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"Johnson, R. P."
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Composite Structures of Steel and Concrete
This book provides an introduction to the theory and design of composite structures of steel and concrete. Material applicable to both buildings and bridges is included, with more detailed information relating to structures for buildings. Throughout, the design methods are illustrated by calculations in accordance with the Eurocode for composite structures, EN 1994, Part 1-1, 'General rules and rules for buildings' and Part 1-2, 'Structural fire design', and their cross-references to ENs 1990 to 1993. The methods are stated and explained, so that no reference to Eurocodes is needed. The use of Eurocodes has been required in the UK since 2010 for building and bridge structures that are publicly funded. Their first major revision began in 2015, with the new versions due in the early 2020s. Both authors are involved in the work on Eurocode 4.
eBook
long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation
Aims/hypothesis Defects in pancreatic beta cell turnover are implicated in the pathogenesis of type 2 diabetes by genetic markers for diabetes. Decreased beta cell neogenesis could contribute to diabetes. The longevity and turnover of human beta cells is unknown; in rodents <1 year old, a half-life of 30 days is estimated. Intracellular lipofuscin body (LB) accumulation is a hallmark of ageing in neurons. To estimate the lifespan of human beta cells, we measured beta cell LB accumulation in individuals aged 1-81 years. Methods LB content was determined by electron microscopical morphometry in sections of beta cells from human (non-diabetic, n = 45; type 2 diabetic, n = 10) and non-human primates (n = 10; 5-30 years) and from 15 mice aged 10-99 weeks. Total cellular LB content was estimated by three-dimensional (3D) mathematical modelling. Results LB area proportion was significantly correlated with age in human and non-human primates. The proportion of human LB-positive beta cells was significantly related to age, with no apparent differences in type 2 diabetes or obesity. LB content was low in human insulinomas (n = 5) and alpha cells and in mouse beta cells (LB content in mouse <10% human). Using 3D electron microscopy and 3D mathematical modelling, the LB-positive human beta cells (representing aged cells) increased from ≥90% (<10 years) to ≥97% (>20 years) and remained constant thereafter. Conclusions/interpretation Human beta cells, unlike those of young rodents, are long-lived. LB proportions in type 2 diabetes and obesity suggest that little adaptive change occurs in the adult human beta cell population, which is largely established by age 20 years.
Journal Article
Entangled Macroscopic Quantum States in Two Superconducting Qubits
We present spectroscopic evidence for the creation of entangled macroscopic quantum states in two current-biased Josephson-junction qubits coupled by a capacitor. The individual junction bias currents are used to control the interaction between the qubits by tuning the energy level spacings of the junctions in and out of resonance with each other. Microwave spectroscopy in the 4 to 6 gigahertz range at 20 millikelvin reveals energy levels that agree well with theoretical results for entangled states. The single qubits are spatially separate, and the entangled states extend over the 0.7-millimeter distance between the two qubits.
Journal Article
Iatrogenic urinary injuries in colorectal surgery: outcomes and risk factors from a nationwide cohort
Background
Iatrogenic urinary injury (IUI) can lead to significant complications after colorectal surgery, especially when diagnosis is delayed. This study analyzes risk factors associated with IUI and delayed IUI among patients undergoing colorectal procedures.
Methods
Adults undergoing colorectal surgery between 2012 and 2021 were identified in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP
®
) database. Multivariable regression analysis was used to determine risk factors and outcomes associated with IUI and delayed IUI.
Results
Among 566,036 patients, 5836 patients (1.0%) had IUI after colorectal surgery, of whom 236 (4.0%) had delayed IUI. Multiple preoperative risk factors for IUI and delayed IUI were identified, with disseminated cancer [adjusted odds ratio (aOR) 1.4, 95% confidence interval (CI) 1.2–1.5;
p
< 0.001] and diverticular disease [aOR 1.1, 95% CI 1.0–1.2;
p
= 0.009] correlated with IUI and increased body mass index [aOR 1.6, 95% CI 1.2–2.1;
p
= 0.003] and ascites [aOR 5.6, 95% CI 2.1–15.4;
p
= 0.001] associated with delayed IUI. Laparoscopic approach was associated with decreased risk of IUI [aOR 0.4, 95% CI 0.4–0.5;
p
< 0.001] and increased risk of delayed IUI [aOR 1.8, 95% CI 1.4–2.5;
p
< 0.001]. Both IUI and delayed IUI were associated with significant postoperative morbidity, with severe multiorgan complications seen in delayed IUI.
Conclusions
While IUI occurs infrequently in colorectal surgery, unrecognized injuries can complicate repair and cause other negative postoperative outcomes. Patients with complex intra-abdominal pathology are at increased risk of IUI, and patients with large body habitus undergoing laparoscopic procedures are at increased risk of delayed IUI.
Journal Article
Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells
Aims/hypothesis The aim of this study was to characterise electrical activity, ion channels, exocytosis and somatostatin release in human delta cells/pancreatic islets. Methods Glucose-stimulated somatostatin release was measured from intact human islets. Membrane potential, currents and changes in membrane capacitance (reflecting exocytosis) were recorded from individual human delta cells identified by immunocytochemistry. Results Somatostatin secretion from human islets was stimulated by glucose and tolbutamide and inhibited by diazoxide. Human delta cells generated bursting or sporadic electrical activity, which was enhanced by tolbutamide but unaffected by glucose. Delta cells contained a tolbutamide-insensitive, Ba²⁺-sensitive inwardly rectifying K⁺ current and two types of voltage-gated K⁺ currents, sensitive to tetraethylammonium/stromatoxin (delayed rectifying, Kv2.1/2.2) and 4-aminopyridine (A current). Voltage-gated tetrodotoxin (TTX)-sensitive Na⁺ currents contributed to the action potential upstroke but TTX had no effect on somatostatin release. Delta cells are equipped with Ca²⁺ channels blocked by isradipine (L), ω-agatoxin (P/Q) and NNC 55-0396 (T). Blockade of any of these channels interferes with delta cell electrical activity and abolishes glucose-stimulated somatostatin release. Capacitance measurements revealed a slow component of depolarisation-evoked exocytosis sensitive to ω-agatoxin. Conclusions/interpretation Action potential firing in delta cells is modulated by ATP-sensitive K⁺-channel activity. The membrane potential is stabilised by Ba²⁺-sensitive inwardly rectifying K⁺ channels. Voltage-gated L- and T-type Ca²⁺ channels are required for electrical activity, whereas Na⁺ currents and P/Q-type Ca²⁺ channels contribute to (but are not necessary for) the upstroke of the action potential. Action potential repolarisation is mediated by A-type and Kv2.1/2.2 K⁺ channels. Exocytosis is tightly linked to Ca²⁺-influx via P/Q-type Ca²⁺ channels. Glucose stimulation of somatostatin secretion involves both KATP channel-dependent and -independent processes.
Journal Article
Demonstration of active neutron interrogation of special nuclear materials using a high-intensity short-pulse-laser-driven neutron source
Detecting shielded special nuclear material, such as nuclear explosives, is a difficult challenge pursued by non-proliferation, anti-terrorism, and nuclear security programs worldwide. Interrogation with intense fast-neutron pulses is a promising method to characterize concealed nuclear material rapidly but is limited by suitable source availability and proven instrumentation. In this study we have pioneered a demonstration of such an interrogation method using a high-intensity, short-pulse, laser-driven neutron source that offers potential benefits compared to conventional neutron sources. The measurement results reported here represent the first experimental demonstration of this interrogation approach on enriched uranium items and demonstrate the feasibility of a precise measurement using realistic nuclear materials, representative of field scenarios, even with just a single laser-driven neutron pulse. Bright pulsed sources can overcome the nuisance background of items with strong internal neutron sources, improving analytical power, while single-shot assay is attractive in high-throughput situations where time is at a premium. The science and technology of this type of neutron production is developing rapidly, and we anticipate that practical mobile interrogation systems will become available based on the detection concepts demonstrated here to meet the growing measurement needs.
Journal Article
Oral Delivery Systems for Encapsulated Bacteriophages Targeted at Escherichia coli O157:H7 in Feedlot Cattle
Bacteriophages are natural predators of bacteria and may mitigate Escherichia coli O157:H7 in cattle and their environment. As bacteriophages targeted to E. coli O157:H7 (phages) lose activity at low pH, protection from gastric acidity may enhance efficacy of orally administered phages. Polymer encapsulation of four phages, wV8, rV5, wV7, and wV11, and exposure to pH 3.0 for 20 min resulted in an average 13.6% recovery of phages after release from encapsulation at pH 7.2. In contrast, untreated phages under similar conditions had a complete loss of activity. Steers (n = 24) received 10(11) CFU of naladixic acid-resistant E. coli O157:H7 on day 0 and were housed in six pens of four steers. Two pens were control (naladixic acid-resistant E. coli O157:H7 only), and the remaining pens received polymer-encapsulated phages (Ephage) on days -1, 1, 3, 6, and 8. Two pens received Ephage orally in gelatin capsules (bolus; 10(10) PFU per steer per day), and the remaining two pens received Ephage top-dressed on their feed (feed; estimated 10(11) PFU per steer per day). Shedding of E. coli O157:H7 was monitored for 10 weeks by collecting fecal grab and hide swab samples. Acceptable activity of mixed phages at delivery to steers was found for bolus and feed, averaging 1.82 and 1.13 x 10(9) PFU/g, respectively. However, Ephage did not reduce shedding of naladixic acid-resistant E. coli O157:H7, although duration of shedding was reduced by 14 days (P < 0.1) in bolus-fed steers as compared with control steers. Two successful systems for delivery of Ephage were developed, but a better understanding of phage-E. coli O157:H7 ecology is required to make phage therapy a viable strategy for mitigation of this organism in feedlot cattle.
Journal Article
Laser-driven acceleration of quasi-monoenergetic, near-collimated titanium ions via a transparency-enhanced acceleration scheme
Laser-driven ion acceleration has been an active research area in the past two decades with the prospects of designing novel and compact ion accelerators. Many potential applications in science and industry require high-quality, energetic ion beams with low divergence and narrow energy spread. Intense laser ion acceleration research strives to meet these challenges and may provide high charge state beams, with some successes for carbon and lighter ions. Here we demonstrate the generation of well collimated, quasi-monoenergetic titanium ions with energies ∼145 and 180 MeV in experiments using the high-contrast (<10−9) and high-intensity ( 6 × 10 20 W cm − 2 ) Trident laser and ultra-thin (∼100 nm) titanium foil targets. Numerical simulations show that the foils become transparent to the laser pulses, undergoing relativistically induced transparency (RIT), resulting in a two-stage acceleration process which lasts until ∼2 ps after the onset of RIT. Such long acceleration time in the self-generated electric fields in the expanding plasma enables the formation of the quasi-monoenergetic peaks. This work contributes to the better understanding of the acceleration of heavier ions in the RIT regime, towards the development of next generation laser-based ion accelerators for various applications.
Journal Article
Bacteriophages for prophylaxis and therapy in cattle, poultry and pigs
The successful use of virulent (lytic) bacteriophages (phages) in preventing and treating neonatal enterotoxigenic Escherichia coli infections in calves, lambs and pigs has prompted investigation of other applications of phage therapy in food animals. While results have been very variable, some indicate that phage therapy is potentially useful in virulent Salmonella and E. coli infections in chickens, calves and pigs, and in control of the food-borne pathogens Salmonella and Campylobacter jejuni in chickens and E. coli O157:H7 in cattle. However, more rigorous and comprehensive research is required to determine the true potential of phage therapy. Particular challenges include the selection and characterization of phages, practical modes of administration, and development of formulations that maintain the viability of phages for administration. Also, meaningful evaluation of phage therapy will require animal studies that closely represent the intended use, and will include thorough investigation of the emergence and characteristics of phage resistant bacteria. As well, effective use will require understanding the ecology and dynamics of the endemic and therapeutic phages and their interactions with target bacteria in the farm environment. In the event that the potential of phage therapy is realized, adoption will depend on its efficacy and complementarity relative to other interventions. Another potential challenge will be regulatory approval.
Journal Article