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Objectives/Goals: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants (Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.
Patients undergoing total laryngectomy who have chronic obstructive pulmonary disease are unable to use dry-powder inhalers due to the anatomical changes after surgery and are therefore at greater risk of post-operative pulmonary complications. In our practice, we identified a scarcity of resources available to help clinicians decide on a suitable alternative. Hence, we sought to provide a solution that would address this issue.
Methods
Within our head and neck centre, we worked with the respiratory team and specialist pharmacists to create a simple conversion table to help clinicians identify alternatives to dry-powder inhalers.
Results
A table was designed that shows which metered-dose inhalers when connected to a spacer and an infant face mask overlying the laryngeal stoma can be used.
Conclusion
Our table can be used as a resource by clinicians to improve the perioperative and long-term care of patients who cannot use dry-powder inhalers.
Fluridone was registered for use in rice production in 2023, offering a new herbicide site of action for growers. However, little information is available on the degree of rice tolerance to this herbicide. Field experiments conducted in 2022 and replicated in 2023 near Colt, AR, evaluated the tolerance of 12 rice cultivars to fluridone, applied preemergence or at the 3-leaf growth stage, in separate experiments. Each experiment consisted of one cultivar. Fluridone rates included 0, 168 (1 × label rate), and 336 (2 × label rate) g ai ha−1 in all experiments. Visible injury varied between years in all experiments, likely due to different environmental conditions. In 2022, injury following preemergence applications of fluridone was below 25% across cultivars. In contrast, in 2023, injury ≥30% occurred to five cultivars, with a maximum of 58% observed for the cultivar ‘DG263L’. In both years, only three cultivars exhibited injury ≥20% following fluridone applications at the 3-leaf stage. Fluridone negatively affected shoot density, groundcover, chlorophyll content, and days to 50% heading in most cultivars when applied preemergence. When fluridone was applied to 3-leaf rice, at least one of the variables evaluated was negatively affected in two and nine cultivars in 2022 and 2023, respectively. Grain yield reductions of at least 18% were observed from eight cultivars in 2022, and a grain yield decrease from 9% to 49% from eight cultivars occurred in 2023 in the preemergence experiments. Fluridone applied to rice at the 3-leaf stage did not cause a yield penalty to any cultivar in 2022, whereas in 2023, a yield loss occurred from eight cultivars. Yield loss from the DG263L cultivar occurred at the 1 × rate in both experiments, indicating that this cultivar appears to be sensitive to fluridone, regardless of the application timing. Based on these findings, fluridone tolerance is cultivar-dependent. Furthermore, preemergence applications of fluridone to rice should be avoided.
This article is situated within the framework of a definition of curation of new music that includes, in addition to the choice of pieces, venues and players, the active choice of specific tools and roles that will be filled by people, roles that have rich traditions and expectations and are thus ripe for instrumentalisation. In earlier research we have demonstrated that the roles of musicians within new music have been instrumentalised, and in this article we aim to better understand the musicians’ response. One such observable response has been dubbed by artist–researchers Håkon Stene and Louise Devenish as ‘post-instrumental practice’. In this article we will discuss how and where we also observe this trend. We then test its sustainability through in-depth interviews with venue organisers and artistic directors as well as analysing funding and employers’ organisations’ published policies on socially and economically sustainable practices.
To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin.
Design:
Retrospective cohort study.
Setting:
Community health system.
Patients:
Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10–14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen.
Methods:
Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI.
Results:
The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07–0.56, p < 0.002).
Conclusions:
Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.
The oxidation of As(III) to As(V) by K-birnessite was examined at different temperatures, pHs, and birnessite/As(III) ratios. Experiments ranged in duration from 5 to 64 hr, and solution and solid products were determined at several intervals. All experiments showed that the reaction produced large amounts of K+ to solution and very little Mn2+. As(V) was released to solution and incorporated into the K-birnessite. The oxidation was initially rapid and then slowed. The oxidation of As(III) was probably facilitated initially by autocatalytic Mn-As(V) reactions occurring mostly in the interlayer, in which large amounts of As(V) and K+ could be easily released to solution. The reaction also slowed when interlayer Mn was exhausted by forming Mn-As(V) complexes. Mn(IV) could only be acquired from the octahedral sheets of the birnessite. The two-stage reaction process proposed here depended on the layered structure of birnessite, the specific surface, and presence of exchangeable cations in K-birnessite.
Little research has explored relationships between prenatal substance use policies and rates of maternal mortality across all 50 states, despite evidence that prenatal substance use elevates risk of maternal death. This study, utilizing publicly available data, revealed that state-level mandated testing laws predicted maternal mortality after controlling for population characteristics.
We investigated concurrent outbreaks of Pseudomonas aeruginosa carrying blaVIM (VIM-CRPA) and Enterobacterales carrying blaKPC (KPC-CRE) at a long-term acute-care hospital (LTACH A).
Methods:
We defined an incident case as the first detection of blaKPC or blaVIM from a patient’s clinical cultures or colonization screening test. We reviewed medical records and performed infection control assessments, colonization screening, environmental sampling, and molecular characterization of carbapenemase-producing organisms from clinical and environmental sources by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing.
Results:
From July 2017 to December 2018, 76 incident cases were identified from 69 case patients: 51 had blaKPC, 11 had blaVIM, and 7 had blaVIM and blaKPC. Also, blaKPC were identified from 7 Enterobacterales, and all blaVIM were P. aeruginosa. We observed gaps in hand hygiene, and we recovered KPC-CRE and VIM-CRPA from drains and toilets. We identified 4 KPC alleles and 2 VIM alleles; 2 KPC alleles were located on plasmids that were identified across multiple Enterobacterales and in both clinical and environmental isolates.
Conclusions:
Our response to a single patient colonized with VIM-CRPA and KPC-CRE identified concurrent CPO outbreaks at LTACH A. Epidemiologic and genomic investigations indicated that the observed diversity was due to a combination of multiple introductions of VIM-CRPA and KPC-CRE and to the transfer of carbapenemase genes across different bacteria species and strains. Improved infection control, including interventions that minimized potential spread from wastewater premise plumbing, stopped transmission.
OBJECTIVES/GOALS: The aim of this study was to design and implement the Pharos application to map the cellular network support structure around Lake Victoria in Western Kenya. Additionally, the Pharos app was used to collect images of disease-relevant vector and plant life surrounding the study sites to train a computer vision algorithm to map disease-relevant areas. METHODS/STUDY POPULATION: Pharos was provided to a 4-person team of healthcare workers. The app was pre-loaded on both iOS and Android devices to be used during the course of normal field activity. Pharos ambiently collects network data and the team was asked to capture images of landmarks relevant to their work in schistosomiasis control. The field team traveled to 4 counties of differing schistosomiasis risk surrounding Kisumu, Kenya in autumn 2022 and will return to these areas in early spring 2023. Cell signal indicators (upload and download speed) were collected and asynchronously uploaded to a database for further analysis. Additionally, all landmark images (cell network towers, landmarks (e.g. schools, churches, public centers), plant life, vectors, and water bodies) were recorded and tagged with GPS coordinates and time stamps. RESULTS/ANTICIPATED RESULTS: Iterative development powered by small, informal, user-centered focus group discussions with the field team led to several key adaptations to the Pharos software. On the first deployment, 1,297 unique upload and download events were recorded across 3 Kenyan cell providers and 1 American provider. 1,197 data points were collected in Kenya using both Android and iOS devices using several versions of the Pharos application. 154 unique landmarks were photographed, but a distinct difference in landmark recording was observed between devices, prompting a transition to iOS-only data collection. Of the landmarks recorded, the majority (120, 77.9%) were landmarks or cell network towers, while 22.1% were water bodies, plant life, or schistosomiasis vectors. DISCUSSION/SIGNIFICANCE: For the first time, high-detail maps of cellular signal and critical schistosomiasis-related landmarks were generated. Future work on this project is focused on training computer vision algorithms using the captured images of environmental and ecological factors to isolate possible areas of human disease transmission.
This article traces the creative process of six to five, a work for 20 guitarists with a special role for the conductor, premiered by the Royal Conservatoire of Antwerp's guitar ensemble. The piece was commissioned by the author from the American composer Jessie Marino as part of research into the role of the instrumentalised conductor. The article explores the ways in which Marino deployed the conductor to meet her artistic goals, testing at each step the extent to which her utilisation rises to the level of instrumentalisation. Applying political theories offered by, among others, Michael Hardt and Antonio Negri, the article also considers the extent to which Marino deployed the conductor as a tactical leader in both the rehearsal process and the performance of six to five.
Characterizing the cultural evolution of imaginary worlds as a hedonic but non-adaptive exaptation from evolved exploratory tendencies, Dubourg and Baumard defend too narrow a conception of the adaptive evolution of imaginary worlds. Imagination and its imaginary worlds are ancient and adaptive, allowing deliberation over actions, consequences, and futures worth aspiring to, often engendering the world we see around us.
COVID-19 has further exacerbated trends of widening health inequalities in the UK. Shockingly, the number of years of life lived in general good health differs by over 18 years between the most and least deprived areas of England. Poor diets and obesity are established major risk factors for chronic cardiometabolic diseases and cancer, as well as severe COVID-19. For doctors to provide the best care to their patients, there is an urgent need to improve nutrition education in undergraduate medical school training.
With this imperative, the Association for Nutrition established an Interprofessional Working Group on Medical Education (AfN IPG) to develop a new, modern undergraduate nutrition curriculum for medical doctors. The AfN IPG brought together expertise from nutrition, dietetic and medical professionals, representing the National Health Service (NHS), royal colleges, medical schools and universities, government public health departments, learned societies, medical students, and nutrition educators. The curriculum was developed with the key objective of being implementable through integration with the current undergraduate training of medical doctors.
Through an iterative and transparent consultative process, thirteen key nutritional competencies, to be achieved through mastery of eleven graduation fundamentals, were established. The curriculum to facilitate the achievement of these key competencies is divided into eight topic areas, each underpinned by a learning objective statement and teaching points detailing the knowledge and skills development required. The teaching points can be achieved through clinical teaching and a combination of facilitated learning activities and practical skill acquisition. Therefore, the nutrition curriculum enables mastery of these nutritional competencies in a way that will complement and strengthen medical students’ achievement of the General Medical Council (GMC) Outcome for Graduates.
As nutrition is an integrative science, the AfN IPG recommends that the curriculum is incorporated into initial undergraduate medical studies before specialist training. This will enable our future doctors to recognise how nutrition is related to multiple aspects of their training, from physiological systems to patient-centred care, and acquire a broad, inclusive understanding of health and disease. In addition, it will facilitate medical schools to embed nutrition learning opportunities within the core medical training, without the need to add in a large number of new components to an already crowded programme or with additional burden for teaching staff.
The undergraduate nutrition curriculum for medical doctors is designed to support medical schools to create future doctors who will understand and recognise the role of nutrition in health. Moreover, it will equip frontline staff to feel empowered to raise nutrition-related issues with their patients as a fundamental part of enhanced care and to appropriately refer on for nutrition support with a registered associate nutritionist/registered nutritionist (ANutr/RNutr) or registered dietitian (RD) where this is likely to be beneficial.
Glufosinate resistance in Palmer amaranth (Amaranthus palmeri S. Watson) was recently detected in three accessions from Arkansas, USA. Amaranthus palmeri is the first and only broadleaf weed species resistant to this herbicide, and the resistance mechanism is still unclear. A previous study characterized the glufosinate resistance level in the accessions from Arkansas. A highly glufosinate-resistant accession was further used to investigate the mechanism conferring glufosinate resistance in A. palmeri. Experiments were designed to sequence the herbicide target enzyme cytosolic and chloroplastic glutamine synthetase isoforms (GS1 and GS2, respectively) and quantify copy number and expression. Absorption, translocation, and metabolism of glufosinate using the 14C-labeled herbicide were also evaluated in the resistant and susceptible accessions. The glufosinate-resistant accession had an increase in copy number and expression of GS2 compared with susceptible plants. All accessions showed only one GS1 copy and no differences in expression. No mutations were identified in GS1 or GS2. Absorption (54% to 60%) and metabolism (13% to 21%) were not different between the glufosinate-resistant and glufosinate-susceptible accessions. Most residues of glufosinate (94% to 98%) were present in the treated leaf. Glufosinate translocation to tissues above the treated leaf and in the roots was not different among accessions. However, glufosinate translocation to tissues below the treated leaf (not including roots) was greater in the resistant A. palmeri (2%) compared with the susceptible (less than 1%) accessions. The findings of this paper strongly indicate that gene amplification and increased expression of the chloroplastic glutamine synthetase enzyme are the mechanisms conferring glufosinate resistance in the A. palmeri accession investigated. Thus far, no additional resistance mechanism was observed, but further investigations are ongoing.
Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures.
We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission.
Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%).
Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.
Field studies were conducted to determine the effects of synthetic auxin herbicides at simulated exposure rates applied to ‘Covington’ sweetpotato propagation beds on the quality of nonrooted stem cuttings (slips). Treatments included diglycolamine salt of dicamba, 2,4-D choline plus nonionic surfactant (NIS), and 2,4-D choline plus glyphosate at 1/10, 1/33, or 1/66 of a 1X application rate (560 g ae ha−1 dicamba, 1,065 g ae ha−1 2,4-D choline, 1,130 g ae ha−1 glyphosate) applied at 2 or 4 wk after first slip harvest (WASH). Injury to sweetpotato 2 wk after treatment was greatest when herbicides were applied 2 WASH (21%) compared to 4 WASH (16%). More slip injury was caused by 2,4-D choline than by dicamba, and the addition of glyphosate did not increase injury over 2,4-D choline alone. Two weeks after the second application, sweetpotato slips were cut 2 cm above the soil surface and transplanted into production fields. In 2019, sweetpotato ground coverage 8 wk after transplanting was reduced 37% and 26% by the 1/10X rates of dicamba and 2,4-D choline plus NIS, respectively. Though dicamba caused less injury to propagation beds than 2,4-D choline with or without glyphosate, after transplanting, slips treated with 1/10X dicamba did not recover as quickly as those treated with 2,4-D choline. In 2020, sweetpotato ground coverage was 90% or greater for all treatments. Dicamba applied 2 WASH decreased marketable sweetpotato storage root yield by 59% compared to the nontreated check, whereas treatments including 2,4-D choline reduced marketable yield 22% to 29%. All herbicides applied at 4 WASH reduced marketable yield 31% to 36%. The addition of glyphosate to 2,4-D choline did not increase sweetpotato yield. Results indicate that caution should be taken when deciding whether to transplant sweetpotato slips that are suspected to have been exposed to dicamba or 2,4-D choline.
To quantify the extent of food and beverage advertising on bus shelters in a deprived area of the UK, to identify the healthfulness of advertised products, and any differences by level of deprivation. The study also sought to assess the creative strategies used and extent of appeal to young people.
Design:
Images of bus shelter advertisements were collected via in person photography (in 2019) and Google Street View (photos recorded in 2018). Food and beverage advertisements were grouped into one of seventeen food categories and classified as healthy/less healthy using the UK Nutrient Profile Model. The deprivation level of the advertisement location was identified using the UK Index of Multiple Deprivation.
Setting:
Middlesbrough and Redcar and Cleveland in South Teesside.
Participants:
N/A
Results:
Eight hundred and thirty-two advertisements were identified, almost half (48·9 %) of which were for foods or beverages. Of food and non-alcoholic beverage adverts, 35·1 % were less healthy. Most food advertisements (98·9 %) used at least one of the persuasive creative strategies. Food advertisements were found to be of appeal to children under 18 years of age (71·9 %). No differences in healthiness of advertised foods were found by level of deprivation.
Conclusions:
Food advertising is extensive on bus shelters in parts of the UK, and a substantial proportion of this advertising is classified as less healthy and would not be permitted to be advertised around television programming for children. Bus shelter advertising should be considered part of the UK policy deliberations around restricting less healthy food marketing exposure.
This article explores ways in which artistic directors and composers of new music ensembles have developed and redefined the role of the conductor to achieve specific goals and fulfil musical and artistic need. It will explore various manners in which they have instrumentalised the conductor – literally an embodied role – and opened new possibilities for musical expression. The analysis and examples provided will rely for the most part on material gathered during in-depth interviews conducted with artistic directors, composers, conductors and musicians who are professionally active in the new music field in Europe and beyond. The article endeavours to bring into greater detail artistic and socio-economic motivations for utilising conductors in new music ensembles.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.