Deconvolution of Serum Cortisol Levels by Using Compressed Sensing

The pulsatile release of cortisol from the adrenal glands is controlled by a hierarchical system that involves corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropin hormone (ACTH) from the pituitary, and cortisol from the adrenal glands. Determining the number, timing, and amplitude of the cortisol secretory events and recovering the infusion and clearance rates from serial measurements of serum cortisol levels is a challenging problem. Despite many years of work on this problem, a complete satisfactory solution has been elusive. We formulate this question as a non-convex optimization problem, and solve it using a coordinate descent algorithm that has a principled combination of (i) compressed sensing for recovering the amplitude and timing of the secretory events, and (ii) generalized cross validation for choosing the regularization parameter. Using only the observed serum cortisol levels, we model cortisol secretion from the adrenal glands using a second-order linear differential equation with pulsatile inputs that represent cortisol pulses released in response to pulses of ACTH. Using our algorithm and the assumption that the number of pulses is between 15 to 22 pulses over 24 hours, we successfully deconvolve both simulated datasets and actual 24-hr serum cortisol datasets sampled every 10 minutes from 10 healthy women. Assuming a one-minute resolution for the secretory events, we obtain physiologically plausible timings and amplitudes of each cortisol secretory event with R[superscript 2] above 0.92. Identification of the amplitude and timing of pulsatile hormone release allows (i) quantifying of normal and abnormal secretion patterns towards the goal of understanding pathological neuroendocrine states, and (ii) potentially designing optimal approaches for treating hormonal disorders.National Science Foundation (U.S.). Graduate Research Fellowship ProgramNational Institutes of Health (U.S.) (NIH DP1 OD003646)National Science Foundation (U.S.) (0836720)National Science Foundation (U.S.). Office of Emerging Frontiers in Research and Innovation (EFRI-0735956

Evidence-based medicine in primary care: qualitative study of family physicians

BACKGROUND: The objectives of this study were: a) to examine physician attitudes to and experience of the practice of evidence-based medicine (EBM) in primary care; b) to investigate the influence of patient preferences on clinical decision-making; and c) to explore the role of intuition in family practice. METHOD: Qualitative analysis of semi-structured interviews of 15 family physicians purposively selected from respondents to a national survey on EBM mailed to a random sample of Canadian family physicians. RESULTS: Participants mainly welcomed the promotion of EBM in the primary care setting. A significant number of barriers and limitations to the implementation of EBM were identified. EBM is perceived by some physicians as a devaluation of the 'art of medicine' and a threat to their professional/clinical autonomy. Issues regarding the trustworthiness and credibility of evidence were of great concern, especially with respect to the influence of the pharmaceutical industry. Attempts to become more evidence-based often result in the experience of conflicts. Patient factors exert a powerful influence on clinical decision-making and can serve as trumps to research evidence. A widespread belief that intuition plays a vital role in primary care reinforced views that research evidence must be considered alongside other factors such as patient preferences and the clinical judgement and experience of the physician. DISCUSSION: Primary care physicians are increasingly keen to consider research evidence in clinical decision-making, but there are significant concerns about the current model of EBM. Our findings support the proposed revisions to EBM wherein greater emphasis is placed on clinical expertise and patient preferences, both of which remain powerful influences on physician behaviour

RIG-I contributes to the innate immune response after cerebral ischemia

BACKGROUND: Focal cerebral ischemia induces an inflammatory response that when exacerbated contributes to deleterious outcomes. The molecular basis regarding the regulation of the innate immune response after focal cerebral ischemia remains poorly understood. METHODS: In this study we examined the expression of retinoic acid-inducible gene (RIG)-like receptor-I (RIG-I) and its involvement in regulating inflammation after ischemia in the brain of rats subjected to middle cerebral artery occlusion (MCAO). In addition, we studied the regulation of RIG-I after oxygen glucose deprivation (OGD) in astrocytes in culture. RESULTS: In this study we show that in the hippocampus of rats, RIG-I and IFN-α are elevated after MCAO. Consistent with these results was an increased in RIG-I and IFN-α after OGD in astrocytes in culture. These data are consistent with immunohistochemical analysis of hippocampal sections, indicating that in GFAP-positive cells there was an increase in RIG-I after MCAO. In addition, in this study we have identified n-propyl gallate as an inhibitor of IFN-α signaling in astrocytes. CONCLUSION: Our findings suggest a role for RIG-I in contributing to the innate immune response after focal cerebral ischemia

Increased mortality and photoinhibition in the symbiotic dinoflagellates of the Indo-Pacific coral Stylophora pistillata (Esper) after summer bleaching

Coral bleaching (the loss of symbiotic dinoflagellates from reef-building corals) is most frequently caused by high-light and temperature conditions. We exposed the explants of the hermatypic coral Stylophora pistillata to four combinations of light and temperature in late spring and also in late summer. During mid-summer, two NOAA bleaching warnings were issued for Heron Island reef (Southern Great Barrier Reef, Australia) when sea temperature exceeded the NOAA bleaching threshold, and a ‘mild’ (in terms of the whole coral community) bleaching event occurred, resulting in widespread S. pistillata bleaching and mortality. Symbiotic dinoflagellate biomass decreased by more than half from late spring to late summer (from 2.5×106 to 0.8×106 dinoflagellates cm2 coral tissue), and those dinoflagellates that remained after summer became photoinhibited more readily (dark-adapted F V : F M decreased to (0.3 compared with 0.4 in spring), and died in greater numbers (up to 17% dinoflagellate mortality compared with 5% in the spring) when exposed to artificially elevated light and temperature. Adding exogenous antioxidants (d-mannitol and l-ascorbic acid) to the water surrounding the coral had no clear effect on either photoinhibition or symbiont mortality. These data show that light and temperature stress cause mortality of the dinoflagellate symbionts within the coral, and that susceptibility to light and temperature stress is strongly related to coral condition. Photoinhibitory mechanisms are clearly involved, and will increase through a positive feedback mechanism: symbiont loss promotes further symbiont loss as the light microenvironment becomes progressively harsher