Modelling a silent epidemic:A review of the in vitro models of latent tuberculosis

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance

Enhancing the management of anorexia of ageing to counteract malnutrition : are physical activity guidelines optimal?

Funding Information: NJC and SERL receive funding from by The National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.Peer reviewedPublisher PD

Expanding the application of cassava value chain technologies through UPoCA project

Root and Tuber . IITA TechnologiesCassava has long been expected to play a key role in rural economic growth in Africa, but are we there yet? Although research partnerships have produced elite cassava varieties with 50% more yielding potential and demonstrated technologies to boost processing and marketing of cassava, the sub-sector is constrained by low productivity and marketing dificulties. In DR Congo, Ghana, Malawi and Sierra Leone, for example, cassava value chain actors are yet to respond to 2007 estimated $59 million trade opportunities through substitution of imported wheat lour with locally produced high quality cassava lour. Industrial pull for cassava would also aggravate hunger and poverty if yields do not increase from current national averages of 5 to 19t/ha to more than 25t/ha expected of released varieties under low input agriculture. In 2008, USAID and IITA initiated the project “Unleashing the Power of Cassava in Response to Food Price Crisis (UPOCA) as a multi-country and inter-institutional partnership enabling cassava sub-sectors to realize their full potential in rural economies. UPoCA project covers DR Congo, Ghana, Malawi, Mozambique, Nigeria, Sierra Leone, and Tanzania. UPoCA project draws on prior research results to increase on-farm cassava productivity and value adding processing for markets. By end 2009, small holder beneiciaries associated with 55 partner organizations and 11 agricultural related irms established 306 community cassava stem multiplication sites and root production farms totalling 10,097ha with 58 improved varieties. Through experiential learning at 24 hands-on short-term courses, 345 men and 142 women learnt improved techniques in cassava production, processing, product development, and packaging/labelling and 8 technologies were introduced to rural communities. Seven other papers in this symposium, based on these evolving UPoCA achievements, show that a longer-term cassava research for development partnership platform of this nature will enable cassava sub-sectors to contribute signiicantly to rural economic growth in Africa

On the Regularity Property of Differential Polynomials Modulo Regular Differential Chains

International audienceThis paper provides an algorithm which computes the normal form of a rational differential fraction modulo a regular differential chain if, and only if, this normal form exists. A regularity test for polynomials modulo regular chains is revisited in the nondifferential setting and lifted to differential algebra. A new characterization of regular chains is provided

Anomalous diffusion and the first passage time problem

We study the distribution of first passage time (FPT) in Levy type of anomalous diffusion. Using recently formulated fractional Fokker-Planck equation we obtain three results. (1) We derive an explicit expression for the FPT distribution in terms of Fox or H-functions when the diffusion has zero drift. (2) For the nonzero drift case we obtain an analytical expression for the Laplace transform of the FPT distribution. (3) We express the FPT distribution in terms of a power series for the case of two absorbing barriers. The known results for ordinary diffusion (Brownian motion) are obtained as special cases of our more general results.Comment: 25 pages, 4 figure

Non-linear response of a Kondo system: Perturbation approach to the time dependent Anderson impurity model

Nonlinear tunneling current through a quantum dot (an Anderson impurity system) subject to both constant and alternating electric fields is studied in the Kondo regime. A systematic diagram technique is developed for perturbation study of the current in physical systems out of equilibrium governed by time - dependent Hamiltonians of the Anderson and the Kondo models. The ensuing calculations prove to be too complicated for the Anderson model, and hence, a mapping on an effective Kondo problem is called for. This is achieved by constructing a time - dependent version of the Schrieffer - Wolff transformation. Perturbation expansion of the current is then carried out up to third order in the Kondo coupling J yielding a set of remarkably simple analytical expressions for the current. The zero - bias anomaly of the direct current differential conductance is shown to be suppressed by the alternating field while side peaks develop at finite source - drain voltage. Both the direct component and the first harmonics of the time - dependent response are equally enhanced due to the Kondo effect, while amplitudes of higher harmonics are shown to be relatively small. A zero alternating bias anomaly is found in the alternating current differential conductance, that is, it peaks around zero alternating bias. This peak is suppressed by the constant bias. No side peaks show up in the differential alternating - conductance but their counterpart is found in the derivative of the alternating current with respect to the direct bias. The results pertaining to nonlinear response are shown to be valid also below the Kondo temperature.Comment: 55 latex pages 11 ps figure

Stability of the monoclinic phase in the ferroelectric perovskite PbZr(1-x)TixO3

Recent structural studies of ferroelectric PbZr(1-x)TixO3 (PZT) with x= 0.48, have revealed a new monoclinic phase in the vicinity of the morphotropic phase boundary (MPB), previously regarded as the the boundary separating the rhombohedral and tetragonal regions of the PZT phase diagram. In the present paper, the stability region of all three phases has been established from high resolution synchrotron x-ray powder diffraction measurements on a series of highly homogeneous samples with 0.42 <=x<= 0.52. At 20K the monoclinic phase is stable in the range 0.46 <=x<= 0.51, and this range narrows as the temperature is increased. A first-order phase transition from tetragonal to rhombohedral symmetry is observed only for x= 0.45. The MPB, therefore, corresponds not to the tetragonal-rhombohedral phase boundary, but instead to the boundary between the tetragonal and monoclinic phases for 0.46 <=x<= 0.51. This result provides important insight into the close relationship between the monoclinic phase and the striking piezoelectric properties of PZT; in particular, investigations of poled samples have shown that the monoclinic distortion is the origin of the unusually high piezoelectric response of PZT.Comment: REVTeX file, 7 figures embedde

Joint modeling of longitudinal outcomes and survival using latent growth modeling approach in a mesothelioma trial

Joint modeling of longitudinal and survival data can provide more efficient and less biased estimates of treatment effects through accounting for the associations between these two data types. Sponsors of oncology clinical trials routinely and increasingly include patient-reported outcome (PRO) instruments to evaluate the effect of treatment on symptoms, functioning, and quality of life. Known publications of these trials typically do not include jointly modeled analyses and results. We formulated several joint models based on a latent growth model for longitudinal PRO data and a Cox proportional hazards model for survival data. The longitudinal and survival components were linked through either a latent growth trajectory or shared random effects. We applied these models to data from a randomized phase III oncology clinical trial in mesothelioma. We compared the results derived under different model specifications and showed that the use of joint modeling may result in improved estimates of the overall treatment effect