In the interests of time: Improving HIV allocative efficiency modelling via optimal time-varying allocations

Introduction: International investment in the response to HIV and AIDS has plateaued and its future level is uncertain. With many countries committed to ending the epidemic, it is essential to allocate available resources efficiently over different response periods to maximize impact. The objective of this study is to propose a technique to determine the optimal allocation of funds over time across a set of HIV programmes to achieve desirable health outcomes. Methods: We developed a technique to determine the optimal time-varying allocation of funds (1) when the future annual HIV budget is pre-defined and (2) when the total budget over a period is pre-defined, but the year-on-year budget is to be optimally determined. We use this methodology with Optima, an HIV transmission model that uses non-linear relationships between programme spending and associated programmatic outcomes to quantify the expected epidemiological impact of spending.We apply these methods to data collected from Zambia to determine the optimal distribution of resources to fund the right programmes, for the right people, at the right time. Results and discussion: Considering realistic implementation and ethical constraints, we estimate that the optimal time-varying redistribution of the 2014 Zambian HIV budget between 2015 and 2025 will lead to a 7.6% (7.3% to 7.8%) decrease in cumulative new HIV infections compared with a baseline scenario where programme allocations remain at 2014 levels. This compares to a 5.1% (4.6% to 5.6%) reduction in new infections using an optimal allocation with constant programme spending that recommends unrealistic programmatic changes. Contrasting priorities for programme funding arise when assessing outcomes for a five-year funding period over 5-, 10- and 20-year time horizons. Conclusions: Countries increasingly face the need to do more with the resources available. The methodology presented here can aid decision-makers in planning as to when to expand or contract programmes and to which coverage levels to maximize impact

Phylogeny of Prokaryotes and Chloroplasts Revealed by a Simple Composition Approach on All Protein Sequences from Complete Genomes Without Sequence Alignment

The complete genomes of living organisms have provided much information on their phylogenetic relationships. Similarly, the complete genomes of chloroplasts have helped to resolve the evolution of this organelle in photosynthetic eukaryotes. In this paper we propose an alternative method of phylogenetic analysis using compositional statistics for all protein sequences from complete genomes. This new method is conceptually simpler than and computationally as fast as the one proposed by Qi et al. (2004b) and Chu et al. (2004). The same data sets used in Qi et al. (2004b) and Chu et al. (2004) are analyzed using the new method. Our distance-based phylogenic tree of the 109 prokaryotes and eukaryotes agrees with the biologists tree of life based on 16S rRNA comparison in a predominant majority of basic branching and most lower taxa. Our phylogenetic analysis also shows that the chloroplast genomes are separated to two major clades corresponding to chlorophytes s.l. and rhodophytes s.l. The interrelationships among the chloroplasts are largely in agreement with the current understanding on chloroplast evolution

Alemtuzumab preconditioning with tacrolimus monotherapy - The impact of serial monitoring for donor-specific antibody

BACKGROUND. Antibody preconditioning with tacrolimus monotherapy has allowed many renal allograft recipients to be maintained on spaced weaning. METHODS. Of 279 renal allograft recipients transplanted between March 2003 and December 2004, 222 (80%) had spaced weaning (i.e., reduction of tacrolimus monotherapy dosing to every other day, three times a week, twice a week, or once a week) attempted. Routine monitoring for donor-specific antibody (DSA) was begun in September 2004. Mean follow-up is 34±6.5 months after transplantation and 26±8.1 months after the initiation of spaced weaning. RESULTS. One hundred and twenty-two (44%) patients remained on spaced weaning. One- and 2-year actual patient/graft survival was 99%/99%, and 97%/96%. Fifty-six (20%) patients experienced acute rejection after initiation of spaced weaning. One- and 2-year actual patient/graft survival was 100%/98%, and 94%/78%. Forty-two (15%) patients with stable renal function had spaced weaning stopped because of the development of DSA, which disappeared in 17 (40%). One- and 2-year actual patient and graft survival was 100% and 100%. CONCLUSION. Adult renal transplant recipients who are able to be maintained on spaced weaning have excellent outcomes. Patients with stable renal function who have reversal of weaning because of the development of DSA also have excellent outcomes. Routine monitoring for DSA may allow patients to avoid late rejection after spaced weaning. © 2008 Lippincott Williams & Wilkins, Inc

Two-Loop O(αsGFmt2){\cal O}(\alpha_sG_Fm_t^2) Corrections to the Fermionic Decay Rates of the Standard-Model Higgs Boson

Low- and intermediate mass Higgs bosons decay preferably into fermion pairs. The one-loop electroweak corrections to the respective decay rates are dominated by a flavour-independent term of ${\cal O}(G_Fm_t^2)$. We calculate the two-loop gluon correction to this term. It turns out that this correction screens the leading high-$m_t$ behaviour of the one-loop result by roughly 10\%. We also present the two-loop QCD correction to the contribution induced by a pair of fourth-generation quarks with arbitrary masses. As expected, the inclusion of the QCD correction considerably reduces the renormalization-scheme dependence of the prediction.Comment: 14 pages, latex, figures 2-5 appended, DESY 94-08

The Nielsen Identities of the SM and the definition of mass

In a generic gauge theory the gauge parameter dependence of individual Green functions is controlled by the Nielsen identities, which originate from an enlarged BRST symmetry. We give a practical introduction to the Nielsen identities of the Standard Model (SM) and to their renormalization and illustrate the power of this elegant formalism in the case of the problem of the definition of mass.We prove to all orders in perturbation theory the gauge-independence of the complex pole of the propagator for all physical fields of the SM, in the most general case with mixing and CP violation. At the amplitude level, the formalism provides an intuitive and general understanding of the gauge recombinations which makes it particularly useful at higher orders. We also include in an appendix the explicit expressions for the fermionic two-point functions in a generic R_\xi gauge.Comment: 28 pages, LaTeX2e, 4 Postscript Figures, final version to appear on PRD, extensive revision

Two-loop scalar self-energies in a general renormalizable theory at leading order in gauge couplings

I present results for the two-loop self-energy functions for scalars in a general renormalizable field theory, using mass-independent renormalization schemes based on dimensional regularization and dimensional reduction. The results are given in terms of a minimal set of loop-integral basis functions, which are readily evaluated numerically by computers. This paper contains the contributions corresponding to the Feynman diagrams with zero or one vector propagator lines. These are the ones needed to obtain the pole masses of the neutral and charged Higgs scalar bosons in supersymmetry, neglecting only the purely electroweak parts at two-loop order. A subsequent paper will present the results for the remaining diagrams, which involve two or more vector lines.Comment: 26 pages, 4 figures, revtex4, axodraw.sty. Version 2: sentence after eq. (A.13) corrected, references added. Version 3: typos in eqs. (5.17), (5.20), (5.21), (5.32) are corrected. Also, the MSbar versions of eqs. (5.32) and (5.33) are now include

Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment

Study of Constrained Minimal Supersymmetry

Taking seriously phenomenological indications for supersymmetry, we have made a detailed study of unified minimal SUSY, including effects at the few percent level in a consistent fashion. We report here a general analysis without choosing a particular unification gauge group. We find that the encouraging SUSY unification results of recent years do survive the challenge of a more complete and accurate analysis. Taking into account effects at the 5-10% level leads to several improvements of previous results, and allows us to sharpen our predictions for SUSY in the light of unification. We perform a thorough study of the parameter space. The results form a well-defined basis for comparing the physics potential of different facilities. Very little of the acceptable parameter space has been excluded by LEP or FNAL so far, but a significant fraction can be covered when these accelerators are upgraded. A number of initial applications to the understanding of the SUSY spectrum, detectability of SUSY at LEP II or FNAL, BR($b\to s\gamma$), Width($Z\to b\bar b$), dark matter, etc, are included in a separate section. We formulate an approach to extracting SUSY parameters from data when superpartners are detected. For small tan(beta) or large $m_top$ both $M_half$ and $M_0$ are entirely bounded from above at O(1 tev) without having to use a fine-tuning constraint.Comment: Michigan preprint UM-TH-93-24, LaTeX, 60 pages without figures. Complete paper with inline figures available by anonymous ftp to williams.physics.lsa.umich.edu in /pub/preprints/UM-TH-93-24.ps.Z (uncompresses to 10MB / 77 pages), or by e-mailing reques

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199