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"Adrian, P H"
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Supertall/megatall : how high can we go?
\"Drawing from the unique design experience at Adrian Smith + Gordon Gill Architecture (AS+GG) as architects of the next world's tallest tower and several others under construction, \"Supertall Megatall: How High Can We Go?\" highlights the design, sustainability, innovative technology, programming, and contextualism that defines supertall and megatall towers.The book is a mixture of under construction and design-only projects divided into several chapters that are organized according to their special characteristics: Innovative Systems, Harnessing Energies, Designing an Icon, Extending Ecologies, and Achieving Megatall. Each project, completed between 2007-2020 at AS+GG, is discovered through context, program, form, research and development, and performance, highlighting the stories, challenges, and lessons learned.\" Vendor website.
Book
Long-term Follow-up of Griggs Percutaneous Tracheostomy With Spiral CT and Questionnaire
To assess late complications following percutaneous tracheostomy using the Griggs technique.
Observational cohort study
General ICU of a 700-bed district general hospital in the United Kingdom.
Twenty-five patients who underwent Griggs tracheostomy in the ICU and survived for at least 6 months after decannulation.
Patients were invited to attend for assessment by questionnaire and for spiral CT of the trachea.
Eight patients had moderate tracheal dilatation, two patients were permanently hoarse, nine patients had minor voice changes, no patient had tracheal stenosis, and no patient had a disfiguring scar.
Following Griggs percutaneous tracheostomy, 8 of 25 patients developed moderate tracheal dilatation, and none developed a tracheal stenosis. The cosmetic result after Griggs tracheostomy is good, but the number of patients with minor voice changes is high. A further investigation of long-term outcome following Griggs tracheostomy is necessary.
Journal Article
Searching for Prompt and Long-Lived Dark Photons in Electro-Produced \\(e^+e^-\\) Pairs with the Heavy Photon Search Experiment at JLab
The Heavy Photon Search experiment (HPS) at the Thomas Jefferson National Accelerator Facility searches for electro-produced dark photons. We report results from the 2016 Engineering Run consisting of 10608/nb of data for both the prompt and displaced vertex searches. A search for a prompt resonance in the \\(e^+e^-\\) invariant mass distribution between 39 and 179 MeV showed no evidence of dark photons above the large QED background, limiting the coupling of ^2 10^-5, in agreement with previous searches. The search for displaced vertices showed no evidence of excess signal over background in the masses between 60 and 150 MeV, but had insufficient luminosity to limit canonical heavy photon production. This is the first displaced vertex search result published by HPS. HPS has taken high-luminosity data runs in 2019 and 2021 that will explore new dark photon phase space.
Paper
Swan-Ganz catheter can help patients--but which ones?
1 Several studies have shown the inaccuracy of the results of clinical assessment compared with the information derived from a pulmonary artery catheter. 2 3 In a mixed population of patients receiving intensive care Steingrub et al compared physicians' estimates of pulmonary artery wedge pressure with the measured values. 4 In 53% of cases the physician was unable to predict correctly whether the pressure was low (<10 mm Hg), medium (10-18 mm Hg), or high (>18 mm Hg).
Journal Article
Search for a Dark Photon in Electro-Produced \\(e^+e^-\\) Pairs with the Heavy Photon Search Experiment at JLab
The Heavy Photon Search experiment took its first data in a 2015 engineering run at the Thomas Jefferson National Accelerator Facility, searching for a prompt, electro-produced dark photon with a mass between 19 and 81 MeV/\\(c^2\\). A search for a resonance in the \\(e^+e^-\\) invariant mass distribution, using 1.7 days (1170 nb\\(^-1\\)) of data, showed no evidence of dark photon decays above the large QED background, confirming earlier searches and demonstrating the full functionality of the experiment. Upper limits on the square of the coupling of the dark photon to the Standard Model photon are set at the level of 6\\(\\)10\\(^-6\\). Future runs with higher luminosity will explore new territory.
Paper
Clinical skills still provoke debate
Clinical skills are complemented by technology EDITOR,--J Goodwin's editorial on the importance of clinical skills fails to offer any worthwhile evidence for the hypotheses proposed. 1 The author opines that only the \"clinically inexperienced\" depend on the Swan-Ganz catheter for measuring intracardiac pressures in critically ill patients, yet the author offers no evidence to support this \"good example\" of undue reliance on technology and ignores objective studies that show that clinical assessment of the haemodynamic status of critically ill patients is extremely unreliable. 2 Having insulted those of us who use pulmonary artery catheterisation, Goodwin then accuses those of us who teach of allowing our clinical skills to wane by citing a \"recent\" (1988) story in a Sunday newspaper (fictitious) and two articles from a single issue of Annals of Internal Medicine in 1992 (both wrongly referenced), 3 4 which are of no relevance to medical training in Britain and do not show that doctors are less skilful now than they were in Goodwin's imaginary good old days.
Journal Article
Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes
We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic “tension globule.” In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Bothmodels are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.
Journal Article
The Poor Old Heart of the Milky Way
Our Milky Way should host an ancient, metal-poor, and centrally concentrated stellar population, which reflects the star formation and enrichment in the few most massive progenitors that coalesced at high redshift to form the proto-Galaxy. While metal-poor stars are known to reside in the inner few kiloparsecs of our Galaxy, current data do not yet provide a comprehensive picture of such a metal-poor “heart” of the Milky Way. We use information from Gaia Data Release 3, especially the XP spectra, to construct a sample of 2 million bright (G BP < 15.5 mag) giant stars within 30° of the Galactic center (GC) with robust [M/H] estimates, δ[M/H] ≲ 0.1. For ∼1.25 million stars we calculate orbits from Gaia Radial Velocity Spectrometer velocities and astrometry. This sample reveals an extensive, ancient, and metal-poor population that includes ∼18,000 stars with −2.7 < [M/H] < −1.5, representing a stellar mass of ≳5 × 107 M ⊙. The spatial distribution of these [M/H] < −1.5 stars has a Gaussian extent of only σRGC∼2.7kpc around the GC, with most orbits confined to the inner Galaxy. At high orbital eccentricities, there is clear evidence for accreted halo stars in their pericentral orbit phase. Most stars show [α/Fe] enhancement and [Al/Fe]–[Mn/Fe] abundances expected for an origin in the more massive portions of the proto-Galaxy. Stars with [M/H] < −2 show no net rotation, whereas those with [M/H] ∼ −1 are rotation dominated. These central, metal-poor stars most likely predate the oldest disk population (τ age ≈ 12.5 Gyr), which implies that they formed at z ≳ 5, forging the proto-Milky Way.
Journal Article
Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency
Adrian Clark and colleagues report mutations in the
NNT
gene encoding nicotinamide nucleotide transhydrogenase in familial glucocorticoid deficiency (FGD).
Using targeted exome sequencing, we identified mutations in
NNT
, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with
Nnt
loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed.
NNT
knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.
Journal Article
Understanding the impact of lumbar disc degeneration and chronic low back pain: A cross-sectional electromyographic analysis of postural strategy during predicted and unpredicted postural perturbations
People with chronic low back pain (LBP) exhibit changes in postural control. Stereotypical muscle activations resulting from external perturbations include anticipatory (APAs) and compensatory (CPAs) postural adjustments. The aim and objective of this study was to determine differences in postural control strategies (peak amplitude, APAs and CPAs) between symptomatic and asymptomatic adults with and without Lumbar Disc Degeneration (LDD) using surface electromyography during forward postural perturbation. Ninety-seven subjects participated in the study (mean age 50 years (SD 12)). 3T MRI was used to acquire T2 weighted images (L1-S1). LDD was determined using Pfirrmann grading. A bespoke translational platform was designed to deliver horizontal perturbations in sagittal and frontal planes. Electromyographic activity was analysed bilaterally from 8 trunk and lower limb muscles during four established APA and CPA epochs. A Kruskal-Wallis H test with Bonferroni correction for multiple comparisons was conducted. Four groups were identified: no LDD no pain (n = 19), LDD no pain (n = 38), LDD pain (n = 35) and no LDD pain (n = 5). There were no significant differences in age or gender between groups. The most significant difference between groups was observed during forward perturbation. In the APA and CPA phases of predictable forward perturbation there were significant differences ankle strategy between groups (p = 0.007–0.008); lateral gastrocnemius and tibialis anterior activity was higher in the LDD pain than the LDD no pain group. There were no significant differences in the unpredictable condition (p>0.05). These findings were different from the remaining groups, where significant differences in hip strategy were observed during both perturbation conditions (p = 0.004–0.006). Symptomatic LDD patients exhibit different electromyographic strategies to asymptomatic LDD controls. Future LBP electromyographic research should benefit from considering assessment of both lower limbs in addition to the spine. This approach could prevent underestimation of postural control deficits and guide targeted rehabilitation.
Journal Article