Aspirin Use in Children for Fever or Viral Syndromes

Aspirin should not be used to treat acute febrile viral illness in children. (Strength of Recommendation [SOR]: C, based on case- control studies). Although no causal link has been proven, data from case-control and historic cohort studies demonstrate an association between aspirin use and Reye syndrome

Systematic Transfer of Prokaryotic Sensors and Circuits to Mammalian Cells

Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >10[superscript 5] members that use a simple mechanism to respond to stimuli and bind distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, which is demonstrated using human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells. The repressors are modified to include nuclear localization signals (NLS) and responsive promoters are built by incorporating multiple operators. Activators are also constructed by modifying the protein to include a VP16 domain. Together, this approach yields 15 new regulators that demonstrate 19- to 551-fold induction and retain both the low levels of crosstalk in DNA binding specificity observed between the parent regulators in Escherichia coli, as well as their dynamic range of activity. By taking advantage of the DAPG small molecule sensing mediated by the PhlF repressor, we introduce a new inducible system with 50-fold induction and a threshold of 0.9 μM DAPG, which is comparable to the classic Dox-induced TetR system. A set of NOT gates is constructed from the new repressors and their response function quantified. Finally, the Dox- and DAPG- inducible systems and two new activators are used to build a synthetic enhancer (fuzzy AND gate), requiring the coordination of 5 transcription factors organized into two layers. This work introduces a generic approach for the development of mammalian genetic sensors and circuits to populate a toolbox that can be applied to diverse applications from biomanufacturing to living therapeutics.United States. Defense Advanced Research Projects Agency (DARPA-BAA-11-23)National Institutes of Health (U.S.) (P50GM098792)Life Technologies, Inc. (Research Contract A114510)United States. Office of Naval Research. Multidisciplinary University Research Initiative (N00014-13-1-0074)National Institute of General Medical Sciences (U.S.) (Award R01 GM095765

In vivo assessment of architecture and micro-finite element analysis derived indices of mechanical properties of trabecular bone in the radius

Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (microFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n = 22, mean age 58 +/- 7 years) and (II) postmenopausal women with spine or femur BMD -1 SD to -2.5 SD below young normal (n = 37, mean age 62 +/- 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young's moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (

A randomized double-blind placebo-controlled trial to investigate the effects of nasal calcitonin on bone microarchitecture measured by high-resolution peripheral quantitative computerized tomography in postmenopausal women — Study protocol

<p>Abstract</p> <p>Background</p> <p>Bone microarchitecture is a significant determinant of bone strength. So far, the assessment of bone microarchitecture has required bone biopsies, limiting its utilization in clinical practice to one single skeletal site. With the advance of high-resolution imaging techniques, non-invasive in vivo measurement of bone microarchitecture has recently become possible. This provides an opportunity to efficiently assess the effects of anti-osteoporotic therapies on bone microarchitecture. We therefore designed a protocol to investigate the effects of nasal salmon calcitonin, an inhibitor of osteoclast activity, on bone microarchitecture in postmenopausal women, comparing weight bearing and non-weight bearing skeletal sites.</p> <p>Methods</p> <p>One hundred postmenopausal women will be included in a randomized, placebo-controlled, double-blind trial comparing the effect of nasal salmon calcitonin (200 UI/day) to placebo over two years. Bone microarchitecture at the distal radius and distal tibia will be determined yearly by high-resolution peripheral quantitative computerized tomography (p-QCT) with a voxel size of 82 μm and an irradiation of less than 5 μSv. Serum markers of bone resorption and bone formation will be measured every 6 months. Safety and compliance will be assessed. Primary endpoint is the change in bone microarchitecture; secondary endpoint is the change in markers of bone turnover.</p> <p>Hypothesis</p> <p>The present study should provide new information on the mode of action of nasal calcitonin. We hypothezise that - compared to placebo - calcitonin impacts on microstructural parameters, with a possible difference between weight bearing and non-weight bearing bones.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00372099</p

Statistics of low-energy levels of a one-dimensional weakly localized Frenkel exciton: A numerical study

Numerical study of the one-dimensional Frenkel Hamiltonian with on-site randomness is carried out. We focus on the statistics of the energy levels near the lower exciton band edge, i. e. those determining optical response. We found that the distribution of the energy spacing between the states that are well localized at the same segment is characterized by non-zero mean, i.e. these states undergo repulsion. This repulsion results in a local discrete energy structure of a localized Frenkel exciton. On the contrary, the energy spacing distribution for weakly overlapping local ground states (the states with no nodes within their localization segments) that are localized at different segments has zero mean and shows almost no repulsion. The typical width of the latter distribution is of the same order as the typical spacing in the local discrete energy structure, so that this local structure is hidden; it does not reveal itself neither in the density of states nor in the linear absorption spectra. However, this structure affects the two-exciton transitions involving the states of the same segment and can be observed by the pump-probe spectroscopy. We analyze also the disorder degree scaling of the first and second momenta of the distributions.Comment: 10 pages, 6 figure

Finite strain Landau theory of high pressure phase transformations

The properties of materials near structural phase transitions are often successfully described in the framework of Landau theory. While the focus is usually on phase transitions, which are induced by temperature changes approaching a critical temperature T-c, here we will discuss structural phase transformations driven by high hydrostatic pressure, as they are of major importance for understanding processes in the interior of the earth. Since at very high pressures the deformations of a material are generally very large, one needs to apply a fully nonlinear description taking physical as well as geometrical nonlinearities (finite strains) into account. In particular it is necessary to retune conventional Landau theory to describe such phase transitions. In Troster et al (2002 Phys. Rev. Lett. 88 55503) we constructed a Landau-type free energy based on an order parameter part, an order parameter-(finite) strain coupling and a nonlinear elastic term. This model provides an excellent and efficient framework for the systematic study of phase transformations for a wide range of materials up to ultrahigh pressures

Lack of Effect of Induction of Hypothermia after Acute Brain Injury

Background Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies, but the results were not definitive. To study this issue, we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury. Methods The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were randomly assigned to be treated with hypothermia (body temperature, 33°C), which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling, or normothermia. All patients otherwise received standard treatment. The primary outcome measure was functional status six months after the injury. Results The mean age of the patients and the type and severity of injury in the two treatment groups were similar. The mean (±SD) time from injury to randomization was 4.3±1.1 hours in the hypothermia group and 4.1±1.2 hours in the normothermia group, and the mean time from injury to the achievement of the target temperature of 33°C in the hypothermia group was 8.4±3.0 hours. The outcome was poor (defined as severe disability, a vegetative state, or death) in 57 percent of the patients in both groups. Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group (P=0.79). The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group. Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group. Conclusions Treatment with hypothermia, with the body temperature reaching 33°C within eight hours after injury, is not effective in improving outcomes in patients with severe brain injury. (N Engl J Med 2001; 344:556-63.

Guidelines for the Management of Severe Traumatic Brain Injury: 2020 Update of the Decompressive Craniectomy Recommendations

© Congress of Neurological Surgeons 2020. When the fourth edition of the Brain Trauma Foundation\u27s Guidelines for the Management of Severe Traumatic Brain Injury were finalized in late 2016, it was known that the results of the RESCUEicp (Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension) randomized controlled trial of decompressive craniectomy would be public after the guidelines were released. The guideline authors decided to proceed with publication but to update the decompressive craniectomy recommendations later in the spirit of living guidelines, whereby topics are updated more frequently, and between new editions, when important new evidence is published. The update to the decompressive craniectomy chapter presented here integrates the findings of the RESCUEicp study as well as the recently published 12-mo outcome data from the DECRA (Decompressive Craniectomy in Patients With Severe Traumatic Brain Injury) trial. Incorporation of these publications into the body of evidence led to the generation of 3 new level-IIA recommendations; a fourth previously presented level-IIA recommendation remains valid and has been restated. To increase the utility of the recommendations, we added a new section entitled Incorporating the Evidence into Practice. This summary of expert opinion provides important context and addresses key issues for practitioners, which are intended to help the clinician utilize the available evidence and these recommendations. The full guideline can be found at: https://braintrauma.org/guidelines/guidelines-for-the-management-of-severe-tbi-4th-ed#/