Evaluation of potential gastrointestinal carcinogenicity associated with the ingestion of asbestos

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Thales J. Cheng ◽  
Sharlee L. More ◽  
Mark A. Maddaloni ◽  
Ernest S. Fung
Keyword(s):  
Animal Studies ◽  
Distribution Systems ◽  
Fiber Type ◽  
Small Sample Size ◽  
Small Sample ◽  
Smoking History ◽  
Weight Of Evidence ◽  
Critical Study ◽  
Asbestos Fibers ◽  
Gi Cancers

AbstractThe inhalation of asbestos, depending on the fiber type and dose, may be associated with the development of mesothelioma and other asbestos-related diseases. However, little is known about the potential adverse effects associated with the ingestion of asbestos. Evidence of asbestos fibers released from asbestos-cement pipes used in water distribution systems has led to concerns of potentially contaminated drinking water. The purpose of this study is to determine whether ingestion of asbestos fibers may lead to cancerous effects on the gastrointestinal (GI) tract. Data from animal and human studies were analyzed using a weight-of-evidence approach to evaluate the potential risk of GI cancers associated with asbestos ingestion. Seventeen human and 23 animal studies were identified and evaluated in this study. Animal studies were conducted in multiple species with inconsistent dosing protocols. Overall, animal studies reported that the asbestos fibers, irrespective of fiber type and dose, failed to produce any definitive GI carcinogenic effect. The 17 identified human epidemiological studies reported the ingestion of asbestos-contaminated water with concentrations from 1 to 71,350 million fibers per liter (MFL). A majority of the epidemiology studies reported statistically significant increases in multiple GI-specific cancers. However, these findings are confounded due to several critical study limitations including flawed study design, small sample size, selection bias, lack of individual exposure history, lack of adequate latency, and the inability to account for confounders including occupational history, diet, and smoking history. Based on our weight-of-evidence assessment, there is insufficient evidence of causality between the ingestion of asbestos and an increased incidence of GI cancers.

Essential tremor: genetic update

2019 ◽  
Vol 21 ◽  
Author(s):  
Hao Deng ◽  
Shan Wu ◽  
Joseph Jankovic
Keyword(s):  
Essential Tremor ◽  
Animal Studies ◽  
Genetic Factors ◽  
Small Sample Size ◽  
Small Sample ◽  
Lower Limbs ◽  
Body Parts ◽  
Genetic Analyses ◽  
Disease Definition ◽  
Neurological Movement Disorder

Abstract Essential tremor (ET) is a neurological movement disorder characterised by bilateral limb kinetic/postural tremor, with or without tremor in other body parts including head, voice and lower limbs. Since no causative genes for ET have been identified, it is likely that the disorder occurs as a result of complex genetic factors interacting with various cellular and environmental factors that can result in abnormal function of circuitry involving the cerebello–thalamo–cortical pathway. Genetic analyses have uncovered at least 14 loci and 11 genes that are related to ET, as well as various risk or protective genetic factors. Limitations in ET genetic analyses include inconsistent disease definition, small sample size, varied ethnic backgrounds and many other factors that may contribute to paucity of relevant genetic data in ET. Genetic analyses, coupled with functional and animal studies, have led to better insights into possible pathogenic mechanisms underlying ET. These genetic studies may guide the future development of genetic testing and counselling, and specific, pathogenesis-targeted, therapeutic strategies.

scholarly journals Sequencing Alpha-1 MZ Individuals Shows Frequent Biallelic Mutations

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Kimberly E. Foil ◽  
M. Gwen Blanton ◽  
Chris Sanders ◽  
Joannah Kim ◽  
Haitham S. Al Ashry ◽  
...  
Keyword(s):  
Severity Score ◽  
Small Sample Size ◽  
Genetic Counselor ◽  
Familial Risk ◽  
Small Sample ◽  
Smoking History ◽  
Augmentation Therapy ◽  
Clinical Trial Registration ◽  
Increased Risk ◽  
Severity Scores

Rationale. Individuals with a single Z mutation in the SERPINA1 gene that codes for alpha-1 antitrypsin (AAT) are at increased risk for COPD if they have ever-smoked. Whether additional variants alter the risk for COPD in this population remains unknown. Objectives. To determine whether additional SERPINA1 variants impact COPD development in a previously identified MZ (carrier) cohort. Methods. Individuals with prior MZ results and AAT serum level <16uM were recruited from the Alpha-1 Coded Testing study and Alpha-1 Foundation Research Registry. Participants completed smoking history, demographics, and COPD Severity Score (Range 0-33) using REDCap data capture. At-home finger-stick tests were performed for next generation sequencing (NGS) at the Biocerna LLC laboratory. A genetic counselor reviewed records and interviewed participants with additional variants by NGS. A Wilcoxon Rank Sum test was used to assess correlation between variants and the COPD severity score. Results. A second SERPINA1 variant of known or possible significance was identified in 6 (5.8%) participants. One each of ZZ, SZ, FZ, ZSmunich, ZM2obernburg, and Z/c.922G>T genotypes were identified. ZZ, SZ, and FZ are known pathogenic genotypes. Smunich is a likely pathogenic variant. M2obernburg and c.922G>T are variants of uncertain significance. The ZZ individual was on augmentation therapy when determined MZ by protease inhibitor (Pi) phenotyping; the others had limited targeted genotyping with MZ results. These six participants with biallelic variants had positive COPD severity scores >1. Presence of additional variants was not significantly associated with COPD symptoms in this small sample size. Conclusions. Some diagnosed MZ individuals instead have biallelic variants. Larger studies are needed to determine COPD-risk liability of variants. Accurate diagnosis impacts medical management and familial risk assessment. Pi phenotyping can be confounded by augmentation therapy and liver transplantation. Because a normal M allele may be reported in the absence of tested mutation(s) in AATD genotyping, clinicians should consider clinical circumstances and laboratory methods when selecting and interpreting AATD tests. Advanced testing, including NGS, may be beneficial for select individuals with prior MZ results. Clinical Trial Registration. This study was registered with clinicaltrials.gov (NCT NCT02810327).

Is cigarette smoke associated with increased catabolism of gemcitabine in patients with advanced solid tumors?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2602-2602
Author(s):  
Meaghan Working O'Malley ◽  
Stephanie Daignault ◽  
Patrick N. Healy ◽  
Lindsay A. Schmidt ◽  
Nithya Ramnath
Keyword(s):  
Logistic Regression ◽  
Cigarette Smoking ◽  
Small Sample Size ◽  
Plasma Concentrations ◽  
Small Sample ◽  
Stage Iii ◽  
Disease Stage ◽  
Smoking History ◽  
Unknown Primary ◽  
Never Smokers

2602 Background: Cigarette smoking can accelerate chemotherapy metabolism and result in lower plasma concentrations of the chemotherapeutic agent. Reduced drug levels may lead to undertreatment in smokers and, conversely, increased treatment-related neutropenia in nonsmokers. Methods: An IRB-approved retrospective chart review was performed on 151 patients with solid tumor malignancies who received gemcitabine alone or in combination with oral chemotherapy agents from July 1, 2009 to June 30, 2011 at the University of Michigan. Using logistic regression, we compared toxicity, including neutropenia, and smoking history measured in pack-years in smokers vs. nonsmokers to ascertain whether cigarette smoking is an independent factor predictive of toxicity to gemcitabine. Results: Tumor types included breast (9.3%), lung (4.6%), pancreatobiliary (70.9%), or other/unknown primary (15.2%). Most patients had advanced disease (stage III-IV; 78.1%); specifically, of the pancreatobiliary cohort (PB; n=107), 77.6% patients had stage III-IV disease. Within the PB cohort, most patients were “ever” smokers as compared to “never” smokers (60.7% vs. 39.3%). Logistic regression of this cohort showed that current smokers had decreased CTC-AE grade 3-4 neutropenia vs. never smokers (OR 0.667; 95% CI [0.156-2.859]). This effect was more pronounced with higher pack-year history: smokers with >50 pack-years had even less neutropenia as compared to never smokers (OR 0.333; 95% CI [0.065-1.699]). Further statistical analysis of subgroups was not performed due to small sample size. Conclusions: Smokers with pancreatobiliary malignancies receiving gemcitabine had less treatment-related neutropenia as compared to never smokers, a finding that was more pronounced as pack-years increased. Decreased toxicity, including neutropenia, may be due to increased metabolism and drug clearance as a result of smoking. This may lead to potential undertreatment of smokers and, conversely, increased treatment-related toxicity in never smokers. A prospective clinical trial is needed to further elucidate this correlation, and is currently being designed.

Probing the ultrastructure of the mitotic and meiotic spindle in eggs: An expeditious approach based on semi-thin (0.25 μm) serial sections

1983 ◽  
Vol 41 ◽  
pp. 552-555
Author(s):  
Conly L. Rieder ◽  
S. Bowser ◽  
R. Nowogrodzki ◽  
K. Ross ◽  
G. Sluder
Keyword(s):  
Small Sample Size ◽  
Small Sample ◽  
Meiotic Spindle ◽  
Serial Sections ◽  
Mitotic Apparatus ◽  
Thin Sections ◽  
Cell Cycles ◽  
Ultrastructural Studies

Eggs have long been a favorite material for studying the mechanism of karyokinesis in-vivo and in-vitro. They can be obtained in great numbers and, when fertilized, divide synchronously over many cell cycles. However, they are not considered to be a practical system for ultrastructural studies on the mitotic apparatus (MA) for several reasons, the most obvious of which is that sectioning them is a formidable task: over 1000 ultra-thin sections need to be cut from a single 80-100 μm diameter egg and of these sections only a small percentage will contain the area or structure of interest. Thus it is difficult and time consuming to obtain reliable ultrastructural data concerning the MA of eggs; and when it is obtained it is necessarily based on a small sample size.We have recently developed a procedure which will facilitate many studies concerned with the ultrastructure of the MA in eggs. It is based on the availability of biological HVEM's and on the observation that 0.25 μm thick serial sections can be screened at high resolution for content (after mounting on slot grids and staining with uranyl and lead) by phase contrast light microscopy (LM; Figs 1-2).

Validating the Factor Structure of the Stigma of Suicide Scale–Short Form Spanish Version Among Healthcare Students

Crisis ◽  
2020 ◽  
pp. 1-5
Author(s):  
Ruthmarie Hernández-Torres ◽  
Paola Carminelli-Corretjer ◽  
Nelmit Tollinchi-Natali ◽  
Ernesto Rosario-Hernández ◽  
Yovanska Duarté-Vélez ◽  
...  
Keyword(s):  
Factor Structure ◽  
Structural Equation ◽  
Short Form ◽  
Small Sample Size ◽  
Small Sample ◽  
Spanish Version ◽  
Equation Modeling ◽  
Cross Sectional ◽  
Healthcare Students ◽  
Spanish Speaking

Abstract. Background: Suicide is a leading cause of death among Spanish-speaking individuals. Suicide stigma can be a risk factor for suicide. A widely used measure is the Stigma of Suicide Scale-Short Form (SOSS-SF; Batterham, Calear, & Christensen, 2013 ). Although the SOSS-SF has established psychometric properties and factor structure in other languages and cultural contexts, no evidence is available from Spanish-speaking populations. Aim: This study aims to validate a Spanish translation of the SOSS-SF among a sample of Spanish-speaking healthcare students ( N = 277). Method: We implemented a cross-sectional design with quantitative techniques. Results: Following a structural equation modeling approach, a confirmatory factor analysis (CFA) supported the three-factor model proposed by Batterham and colleagues (2013) . Limitations: The study was limited by the small sample size and recruitment by availability. Conclusion: Findings suggest that the Spanish version of the SOSS-SF is a valid and reliable tool with which to examine suicide stigma among Spanish-speaking populations.

An Initial Investigation of Suicide Attempt Disclosures Among US Veterans

Crisis ◽  
2020 ◽  
pp. 1-7
Author(s):  
Brooke A. Ammerman ◽  
Sarah P. Carter ◽  
Heather M. Gebhardt ◽  
Jonathan Buchholz ◽  
Mark A. Reger
Keyword(s):  
Suicide Attempt ◽  
Mental Health Professionals ◽  
Help Seeking ◽  
Psychiatric Treatment ◽  
Small Sample Size ◽  
Romantic Partners ◽  
Small Sample ◽  
Professional Care ◽  
Patient Disclosure ◽  
Previous Suicide Attempt

Abstract. Background: Patient disclosure of prior suicidal behaviors is critical for effectively managing suicide risk; however, many attempts go undisclosed. Aims: The current study explored how responses following a suicide attempt disclosure may relate to help-seeking outcomes. Method: Participants included 37 veterans with a previous suicide attempt receiving inpatient psychiatric treatment. Veterans reported on their most and least helpful experiences disclosing their suicide attempt to others. Results: Veterans disclosed their suicide attempt to approximately eight individuals. Mental health professionals were the most cited recipient of their most helpful disclosure; romantic partners were the most common recipient of their least helpful disclosures. Positive reactions within the context of the least helpful disclosure experience were positively associated with a sense of connection with the disclosure recipient. Positive reactions within the most helpful disclosure experience were positively associated with the likelihood of future disclosure. No reactions were associated with having sought professional care or likelihood of seeking professional care. Limitations: The results are considered preliminary due to the small sample size. Conclusion: Findings suggest that while positive reactions may influence suicide attempt disclosure experiences broadly, additional research is needed to clarify factors that drive the decision to disclose a suicide attempt to a professional.

Investigating the Dynamics of Suicidal Ideation

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Nina Hallensleben ◽  
Lena Spangenberg ◽  
Thomas Forkmann ◽  
Dajana Rath ◽  
Ulrich Hegerl ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Small Sample Size ◽  
Unipolar Depression ◽  
Small Sample ◽  
History Of ◽  
Severity Of Depression ◽  
Ecological Momentary ◽  
Depressive Episodes ◽  
Ema Method ◽  
Shed Light

Abstract. Background: Although the fluctuating nature of suicidal ideation (SI) has been described previously, longitudinal studies investigating the dynamics of SI are scarce. Aim: To demonstrate the fluctuation of SI across 6 days and up to 60 measurement points using smartphone-based ecological momentary assessments (EMA). Method: Twenty inpatients with unipolar depression and current and/or lifetime suicidal ideation rated their momentary SI 10 times per day over a 6-day period. Mean squared successive difference (MSSD) was calculated as a measure of variability. Correlations of MSSD with severity of depression, number of previous depressive episodes, and history of suicidal behavior were examined. Results: Individual trajectories of SI are shown to illustrate fluctuation. MSSD values ranged from 0.2 to 21.7. No significant correlations of MSSD with several clinical parameters were found, but there are hints of associations between fluctuation of SI and severity of depression and suicidality. Limitations: Main limitation of this study is the small sample size leading to low power and probably missing potential effects. Further research with larger samples is necessary to shed light on the dynamics of SI. Conclusion: The results illustrate the dynamic nature and the diversity of trajectories of SI across 6 days in psychiatric inpatients with unipolar depression. Prediction of the fluctuation of SI might be of high clinical relevance. Further research using EMA and sophisticated analyses with larger samples is necessary to shed light on the dynamics of SI.

Participant Reactions to Suicide-Focused Research

Crisis ◽  
2020 ◽  
Vol 41 (5) ◽  
pp. 367-374
Author(s):  
Sarah P. Carter ◽  
Brooke A. Ammerman ◽  
Heather M. Gebhardt ◽  
Jonathan Buchholz ◽  
Mark A. Reger
Keyword(s):  
Medical Records ◽  
Research Study ◽  
Small Sample Size ◽  
Psychiatric Inpatient ◽  
Small Sample ◽  
Inpatient Unit ◽  
Online Laboratory ◽  
Psychiatric Inpatient Unit ◽  
Before And After ◽  
Participant Reactions

Abstract. Background: Concerns exist regarding the perceived risks of conducting suicide-focused research among an acutely distressed population. Aims: The current study assessed changes in participant distress before and after participation in a suicide-focused research study conducted on a psychiatric inpatient unit. Method: Participants included 37 veterans who were receiving treatment on a psychiatric inpatient unit and completed a survey-based research study focused on suicide-related behaviors and experiences. Results: Participants reported no significant changes in self-reported distress. The majority of participants reported unchanged or decreased distress. Reviews of electronic medical records revealed no behavioral dysregulation and minimal use of as-needed medications or changes in mood following participation. Limitations: The study's small sample size and veteran population may limit generalizability. Conclusion: Findings add to research conducted across a variety of settings (i.e., outpatient, online, laboratory), indicating that participating in suicide-focused research is not significantly associated with increased distress or suicide risk.

Measurements method of the audio recordings acoustic quality indicator prepared for registration and processing in the Unified Biometric System

2019 ◽  
pp. 40-46 ◽  
Author(s):  
V.V. Savchenko ◽  
A.V. Savchenko
Keyword(s):  
Quality Control ◽  
Small Sample Size ◽  
Personal Data ◽  
Digital Processing ◽  
Small Sample ◽  
Practical Implementation ◽  
Acoustic Measurements ◽  
Pitch Frequency ◽  
Wide Range ◽  
Automated Quality Control

We consider the task of automated quality control of sound recordings containing voice samples of individuals. It is shown that in this task the most acute is the small sample size. In order to overcome this problem, we propose the novel method of acoustic measurements based on relative stability of the pitch frequency within a voice sample of short duration. An example of its practical implementation using aninter-periodic accumulation of a speech signal is considered. An experimental study with specially developed software provides statistical estimates of the effectiveness of the proposed method in noisy environments. It is shown that this method rejects the audio recording as unsuitable for a voice biometric identification with a probability of 0,95 or more for a signal to noise ratio below 15 dB. The obtained results are intended for use in the development of new and modifying existing systems of collecting and automated quality control of biometric personal data. The article is intended for a wide range of specialists in the field of acoustic measurements and digital processing of speech signals, as well as for practitioners who organize the work of authorized organizations in preparing for registration samples of biometric personal data.

A randomized, double-blind, placebo-controlled study of polyunsaturated fatty acids efficacy in adolescents with anorexia nervosa

2020 ◽  
Vol 36 (2) ◽  
pp. 95-106
Author(s):  
Agnieszka M. Piróg-Balcerzak ◽  
Anna K. Bażyńska ◽  
Katarzyna Biernacka ◽  
Joanna Brągoszewska ◽  
Lidia Popek ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Anorexia Nervosa ◽  
Polyunsaturated Fatty Acids ◽  
Small Sample Size ◽  
Small Sample ◽  
Female Adolescent ◽  
Eating Attitude ◽  
Controlled Study ◽  
Omega 3 ◽  
Eat 26

Objective. Omega–3 polyunsaturated fatty acids (PUFAs) were tested in adolescent depression and in several neurodevelopmental disorders with partial success. Anorexia nervosa (AN) is characterised by deficiencies in fatty food intake and frequent comorbidity, including depressive and cognitive symptoms. Thus supplementation with PUFAs may be beneficial in this group of patients. The aim of the study was to assess whether PUFAs as an add-on treatment is associated with better improvement of body mass index (BMI) and psychopathological symptoms than placebo in patients with AN. Method. 61 female adolescent inpatients with AN were randomly allocated to omega–3 PUFAs supplementation or placebo for 10 weeks. Patients also participated in the behavioural programme and eclectic psychotherapy (treatment as usual, TAU). At baseline and follow-up visits, patients’ BMI and psychopathology were assessed with Clinical Global Impression Scale (CGI), Patient Global Impression Scale (PGI), and Eating Attitude Test (EAT-26). Results. After 10 weeks, both groups showed improvement in all parameters. Improvement in CGI scores was observed greater in placebo vs. PUFA-s group (p = 0.015) while other differences were not statistically significant. Omega–3 PUFAs supplementation appears not to be effective as an add-on treatment in inpatient adolescent girls with anorexia nervosa. Conclusions. The results should be analysed with caution due to small sample size and heterogeneity in TAU. As the TAU turned out to be highly effective, additional therapeutic effect of PUFA might not be visible. Nevertheless, that does not explain the tendency for better improvement in the placebo group.

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