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3. The discrete Green's function paradigm for two-way coupled Euler-Lagrange simulation

Author

Horwitz, J. A. K., Iaccarino, G., Eaton, J. K., and Mani, A.

Subjects
Physics - Fluid Dynamics, Physics - Computational Physics
Abstract

We outline a methodology for the simulation of particle-laden flows whereby the dispersed and fluid phases are two-way coupled. The drag force which couples fluid and particle momentum depends on the undisturbed fluid velocity at the particle location, and this latter quantity requires modelling. We demonstrate that the undisturbed fluid velocity, in the low particle Reynolds number limit, can be related exactly to the discrete Green's function of the discrete Stokes equations. The method is general in that it can be extended to other partial differential equations which may be associated with particle-laden flows, such as the thermal energy equation or Maxwell's equations. In this work, we demonstrate the method of discrete Green's functions by obtaining these functions for the Navier-Stokes equations at low particle Reynolds number in a two-plane channel geometry. We perform verification at low and finite particle Reynolds number for the case of a point-particle settling under gravity parallel to a plane wall, for different wall normal separations. In comparing to other point-particle schemes the discrete Green's function approach is the most robust at low particle Reynolds number, accurate at all wall-normal separations and is the most accurate in the near wall region at finite Reynolds number. We discuss how the accuracy away from the wall at finite Reynolds number could be improved by appealing to Oseen-like discrete Green's functions. Finally we demonstrate that the discrete Green's function approach can have important implications on statistics of particle-laden turbulent channel flow.

Published
2020

4. The mechanisms of transcription termination by RNA polymerase II

Author

Eaton, J. and West, S.

Subjects
572.8, transcriptional termination, XRN2, CPSF73, Protein phosphatase 1, polyadenylation signal
Abstract

RNA polymerase II (Pol II) catalyses the transcription of many RNA classes including protein-coding, small nuclear RNA (snRNAs) and some non-coding RNA classes within eukaryotes. Its journey is ended by the cessation of transcription and the dissolution of the DNA-bound complex in a process known as transcriptional termination. Given the diverse array of transcript classes, several termination mechanisms can induce Pol II termination. One of the most studied is polyadenylation signal (PAS)-dependent termination and occurs at the ends of most protein-coding as well as some other transcript classes. Two long-standing models have been used to explain the role of the PAS in termination and their relevance has been a topic of much debate. The allosteric model suggests Pol II undergoes conformational changes after the PAS to instigate termination, while the torpedo model suggests degradation of the downstream RNA product of PAS-cleavage is important to instigate termination. Here, rapid depletion cell lines are employed to describe the widespread dependence of protein-coding transcript termination on the XRN2 torpedo and the CPSF73 PAS-cleaving endonuclease. CPSF73 depletion leads to profound "run-away" transcription, whereas XRN2 depletion results in a more limited read-through. XRN2 targets Pol II complexes that have undergone slowing or pausing in a protein phosphatase 1 (PP1)-mediated process occurring downstream of the PAS. Additionally, XRN2 can degrade RNA and cause torpedo termination from some other PAS-independent cleavage events. However, this is not a universal process with XRN2 dispensable at snRNA and histone transcripts. Together these results suggest a unified allosteric/torpedo mechanism at protein-coding transcripts, where PAS cleavage precedes a PP1-dependent slowing of Pol II. This facilitates the degradation of downstream RNA by XRN2 and thereby instigates transcriptional termination.

Published
2021

5. Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

Author

Corpechot, C, Lemoinne, S, Soret, P, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Pares, A, Olivas, I, Eaton, J, Osman, K, Schramm, C, Sebode, M, Lohse, A, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, Van Der Meer, A, De Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Bruns, T, Grosse, K, Wetten, A, Dyson, J, Jones, D, Dumortier, J, Pageaux, G, De Ledinghen, V, Chazouilleres, O, Carrat, F, Corpechot C., Lemoinne S., Soret P. -A., Hansen B., Hirschfield G., Gulamhusein A., Montano-Loza A. J., Lytvyak E., Pares A., Olivas I., Eaton J. E., Osman K. T., Schramm C., Sebode M., Lohse A. W., Dalekos G., Gatselis N., Nevens F., Cazzagon N., Zago A., Russo F. P., Floreani A., Abbas N., Trivedi P., Thorburn D., Saffioti F., Barkai L., Roccarina D., Calvaruso V., Fichera A., Delamarre A., Sobenko N., Villamil A. M., Medina-Morales E., Bonder A., Patwardhan V., Rigamonti C., Carbone M., Invernizzi P., Cristoferi L., Van Der Meer A., De Veer R., Zigmond E., Yehezkel E., Kremer A. E., Deibel A., Bruns T., Grosse K., Wetten A., Dyson J. K., Jones D., Dumortier J., Pageaux G. -P., De Ledinghen V., Chazouilleres O., Carrat F., Corpechot, C, Lemoinne, S, Soret, P, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Pares, A, Olivas, I, Eaton, J, Osman, K, Schramm, C, Sebode, M, Lohse, A, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, Van Der Meer, A, De Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Bruns, T, Grosse, K, Wetten, A, Dyson, J, Jones, D, Dumortier, J, Pageaux, G, De Ledinghen, V, Chazouilleres, O, Carrat, F, Corpechot C., Lemoinne S., Soret P. -A., Hansen B., Hirschfield G., Gulamhusein A., Montano-Loza A. J., Lytvyak E., Pares A., Olivas I., Eaton J. E., Osman K. T., Schramm C., Sebode M., Lohse A. W., Dalekos G., Gatselis N., Nevens F., Cazzagon N., Zago A., Russo F. P., Floreani A., Abbas N., Trivedi P., Thorburn D., Saffioti F., Barkai L., Roccarina D., Calvaruso V., Fichera A., Delamarre A., Sobenko N., Villamil A. M., Medina-Morales E., Bonder A., Patwardhan V., Rigamonti C., Carbone M., Invernizzi P., Cristoferi L., Van Der Meer A., De Veer R., Zigmond E., Yehezkel E., Kremer A. E., Deibel A., Bruns T., Grosse K., Wetten A., Dyson J. K., Jones D., Dumortier J., Pageaux G. -P., De Ledinghen V., Chazouilleres O., and Carrat F.

Abstract

Background and Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Published
2024

7. Biomechanical, ultrastructural, and electrophysiological characterization of the non-human primate experimental glaucoma model.

Author

Raghunathan, VijayKrishna, Eaton, J Seth, Christian, Brian J, Morgan, Joshua T, Ver Hoeve, James N, Yang, Chen-Yuan Charlie, Gong, Haiyan, Rasmussen, Carol A, Miller, Paul E, Russell, Paul, Nork, T Michael, and Murphy, Christopher J

Subjects
Eye, Trabecular Meshwork, Animals, Primates, Humans, Glaucoma, Hypertension, Proteome, Models, Animal, Lasers, Intraocular Pressure, Electrophysiological Phenomena, Models, Animal
Abstract

Laser-induced experimental glaucoma (ExGl) in non-human primates (NHPs) is a common animal model for ocular drug development. While many features of human hypertensive glaucoma are replicated in this model, structural and functional changes in the unlasered portions of trabecular meshwork (TM) of laser-treated primate eyes are understudied. We studied NHPs with ExGl of several years duration. As expected, ExGl eyes exhibited selective reductions of the retinal nerve fiber layer that correlate with electrophysiologic measures documenting a link between morphologic and elctrophysiologic endpoints. Softening of unlasered TM in ExGl eyes compared to untreated controls was observed. The degree of TM softening was consistent, regardless of pre-mortem clinical findings including severity of IOP elevation, retinal nerve fiber layer thinning, or electrodiagnostic findings. Importantly, this softening is contrary to TM stiffening reported in glaucomatous human eyes. Furthermore, microscopic analysis of unlasered TM from eyes with ExGl demonstrated TM thinning with collapse of Schlemm's canal; and proteomic analysis confirmed downregulation of metabolic and structural proteins. These data demonstrate unexpected and compensatory changes involving the TM in the NHP model of ExGl. The data suggest that compensatory mechanisms exist in normal animals and respond to elevated IOP through softening of the meshwork to increase outflow.

Published
2017

8. Effects of topically applied heterologous serum on reepithelialization rate of superficial chronic corneal epithelial defects in dogs.

Author

Eaton, J Seth, Hollingsworth, Steven R, Holmberg, Bradford J, Brown, Michael H, Smith, Patricia J, and Maggs, David J

Subjects
Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Animals, Anti-Bacterial Agents, Atropine, Corneal Diseases, Dog Diseases, Dogs, Double-Blind Method, Drug Therapy, Combination, Female, Keratotomy, Radial, Male, Muscarinic Antagonists, Ophthalmic Solutions, Serum, Tobramycin, Treatment Outcome, Wound Healing, Veterinary Sciences
Abstract

OBJECTIVE To assess the effects of topical application of undiluted heterologous serum on time to corneal reepithelialization in dogs with superficial chronic corneal epithelial defects (SCCEDs). DESIGN Multicenter, randomized, double-masked, controlled clinical trial. ANIMALS 41 client-owned dogs. PROCEDURES After collection of baseline clinical and historical data, dogs were randomly assigned to receive topically applied undiluted heterologous serum (n = 22) or isotonic saline (0.9% NaCl) solution (19) along with tobramycin and atropine. Epithelial debridement (at all visits) and grid keratotomy (at visits 2, 3, and 4) of SCCEDs were performed. Ophthalmic examination including fluorescein application was performed once weekly for 4 weeks or until corneal reepithelialization. Clinicians and owners were masked to treatment group. RESULTS No differences in baseline data were detected between treatment groups. No difficulties with medication administration, noncompliance, or adverse reactions were noted. All SCCEDs in both groups healed by 4 weeks after treatment began. Median time to reepithelialization (2 weeks) was not significantly different between serum-treated and placebo-treated eyes. Irrespective of treatment group, median time to reepithelialization was not significantly different for Boxers versus non-Boxer breeds. Direct correlations were detected between time to reepithelialization and vascularization score at study entry, vascularization score at time of reepithelialization, and ulcer area at study entry in both groups. Time to reepithelialization was not correlated with age, sex, or duration of signs in either group. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of undiluted heterologous serum was well tolerated by dogs with SCCEDs but, as an adjunct to standard treatment, did not reduce time to corneal reepithelialization.

Published
2017

14. Species Differences in the Geometry of the Anterior Segment Differentially Affect Anterior Chamber Cell Scoring Systems in Laboratory Animals

Author

Thomasy, Sara M, Eaton, J Seth, Timberlake, Matthew J, Miller, Paul E, Matsumoto, Steven, and Murphy, Christopher J

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Animals, Animals, Laboratory, Anterior Chamber, Anterior Eye Segment, Cats, Cell Count, Dogs, Humans, Mice, Rabbits, Rats, Species Specificity, Swine, Tomography, Optical Coherence, Opthalmology and Optometry, Pharmacology and Pharmaceutical Sciences, Ophthalmology & Optometry, Ophthalmology and optometry, Pharmacology and pharmaceutical sciences
Abstract

PurposeTo determine the impact of anterior segment geometry on ocular scoring systems quantifying anterior chamber (AC) cells in humans and 7 common laboratory species.MethodsUsing normative anterior segment dimensions and novel geometric formulae, ocular section volumes measured by 3 scoring systems; Standardization of Uveitis Nomenclature (SUN), Ocular Services On Demand (OSOD), and OSOD-modified SUN were calculated for each species, respectively. Calculated volumes were applied to each system's AC cell scoring scheme to determine comparative cell density (cells/mm(3)). Cell density values for all laboratory species were normalized to human values and conversion factors derived to create modified scoring schemes, facilitating interspecies comparison with each system, respectively.ResultsDifferences in anterior segment geometry resulted in marked differences in optical section volume measured. Volumes were smaller in rodents than dogs and cats, but represented a comparatively larger percentage of AC volume. AC cell density (cells/mm(3)) varied between species. Using the SUN and OSOD-modified SUN systems, values in the pig, dog, and cat underestimated human values; values in rodents overestimated human values. Modified normalized scoring systems presented here account for species-related anterior segment geometry and facilitate both intra- and interspecies analysis, as well as translational comparison.ConclusionsEmployment of modified AC cell scoring systems that account for species-specific differences in anterior segment anatomy would harmonize findings across species and may be more predictive for determining ocular toxicological consequences in ocular drug and device development programs.

Published
2016

21. Welcome back, Polaris the Cepheid

Author

Bruntt, H., Penny, A. J., Stello, D., Evans, N. R., and Eaton, J. A.

Subjects
Astrophysics
Abstract

For about 100 years the amplitude of the 4-day pulsation in Polaris has decreased. We present new results showing a significant increase in the amplitude based on 4.5 years of continuous monitoring from the ground and with two satellite missions., Comment: 5 pages; to appear in the proceedings of the "Cool Stars 15" workshop held at St Andrews, UK

Published
2008
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22. Polaris the Cepheid returns: 4.5 years of monitoring from ground and space

Author

Bruntt, H., Evans, N. R., Stello, D., Penny, A. J., Eaton, J. A., Buzasi, D. L., Sasselov, D. D., Preston, H. L., and Miller-Ricci, E.

Subjects
Astrophysics
Abstract

We present the analysis of 4.5 years of nearly continuous observations of the classical Cepheid Polaris, which comprise the most precise data available for this star. We have made spectroscopic measurements from ground and photometric measurements from the WIRE star tracker and the SMEI instrument on the Coriolis satellite. Measurements of the amplitude of the dominant oscillation (P = 4 days), that go back more than a century, show a decrease from 120 mmag to 30 mmag (V magnitude) around the turn of the millennium. It has been speculated that the reason for the decrease in amplitude is the evolution of Polaris towards the edge of the instability strip. However, our new data reveal an increase in the amplitude by about 30% from 2003-2006. It now appears that the amplitude change is cyclic rather than monotonic, and most likely the result of a pulsation phenomenon. In addition, previous radial velocity campaigns have claimed the detection of long-period variation in Polaris (P > 40 days). Our radial velocity data are more precise than previous datasets, and we find no evidence for additional variation for periods in the range 3-50 days with an upper limit of 100 m/s. However, in the WIRE data we find evidence of variation on time-scales of 2-6 days, which we interpret as being due to granulation., Comment: Accepted by ApJ. 8 pages. Quality of figures 1+3+7 degraded

Published
2008
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31. A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France

Author

Taipale K, Winfree KB, Boye M, Basson M, Sleilaty G, Eaton J, Evans R, and Chouaid C

Subjects
Advanced nonsquamous NSCLC, Cost-effectiveness, France, Induction–maintenance, Pemetrexed, Quality-adjusted life-years, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Kaisa Taipale,1 Katherine B Winfree,2 Mark Boye,2 Mickael Basson,3 Ghassan Sleilaty,4 James Eaton,5 Rachel Evans,5 Christos Chouaid6 1Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Corporate Affairs, Lilly France, Neuilly-sur-Seine, 4Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France; 5ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK; 6Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France Background: Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M) sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC) are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS) and overall survival (OS) relative to gemcitabine + cisplatin (induction sequences) or best supportive care (BSC) (maintenance sequences). Modeled health-care benefits were expressed as life-years (LYs) and quality-adjusted LYs (QALYs) (estimated using French EuroQol five-dimension questionnaire tariffs). The study was conducted from the payer perspective (National Health Insurance). Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results: Base-case results showed pemetrexed + cisplatin induction followed by (→) pemetrexed maintenance had the longest mean OS and PFS and highest LYs and QALYs. Costs ranged from €12,762 for paclitaxel + carboplatin → BSC to €35,617 for pemetrexed + cisplatin → pemetrexed (2015 values). Gemcitabine + cisplatin → BSC, pemetrexed + cisplatin → BSC, and pemetrexed + cisplatin → pemetrexed were associated with fully incremental cost-effectiveness ratios (ICERs) of €16,593, €80,656, and €102,179, respectively, per QALY gained versus paclitaxel + carboplatin → BSC. All other treatment sequences were either dominated (ie, another sequence had lower costs and better/equivalent outcomes) or extendedly dominated (ie, the comparator had a higher ICER than a more effective comparator) in the model. Sensitivity analyses showed the model to be relatively insensitive to plausible changes in the main assumptions, with none increasing or decreasing the ICER by more than ~€20,000 per QALY gained. Conclusion: In the absence of direct comparative trial evidence, this cost-effectiveness analysis indicated that of a large number of I–M sequences used for the treatment of patients with nsqNSCLC in France, pemetrexed + cisplatin → pemetrexed achieved the best clinical outcomes (0.28 incremental QALYs gained) versus paclitaxel + carboplatin → BSC. Keywords: advanced nonsquamous NSCLC, cost-effectiveness, France, induction–maintenance, pemetrexed, quality-adjusted life-years

Published
2017

39. Trends and country-level variation in age at first sex in sub-Saharan Africa among birth cohorts entering adulthood between 1985 and 2020

Author

Nguyen, VK, Eaton, J, Bill & Melinda Gates Foundation, and Medical Research Council (MRC)

Subjects
Adult, Male, Acquired Immunodeficiency Syndrome, Adolescent, Sexual Behavior, Sexually Transmitted Diseases, Public Health, Environmental and Occupational Health, Bayes Theorem, HIV Infections, 1117 Public Health and Health Services, Pregnancy, Child, Preschool, Humans, Birth Cohort, Female, Public Health, Africa South of the Sahara
Abstract

Background Debuting sexual intercourse marks exposure to pregnancy or fatherhood and sexually transmitted infections (STIs), including HIV. In sub-Saharan Africa (SSA), sexual debut varies according to cultural, religious, and economic factors, and encouraging delay has been a longstanding component of behavioural HIV prevention strategies. Age at first sex (AFS) is routinely collected in national household surveys, but data are affected by reporting biases, limiting utility to monitor trends and guide sexual health interventions. Methods We collated individual-level data from nationally-representative household surveys to analyse timing and national trends in AFS in 42 SSA countries. We used a log-skew-logistic distribution to characterize the time to AFS in a Bayesian spatio-temporal model, providing estimates of the sexual debut rate by sex, age, time, and country. We statistically adjusted for reporting biases by comparing AFS reported by the same birth cohorts in multiple survey rounds, allowing different reporting biases by sex and country. Results Median AFS in 2015 ranged from 15.8 among Angolan women to 25.3 among men in Niger. AFS was younger for women than men in 37/40 countries. The gap was largest for Sahel region countries and minimal in southern African countries. The distribution of female AFS was asymmetric with half debuting sex in an age range of 3.9 years [IQR 3.4–5.0 across countries]. Median AFS increased slightly between 1985 and 2020, ranging 0.84 years [IQR 0.11–1.55] and 0.79 [IQR -0.23–1.98] for females and males, respectively. The gender gap changed little over time in most countries. Female teens often reported higher AFS compared to when asked in their late twenties while male teens reported lower AFS; both sexes recalled a higher AFS in older ages compared to their thirties. Conclusions AFS increased slightly in most SSA countries, but changes were modest relative to large and persistent variation between countries and sexes, indicating relatively entrenched socio-cultural practices around sexual debut. Sexual health, family planning, and HIV/STI prevention services should adapt to local practices rather than focusing interventions to change AFS. These estimates for rates of sexual debut provide data to guide programmatic prioritization and implementation of sexual health services.

Published
2022

40. Mental health support for children and adolescents with hearing loss: scoping review

Author

Scherer, N, Bright, T, Musendo, DJ, O'Fallon, T, Kubwimana, C, Eaton, J, Kakuma, R, Smythe, T, Polack, S, Scherer, N, Bright, T, Musendo, DJ, O'Fallon, T, Kubwimana, C, Eaton, J, Kakuma, R, Smythe, T, and Polack, S

Abstract

Background : Children with hearing loss are at increased risk of mental health conditions, including behavioural problems, but there is limited evidence about available mental health support. Aims : We aimed to map the evidence on mental health support for children and adolescents with hearing loss. Method : Medline, Embase, PsycINFO and grey literature databases were searched until April 2021. Articles of any study design were eligible if they described an intervention supporting the mental health of children with hearing loss. No restrictions were placed on geography or publication date. Four reviewers independently screened results by title, abstract and full text. Study characteristics and outcome data were extracted, with results narratively synthesised. Results : From 5629 search results, 27 articles were included. A large majority of the studies (81%, n = 22) were from high-income settings, with two-thirds (67%, n = 18) conducted in the USA. Less than half (41%, n = 11) of the articles adopted experimental research designs, and the majority of studies included small samples. The interventions presented were diverse, with the majority either therapy based (30%, n = 8) or skills training (30%, n = 8). Interventions included ice-skating, parent–child interaction therapy and resilience training. When measured, interventions demonstrated at least some evidence of effectiveness, although this was not always assessed with gold-standard methodology. Conclusions : The evidence is lacking in breadth, study quality and geographical spread. That said, what is available indicates a range of effective approaches to support the mental health of children with hearing loss. Additional research is needed to improve the breadth of evidence on mental health support for this population.

Published
2022

41. Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis

Author

Corpechot, C, Carrat, F, Gaouar, F, Chau, F, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Schramm, C, Pares, A, Olivas, I, Eaton, J, Osman, K, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A, de Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Dumortier, J, Bruns, T, Große, K, Pageaux, G, Wetten, A, Dyson, J, Jones, D, Chazouillères, O, Hansen, B, de Lédinghen, V, Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John E, Osman, Karim T, Dalekos, George, Gatselis, Nikolaos, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Douglas, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vicenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vilas, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, de Lédinghen, Victor, Corpechot, C, Carrat, F, Gaouar, F, Chau, F, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Schramm, C, Pares, A, Olivas, I, Eaton, J, Osman, K, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A, de Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Dumortier, J, Bruns, T, Große, K, Pageaux, G, Wetten, A, Dyson, J, Jones, D, Chazouillères, O, Hansen, B, de Lédinghen, V, Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John E, Osman, Karim T, Dalekos, George, Gatselis, Nikolaos, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Douglas, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vicenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vilas, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, and de Lédinghen, Victor

Abstract

Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. Methods: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. Results: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026–1.054) and 1.042 (1.029–1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79–0.87) and 0.92 (0.89–0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM. Conclusions: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered. Lay summary: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses

Published
2022

42. Who is at risk of death from nephrectomy? An analysis of thirty‐day mortality after 21 380 nephrectomies in 3 years of the British Association of Urological Surgeons (BAUS) National Nephrectomy Audit

Author

Fernando, Archie, Fowler, Sarah, Van Hemelrijck, Mieke, OʼBrien, Tim, Abbasi, Z., Adamson, A. S., Addla, S. K., Adeyoju, A. A., Adshead, J. M., Afzal, N., Aho, T. F., Akhtar, M., Al‐Akraa, M., Al‐Sudani, M., Alam, A., Allan, J., Almond, D. J., Anderson, C. J., Andrews, S. J., Apakama, I., Armitage, T., Armitage, J., Awsare, N., Ayres, B., Banerjee, G. K., Barber, N. J., Barua, J. M., Basu, S., Bdesha, A. S., Beacock, C. J. M., Beatty, J., O Beck, R., Belal, M., Bell, C. R. W., Bhanot, S. M., Bhatt, R., Bhatti, A., Biyani, C. S., Blacker, A. J., Blades, R. A., Blake, C., Blake‐James, B., Boddy, J., Bromage, S. J., Bromwich, E., Brown, C., Browning, A. J., Bryan, N. P., Burgess, N. A., Burns‐Cox, N., Butterworth, P. C., Bycroft, J., Calleary, J. G., Calvert, R. C., Campbell, I., Campbell, C. A., Cannon, A., Carter, P. G., Carter, C. J. M., Cartledge, J. J., Casey, R., Chakravarti, A., Challacombe, B., Chandrasekharan, S., Chappell, B. G., Chaudry, A., Chen, T. F., Cherian, J., Choi, W. H., Chow, K., Clavijo Eisele, J., Cliff, A. M., Cohen, N. P., Cole, O. J., Collins, J., Connolly, S., Cooke, P. W., Cooksey, G., Cornaby, A. J., Cornford, P. A., Corr, J. G., Coulthard, R., Cranston, D. W., Cresswell, J., Crundwell, M. C., Cutinha, P. E., Cynk, M., Daruwala, P. D., Dasgupta, P., Datta, S. N., Davenport, K., de Bolla, A. R., Devarajan, R., Dickerson, D. A. G., Dickinson, A. J., Doherty, A. P., Donaldson, P. J., Dudderidge, T., Dyer, J., Eaton, J., Eddy, B., Eden, C. G., Elsaghir, M., Evans, S. D., Fiala, R., Fordham, M. V. P., Foster, M. C., French, A. J., Frymann, R. J., Gall, Z. J., Gallegos, C. R. R., Gana, H. B. Y., Garnett, S., Ghei, M., Gibbons, N., Gilbert, H. W., Gillatt, D. A., Glackin, A., Godbole, H. C., Golash, A., Goodman, C. M., Gowardhan, B., Green, J. S. A., Griffiths, T. R. L., Gujral, S., Gunendran, T., Hagan, C. M., Haldar, N., Hanbury, D. C., Harney, J., Hasan, S. T., Hawkyard, S. J., Hayes, M. C., Haynes, M. D., Henderson, A., Hicks, J. A., Hindley, R. G., Hodgson, D. J., Hotston, M., Howell, G. P., Hrouda, D., Hughes, O. D. M., Hunter‐Campbell, P., Ilie, C., Issa, R., Jain, S., Jain, A., Janjua, K. S., Javle, P., Johnson, P., Johnson, M. I., Jones, A., Joshi, H., Joyce, A. D., Kanaga‐Sundaram, S., Karim, O. M. A., Keeley, F. X., Kelkar, A., Kelleher, J. P., Khan, A., Khattak, A. Q., Khoubehi, B., Kimuli, M., Kirollos, M. M., Kockelbergh, R. C., Kooiman, G., Koupparis, A., Kumar, P., Kynaston, H. G., Laniado, M. E., Larner, T., Latif, Z., Lau, M. W., le Roux, P. J., Leung, S., Leveckis, J., Lewis, G., Liston, T. G., Lockyer, C. R. W., Lodge, R. N., Luscombe, C. J., Lynch, M., Lynch, C., Lynn, N. N. K., MacDermott, J. P., Mackie, S., Madaan, S., Maddineni, S.B., Maheshkumar, P., Makar, A. A., Makunde, J. T., Manikandan, R., Mann, G. S., Mantle, M., Mark, I. R., Matanhelia, S. S., McCabe, J., McClinton, S., McFarlane, J. P., McInerney, P. D., McIntyre, I. G., McLarty, E., McLornan, M. E., McLoughlin, J., McNeill, S. A., Mehta, S., Mellon, J. K., Menezes, P., Mills, R. D., Mokete, M., Montague, R., Morton, A. L., Motiwala, H. G., Mulholland, C. K., Mumtaz, F. H., Munro, N., Myatt, A., Nair, M., Namasivayam, S., Napier‐Hemy, R. D., Nathan, S., Neilson, D., Nicol, D. L., Nuttall, M., OʼBrien, T. S., OʼKane, H. F., OʼRiordan, A., Oades, G., Oakley, N., Okeke, A. A., Olsburgh, J., Paez, E., Page, T., Parkin, J., Parys, B. T., Patel, P., Patel, N., Patel, B., Pathak, S., Patil, K., Paul, A. B., Payne, D., Peracha, A. M., Peters, J. L., Phillips, S. M. A., Phillips, J. T., Phipps, S., Pillai, M. K., Potter, J. M., Prescott, S., Rajan, T. N., Rajjayabun, P., Ramani, V. A. C., Rane, A., Ravi, R., Ravichandran, S., Riddick, A. C. P., Rimington, P. D., Rix, G. H., Rix, D., Robinson, L. Q., Rochester, M., Rogawski, K. M., Rogers, A. G., Rowe, E., Sahadevan, K., Samsudin, A., Sandhu, S., Sangar, V. K., Sells, H., Shackley, D. C., Shah, Z., Shaikh, N. N. A., Sharma, H., Sherwood, B., Singh, S., Singh, G., Smith, D. J., Solomon, L., Soomro, N. A., Srinivasan, V., Sriprasad, S. I., Stephenson, R. N., Stewart, A., Stubington, S. R., Subramonian, K., Sullivan, M. E., Taneja, S., Thilagarajah, R., Thomas, S. A., Thomas, D. J., Thomas, B., Thompson, A. C., Thurston, A.V., Turner, K. J., Umez‐Eronini, O. N., Upsdell, S. M., Vale, J. A., Varadaraj, H., Vesey, S. G., Viney, R., Vohra, A. K., Walton, T., Warburton, H. E., Waymont, B., Webster, J. J., Webster, G. M., Wedderburn, A., Wemyss‐Holden, G. D., Weston, R., Whittlestone, T., Wilkinson, S., Wilkinson, B., Williams, S., Wills, M. I., Wilson, J. R., Wilson, I. D., Woodhouse, C. R. J., Wright, M., Yates, D. R., and Young, J. G.

Published
2017
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49. Education for Efficiency in Railroad Service. Bulletin, 1909, No. 10. Whole Number 420

Author

Department of the Interior, United States Bureau of Education (ED) and Eaton, J. Shirley

Abstract

When the writer, nine years ago, investigated for the Bureau of Education the subject of education for railroad service, the whole matter was in a very indefinite status. The monograph published at that time was little more than a collation of widely diverse opinions of railroad men. The advance made in the present decade is very surprising to those who may not be informed. Ideas of practical men on the subject are now less indefinite and conflicting. The relation between education and efficiency in railroad service is coming to be generally conceded. The most successful managers have seized on its financial import, and in their fiscal policies and operating organizations are giving it recognition. The large educational value of the railroad service itself is being turned to systematic practical account, and the value of educational agencies in preparing for specific industrial efficiency is better understood. The railroad service in the United States will shortly reach a total of 2,000,000 men. It is the largest and most highly organized example of associate effort in an epoch conspicuous for industrial and commercial concentration. In this view, the methods here evolved for preserving the proper balance between individual and group efficiency at any one time, and so of assuring the largest continuing effectiveness of the whole working body for the longest period of time--these methods take on especial significance. Among such methods, education in a broad sense must always be a large factor. The review of the subject here given is not intended to be statistical. The schools and railroads described have been cited merely in illustration of the particular methods which their practice typifies. Two appendixes present: (1) Statistics of railway apprenticeship; and (2) Educational and welfare work on European railroads. An index is included. Individual sections contain footnotes. [Best copy available has been provided.]

Published
1909

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