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Intranasal corticosteroids are widely used for management of many upper airway diseases because of their ability to effectively deliver local relief of inflammation.
This paper presents the case of a 51-year-old man with human immunodeficiency virus treated with ritonavir who was started on fluticasone intranasal spray for presumed chronic rhinosinusitis. Months after starting this therapy, he developed symptoms of Cushing's syndrome and avascular necrosis of the shoulder due to the pharmacological interactions between fluticasone and ritonavir.
Although intranasal corticosteroids are deemed a low-risk route of drug administration, clinicians need to be vigilant in appropriately prescribing corticosteroids in the setting of drug potentiators, particularly in these high-risk patients. Alternative corticosteroids such as beclomethasone dipropionate should be considered in such cases.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Background: In November 2020, bamlanivimab received emergency use authorization (EUA) to treat patients with early, mild-to-moderate COVID-19 who are at high risk of progression. Montefiore Medical Center serves an economically underserved community of >1.4 million residents in the Bronx, New York. Montefiore’s antimicrobial stewardship team (AST) developed a multidisciplinary treatment pathway for patients meeting EUA criteria: (1) outpatients and hospital associates and (2) acute-care patients (EDs or inpatient). Methods: The Montefiore AST established a centralized process for screening high-risk COVID-19 patients 7 days a week. Referrals were sent by e-mail from occupational health, primary care practices, specialty practices, emergency departments, and urgent care centers. Patients were screened in real time and were treated in the ED or a newly established infusion center within 24 hours. After infusion, all patients received phone calls from nurses and had an infectious diseases televisit. Demographics, clinical symptoms, subsequent ED visit or hospital admission, and timing from infusion to ED or hospitalization were obtained from the electronic health record. Results: In total, 281 high-risk patients (median age, 62 years; 57% female) received bamlanivimab at the infusion center or in the acute-care setting between December 2, 2020, and January 27, 2021 (Table 1). The number of treated patients increased weekly (Figure 1). Also, 62% were Hispanic or black, and 96% met EUA criteria. Furthermore, 51 (18%) were referred from occupational health, 205 (73%) were referred from the community, and 25 (9%) were inpatients (https://www.fda.gov/media/143605/download). All patients were successfully infused without adverse reactions. In addition, 23 patients (8.2%) were hospitalized and 6 (2.1%) visited EDs within 30 days of treatment. The average number of days between symptom onset and infusion was 4.9. The median age of admitted versus nonadmitted patients was 68 years versus 61.5 years (P = .07). Conclusions: An AST-coordinated bamlanivimab treatment program successfully treated multiple high-risk COVID-19 patients and potentially reduced hospitalizations. However, the effort, personnel, and resources required are significant. Dedicated hospital investment is necessary for maximal success.
The aim of this study was to provide insights learned from disaster research response (DR2) efforts following Hurricane Harvey in 2017 to launch DR2 activities following the Intercontinental Terminals Company (ITC) fire in Deer Park, Texas, in 2019.
A multidisciplinary group of academic, community, and government partners launched a myriad of DR2 activities.
The DR2 response to Hurricane Harvey focused on enhancing environmental health literacy around clean-up efforts, measuring environmental contaminants in soil and water in impacted neighborhoods, and launching studies to evaluate the health impact of the disaster. The lessons learned after Harvey enabled rapid DR2 activities following the ITC fire, including air monitoring and administering surveys and in-depth interviews with affected residents.
Embedding DR2 activities at academic institutions can enable rapid deployment of lessons learned from one disaster to enhance the response to subsequent disasters, even when those disasters are different. Our experience demonstrates the importance of academic institutions working with governmental and community partners to support timely disaster response efforts. Efforts enabled by such experience include providing health and safety training and consistent and reliable messaging, collecting time-sensitive and critical data in the wake of the event, and launching research to understand health impacts and improve resiliency.
In order to maximize the utility of future studies of trilobite ontogeny, we propose a set of standard practices that relate to the collection, nomenclature, description, depiction, and interpretation of ontogenetic series inferred from articulated specimens belonging to individual species. In some cases, these suggestions may also apply to ontogenetic studies of other fossilized taxa.
Errors inherent in self-reported measures of energy intake (EI) are substantial and well documented, but correlates of misreporting remain unclear. Therefore, potential predictors of misreporting were examined. In Study One, fifty-nine individuals (BMI = 26·1 (sd 3·8) kg/m2, age = 42·7 (sd 13·6) years, females = 29) completed a 14-d stay in a residential feeding behaviour suite where eating behaviour was continuously monitored. In Study Two, 182 individuals (BMI = 25·7 (sd 3·9) kg/m2, age = 42·4 (sd 12·2) years, females = 96) completed two consecutive days in a residential feeding suite and five consecutive days at home. Misreporting was directly quantified by comparing covertly measured laboratory weighed intakes (LWI) with self-reported EI (weighed dietary record (WDR), 24-h recall, 7-d diet history, FFQ). Personal (age, sex and %body fat) and psychological traits (personality, social desirability, body image, intelligence quotient and eating behaviour) were used as predictors of misreporting. In Study One, those with lower psychoticism (P = 0·009), openness to experience (P = 0·006) and higher agreeableness (P = 0·038) reduced EI on days participants knew EI was being measured to a greater extent than on covert days. Isolated associations existed between personality traits (psychoticism and openness to experience), eating behaviour (emotional eating) and differences between the LWI and self-reported EI, but these were inconsistent between dietary assessment techniques and typically became non-significant after accounting for multiplicity of comparisons. In Study Two, sex was associated with differences between LWI and the WDR (P = 0·009), 24-h recall (P = 0·002) and diet history (P = 0·050) in the laboratory, but not home environment. Personal and psychological correlates of misreporting identified displayed no clear pattern across studies or dietary assessment techniques and had little utility in predicting misreporting.
In Chapter 3, James Hopkins cautions that modern trade agreements benefit an elite few and that the agreements are reliant upon overly ambitious macroeconomic theories. There is a growing awareness that international trade’s net effect is widening the gap between economic winners and losers, much to the detriment of Indigenous peoples. In his chapter, Professor Hopkins examines the impacts of international trade on the Indigenous peoples of Mexico and provides some hope that the USMCA, if ratified, may be an improvement to the NAFTA, which has contributed to a dire human rights situation which threatens the lives and livelihoods of Indigenous peoples.
Around 30% of individuals with schizophrenia remain symptomatic and significantly impaired despite antipsychotic treatment and are considered to be treatment resistant. Clinicians are currently unable to predict which patients are at higher risk of treatment resistance.
To determine whether genetic liability for schizophrenia and/or clinical characteristics measurable at illness onset can prospectively indicate a higher risk of treatment-resistant psychosis (TRP).
In 1070 individuals with schizophrenia or related psychotic disorders, schizophrenia polygenic risk scores (PRS) and large copy number variations (CNVs) were assessed for enrichment in TRP. Regression and machine-learning approaches were used to investigate the association of phenotypes related to demographics, family history, premorbid factors and illness onset with TRP.
Younger age at onset (odds ratio 0.94, P = 7.79 × 10−13) and poor premorbid social adjustment (odds ratio 1.64, P = 2.41 × 10−4) increased risk of TRP in univariate regression analyses. These factors remained associated in multivariate regression analyses, which also found lower premorbid IQ (odds ratio 0.98, P = 7.76 × 10−3), younger father's age at birth (odds ratio 0.97, P = 0.015) and cannabis use (odds ratio 1.60, P = 0.025) increased the risk of TRP. Machine-learning approaches found age at onset to be the most important predictor and also identified premorbid IQ and poor social adjustment as predictors of TRP, mirroring findings from regression analyses. Genetic liability for schizophrenia was not associated with TRP.
People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment resistant. The genetic architecture of susceptibility to schizophrenia may be distinct from that of treatment outcomes.
We measure the cosmic star formation history out to z = 1.3 using a sample of 918 radio-selected star-forming galaxies within the 2-deg2 COSMOS field. To increase our sample size, we combine 1.4-GHz flux densities from the VLA-COSMOS catalogue with flux densities measured from the VLA-COSMOS radio continuum image at the positions of I < 26.5 galaxies, enabling us to detect 1.4-GHz sources as faint as 40 μJy. We find that radio measurements of the cosmic star formation history are highly dependent on sample completeness and models used to extrapolate the faint end of the radio luminosity function. For our preferred model of the luminosity function, we find the star formation rate density increases from 0.017 M⊙ yr−1 Mpc−3 at z ∼ 0.225 to 0.092 M⊙ yr−1 Mpc−3 at z ∼ 1.1, which agrees to within 40% of recent UV, IR and 3-GHz measurements of the cosmic star formation history.
Binge eating disorder (BED) is the most common eating disorder in the US, with a lifetime prevalence of 2.8%. Disturbances in reward circuitry have been implicated in its pathogenesis. Dasotraline is a novel and potent dopamine and norepinephrine reuptake inhibitor with slow absorption and a long half-life resulting in stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated the efficacy and safety of flexibly-dosed dasotraline (4, 6, and 8 mg/day) vs placebo in adults with moderate to severe BED over a 12-week period (NCT02564588).
Key inclusion criteria included moderate to severe BED based on a history of ≥2 binge eating days/week for ≥6 months prior to screening, and ≥3 binge eating days for each of2 weeks prior to randomization, as documented in participant’s binge eating diary. Patients were randomized 1:1 to flexibly-dosed dasotraline (4, 6, 8 mg/day) or placebo. Theprimary endpoint was change from baseline (CFB) in the number of binge eating days per week at Week 12. Key secondary endpoints were: CFB in Clinical Global Impression–Severity (CGI-S) Scale at Week 12; CFB in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (YBOCS-BE) at Week 12; and the percentage ofsubjects with a 4-week cessation from binge eating prior to Week 12 or end of treatment (EOT). Except for 4-week cessation, the other three variables were analyzed using amixed model for repeated measures (MMRM).
317 subjects (84% female) received ≥1 dose of study medication (mean age was 38.2 years; mean number of binge eating days per week, 4.25; mean CGI-S score, 4.5; mean BMI, 34.7). The MMRM analysis of CFB at Week 12 in the number of binge days/week yielded a significant mean difference of –0.99 (95% CI: –0.65 to –1.33; p<0.001) infavour of dasotraline (–3.74 in the dasotraline group vs –2.75 in the placebo group). All three key secondary endpoints were met at Week 12 or EOT: 46.5% of subjects in thedasotraline group achieved at least 4 consecutive weeks’ cessation from binge eating vs 20.6% in the placebo group (p<0.001); CFB in CGI-S and YBOCS-BE scores were also statistically significant in favour of dasotraline (p<0.001). The treatment-emergent adverse events (TEAEs) that occurred more frequently with dasotraline vs placebo at >2% incidence included: insomnia (44.6% vs 8.1%), dry mouth (27.4% vs 5.0%), decreased appetite (19.7% vs 6.9%), anxiety (17.8% vs 2.5%), nausea (12.7% vs 6.9%) and decreased body weight (12.1% vs 0%). Discontinuation due to AEs occurred in 11.5% of patients taking dasotraline vs 2.5% taking placebo.
In adults with moderate to severe BED, there were highly significant and clinically meaningful reductions with dasotraline vs placebo in the frequency of binge eating, global severity of illness, and obsessive-compulsive symptoms related to binge eating. These results suggest dasotraline may offer a novel, well-tolerated and efficacious treatmentfor BED.
The local electrode atom probe (LEAP) has become the primary instrument used for atom probe tomography measurements. Recent advances in detector and laser design, together with updated hit detection algorithms, have been incorporated into the latest LEAP 5000 instrument, but the implications of these changes on measurements, particularly the size and chemistry of small clusters and elemental segregations, have not been explored. In this study, we compare data sets from a variety of materials with small-scale chemical heterogeneity using both a LEAP 3000 instrument with 37% detector efficiency and a 532-nm green laser and a new LEAP 5000 instrument with a manufacturer estimated increase to 52% detector efficiency, and a 355-nm ultraviolet laser. In general, it was found that the number of atoms within small clusters or surface segregation increased in the LEAP 5000, as would be expected by the reported increase in detector efficiency from the LEAP 3000 architecture, but subtle differences in chemistry were observed which are attributed to changes in the way multiple hit detection is calculated using the LEAP 5000.
Scholarly assessments of Chaucer's fabliaux seldom acknowledge that these tales are erotic as well as funny; even less frequently do such investigations delve into why fabliaux are a source of pleasure. As Tom Hanks and W. W. Allman note in their article ‘Rough Love: Notes toward an Erotics of The Canterbury Tales’, scholars seem ‘to have averted their gaze when Chaucer's characters leap into bed’. Allman and Hanks, as their title implies, study an erotics of violence, mostly of men doing violence to women, and they focus in particular on the Merchant's Tale and its ‘erotics of stabbing’. A more positive erotic reading of the Merchant's Tale appears in Andrew Taylor's 1996 essay ‘Reading the Dirty Bits’. Taylor notes the lingering gaze of another scholar, E. Talbot Donaldson, upon a description of young May's body:
Hir fresshe beautee and hir age tendre,
Hir myddel smal, hire armes longe and sklendre,
Hir wise governaunce, hir gentilesse,
Hir wommanly berynge, and hire sadnesse.
Donaldson writes, ‘the Spring of pretty young girls is a permanent thing, and that May in their personas will always warm the masculine heart’. Taylor suggests that pleasure taken in this description and in Donaldson's gloss of it is mimetic: ‘For the young college man to share Donaldson's and Chaucer's pleasure in May is to become, like them, a connoisseur of both good writing and pretty girls, a master of ironic detachment and well-modulated heterosexual desire’.
As Roger Ascham famously observed, Malory's Morte Darthur is primarily concerned with ‘open manslaughter, and bold bawdry’. I would not disagree; in fact, I would say that these themes are not only dominant but are inextricably interwoven. Male sexuality, in Malory, is consistently portrayed as potentially violent and disruptive, dangerous not only to individuals but to the whole structure of society, and therefore in need of controlling measures. The medieval world did not, of course, often portray any form of sexuality positively. Sexual desire leads both men and women to sin: both directly in committing fornication, incest and adultery, and indirectly in committing treason or disregarding their duties. It could easily be assumed that this is a divide between the clergy on the one side, themselves compelled to live in celibacy and thus suspicious of sexual desire, and the more relaxed nobility and commons on the other, cheerfully ignoring the rules when it suited them. However, this is too simple a dichotomy. Malory himself, despite the bold bawdry, shares in the suspicion of unregulated desire, in his nostalgia for a chaster time,
nowadayes men can nat love sevennyght but they muste have all their desyres … But the olde love was nat so. for men and women coulde love togydirs seven yerys, and no lycoures lustis was betwyxte them, and than was love trouthe and faythefulnes.