The influence of human immunodeficiency virus and early antiretroviral therapy on the immunology and virology of infants and children

In children infected with human immunodeficiency virus (HIV) CD4 T-cell loss results in profound immunodeficiency and susceptibility to infection, however loss of CD4 Tcells can be partially reversed by antiretroviral therapy (ART). Although the Children with HIV Early Antiretroviral Therapy (CHER) trial demonstrated significant reduction in morbidity and mortality from early ART among South African infants, the immunological and virological mechanisms by which this survival advantage occurs are not completely understood. The work described here used stored specimens of peripheral blood mononuclear cells and plasma from HIV-infected children in CHER and HIV-uninfected children from the Child Wellness Clinic, a cross-sectional study of healthy South African children. The overall aims were to explore the influence of HIV and ART on immunophenotypes, thymic and naïve B-cell output, HIV serostatus and HIV proviral DNA. The main outcomes included: development of haematological and immunological reference ranges for South African children; and an observation of a naïve/memory T-cell ratio of 1:1 within the first decade of life in South African children compared with the third decade in industrialised countries. Trajectories of thymic and naïve Bcell output were created for healthy South African children. Overall early ART sustained thymic output and increased naïve B-cell output in CHER participants compared to healthy controls. Higher CD4 counts were significantly associated with increased thymic output, and deferred/interrupted ART or poor clinical outcome were associated with lower thymic and naïve B-cell output. Early ART and continuous HIV RNA suppression reduces HIV proviral DNA, however despite adequate viral suppression, immunological disturbances persist. Finally, almost half children receiving early ART were HIV-antibody seronegative by 2 years. These insights develop understanding of the interplay between the immunology and virology of HIV-infected children on ART, and could support further research to advance ART-strategies and optimise the immunological fitness and clinical health of HIV-infected children

A formal analysis of Correspondence Theory

This paper provides a computational analysis of the complexity of GEN and Correspondence Theory in terms of the nature of the logic involved in their formulation. The first result of this analysis shows that the GEN function is not definable in Monadic Second Order (MSO) logic. Second, we show that the set of input-output Correspondence-theoretic candidates from a given underlying representation is definable in First Order (FO) logic, which is less complex than MSO-logic. Third, we present some case studies where the correct input-output Correspondence-theoretic candidate from a given underlying representation can be accomplished with FO-definable, language-specific, inviolable constraints without recourse to optimization

Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests.

ABSTRACT: BACKGROUND: The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. METHODS: A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 hours and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. RESULTS: A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p=0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p<0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67) CONCLUSION: Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc) may be needed to improve ACT targeting during low transmission seasons

A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains

In the first (and abstract) part of this survey we prove the unitary equivalence of the inverse of the Krein--von Neumann extension (on the orthogonal complement of its kernel) of a densely defined, closed, strictly positive operator, $S\geq \varepsilon I_{\mathcal{H}}$ for some $\varepsilon >0$ in a Hilbert space $\mathcal{H}$ to an abstract buckling problem operator. This establishes the Krein extension as a natural object in elasticity theory (in analogy to the Friedrichs extension, which found natural applications in quantum mechanics, elasticity, etc.). In the second, and principal part of this survey, we study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ (in short, the perturbed Krein Laplacian) defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$.Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144

Ocean forced variability of Totten Glacier mass loss

This is the author accepted manuscript. The final version is available from the Geological Society of London via the DOI in this record.A large volume of the East Antarctic Ice Sheet drains through the Totten Glacier (TG) and is thought to be a potential source of substantial global sea level rise over the coming centuries. We show the surface velocity and heightof the floating part of TG, which buttresses the grounded component, have varied substantially over two decades (1989–2011), with variations in surface height strongly anti-correlated with simulated basal melt rates (r=0.70, p<0.05). Coupled glacier/ice-shelf simulations confirm ice flow and thickness respond to both basal melting of the ice shelf and grounding on bed obstacles. We conclude the observed variability of TG is primarily ocean-driven. Ocean warming in this region will lead to enhanced ice-sheet dynamism and loss of upstream grounded ice.This work was supported by, Australian Antarctic Division projects 3103, 4077, 4287 and 4346, National Computing Infrastructure grant m68, NSF grant ANT-0733025, NASA grant NNX09AR52G (Operation Ice Bridge), NERC grant NE/F016646/1, NERC fellowship NE/G012733/2, the Jackson School of Geoscience, the Jet Propulsion Laboratory and the G. Unger Vetlesen Foundation. This research was also supported by the Australian Government’s Cooperative Research Centres Programme through the Antarctic Climate & Ecosystems Cooperative Research Centre. The work is also supported under the Australian Research Councils Special Research Initiative for Antarctic Gateway Partnership SR140300001. Landsat 4 and 7 images courtesy of the U.S. Geological Survey. This is UTIG contribution 2486. Thanks to Benoit Legresy for useful discussions

Application of network traffic flow model to road maintenance

The study shows how the evolution of two-way traffic flows on a local highway network can be predicted over time using a network-level traffic flow model (NTFM) to model both urban and motorway road networks. After a brief review of the main principles of the NTFM and its associated sub-models, the paper describes how a maintenance worksite can be modelled using a roadwork-node sub-model and a network solution routine in the NTFM. In order to model the two-way traffic flow in the road network, an iterative simulation method is used to generate the evolution of dependent traffic flows and queues. The NTFM has been applied to model the traffic characteristics and the effects of maintenance activities on the local Loughborough–Nottingham highway network. The study has demonstrated that the methodology is useful in selecting various worksite arrangements in order to reduce the effects of maintenance on road users

Computational Physics on Graphics Processing Units

The use of graphics processing units for scientific computations is an emerging strategy that can significantly speed up various different algorithms. In this review, we discuss advances made in the field of computational physics, focusing on classical molecular dynamics, and on quantum simulations for electronic structure calculations using the density functional theory, wave function techniques, and quantum field theory.Comment: Proceedings of the 11th International Conference, PARA 2012, Helsinki, Finland, June 10-13, 201

Standardizing Clinical Trials Workflow Representation in UML for International Site Comparison

BACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows

Variation in the distribution and properties of Circumpolar Deep Water in the eastern Amundsen Sea, on seasonal timescales, using seal‐borne tags

In the Amundsen Sea, warm saline Circumpolar Deep Water (CDW) crosses the continental shelf toward the vulnerable West Antarctic ice shelves, contributing to their basal melting. Due to lack of observations, little is known about the spatial and temporal variability of CDW, particularly seasonally. A new dataset of 6704 seal‐tag temperature and salinity profiles in the easternmost trough between February and December 2014 reveals a CDW layer on average 49 db thicker in late winter (August to October) than in late summer (February to April), the reverse seasonality of that seen at moorings in the western trough. This layer contains more heat in winter, but on the 27.76 kg/m3 density surface CDW is 0.32° C warmer in summer than winter, across the northeastern Amundsen sea, which may indicate wintertime shoaling offshelf changes CDW properties onshelf. In Pine Island Bay these seasonal changes on density surfaces are reduced, likely by gyre circulation