Publications by authors named "Peter Green"

541 Publications

Navigating celiac disease and the gluten-free diet in China.

Nutr Health 2021 Apr 11:260106021990254. Epub 2021 Apr 11.

Celiac Disease Center, 21611Columbia University Irving Medical Center, USA.

Background: Little is known about celiac disease (CeD) diagnosis and management in China.

Aim: This pilot aimed to be the first study to describe, quantitatively and qualitatively, how individuals living in China navigate CeD and the gluten-free diet (GFD).

Methods: Participants were 13 adults and four parents of children with reported CeD, recruited from 11 mainland China cities via an online GFD support group. CeD-specific quality of life (CD-QOL and CD-PQOL) and diet adherence (CDAT) were assessed. In-depth interviews addressed experiences with CeD and the GFD.

Results: Six of 17 participants reported biopsy- or serology-confirmed CeD. The mean (SD) adult CDAT score was 15.2 (3.6), > 13 indicating inadequate GFD adherence. The mean adult CD-QOL score was 62.1 (24.1) out of 100, in the "medium" to "good" range. Results were similar in children. Major interview themes included: (1) a challenging journey to obtain diagnosis; (2) social and structural barriers to maintaining the GFD; and (3) reliance on self in management of CeD.

Conclusion: Obtaining a diagnosis, maintaining a GFD, and living with CeD can be extremely challenging in mainland China. Results suggest an urgent need for CeD-specific education and Asian-adapted GFD guidance for both healthcare practitioners and patients.
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http://dx.doi.org/10.1177/0260106021990254DOI Listing
April 2021

Automated interpretation of biopsy images for the detection of celiac disease using a machine learning approach.

Comput Methods Programs Biomed 2021 Feb 27;203:106010. Epub 2021 Feb 27.

Department of Electronics and Computer Engineering, Ngee Ann Polytechnic, Singapore; School of Science and Technology, Singapore University of Social Sciences, Singapore; School of Business, University of Southern Queensland Springfield, Australia; Department of Bioinformatics and Medical Engineering, Asia University, Taiwan; International Research Organization for Advanced Science and Technology (IROAST) Kumamoto University, Kumamoto, Japan. Electronic address:

Background And Objectives: Celiac disease is an autoimmune disease occurring in about 1 in 100 people worldwide. Early diagnosis and efficient treatment are crucial in mitigating the complications that are associated with untreated celiac disease, such as intestinal lymphoma and malignancy, and the subsequent high morbidity. The current diagnostic methods using small intestinal biopsy histopathology, endoscopy, and video capsule endoscopy (VCE) involve manual interpretation of photomicrographs or images, which can be time-consuming and difficult, with inter-observer variability. In this paper, a machine learning technique was developed for the automation of biopsy image analysis to detect and classify villous atrophy based on modified Marsh scores. This is one of the first studies to employ conventional machine learning to automate the use of biopsy images for celiac disease detection and classification.

Methods: The Steerable Pyramid Transform (SPT) method was used to obtain sub bands from which various types of entropy and nonlinear features were computed. All extracted features were automatically classified into two-class and multi-class, using six classifiers.

Results: An accuracy of 88.89%, was achieved for the classification of two-class villous abnormalities based on analysis of Hematoxylin and Eosin (H&E) stained biopsy images. Similarly, an accuracy of 82.92% was achieved for the two-class classification of red-green-blue (RGB) biopsy images. Also, an accuracy of 72% was achieved in the classification of multi-class biopsy images.

Conclusion: The results obtained are promising, and demonstrate the possibility of automating biopsy image interpretation using machine learning. This can assist pathologists in accelerating the diagnostic process without bias, resulting in greater accuracy, and ultimately, earlier access to treatment.
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http://dx.doi.org/10.1016/j.cmpb.2021.106010DOI Listing
February 2021

Risk perception and knowledge of COVID-19 in patients with celiac disease.

World J Gastroenterol 2021 Mar;27(12):1213-1225

Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton L8S4K1, ON, Canada.

Background: We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk.

Aim: To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception.

Methods: We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visits, and social media. Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population. Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception, such as age, sex, adherence to a gluten-free diet (GFD), and comorbidities such as cardiac conditions, respiratory conditions, and diabetes. Data was presented as adjusted odds ratios (aORs).

Results: A total of 10737 participants with CeD completed the survey. From them, 6019 (56.1%) patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population. A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD (56.1% 26.7%, < 0.0001). Consequently, 34.8% reported taking extra COVID-19 precautions as a result of their CeD. Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members (49.5% 57.4%, < 0.0001). Older age (aOR: 0.99; 95%CI: 0.99 to 0.99, < 0.001), male sex (aOR: 0.84; 95%CI: 0.76 to 0.93, = 0.001), and strict adherence to a GFD (aOR: 0.89; 95%CI: 0.82 to 0.96, = 0.007) were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk (aOR: 1.38; 95%CI: 1.22 to 1.54, < 0.001).

Conclusion: Overall, high levels of risk perceptions, such as those found in patients with CeD, may increase an individual's pandemic-related stress and contribute to negative mental health consequences. Therefore, it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community. Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population.
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http://dx.doi.org/10.3748/wjg.v27.i12.1213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006100PMC
March 2021

Casework applications of probabilistic genotyping methods for DNA mixtures that allow relationships between contributors.

Forensic Sci Int Genet 2021 May 17;52:102482. Epub 2021 Feb 17.

Forensic Sciences Institute, University of Santiago de Compostela, Spain; Comisaría General de Policía Científica, DNA Laboratory, Madrid, Spain.

In both criminal cases and civil cases there is an increasing demand for the analysis of DNA mixtures involving relationships. The goal might be, for example, to identify the contributors to a DNA mixture where the unknown donors may be related, or to infer the relationship between individuals based on a DNA mixture. This paper applies a new approach to modelling and computation for DNA mixtures involving contributors with arbitrarily complex relationships to two real cases from the Spanish Forensic Police.
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http://dx.doi.org/10.1016/j.fsigen.2021.102482DOI Listing
May 2021

Characteristics and Outcomes of Endoscopies Before and During the COVID-19 Pandemic in New York.

Dig Dis 2021 Feb 25. Epub 2021 Feb 25.

Introduction The COVID-19 pandemic drastically changed hospital workflows. This study aimed to characterize differences in gastrointestinal endoscopies in the New York metropolitan region before, during, and after the first wave of the pandemic. Methods Across three hospitals, we compared demographics, indications, and yield of endoscopies before and after March 16, 2020, the date on which elective procedures were cancelled, as well as a recovery period for five months after they were resumed. Results A total of 9,401 procedures before and 332 procedures were performed during the first wave. Females comprised 57% and 44% of patients (p <0.01), respectively. There was a decline in the proportion of Black (15% vs. 7%, p <0.02) and Hispanic patients (29% vs. 16%, p <0.02) undergoing outpatient procedures. There was a significant rise in urgent indications such as bleeding and jaundice. There was an increase in the diagnostic yield of all esophagogastroduodenoscopies for bleeding (p <0.01) and in outpatient endoscopic ultrasounds for malignancy (p = 0.01), but no increase in yield of inpatient colonoscopy for bleeding. Review of 7,475 procedures during the recovery period showed a return to many non-urgent indications, but still showed decreased proportions of Hispanic and male patients compared to the pre-pandemic period. Discussion / Conclusion Lower proportions of Black and Hispanic patients underwent outpatient endoscopies during and after the first wave. The proportion of procedures done for emergent indications, and their diagnostic yield, increased during the pandemic, suggesting a higher threshold to perform endoscopy. In resource-sparing conditions, clinicians should pay attention to thresholds to perform colonoscopy for bleeding, and to racial disparities in outpatient healthcare access.
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http://dx.doi.org/10.1159/000515431DOI Listing
February 2021

Risk of Severe Covid-19 in Patients with Celiac Disease: A Population-Based Cohort Study.

Clin Epidemiol 2021 18;13:121-130. Epub 2021 Feb 18.

Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA.

Background: Patients with celiac disease (CeD) are at increased risk of certain viral infections and of pneumococcal pneumonia, raising concerns that they may be susceptible to severe coronavirus disease 2019 (Covid-19). We aimed to quantify the association between CeD and severe outcomes related to Covid-19.

Methods: We performed a population-based cohort study, identifying individuals with CeD in Sweden, as defined by small intestinal villus atrophy diagnosed at all (n=28) Swedish pathology departments during the years spanning 1969-2017, and alive on February 1, 2020. We compared these patients to controls matched by sex, age, county, and calendar period. We performed Cox proportional hazards with follow-up through July 31, 2020, assessing risk of 1) hospital admission with a primary diagnosis of laboratory-confirmed Covid-19 (co-primary outcome); and 2) severe disease as defined by admission to intensive care unit and/or death attributed to Covid-19 (co-primary outcome).

Results: Among patients with CeD (n=40,963) and controls (n=183,892), the risk of hospital admission for Covid-19 was 2.9 and 2.2 per 1000 person-years respectively. After adjusting for comorbidities, the risk of hospitalization for Covid-19 was not significantly increased in patients with CeD (HR 1.10; 95% CI 0.80-1.50), nor was the risk of severe Covid-19 increased (HR 0.97; 95% CI 0.59-1.59). Results were similarly null when we compared CeD patients to their non-CeD siblings with regard to these outcomes. Among all patients with CeD and controls hospitalized with a diagnosis of Covid-19 (n=58 and n=202, respectively), there was no significant difference in mortality (HR for CeD compared to controls 0.96; 95% CI 0.46-2.02).

Conclusion: In this population-based study, CeD was not associated with an increased risk of hospitalization for Covid-19 or intensive care unit and/or death attributed to Covid-19.
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http://dx.doi.org/10.2147/CLEP.S294391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899312PMC
February 2021

Chemical and Toxicological Properties of Emissions from a Light-Duty Compressed Natural Gas Vehicle Fueled with Renewable Natural Gas.

Environ Sci Technol 2021 Mar 8;55(5):2820-2830. Epub 2021 Feb 8.

Department of Civil and Environmental Engineering, University of California - Davis, Davis, California 95616, United States.

Biogas consisting primarily of methane (CH) and carbon dioxide (CO) can be upgraded to a transportation fuel referred to as renewable natural gas (RNG) by removing CO and other impurities. RNG has energy content comparable to fossil compressed natural gas (CNG) but with lower life-cycle greenhouse gas (GHG) emissions. In this study, a light-duty cargo van was tested with CNG and two RNG blends on a chassis dynamometer in order to compare the toxicity of the resulting exhaust. Tests for reactive oxygen species (ROS), biomarker expressions (CYP1A1, IL8, COX-2), and mutagenicity (Ames) show that RNG exhaust has toxicity that is comparable or lower than CNG exhaust. Statistical analysis reveals associations between toxicity and tailpipe emissions of benzene, dibenzofuran, and dihydroperoxide dimethyl hexane (the last identification is considered tentative/uncertain). Further gas-phase toxicity may be associated with tailpipe emissions of formaldehyde, dimethyl sulfide, propene, and methyl ketene. CNG exhaust contained higher concentrations of these potentially toxic chemical constituents than RNG exhaust in all of the current tests. Photochemical aging of the vehicle exhaust did not alter these trends. These preliminary results suggest that RNG adoption may be a useful strategy to reduce the carbon intensity of transportation fuels without increasing the toxicity of the vehicle exhaust.
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http://dx.doi.org/10.1021/acs.est.0c04962DOI Listing
March 2021

Immunophenotypic Spectrum and Genomic Landscape of Refractory Celiac Disease Type II.

Am J Surg Pathol 2021 Feb 2. Epub 2021 Feb 2.

*Department of Pathology and Cell Biology, Columbia University Irving Medical Center †Department of Medicine, Celiac Disease Center, Columbia University Irving Medical Center, New York, NY ‡Department of Pathology, University of Virginia, Charlottesville, VA §Bacchi Laboratory, Pathology Reference Laboratory, Botucatu, Brazil.

Refractory celiac disease type II (RCD II), also referred to as "cryptic" enteropathy-associated T-cell lymphoma (EATL) or "intraepithelial T-cell lymphoma," is a rare clonal lymphoproliferative disorder that arises from innate intraepithelial lymphocytes. RCD II has a poor prognosis and frequently evolves to EATL. The pathogenesis of RCD II is not well understood and data regarding the immunophenotypic spectrum of this disease and underlying genetic alterations are limited. To gain further biological insights, we performed comprehensive immunophenotypic, targeted next-generation sequencing, and chromosome microarray analyses of 11 RCD II cases: CD4/CD8 (n=6), CD8 (n=4), and CD4 (n=1), and 2 of 3 ensuing EATLs. Genetic alterations were identified in 9/11 (82%) of the RCD II cases. All 9 displayed mutations in members of the JAK-STAT signaling pathway, including frequent, recurrent STAT3 (7/9, 78%) and JAK1 (4/9, 44%) mutations, and 9/10 evaluable cases expressed phospho-STAT3. The mutated cases also harbored recurrent alterations in epigenetic regulators (TET2, n=5 and KMT2D, n=5), nuclear factor-κB (TNFAIP3, n=4), DNA damage repair (POT1, n=3), and immune evasion (CD58, n=2) pathway genes. The CD4/CD8 and other immunophenotypic subtypes of RCD II exhibited similar molecular features. Longitudinal genetic analyses of 4 RCD II cases revealed stable mutation profiles, however, additional mutations were detected in the EATLs, which occurred at extraintestinal sites and were clonally related to antecedent RCD II. Chromosome microarray analysis demonstrated copy number changes in 3/6 RCD II cases, and 1 transformed EATL with sufficient neoplastic burden for informative analysis. Our findings provide novel information about the immunophenotypic and genomic characteristics of RCD II, elucidate early genetic events in EATL pathogenesis, and reveal potential therapeutic targets.
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http://dx.doi.org/10.1097/PAS.0000000000001658DOI Listing
February 2021

Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific translation in epithelial cells.

Gut 2021 Feb 1. Epub 2021 Feb 1.

Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV-EHU), Leioa, Spain

Objectives: Coeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nucleotide polymorphism (SNP) located in the 5'UTR of in the inflammatory environment characteristic of the coeliac intestinal epithelium.

Design: The function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (mA)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD.

Results: Individuals harbouring the risk allele had higher mA methylation in the 5'UTR of RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall mA methylation in humans as well as in in vitro and in vivo models.

Conclusion: We identify a novel mA-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at mA proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.
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http://dx.doi.org/10.1136/gutjnl-2020-322566DOI Listing
February 2021

All Things Gluten: A Review.

Gastroenterol Clin North Am 2021 Mar;50(1):29-40

Division of Gastroenterology and Hepatology, Department of Medicine, University of Florida, 1329 Southwest 16th Street, Suite 5251, Gainesville, FL 32608, USA. Electronic address:

Gluten is a common dietary component with a complex protein structure. It forms incomplete products of digestion, which have the potential to mount an immune response in genetically predisposed individuals, resulting in celiac disease. It also has been linked with nonceliac gluten sensitivity and irritable bowel syndrome due to wheat allergy. A gluten-free diet is an effective treatment of these conditions; however, it can lead to micronutrient and mineral deficiencies and a macronutrient imbalance with higher sugar and lipid intake. Recent popularity has led to greater availability, but increasing cost, of commercially available gluten-free products.
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http://dx.doi.org/10.1016/j.gtc.2020.10.007DOI Listing
March 2021

Innate Lymphoid Cells and Celiac Disease: Current Perspective.

Cell Mol Gastroenterol Hepatol 2021 10;11(3):803-814. Epub 2020 Dec 10.

Department of Medicine, Celiac Disease Center, Columbia University Irving Medical Center, New York, New York; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York. Electronic address:

Celiac disease (CD) is a common autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals. Although the mechanisms underlying gliadin-mediated activation of adaptive immunity in CD have been well-characterized, regulation of innate immune responses and the functions of certain immune cell populations within the epithelium and lamina propria are not well-understood at present. Innate lymphoid cells (ILCs) are types of innate immune cells that have lymphoid morphology, lack antigen-specific receptors, and play important roles in tissue homeostasis, inflammation, and protective immune responses against pathogens. Information regarding the diversity and functions of ILCs in lymphoid organs and at mucosal sites has grown over the past decade, and roles of different ILC subsets in the pathogenesis of some inflammatory intestinal diseases have been proposed. However, our understanding of the contribution of ILCs toward the initiation and progression of CD is still limited. In this review, we discuss current pathophysiological aspects of ILCs within the gastrointestinal tract, findings of recent investigations characterizing ILC alterations in CD and refractory CD, and suggest avenues for future research.
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http://dx.doi.org/10.1016/j.jcmgh.2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851184PMC
December 2020

The Distribution of Gastrointestinal Pathogens on Stool PCR Prior to the Development of IBD.

J Clin Gastroenterol 2020 Nov 25. Epub 2020 Nov 25.

Division of Digestive and Liver Diseases, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.

Goals: We investigated the distribution of pathogens on stool gastrointestinal (GI) polymerase chain reaction (PCR) testing in those who subsequently developed inflammatory bowel disease (IBD).

Background: Infectious gastroenteritis has been associated with later development of IBD.

Study: This retrospective study includes patients of all ages hospitalized for diarrhea with positive GIPCR panel and subsequently a new diagnosis of IBD [confirmed by chart review and International Classification of Disease, Clinical Modification code for Crohn's disease (CD) or ulcerative colitis (UC)], between March 2015 to September 2019 at our quaternary care institution. Patients with IBD diagnosis before GIPCR were excluded. Descriptive statistics characterized the distribution of microbial pathogens in relation to later IBD diagnosis.

Results: Fifty-four participants were eligible (UC 44%; CD 56%). Median age at time of IBD diagnosis was 35 years [interquartile range (IQR) 18 to 65]. Median time between GIPCR and IBD diagnosis was 3 months (IQR 2 to 9) for all patients. When stratified by organism class, median time to diagnosis was 6 months (IQR 2 to 10) for patients with bacteria, 3 months (IQR 1 to 8) for patients with viruses, and 1 month (IQR 0.75 to 1) for patients with parasites (log-rank P=0.001). Sixty-nine unique pathogens (83% bacteria) were identified on all tests. Escherichia coli was the most common species (71%), of which enteropathogenic E. coli was predominant (38%).

Conclusions: The E. coli species, specifically enteropathogenic E. coli, may be implicated in the development of IBD. This is one of the first studies to evaluate the results of stool GIPCR in the link between the microbiome and IBD pathogenesis.
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http://dx.doi.org/10.1097/MCG.0000000000001470DOI Listing
November 2020

Elucidating nanoscale mechanical properties of diabetic human adipose tissue using atomic force microscopy.

Sci Rep 2020 11 24;10(1):20423. Epub 2020 Nov 24.

Department of Surgery, Section of General Surgery, University of Michigan Medical School, 2210 Taubman Center-5343, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109-5343, USA.

Obesity-related type 2 diabetes (DM) is a major public health concern. Adipose tissue metabolic dysfunction, including fibrosis, plays a central role in DM pathogenesis. Obesity is associated with changes in adipose tissue extracellular matrix (ECM), but the impact of these changes on adipose tissue mechanics and their role in metabolic disease is poorly defined. This study utilized atomic force microscopy (AFM) to quantify difference in elasticity between human DM and non-diabetic (NDM) visceral adipose tissue. The mean elastic modulus of DM adipose tissue was twice that of NDM adipose tissue (11.50 kPa vs. 4.48 kPa) to a 95% confidence level, with significant variability in elasticity of DM compared to NDM adipose tissue. Histologic and chemical measures of fibrosis revealed increased hydroxyproline content in DM adipose tissue, but no difference in Sirius Red staining between DM and NDM tissues. These findings support the hypothesis that fibrosis, evidenced by increased elastic modulus, is enhanced in DM adipose tissue, and suggest that measures of tissue mechanics may better resolve disease-specific differences in adipose tissue fibrosis compared with histologic measures. These data demonstrate the power of AFM nanoindentation to probe tissue mechanics, and delineate the impact of metabolic disease on the mechanical properties of adipose tissue.
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http://dx.doi.org/10.1038/s41598-020-77498-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686328PMC
November 2020

Risk of Skin Disorders in Patients with Celiac Disease: A Population-Based Cohort Study.

J Am Acad Dermatol 2020 Oct 31. Epub 2020 Oct 31.

Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York NY, USA; Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden.

Background And Aims: Although dermatitis herpetiformis is closely associated with celiac disease (CD), data on the relationship between CD and other dermatologic disorders have been mixed. We aimed to quantify the risk of skin disorders in patients after CD diagnosis in a population-based setting.

Methods: Using data from all 28 pathology departments in Sweden 1969-2016, we identified patients with CD. Each patient was matched by age, sex, calendar year, and geographic region to up to 5 population controls. We calculated the risk of any skin disease and specific skin diseases using Cox proportional hazards.

Results: We identified 43,300 patients with CD and 198,532 matched controls. After a median follow-up time of 11.4 years, the incidences of skin disease in CD patients and controls were 22.6 and 14.8 per 1000 person-years respectively (HR=1.55; 95%CI 1.51-1.58). Increased risks were present for eczema (HR=1.67; 95%CI 1.56-1.79), psoriasis (HR=1.55; 95%CI 1.43-1.68), urticaria (HR=1.52; 95% CI 1.42-1.64), vitiligo (HR=1.90; 95%CI 1.52-2.39), acne (HR=1.39; 95%CI 1.29-1.50), and alopecia areata (HR=1.78; 95%CI 1.43-2.20).

Conclusions: Compared to the general population, patients with CD are at increased risk of multiple common skin disorders, a risk that persists in the long-term.
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http://dx.doi.org/10.1016/j.jaad.2020.10.079DOI Listing
October 2020

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

Gut 2021 May 2;70(5):876-883. Epub 2020 Nov 2.

Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK

Objective: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.

Design: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD.

Results: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively.

Conclusion: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.
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http://dx.doi.org/10.1136/gutjnl-2020-320913DOI Listing
May 2021

Risk of Adverse Outcomes in Hospitalized Patients With Autoimmune Disease and COVID-19: A Matched Cohort Study From New York City.

J Rheumatol 2020 Nov 1. Epub 2020 Nov 1.

This work was supported by the National Institutes of Health (T32 DK083256 to ASF, K23AR075112 to EJB) and The Louis and Gloria Flanzer Philanthropic Trust (to BL). A.S. Faye, MD, MS, Department of Medicine, Division of Digestive and Liver Diseases, NewYork-Presbyterian/Columbia University Irving Medical Center, Department of Medicine, Henry D. Janowitz Division of Gastroenterology, Mount Sinai Hospital; K.E. Lee, BA, Vagelos College of Physicians and Surgeons, Columbia University; M. Laszkowska, MD, MS, J. Kim, MD, J.W. Blackett, MD, A. Krigel, MD, MS, P.H. Green, MD, S. Krishnareddy, MD, MS, C. Hur, MD, MPH, B. Lebwohl, MD, MS, Department of Medicine, Division of Digestive and Liver Diseases, NewYork-Presbyterian/Columbia University Irving Medical Center; A.S. McKenney, MD, PhD, MPH, Department of Radiology, NewYork-Presbyterian/Weill Cornell Medical College; J.T. Giles, MD, MPH, R. Wang, MD, MHS, E.J. Bernstein, MD, MSc, Department of Medicine, Division of Rheumatology, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, New York, USA. The authors report no conflicts of interest. Address correspondence to Dr. A.S. Faye, Present/Levison Advanced IBD Fellow, The Susan and Leonard Feinstein IBD Center, The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, 1468 Madison Ave, Annenberg RM 5-12, New York, NY 10029. Email: Accepted for publication October 8, 2020.

Objective: To examine the effect of autoimmune (AI) disease on the composite outcome of intensive care unit (ICU) admission, intubation, or death from COVID-19 in hospitalized patients.

Methods: Retrospective cohort study of 186 patients hospitalized with COVID-19 between March 1, 2020, and April 15, 2020 at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center. The cohort included 62 patients with AI disease and 124 age- and sex-matched controls. The primary outcome was a composite of ICU admission, intubation, and death, with secondary outcome as time to in-hospital death. Baseline demographics, comorbidities, medications, vital signs, and laboratory values were collected. Conditional logistic regression and Cox proportional hazards regression were used to assess the association between AI disease and clinical outcomes.

Results: Patients with AI disease were more likely to have at least one comorbidity (87.1% vs 74.2%, = 0.04), take chronic immunosuppressive medications (66.1% vs 4.0%, < 0.01), and have had a solid organ transplant (16.1% vs 1.6%, < 0.01). There were no significant differences in ICU admission (13.7% vs 19.4%, = 0.32), intubation (13.7% vs 17.7%, = 0.47), or death (16.1% vs 14.5%, = 0.78). On multivariable analysis, patients with AI disease were not at an increased risk for a composite outcome of ICU admission, intubation, or death (OR 0.79, 95% CI 0.37-1.67). On Cox regression, AI disease was not associated with in-hospital mortality (HR 0.73, 95% CI 0.33-1.63).

Conclusion: Among patients hospitalized with COVID-19, individuals with AI disease did not have an increased risk of a composite outcome of ICU admission, intubation, or death.
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http://dx.doi.org/10.3899/jrheum.200989DOI Listing
November 2020

The Risk of Contracting COVID-19 Is Not Increased in Patients With Celiac Disease.

Clin Gastroenterol Hepatol 2021 02 12;19(2):391-393. Epub 2020 Oct 12.

Farncombe Family Digestive Health Research Institute, McMaster University Medical Center, Hamilton Health Sciences, Hamilton, Ontario, Canada. Electronic address:

The World Health Organization declared coronavirus disease-2019 (COVID-19) a global pandemic in March 2020. Since then, there are more than 34 million cases of COVID-19 leading to more than 1 million deaths worldwide. Numerous studies suggest that celiac disease (CeD), a chronic immune-mediated gastrointestinal condition triggered by gluten, is associated with an increased risk of respiratory infections. However, how it relates to the risk of COVID-19 is unknown. To address this gap, we conducted a cross-sectional study to evaluate whether patients with self-reported CeD are at an increased risk of contracting COVID-19.
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http://dx.doi.org/10.1016/j.cgh.2020.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548761PMC
February 2021

High-Frequency Palatal Tremor and Stimulus-Sensitive Leg Myoclonus with Degeneration of Inferior Olivary Nuclei in Celiac Disease.

Mov Disord Clin Pract 2020 Sep 29;7(Suppl 3):S93-S95. Epub 2020 Sep 29.

Division of Movement Disorders, Department of Neurology Columbia University New York City New York USA.

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http://dx.doi.org/10.1002/mdc3.13079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525195PMC
September 2020

Celiac disease serology and gut microbiome following proton pump inhibitor treatment.

Medicine (Baltimore) 2020 08;99(35):e21488

Department of Medicine.

Background: Celiac disease is an autoimmune enteropathy characterized by an aberrant immune response to ingested gluten in genetically predisposed individuals. Studies have pointed to a rising prevalence of celiac disease in recent decades. Changes in diet and use of medication that may impact the gut microbiome have been suggested as potential contributors. Exposure to proton pump inhibitors (PPIs) was recently found to be associated with an increased risk for subsequent diagnosis of celiac disease. We aimed to investigate potential mechanisms for this link by examining the relationship between PPI use and gluten-related immune responses in the context of changes in gut microbiome.

Methods: We performed a post hoc analysis of blood and fecal samples from a recent randomized trial in order to assess the potential association between PPI use and development of celiac disease serology in conjunction with alterations in gastrointestinal microbial composition. The study included 12 healthy participants who were administered a PPI (Omeprazole; 40 mg twice daily) for 4 or 8 weeks.

Results: The analysis did not reveal an overall significant change in levels of serologic markers of celiac disease for the study cohort in response to PPI treatment. However, one individual developed a marked increase in the celiac disease-specific autoantibody response to transglutaminase 2 in conjunction with enhanced immune reactivity to gluten during the trial. Genotyping revealed positivity for the celiac disease-associated HLA-DQ2 and -DQ8 alleles. Furthermore, the observed elevation in antibody responses was closely associated with a sharp increase in fecal abundance of bacteria of the order Actinomycetales.

Conclusions: The results of this exploratory analysis support further investigation of molecular mechanisms involved in the contribution of PPIs to celiac disease risk through the potential enhancement of gluten immunopathology and changes in gut microbial population.
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http://dx.doi.org/10.1097/MD.0000000000021488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458245PMC
August 2020

Veritable Vascular Changes: Answer.

Am J Dermatopathol 2020 09;42(9):706-707

Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.

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http://dx.doi.org/10.1097/DAD.0000000000001425DOI Listing
September 2020

Quality and Content of Online Patient Resources for Celiac Disease.

Dig Dis Sci 2020 Aug 20. Epub 2020 Aug 20.

The Celiac Disease Center at Columbia University, 180 Fort Washington Avenue, Suite 936, New York, NY, 10032, USA.

Background And Aims: Patient-directed information on celiac disease has been reported to be of variable quality. We assessed the quantity and quality of information on blogs and Web sites intended to inform the layperson of celiac disease information.

Methods: We performed a cross-sectional study analyzing celiac disease blogs and Web sites intended for the layperson. We searched from 20 cities, resulting in 55 Web sites. These sites were analyzed for 38 criteria that considered relevant clinical information for people with celiac disease. Claims were classified as true, false, or not proven. The readability level of each Web site was determined.

Results: The 55 Web sites were categorized as national organizations, personal blogs, recipe-based blogs, or commercial/marketing Web sites. Only 40% of Web sites contained more than 50% of criteria. Of 212 claims assessed, 97% were found to be accurate. National organizations included the most criteria, followed by recipe-based blogs, then personal blogs, and lastly commercial/marketing Web sites. Additionally, national organizations had the highest proportion of accurate claims, followed by personal blogs, then commercial/marketing Web sites, and recipe-based blogs with the most inaccurate information. The average readability level of overall was 9.7, above the recommended readability level for patient education materials.

Conclusions: A significant number of online claims regarding celiac disease were true, but the majority of patient-facing Web sites are missing large amounts of relevant information. This warrants efforts to improve the quality of medical information published online.
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http://dx.doi.org/10.1007/s10620-020-06537-3DOI Listing
August 2020

Psychiatric Disorders in Patients With a Diagnosis of Celiac Disease During Childhood From 1973 to 2016.

Clin Gastroenterol Hepatol 2020 Aug 12. Epub 2020 Aug 12.

Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, New York; Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden. Electronic address:

Background & Aims: Few studies have explored the link between childhood celiac disease and long-term psychiatric comorbidities. We performed a population-based cohort study of associations between childhood celiac disease and psychiatric disorders and investigated whether risk persists into adulthood.

Methods: We performed a nationwide study in Sweden using data from the Epidemiology Strengthened by histoPathology Reports in Sweden cohort. In this cohort, 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016 were identified from Sweden's 28 pathology departments. Each patient was matched with as many as 5 reference children (controls, n = 94,249). Data on psychiatric disorders were obtained from the patient register. We used Cox proportional modeling to estimate hazard ratios (HRs).

Results: During a median follow-up period of 12.3 years, 3174 children (16.5%) with celiac disease received a new diagnosis of a psychiatric disorder, compared with 13,286 controls (14.1%). Corresponding incidence rates were 12.2 per 1000 person-years (95% CI, 11.8-12.7) vs 10.3 per 1000 person-years (95% Cl, 10.2-10.5). Childhood celiac disease was associated with a 19% increase in risk of any psychiatric disorder (95% CI, 1.14-1.23); the increase in risk was observed in all childhood age groups. The highest HRs were seen in the first year after celiac diagnosis (HR, 1.70; 95% CI, 1.41-2.05). The risk increase persisted into adulthood (age, >18 y: HR, 1.11; 95% CI, 1.04-1.17). We found increased risks of mood disorders (HR, 1.20; 95% CI, 1.12-1.28), anxiety disorders (HR, 1.12; 95% CI, 1.06-1.19), eating disorders (HR, 1.34; 95% CI, 1.18-1.51), attention deficit hyperactivity disorder (HR, 1.29; 95% CI, 1.20-1.39), and autism spectrum disorder (HR, 1.47; 95% CI, 1.32-1.64). We found no statistically significant risk increase for psychotic disorders, psychoactive substance misuse, behavioral disorders, personality disorders, suicide attempt, or suicide. Celiac disease also was linked to an increased use of psychiatric drugs (HR, 1.34; 95% CI, 1.24-1.43). A conditional logistic regression found that psychiatric disorders also were more common before a diagnosis of celiac disease (odds ratio, 1.56; 95% CI, 1.39-1.76).

Conclusions: Childhood celiac disease is associated with an increased risk of subsequent psychiatric disorders, which persists into adulthood. Mental health surveillance should be integral in the care of celiac disease.
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http://dx.doi.org/10.1016/j.cgh.2020.08.018DOI Listing
August 2020

Correction to: Hispanic Spinocerebellar Ataxia Type 35 (SCA35) with a Novel Frameshift Mutation.

Cerebellum 2021 Feb;20(1):140

Department of Neurology, Columbia UniversityMedical Center, 650 West 168th Street, Room 305, New York, NY, 10032, USA.

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http://dx.doi.org/10.1007/s12311-020-01169-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022887PMC
February 2021

Subclass Profile of IgG Antibody Response to Gluten Differentiates Nonceliac Gluten Sensitivity From Celiac Disease.

Gastroenterology 2020 11 21;159(5):1965-1967.e2. Epub 2020 Jul 21.

Department of Medicine, Columbia University Medical Center, New York, New York; Institute of Human Nutrition, Columbia University Medical Center, New York, New York; Celiac Disease Center, Columbia University Medical Center, New York, New York; Department of Medicine, New York Medical College, Valhalla, New York. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.07.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680445PMC
November 2020

Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease.

Gastroenterology 2020 11 15;159(5):1686-1694.e2. Epub 2020 Jul 15.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.

Background & Aims: The incidence of small bowel cancers is increasing. Associations have been made between celiac disease (CD) and small bowel cancers, but there have been no detailed studies of large cohorts.

Methods: Through the nationwide Epidemiology Strengthened by Histopathology Reports in Sweden cohort study, we retrieved data from Sweden's 28 pathology departments on all individuals who received a diagnosis of CD from 1965 through 2017. Individuals with CD, defined as duodenal or jejunal villous atrophy (stage 3 Marsh score), were matched with as many as 5 randomly selected reference individuals from the general population. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids.

Results: During a median follow-up of 11 years, we identified 48,119 individuals with CD (patients) and 239,249 reference individuals. Beginning at 1 year after a diagnosis of CD, 29 patients (0.06%) received a diagnosis of small bowel adenocarcinoma vs 45 reference individuals (0.02%), 7 patients received a diagnosis of carcinoids vs 31 reference individuals, and 48 patients received a diagnosis of adenomas vs 50 reference individuals. Corresponding HRs were small bowel adenocarcinoma 3.05 (95% confidence interval [CI], 1.86-4.99), carcinoids 0.59 (95% CI, 0.16-2.10), and adenomas 5.73 (95% CI, 3.70-8.88). HRs were independent of sex and age. Overall, there was 1 extra case of small bowel adenocarcinoma in every 2944 patients with CD followed for 10 years. There was an inverse association between mucosal healing risk of future small bowel adenocarcinoma (HR, 0.18; 95% CI, 0.02-1.61), although the HR failed to attain statistical significance.

Conclusions: In an analysis of a nationwide pathology database in Sweden, we found the absolute risk of small bowel adenocarcinoma is low in individuals with CD. However, risks of small bowel adenocarcinoma and adenomas (but not carcinoids) are significantly increased in people with CD compared to people without this disease.
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http://dx.doi.org/10.1053/j.gastro.2020.07.007DOI Listing
November 2020

Delays in colonoscopy start time are associated with reductions in adenoma detection rates.

Dig Liver Dis 2020 08 2;52(8):905-908. Epub 2020 Jul 2.

Celiac Disease Center, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address:

Background: Prior investigations of the impact of case delays on adenoma detection rates have not found a significant association, though these studies included modest delays, with few cases delayed by more than one hour.

Aims: The aim of this study was to measure the impact of prolonged case delays on the colonoscopy outcome measures of adenoma detection rate and withdrawal time.

Methods: We performed a single center cohort study including patients aged ≥50 years undergoing screening colonoscopy during a 4.5 year period. Using multivariate regression, we measured the impact of delays on adenoma detection rate and withdrawal time, adjusting for age, gender, endoscopist, time of day of the procedure, and bowel preparation quality.

Results: Of 7905 screening colonoscopies, 2503 (32%) were delayed by >1 h. On multivariable analysis, cases delayed 1-2 h were associated with a significant decrease in adenoma detection rate relative to cases delayed ≤1 h (OR 0.88, 95% CI 0.78-1.00, p = 0.049). Withdrawal time was not significantly associated with case delays.

Conclusions: Prolonged case delays over 1 h are associated with reduced adenoma detection rates. Future research on factors underlying prolonged delays may help mitigate these barriers to care and improve quality outcomes.
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http://dx.doi.org/10.1016/j.dld.2020.06.011DOI Listing
August 2020

Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs.

Genome Biol 2020 06 29;21(1):153. Epub 2020 Jun 29.

Hackensack-Meridian Health Center for Discovery and Innovation, Nutley, NJ, 07110, USA.

Background: Mapping of allele-specific DNA methylation (ASM) can be a post-GWAS strategy for localizing regulatory sequence polymorphisms (rSNPs). The advantages of this approach, and the mechanisms underlying ASM in normal and neoplastic cells, remain to be clarified.

Results: We perform whole genome methyl-seq on diverse normal cells and tissues and three cancer types. After excluding imprinting, the data pinpoint 15,112 high-confidence ASM differentially methylated regions, of which 1838 contain SNPs in strong linkage disequilibrium or coinciding with GWAS peaks. ASM frequencies are increased in cancers versus matched normal tissues, due to widespread allele-specific hypomethylation and focal allele-specific hypermethylation in poised chromatin. Cancer cells show increased allele switching at ASM loci, but disruptive SNPs in specific classes of CTCF and transcription factor binding motifs are similarly correlated with ASM in cancer and non-cancer. Rare somatic mutations affecting these same motif classes track with de novo ASM. Allele-specific transcription factor binding from ChIP-seq is enriched among ASM loci, but most ASM differentially methylated regions lack such annotations, and some are found in otherwise uninformative "chromatin deserts."

Conclusions: ASM is increased in cancers but occurs by a shared mechanism involving disruptive SNPs in CTCF and transcription factor binding sites in both normal and neoplastic cells. Dense ASM mapping in normal plus cancer samples reveals candidate rSNPs that are difficult to find by other approaches. Together with GWAS data, these rSNPs can nominate specific transcriptional pathways in susceptibility to autoimmune, cardiometabolic, neuropsychiatric, and neoplastic diseases.
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http://dx.doi.org/10.1186/s13059-020-02059-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322865PMC
June 2020

Statistical analysis of trace contaminants measured in biogas.

Sci Total Environ 2020 Aug 15;729:138702. Epub 2020 Apr 15.

Department of Civil and Environmental Engineering, University of California at Davis, 1 Shields Avenue, Davis, CA 95616, United States of America. Electronic address:

Biogas is a renewable energy fuel that can be treated to increase purity so that the resulting "biomethane" can be injected into the natural gas pipeline grid. The trace contaminants in biogas and biomethane make up a small fraction of the total gas but they still have the potential to cause adverse health effects and pipeline corrosion. This study investigates the statistical distributions of 17 trace metals, six mercaptans, hydrogen sulfide, ammonia, and six additional trace organic compounds. Twelve of these 31 trace contaminants have been previously identified as constituents of concern based on their toxicity profiles and through health risk assessment studies. Untreated and treated samples of biogas were collected from 12 different biogas production facilities using diverse feedstocks throughout California. Results show that most biogas trace contaminants follow a single log-normal distribution or a bi-modal lognormal distribution depending on the type of production facility. Treatment of biogas demonstrates some removal for all trace contaminants, but four constituents of concern (copper, lead, hydrogen sulfide, and methyl mercaptan) are predicted to have a >1% probability of exceeding trigger levels even after common treatments. This finding suggests that enhanced monitoring may be warranted for these contaminants. Several trace metals and volatile organic compounds (VOCs) were found to have seasonal trends with greater concentrations in the summer and lower concentrations in the winter suggesting that seasonal variation should be considered in future monitoring plans.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138702DOI Listing
August 2020

COVID-19 and the difficulty of inferring epidemiological parameters from clinical data.

Lancet Infect Dis 2021 01 28;21(1):27-28. Epub 2020 May 28.

School of Mathematics, University of Bristol, Bristol BS8 1UG, UK.

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http://dx.doi.org/10.1016/S1473-3099(20)30437-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255708PMC
January 2021