The Effects of Patient Demographics on Outpatient Endoscopy Utilization in Children with Eosinophilic Esophagitis

Objectives: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that requires esophagogastroduodenoscopy (EGD) for diagnosis and treatment monitoring. We aimed to identify the frequency of endoscopic monitoring in children with EoE and observe the effect of age, race, socioeconomic factors, and atopy on the rate of endoscopy. Methods: We queried the Pediatric Health Information System over a 15-year period for ambulatory EGDs in children with EoE. Subjects with at least 1 year of data were included. Age, sex, ethnicity, race, insurance type, median household income, and atopy were collected for each subject. Results: 16,517 subjects were included (mean age 8.5 years). 3211 (19%) of subjects had ≥1 EGD per subject year (EGD/SY). Subjects >13 years old were more likely to have ≥1 EGD/SY compared to children 6–12 years (odds ratio [OR] 2.29, P < 0.001, 95% confidence interval [CI] = 2.06–2.54). Males were more likely to have ≥1 EGD/SY compared to females (OR 1.19, P < 0.001, 95% CI = 1.08–1.31). African-American subjects were 16% less likely than Caucasian subjects to have ≥1 EGD/SY (OR 0.84, P = 0.05, 95% CI = 0.71–1.00). Subjects with allergic rhinitis or anaphylaxis, food allergy, and/or oral allergy syndrome were more likely to have ≥1 EGD/SY (OR 1.67, P < 0.001, 95% CI = 1.47–1.90 and OR 3.65, P < 0.001, 95% CI = 3.25–4.11, respectively). Conclusions: Nineteen percent of subjects had ≥1 EGD/SY. Older age, male sex, allergic rhinitis, and food allergies were associated with more frequent endoscopic monitoring in children with EoE. Caucasian subjects had more frequent endoscopy than African-American subjects. This study raises awareness about underrecognized variation in the care of children with EoE

'Everyday memory' impairments in autism spectrum disorders

‘Everyday memory’ is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead Behavioural Memory Test (RBMT) and a standard word recall task (Children’s Auditory Verbal Learning Test-2: CAVLT-2). The ASD group showed significant impairments on the RBMT, including in prospective memory, alongside impaired performance on the CAVLT-2. Social and communication ability was significantly associated with prospective remembering in an everyday memory context but not with the CAVLT-2. The complex nature of everyday memory and its relevance to ASD is discussed

Comprehensive analysis of dose intensity of acute lymphoblastic leukemia chemotherapy

Chemotherapy dosages are often compromised, but most reports lack data on dosages that are actually delivered. In two consecutive acute lymphoblastic leukemia trials that differed in their asparaginase formulation, native E. coli L-asparaginase in St. Jude Total 15 (T15, n=365) and pegaspargase in Total 16 (T16, n=524), we tallied the dose intensities for all drugs on the low-risk or standard-risk arms, analyzing 504,039 dosing records. The median dose intensity for each drug ranged from 61-100%. Dose intensities for several drugs were more than 10% higher on T15 than on T16: cyclophosphamide (P<0.0001 for the standard- risk arm), cytarabine (P<0.0001 for the standard-risk arm), and mercaptopurine (P<0.0001 for the low-risk arm and P<0.0001 for the standardrisk arm). We attributed the lower dosages on T16 to the higher asparaginase dosages on T16 than on T15 (P<0.0001 for both the low-risk and standard-risk arms), with higher dose-intensity for mercaptopurine in those with anti-asparaginase antibodies than in those without (P=5.62x10-3 for T15 standard risk and P=1.43x10-4 for T16 standard risk). Neutrophil count did not differ between protocols for low-risk patients (P=0.18) and was actually lower for standard-risk patients on T16 than on T15 (P<0.0001) despite lower dosages of most drugs on T16. Patients with low asparaginase dose intensity had higher methotrexate dose intensity with no impact on prognosis. The only dose intensity measure predicting a higher risk of relapse on both studies was higher mercaptopurine dose intensity, but this did not reach statistical significance (P=0.03 T15; P=0.07 T16). In these intensive multiagent trials, higher dosages of asparaginase compromised the dosing of other drugs for acute lymphoblastic leukemia, particularly mercaptopurine, but lower chemotherapy dose intensity was not associated with relapse

Cross-species inference of long non-coding RNAs greatly expands the ruminant transcriptome

Additional file 3. This file contains all supplementary tables relating to lncRNA identification via the conservation of synteny. Table S3. lncRNAs inferred in one species by the genomic alignment of a transcript assembled with the RNA-seq libraries from a related spdecies. Table S12. Presence of intergenic lncRNAs both in sheep and cattle, in regions of conserved synteny. Table S13. Presence of intergenic lncRNAs both in sheep and goat, in regions of conserved synteny. Table S14. Presence of intergenic lncRNAs both in cattle and goat, in regions of conserved synteny. Table S15. Presence of intergenic lncRNAs both in sheep and humans, in regions of conserved synteny. Table S16. Presence of intergenic lncRNAs both in goat and humans, in regions of conserved synteny. Table S17. Presence of intergenic lncRNAs both in cattle and humans, in regions of conserved synteny. Table S18. High-confidence lncRNA pairs, those conserved across species both sequentially and positionally

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe

Tropical field stations yield high conservation return on investment

Conservation funding is currently limited; cost‐effective conservation solutions are essential. We suggest that the thousands of field stations worldwide can play key roles at the frontline of biodiversity conservation and have high intrinsic value. We assessed field stations’ conservation return on investment and explored the impact of COVID‐19. We surveyed leaders of field stations across tropical regions that host primate research; 157 field stations in 56 countries responded. Respondents reported improved habitat quality and reduced hunting rates at over 80% of field stations and lower operational costs per km 2 than protected areas, yet half of those surveyed have less funding now than in 2019. Spatial analyses support field station presence as reducing deforestation. These “earth observatories” provide a high return on investment; we advocate for increased support of field station programs and for governments to support their vital conservation efforts by investing accordingly

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest