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We present continuous estimates of snow and firn density, layer depth and accumulation from a multi-channel, multi-offset, ground-penetrating radar traverse. Our method uses the electromagnetic velocity, estimated from waveform travel-times measured at common-midpoints between sources and receivers. Previously, common-midpoint radar experiments on ice sheets have been limited to point observations. We completed radar velocity analysis in the upper ~2 m to estimate the surface and average snow density of the Greenland Ice Sheet. We parameterized the Herron and Langway (1980) firn density and age model using the radar-derived snow density, radar-derived surface mass balance (2015–2017) and reanalysis-derived temperature data. We applied structure-oriented filtering to the radar image along constant age horizons and increased the depth at which horizons could be reliably interpreted. We reconstructed the historical instantaneous surface mass balance, which we averaged into annual and multidecadal products along a 78 km traverse for the period 1984–2017. We found good agreement between our physically constrained parameterization and a firn core collected from the dry snow accumulation zone, and gained insights into the spatial correlation of surface snow density.
Pertussis is a highly contagious infectious disease and remains an important cause of mortality and morbidity worldwide. Over the last decade, vaccination has greatly reduced the burden of pertussis. Yet, uncertainty in individual vaccination coverage and ineffective case surveillance systems make it difficult to estimate burden and the related quantity of population-level susceptibility, which determines population risk. These issues are more pronounced in low-income settings where coverage is often overestimated, and case numbers are under-reported. Serological data provide a direct characterisation of the landscape of susceptibility to infection; and can be combined with vaccination coverage and basic theory to estimate rates of exposure to natural infection. Here, we analysed cross-sectional data on seropositivity against pertussis to identify spatial and age patterns of susceptibility in children in Madagascar. A large proportion of individuals surveyed were seronegative; however, there were patterns suggestive of natural infection in all the regions analysed. Improvements in vaccination coverage are needed to help prevent additional burden of pertussis in the country.
Background: Outpatients with uncomplicated urinary tract infections (UTIs) are often treated empirically without culture, whereas urine cultures are typically collected from patients with complicated UTI. Susceptibilities for fosfomycin (a first-line agent) are not routinely performed or reported in the antibiogram. Understanding the prevalence of antibiotic resistance for UTI is critical for empiric treatment and antibiotic stewardship in primary care. Methods: We developed a UTI-focused antibiogram from a prospective sample of outpatients (women and men) with UTIs from 2 public family medicine clinics in an urban area with a diverse, international population (November 2018 to present). During the study period, providers ordered a urine culture for any adult patient presenting with UTI symptoms, including uncomplicated and complicated infections. We estimated the prevalence of resistance to UTI-relevant antibiotics in the overall study population and compared it between patients born in the United States and other countries. Results: We collected 678 urine cultures from 644 unique patients (79% female). Of these cultures, 158 (23.3%) had no growth, 330 (48.7%) grew mixed urogenital flora, and 190 (28.0%) were positive (>10,000 CFU/mL). Patients with positive cultures were mostly female (88.2%), and their mean age was 46.6 ± 14.8 years. Among patients with positive cultures, 42.7% were born in the United States and 57.3% were born Mexico or Central America. Escherichia coli was the most commonly isolated organism (Fig. 1). Susceptibility results for E. coli and all gram-negative organisms combined are presented in Fig. 2. Susceptibility of uropathogens to TMP-SMX was significantly higher in patients born in the United States compared to patients from Mexico or Central America (82% vs 61%; P = .03). Susceptibility to ciprofloxacin was similar in patients born in the United States and other countries (79% vs 72%; P = .50). Of 77 E. coli isolates, 11 (14%) were positive for extended-spectrum β-lactamase production, including 8 isolates from patients whose country of origin was Mexico or a Central American country. Conclusions: More than 20% of outpatients presenting with UTI symptoms had a negative urine culture. Among outpatients with uncomplicated and complicated UTI, uropathogens had a high prevalence of resistance to ciprofloxacin and TMP-SMX, but susceptibility to fosfomycin (restricted in our system) was 100%. Resistance rates for TMP-SMX were higher in patients from Mexico and Central America. Our findings question whether TMP-SMX should remain a first-line agent in US primary-care settings.
Funding: This project was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681.
Confederate monuments are a contested piece of the public landscape. Debates generally focus on the division between “heritage” and “hate,” but some scholars have argued that the meaning of monuments is more complex. There is little research examining variation among Confederate monuments, but this may be critical to understanding their social foundations and consequences. We provide insight into Confederate monuments and their complexity by examining their inscriptions and how the use of different inscriptions changed over time and varies between the Upper South and Deep South. We employ content analysis to organize the inscriptions associated with 856 Confederate monuments located in public spaces throughout the U.S. South into common themes. Our results suggest three distinct types of inscriptions: those connected to the lost cause ideology that glorifies the Confederacy and its cause; those that were comparatively plain in their description of people, places, and events; and others that focused exclusively on mourning the death of Confederate soldiers. The majority of monuments (59%) contain a Lost Cause inscription. Plain monuments comprise 35%, and only 6% of public Confederate monuments were dedicated purely to the dead. Our descriptive analysis also indicates substantial temporal and spatial variation in the use of these different types of inscriptions. Despite sharing a connection to the Confederacy, we assert that the specific messages associated with a monument are more varied and, in part, reflect the social conditions of the time and place in which they were built.
The benefits of school and community partnerships are well documented in government reports and the academic literature. A number of government initiatives have been introduced to actively involve parents and the community in school matters. In addition, various agencies have produced resource kits and guidelines to assist schools and communities to develop and foster partnerships, and partnership agreements. Much of this study has focused on working with Aboriginal peoples. The use of the term, ‘Aboriginal’ in this paper refers to Aboriginal and Torres Strait Islander people. Initiatives such as ‘What Works’ have had some success in building strong Aboriginal community and school partnerships, however, the literature also reveals that despite such initiatives, the levels of success vary from school to school, with some partnerships unable to develop or be sustained. In responding to a gap in the current knowledge, the authors examine the value of school–community partnerships in a rural and remote school where the percentage of Aboriginal Australian students is high. A brief summary of the outcomes of some of the major initiatives with aims to build effective school and community partnerships is provided. This is followed by the findings from a small pilot research study on the implementation of initiatives to build strong school–community relationships in rural and remote Indigenous school settings in Western Australia. The challenges that may inhibit the establishment of successful school–community relationships/collaboration are discussed and suggestions provided on how these challenges can be addressed.
Eating-disorder severity indicators should theoretically index symptom intensity, impairment, and level of needed treatment. Two severity indicators for binge-eating disorder (BED) have been proposed (categories of binge-eating frequency and shape/weight overvaluation) but have mixed empirical support including modest clinical utility. This project uses structural equation model (SEM) trees – a form of exploratory data mining – to empirically determine the precise levels of binge-eating frequency and/or shape/weight overvaluation that most significantly differentiate BED severities.
Participants were 788 adults with BED enrolled in BED treatment studies. Participants completed interviews and self-report measures assessing eating-disorder and comorbid symptoms. SEM Tree analyses were performed by specifying an outcome model of BED severity and then recursively partitioning the outcome model into subgroups. Subgroups were split based on empirically determined values of binge-eating frequency and/or shape/weight overvaluation. SEM Forests also quantified which variable contributed more improvement in model fit.
SEM Tree analyses yielded five subgroups, presented in ascending order of severity: overvaluation <1.25, overvaluation = 1.25–2.74, overvaluation = 2.75–4.24, overvaluation ⩾4.25 with weekly binge-eating frequency <4.875, and overvaluation ⩾4.25 with weekly binge-eating frequency ⩾4.875. SEM Forest analyses revealed that splits that occurred on shape/weight overvaluation resulted in much more improvement in model fit than splits that occurred on binge-eating frequency.
Shape/weight overvaluation differentiated BED severity more strongly than binge-eating frequency. Findings indicate a nuanced potential BED severity indicator scheme, based on a combination of cognitive and behavioral eating-disorder symptoms. These results inform BED classification and may allow for the provision of more specific and need-matched treatment formulations.
During his lifetime, Johann Wolfgang von Goethe (1749–1832) was not a frequent traveler, aside from his famous Italian journeys, but he engaged frequently with reports of faraway places in letters, scientific treatises, statistics, and other media. Especially later in life, Goethe read a variety of accounts of foreign countries from home in order to form his own impressions of these places and people. In Goethe: Journeys of the Mind, Gabrielle Bersier and Nancy Boerner continue the work of the late Peter Boerner (1926–2015), as they cogently interpret Goethe's correspondence and literary work in conversation with a network of travelers’, explorers’, and scientists’ correspondence and writings to contour the limits of his knowledge.
This study is divided into eight chapters, which examine the possibilities of documenting when and under what conditions Goethe engaged with travel literature. Although he never traveled to England, this study emphasizes the fact that England was the non-German speaking country with which Goethe was most familiar, due to his lifelong exposure to English culture through a variety of media that many educated Germans had at their disposal in the late eighteenth century. Through cross-referencing Dichtung und Wahrheit with epistolary correspondence and library records, the authors explore the broad horizons of Goethe's knowledge of England, which extended from drama to political theory.
The authors remark that Goethe admired England in a way similar to his contemporary, Johann Caspar Lavater, who, like Goethe, never traveled to England, but espoused the idea in his 1775 Physiognomische Fragmente that one could make judgments about the English character based on superficial physical attributes. Thus, the authors approximate Goethe's attitude toward English culture as extending to preconceptions of individual personality traits. The authors astutely address England first in the study's sequence in order to articulate the pedagogical impact Goethe saw in learning through armchair travel, not only as a means to rear cosmopolitan subjects, but also for readers to learn about themselves.
In the second chapter, the authors discuss Goethe's West-östlicher Divan and its intimate intertextual engagement with medieval Sufi poetry by Hafez as another example of vicarious travel. Bearing a bilingual title page and chapter headings, Goethe's poetry collection imagines a particular intercultural openness that contrasted with contemporaneous views on Eastern culture.
For several decades, mental health services within the UK's National Health Service were provided by specialist mental health trusts. More recently many of these trusts have integrated community physical health services into their operations. We describe here how two integrated mental health trusts in England were able to make an enhanced response to the COVID-19 pandemic.
Introduction: One of the most common adverse effects of habitual cannabis use is hyperemesis—recurrent bouts of protracted vomiting, retching and abdominal pain superimposed on a baseline of daily nausea and anorexia. Largely anecdotal evidence supports the use of haloperidol, benzodiazepines or topical capsaicin over traditional antiemetics, yet little is known about the cause or optimal treatment of this newly recognized disorder. We report the results of one of the first clinical trials on so-called cannabis hyperemesis syndrome (NCT03056482). Methods: We approached adults with a working diagnosis of hyperemesis due to cannabis, provided they had ongoing emesis for >2 hours, a cyclic pattern of 3+ episodes in the last 2 years, and near daily use of cannabis by inhalation. We excluded those who were pregnant, deemed unreliable, or using opioids. Subjects provided written consent to be randomized during the index or any subsequent visit to either haloperidol (with a nested randomization to either 0.05 mg/kg or 0.1 mg/kg) or ondansetron 8 mg intravenously in a quadruple-blind fashion, and to be followed for 7 days. The primary outcome was the average reduction from baseline in abdominal pain and nausea (each measured on a 10-cm VAS) at 2 hours. While the original trial design allowed for crossover, the primary analysis used only the first treatment period since fewer than the prespecified threshold of 20% of subjects crossed over. Results: We enrolled 33 subjects, of whom 30 (16 men, 29+/-11 years old, using 1.5+/-0.9 g/day since age 19+/-2 years) were treated at least once (haloperidol 13, ondansetron 17). Haloperidol at either dose was superior to ondansetron (difference 2.3 cm [95%CI 0.6, 4.0]; p = 0.01), with similar improvements in both pain and nausea, as well as less rescue antiemetics (27% vs 61%; p = 0.04), and shorter time to ED departure (3.1+/-1.7 vs 5.6+/-4.5 hours; p = 0.03 Wilcoxon rank sum). There were two (haloperidol) vs six (ondansetron) return visits for ongoing nausea/vomiting, as well as two return visits for acute dystonia, both in the higher dose haloperidol group. Conclusion: Haloperidol is superior to ondansetron for the acute symptomatic treatment of patients with ongoing hyperemesis attributed to habitual cannabis use. The efficacy of this agent over ondansetron provides insight into the mechanism of this new disorder, now almost a daily diagnosis in many Canadian emergency departments.
The provision of support for people with autism spectrum disorder (ASD) within the community is improving as a consequence of policy and legislative changes. However, specialist services are not currently provided in prisons.
This aim of the study was to determine the extent of ASD and co-occurring mental health problems among prisoners. We tested the hypothesis that ASD traits would be unrecognised by prison staff and would be significantly associated with increased rates of anxiety, depression and suicidality.
ASD traits were measured among 240 prisoners in a resettlement prison in London, UK using the 20-item Autism Quotient (AQ-20). Anxiety, depression and suicidality were assessed using the Mini International Neuropsychiatric Interview (MINI).
There were 39 participants (16%) with an AQ-20 score ≥10; indicating significant autistic traits. Mental health data were available for 37 ‘high autistic trait’ participants and another 101 prisoners with no/low ASD traits. There was a significant positive association between AQ-20 and suicidality scores (r=.29, p=0.001). Participants with ASD traits had significantly higher suicidality scores (means=15.1 vs. 5, p= 0.001) and chi-square analysis showed that they were more likely to have a high suicidality rating (27% vs. 8%, p=0.003) than those without ASD traits. Moreover, those with ASD were significantly more likely to be experiencing a current episode of depression (30% vs. 6%, p<0.001) or Generalised Anxiety Disorder (GAD) (27% vs. 11% p=0.019).
Our initial data suggests that severity of ASD traits is a risk factor for suicidality and common mental health problems among prisoners.
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the hyperkinetic movements of motor and phonic tics manifested in young age. Currently approved treatments in the United States are antipsychotics: haloperidol, pimozide, and aripiprazole, which are associated with serious side effects, including tardive dyskinesia (TD). Deutetrabenazine, a vesicular monoamine transporter type 2 (VMAT2) inhibitor, was approved in 2017 by the US FDA for the treatment of chorea associated with Huntington’s disease and TD. Three ongoing studies (Alternatives for Reducing Tics in TS [ARTISTS]) are evaluating the efficacy, safety, and tolerability of deutetrabenazine in reducing tics in TS in children and adolescents (age 6-16 years).
ARTISTS 1, a phase 2/3, response-driven, dose-titration, placebo-controlled study, randomizes patients (N=116) 1:1 to deutetrabenazine or placebo for 12 weeks. ARTISTS 2, a phase 3, fixed-dose study, randomizes patients (N=150) 1:1:1 to deutetrabenazine high or low dose, or placebo for 8 weeks. The primary efficacy outcome in these pivotal studies is change from baseline to end of treatment in the Total Tic Score (TTS) of the Yale Global Tic Severity Scale (YGTSS). Additional efficacy endpoints and safety/tolerability are also evaluated. ARTISTS is a 56-week, open-label, single-arm, long-term safety/tolerability study in patients who have successfully completed either ARTISTS 1 or ARTISTS 2.
Not available yet.
TS can have potentially long-term life impact, and there remains unmet medical need for effective and well-tolerated treatments. Three ARTISTS studies will evaluate the efficacy, safety, and tolerability of deutetrabenazine in patients with tics in TS.
The studies are sponsored by Teva Pharmaceuticals and operationalized by Teva’s development partner, Nuvelution TS Pharma INC.
Deutetrabenazine (Austedo) is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The objective of this study was to evaluate the long-term safety and tolerability of deutetrabenazine in patients with TD at 3 years.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used for calculating AE frequencies. This analysis reports results up to Week 158.
A total of 343 patients were enrolled (111 received placebo and 232 received deutetrabenazine in the parent studies). At the time of this analysis, 183 patients were still receiving treatment; 259 completed 1 year, 172 completed 2 years, and 41 completed 3 years. There were 623 patient-years of exposure. More than 40% of patients reached the maximum dose. EAIRs of AEs were comparable to or lower than those observed in the ARM-TD and AIM-TD short-term randomized trials of deutetrabenazine vs. placebo. The frequency of SAEs (EAIR 0.10) was similar to that observed with short-term placebo (0.33) and short-term deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.06), dose reduction (0.10), and dose suspension (0.05) were uncommon.
These results support the safety outcomes observed in the ARM-TD and AIM-TD parent studies and the safety of deutetrabenazine for long-term use in patients with TD.
Funding Acknowledgements: This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel
In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.
Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.
343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.
Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.
This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.
Barry Hines's 1968 novel A Kestrel for a Knave follows Billy Casper, a school leaver living on the edge of poverty in an unidentified northern English town. Bullied mercilessly by his brother and his classmates, Billy finds new purpose and hope through his relationship with a kestrel, Kes. In 1999, Penguin chose to re-publish the novel in its Modern Classics series, and yet the image on its front cover is of David Bradley, the star of the 1969 film Kes which was adapted for the screen by Hines, along with Ken Loach and Tony Garnett. Bradley's face is indelibly associated in the British national imaginary with a production that was ranked seventh on the BFI's list of the top 100 British films of all time, and which is marked as a foundational work of its much-admired director. While the decision to use an image from the film as the cover image is clearly justifiable for marketing reasons, it irrevocably positions the page as secondary to the screen: A Kestrel for a Knave, we are told, is the book of Kes. This privileging of film over book is symbolic of a wider failure in both academic scholarship and popular criticism to adequately register the complexities of artistic labour in works like Kes that are subject – as many films of the 1960s are – to the mythology of the auteur. This chapter will therefore aim to examine and acknowledge the role of the writer, Barry Hines, in the ecology of Kes as a means of inviting a more holistic view of convergent authorial practices in the period.
Given his status and the prolific nature of his output, Ken Loach has understandably attracted a great deal of academic attention. For example, both Jacob Leigh and John Hill have written monographs on the director, and these will be referenced in this chapter, but it is first worth examining briefly the ways in which accounts such as these have examined Hines’s roles in Kes. While Hill acknowledges that the ‘novel's themes, dialogue and structure resemble those in the film … this does not necessarily imply that Hines took the majority of creative decisions in adapting the book’, and adds of Loach that while ‘the subject of Kes comes from Hines’ imagination and experience, he (and Garnett) chose to film Hines’ novel’.
Injuries may occur when putting up and taking down hurricane (storm) shutters. This study described hurricane shutter-related injuries managed at emergency departments (EDs).
Hurricane shutter-related injuries were identified through the National Electronic Injury Surveillance System (NEISS), a database of consumer product-related injuries collected from the EDs of approximately 100 United States hospitals.
There were 329 hurricane shutter-related injuries during 2001-2017. Thirty-six injuries were reported during October 2005 (Hurricane Wilma), 30 during August 2008 (Tropical Storm Fay), and 103 during September 2017 (Hurricane Irma). Patients were 20 years or older in 90.6% of the cases; 76.3% of the patients were male. The most frequently reported injuries were laceration (48.9%), sprain or strain (15.2%), and fracture (9.4%). Lower extremities (34.0%) were the most commonly affected body part followed by upper extremities (29.5%) and head or neck (17.0%). The patient was treated or examined at the ED and released in 86.6% of the cases.
Over half of the hurricane shutter-related injuries appeared to occur in association with hurricanes and tropical storms. The most frequently reported injuries were laceration followed by sprain or strain and fracture. The majority of patients were treated or examined at the ED and released.
First Peoples' knowledge at university lies within a contested knowledge space. The incompatibilities and differences between Western and First Peoples' knowledge systems means attempts to superficially ‘add’ First Peoples' content to university courses are often ineffective and tokenistic. Considering these issues, this paper reflects on the design and implementation of weaving First Peoples' knowledge and perspectives throughout a service-learning course. The course is a nationally awarded work-integrated learning programme delivered to undergraduate and postgraduate students. Drawing on a theoretical framework of Woven Law, the design of the module was led and authored by First Peoples. Throughout the design process, the module was critically examined in terms of the content developed and methods of content inclusion, while also responding to institutional demands of student learning outcomes. Survey results show a positive student reception and early success in enabling students to achieve learning outcomes. While initial results are promising, data are limited due to this being the first assessment of the programme and the fact that students were asked to rate their own experience. Nonetheless, Woven Law and carefully weaving First Peoples' knowledge throughout the curriculum represents a promising methodology and area for future research.