Force Dependence of the Michaelis Constant in a Two-State Ratchet Model for Molecular Motors

We present a quantitative analysis of recent data on the kinetics of ATP hydrolysis, which has presented a puzzle regarding the load dependence of the Michaelis constant. Within the framework of coarse grained two-state ratchet models, our analysis not only explains the puzzling data, but provides a modified Michaelis law, which could be useful as a guide for future experiments.Comment: 4 pages, 3 eps figures, accepted for publication on Physical Review Letter

Group-based pelvic floor muscle training is a more cost-effective approach to treat urinary incontinence in older women: economic analysis of a randomised trial

Question(s): How cost-effective is group-based pelvic floor muscle training (PFMT) for treating urinary incontinence in older women? Design: Economic evaluation conducted alongside an assessor-blinded, multicentre randomised non-inferiority trial with 1-year follow-up. Participants: A total of 362 women aged 60 years with stress or mixed urinary incontinence. Intervention: Twelve weekly 1-hour PFMT sessions delivered individually (one physiotherapist per woman) or in groups (one physiotherapist per eight women). Outcome measures: Urinary incontinence-related costs per woman were estimated from a participant and provider perspective over 1 year in Canadian dollars, 2019. Effectiveness was based on reduction in leakage episodes and quality-adjusted life years. Incremental cost-effectiveness ratios and net monetary benefit were calculated for each of the effectiveness outcomes and perspectives. Results: Both group-based and individual PFMT were effective in reducing leakage and promoting gains in quality-adjusted life years. Furthermore, group-based PFMT was 60% less costly than individual treatment, regardless of the perspective studied: –$914 (95$509 (95% CI –523 to –496) from the provider’s perspective. Differences in effects between study arms were minor and negligible. Adherence to treatment was high, with low loss to follow-up and no between-group differences. Conclusion: Compared with standard individual PFMT, group-based PFMT was less costly and as clinically effective and widely accepted. These results indicate that patients and healthcare decisionmakers should consider group-based PFMT to be a cost-effective first-line treatment option for urinary incontinence. Trial registration: ClinicalTrials.gov NCT0203983

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials

Systematic review of economic evaluations and cost analyses of guideline implementation strategies

Objectives To appraise the quality of economic studies undertaken as part of evaluations of guideline implementation strategies; determine their resources use; and recommend methods to improve future studies. Methods Systematic review of economic studies undertaken alongside robust study designs of clinical guideline implementation strategies published (1966-1998). Studies assessed against the BMJ economic evaluations guidelines for each stage of the guideline process (guideline development, implementation and treatment). Results 235 studies were identified, 63 reported some information on cost. Only 3 studies provided evidence that their guideline was effective and efficient. 38 reported the treatment costs only, 12 implementation and treatment costs, 11 implementation costs alone, and two guideline development, implementation and treatment costs. No study gave reasonably complete information on costs. Conclusions Very few satisfactory economic evaluations of guideline implementation strategies have been performed. Current evaluations have numerous methodological defects and rarely consider all relevant costs and benefits. Future evaluations should focus on evaluating the implementation of evidence based guidelines. Keywords: Cost-effectiveness analysis, physician (or health care professional) behaviour, practice guidelines, quality improvement, systematic review.Peer reviewedAuthor versio

Disentangling galaxy environment and host halo mass

[Abridged] The properties of observed galaxies and dark matter haloes in simulations depend on their environment. The term environment has been used to describe a wide variety of measures that may or may not correlate with each other. Popular measures of environment include the distance to the N'th nearest neighbour, the number density of objects within some distance, or the mass of the host dark matter halo. We use results from the Millennium simulation and a semi-analytic model for galaxy formation to quantify the relations between environment and halo mass. We show that the environmental parameters used in the observational literature are in effect measures of halo mass, even if they are measured for a fixed stellar mass. The strongest correlation between environment and halo mass arises when the number of objects is counted out to a distance of 1.5-2 times the virial radius of the host halo and when the galaxies/haloes are required to be relatively bright/massive. For observational studies the virial radius is not easily determined, but the number of neighbours out to 1-2 Mpc/h gives a similarly strong correlation. For the distance to the N'th nearest neighbour the correlation with halo mass is nearly as strong provided N>2. We demonstrate that this environmental parameter becomes insensitive to halo mass if it is constructed from dimensionless quantities. This can be achieved by scaling the minimum luminosity/mass of neighbours to that of the object in question and by dividing the distance to a length scale associated with either the neighbour or the galaxy under consideration. We show how such a halo mass independent environmental parameter can be defined for observational and numerical studies. The results presented here will help future studies to disentangle the effects of halo mass and external environment on the properties of galaxies and dark matter haloes.Comment: 15 pages, 9 figures, 2 tables. Accepted by MNRA

Accelerated expansion from structure formation

We discuss the physics of backreaction-driven accelerated expansion. Using the exact equations for the behaviour of averages in dust universes, we explain how large-scale smoothness does not imply that the effect of inhomogeneity and anisotropy on the expansion rate is small. We demonstrate with an analytical toy model how gravitational collapse can lead to acceleration. We find that the conjecture of the accelerated expansion being due to structure formation is in agreement with the general observational picture of structures in the universe, and more quantitative work is needed to make a detailed comparison.Comment: 44 pages, 1 figure. Expanded treatment of topics from the Gravity Research Foundation contest essay astro-ph/0605632. v2: Added references, clarified wordings. v3: Published version. Minor changes and corrections, added a referenc

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Double Spin Asymmetry of Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s)=200 GeV

We report on the first measurement of double-spin asymmetry, A_LL, of electrons from the decays of hadrons containing heavy flavor in longitudinally polarized p+p collisions at sqrt(s)=200 GeV for p_T= 0.5 to 3.0 GeV/c. The asymmetry was measured at mid-rapidity (|eta|<0.35) with the PHENIX detector at the Relativistic Heavy Ion Collider. The measured asymmetries are consistent with zero within the statistical errors. We obtained a constraint for the polarized gluon distribution in the proton of |Delta g/g(log{_10}x= -1.6^+0.5_-0.4, {mu}=m_T^c)|^2 < 0.033 (1 sigma), based on a leading-order perturbative-quantum-chromodynamics model, using the measured asymmetry.Comment: 385 authors, 17 pages, 15 figures, 5 tables. Submitted to Phys. Rev. D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm