Theorems on existence and global dynamics for the Einstein equations

This article is a guide to theorems on existence and global dynamics of solutions of the Einstein equations. It draws attention to open questions in the field. The local-in-time Cauchy problem, which is relatively well understood, is surveyed. Global results for solutions with various types of symmetry are discussed. A selection of results from Newtonian theory and special relativity that offer useful comparisons is presented. Treatments of global results in the case of small data and results on constructing spacetimes with prescribed singularity structure or late-time asymptotics are given. A conjectural picture of the asymptotic behaviour of general cosmological solutions of the Einstein equations is built up. Some miscellaneous topics connected with the main theme are collected in a separate section.Comment: Submitted to Living Reviews in Relativity, major update of Living Rev. Rel. 5 (2002)

Quantum Gravity in 2+1 Dimensions: The Case of a Closed Universe

In three spacetime dimensions, general relativity drastically simplifies, becoming a ``topological'' theory with no propagating local degrees of freedom. Nevertheless, many of the difficult conceptual problems of quantizing gravity are still present. In this review, I summarize the rather large body of work that has gone towards quantizing (2+1)-dimensional vacuum gravity in the setting of a spatially closed universe.Comment: 61 pages, draft of review for Living Reviews; comments, criticisms, additions, missing references welcome; v2: minor changes, added reference

Quantization of Midisuperspace Models

We give a comprehensive review of the quantization of midisuperspace models. Though the main focus of the paper is on quantum aspects, we also provide an introduction to several classical points related to the definition of these models. We cover some important issues, in particular, the use of the principle of symmetric criticality as a very useful tool to obtain the required Hamiltonian formulations. Two main types of reductions are discussed: those involving metrics with two Killing vector fields and spherically symmetric models. We also review the more general models obtained by coupling matter fields to these systems. Throughout the paper we give separate discussions for standard quantizations using geometrodynamical variables and those relying on loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit

The 100 most cited articles investigating the radiological staging of oesophageal and junctional cancer: a bibliometric analysis

Objectives Accurate staging of oesophageal cancer (OC) is vital. Bibliometric analysis highlights key topics and publications that have shaped understanding of a subject. The 100 most cited articles investigating radiological staging of OC are identified. Methods The Thomas Reuters Web of Science database with search terms including “CT, PET, EUS, oesophageal and gastro-oesophageal junction cancer” was used to identify all English language, full-script articles. The 100 most cited articles were further analysed by topic, journal, author, year and institution. Results A total of 5,500 eligible papers were returned. The most cited paper was Flamen et al. (n = 306), investigating the utility of positron emission tomography (PET) for the staging of patients with potentially operable OC. The most common research topic was accuracy of staging investigations (n = 63). The article with the highest citation rate (38.00), defined as the number of citations divided by the number of complete years published, was Tixier et al. investigating PET texture analysis to predict treatment response to neo-adjuvant chemo-radiotherapy, cited 114 times since publication in 2011. Conclusion This bibliometric analysis has identified key publications regarded as important in radiological OC staging. Articles with the highest citation rates all investigated PET imaging, suggesting this modality could be the focus of future research

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

Dysplasia of the Upper Aerodigestive Tract Squamous Epithelium

Dysplasia of the oral, laryngeal and oropharyngeal stratified squamous epithelia is a microscopically defined change that may occur in clinically identifiable lesions including erythroplakia, leukoplakia and erythroleukoplakia, lesions that convey a heightened risk for carcinomatous progression. Dysplastic lesions have been classified microscopically according to degree of cytologic atypia and changes in architectural patterns, usually on a three part or four part gradation scale. Vocal cord epithelial lesions are graded according to either the Ljubljana or the World Health Organization (WHO) system whereas oral dysplasias are generally classified according to WHO criteria. Cytologically atypical cells are considered to represent precancerous changes predicting an increase risk for carcinomatous transformation. Inter- and intra-rater reliability studies among pathologists have disclosed low correlation coefficients for four part grading systems, whereas improved agreement is achieved (kappa correlation values) using the Ljubljana systems. Evidence forwarded by some studies supports the prognostic value of progressively severe dysplastic changes for carcinomatous transformation; however, some studies indicate that the presence of a clinically defined lesion without microscopic evidence of dysplasia also connotes increased risk for carcinomatous transformation. Loss of heterozygosity (LOH) at 3p and 9p microsatellite domains, DNA ploidy analysis and nuclear image analyses may have predictive value as molecular and histomorphological biomarkers

pncA mutations in clinical Mycobacterium tuberculosis isolates from Korea

BACKGROUND: Pyrazinamide (PZA) is among the first-line drugs for the treatment of tuberculosis. In vitro, it kills semidormant mycobacteria only at low pH. The purpose of this study was to compare PZA resistance with pyrazinamidase (PZase) activity and the genotype to better understand the molecular basis of PZA resistance and to expand the profile of pncA mutations worldwide. RESULTS: Of the 28 tested strains of Mycobacterium tuberculosis, 6 were susceptible to PZA and positive for PZase activity and had no pncA mutations. Twenty-one strains were resistant to PZA and negative for PZase activity and had mutations in the pncA gene, including 15 point mutations, 5 insertions, and 2 deletions. One strain had no mutation in the pncA gene, even though it was resistant to PZA and negative for PZase activity. Three isolates had adenine to guanine point mutations in the -11 upstream region, making this the most common type of pncA mutations in this study, with at least two different RFLP patterns. CONCLUSION: These data help in the understanding of the molecular basis of PZA resistance. An adenine to guanine point mutation in the -11 upstream region was the most common type of pncA mutation in our isolates. The results of pncA mutation analyses should be carefully interpreted for epidemiologic purposes

Elevated platelet-derived growth factor-BB concentrations in premature neonates who develop chronic lung disease

BACKGROUND: Chronic lung disease (CLD) in the preterm newborn is associated with inflammation and fibrosis. Platelet-derived growth factor-BB (PDGF-BB), a potent chemotactic growth factor, may mediate the fibrotic component of CLD. The objectives of this study were to determine if tracheal aspirate (TA) concentrations of PDGF-BB increase the first 2 weeks of life in premature neonates undergoing mechanical ventilation for respiratory distress syndrome (RDS), its relationship to the development of CLD, pulmonary hemorrhage (PH) and its relationship to airway colonization with Ureaplasma urealyticum (Uu). METHODS: Infants with a birth weight less than 1500 grams who required mechanical ventilation for RDS were enrolled into this study with parental consent. Tracheal aspirates were collected daily during clinically indicated suctioning. Uu cultures were performed on TA collected in the first week of life. TA supernatants were assayed for PDGF-BB and secretory component of IgA concentrations using ELISA techniques. RESULTS: Fifty premature neonates were enrolled into the study. Twenty-eight infants were oxygen dependent at 28 days of life and 16 infants were oxygen dependent at 36 weeks postconceptual age. PDGF-BB concentrations peaked between 4 and 6 days of life. Maximum PDGF-BB concentrations were significantly higher in infants who developed CLD or died from respiratory failure. PH was associated with increased risk of CLD and was associated with higher PDGF-BB concentrations. There was no correlation between maximum PDGF-BB concentrations and Uu isolation from the airway. CONCLUSIONS: PDGF-BB concentrations increase in TAs of infants who undergo mechanical ventilation for RDS during the first 2 weeks of life and maximal concentrations are greater in those infants who subsequently develop CLD. Elevation in lung PDGF-BB may play a role in the development of CLD

Emergency Portacaval Shunt Versus Rescue Portacaval Shunt in a Randomized Controlled Trial of Emergency Treatment of Acutely Bleeding Esophageal Varices in Cirrhosis—Part 3

Emergency treatment of bleeding esophageal varices in cirrhosis is of singular importance because of the high mortality rate. Emergency portacaval shunt is rarely used today because of the belief, unsubstantiated by long-term randomized trials, that it causes frequent portal-systemic encephalopathy and liver failure. Consequently, portacaval shunt has been relegated solely to salvage therapy when endoscopic and pharmacologic therapies have failed. Question: Is the regimen of endoscopic sclerotherapy with rescue portacaval shunt for failure to control bleeding varices superior to emergency portacaval shunt? A unique opportunity to answer this question was provided by a randomized controlled trial of endoscopic sclerotherapy versus emergency portacaval shunt conducted from 1988 to 2005. Unselected consecutive cirrhotic patients with acute bleeding esophageal varices were randomized to endoscopic sclerotherapy (n = 106) or emergency portacaval shunt (n = 105). Diagnostic workup was completed and treatment was initiated within 8 h. Failure of endoscopic sclerotherapy was defined by strict criteria and treated by rescue portacaval shunt (n = 50) whenever possible. Ninety-six percent of patients had more than 10 years of follow-up or until death. Comparison of emergency portacaval shunt and endoscopic sclerotherapy followed by rescue portacaval shunt showed the following differences in measurements of outcomes: (1) survival after 5 years (72% versus 22%), 10 years (46% versus 16%), and 15 years (46% versus 0%); (2) median post-shunt survival (6.18 versus 1.99 years); (3) mean requirements of packed red blood cell units (17.85 versus 27.80); (4) incidence of recurrent portal-systemic encephalopathy (15% versus 43%); (5) 5-year change in Child’s class showing improvement (59% versus 19%) or worsening (8% versus 44%); (6) mean quality of life points in which lower is better (13.89 versus 27.89); and (7) mean cost of care per year ($39,200 versus$216,700). These differences were highly significant in favor of emergency portacaval shunt (all p < 0.001). Emergency portacaval shunt was strikingly superior to endoscopic sclerotherapy as well as to the combination of endoscopic sclerotherapy and rescue portacaval shunt in regard to all outcome measures, specifically bleeding control, survival, incidence of portal-systemic encephalopathy, improvement in liver function, quality of life, and cost of care. These results strongly support the use of emergency portacaval shunt as the first line of emergency treatment of bleeding esophageal varices in cirrhosis

Gender differences in disability after sickness absence with musculoskeletal disorders: five-year prospective study of 37,942 women and 26,307 men

<p>Abstract</p> <p>Background</p> <p>Gender differences in the prevalence and occupational consequences of musculoskeletal disorders (MSDs) are consistently found in epidemiological studies. The study investigated whether gender differences also exist with respect to chronicity, measured as the rate of transition from sickness absence into permanent disability pension (DP).</p> <p>Methods</p> <p>Prospective national cohort study in Norway including all cases with a spell of sickness absence > eight weeks during 1997 certified with a MSD, 37,942 women and 26,307 men. The cohort was followed-up for five years with chronicity measured as granting of DP as the endpoint. The effect of gender was estimated in the full sample adjusting for sociodemographic factors and diagnostic distribution. Gender specific analyses were performed with the same explanatory variables. Finally, the gender difference was estimated for nine diagnostic subgroups.</p> <p>Results</p> <p>The crude rate of DP was 22% for women and 18% for men. After adjusting for all sociodemographic variables, a slightly higher female risk of DP remained. However, additional adjustment for diagnostic distribution removed the gender difference completely. Having children and working full time decreased the DP risk for both genders, whereas low socioeconomic status increased the risk similarly. There was a different age effect as more women obtained a DP below the age of 50. Increased female risk of chronicity remained for myalgia/fibromyalgia, back disorders and "other/unspecified" after relevant adjustments, whereas men with neck disorders were at higher risk of chronicity.</p> <p>Conclusions</p> <p>Women with MSDs had a moderately increased risk of chronicity compared to men, when including MSDs with a traumatic background. Possible explanations are lower income, a higher proportion belonging to diagnostic subgroups with poor prognosis, and a younger age of chronicity among women. When all sociodemographic and diagnostic variables were adjusted for, no gender difference remained, except for some diagnostic subgroups.</p