Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis.

OBJECTIVE: To investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa. METHODS: We used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage. RESULTS: All the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year. CONCLUSIONS: Despite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART

How acceptable are antiretrovirals for the prevention of sexually transmitted HIV? A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention

Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence

Discovery and saturation analysis of cancer genes across 21 tumour types

Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2–20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600–5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics

On the Polynomial Measurement Error Model

This paper discusses point estimation of the coefficients of polynomial measurement error (errors-in-variables) models. This includes functional and structural models. The connection between these models and total least squares (TLS) is also examined. A compendium of existing as well as new results is presented

Numerical solutions of random mean square Fisher-KPP models with advection

[EN] This paper deals with the construction of numerical stable solutions of random mean square Fisher-Kolmogorov-Petrosky-Piskunov (Fisher-KPP) models with advection. The construction of the numerical scheme is performed in two stages. Firstly, a semidiscretization technique transforms the original continuous problem into a nonlinear inhomogeneous system of random differential equations. Then, by extending to the random framework, the ideas of the exponential time differencing method, a full vector discretization of the problem addresses to a random vector difference scheme. A sample approach of the random vector difference scheme, the use of properties of Metzler matrices and the logarithmic norm allow the proof of stability of the numerical solutions in the mean square sense. In spite of the computational complexity, the results are illustrated by comparing the results with a test problem where the exact solution is known.Ministerio de Economia y Competitividad, Grant/Award Number: MTM2017-89664-PCasabán Bartual, MC.; Company Rossi, R.; Jódar Sánchez, LA. (2020). Numerical solutions of random mean square Fisher-KPP models with advection. Mathematical Methods in the Applied Sciences. 43(14):8015-8031. https://doi.org/10.1002/mma.5942S801580314314FISHER, R. A. (1937). THE WAVE OF ADVANCE OF ADVANTAGEOUS GENES. Annals of Eugenics, 7(4), 355-369. doi:10.1111/j.1469-1809.1937.tb02153.xBengfort, M., Malchow, H., & Hilker, F. M. (2016). The Fokker–Planck law of diffusion and pattern formation in heterogeneous environments. Journal of Mathematical Biology, 73(3), 683-704. doi:10.1007/s00285-016-0966-8Okubo, A., & Levin, S. A. (2001). Diffusion and Ecological Problems: Modern Perspectives. Interdisciplinary Applied Mathematics. doi:10.1007/978-1-4757-4978-6SKELLAM, J. G. (1951). RANDOM DISPERSAL IN THEORETICAL POPULATIONS. Biometrika, 38(1-2), 196-218. doi:10.1093/biomet/38.1-2.196Aronson, D. G., & Weinberger, H. F. (1975). Nonlinear diffusion in population genetics, combustion, and nerve pulse propagation. Partial Differential Equations and Related Topics, 5-49. doi:10.1007/bfb0070595Aronson, D. ., & Weinberger, H. . (1978). Multidimensional nonlinear diffusion arising in population genetics. Advances in Mathematics, 30(1), 33-76. doi:10.1016/0001-8708(78)90130-5Weinberger, H. F. (2002). On spreading speeds and traveling waves for growth and migration models in a periodic habitat. Journal of Mathematical Biology, 45(6), 511-548. doi:10.1007/s00285-002-0169-3Weinberger, H. F., Lewis, M. A., & Li, B. (2007). Anomalous spreading speeds of cooperative recursion systems. Journal of Mathematical Biology, 55(2), 207-222. doi:10.1007/s00285-007-0078-6Liang, X., & Zhao, X.-Q. (2006). Asymptotic speeds of spread and traveling waves for monotone semiflows with applications. Communications on Pure and Applied Mathematics, 60(1), 1-40. doi:10.1002/cpa.20154E. Fitzgibbon, W., Parrott, M. E., & Webb, G. (1995). Diffusive epidemic models with spatial and age dependent heterogeneity. Discrete & Continuous Dynamical Systems - A, 1(1), 35-57. doi:10.3934/dcds.1995.1.35Kinezaki, N., Kawasaki, K., & Shigesada, N. (2006). Spatial dynamics of invasion in sinusoidally varying environments. Population Ecology, 48(4), 263-270. doi:10.1007/s10144-006-0263-2Jin, Y., Hilker, F. M., Steffler, P. M., & Lewis, M. A. (2014). Seasonal Invasion Dynamics in a Spatially Heterogeneous River with Fluctuating Flows. Bulletin of Mathematical Biology, 76(7), 1522-1565. doi:10.1007/s11538-014-9957-3Faou, E. (2009). Analysis of splitting methods for reaction-diffusion problems using stochastic calculus. Mathematics of Computation, 78(267), 1467-1483. doi:10.1090/s0025-5718-08-02185-6Doering, C. R., Mueller, C., & Smereka, P. (2003). Interacting particles, the stochastic Fisher–Kolmogorov–Petrovsky–Piscounov equation, and duality. Physica A: Statistical Mechanics and its Applications, 325(1-2), 243-259. doi:10.1016/s0378-4371(03)00203-6Siekmann, I., Bengfort, M., & Malchow, H. (2017). Coexistence of competitors mediated by nonlinear noise. The European Physical Journal Special Topics, 226(9), 2157-2170. doi:10.1140/epjst/e2017-70038-6McKean, H. P. (1975). Application of brownian motion to the equation of kolmogorov-petrovskii-piskunov. Communications on Pure and Applied Mathematics, 28(3), 323-331. doi:10.1002/cpa.3160280302Berestycki, H., & Nadin, G. (2012). Spreading speeds for one-dimensional monostable reaction-diffusion equations. Journal of Mathematical Physics, 53(11), 115619. doi:10.1063/1.4764932Cortés, J. C., Jódar, L., Villafuerte, L., & Villanueva, R. J. (2007). Computing mean square approximations of random diffusion models with source term. Mathematics and Computers in Simulation, 76(1-3), 44-48. doi:10.1016/j.matcom.2007.01.020Villafuerte, L., Braumann, C. A., Cortés, J.-C., & Jódar, L. (2010). Random differential operational calculus: Theory and applications. Computers & Mathematics with Applications, 59(1), 115-125. doi:10.1016/j.camwa.2009.08.061Casabán, M.-C., Cortés, J.-C., & Jódar, L. (2016). Solving linear and quadratic random matrix differential equations: A mean square approach. Applied Mathematical Modelling, 40(21-22), 9362-9377. doi:10.1016/j.apm.2016.06.017Sarmin, E. N., & Chudov, L. A. (1963). On the stability of the numerical integration of systems of ordinary differential equations arising in the use of the straight line method. USSR Computational Mathematics and Mathematical Physics, 3(6), 1537-1543. doi:10.1016/0041-5553(63)90256-8Sanz-Serna, J. M., & Verwer, J. G. (1989). 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Preference for novel faces in male infant monkeys predicts cerebrospinal fluid oxytocin concentrations later in life

The ability to recognize individuals is a critical skill acquired early in life for group living species. In primates, individual recognition occurs predominantly through face discrimination. Despite the essential adaptive value of this ability, robust individual differences in conspecific face recognition exist, yet its associated biology remains unknown. Although pharmacological administration of oxytocin has implicated this neuropeptide in face perception and social memory, no prior research has tested the relationship between individual differences in face recognition and endogenous oxytocin concentrations. Here we show in a male rhesus monkey cohort (N = 60) that infant performance in a task used to determine face recognition ability (specifically, the ability of animals to show a preference for a novel face) robustly predicts cerebrospinal fluid, but not blood, oxytocin concentrations up to five years after behavioural assessment. These results argue that central oxytocin biology may be related to individual face perceptual abilities necessary for group living, and that these differences are stable traits

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

A boosting method for maximizing the partial area under the ROC curve

<p>Abstract</p> <p>Background</p> <p>The receiver operating characteristic (ROC) curve is a fundamental tool to assess the discriminant performance for not only a single marker but also a score function combining multiple markers. The area under the ROC curve (AUC) for a score function measures the intrinsic ability for the score function to discriminate between the controls and cases. Recently, the partial AUC (pAUC) has been paid more attention than the AUC, because a suitable range of the false positive rate can be focused according to various clinical situations. However, existing pAUC-based methods only handle a few markers and do not take nonlinear combination of markers into consideration.</p> <p>Results</p> <p>We have developed a new statistical method that focuses on the pAUC based on a boosting technique. The markers are combined componentially for maximizing the pAUC in the boosting algorithm using natural cubic splines or decision stumps (single-level decision trees), according to the values of markers (continuous or discrete). We show that the resulting score plots are useful for understanding how each marker is associated with the outcome variable. We compare the performance of the proposed boosting method with those of other existing methods, and demonstrate the utility using real data sets. As a result, we have much better discrimination performances in the sense of the pAUC in both simulation studies and real data analysis.</p> <p>Conclusions</p> <p>The proposed method addresses how to combine the markers after a pAUC-based filtering procedure in high dimensional setting. Hence, it provides a consistent way of analyzing data based on the pAUC from maker selection to marker combination for discrimination problems. The method can capture not only linear but also nonlinear association between the outcome variable and the markers, about which the nonlinearity is known to be necessary in general for the maximization of the pAUC. The method also puts importance on the accuracy of classification performance as well as interpretability of the association, by offering simple and smooth resultant score plots for each marker.</p

Multilevel analysis of clinical parameters in chronic periodontitis after root planing/scaling, surgery, and systemic and local antibiotics: 2-year results

Aim: Find the periodontal treatment that best maintained clinical results over time evaluated by changes in pocket depth (PD) and clinical attachment level (CAL). Methods: 229 patients with chronic periodontitis from USA (n=134) and Sweden (n=95) were randomly assigned to eight groups receiving 1 scaling+root planing (SRP) alone or combined with 2 surgery (SURG)+systemic amoxicillin (AMOX)+systemic metronidazole (MET); 3 SURG+local tetracycline (TET); 4 SURG; 5 AMOX+MET+TET; 6 AMOX+MET; 7 TET; and 8 SURG+AMOX+MET+TET. Antibiotics were given immediately after SRP. Plaque, gingival redness, bleeding on probing, suppuration, PD, and CAL were recorded at baseline and after 3, 6, 12, 18, and 24 months. Treatment effects were evaluated by linear multilevel regression and logistic multilevel regression models. We considered only data from sites with a baseline PD of at least 5 mm of 187 patients completing the study. Results: Surgically treated patients experienced most CAL loss. Adjunctive therapy including SURG was most effective in reducing PD. Combining SURG with AMOX, MET, and TET gave significant clinical benefits. Past and current smoking habits were significant predictors of deeper PD. Only current smoking was a significant predictor of CAL loss. Bleeding, accumulation of plaque, gingival redness, and suppuration were significant predictors of further CAL loss and deeper PD. Conclusions: Both surgical and non-surgical therapies can be used to arrest chronic periodontitis. SURG+AMOX+MET+TET gave best maintenance of clinical results