Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Apr 2012
ReviewPediatric neuroimaging in early childhood and infancy: challenges and practical guidelines.
Structural and functional magnetic resonance imaging (fMRI) has been used increasingly to investigate typical and atypical brain development. However, in contrast to studies in school-aged children and adults, MRI research in young pediatric age groups is less common. ⋯ These include procedural difficulties (e.g., participant anxiety or movement restrictions), technical obstacles (e.g., availability of child-appropriate equipment or pediatric MR head coils), and the challenge of choosing the most appropriate analysis methods for pediatric imaging data. Here, we summarize and review pediatric imaging and analysis tools and present neuroimaging protocols for young nonsedated children and infants, including guidelines and procedures that have been successfully implemented in research protocols across several research sites.
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Systems biology, the approach that combines reduction and integration to explore dynamic structure-function interrelations across biomedically relevant spatio-temporal scales, is applied to heart research.
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The discovery that loss-of-function mutations in the gene DOCK8 are responsible for most forms of autosomal recessive hyper-IgE syndrome and some forms of combined immunodeficiency without elevated serum IgE has led to studies into the immunopathogenesis of this disease. In this review, we relate the clinical features of this disease to studies using patients' cells and a mouse model of Dock8 deficiency, which have revealed how DOCK8 regulates T and B cell numbers and functions. The results of these studies help to explain how the absence of DOCK8 contributes to patients' susceptibility to viral, fungal, and bacterial infections. However, unanswered questions remain regarding how the absence of DOCK8 also leads to high IgE and allergic disease, predisposition for malignancy, and unusual clinical features, such as CNS abnormalities and autoimmunity, observed in some patients.
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Ann. N. Y. Acad. Sci. · Dec 2011
ReviewUnderstanding the regulatory hurdles for antibacterial drug development in the post-Ketek world.
The antibiotic telithromycin (Ketek, Sanofi-aventis) had two of three treatment indications withdrawn after postmarketing reports of serious and fatal adverse events. The rationale for the withdrawal of specific indications (acute bacterial sinusitis and acute exacerbations of chronic bronchitis), while permitting the drug to remain available for the treatment of community-acquired pneumonia, focused on the lack of demonstrated efficacy from clinical trials that included an active control to which the investigational drug, telethromycin, was determined to be statistically noninferior. ⋯ New clinical trial guidelines have been published that will increase the time and resources required to achieve regulatory marketing approval. This paper reviews recent regulatory actions and discusses the impact these new guidelines will have on future antibacterial clinical trial designs and challenges.
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Ann. N. Y. Acad. Sci. · Oct 2011
ReviewNear-death experiences: the experience of the self as real and not as an illusion.
Because the publication of several prospective studies on near-death experience (NDE) in survivors of cardiac arrest have shown strikingly similar results and conclusions, the phenomenon of the NDE can no longer be scientifically ignored. The NDE is an authentic experience that cannot be simply reduced to imagination, fear of death, hallucination, psychosis, the use of drugs, or oxygen deficiency. Patients appear to be permanently changed by an NDE during a cardiac arrest of only some minutes' duration. ⋯ The current materialistic view of the relationship between consciousness and the brain, as held by most physicians, philosophers, and psychologists, seems to be too restricted for a proper understanding of this phenomenon. There are good reasons to assume that our consciousness, with the continuous experience of self, does not always coincide with the functioning of our brain: enhanced or nonlocal consciousness, with unaltered self-identity, apparently can be experienced independently from the lifeless body. People are convinced that the self they experienced during their NDE is a reality and not an illusion.