS: 230 patients were included, of whom 173 were in the control group, with 52 examinations performed for anteriorly displaced anus and 5 examinations performed for vestibular anus. The mean UAD for infants under the age of 3 months was: 22.9 mm (±1.7) in healthy infants, 21.4 mm (±2.4) in infants with non-operated ADA, 17.5 mm (±1.8) in infants with operated ADA, and 10.8 mm (±1.3) in infants with anorectal malformation (ARM). A statistically significant difference was observed between the control group and the ARM group (p = 0.0001) and between the control group and the operated ADA group (p = 0.0001). The mean UAD for infants over the age of 3 months was: 25.5 mm (±4.1) in infants with non-operated ADA and 26 mm (±3) in infants with operated ADA.

CONCLUSION: A urethra-to-anus distance of less than 17 mm appears to be a cut-off for anteriorly displaced anus in anorectal malformations.

PMID:34303148 | DOI:10.1016/j.ejrad.2021.109854

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Supporting pandemic disease preparedness: Development of a composite index of area vulnerability

Health Place. 2021 Jul 21;70:102629. doi: 10.1016/j.healthplace.2021.102629. Online ahead of print.

ABSTRACT

Although pandemics are rare, planning and preparation for responding to them plays a crucial role in preventing their spread. The management and control of pandemics such as COVID-19 relies heavily on a country’s health capacity. Measuring vulnerability to pandemics in geographical areas could potentially delay a pandemic’s exponential growth and reduce the number of cases, which would alleviate the disease impact on communities and the health care sector. The aim of this study is to generate an area-level COVID-19 Pandemic Vulnerability Index (CPVI) and to assess its correlation with COVID-19 cases. Data were collected for Local Government Areas (LGAs) across Australia from different sources including Australia Bureau of Statistics, Australian Institute of Health and Welfare, and General Transit Feed Specification. Based on recent official reports about the COVID-19 outbreak, 18 factors were identified as influencing vulnerability to the disease within LGAs. Using factor analysis, four latent factors were identified and named as sociodemographic, medical conditions, transportation, and land use. Predicted factor scores were summed to generate a CPVI for each LGA. The CPVI was evaluated by correlating with confirmed cases of COVID-19 standardised by adult population in New South Wales and Victoria, the two Australian states with the highest numbers of confirmed cases. There was a statistically significant correlation between the CPVI and COVID-19 in New South Wales (r = 0.49) and Victoria (r = 0.48). LGAs scoring higher on the CPVI also had a higher absolute number of cases. The CPVI could be used by policymakers to identify at-risk areas and to develop preparedness and response plans to help mitigate the spread of COVID-19 and future pandemics.

PMID:34303129 | DOI:10.1016/j.healthplace.2021.102629

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Comparison of Sexual Behavior and Inflammatory Parameters in Prostate Cancer Patients with Control Group: Prospective Controlled Study

Urol J. 2021 Jul 24:6464. doi: 10.22037/uj.v18i.6464. Online ahead of print.

ABSTRACT

PURPOSE: In spite of extraordinary developments in diagnostic and treatment methods for prostate cancer (PCa), the reason for this disease is not known. Our study aimed to compare men in the PCa group with a control group in terms of sexual behavior like partner numbers and ejaculation frequency, and inflammatory parameters examined in serum.

MATERIAL AND METHODS: This study was performed prospectively between 2013 and April 2020 and the record system was kept by a single doctor. Patients were prospectively recorded by a single person. Patients with diagnosis of PCa were compared with a control group in terms of sexual behavior and in terms of inflammatory parameters like neutrophil lymphocyte ratio (NLR, neutrophil count/lymphocyte count), systemic inflammatory index (SII, neutrophil count x platelet count/lymphocyte count).

RESULTS: In this study, median marriage age was 18 ± 6 years in the control group and 20 ± 2.97 in the PCa group (P = .001). The median lifelong partner number was observed to be 1 ± 1 in the control group and 1 ± 9 in the PCa group (median ± IQR). Additionally, lifelong median ejaculation frequency was determined as 12 ± 5 for controls and 10 ± 4 for the PCa group. Inflammatory markers examined in serum and SII scores were observed to be statistically significantly increased in the cancer group.

CONCLUSION: The sexual behavior and inflammatory parameters among patients with PCa diagnosis were identified to be significantly high compared to the control group and appear to be possible correctable risk factors. Informing men about sexual behavior from an early age and taking precautions for people at risk in the early period may be protective against this disease.

PMID:34302738 | DOI:10.22037/uj.v18i.6464

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Increasing Rates of Buprenorphine Diversion in the United States, 2002 to 2019

Pharmacoepidemiol Drug Saf. 2021 Jul 24. doi: 10.1002/pds.5334. Online ahead of print.

ABSTRACT

PURPOSE: Recent reports suggest that buprenorphine is being diverted and used non-medically. However, no apparent studies have reported national-level data on buprenorphine diversion.

METHODS: Case report data were drawn from a quarterly survey of prescription drug diversion completed by a national sample of law enforcement and regulatory agencies who engage in drug diversion investigations. Quarterly rates of buprenorphine diversion per 100 000 population and 100 000 prescriptions dispensed were calculated for the period 2002 through 2019. Population-based diversion rates were also calculated by U.S. region.

RESULTS: In total, 9670 cases of diverted buprenorphine were reported across all 50 states and the District of Columbia during the study period. Buprenorphine diversion rates, per 100 000 population, were characterized by an accelerating increase over time; increases in diversion rates from 1st quarter 2002 through 4th quarter 2006 were not statistically significant, yet from 1st quarter 2007 through 4th quarter 2019, the rate of diversion cases increased by 0.0067 cases per 100 000 per quarter (p < 0.001). Buprenorphine diversion rates per 100 000 prescriptions dispensed indicated a gradual increase over time; from 3rd quarter 2010 through 4th quarter 2019, diversion rates showed a statistically significant increase of 0.28 cases (p = 0.037) per quarter on average. The Northeast was the only region that did not observe an increase in the average quarterly change in buprenorphine diversion rates after 2006.

CONCLUSIONS: Findings from this study illustrate longitudinal national trends of increasing buprenorphine diversion. Continued systematic surveillance of this phenomenon is needed.

PMID:34302707 | DOI:10.1002/pds.5334

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Epidemiological characteristics and incubation period of SARS-CoV-2 during the 2020-2021 winter pandemic wave in north China: an observational study

J Med Virol. 2021 Jul 24. doi: 10.1002/jmv.27226. Online ahead of print.

ABSTRACT

As the emergence of new variants of SARS-CoV-2 persists across the world, it is of importance to understand the distributional behavior of incubation period of the variants for both medical research and public health policy-making. We collected the published individual level data of 941 patients of the 2020-2021 winter pandemic wave in Hebei province, north China. We computed some epidemiological characteristics of the wave and estimated the distribution of the incubation period. We further assessed the covariate effects of sex, age and living with a case with respect to incubation period by a model. The infection-fatality rate was only 0.1%. The estimated median incubation period was at least 22 days, significantly extended from the estimates (ranging from 4 to 8.5 days) of the previous wave in mainland China and those ever reported elsewhere around the world. The proportion of asymptomatic patients was 90.6%. No significant covariate effect was found. The distribution of incubation period of the new variants showed a clear extension from their early generations. This article is protected by copyright. All rights reserved.

PMID:34302700 | DOI:10.1002/jmv.27226

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Comparison of Outcomes for Laser Trabeculoplasty after Kahook Dual Blade Goniotomy Versus in Goniotomy-Naive Eyes

Ophthalmol Ther. 2021 Jul 24. doi: 10.1007/s40123-021-00378-7. Online ahead of print.

ABSTRACT

INTRODUCTION: This was a comparison of laser trabeculoplasty (LTP) outcomes in eyes with prior Kahook Dual Blade (KDB) goniotomy versus in goniotomy-naive control eyes.

METHODS: This was a retrospective matched comparative case series. We identified a cohort of patients undergoing LTP between February 2017 and July 2020 at University of Missouri. Patients were grouped by history of KDB goniotomy versus goniotomy-naivety as a control group. Inclusion criteria included age at least 18 years, minimum of 6 months follow-up after LTP, and minimum period of 6 months between KDB goniotomy and LTP. All KDB procedures were combined with uncomplicated phacoemulsification. Patients who had any additional intraocular pressure (IOP)-lowering procedures between KDB goniotomy and LTP were excluded. Patients in the control group received a single LTP procedure. Primary outcome consisted of the comparison of LTP success, defined as IOP reduction of at least 20% or reduction of glaucoma medications from pre-LTP baseline. Secondary outcomes included IOP and medication reduction from pre-LTP baseline.

RESULTS: Twenty-one eyes of 19 patients with history of KDB goniotomy and 42 eyes of 36 control patients without previous angle or laser procedures were included. Baseline characteristics including age, gender, ethnicity, type and severity of glaucoma, baseline IOP, and baseline medications were matched between groups. The LTP success rate was higher in the control group, but was not statistically significant (64% vs 57%, p = 0.58). IOP reduction was only significant in the control eyes (2.50 ± 4.0 mmHg, p = 0.01 vs 2.35 ± 4.7 mmHg, p = 0.08). The number of glaucoma medications was not significantly reduced in either group.

CONCLUSION: LTP may have a limited IOP- and medication-lowering effect in eyes with a history of KDB goniotomy compared to goniotomy-naive eyes.

PMID:34302639 | DOI:10.1007/s40123-021-00378-7