Can herpes simplex virus type 2 suppression slow HIV disease progression: a study protocol for the VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial

<p>Abstract</p> <p>Background</p> <p>Although highly active antiretroviral therapy (HAART) has dramatically decreased HIV-related morbidity and mortality, the associated costs, toxicities, and resistance risks make the potential delay of HAART initiation an attractive goal. Suppression of herpes simplex virus type 2 (HSV-2) may be a novel strategy for achieving this goal because HSV-2 is associated with clinically significant increases in HIV viral load, the primary driver of HIV disease progression.</p> <p>Methods/Design</p> <p>The VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial is a multicentre, randomized, fully blinded, clinical trial of twice daily valacyclovir 500 mg versus placebo for delaying the need for initiating HAART among HIV-1, HSV-2 co-infected HAART-naïve adults. 480 participants from Canada, Brazil and Argentina will undergo quarterly clinical follow-up until reaching the composite primary endpoint of having a CD4+ T-cell count ≤ 350 cells/mm³or initiation of HAART for any reason, whichever occurs first. The primary analysis will use a proportional hazards model, stratified by site, to estimate the relative risk of progression to this endpoint associated with valacyclovir. Secondary analyses will compare the rates of change in CD4 count, median log₁₀HIV viral load, drug-related adverse events, frequency of HSV reactivations, rate of acyclovir-resistant HSV, and quality of life between study arms.</p> <p>Discussion</p> <p>Although HIV treatment guidelines continue to evolve, with some authorities recommending earlier HAART among asymptomatic individuals, the potential delay of HAART remains a clinically relevant goal for many. If shown to be of benefit, implementation of the VALIDATE intervention will require careful consideration of both individual patient-level and public health implications.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN66756285</p> <p>ClinicalTrials.gov NCT00860977</p

Phosphorus availability determines the response of tundra ecosystem carbon stocks to nitrogen enrichment.

This study was funded by NERC (NE/I016899/1) and facilitated by use of NERC facilities at Harland Huset, Ny-Ålesund and the kind support of Nick Cox and colleagues. Nancy Burns assisted with field sampling and Brodie Shaw and Rob Mills assisted with laboratory analyses. Open access via Springer Compact Agreement.Peer reviewedPublisher PD

Methods for Specifying Scientific Data Standards and Modeling Relationships with Applications to Neuroscience

Neuroscience continues to experience a tremendous growth in data; in terms of the volume and variety of data, the velocity at which data is acquired, and in turn the veracity of data. These challenges are a serious impediment to sharing of data, analyses, and tools within and across labs. Here, we introduce BRAINformat, a novel data standardization framework for the design and management of scientific data formats. The BRAINformat library defines application-independent design concepts and modules that together create a general framework for standardization of scientific data. We describe the formal specification of scientific data standards, which facilitates sharing and verification of data and formats. We introduce the concept of Managed Objects, enabling semantic components of data formats to be specified as self-contained units, supporting modular and reusable design of data format components and file storage. We also introduce the novel concept of Relationship Attributes for modeling and use of semantic relationships between data objects. Based on these concepts we demonstrate the application of our framework to design and implement a standard format for electrophysiology data and show how data standardization and relationship-modeling facilitate data analysis and sharing. The format uses HDF5, enabling portable, scalable, and self-describing data storage and integration with modern high-performance computing for data-driven discovery. The BRAINformat library is open source, easy-to-use, and provides detailed user and developer documentation and is freely available at: https://bitbucket.org/oruebel/brainformat

Methods for specifying scientific data standards and modeling relationships with applications to neuroscience

© 2016 Rübel, Dougherty, Prabhat, Denes, Conant, Chang and Bouchard.Neuroscience continues to experience a tremendous growth in data; in terms of the volume and variety of data, the velocity at which data is acquired, and in turn the veracity of data. The

Doença de Mondor: achados mamográficos e ultra-sonográficos Mondor's disease: mammography and ultrasound findings

A doença de Mondor da mama é uma tromboflebite superficial da mama que se apresenta como um cordão fibroso e espessado na região subcutânea da mama. É uma enfermidade rara, benigna e autolimitada que apresenta dor e retração da pele no nível do vaso afetado. Neste trabalho relatamos dois casos mostrando os achados mamográficos (caso 1) e ultra-sonográficos (caso 2) típicos desta anomalia.<br>Mondor's disease of the breast is a superficial thrombophlebitis of the veins of the breast characterized by the appearance of a thickened fibrotic cord in the subcutaneous tissue. This is a rare, benign and self-limited disease, which presents with pain and skin retraction at the site of the affected vase. We report two cases of patients with Mondor's disease and show the typical mammography (case 1) and ultrasound (case 2) findings

Mucocele-like lesions of the breast: a benign cause for indeterminate or suspicious mammographic microcalcifications

Most earlier reports of mucocele-like lesions (MLL) of the breast have dealt with symptomatic cases in premenopausal women or lesions found incidentally in breast biopsies performed for other reasons. The diagnosis of this lesion has special challenges in the setting of mammographic screening for breast cancer because the imaging characteristics of MLL may mimic those of ductal carcinoma in situ (DCIS), while mucinous carcinoma enters the differential diagnosis on cytologic grounds. This report focuses on our experience with MLLs detected during screening mammography. Cases with MLL as the final histologic diagnosis in our database during January 1992-June 2000 are included. The results of clinical, imaging, cytologic, core biopsy, and histologic examination of these lesions are recorded. The relevant literature is reviewed. Twenty-six cases were found, with a mean patient age of 57.5 years. Microcalcifications were the dominant radiologic abnormality in 22 cases (84.6%). Imaging was considered suspicious or almost certainly malignant in 17 cases (65.4%). Cytology was classified as atypical or suspicious in 17 cases (70.9%). However, open biopsy showed mostly benign changes, including atypical ductal hyperplasia (ADH) in five cases (19.2%). In one case, ADH merged with a 3-4 mm focus of low-grade DCIS. This, the largest series focusing purely on screen-detected MLL, suggests that the combination of clinical, imaging, and cytologic features of screen-detected MLL are different from those of mucinous carcinoma, symptomatic MLL, or incidental MLL. Correlating the cytomorphology of mucinous lesions of the breast with their mammographic appearance may permit more precise preoperative diagnosis.Gelareh Farshid, Steve Pieterse, John M. King, Jill Robinso