Publications by authors named "David Buckley"

255 Publications

Update Alert 8: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Ann Intern Med 2021 03 30. Epub 2021 Mar 30.

Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon (R.C., T.D., S.S., A.M.T.).

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http://dx.doi.org/10.7326/L21-0143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017477PMC
March 2021

Efficacy of Chlorine Dioxide Gas Against Hepatitis A Virus on Blueberries, Blackberries, Raspberries, and Strawberries.

Food Environ Virol 2021 Mar 10. Epub 2021 Mar 10.

U.S. Department of Agriculture, Agricultural Research Service, Food Safety and Intervention Technologies Research Unit, Delaware State University, 1200 North DuPont Hwy, Dover, DE, 19901, USA.

Seeking a means of sanitizing berries, the effectiveness of steady state levels of gaseous chlorine dioxide (ClO) against hepatitis A virus (HAV) on laboratory-contaminated berries was determined. The generated ClO was maintained with 1 or 2 mg/l air inside a 269-l glove box to treat 50 g batches of blueberries, raspberries, and blackberries, and 100 g batches of strawberries that were immersion coated with HAV. Normalized data for ClO (ppm-h/g product) is reported as a function of ClO concentration, treatment time, and weight of treated product. Treatments of ClO ranging from 1.00 to 6.27 ppm-h/g berry were evaluated. When compared to untreated HAV-contaminated berries, log reductions of HAV were > 2.1 for all berry types and conditions tested indicating the gaseous ClO was effective. The average log reduction with strawberries, raspberries, blueberries and blackberries treated with 1.00 ppm-h/g, the lowest ClO treatment tested, were 2.44, 2.49, 3.23, and 3.45, respectively. The highest treatment of 6.27 ppm-h/g was applied at two different gas concentrations of 1 mg/l and 2 mg/l. Average log reductions for blueberries and strawberries treated with 6.27 ppm-h/g were 4.34 and 4.42, and 4.03 and 3.51, applied at 1 mg/l and 2 mg/l, respectively. For blackberries and raspberries 3.20 and 3.24, and 3.23 and 3.97 log reductions were observed for 6.27 ppm-h/g treatments applied at 1 mg/l and 2 mg/l, respectively. Results indicate that HAV contamination of berries can be substantially reduced by gaseous ClO and offer industry a waterless means of sanitizing berries against HAV.
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http://dx.doi.org/10.1007/s12560-021-09465-1DOI Listing
March 2021

Update Alert 7: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Ann Intern Med 2021 02 9. Epub 2021 Feb 9.

Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon (R.C., T.D., S.S., A.M.T.).

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http://dx.doi.org/10.7326/L21-0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893536PMC
February 2021

Variants of leading to congenital myasthenic syndrome in two children with varying presentations.

BMJ Case Rep 2021 Jan 18;14(1). Epub 2021 Jan 18.

Genetics, Memorial University of Newfoundland Faculty of Medicine, St. John's, Newfoundland and Labrador, Canada.

This report describes the variation in presentation of two unrelated patients found to have a rare form of presynaptic congenital myasthenic syndrome. Both patients presented with hypotonia, ptosis, poor weight gain and apneic episodes. Through whole exome sequencing, our patients were found to have the same likely pathogenic biallelic variants in W315X and I200N of , encoding vesicular acetylcholine transporter (VAChT). These specific variants in have not been previously described in the literature. We illustrate the variety in clinical presentation and course of children with mutations in , leading to presynaptic congenital myasthenic syndrome through VAChT deficiency.
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http://dx.doi.org/10.1136/bcr-2020-237799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813295PMC
January 2021

Multicentre, deep learning, synthetic-CT generation for ano-rectal MR-only radiotherapy treatment planning.

Radiother Oncol 2021 Mar 29;156:23-28. Epub 2020 Nov 29.

Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, United Kingdom; Radiotherapy Research Group, Leeds Institute of Medical Research, University of Leeds, United Kingdom.

Background And Purpose: Comprehensive dosimetric analysis is required prior to the clinical implementation of pelvic MR-only sites, other than prostate, due to the limited number of site specific synthetic-CT (sCT) dosimetric assessments in the literature. This study aims to provide a comprehensive assessment of a deep learning-based, conditional generative adversarial network (cGAN) model for a large ano-rectal cancer cohort. The following challenges were investigated; T2-SPACE MR sequences, patient data from multiple centres and the impact of sex and cancer site on sCT quality.

Method: RT treatment position CT and T2-SPACE MR scans, from two centres, were collected for 90 ano-rectal patients. A cGAN model trained using a focal loss function, was trained and tested on 46 and 44 CT-MR ano-rectal datasets, paired using deformable registration, respectively. VMAT plans were created on CT and recalculated on sCT. Dose differences and gamma indices assessed sCT dosimetric accuracy. A linear mixed effect (LME) model assessed the impact of centre, sex and cancer site.

Results: A mean PTV D95% dose difference of 0.1% (range: -0.5% to 0.7%) was found between CT and sCT. All gamma index (1%/1 mm threshold) measurements were >99.0%. The LME model found the impact of modality, cancer site, sex and centre was clinically insignificant (effect ranges: -0.4% and 0.3%). The mean dose difference for all OAR constraints was 0.1%.

Conclusion: Focal loss cGAN models using T2-SPACE MR sequences from multiple centres can produce generalisable, dosimetrically accurate sCTs for ano-rectal cancers.
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http://dx.doi.org/10.1016/j.radonc.2020.11.027DOI Listing
March 2021

The prevalence, child characteristics, and maternal risk factors for the continuum of fetal alcohol spectrum disorders: A sixth population-based study in the same South African community.

Drug Alcohol Depend 2021 Jan 13;218:108408. Epub 2020 Nov 13.

Sanford Children's Genomic Medicine Consortium, Sanford Health, and the University of South Dakota Sanford School of Medicine, Department of Pediatrics, 1600 W. 22nd St., Sioux Falls, SD, 57117, United States; Department of Pediatrics and the Center for Applied Genetics and Genomic Medicine, The University of Arizona College of Medicine, 1501 N. Campbell Avenue, Tucson, Arizona, 85724, United States.

Background: Prevalence and characteristics of fetal alcohol spectrum disorders (FASD) have been described previously in this community.

Methods: Active case ascertainment methods were employed in a new cross-sectional study with Revised Institute of Medicine criteria among first grade students (n = 735) via dysmorphology examinations and neurobehavioral assessments. Their mothers were interviewed regarding risk factors. Final diagnoses were assigned via structured case conferences.

Results: Children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and alcohol related-neurodevelopmental disorder (ARND) were significantly different from controls on all cardinal variables, multiple dysmorphology traits and neurobehavioral performance. Mothers of children with FASD reported significantly more drinking before and during pregnancy (mothers of children with FAS reported 7.8 (±6.1) drinks per drinking day (DDD) prior to pregnancy and 5.1 (±5.9) after pregnancy recognition). Distal risk variables for a diagnosis on the continuum of FASD were: lower maternal height, weight, and body mass index; higher gravidity; lower education and household income; and later pregnancy recognition. Alcohol and tobacco remain the only commonly used drugs. Women reporting first trimester drinking of two DDD were 13 times more likely (95 % CI:1.3-133.4) to have a child with FASD than non-drinkers; and those who reported drinking throughout pregnancy were 19.4 times more likely (95 % CI:8.2-46.0) to have a child with FASD.

Conclusion: Seventeen years after the first study in this community, FASD prevalence remains high at 16 %-31 %. The FAS rate may have declined somewhat, but rates of PFAS and ARND seemed to plateau, at a high rate.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756187PMC
January 2021

Update Alert 6: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Ann Intern Med 2021 01 24;174(1):W18-W19. Epub 2020 Nov 24.

Pacific Northwest Evidence-based Practice Center and School of Public Health, Oregon Health & Science University-Portland State University, Portland, Oregon.

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http://dx.doi.org/10.7326/L20-1323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711654PMC
January 2021

Update Alert 5: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Ann Intern Med 2020 12 20;173(11):W154-W55. Epub 2020 Oct 20.

Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon (R.C., T.D., S.S., A.M.T.).

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http://dx.doi.org/10.7326/L20-1227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576469PMC
December 2020

Update Alert 4: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Ann Intern Med 2020 10 11;173(8):143-144. Epub 2020 Sep 11.

Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon (R.C., T.D., S.S., A.M.T.).

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http://dx.doi.org/10.7326/L20-1134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505020PMC
October 2020

Complementary and Alternative Therapy Use in Children with Cerebral Palsy.

Can J Neurol Sci 2020 Aug 28:1-7. Epub 2020 Aug 28.

Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Objective: To describe complementary and alternative medicine (CAM) use amongst children with cerebral palsy (CP) in Canada and to identify factors associated with CAM use.

Methods: We conducted a cross-sectional study, utilising data from the Canadian CP Registry. We explored the association between CAM use and regional, socioeconomic and CP phenotypic variables, and parental perception of the family-centredness of clinical care using the Measures of Process of Care-56 (MPOC-56). Chi-square analyses were performed, and odds ratios (OR) and 95% confidence intervals (CI) were obtained. Mann-Whitney U tests were used to compare MPOC-56 scores between CAM users and non-CAM users.

Results: The study sample consisted of 313 families of which 27% reported CAM use in the past year. Children with CP using CAM were more likely to reside in Western Canada (OR 3.3, 95% CI 1.6-6.7), live in a two-parent household (OR 3.5, 95% CI 1.5-8.4), have an ataxic/hypotonic or dyskinetic CP subtype (OR 3.0, 95% CI 1.5-6.1) and have a greater motor impairment (OR 2.8, 95% CI 1.7-4.9). MPOC-56 subscale scores were not significantly associated with CAM use.

Conclusion: Physicians need to be aware of existing CAM therapies, the level of evidence supporting their efficacy (beneficence), their associated risks of adverse events (non-maleficence) and enable fair access to care that may be of benefit to each child.
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http://dx.doi.org/10.1017/cjn.2020.188DOI Listing
August 2020

Update Alert 3: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Ann Intern Med 2020 09 3;173(6):W123-W124. Epub 2020 Aug 3.

Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon (R.C., T.D., S.S., A.M.T.).

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http://dx.doi.org/10.7326/L20-1005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418491PMC
September 2020

Ocular measurements in fetal alcohol spectrum disorders.

Am J Med Genet A 2020 10 17;182(10):2243-2252. Epub 2020 Jul 17.

Department of Genetic Medicine, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Fetal alcohol spectrum disorders (FASD) describe a range of physical, behavioral, and neurologic deficits in individuals exposed to alcohol prenatally. Reduced palpebral fissure length is one of the cardinal facial features of FASD. However, other ocular measurements have not been studied extensively in FASD. Using the Fetal Alcohol Syndrome Epidemiologic Research (FASER) database, we investigated how inner canthal distance (ICD), interpupillary distance (IPD), and outer canthal distance (OCD) centiles differed between FASD and non-FASD individuals. We compared ocular measurement centiles in children with FASD to non-FASD individuals and observed reductions in all three centiles for ICD, IPD, and OCD. However, when our non-FASD children who had various forms of growth deficiency (microcephaly, short-stature, or underweight) were compared to controls, we did not observe a similar reduction in ocular measurements. This suggests that reductions in ocular measurements are a direct effect of alcohol on ocular development independent of its effect on growth parameters, which is consistent with animal models showing a negative effect of alcohol on developing neural crest cells. Interpupillary distance centile appeared to be the most significantly reduced ocular measure we evaluated, suggesting it may be a useful measure to be considered in the diagnosis of FASD.
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http://dx.doi.org/10.1002/ajmg.a.61759DOI Listing
October 2020

Update Alert 2: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Ann Intern Med 2020 08 14;173(4):W77. Epub 2020 Jul 14.

Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon (R.C., T.D., S.S., A.M.T.).

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http://dx.doi.org/10.7326/M20-4806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384269PMC
August 2020

Genome-wide DNA methylation analysis of KRAS mutant cell lines.

Sci Rep 2020 06 23;10(1):10149. Epub 2020 Jun 23.

Department of Translational Genomics, University of Southern California, Los Angeles, CA, 90033, USA.

Oncogenic RAS mutations are associated with DNA methylation changes that alter gene expression to drive cancer. Recent studies suggest that DNA methylation changes may be stochastic in nature, while other groups propose distinct signaling pathways responsible for aberrant methylation. Better understanding of DNA methylation events associated with oncogenic KRAS expression could enhance therapeutic approaches. Here we analyzed the basal CpG methylation of 11 KRAS-mutant and dependent pancreatic cancer cell lines and observed strikingly similar methylation patterns. KRAS knockdown resulted in unique methylation changes with limited overlap between each cell line. In KRAS-mutant Pa16C pancreatic cancer cells, while KRAS knockdown resulted in over 8,000 differentially methylated (DM) CpGs, treatment with the ERK1/2-selective inhibitor SCH772984 showed less than 40 DM CpGs, suggesting that ERK is not a broadly active driver of KRAS-associated DNA methylation. KRAS G12V overexpression in an isogenic lung model reveals >50,600 DM CpGs compared to non-transformed controls. In lung and pancreatic cells, gene ontology analyses of DM promoters show an enrichment for genes involved in differentiation and development. Taken all together, KRAS-mediated DNA methylation are stochastic and independent of canonical downstream effector signaling. These epigenetically altered genes associated with KRAS expression could represent potential therapeutic targets in KRAS-driven cancer.
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http://dx.doi.org/10.1038/s41598-020-66797-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311523PMC
June 2020

Update Alert: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

Ann Intern Med 2020 07 9;173(2):W46-W47. Epub 2020 Jun 9.

Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon (R.C., T.D., S.S., A.M.T.).

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http://dx.doi.org/10.7326/L20-0768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304657PMC
July 2020

Congenital Malformations in Children With Cerebral Palsy: Is Prematurity Protective?

Pediatr Neurol 2020 07 12;108:70-76. Epub 2020 Feb 12.

Department of Pediatrics, McGill University, Montreal, Quebec City, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, Canada. Electronic address:

Background: Congenital malformations are more common in children who are born prematurely, and prematurity is the leading risk factor for cerebral palsy. The primary objective of this study was to describe the profile of congenital malformations in a Canadian cohort of children with cerebral palsy. The secondary objectives were to compare the profiles of children with cerebral palsy with and without a congenital malformation and explore the possible role of prematurity.

Methods: This retrospective cohort study utilized data from the Canadian Cerebral Palsy Registry, a population based registry of children with a confirmed diagnosis of cerebral palsy. Differences between groups were compared using Pearson's chi-square and Student t test as appropriate. Odds ratios and 95% confidence intervals were calculated RESULTS: Congenital malformations were present in 23% participants. In term-born children, brain malformations were the most common, whereas heart and gastrointestinal malformations were more common in children born prematurely. Children with a malformation had higher odds of being born at term (odds ratio 1.57, 95% confidence interval 1.20 to 2.04); having hypotonic, ataxic, or dyskinetic cerebral palsy (odds ratio 1.92, 95% confidence interval 1.35 to 2.72; being nonambulatory (odds ratio 1.70, 95% confidence interval 1.29 to 2.25); and having cerebral palsy-associated comorbidities.

Conclusions: One in four children with cerebral palsy have an associated congenital malformation. Their profile of term birth, higher Apgar scores, and lower frequency of perinatal seizures suggests a distinct causal pathway.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.02.002DOI Listing
July 2020

Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers: A Living Rapid Review.

Ann Intern Med 2020 07 5;173(2):120-136. Epub 2020 May 5.

Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon (R.C., T.D., S.S., A.M.T.).

Background: Health care workers (HCWs) are at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Purpose: To examine the burden of SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome (MERS)-CoV on HCWs and risk factors for infection, using rapid and living review methods.

Data Sources: Multiple electronic databases, including the WHO database of publications on coronavirus disease and the medRxiv preprint server (2003 through 27 March 2020, with ongoing surveillance through 24 April 2020), and reference lists.

Study Selection: Studies published in any language reporting incidence of or outcomes associated with coronavirus infections in HCWs and studies on the association between risk factors (demographic characteristics, role, exposures, environmental and administrative factors, and personal protective equipment [PPE] use) and HCW infections. New evidence will be incorporated on an ongoing basis by using living review methods.

Data Extraction: One reviewer abstracted data and assessed methodological limitations; verification was done by a second reviewer.

Data Synthesis: 64 studies met inclusion criteria; 43 studies addressed burden of HCW infections (15 on SARS-CoV-2), and 34 studies addressed risk factors (3 on SARS-CoV-2). Health care workers accounted for a significant proportion of coronavirus infections and may experience particularly high infection incidence after unprotected exposures. Illness severity was lower than in non-HCWs. Depression, anxiety, and psychological distress were common in HCWs during the coronavirus disease 2019 outbreak. The strongest evidence on risk factors was on PPE use and decreased infection risk. The association was most consistent for masks but was also observed for gloves, gowns, eye protection, and handwashing; evidence suggested a dose-response relationship. No study evaluated PPE reuse. Certain exposures (such as involvement in intubations, direct patient contact, or contact with bodily secretions) were associated with increased infection risk. Infection control training was associated with decreased risk.

Limitation: There were few studies on risk factors for SARS-CoV-2, the studies had methodological limitations, and streamlined rapid review methods were used.

Conclusion: Health care workers experience significant burdens from coronavirus infections, including SARS-CoV-2. Use of PPE and infection control training are associated with decreased infection risk, and certain exposures are associated with increased risk.

Primary Funding Source: World Health Organization.
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http://dx.doi.org/10.7326/M20-1632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240841PMC
July 2020

Feasibility of MRI based extracellular volume fraction and partition coefficient measurements in thigh muscle.

Br J Radiol 2020 Jul 11;93(1111):20190931. Epub 2020 May 11.

Department Of Medical Physics and Engineering, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Objective: This study aimed to assess the feasibility of extracellular volume-fraction (ECV) measurement, and time to achieve contrast equilibrium (CE), in healthy muscles, and to determine whether in-flow and partial-volume errors in the femoral artery affect measurements, and if there are differences in the partition coefficient (λ) between muscles.

Methods: T1 was measured in the biceps femoris, vastus intermedius, femoral artery and aorta of 10 healthy participants. This was repeated alternately between the thigh and aorta for ≥25 min following a bolus of gadoterate meglumine. λ was calculated for each muscle/blood measurement. Time to CE was assessed semi-quantitatively.

Results: 8/10 participants achieved CE. Time to CE = 19±2 min (mean ± 95% confidence interval). Measured λ: biceps femoris/aorta = 0.210±0.034, vastus intermedius/aorta = 0.165±0.015, biceps femoris/femoral artery = 0.265±0.054, vastus intermedius/femoral artery = 0.211±0.026. There were significant differences in λ between the muscles when using the same vessel ( < 0.05), and between λ calculated in the same muscle when using different vessels ( < 0.05).

Conclusion: ECV measurements in the thigh are clinically feasible. The use of the femoral artery for the blood measurement is associated with small but significant differences in λ. ECV measurements are sensitive to differences between muscles within the healthy thigh.

Advances In Knowledge: This paper determines the time to contrast equilibrium in the healthy thigh and describes a method for measuring accurately ECV in skeletal muscle. This can aid in the diagnosis and understanding of inflammatory auto-immune diseases.
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http://dx.doi.org/10.1259/bjr.20190931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336063PMC
July 2020

Ataxic-hypotonic cerebral palsy in a cerebral palsy registry: Insights into a distinct subtype.

Neurol Clin Pract 2020 Apr;10(2):131-139

Faculty of Medicine (JPL), McGill University, Montreal, QC; Department of Pediatrics and Neurology and Neurosurgery (MO, MS), McGill University, Montreal, QC; Centre for Outcomes Research and Evaluation (MO, PN, MS), Research Institute of the McGill University Health Centre, Montreal, QC; Department of Pediatrics (JA), University of Alberta, Edmonton, AB; Janeway Children's Hospital (DB), St. John's, NL; Department of Paediatrics (DF), University of Toronto, Bloorview Research Institute, Toronto, ON; Departments of Pediatrics and Clinical Neurosciences (AK), Cumming School of Medicine, University of Calgary, AB; Centre de réadaptation Marie Enfant du CHU Sainte-Justine (LK), Montreal, QC; Centre hospitalier universitaire de Sherbrooke (NP), Sherbrooke, QC; BC Children's Hospital (EvR), Vancouver, BC; and IWK Health Centre (EW), Halifax, NS, Canada.

Objective: To specifically report on ataxic-hypotonic cerebral palsy (CP) using registry data and to directly compare its features with other CP subtypes.

Methods: Data on prenatal, perinatal, and neonatal characteristics and gross motor function (Gross Motor Function Classification System [GMFCS]) and comorbidities in 35 children with ataxic-hypotonic CP were extracted from the Canadian Cerebral Palsy Registry and compared with 1,804 patients with other subtypes of CP.

Results: Perinatal adversity was detected significantly more frequently in other subtypes of CP (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.5-11.7). The gestational age at birth was higher in ataxic-hypotonic CP (median 39.0 weeks vs 37.0 weeks, = 0.027). Children with ataxic-hypotonic CP displayed more intrauterine growth restriction (OR 2.6, 95% CI 1.0-6.8) and congenital malformation (OR 2.4, 95% CI 1.2-4.8). MRI was more likely to be either normal (OR 3.8, 95% CI 1.4-10.5) or to show a cerebral malformation (OR 4.2, 95% CI 1.5-11.9) in ataxic-hypotonic CP. There was no significant difference in terms of GMFCS or the presence of comorbidities, except for more frequent communication impairment in ataxic-hypotonic CP (OR 4.2, 95% CI 1.5-11.6).

Conclusions: Our results suggest a predominantly genetic or prenatal etiology for ataxic-hypotonic CP and imply that a diagnosis of ataxic-hypotonic CP does not impart a worse prognosis with respect to comorbidities or functional impairment. This study contributes toward a better understanding of ataxic-hypotonic CP as a distinct nosologic entity within the spectrum of CP with its own pathogenesis, risk factors, clinical profile, and prognosis compared with other CP subtypes.
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http://dx.doi.org/10.1212/CPJ.0000000000000713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156190PMC
April 2020

Fetal Alcohol Spectrum Disorders in a Midwestern City: Child Characteristics, Maternal Risk Traits, and Prevalence.

Alcohol Clin Exp Res 2020 04 15;44(4):919-938. Epub 2020 Apr 15.

Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota.

Objective: To determine the characteristics of children with fetal alcohol spectrum disorders (FASD) and their mothers in a Midwestern city.

Methods: Case-control samples were drawn from 2 separate first-grade cohorts (combined N = 4,047) in every city school using different methods. In Cohort Sample 1, all consented small children (≤25th centile on height, weight, and/or head circumference) entered the study along with a random sample from all enrolled students. Cohort Sample 2 was drawn totally at random. Child growth, dysmorphology, and neurobehavior were assessed using the Collaboration on FASD Prevalence (CoFASP) criteria, and mothers were interviewed.

Results: For the samples combined, 891 children received dysmorphology examinations, and 692 were case-conferenced for final diagnosis. Forty-four children met criteria for FASD. Total dysmorphology scores differentiated diagnostic groups: fetal alcohol syndrome (FAS), 16.7; partial FAS, 11.8; alcohol-related neurodevelopmental disorder (ARND), 6.1; and typically developing controls, 4.2. Neurobehavioral tests distinguished children with FASD from controls, more for behavioral problems than cognitive delay. Children with ARND demonstrated the poorest neurobehavioral indicators. An adjusted regression model of usual prepregnancy drinking indicated that maternal reports of 3 drinks per drinking day (DDD) were significantly associated with a FASD diagnosis (p = 0.020, OR = 10.1, 95% CI = 1.44 to 70.54), as were 5 or more DDD (p < 0.001, OR = 26.47, 95% CI = 4.65 to 150.62). Other significant maternal risk factors included the following: self-reported drinking in any trimester; smoking and cocaine use during pregnancy; later pregnancy recognition and later and less prenatal care; lower maternal weight, body mass index (BMI), and head circumference; and unmarried status. There was no significant difference in FASD prevalence by race, Hispanic ethnicity, or socioeconomic status at this site, where the prevalence of FASD was 14.4 to 41.2 per 1,000 (1.4 to 4.1%).

Conclusion: This city displayed the lowest prevalence of FASD of the 4 CoFASP sites. Nevertheless, FASD were common, and affected children demonstrated a common, recognizable, and measurable array of traits.
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http://dx.doi.org/10.1111/acer.14314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166178PMC
April 2020

Fetal Alcohol Spectrum Disorders in a Southeastern County of the United States: Child Characteristics and Maternal Risk Traits.

Alcohol Clin Exp Res 2020 04 15;44(4):939-959. Epub 2020 Apr 15.

Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota.

Objective: To detail the characteristic traits of children with fetal alcohol spectrum disorders (FASDs) and maternal risk factors in a southeastern U.S. County.

Methods: Independent samples were drawn from 2 different cohorts of first-grade students. All consented children (49.8%) were measured for height, weight, and head circumference, and those ≤ 25th centile entered the study along with a random sample drawn from all enrolled students. Study children were examined for physical growth, dysmorphology, and neurobehavior, and their mothers were interviewed.

Results: Total dysmorphology scores discriminated well the physical traits of children across the FASD continuum: fetal alcohol syndrome (FAS) = 15.8, partial FAS (PFAS) = 10.8, alcohol-related neurobehavioral disorder (ARND) = 5.2, and typically developing controls = 4.4. Additionally, a neurobehavioral battery distinguished children with each FASD diagnosis from controls. Behavioral problems qualified more children for FASD diagnoses than cognitive traits. Significant proximal maternal risk variables were as follows: reports of prepregnancy drinking, drinking in any trimester, and comorbid use of other drugs in lifetime and during pregnancy, especially alcohol and marijuana (14.9% among mothers of children with FASD vs. 0.4% for controls). Distal maternal risks included reports of other health problems (e.g., depression), living unmarried with a partner during pregnancy, and a lower level of spirituality. Controlling for other drug use during pregnancy, having a child diagnosed with a FASD was 17.5 times greater for women who reported usual consumption of 3 drinks per drinking day prior to pregnancy than for nondrinking mothers (p < 0.001, 95% CI = 5.1 to 59.9). There was no significant difference in the prevalence of FASD by race, Hispanic ethnicity, or socioeconomic status. The prevalence of FASD was not lower than 17.3 per 1,000, and weighted estimated prevalence was 49.0 per 1,000 or 4.9%.

Conclusion: This site had the second lowest rate in the CoFASP study, yet children with FASD are prevalent.
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http://dx.doi.org/10.1111/acer.14313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169982PMC
April 2020

Fetal Alcohol Spectrum Disorders in a Rocky Mountain Region City: Child Characteristics, Maternal Risk Traits, and Prevalence.

Alcohol Clin Exp Res 2020 04 15;44(4):900-918. Epub 2020 Apr 15.

Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota.

Objective: To document prevalence and traits of children with fetal alcohol spectrum disorders (FASD) and maternal risk factors in a Rocky Mountain city.

Methods: Variations on active case ascertainment methods were used in 2 first-grade cohorts in all city schools. The consent rate was 59.2%. Children were assessed for physical growth, dysmorphology, and neurobehavior and their mothers interviewed.

Results: Thirty-eight children were diagnosed with FASD and compared with 278 typically developing controls. Total dysmorphology scores summarized well the key physical indicators of FASD and defined specific diagnostic groups. On average, children with FASD performed significantly poorer than controls on intellectual, adaptive, learning, attention, and behavioral tasks. More mothers of children with FASD reported drinking prior to pregnancy and in the first and second trimesters, and had partners with drinking problems than mothers of controls; however, reports of comorbid alcohol use and 6 other drugs were similar for mothers of children with FASD and mothers of controls. Mothers of children with FASD were significantly younger at pregnancy, had lower average weight before pregnancy and less education, initiated prenatal clinic visits later, and reported more health problems (e.g., stomach ulcers and accidents). Children with FASD had significantly lower birth weight and more problems at birth, and were less likely to be living with biological mother and father. Controlling for other drug and tobacco use, a FASD diagnosis is 6.7 times (OR = 6.720, 95% CI = 1.6 to 28.0) more likely among children of women reporting prepregnancy drinking of 3 drinks per drinking day (DDD) and 7.6 times (OR = 7.590, 95% CI = 2.0 to 31.5) more likely at 5 DDD. Prevalence of FAS was 2.9-5.8 per 1,000 children, and total FASD was 34.9 to 82.5 per 1,000 children or 3.5 to 8.3% at this site.

Conclusion: This site had the second highest prevalence of FASD of the 4 Collaboration on FASD Prevalence sites and clearly identifiable child and maternal risk traits.
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http://dx.doi.org/10.1111/acer.14315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166196PMC
April 2020

Thermal Decomposition of Ternary Sodium Graphite Intercalation Compounds.

Chemistry 2020 May 7;26(29):6545-6553. Epub 2020 Apr 7.

Department of Chemistry and Materials, Imperial College London, London, SW7 2AZ, UK.

Graphite intercalation compounds (GICs) are often used to produce exfoliated or functionalised graphene related materials (GRMs) in a specific solvent. This study explores the formation of the Na-tetrahydrofuran (THF)-GIC and a new ternary system based on dimethylacetamide (DMAc). Detailed comparisons of in situ temperature dependent XRD with TGA-MS and Raman measurements reveal a series of dynamic transformations during heating. Surprisingly, the bulk of the intercalation compound is stable under ambient conditions, trapped between the graphene sheets. The heating process drives a reorganisation of the solvent and Na molecules, then an evaporation of the solvent; however, the solvent loss is arrested by restacking of the graphene layers, leading to trapped solvent bubbles. Eventually, the bubbles rupture, releasing the remaining solvent and creating expanded graphite. These trapped dopants may provide useful property enhancements, but also potentially confound measurements of grafting efficiency in liquid-phase covalent functionalization experiments on 2D materials.
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http://dx.doi.org/10.1002/chem.202000422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317426PMC
May 2020

Cryosurgery for basal cell carcinoma treated in primary care.

Ir J Med Sci 2020 Nov 29;189(4):1183-1187. Epub 2020 Feb 29.

The Ashe Street Clinic, Tralee, Co Kerry, Ireland.

Background: Basal cell carcinoma (BCC) is a very common skin cancer in Caucasians. Although rarely life-threatening, it can be locally destructive and consumes a considerable amount of health expenditure. Treatments that are safe, cost-effective and can be carried out in primary care with a high cure rate and good cosmetic results for selected cases of BCC need to be explored.

Aims: This retrospective study was carried out to assess whether cryosurgery is a reasonable option for treating select cases of basal cell carcinomas (BCCs) in primary care under local anaesthetic by an expert cryosurgeon.

Method: The treatment and outcome of 184 consecutive, histologically diagnosed BCCs in 138 patients in one primary care setting over a 5-year period was analysed.

Results: One hundred (54%) BCCs were treated with cryosurgery, 57 (31%) treated by excision in primary care, 13 (7%) by photodynamic therapy (PDT), 12 (7%) by referral to plastic surgery mostly for flaps or grafts and 2 (1%) by imiquimod 5%.

Conclusions: Just over half of all BCCs in this survey were treated using cryosurgery (100 = 54%) and 79 were followed up for more than 5 years. The cure rate with cryosurgery was 95% after 5 years (95% CI, 0.8686-0.9837) with an excellent or good cosmetic outcome in 92%.
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http://dx.doi.org/10.1007/s11845-020-02188-5DOI Listing
November 2020

Evaluation of Chlorine Dioxide Gas against Four Salmonella enterica Serovars Artificially Contaminated on Whole Blueberries.

J Food Prot 2020 Mar;83(3):412-417

Food Safety and Intervention Technologies Research Unit, U.S. Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center, 600 East Mermaid Lane, Wyndmoor, Pennsylvania 19038, USA.

Abstract: Fresh produce, such as blueberries, continues to be a source of foodborne illness in the United States. Despite new practices and intervention technologies, blueberries and other produce are contaminated with foodborne pathogens, such as Salmonella. The aim of this study was to evaluate the efficacy of chlorine dioxide gas (CDG) against Salmonella enterica serovars Newport, Stanley, Muenchen, and Anatum on artificially contaminated whole fresh blueberries. Blueberries were dip inoculated into a 400-mL bath containing a Salmonella serovar cocktail of either ca. 6 or 9 log CFU/mL. Samples were dried for either 2 or 24 h before treatment with 1.5 or 3 mg of CDG/L of air to a final treatment of 3.55 to 6 ppm/h/g of blueberry. Salmonella cells were recovered by stomaching CDG-treated and nontreated control samples with 0.1% peptone and enumerated on xylose lysine Tergitol 4 agar. CDG treatments achieved up to a 5.63-log CFU/g reduction of the cocktail using 5.5 ppm/h/g, whereas the lowest treatment, 4 ppm/h/g (1.5 mg of CDG/L), was still capable of a 4.45-log CFU/g reduction. Incubation time significantly (P < 0.001) affected CDG efficacy against both inoculation concentrations. Additionally, all serovars responded similarly to CDG treatment when tested individually (P > 0.0691). Finally, the availability of a water reservoir during treatments did not have a significant effect (P = 0.9818) on CDG efficacy in this study. Our results demonstrate that CDG can be an efficacious treatment option for whole blueberry decontamination.

Highlights:
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http://dx.doi.org/10.4315/0362-028X.JFP-19-452DOI Listing
March 2020

Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI.

MAGMA 2020 Feb 22;33(1):163-176. Epub 2019 Nov 22.

Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation.
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http://dx.doi.org/10.1007/s10334-019-00797-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021750PMC
February 2020

Early-Life Predictors of Fetal Alcohol Spectrum Disorders.

Pediatrics 2019 12 19;144(6). Epub 2019 Nov 19.

Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa;

Background And Objectives: Fetal alcohol spectrum disorders (FASD) comprise the continuum of disabilities associated with prenatal alcohol exposure. Although infancy remains the most effective time for initiation of intervention services, current diagnostic schemes demonstrate the greatest confidence, accuracy, and reliability in school-aged children. Our aims for the current study were to identify growth, dysmorphology, and neurodevelopmental features in infants that were most predictive of FASD at age 5, thereby improving the timeliness of diagnoses.

Methods: A cohort of pregnant South African women attending primary health care clinics or giving birth in provincial hospitals was enrolled in the project. Children were followed longitudinally from birth to 60 months to determine their physical and developmental trajectories ( = 155). Standardized protocols were used to assess growth, dysmorphology, and development at 6 weeks and at 9, 18, 42, and 60 months. A structured maternal interview, including estimation of prenatal alcohol intake, was administered at 42 or 60 months.

Results: Growth restriction and total dysmorphology scores differentiated among children with and without FASD as early as 9 months (area under the receiver operating characteristic curve = 0.777; < .001; 95% confidence interval: 0.705-0.849), although children who were severely affected could be identified earlier. Assessment of developmental milestones revealed significant developmental differences emerging among children with and without FASD between 18 and 42 months. Mothers of children with FASD were significantly smaller, with lower BMIs and higher alcohol intake during pregnancy, than mothers of children without FASD.

Conclusions: Assessment of a combination of growth, dysmorphology, and neurobehavioral characteristics allows for accurate identification of most children with FASD as early as 9 to 18 months.
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http://dx.doi.org/10.1542/peds.2018-2141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889972PMC
December 2019

Patient-derived xenografts of central nervous system metastasis reveal expansion of aggressive minor clones.

Neuro Oncol 2020 01;22(1):70-83

Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Background: The dearth of relevant tumor models reflecting the heterogeneity of human central nervous system metastasis (CM) has hindered development of novel therapies.

Methods: We established 39 CM patient-derived xenograft (PDX) models representing the histological spectrum, and performed phenotypic and multi-omic characterization of PDXs and their original patient tumors. PDX clonal evolution was also reconstructed using allele-specific copy number and somatic variants.

Results: PDXs retained their metastatic potential, with flank-implanted PDXs forming spontaneous metastases in multiple organs, including brain, and CM subsequent to intracardiac injection. PDXs also retained the histological and molecular profiles of the original patient tumors, including retention of genomic aberrations and signaling pathways. Novel modes of clonal evolution involving rapid expansion by a minor clone were identified in 2 PDXs, including CM13, which was highly aggressive in vivo forming multiple spontaneous metastases, including to brain. These PDXs had little molecular resemblance to the patient donor tumor, including reversion to a copy number neutral genome, no shared nonsynonymous mutations, and no correlation by gene expression.

Conclusions: We generated a diverse and novel repertoire of PDXs that provides a new set of tools to enhance our knowledge of CM biology and improve preclinical testing. Furthermore, our study suggests that minor clone succession may confer tumor aggressiveness and potentiate brain metastasis.
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http://dx.doi.org/10.1093/neuonc/noz137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954401PMC
January 2020