Dickens and The Literary City:A Study of London as Stage and Protagonist in Charles Dickens` Works.

This paper seeks to discuss Charles Dickens’ literary depiction of the city of London, and its effect upon his protagonists. Dickens` London provides the vocational setting for many of his characters, affording him the chance to illustrate the hard conditions endured by the city`s working population. His characters also draw much from pantomime and theatre, often resembling stage caricatures set against the backdrop of London. However, the city is more than just a stage or setting in Dickens` texts; often presented as a great immoral hub of activity which determines the fate of those living within its environs. Many characters trapped within its confines are subjected to exploitation, whilst others are depicted as inhuman, viewing the world purely in economic terms of profit and loss. This paper will also discuss how Dickens employs rural surroundings as a favourable counterpoint to that of London, whilst examining how on many occasions the contamination which the city precipitates proves too strong for Dickens` characters to evade. Finally this paper will conclude with an examination of Dickens proffered remedy; moralistic characters who attempt to aid or rejuvenate those contaminated by the ills of the city

Diglossia and Language Legitimacy:Examining how divergences in languages function as discourses of power.

It is the intention of this paper to pursue the argument that diglossia exists as a tool of control which can restrict the access of lower language status speakers to global discourse. Starting with Bakhtin’s definition of language as heteroglot, this paper will proceed with an analysis of Fergusson’s diglossia, and attempts will be made to analyze what diglossia is, and how it leads to conflict between high status and dialectical language users. English’s role as a high status language is also examined, and it is argued that English, whilst offering opportunity and emancipation for some language learners, can also operate as a barrier to progress for others. This paper will then pursue the argument that, due to the relationship between English and economic market forces, English ultimately bestows the most advantages and power upon language users from native speaker countries, and in doing so threatens to marginalize the position of other languages. Finally this discussion will conclude by looking at what can be done to avoid the exclusion of other languages and language users from access to global voice

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

Abstract: CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Association of baseline hematoma and edema volumes with one-year outcome and long-term survival after spontaneous intracerebral hemorrhage: A community-based inception cohort study

Background Hospital-based studies have reported variable associations between outcome after spontaneous intracerebral hemorrhage and peri-hematomal edema volume. Aims In a community-based study, we aimed to investigate the existence, strength, direction, and independence of associations between intracerebral hemorrhage and peri-hematomal edema volumes on diagnostic brain CT and one-year functional outcome and long-term survival. Methods We identified all adults, resident in Lothian, diagnosed with first-ever, symptomatic spontaneous intracerebral hemorrhage between June 2010 and May 2013 in a community-based, prospective inception cohort study. We defined regions of interest manually and used a semi-automated approach to measure intracerebral hemorrhage volume, peri-hematomal edema volume, and the sum of these measurements (total lesion volume) on first diagnostic brain CT performed at ≤3 days after symptom onset. The primary outcome was death or dependence (scores 3–6 on the modified Rankin Scale) at one-year after intracerebral hemorrhage. Results Two hundred ninety-two (85%) of 342 patients (median age 77.5 y, IQR 68–83, 186 (54%) female, median time from onset to CT 6.5 h (IQR 2.9–21.7)) were dead or dependent one year after intracerebral hemorrhage. Peri-hematomal edema and intracerebral hemorrhage volumes were colinear ( R2 = 0.77). In models using both intracerebral hemorrhage and peri-hematomal edema, 10 mL increments in intracerebral hemorrhage (adjusted odds ratio (aOR) 1.72 (95% CI 1.08–2.87); p = 0.029) but not peri-hematomal edema volume (aOR 0.92 (0.63–1.45); p = 0.69) were independently associated with one-year death or dependence. 10 mL increments in total lesion volume were independently associated with one-year death or dependence (aOR 1.24 (1.11–1.42); p = 0.0004). Conclusion Total volume of intracerebral hemorrhage and peri-hematomal edema, and intracerebral hemorrhage volume alone on diagnostic brain CT, undertaken at three days or sooner, are independently associated with death or dependence one-year after intracerebral hemorrhage, but peri-hematomal edema volume is not. Data access statement Anonymized summary data may be requested from the corresponding author. </jats:sec

Association of baseline hematoma and edema volumes with one-year outcome and long-term survival after spontaneous intracerebral hemorrhage: A community-based inception cohort study

Background Hospital-based studies have reported variable associations between outcome after spontaneous intracerebral hemorrhage and peri-hematomal edema volume. Aims In a community-based study, we aimed to investigate the existence, strength, direction, and independence of associations between intracerebral hemorrhage and peri-hematomal edema volumes on diagnostic brain CT and one-year functional outcome and long-term survival. Methods We identified all adults, resident in Lothian, diagnosed with first-ever, symptomatic spontaneous intracerebral hemorrhage between June 2010 and May 2013 in a community-based, prospective inception cohort study. We defined regions of interest manually and used a semi-automated approach to measure intracerebral hemorrhage volume, peri-hematomal edema volume, and the sum of these measurements (total lesion volume) on first diagnostic brain CT performed at ≤3 days after symptom onset. The primary outcome was death or dependence (scores 3–6 on the modified Rankin Scale) at one-year after intracerebral hemorrhage. Results Two hundred ninety-two (85%) of 342 patients (median age 77.5 y, IQR 68–83, 186 (54%) female, median time from onset to CT 6.5 h (IQR 2.9–21.7)) were dead or dependent one year after intracerebral hemorrhage. Peri-hematomal edema and intracerebral hemorrhage volumes were colinear ( R2 = 0.77). In models using both intracerebral hemorrhage and peri-hematomal edema, 10 mL increments in intracerebral hemorrhage (adjusted odds ratio (aOR) 1.72 (95% CI 1.08–2.87); p = 0.029) but not peri-hematomal edema volume (aOR 0.92 (0.63–1.45); p = 0.69) were independently associated with one-year death or dependence. 10 mL increments in total lesion volume were independently associated with one-year death or dependence (aOR 1.24 (1.11–1.42); p = 0.0004). Conclusion Total volume of intracerebral hemorrhage and peri-hematomal edema, and intracerebral hemorrhage volume alone on diagnostic brain CT, undertaken at three days or sooner, are independently associated with death or dependence one-year after intracerebral hemorrhage, but peri-hematomal edema volume is not. Data access statement Anonymized summary data may be requested from the corresponding author. </jats:sec

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of r < 0.001 at $95\%$ CL