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Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.
While unobscured and radio-quiet active galactic nuclei are regularly being found at redshifts
$z > 6$
, their obscured and radio-loud counterparts remain elusive. We build upon our successful pilot study, presenting a new sample of low-frequency-selected candidate high-redshift radio galaxies (HzRGs) over a sky area 20 times larger. We have refined our selection technique, in which we select sources with curved radio spectra between 72–231 MHz from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. In combination with the requirements that our GLEAM-selected HzRG candidates have compact radio morphologies and be undetected in near-infrared
$K_{\rm s}$
-band imaging from the Visible and Infrared Survey Telescope for Astronomy Kilo-degree Infrared Galaxy (VIKING) survey, we find 51 new candidate HzRGs over a sky area of approximately
$1200\ \mathrm{deg}^2$
. Our sample also includes two sources from the pilot study: the second-most distant radio galaxy currently known, at
$z=5.55$
, with another source potentially at
$z \sim 8$
. We present our refined selection technique and analyse the properties of the sample. We model the broadband radio spectra between 74 MHz and 9 GHz by supplementing the GLEAM data with both publicly available data and new observations from the Australia Telescope Compact Array at 5.5 and 9 GHz. In addition, deep
$K_{\rm s}$
-band imaging from the High-Acuity Widefield K-band Imager (HAWK-I) on the Very Large Telescope and from the Southern Herschel Astrophysical Terahertz Large Area Survey Regions
$K_{\rm s}$
-band Survey (SHARKS) is presented for five sources. We discuss the prospects of finding very distant radio galaxies in our sample, potentially within the epoch of reionisation at
$z \gtrsim 6.5$
.
A developing application of laser-driven currents is the generation of magnetic fields of picosecond–nanosecond duration with magnitudes exceeding $B=10~\text{T}$. Single-loop and helical coil targets can direct laser-driven discharge currents along wires to generate spatially uniform, quasi-static magnetic fields on the millimetre scale. Here, we present proton deflectometry across two axes of a single-loop coil ranging from 1 to 2 mm in diameter. Comparison with proton tracking simulations shows that measured magnetic fields are the result of kiloampere currents in the coil and electric charges distributed around the coil target. Using this dual-axis platform for proton deflectometry, robust measurements can be made of the evolution of magnetic fields in a capacitor coil target.
The Virtual Personalities Model is a motive-based neural network model that provides both a psychological model and a computational implementation that explicates the dynamics and often large within-person variability in behavior that arises over time. At the same time the same model can produce—across many virtual personalities—between-subject variability in behavior that when factor analyzed yields familiar personality structure (e.g., the Big Five). First, we describe our personality model and its implementation as a neural network model. Second, we focus on detailing the neurobiological underpinnings of this model. Third, we examine the learning mechanisms, and their biological substrates, as ways that the model gets “wired up,” discussing Pavlovian and Instrumental conditioning, Pavlovian to Instrumental transfer, and habits. Finally, we describe the dynamics of how initial differences in propensities (e.g., dopamine functioning), wiring differences due to experience, and other factors could operate together to develop and change personality over time, and how this might be empirically examined. Thus, our goal is to contribute to the rising chorus of voices seeking a more precise neurobiologically based science of the complex dynamics underlying personality.
Millimetric, ellipsoidal monazite nodules found within Lower Palaeozoic sedimentary rocks in Wales, south-west England and Brittany are characterised by a pronounced zonation of light and heavy REE, an inclusion fabric of low-grade metamorphic minerals indistinguishable from the host rock and a low Th content. They are interpreted as the product of in situ recrystallization of detrital monazites derived from pegmatitic or granitic source rocks and are potentially useful as indicators of Lower Palaeozoic sedimentary rock provenance.
Rectangular specimens of ice (c. 5 cm × 2 cm × 0.5 cm) were cut from large single crystals (c, 10 cm × 5 cm2) grown from pure water by a modified Bridgman technique. When these specimens were deformed under controlled conditions, slip lines which were predominantly parallel to the basal plane became visible. In some cases short. perpendicular segments were also seen which can be interpreted as evidence for cross-slip in ice. Measurements of slip-band spacings were made on silvered “formvar” replicas of some deformed crystals. These measurements showed that “coarse” slip occurred when the resolved shear stress on the basal plane. σ, was greater than about 0.2 bars, and that the average thickness of the slip lamellae, d (cm) was approximately given by Wakahama’s relationship. (σ−0.2) d = 0.45 × 10−3. At lower stresses “fine” slip occurred, and the relationship between the average thickness of the lamellae and the resolved shear stress was more adequately described by Taylor’s formula, σd = 7.2 × 10−5. It is. however, possible that both coarse and fine slip occurred at higher stresses, but that the fine slip was then below the limit of resolution.
The rapid rise in syphilis cases has prompted a number of public health campaigns to assist men who have sex with men (MSM) recognize and present early with symptoms. This study aimed to investigate the temporal trend of the duration of self-report symptoms and titre of rapid plasma reagin (RPR) in MSM with infectious syphilis. Seven hundred and sixty-one syphilis cases in MSM diagnosed at the Melbourne Sexual Health Centre (MSHC) from 2007–2013 were reviewed. Median duration of symptoms and RPR titres in each year were calculated. The median durations of symptoms with primary and secondary syphilis were 9 [interquartile range (IQR) 6–14] days and 14 (IQR 7–30) days, respectively. The overall median titre of RPR in secondary syphilis (median 128, IQR 64–256) was higher than in primary syphilis (median 4, IQR 1–32) and in early latent syphilis (median 32, IQR 4–64). The median duration of symptoms for primary syphilis, secondary syphilis and titre of RPR level did not change over time. Public health campaigns were not associated with a significant shorter time from onset of symptoms to treatment. Alternative strategies such as more frequent testing of MSM should be promoted to control the syphilis epidemic in Australia.
Objectives: Assess the bioavailability of mixed amphetamine salts extended-release (MAS XR) 30-mg capsules and the dose proportionality of pharmacokinetic measures for MAS XR 20,40, and 60 mg.
Methods: Study A, an open-label single-period study, and Study B, a randomized, open-label, three threeway crossover study, were conducted in healthy adults in a clinical research unit. In Study A, 20 subjects received a single MAS XR 30-mg capsule by mouth daily for 7 days. In Study B, 12 subjects received single oral doses of MAS XR 20,40, and 60 mg separated by 7-14-day washout periods.
Findings: Plasma dextroamphetamine (D-amphetamine) and levoamphetamine (L-amphetamine) concentrations were measured using a validated LC-MS/MS method. In Study A, a 3:1 ratio of D-amphetamine to L-amphetamine was observed for AUC0-∞ and Cmax. Tmax was 4.2 and 4.3 hours for D-amphetamine to Lamphetamine, respectively. In Study B, for D- and Lamphetamine, statistically significant differences were observed for AUC0-t, AVC0-∞, and Cmax between all doses; there was a linear relationship between pharmacokinetic variables and dose and Tmax was similar for each isomer (range: 4.5–5.3 hours) with all given MAS XR doses.
Conclusion: The extent of exposure as assessed by mean AUC0-24 and Cmax reflected the 3:1 ratio of D-amphetamine to L-amphetamine in MAS XR 30-mg capsules. The pharmacokinetic profiles of MAS XR 20, 40, and 60 mg are dose proportional for the isomers.
Objective: Assess the long-term safety and effectiveness of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.
Methods: A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced–dose-escalation study of MAS XR in adults (≥ 18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mgl day for 1 week, with subsequent titration up to 60 mgl day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-N). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs.
Findings: ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (-7.2±13.04 unit points; P<.001); this was sustained for up to 24 months. The most common treatment-related adverse events were dry mouth (43% of subjects reporting at least one occurrence), infection (33%), insomnia (32%), anorexia/decreased appetite (32%), headache (30%), and nervousness (26%). Most adverse events were mild to moderate in intensity.
Conclusion: Treatment with MAS XR 20–60 mgl day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months.
A randomized, open-label, single-dose, three-treatment, three-period, crossover, phase I study was conducted to assess the pharmacokinetics of mixed amphetamine salts extended release (MAS XR) in adolescents with attention-deficit/hyperactivity disorder (ADHD).
Methods
Two cohorts of healthy adolescents 13–17 years of age with ADHD were enrolled in the study. Seventeen subjects, weighing ≤75 kg (≤ 65 lbs), were randomized to one of three dosing sequence groups (a single oral dose of MAS XR 10, 20, or 40 mg, follwed by crossover to the alternate treatments, with a 7-day washout between treatments). Six additional subjects, weighing >75 kg (>165 lbs), were randomized simihrly but received larger doses of MAS XR (20, 40, and 60 mg). Blood samples were collected before and at hours 1–12 after drug administration, as well as before and at hours 14, 24,48, and 60.
Findings
Linear pharmacokinetics of dextroamphetamine (D-amphetamine) and loamphetamine (L-amphetamine) were observed with MAS XR in both cohorts. The pharmacokinetics of D-amphetamine and L-amphetamine did not differ between male and female adolescents. A significant decrease in maximum exposure (Cmax) and increase in half-life were seen for both isomers with increasing age, but overall exposure (AUC∞ was not affected. Cmax and AUC∞ for both isomers decreased as body weight increased.
Conclusion
Exposure to MAS XR was linear and directly proportional to the dose administered in 13–17-year-old adolescents with ADHD. The time course of drug absorption and elimination did not appear to be affected by dose at 10–40 mg in subjects weighing ≤75 kg, and at 20–60 mg in subjects weighing >75 kg. Gender did not affect the pharmacokinetics of MAS XR; age and body weight influenced the profile of certain pharmacokinetic variables.
Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a serious neurobehavioral disorder of childhood onset that often persists into adolescence and adulthood. Functional impairments, underachievement, and difficult interpersonal relationships illustrate the need for effective treatment of ADHD through adulthood.
Method: This prospective, multisite, randomized, double-blind, placebo-controlled, parallel-group, dose-escalation study was conducted to assess the efficacy, safety, and duration of action of mixed amphetamine salts extended-release (MAS XR) in adults with ADHD, combined type. Adults ≥ 18 years of age were given placebo or MAS XR 20, 40, or 60 mg/day for 4 weeks. The main outcome measures were the ADHD Rating Scale and Conners' Adult ADHD Rating Scale Short Version Self-Report (CAARS-S-S).
Results: Two hundred fifty-five subjects were randomly assigned to treatment with MAS XR or placebo. MAS XR treatment was associated with statistically and clinically significant ADHD symptom reduction at endpoint; mean ADHD Rating Scale scores were 18.5 for the 20-mg group (P=.001), 18.4 for the 40-mg group (P<.001), and 18.5 for the 60-mg group (P<.001). Adults with severe symptoms (ADHD Rating Scale score ≥32 at baseline) had significantly greater symptom reduction with the highest MAS XR dose (60 mg/day), however, this dose-response relationship was determined by post-hoc analysis. The mean MAS XR effect size was 0.8. Statistically significant (P<.05) improvements in CAARS-S-S ADHD index scores occurred at 4- and 12-hours postdose for all MAS XR groups, indicating a 12-hour duration of effect. Symptoms improved within the first treatment week. Most adverse events reported were mild or moderate in intensity, arid the most commonly reported adverse events were consistent with the known profile of stimulant medications. Vital signs and electrocardiograms showed no clinically significant cardiovascular changes.
Conclusion: These results suggest that MAS XR is safe and effective in adults with ADHD and controlled ADHD symptoms for up to 12 hours.
Data were extracted from the case records of UK patients admitted with laboratory-confirmed influenza A(H1N1)pdm09. White and non-White patients were characterized by age, sex, socioeconomic status, pandemic wave and indicators of pre-morbid health status. Logistic regression examined differences by ethnicity in patient characteristics, care pathway and clinical outcomes; multivariable models controlled for potential confounders. Whites (n = 630) and non-Whites (n = 510) differed by age, socioeconomic status, pandemic wave of admission, pregnancy, recorded obesity, previous and current smoking, and presence of chronic obstructive pulmonary disease. After adjustment for a priori confounders non-Whites were less likely to have received pre-admission antibiotics [adjusted odds ratio (aOR) 0·43, 95% confidence interval (CI) 0·28–0·68, P < 0·001) but more likely to receive antiviral drugs as in-patients (aOR 1·53, 95% CI 1·08–2·18, P = 0·018). However, there were no significant differences by ethnicity in delayed admission, severity at presentation for admission, or likelihood of severe outcome.
The group G streptococcus has generally not been considered a prominent pathogen. In a 1982 study of the colonization rate by β-haemoly tic streptococci in apparently healthy children, age 5–11 years, 25 of 69 isolates belonged to group G. This surprisingly high rate of group G colonization (14·3%) led to a retrospective study of school surveys in 1967 which showed that the colonization rate with this organism was 2·3% (range 1·3–3·5%). A review of bacitracin-sensitive streptococcal isolates from hospital admissions of patients with acute glomerulonephritis (AGN), rheumatic fever, and their siblings, between January 1967 and July 1980, was conducted. Of 1063 bacitracin-sensitive isolates, 63 were group G, and 52 of these were isolated from AGN patients and their siblings, i.e. 7 from skin lesions of AGN patients, 40 from the throats of siblings and only 5 from the skins of the siblings. The other 11 group G isolates were from rheumatic-fever patients and their siblings. Thus, the group G colonization rate fluctuates in the population. The isolation of only group G streptococci from skin lesions of patients with AGN suggests a possible association between group G streptococcal pyoderma and acute post-streptococcal glomerulonephritis.
Molecular characterization of the Plasmodium falciparum genome has led to identification of polymorphic loci and the mechanisms generating genetic diversity in this parasite. This information has resulted in the development of molecular methods to type parasite diversity in the field. Consequently, we are now in a position to describe the population genetics and dynamics of P. falciparum. The limited number of field studies that have been conducted to date have revealed an extraordinary degree of genetic diversity in natural parasite populations. Heterozygous recombination which occurs during meiosis appears to be one mechanism for generating genetic diversity. The rate at which such recombination occurs in natural parasite populations defines the genetic structure of the parasite population and can influence the ability of the parasite to respond to selection pressure. The high frequency of single genotype infections and the female-biased gametocyte sex ratios found in hyperendemic malaria areas suggest that self-fertilization occurs frequently. Population- wide surveys of allele frequencies in endemic areas have, however, shown no evidence of linkage disequilibrium and are consistent with a panmictic population structure. We argue that these studies have only sampled symptomatic infections, within which rare or recombinant genotypes may be disproportionately represented. They also take no account of the spatial structure of P. falciparum populations. Systematic investigations of the amount of heterozygosity in small areas as part of population-wide surveys are required to define the genetic structure of P. falciparum populations. Population dynamic studies which consider genetic heterogeneity of P. falciparum have shown fluctuations of different serotypes in space and time. The host immune response appears to play an important role in generating these dynamics. Integrated field and laboratory studies, which consider the interaction between population genetics and dynamics, will be necessary to describe the population biology of P. falciparum.
The notion of approximate amenability was introduced by Ghahramani and Loy, in the hope that it would yield Banach algebras without bounded approximate identity which nonetheless had a form of amenability. So far, however, all known approximately amenable Banach algebras have bounded approximate identities (b.a.i.). In this paper we define approximate amenability and contractibility of Fréchet algebras, and we prove the analogue of the result for Banach algebras that these properties are equivalent. We give examples of Fréchet algebras which are approximately contractible, but which do not have a bounded approximate identity. For a good many Fréchet algebras without b.a.i., we find either that the algebra is approximately amenable, or it is “obviously” not approximately amenable because it has continuous point derivations. So the situation for Fréchet algebras is quite close to what was hoped for Banach algebras.