When the Ideal Meets the Feasible: Constructing a Protocol for Developmental Assessment at Early School-Age

Objective: To describe development of a methodology for an outcome study of children born following in-vitro fertilization or spontaneously-conceived, as a model for defining normal and below-normal development of school-age children for research purposes.Study Design: The main issues addressed were defining the major health and developmental domains to be investigated, selection of age-appropriate validated instruments, considering time constraints to maximize compliance, and budgetary limitations. The final protocol included a half-hour structured telephone interview with mothers of all 759 children and a 2-h developmental assessment of 294 of them. Each of the instruments and recruiting methods are described in terms of the abovementioned considerations.Results: Almost all of the mothers who agreed to be interviewed completed it within the half-hour allotted; however only about half of those who agreed to bring the child for the developmental assessment actually did so. The entire examination battery, assessing cognitive ability, executive functions, attention, and learning skills, was completed by almost all 294 children. There was a significant degree of agreement between the maternal report of the child's reading, writing and arithmetic skills and the in-person examination, as well as regarding the child's weight and height measurements.Conclusion: The findings lend support for a low-budget study, relying on telephone interviews. However, limitations such as the validity of maternal report and recall bias must be taken into consideration

Multicenter Cross-Sectional Study of Nontuberculous Mycobacterial Infections among Cystic Fibrosis Patients, Israel

A multicenter cross-sectional study showed prevalence appears to be increasing

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How cancer cells globally struggle with a chemotherapeutic insult before succumbing to apoptosis is largely unknown. Here we use an integrated systems-level examination of transcription, translation, and proteolysis to understand these events central to cancer treatment. As a model we study myeloma cells exposed to the proteasome inhibitor bortezomib, a first-line therapy. Despite robust transcriptional changes, unbiased quantitative proteomics detects production of only a few critical anti-apoptotic proteins against a background of general translation inhibition. Simultaneous ribosome profiling further reveals potential translational regulation of stress response genes. Once the apoptotic machinery is engaged, degradation by caspases is largely independent of upstream bortezomib effects. Moreover, previously uncharacterized non-caspase proteolytic events also participate in cellular deconstruction. Our systems-level data also support co-targeting the anti-apoptotic regulator HSF1 to promote cell death by bortezomib. This integrated approach offers unique, in-depth insight into apoptotic dynamics that may prove important to preclinical evaluation of any anti-cancer compound. DOI: http://dx.doi.org/10.7554/eLife.01236.00

Multicenter Cross-Sectional Study of Nontuberculous Mycobacterial Infections among Cystic Fibrosis Patients, Israel

A multicenter cross-sectional study showed prevalence appears to be increasing

The Risk of Immunosuppression: A Case of Salmonella Meningitis

Salmonella meningitis is a rare infection, particularly in adults. We report the case of a 75-year-old female with a history of rheumatoid arthritis on TNF-antagonist immunosuppressive therapy who initially presented to the hospital for management of back and leg pain and was ultimately diagnosed with bacterial meningitis secondary to Salmonella species infection. She was treated with ceftriaxone with slow improvement in neurological function. Though the source of infection was never clearly identified from multiple imaging studies, we suspect the severity of her presentation was due to her history of TNF-antagonist use