Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis

OBJECTIVE: To evaluate the cost effectiveness of four disease modifying treatments (interferon betas and glatiramer acetate) for relapsing remitting and secondary progressive multiple sclerosis in the United Kingdom. DESIGN: Modelling cost effectiveness. SETTING: UK NHS. PARTICIPANTS: Patients with relapsing remitting multiple sclerosis and secondary progressive multiple sclerosis. MAIN OUTCOME MEASURES: Cost per quality adjusted life year gained. RESULTS: The base case cost per quality adjusted life year gained by using any of the four treatments ranged from £42 000 ($66 469; 61 630) to £98 000 based on efficacy information in the public domain. Uncertainty analysis suggests that the probability of any of these treatments having a cost effectiveness better than £20 000 at 20 years is below 20%. The key determinants of cost effectiveness were the time horizon, the progression of patients after stopping treatment, differential discount rates, and the price of the treatments. CONCLUSIONS: Cost effectiveness varied markedly between the interventions. Uncertainty around point estimates was substantial. This uncertainty could be reduced by conducting research on the true magnitude of the effect of these drugs, the progression of patients after stopping treatment, the costs of care, and the quality of life of the patients. Price was the key modifiable determinant of the cost effectiveness of these treatments

Human papillomavirus vaccination acceptance and hesitancy in South Africa: Research and policy agenda

Cervical cancer is responsible for one-quarter of a million deaths per year  worldwide. In South Africa (SA), cervical cancer is the leading cause of  cancer deaths among women aged 15 - 44 years. Human papillomavirus  (HPV) vaccines provide a safe and highly effective means to reduce the burden of cervical cancer. The World Health Organization initiated a plan for the elimination of cervical cancer; the programme’s success relies on the introduction and high uptake of HPV vaccines globally. SA introduced a school-based HPV vaccination programme in 2014, but uptake is not as high as expected. Suboptimal HPV vaccination coverage may result from various factors, including vaccine hesitancy. Vaccine-hesitant parents may delay or refuse HPV vaccination for their daughters. Tailored interventions are needed to address this. However, knowledge regarding vaccine  hesitancy and policies to address this hesitancy in SA are currently limited. While SA has taken commendable steps in cervical cancer prevention by implementing and financing the HPV vaccination programme, it is  imperative that there are clear policies in place to help strengthen the programme. These policies need to clarify areas of uncertainty that may lead to mistrust, and pre-empt factors that will cause hesitancy. Equally important is that local research should be conducted to better understand HPV vaccination hesitancy and other determinants of uptake to further inform and shape national policies

Task-set inhibition, conflict, and the n-2 repetition cost: a computational model of task switching

In task switching, the n-2 repetition cost (informally, the elevation in RT associated with performing a recently abandoned task) is an indicator of residual task-set inhibition. One suggestion is that such inhibition is triggered by conflict between task-set elements. We present a novel computational model instantiating this proposal, by adding task-conflict monitoring units to an existing, interactive activation model of task switching. The model produces the empirical pattern, n-1 switch costs and n-2 repetition costs, as an intrinsic property of its architecture, but dependent on the inhibition of task demand units by the conflict detection mechanism. In a further simulation, we make predictions about n-2 repetition costs for asymmetric tasks, and show that one functional benefit of such a conflict-based, task inhibition mechanism is to facilitate top-down control of tasks by automatically reducing cross-task interference

Exercise training and resting blood pressure: a large-scale pairwise and network meta-analysis of randomised controlled trials

Objective: To perform a large-scale pairwise and network meta-analysis on the effects of all relevant exercise training modes on resting blood pressure to establish optimal anti-hypertensive exercise prescription practices. Design: Systematic review and network meta-analysis. Data sources: PubMed (MEDLINE), the Cochrane library and Web of Science were systematically searched. Eligibility criteria: Randomised controlled trials published between 1990 and February 2023. All relevant work reporting systolic blood pressure (sBP) and/or diastolic (dBP) reductions following an exercise intervention ≥2 weeks with an eligible non-intervention control group were included. Results: 270 randomised controlled trials were ultimately included in the final analysis, with a pooled sample size of 15,827 participants. Pairwise analyses demonstrated significant reductions in resting sBP and dBP following aerobic exercise training (-4.49/-2.53mmHg, P<0.001), dynamic resistance training (-4.55/-3.04mmHg, P<0.001), combined training (-6.04/-2.54mmHg, P<0.001), high intensity interval training (-4.08/-2.50mmHg, P<0.001) and isometric exercise training (-8.24/-4.00mmHg, P<0.001). As evidenced in the network meta-analysis, the rank order of effectiveness based on the surface under the cumulative ranking curve (SUCRA) values for sBP were isometric exercise training (SUCRA: 98.3%), combined training (75.7%), dynamic resistance training (46.1%), aerobic exercise training (40.5%) and high intensity interval training (39.4%). Secondary network meta-analyses revealed isometric wall squat and running as the most effective sub-modes for reducing sBP (90.4%) and dBP (91.3%) respectively. Conclusion: Various exercise training modes improve resting blood pressure, particularly isometric exercise. The results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension

Chaos and Preheating

We show evidence for a relationship between chaos and parametric resonance both in a classical system and in the semiclassical process of particle creation. We apply our considerations in a toy model for preheating after inflation.Comment: 7 pages, 9 figures; uses epsfig and revtex v3.1. Matches version accepted for publication in Phys. Rev.

Statistical Model of Superconductivity in a 2D Binary Boson-Fermion Mixture

A two-dimensional (2D) assembly of noninteracting, temperature-dependent, composite-boson Cooper pairs (CPs) in chemical and thermal equilibrium with unpaired fermions is examined in a binary boson-fermion statistical model as the superconducting singularity temperature is approached from above. The model is derived from {\it first principles} for the BCS model interfermion interaction from three extrema of the system Helmholtz free energy (subject to constant pairable-fermion number) with respect to: a) the pairable-fermion distribution function; b) the number of excited (bosonic) CPs, i.e., with nonzero total momenta--usually ignored in BCS theory--and with the appropriate (linear, as opposed to quadratic) dispersion relation that arises from the Fermi sea; and c) the number of CPs with zero total momenta. Compared with the BCS theory condensate, higher singularity temperatures for the Bose-Einstein condensate are obtained in the binary boson-fermion mixture model which are in rough agreement with empirical critical temperatures for quasi-2D superconductorsComment: 16 pages and 4 figures. This is a improved versio

Quantum curves for Hitchin fibrations and the Eynard-Orantin theory

We generalize the topological recursion of Eynard-Orantin (2007) to the family of spectral curves of Hitchin fibrations. A spectral curve in the topological recursion, which is defined to be a complex plane curve, is replaced with a generic curve in the cotangent bundle $T^*C$ of an arbitrary smooth base curve $C$. We then prove that these spectral curves are quantizable, using the new formalism. More precisely, we construct the canonical generators of the formal $\hbar$-deformation family of $D$-modules over an arbitrary projective algebraic curve $C$ of genus greater than $1$, from the geometry of a prescribed family of smooth Hitchin spectral curves associated with the $SL(2,\mathbb{C})$-character variety of the fundamental group $\pi_1(C)$. We show that the semi-classical limit through the WKB approximation of these $\hbar$-deformed $D$-modules recovers the initial family of Hitchin spectral curves.Comment: 34 page

The Point of Origin of the Radio Radiation from the Unresolved Cores of Radio-Loud Quasars

Locating the exact point of origin of the core radiation in active galactic nuclei (AGN) would represent important progress in our understanding of physical processes in the central engine of these objects. However, due to our inability to resolve the region containing both the central compact object and the jet base, this has so far been difficult. Here, using an analysis in which the lack of resolution does not play a significant role, we demonstrate that it may be impossible even in most radio loud sources for more than a small percentage of the core radiation at radio wavelengths to come from the jet base. We find for 3C279 that $\sim85$ percent of the core flux at 15 GHz must come from a separate, reasonably stable, region that is not part of the jet base, and that then likely radiates at least quasi-isotropically and is centered on the black hole. The long-term stability of this component also suggests that it may originate in a region that extends over many Schwarzschild radii.Comment: 7 pages with 3 figures, accepted for publication in Astrophysics and Space Scienc