Casimir effect due to a single boundary as a manifestation of the Weyl problem

The Casimir self-energy of a boundary is ultraviolet-divergent. In many cases the divergences can be eliminated by methods such as zeta-function regularization or through physical arguments (ultraviolet transparency of the boundary would provide a cutoff). Using the example of a massless scalar field theory with a single Dirichlet boundary we explore the relationship between such approaches, with the goal of better understanding the origin of the divergences. We are guided by the insight due to Dowker and Kennedy (1978) and Deutsch and Candelas (1979), that the divergences represent measurable effects that can be interpreted with the aid of the theory of the asymptotic distribution of eigenvalues of the Laplacian discussed by Weyl. In many cases the Casimir self-energy is the sum of cutoff-dependent (Weyl) terms having geometrical origin, and an "intrinsic" term that is independent of the cutoff. The Weyl terms make a measurable contribution to the physical situation even when regularization methods succeed in isolating the intrinsic part. Regularization methods fail when the Weyl terms and intrinsic parts of the Casimir effect cannot be clearly separated. Specifically, we demonstrate that the Casimir self-energy of a smooth boundary in two dimensions is a sum of two Weyl terms (exhibiting quadratic and logarithmic cutoff dependence), a geometrical term that is independent of cutoff, and a non-geometrical intrinsic term. As by-products we resolve the puzzle of the divergent Casimir force on a ring and correct the sign of the coefficient of linear tension of the Dirichlet line predicted in earlier treatments.Comment: 13 pages, 1 figure, minor changes to the text, extra references added, version to be published in J. Phys.

A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.

The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis. We report the generation of a mouse model for human 5q- syndrome using large-scale chromosomal engineering. Haploinsufficiency of the Cd74-Nid67 interval (containing Rps14, encoding the ribosomal protein S14) caused macrocytic anemia, prominent erythroid dysplasia and monolobulated megakaryocytes in the bone marrow. These effects were associated with defective bone marrow progenitor development, the appearance of bone marrow cells expressing high amounts of the tumor suppressor p53 and increased bone marrow cell apoptosis. Notably, intercrossing with p53-deficient mice completely rescued the progenitor cell defect, restoring common myeloid progenitor and megakaryocytic-erythroid progenitor, granulocyte-monocyte progenitor and hematopoietic stem cell bone marrow populations. This mouse model suggests that a p53-dependent mechanism underlies the pathophysiology of the 5q- syndrome

Developing an Individual-level Geodemographic Classification

Geodemographics is a spatially explicit classification of socio-economic data, which can be used to describe and analyse individuals by where they live. Geodemographic information is used by the public sector for planning and resource allocation but it also has considerable use within commercial sector applications. Early geodemographic systems, such as the UK’s ACORN (A Classification of Residential Neighbourhoods), used only area-based census data, but more recent systems have added supplementary layers of information, e.g. credit details and survey data, to provide better discrimination between classes. Although much more data has now become available, geodemographic systems are still fundamentally built from area-based census information. This is partly because privacy laws require release of census data at an aggregate level but mostly because much of the research remains proprietary. Household level classifications do exist but they are often based on regressions between area and household data sets. This paper presents a different approach for creating a geodemographic classification at the individual level using only census data. A generic framework is presented, which classifies data from the UK Census Small Area Microdata and then allocates the resulting clusters to a synthetic population created via microsimulation. The framework is then applied to the creation of an individual-based system for the city of Leeds, demonstrated using data from the 2001 census, and is further validated using individual and household survey data from the British Household Panel Survey

Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA) : a multicentre, open-label, randomised controlled trial

This study was funded by the NIHR Health Technology Assessment programme (12/146/06).Background Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. Methods This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0–35, moderate 36–48, or severe 49–70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. Findings Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19–30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11–46] vs 30 days [14–65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65;Publisher PDFPeer reviewe

Tonsillectomy compared with conservative management in patients over 16 years with recurrent sore throat:the NATTINA RCT and economic evaluation

BACKGROUND: The place of tonsillectomy in the management of sore throat in adults remains uncertain.OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults, and to evaluate the impact of alternative sore throat patient pathways.DESIGN: This was a multicentre, randomised controlled trial comparing tonsillectomy with conservative management. The trial included a qualitative process evaluation and an economic evaluation.SETTING: The study took place at 27 NHS secondary care hospitals in Great Britain.PARTICIPANTS: A total of 453 eligible participants with recurrent sore throats were recruited to the main trial.INTERVENTIONS: Patients were randomised on a 1 : 1 basis between tonsil dissection and conservative management (i.e. deferred surgery) using a variable block-stratified design, stratified by (1) centre and (2) severity.MAIN OUTCOME MEASURES: The primary outcome measure was the total number of sore throat days over 24 months following randomisation. The secondary outcome measures were the number of sore throat episodes and five characteristics from Sore Throat Alert Return, describing severity of the sore throat, use of medications, time away from usual activities and the Short Form questionnaire-12 items. Additional secondary outcomes were the Tonsil Outcome Inventory-14 total and subscales and Short Form questionnaire-12 items 6 monthly. Evaluation of the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes against baseline severity, as assessed by Tonsil Outcome Inventory-14 score at recruitment. The incremental cost per sore throat day avoided, the incremental cost per quality-adjusted life-year gained based on responses to the Short Form questionnaire-12 items and the incremental net benefit based on costs and responses to a contingent valuation exercise. A qualitative process evaluation examined acceptability of trial processes and ramdomised arms.RESULTS: There was a median of 27 (interquartile range 12-52) sore throats over the 24-month follow-up. A smaller number of sore throats was reported in the tonsillectomy arm [median 23 (interquartile range 11-46)] than in the conservative management arm [median 30 (interquartile range 14-65)]. On an intention-to-treat basis, there were fewer sore throats in the tonsillectomy arm (incident rate ratio 0.53, 95% confidence interval 0.43 to 0.65). Sensitivity analyses confirmed this, as did the secondary outcomes. There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). There were 47 re-admissions following tonsillectomy (20.3%), 35 relating to haemorrhage. On average, tonsillectomy was more costly and more effective in terms of both sore throat days avoided and quality-adjusted life-years gained. Tonsillectomy had a 100% probability of being considered cost-effective if the threshold for an additional quality-adjusted life year was £20,000. Tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Trial processes were deemed to be acceptable. Patients who received surgery were unanimous in reporting to be happy to have received it.LIMITATIONS: The decliners who provided data tended to have higher Tonsillectomy Outcome Inventory-14 scores than those willing to be randomised implying that patients with a higher burden of tonsillitis symptoms may have declined entry into the trial.CONCLUSIONS: The tonsillectomy arm had fewer sore throat days over 24 months than the conservative management arm, and had a high probability of being considered cost-effective over the ranges considered. Further work should focus on when tonsillectomy should be offered. National Trial of Tonsillectomy IN Adults has assessed the effectiveness of tonsillectomy when offered for the current UK threshold of disease burden. Further research is required to define the minimum disease burden at which tonsillectomy becomes clinically effective and cost-effective.TRIAL REGISTRATION: This trial is registered as ISRCTN55284102.FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information. </p

Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial.

BACKGROUND Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. METHODS This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0-35, moderate 36-48, or severe 49-70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. FINDINGS Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19-30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11-46] vs 30 days [14-65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65; <0·0001). 191 adverse events in 90 (39%) of 231 participants were deemed related to tonsillectomy. The most common adverse event was bleeding (54 events in 44 [19%] participants). No deaths occurred during the study. INTERPRETATION Compared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. FUNDING National Institute for Health Research