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Abstract We are concerned with the issue of detecting changes and their signs from a data stream. For example, when given time series of COVID-19 cases in a region, we may raise early warning signals of an epidemic by detecting signs of changes in the data. We propose a novel methodology to address this issue. The key idea is to employ a new information-theoretic notion, which we call the differential minimum description length change statistics (D-MDL), for measuring the scores of change sign. We first give a fundamental theory for D-MDL. We then demonstrate its effectiveness using synthetic datasets. We apply it to detecting early warning signals of the COVID-19 epidemic using time series of the cases for individual countries. We empirically demonstrate that D-MDL is able to raise early warning signals of events such as significant increase/decrease of cases. Remarkably, for about $$64\%$$ 64 % of the events of significant increase of cases in studied countries, our method can detect warning signals as early as nearly six days on average before the events, buying considerably long time for making responses. We further relate the warning signals to the dynamics of the basic reproduction number R0 and the timing of social distancing. The results show that our method is a promising approach to the epidemic analysis from a data science viewpoint.

Background: HCV-specific DAAs have transformed treatment of chronic HCV, but few studies have evaluated these therapies in children. Methods: Patients aged 12–17 years old with chronic GT1 HCV were enrolled into an open-label study to receive 12 weeks of LDV/SOF 90 mg/400 mg once daily, and those with HCV GT2 or GT3 to receive SOF (400 mg once daily) + RBV (15 mg/kg/day) for 12 (GT2) or 24 weeks (GT3), respectively. Primary efficacy endpoint was SVR12. Safety was assessed by adverse events and clinical/laboratory data. Pharmacokinetic (PK) sampling was conducted to confirm the appropriateness of the doses. Results: 150 adolescents (100 GT1, 13 GT2 and 37 GT3) were enrolled and treated. The majority were female (56%), white (90%), treatment naive (81%), and vertically infected (80%). The mean age was 15 years (range 12–17). LDV, SOF and GS-331007 (primary metabolite) exposures were within the range of adult exposures observed in the SOF and LDV/SOF phase 2/3 studies. The SVR12 rate was 98% in GT1, 100% in GT2 and 97% in GT3; all 3 patients who were considered not to have achieved SVR12 were lost to follow-up. No adverse event (AE) leading to study drug discontinuation or serious AEs have been reported. Conclusion: In adolescents, LDV/SOF for 12 weeks and SOF + RBV for 12 or 24 weeks, resulted in a SVR12 rate of 97–100% with no virologic failures. These regimens were well tolerated, demonstrating their potential as an important treatment option for children with HCV infection.

Ursodeoxycholic acid (UDCA) is commonly used to treat several liver disorders in adults and children, including primary sclerosing cholangitis (PSC) for which it is not U.S. Food and Drug Administration approved. UDCA treatment has an uncertain impact on disease outcomes and has been reported in high doses to be associated with worse outcome in adults with PSC. In this context, controlled withdrawal and reintroduction of UDCA in children with PSC were studied. Prior to study initiation, participants were required to have alanine aminotransferase (ALT) and gamma‐glutamyl transpeptidase (GGT) 100 IU/L (flare group). None developed elevated bilirubin. All flares responded to UDCA reinstitution. Serum GGT, interleukin‐8, and tumor necrosis factor α levels were higher in the flare group at baseline. Liver biochemistries increased in children with PSC during controlled UDCA withdrawal; one third increased above 100 IU/L and one third remained normal during UDCA withdrawal. Conclusion: The impact of prolonged UDCA use in childhood PSC and the significance of a biochemical flare are unclear. Further studies of the natural history and treatment of pediatric PSC and UDCA use are needed.

Background/Aims: Early weaning has been shown to induce intestinal ornithine decarboxylase (ODC) activities and cell proliferation in rats. No information is available about the effect of early weaning on ODC activity in the stomach. Methods: Suckling rats were prematurely weaned on postnatal day 15 and followed through day 21. Oxyntic gland mucosa of stomach was obtained on postnatal days 15, 16, 18 and 21 (days 0, 1, 3 and 6 after early weaning) and assayed for ODC activity, DNA, protein and pepsinogen activity. α-Difluoromethyl ornithine (DFMO), a specific ODC inhibitor, was given orally to early-weaned pups and its resultant effects were assessed on days 1 and 6 after early weaning. Results: Stomach mucosal wet weight, DNA, protein and pepsinogen activities significantly increased on day 6 after early weaning. ODC activity increased on days 1, 3, and 6 after early weaning, with the highest increase (3-fold) on day 1 when compared to controls. The increases of ODC activity, DNA and protein contents as induced by early weaning were significantly suppressed when pups were exposed to DFMO. However, no suppression of pepsinogen activity was observed. Conclusions: Our study shows that early weaning induces ODC activity and functional growth in the stomach. Gastric ODC activity is essential in gastric mucosal growth processes but not in differentiation. The induction of stomach ODC may act as an early marker in the growth of stomach mucosa induced by early weaning in rats.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE: We performed a prospective, randomized, single-blind study in children undergoing colonoscopy to evaluate the acceptance and efficacy of three different bowel preparations. METHODS: Seventy patients (ages 3-20 yr, 38 males) were randomly assigned to one of the three study preparations: Magnesium citrate with X-prep and clear liquid diet for 2 days (group A); Dulcolax for 2 days and Fleet enema without dietary restriction (group B); and Golytely 20 ml/kg (up to 1 L) per hour for 4 h with clear liquid diet for 1 day (group C). Endoscopists blinded to bowel preparation graded the adequacy of colon cleansing. The preparations were rated by patients for tolerance, willingness to retake them, adverse effects, and compliance. RESULTS: Data analysis using Fisher exact test and trend test showed that colon cleansing in groups A and C was superior to that in group B (p < 0.0001) and better in group C than A (p < 0.075). Overall tolerance and compliance were significantly better for groups A and B than group C (p < 0.003), but not different between A and B. More of group B patients were willing to retake the preparation than in group C (p < 0.002) and group A (p < 0.05), but this was not different between groups A and C. Adverse effects were reported more frequently by patients in group C than in groups A and B (p < 0.01). CONCLUSIONS: Although the least well tolerated. Golytely provided the best cleansing. Dulcolax without dietary restriction provided unsatisfactory colon cleansing. Magnesium citrate with X-prep was acceptable and provided good cleansing. [ABSTRACT FROM AUTHOR]

Presents a review of a study of 32 children and adolescents with chronic inflammatory bowel disease (CIBD), who required surgery. Similarities between CIBD and Crohn's disease; Operations which patients with ulcerative colitis underwent; Results of study.