To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
This collection profiles understudied figures in the book and print trades of the seventeenth century. With an equal balance between women and men, it intervenes in the history of the trades, emphasising the broad range of material, cultural, and ideological work these people undertook. It offers a biographical introduction to each figure, placing them in their social, professional, and institutional settings. The collection considers varied print trade roles including that of the printer, publisher, paper-maker, and bookseller, as well as several specific trade networks and numerous textual forms. The biographies draw on extensive new archival research, with details of key sources for further study on each figure. Chronologically organised, this Element offers a primer both on numerous individual figures, and on the tribulations and innovations of the print trade in the century of revolution.
OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.
To understand the transmission dynamics of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in a hospital outbreak to inform infection control actions.
Retrospective cohort study.
General medical and elderly inpatient wards in a hospital in England.
Coronavirus disease 2019 (COVID-19) patients were classified as community or healthcare associated by time from admission to onset or positivity using European Centre for Disease Prevention and Control definitions. COVID-19 symptoms were classified as asymptomatic, nonrespiratory, or respiratory. Infectiousness was calculated from 2 days prior to 14 days after symptom onset or positive test. Cases were defined as healthcare-associated COVID-19 when infection was acquired from the wards under investigation. COVID-19 exposures were calculated based on symptoms and bed proximity to an infectious patient. Risk ratios and adjusted odds ratios (aORs) were calculated from univariable and multivariable logistic regression.
Of 153 patients, 65 were COVID-19 patients and 45 of these were healthcare-associated cases. Exposure to a COVID-19 patient with respiratory symptoms was associated with healthcare-associated infection irrespective of proximity (aOR, 3.81; 95% CI, 1.6.3–8.87). Nonrespiratory exposure was only significant within 2.5 m (aOR, 5.21; 95% CI, 1.15–23.48). A small increase in risk ratio was observed for exposure to a respiratory patient for >1 day compared to 1 day from 2.04 (95% CI, 0.99–4.22) to 2.36 (95% CI, 1.44–3.88).
Respiratory exposure anywhere within a 4-bed bay was a risk, whereas nonrespiratory exposure required bed distance ≤2.5 m. Standard infection control measures required beds to be >2 m apart. Our findings suggest that this may be insufficient to stop SARS-CoV-2 transmission. We recommend improving cohorting and further studies into bed distance and transmission factors.
To describe a pilot project infection prevention and control (IPC) assessment conducted in skilled nursing facilities (SNFs) in New York State (NYS) during a pivotal 2-week period when the region became the nation’s epicenter for coronavirus disease 2019 (COVID-19).
A telephone and video assessment of IPC measures in SNFs at high risk or experiencing COVID-19 activity.
SNFs in 14 New York counties, including New York City.
A 3-component remote IPC assessment: (1) screening tool; (2) telephone IPC checklist; and (3) COVID-19 video IPC assessment (ie, “COVIDeo”).
In total, 92 SNFs completed the IPC screening tool and checklist: 52 (57%) were conducted as part COVID-19 investigations, and 40 (43%) were proactive prevention-based assessments. Among the 40 proactive assessments, 14 (35%) identified suspected or confirmed COVID-19 cases. COVIDeo was performed in 26 (28%) of 92 assessments and provided observations that other tools would have missed: personal protective equipment (PPE) that was not easily accessible, redundant, or improperly donned, doffed, or stored and specific challenges implementing IPC in specialty populations. The IPC assessments took ∼1 hour each and reached an estimated 4 times as many SNFs as on-site visits in a similar time frame.
Remote IPC assessments by telephone and video were timely and feasible methods of assessing the extent to which IPC interventions had been implemented in a vulnerable setting and to disseminate real-time recommendations. Remote assessments are now being implemented across New York State and in various healthcare facility types. Similar methods have been adapted nationally by the Centers for Disease Control and Prevention.
Precise instrumental calibration is of crucial importance to 21-cm cosmology experiments. The Murchison Widefield Array’s (MWA) Phase II compact configuration offers us opportunities for both redundant calibration and sky-based calibration algorithms; using the two in tandem is a potential approach to mitigate calibration errors caused by inaccurate sky models. The MWA Epoch of Reionization (EoR) experiment targets three patches of the sky (dubbed EoR0, EoR1, and EoR2) with deep observations. Previous work in Li et al. (2018) and (2019) studied the effect of tandem calibration on the EoR0 field and found that it yielded no significant improvement in the power spectrum (PS) over sky-based calibration alone. In this work, we apply similar techniques to the EoR1 field and find a distinct result: the improvements in the PS from tandem calibration are significant. To understand this result, we analyse both the calibration solutions themselves and the effects on the PS over three nights of EoR1 observations. We conclude that the presence of the bright radio galaxy Fornax A in EoR1 degrades the performance of sky-based calibration, which in turn enables redundant calibration to have a larger impact. These results suggest that redundant calibration can indeed mitigate some level of model incompleteness error.
Antibiotics are not indicated for the treatment of bronchitis and bronchiolitis. Using a nationally representative database from 2006–2015, we found that antibiotics were prescribed in 58% of outpatient visits for bronchitis and bronchiolitis in children, serving as a possible baseline for the expanded HEDIS 2020 measure regarding antibiotic prescribing for bronchitis.
We identify characteristics of local health departments, which enhance collaborations with community- and faith-based organizations (CFBOs) for emergency preparedness and response.
Online survey data were collected from a sample of 273 disaster preparedness coordinators working at local health departments across the United States between August and December 2011.
Using multiple linear regression models, we found that perceptions of CFBO trust were associated with more successful partnership planning (β=0.63; P=0.02) and capacity building (β=0.61; P=0.01). Employee layoffs in the past 3 years (β=0.41; P=0.001) and urban location (β=0.41; P=0.005) were positively associated with higher ratings of resource sharing between health agencies and CFBOs. Having 1-3 full-time employees increased the ratings of success in communication and outreach activities compared with health departments having less than 1 full-time employee (β=0.33; P=0.05). Positive attitudes toward CFBOs also enhanced communication and outreach (β=0.16; P=0.03).
Staff-capacity factors are important for quick dissemination of information and resources needed to address emerging threats. Building the trust of CFBOs can help address large-scale disasters by improving the success of more involved activities that integrate the CFBO into emergency plans and operations of the health department and that better align with federal-funding performance measures. (Disaster Med Public Health Preparedness. 2018;12:57–66)
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Significant new opportunities for astrophysics and cosmology have been identified at low radio frequencies. The Murchison Widefield Array is the first telescope in the southern hemisphere designed specifically to explore the low-frequency astronomical sky between 80 and 300 MHz with arcminute angular resolution and high survey efficiency. The telescope will enable new advances along four key science themes, including searching for redshifted 21-cm emission from the EoR in the early Universe; Galactic and extragalactic all-sky southern hemisphere surveys; time-domain astrophysics; and solar, heliospheric, and ionospheric science and space weather. The Murchison Widefield Array is located in Western Australia at the site of the planned Square Kilometre Array (SKA) low-band telescope and is the only low-frequency SKA precursor facility. In this paper, we review the performance properties of the Murchison Widefield Array and describe its primary scientific objectives.
Email your librarian or administrator to recommend adding this to your organisation's collection.