Robert James Graves, a native of Dublin, Ireland, was a physician rather than a surgeon; however, his name is well-known to all general and endocrine surgeons. He was born in Dublin, Ireland, and ...received his BA and MB degrees from Trinity College (formerly, Dublin University). After further studies throughout Europe, he received his “licentiate” from the Royal College of Physicians of Ireland in 1820 and was appointed Physician to the Meath Hospital in Dublin in 1821. Graves received many honors during his career including the following: King’s Professor in the Institute of Medicine (1824); President of the Royal College of Physicians of Ireland (1843-44); and a Fellow of the Royal Society (FRS, 1849). In addition, he was a prominent member of the Irish School of Medicine which also included William Stokes (1804-1878) (Cheyne-Stokes breathing, Stokes-Adams attacks) and Dominic Corrigan (1802-1880) (Corrigan’s pulse). Graves’ description of exophthalmic goiter was in 1835, some 49 years after that of Caleb Hillier Parry (1755-1822) of Bath, England; however, Bath’s report was not published till 1825 or 3 years after his death. Graves' disease is still the eponym applied to this form of hyperthyroidism in the United States.
Recent population‐based data on nonalcoholic fatty liver disease (NAFLD) epidemiology in general, and incidence in particular, are lacking. We examined trends in NAFLD incidence in a U.S. community ...and the impact of NAFLD on incident metabolic comorbidities (MCs), cardiovascular (CV) events, and mortality. A community cohort of all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 was constructed using the Rochester Epidemiology Project database. The yearly incidence rate were calculated. The impact of NAFLD on incident MCs, CV events, and mortality was studied using a multistate model, with a 4:1 age‐ and sex‐matched general population as a reference. We identified 3,869 NAFLD subjects (median age, 53; 52% women) and 15,209 controls; median follow‐up was 7 (1‐20) years. NAFLD incidence increased 5‐fold, from 62 to 329 in 100,000 person‐years. The increase was highest (7‐fold) in young adults, aged 18‐39 years. The 10‐year mortality was higher in NAFLD subjects (10.2%) than controls (7.6%; P < 0.0001). NAFLD was an independent risk factor for incident MCs and death. Mortality risk decreased as the number of incident MCs increased: relative risk (RR) = 2.16 (95% confidence CI, 1.41‐3.31), 1.99 (95% CI, 1.48‐2.66), 1.75 (95% CI, 1.42‐2.14), and 1.08 (95% CI, 0.89‐1.30) when 0, 1, 2, or 3 MCs were present, respectively. The NAFLD impact on CV events was significant only in subjects without MCs (RR = 1.96; 95% CI = 1.35‐2.86). NAFLD reduced life expectancy by 4 years, with more time spent in high metabolic burden. Conclusion: Incidence of NAFLD diagnosis in the community has increased 5‐fold, particularly in young adults. NAFLD is a consequence, but also a precursor of MC. Incident MC attenuates the impact of NAFLD on death and annuls its impact on CV disease. (Hepatology 2018;67:1726‐1736).
Muscle contraction may protect against the effects of chemotherapy to cause skeletal muscle atrophy, but the mechanisms underlying these benefits are unclear. To address this question, we utilized in ...vitro modeling of contraction and mechanotransduction in C2C12 myotubes treated with doxorubicin (DOX; 0.2 μM for 3 days). Myotubes expressed contractile proteins and organized these into functional myofilaments, as electrical field stimulation (STIM) induced intracellular calcium (Ca
) transients and contractions, both of which were prevented by inhibition of membrane depolarization. DOX treatment reduced myotube myosin content, protein synthesis, and Akt (S308) and forkhead box O3a (FoxO3a; S253) phosphorylation and increased muscle RING finger 1 (MuRF1) expression. STIM (1 h/day) prevented DOX-induced reductions in myotube myosin content and Akt and FoxO3a phosphorylation, as well as increases in MuRF1 expression, but did not prevent DOX-induced reductions in protein synthesis. Inhibition of myosin-actin interaction during STIM prevented contraction and the antiatrophic effects of STIM without affecting Ca
cycling, suggesting that the beneficial effect of STIM derives from mechanotransductive pathways. Further supporting this conclusion, mechanical stretch of myotubes recapitulated the effects of STIM to prevent DOX suppression of FoxO3a phosphorylation and upregulation of MuRF1. DOX also increased reactive oxygen species (ROS) production, which led to a decrease in mitochondrial content. Although STIM did not alter DOX-induced ROS production, peroxisome proliferator-activated receptor-γ coactivator-1α and antioxidant enzyme expression were upregulated, and mitochondrial loss was prevented. Our results suggest that the activation of mechanotransductive pathways that downregulate proteolysis and preserve mitochondrial content protects against the atrophic effects of chemotherapeutics.
We measure the static shear viscosity η in a two-component Fermi gas near a broad collisional (Feshbach) resonance, as a function of interaction strength and energy. We find that η has both a ...quadratic and a linear dependence on the interaction strength 1/(k(FI)a), where a is the s-wave scattering length and k(FI) is the Fermi wave vector for an ideal gas at the trap center. For energies above the superfluid transition, the minimum in η as a function of interaction strength is significantly shifted toward the BEC side of resonance, to 1/(k(FI)a)≃0.25.
Abstract Background Physical Activity Across the Curriculum (PAAC) was a three-year cluster randomized controlled trial to promote physical activity and diminish increases in overweight and obesity ...in elementary school children. Methods Twenty-four elementary schools were cluster randomized to the Physical Activity Across the Curriculum intervention or served as control. All children in grades two and three were followed to grades four and five. Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers. Body Mass Index was the primary outcome, daily Physical activity and academic achievement were secondary outcomes. Results The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0 ±1.9 and control 1.9 ± 1.9, respectively (NS). However, change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum. Schools with ≥ 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had < 75 min of Physical Activity Across the Curriculum (1.8 ± 1.8 vs. 2.4 ± 2.0, p = 0.02). Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores. Conclusions The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children. Additionally, 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index.
Since its first identification in the 1950s as a regulator of cell division, cytokinin has been linked to many physiological processes in plants, spanning growth and development and various responses ...to the environment. Studies from the last two and one-half decades have revealed the pathways underlying the biosynthesis and metabolism of cytokinin and have elucidated the mechanisms of its perception and signaling, which reflects an ancient signaling system evolved from two-component elements in bacteria. Mutants in the genes encoding elements involved in these processes have helped refine our understanding of cytokinin functions in plants. Further, recent advances have provided insight into the mechanisms of intracellular and long-distance cytokinin transport and the identification of several proteins that operate downstream of cytokinin signaling. Here, we review these processes through a historical lens, providing an overview of cytokinin metabolism, transport, signaling, and functions in higher plants.
The 2018 GaN power electronics roadmap Amano, H; Baines, Y; Beam, E ...
Journal of physics. D, Applied physics,
04/2018, Letnik:
51, Številka:
16
Journal Article
Recenzirano
Odprti dostop
Gallium nitride (GaN) is a compound semiconductor that has tremendous potential to facilitate economic growth in a semiconductor industry that is silicon-based and currently faced with diminishing ...returns of performance versus cost of investment. At a material level, its high electric field strength and electron mobility have already shown tremendous potential for high frequency communications and photonic applications. Advances in growth on commercially viable large area substrates are now at the point where power conversion applications of GaN are at the cusp of commercialisation. The future for building on the work described here in ways driven by specific challenges emerging from entirely new markets and applications is very exciting. This collection of GaN technology developments is therefore not itself a road map but a valuable collection of global state-of-the-art GaN research that will inform the next phase of the technology as market driven requirements evolve. First generation production devices are igniting large new markets and applications that can only be achieved using the advantages of higher speed, low specific resistivity and low saturation switching transistors. Major investments are being made by industrial companies in a wide variety of markets exploring the use of the technology in new circuit topologies, packaging solutions and system architectures that are required to achieve and optimise the system advantages offered by GaN transistors. It is this momentum that will drive priorities for the next stages of device research gathered here.
RTS,S/AS01E has been tested in a phase 3 malaria vaccine study with partial efficacy in African children and infants. In a cohort of 1028 subjects from one low (Bagomoyo) and two high (Nanoro, ...Kintampo) malaria transmission sites, we analysed IgG plasma/serum concentration and avidity to CSP (NANP-repeat and C-terminal domains) after a 3-dose vaccination against time to clinical malaria events during 12-months. Here we report that RTS,S/AS01E induces substantial increases in IgG levels from pre- to post-vaccination (p < 0.001), higher in NANP than C-terminus (2855 vs 1297 proportional change between means), and higher concentrations and avidities in children than infants (p < 0.001). Baseline CSP IgG levels are elevated in malaria cases than controls (p < 0.001). Both, IgG magnitude to NANP (hazard ratio 95% confidence interval 0.61 0.48-0.76) and avidity to C-terminus (0.07 0.05-0.90) post-vaccination are significantly associated with vaccine efficacy. IgG avidity to the C-terminus emerges as a significant contributor to RTS,S/AS01E-mediated protection.
Background. Data on integrase inhibitor resistance come primarily from clinical trials and in vitro studies. We examined results of all clinically indicated integrase genotypic resistance tests ...(GRTs) performed at a US national referral lab from 2009 through 2012. Methods. Integrase sequences and demographic data were compiled with paired protease–reverse transcriptase (PR-RT) GRT results, when available. Analyses utilized the Stanford HIV Drug Resistance Database. "Major" integrase mutations included T66AIK, E92QV, F121Y, Y143CHR, S147G, Q148HKR, and N155H; multiple accessory mutations were also assessed. Results. Among 3294 sequences from 3012 patients, 471 patients had viruses with ≥1 raltegravir or elvitegravir resistance mutation (15.6%). Q148 and N155 pathways were equally represented (both n = 197); 84 had Y143 mutations. Q148 rarely occurred without accessory mutations (n = 3). Among 224 patients with serial integrase GRTs, 22 with baseline wild-type acquired a major mutation, after a median 224 days between tests (interquartile range, 148– 335 days). Major mutations were observed to persist up to 462 days. Most (62%) had paired PR-RT results. Patients with integrase-resistant viruses were older and more likely to have PR-RT mutations (both P < .001). Among those with PR-RT data, 42 patients had 4-class resistance (2.3%). Sex, geographic region, and test year were not associated with integrase resistance. High-level dolutegravir resistance was predicted in 12% of patients with raltegravir- or elvitegravir-resistant viruses (2% of all patients). Conclusions. Approximately 1 in 6 US patients undergoing integrase GRT for clinical decision making harbors significant resistance, with Q148 and N155 pathways equally common. Dolutegravir is likely to have full or partial activity against most variants observed.
PDF
