Search

Debris flows generated by rainfall runoff can occur in rocky alpine landscapes and burned steeplands. Runoff-generated debris-flow events are commonly composed of a series of dense granular surge fronts separated by water-rich flows. Owing to this intra-event variability in flow composition and mechanics, post-event interpretations of preserved sedimentary deposits, or lack thereof, can result in a dizzying mix of interpretations that range from clearwater flow to debris flow. Accurate identification of the presence or absence of a debris flow during a runoff event is critical for building empirical models used to predict likelihood of debris-flow occurrence, rainfall thresholds, and flow properties. Here, we propose a simple, quantitative method to identify the occurrence of a runoff-generated debris flow, based on a dimensionless discharge Q* calculated as the ratio of the peak event discharge Qp to the theoretical maximum clearwater runoff rate Qw. Using a preliminary compilation of Q* values from floods and runoff-generated debris flows, we find 98% of floods have Q* values < 1.6, whereas 91% of debris flows have Q* values greater than 1.6. Estimating Q* is typically straightforward as part of standard post-event reconnaissance if suitable rainfall estimates are available, and appears to be a robust indicator that runoff-generated debris flows traversed a particular portion of a valley network.

A range of hydrologic responses can be observed in steep, recently burned terrain, which makes predicting the spatial distribution of large debris flows challenging. Studies from rainfall-induced landslides in unburned areas show evidence of hydroclimatic tuning of landslide triggering, such that the spatial distribution of events is best predicted by the observed rainfall anomaly relative to climatic norms rather than by absolute rainfall. In this paper, we test whether the spatial distribution of debris flows in response to rainfall can be similarly predicted by rainfall anomaly. The 520 km2 Dolan Fire burn scar in Monterey County, California, USA, spans a sharp hydroclimatic gradient and experienced a widespread storm in January 2021 that triggered floods and debris flows, providing a natural experiment in which to test this hypothesis. In this study, we use remote and field methods to map debris-flow response and examine its spatial heterogeneity. Together with rainfall data, our mapping reveals that the observed anomalies in peak 15-min rainfall intensity (I15) relative to the intensity of the 1-yr return interval storm predict debris-flow occurrence better than the absolute peak I15. Our findings indicate that debris-flow processes and threshold rainfall required for debris-flow initiation may be tuned to local hydroclimate.

Elizabeth Pleasants,1 Tekou B Koffi,2 Karen Weidert,1 Sandra I McCoy,1 Ndola Prata1 1School of Public Health, University of California at Berkeley, Berkeley, CA, USA; 2Cabinet De Recherche Et D’évaluation (CERA), Lomé, TogoCorrespondence: Ndola PrataSchool of Public Health, University of California at Berkeley, 2121 Berkeley Way West, #6142, Berkeley, CA 94720, USATel +1 510-642-6915Email Ndola@berkeley.eduBackground: Despite improvements in contraception availability, women face persistent barriers that compromise reproductive autonomy and informed choice. Provider bias is one way in which access to contraception can be restricted within clinical encounters and has been established as common in sub-Saharan Africa. This analysis assessed the prevalence of provider restrictions and the potential impact on women’s method uptake in Lomé, Togo.Methods: This sub-analysis used survey data from provider and client interviews collected to assess the impacts of the Agir pour la Planification Familiale (AgirPF) program in Togo. The relationships between provider restrictiveness and women’s receipt of their desired method of contraception were modelled using mixed effects logistic regressions looking at all women and among subgroups hypothesized to be at potentially higher risk of bias.Results: Around 84% of providers reported a restriction in contraceptive provision for the five contraceptive methods explored (pill, male condom, injectable, IUD, and implant). Around 53% of providers reported restricting at least four of the five methods based on age, parity, partner consent, or marital status. Among all women, there were no significant associations between provider restrictiveness and women’s receipt of desired method, including among those who desired long-acting methods. In adjusted modeling, marital status was a covariate significantly associated with desired method, with married women more likely to receive their desired method than unmarried women (aOR 2.73, 95% CI 1.45–5.13).Conclusion: Provider reports of high levels of restrictions in this population are concerning and should be further explored, especially its effects on unmarried women. However, restrictions reported by providers in this study did not appear to statistically significantly influence contraceptive method received.Keywords: provider bias, provider restrictions, contraception, Togo

Sara S McCoy,1 Zubin Mukadam,2 Keith C Meyer,2 Jeffrey P Kanne,3 Cristopher A Meyer,3 Maria D Martin,3 Emmanuel Sampene,4 Scott W Aesif,5 Laurie N Rice,6 Christie M Bartels1 1Division of Rheumatology, Department of Internal Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; 2Division of Pulmonary and Critical Care, Department of Internal Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; 3Department of Radiology, University of Wisconsin, Madison, WI 53792-3252, USA; 4Department of Biostatistics, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA; 5Department of Pathology, University of Wisconsin, Madison, WI 53792-3252, USA; 6Department of Pulmonology, SSM Health Dean Medical Group, Madison, WI 53715, USA Objectives: International experts recently characterized interstitial pneumonia with autoimmune features (IPAF) as a provisional diagnosis for patients with interstitial lung disease who have characteristics of autoimmune disease but do not meet criteria for a specific autoimmune disease. We describe clinical characteristics of IPAF patients and examine responses to mycophenolate as a therapy for IPAF.Methods: This retrospective cohort included adult patients meeting European Respiratory Society/American Thoracic Society classification criteria for IPAF. Sociodemographic, clinical, and pulmonary function test data were abstracted for patients with and without mycophenolate treatment and followed longitudinally from interstitial lung disease diagnosis for change in pulmonary function test results.Results: We identified 52 patients who met criteria for IPAF. Of 52 IPAF patients, 24 did not receive mycophenolate and 28 did, with median time to mycophenolate treatment 22 months. Changes in FVC% and percentage predicted lung diffusion capacity for carbon monoxide (DLCO%) between the mycophenolate-treated and untreated groups were not significantly different (FVC% change P=0.08, DLCO% change P=0.17). However, there was a trend toward more rapid baseline decline of both FVC% and DLCO% in the mycophenolate-treated cohort before vs after mycophenolate therapy. The slope of both FVC% and DLCO% values improved after onset of mycophenolate exposure for the treated group, although this finding was not statistically significant.Conclusion: Patients with IPAF might benefit from mycophenolate therapy. Larger prospective clinical trials are needed to evaluate the efficacy of mycophenolate for patients who meet criteria for IPAF. Keywords: interstitial lung disease, autoimmune disease, connective tissue disease, myco­phenolate

Abstract Background The use of chromium supplements is widespread for the prevention and treatment of diabetes mellitus but there are conflicting reports on efficacy, possibly reflecting discrepant effects across different populations. In the present studies, we test the hypothesis that chromium supplementation raises serum chromium levels and correspondingly improves insulin sensitivity. Methods A double blind placebo-controlled randomized trial was conducted on 31 non-obese, normoglycemic subjects. After baseline studies, the subjects were randomized to placebo or chromium picolinate 500 μg twice a day. The primary endpoint was change in insulin sensitivity as measured by euglycemic hyperinsulinemic clamp. Pre-specified secondary endpoints included fasting lipids, blood pressure, weight, body composition measured by DXA scan. Results After 16 weeks of chromium picolinate therapy there was no significant change in insulin sensitivity between groups (p=0.83). There was, however, a strong association between serum chromium and change in insulin resistance (β = -0.83, p=0.01), where subjects with the highest serum chromium had a worsening of insulin sensitivity. This effect could not be explained by changes in physiological parameters such as body weight, truncal fat and serum lipids with chromium therapy. Conclusions Chromium therapy did not improve insulin sensitivity in non-obese normoglycemic individuals. Further, subjects who have high serum chromium levels paradoxically had a decline in insulin sensitivity. Caution therefore should be exercised in recommending the use of this supplement. Trial registration The study was registered on the NIH registry (clinicaltrials.gov) and the identifier is NCT00846248

Abstract Background Asthma is a major cause of pediatric morbidity and mortality. In acute exacerbations of asthma, corticosteroids reduce relapses, subsequent hospital admission and the need for ß2-agonist therapy. Prednisolone is relatively short-acting with a half-life of 12 to 36 hours, thereby requiring daily dosing. Prolonged treatment course, vomiting and a bitter taste may reduce patient compliance with prednisolone. Dexamethasone is a long-acting corticosteroid with a half-life of 36 to 72 hours. It is used frequently in children with croup and bacterial meningitis, and is well absorbed orally. The purpose of this trial is to examine whether a single dose of oral dexamethasone (0.3 mg/kg) is clinically non-inferior to prednisolone (1 mg/kg/day for three days) in the treatment of exacerbations of asthma in children who attend the Emergency Department. Methods/design This is a randomized, non-inferiority, open-label clinical trial. After informed consent with or without assent, patients will be randomized to either oral dexamethasone 0.3 mg/kg stat or prednisolone 1 mg/kg/day for three days. The primary outcome measure is the comparison between the Pediatric Respiratory Assessment Measure (PRAM) across both groups on Day 4. The PRAM score, a validated, responsive and reliable tool to determine asthma severity in children aged 2 to 16 years, will be performed by a clinician blinded to treatment allocation. Secondary outcomes include relapse, hospital admission and requirement for further steroid therapy. Data will be analyzed on an intention-to-treat and a per protocol basis. With a sample size of 232 subjects (105 in each group with an estimated 10% loss to follow-up), we will be able to reject the null hypothesis - that the population means of the experimental and control groups are equal with a probability (power) of 0.9. The Type I error probability associated with this test (of the null hypothesis) is 0.05. Discussion This clinical trial may provide evidence that a shorter steroid course using dexamethasone can be used in the treatment of acute pediatric asthma, thus eliminating the issue of compliance to treatment. Registration ISRCTN26944158 and EudraCT Number 2010-022001-18

Abstract Background Children with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain. Methods/design This study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05. Discussion This clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting. Trial registration Current Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20

Abstract Background This phase 1b study assessed the maximum tolerated dose (MTD), safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) administered once daily (QD) or twice daily (BID) in combination with erlotinib and gemcitabine in patients with solid tumors. Methods Patients received weekly intravenous gemcitabine (1000 mg/m2) and erlotinib (100 mg QD) alone (control cohort) or in combination with motesanib (50 mg QD, 75 mg BID, 125 mg QD, or 100 mg QD; cohorts 1-4); or erlotinib (150 mg QD) in combination with motesanib (100 or 125 mg QD; cohorts 5 and 6). Results Fifty-six patients were enrolled and received protocol-specified treatment. Dose-limiting toxicities occurred in 11 patients in cohorts 1 (n = 2), 2 (n = 4), 3 (n = 3), and 6 (n = 2). The MTD of motesanib in combination with gemcitabine and erlotinib was 100 mg QD. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Frequently occurring motesanib-related adverse events included diarrhea (n = 19), nausea (n = 18), vomiting (n = 13), and fatigue (n = 12), which were mostly of worst grade < 3. The pharmacokinetics of motesanib was not markedly affected by coadministration of gemcitabine and erlotinib, or erlotinib alone. Erlotinib exposure, however, appeared lower after coadministration with gemcitabine and/or motesanib. Of 49 evaluable patients, 1 had a confirmed partial response and 26 had stable disease. Conclusions Treatment with motesanib 100 mg QD plus erlotinib and gemcitabine was tolerable. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Trial Registration ClinicalTrials.gov NCT01235416

Abstract Background Welwitschia mirabilis is the only extant member of the family Welwitschiaceae, one of three lineages of gnetophytes, an enigmatic group of gymnosperms variously allied with flowering plants or conifers. Limited sequence data and rapid divergence rates have precluded consensus on the evolutionary placement of gnetophytes based on molecular characters. Here we report on the first complete gnetophyte chloroplast genome sequence, from Welwitschia mirabilis, as well as analyses on divergence rates of protein-coding genes, comparisons of gene content and order, and phylogenetic implications. Results The chloroplast genome of Welwitschia mirabilis [GenBank: EU342371] is comprised of 119,726 base pairs and exhibits large and small single copy regions and two copies of the large inverted repeat (IR). Only 101 unique gene species are encoded. The Welwitschia plastome is the most compact photosynthetic land plant plastome sequenced to date; 66% of the sequence codes for product. The genome also exhibits a slightly expanded IR, a minimum of 9 inversions that modify gene order, and 19 genes that are lost or present as pseudogenes. Phylogenetic analyses, including one representative of each extant seed plant lineage and based on 57 concatenated protein-coding sequences, place Welwitschia at the base of all seed plants (distance, maximum parsimony) or as the sister to Pinus (the only conifer representative) in a monophyletic gymnosperm clade (maximum likelihood, bayesian). Relative rate tests on these gene sequences show the Welwitschia sequences to be evolving at faster rates than other seed plants. For these genes individually, a comparison of average pairwise distances indicates that relative divergence in Welwitschia ranges from amounts about equal to other seed plants to amounts almost three times greater than the average for non-gnetophyte seed plants. Conclusion Although the basic organization of the Welwitschia plastome is typical, its compactness, gene content and high nucleotide divergence rates are atypical. The current lack of additional conifer plastome sequences precludes any discrimination between the gnetifer and gnepine hypotheses of seed plant relationships. However, both phylogenetic analyses and shared genome features identified here are consistent with either of the hypotheses that link gnetophytes with conifers, but are inconsistent with the anthophyte hypothesis.