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Comparison of Single-Stage and Staged Progression Models for HIV/AIDS Transmission  [PDF]
F. Baryarama,J. Y. T. Mugisha
International Journal of Mathematics and Mathematical Sciences , 2007, DOI: 10.1155/2007/18908
Abstract: A single-staged (SS) model and a staged progression (SP) model for HIV/AIDS with the same variable contact rate over time were formulated. In both models, analytical expressions for the HIV prevalence were obtained. A comparison of the two models was undertaken. It is shown that prevalence projections from the SS model are lower than projections from the SP model up to and beyond the peak prevalence, although the SS model prevalence may be higher than that of the SP model much later in the epidemic. A switch from faster SP model prevalence changes to faster SS prevalence changes occurs beyond the SP model peak prevalence. Hence using the SS model underestimates HIV prevalence in the early stages of the epidemic but may overestimate prevalence in the declining HIV prevalence phase. Our comparison suggests that the SP model provides better prevalence projections than the SS model. Moreover, the extra parameters that would make the SP model appear difficult to implement may not be sought from national survey data but from existing HIV/AIDS literature.
Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression
Gopeshwar Narayan, Chandra Goparaju, Hugo Arias-Pulido, Andreas M Kaufmann, Achim Schneider, Matthias Dürst, Mahesh Mansukhani, Bhavana Pothuri, Vundavalli V Murty
Molecular Cancer , 2006, DOI: 10.1186/1476-4598-5-16
Abstract: To test whether Slit-Robo pathway genes are targets of inactivation at these sites of deletion, we examined promoter hypermethylation of SLIT1, SLIT2, SLIT3, ROBO1, and ROBO3 genes in invasive CC and its precursor lesions. We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs) in CC cell lines failed to effectively reactivate the down-regulated expression. These results suggest a complex mechanism of inactivation in the Slit-Robo pathway in CC. By analysis of cervical precancerous lesions, we further show that promoter hypermethylation of Slit-Robo pathway occurs early in tumor progression.Taken together, these findings suggest that epigenetic alterations of Slit-Robo pathway genes (i) play a role in CC development, (ii) further delineation of molecular basis of promoter methylation-mediated gene regulation provides a potential basis for epigenetic-based therapy in advanced stage CC, and (iii) form epigenetic signatures to identify precancerous lesions at risk to progression.Metastasis and treatment failure is a significant cause of death in invasive Cervical Cancer (CC). Although combination chemotherapy with cisplatin as a primary agent has been commonly used in CC, the overall survival rate did not significantly improve [1]. Despite the obvious role of invasion and metastasis in treatment failure of CC, the molecular mechanisms remain poorly understood. A wide number of genes implicated in metastasis that play role in the migration of tumor cells have been identified [2]. In particular, chemokines that contribute to tumor cell invasion and growth plays a major role in metastasis [3]. Recently, a regulatory molecular pathway involving proteins of Slit-Robo genes has been shown to modulate chemokine-induced leukocyte migration [4,5]. The Slit family of secreted proteins has been identified as molecular gu
Global gene expression profile progression in Gaucher disease mouse models
You-Hai Xu, Li Jia, Brian Quinn, Matthew Zamzow, Keith Stringer, Bruce Aronow, Ying Sun, Wujuan Zhang, Kenneth DR Setchell, Gregory A Grabowski
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-20
Abstract: To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct Gba1 point-mutated mice (V394L/V394L and D409 V/null). About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change), representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk) of INFγ-regulated pro-inflammatory (13) and IL-4-regulated anti-inflammatory (11) cytokine/mediator networks showed tissue differential profiles in the lung and liver of the Gba1 mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the Gba1 mutation.Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.Gaucher disease, an autosomal recessive disorder, is a common lysosomal storage disease. Insufficient activity of acid β-glucosidase (glucocerebrosidase, GCase, E.C.3.2.1.45) in all cells leads to the substrate accumulation including glucosylceramide and glucosylsphingosine, and the various clinical phenotypes. The pathologic hallmark of Gaucher disease is the presence of lipid laden macrophages, a.k.a., Gaucher cells, in visceral organs [1]. The macrophages are thought to be the primary visceral cells involved in all variants, and these cells become progressively numerous and engorged with glucosylceramide by phagocytic processes. By yet undefined mechanisms, this process leads to tissue dysfunction that can result in fibrosis and scarring during the later stages of the disease.Some of these tissue changes have been att
Evaluating the potential impact of the new Global Plan to Stop TB: Thailand, 2004-2005
Varma,Jay K; Wiriyakitjar,Daranee; Nateniyom,Sriprapa; Anuwatnonthakate,Amornrat; Monkongdee,Patama; Sumnapan,Surin; Akksilp,Somsak; Sattayawuthipong,Wanchai; Charunsuntonsri,Pricha; Rienthong,Somsak; Yamada,Norio; Akarasewi,Pasakorn; Wells,Charles D; Tappero,Jordan W;
Bulletin of the World Health Organization , 2007, DOI: 10.1590/S0042-96862007000800010
Abstract: objective: who's new global plan to stop tb 2006-2015 advises countries with a high burden of tuberculosis (tb) to expand case-finding in the private sector as well as services for patients with hiv and multidrug-resistant tb (mdr-tb). the objective of this study was to evaluate these strategies in thailand using data from the thailand tb active surveillance network, a demonstration project begun in 2004. methods: in october 2004, we began contacting public and private health-care facilities monthly to record data about people diagnosed with tb, assist with patient care, provide hiv counselling and testing, and obtain sputum samples for culture and susceptibility testing. the catchment area included 3.6 million people in four provinces. we compared results from october 2004-september 2005 (referred to as 2005) to baseline data from october 2002-september 2003 (referred to as 2003). findings: in 2005, we ascertained 5841 tb cases (164/100 000), including 2320 new smear-positive cases (65/100 000). compared with routine passive surveillance in 2003, active surveillance increased reporting of all tb cases by 19% and of new smear-positive cases by 13%. private facilities diagnosed 634 (11%) of all tb cases. in 2005, 1392 (24%) cases were known to be hiv positive. the proportion of cases with an unknown hiv status decreased from 66% (3226/4904) in 2003 to 23% (1329/5841) in 2005 (p< 0.01). of 4656 pulmonary cases, mycobacterial culture was performed in 3024 (65%) and mdr-tb diagnosed in 60 (1%). conclusion: in thailand, piloting the new who strategy increased case-finding and collaboration with the private sector, and improved hiv services for tb patients and the diagnosis of mdr-tb. further analysis of treatment outcomes and costs is needed to assess this programme's impact and cost effectiveness.
Staged Mixture Modelling and Boosting  [PDF]
Christopher Meek,Bo Thiesson,David Heckerman
Computer Science , 2012,
Abstract: In this paper, we introduce and evaluate a data-driven staged mixture modeling technique for building density, regression, and classification models. Our basic approach is to sequentially add components to a finite mixture model using the structural expectation maximization (SEM) algorithm. We show that our technique is qualitatively similar to boosting. This correspondence is a natural byproduct of the fact that we use the SEM algorithm to sequentially fit the mixture model. Finally, in our experimental evaluation, we demonstrate the effectiveness of our approach on a variety of prediction and density estimation tasks using real-world data.
Equivalence Classes of Staged Trees  [PDF]
Christiane G?rgen,Jim Q. Smith
Statistics , 2015,
Abstract: In this paper we give a complete characterization of the equivalence classes of CEGs or equivalently of staged trees. This model class cannot be unambiguously indexed by its graphical properties. However, we are able to show that a polynomial defined on an underlying graph codes all relevant characteristics and is common to all representations of the same model. Furthermore, simple transformations on that polynomial enable us to traverse the statistical equivalence class of these graphs. So one can design efficient algorithms over these classes. We illustrate our results throughout the paper, finishing with a real analysis of the implicit dependence relationships found in a dataset.
Optimal Staged Self-Assembly of General Shapes  [PDF]
Cameron Chalk,Eric Martinez,Robert Schweller,Luis Vega,Andrew Winslow,Tim Wylie
Computer Science , 2015,
Abstract: We analyze the number of stages needed to construct $n \times n$ squares and scaled shapes within the staged tile assembly model. We give constructions that use a number of stages within a small additive factor of optimal for all bin and tile type counts. In particular, given a constraint of at most $b$ bins and $t$ tile types, we present an algorithm for the assembly of any $n\times n$ square with stage complexity $\mathcal{O}(\frac{\log{n} - tb - t\log t}{b^2} + \frac{\log b}{t} +1)$, which nearly matches the information theoretic lower bound of $\Omega(\frac{\log{n} - tb - t\log t}{b^2})$ for almost all $n$. For a general shape $S$, we present bounds of $\mathcal{O}(\frac{K(S) - tb - t\log t}{b^2} + \frac{\log b}{t} +1)$ and $\Omega(\frac{K(S) - tb - t\log t}{b^2})$ for the assembly of a scaled version of $S$, where $K(S)$ denotes the Kolmogorov complexity of $S$ with respect to some universal Turing machine. Matching results are also obtained when more powerful \emph{flexible} glue functions are permitted. The constructions use a common method of encoding information into "binary string" assemblies that uses both sources of system complexity (tile types and the mixing graph) efficiently.
Implementing the Global Plan to Stop TB, 2011–2015 – Optimizing Allocations and the Global Fund’s Contribution: A Scenario Projections Study  [PDF]
Eline L. Korenromp, Philippe Glaziou, Christopher Fitzpatrick, Katherine Floyd, Mehran Hosseini, Mario Raviglione, Rifat Atun, Brian Williams
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038816
Abstract: Background The Global Plan to Stop TB estimates funding required in low- and middle-income countries to achieve TB control targets set by the Stop TB Partnership within the context of the Millennium Development Goals. We estimate the contribution and impact of Global Fund investments under various scenarios of allocations across interventions and regions. Methodology/Principal Findings Using Global Plan assumptions on expected cases and mortality, we estimate treatment costs and mortality impact for diagnosis and treatment for drug-sensitive and multidrug-resistant TB (MDR-TB), including antiretroviral treatment (ART) during DOTS for HIV-co-infected patients, for four country groups, overall and for the Global Fund investments. In 2015, China and India account for 24% of funding need, Eastern Europe and Central Asia (EECA) for 33%, sub-Saharan Africa (SSA) for 20%, and other low- and middle-income countries for 24%. Scale-up of MDR-TB treatment, especially in EECA, drives an increasing global TB funding need – an essential investment to contain the mortality burden associated with MDR-TB and future disease costs. Funding needs rise fastest in SSA, reflecting increasing coverage need of improved TB/HIV management, which saves most lives per dollar spent in the short term. The Global Fund is expected to finance 8–12% of Global Plan implementation costs annually. Lives saved through Global Fund TB support within the available funding envelope could increase 37% if allocations shifted from current regional demand patterns to a prioritized scale-up of improved TB/HIV treatment and secondly DOTS, both mainly in Africa ? with EECA region, which has disproportionately high per-patient costs, funded from alternative resources. Conclusions/Significance These findings, alongside country funding gaps, domestic funding and implementation capacity and equity considerations, should inform strategies and policies for international donors, national governments and disease control programs to implement a more optimal investment approach focusing on highest-impact populations and interventions.
Economic Support to Patients in HIV and TB Grants in Rounds 7 and 10 from the Global Fund to Fight AIDS, Tuberculosis and Malaria  [PDF]
Linda M. Richter, Knut L?nnroth, Chris Desmond, Robin Jackson, Ernesto Jaramillo, Diana Weil
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086225
Abstract: People with TB and/or HIV frequently experience severe economic barriers to health care, including out-of-pocket expenses related to diagnosis and treatment, as well as indirect costs due to loss of income. These barriers can both aggravate economic hardship and prevent or delay diagnosis, treatment and successful outcome, leading to increased transmission, morbidity and mortality. WHO, UNAIDS and the ILO argue that economic support of various kinds is essential to enable vulnerable people to protect themselves from infection, avoid delayed diagnosis and treatment, overcome barriers to adherence, and avert destitution. This paper analyses successful country proposals to the Global Fund to Fight AIDS, Tuberculosis and Malaria that include economic support in Rounds 7 and 10; 36 and 20 HIV and TB grants in Round 7 and 32 and 26, respectively, in Round 10. Of these, up to 84 percent included direct or indirect economic support for beneficiaries, although the amount constituted a very small proportion of the total grant. In TB grants, the objectives of economic support were generally clearly stated, and focused on mechanisms to improve treatment uptake and adherence, and the case was most clearly made for MDR-TB patients. In HIV grants, the objectives were much broader in scope, including mitigation of adverse economic and social effects of HIV and its treatment on both patients and families. The analysis shows that economic support is on the radar for countries developing Global Fund proposals, and a wide range of economic support activities are in place. In order to move forward in this area, the wealth of country experience that exists needs to be collated, assessed and disseminated. In addition to trials, operational research and programme evaluations, more precise guidance to countries is needed to inform evidence-based decision about activities that are cost-effective, affordable and feasible.
A Novel Surgical Template Design in Staged Dental Implant Rehabilitations  [cached]
Michael Patras,William Martin,Nikitas Sykaras
Journal of Oral & Maxillofacial Research , 2012,
Abstract: Background: The philosophy of a gradual transition to an implant retained prosthesis in cases of full-mouth or extensive rehabilitation usually involves a staged treatment concept. In this therapeutic approach, the placement of implants may sometimes be divided into phases. During a subsequent surgical phase of treatment, the pre-existing implants can serve as anchors for the surgical template. Those modified surgical templates help in the precise transferring of restorative information into the surgical field and guide the optimal three-dimensional implant positioning. Methods: This article highlights the rationale of implant-retained surgical templates and illustrates them through the presentation of two clinical cases. The templates are duplicates of the provisional restorations and are secured to the existing implants through the utilization of implant mounts. Results: This template design in such staged procedures provided stability in the surgical field and enhanced the accuracy in implant positioning based upon the planned restoration, thus ensuring predictable treatment outcomes.Conclusions: Successful rehabilitation lies in the correct sequence of surgical and prosthetic procedures. Whenever a staged approach of implant placement is planned, the clinician can effectively use the initially placed implants as anchors for the surgical template during the second phase of implant surgery.
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