Charge density and electric charge in quantum electrodynamics

The convergence of integrals over charge densities is discussed in relation with the problem of electric charge and (non-local) charged states in Quantum Electrodynamics (QED). Delicate, but physically relevant, mathematical points like the domain dependence of local charges as quadratic forms and the time smearing needed for strong convergence of integrals of charge densities are analyzed. The results are applied to QED and the choice of time smearing is shown to be crucial for the removal of vacuum polarization effects responible for the time dependence of the charge (Swieca phenomenon). The possibility of constructing physical charged states in the Feynman-Gupta-Bleuler gauge as limits of local states vectors is discussed, compatibly with the vanishing of the Gauss charge on local states. A modification by a gauge term of the Dirac exponential factor which yields the physical Coulomb fields from the Feynman-Gupta-Bleuler fields is shown to remove the infrared divergence of scalar products of local and physical charged states, allowing for a construction of physical charged fields with well defined correlation functions with local fields

Learning effect of humphrey matrix frequency doubling technology perimetry in patients with ocular hypertension

Aim: To evaluate the learning effect of Frequency Doubling Technology (FDT) perimetry using the Humphrey Matrix-FDT perimetry (Matrix) 24-2 full-threshold program on patients with 7 ocular hypertension experienced with standard automated perimetry. Methods: Twenty-four patients with Ocular hypertension underwent 5 full-threshold Matrix tests at intervals of 5 2 days. Learning effect was defined as an improvement at results for duration, perimetric indices, foveal sensitivity, Glaucoma Hemifield Test, and the number of points with a P < 5% and < 1% in the total and pattern deviation maps. Eccentricity, hemifield, and quadrant sensitivities were also addressed as Sources of differences in learning effect. Test-retest variability was also calculated for each repetition as the mean of the point-to-point interindividual standard deviations. Results: A learning effect was demonstrated for mean defect (P = 0.031, analysis of variance) and foveal sensitivity (P = 0.009) and it only affected the first test for both parameters. All the other parameters did not show any significant learning effect. The effect was independent From eccentricity and quadrant or hemifield sensitivities. Conclusions: The results of this study demonstrate that the learning effect for Matrix-FDT is mild and it may affect only the first test. Caution is needed in the analysis of the first Matrix-FDT examination and retest may be advisable in the presence of low mean defect

Circadian variations in central corneal thickness and intraocular pressure in patients with glaucoma

AIM: To analyse 24 hour variations in intraocular pressure (IOP) and central corneal thickness (CCT) in a group of glaucomatous patients. METHODS: 30 patients with primary open angle glaucoma were hospitalised and underwent circadian evaluations (at 8 pm, midnight, 4 am, 8 am, noon, and 4 pm) of supine and sitting IOP, respectively, measured using a Perkins and a Goldmann tonometer, and CCT measured using an ultrasonic pachymeter (the mean value of three measurements within 5 mum). All patients were treated with timolol 0.5% twice daily and latanoprost 0.005% once daily. RESULTS: Mean supine IOP was 15.3 (SD 3.7) mm Hg (range 10-25), with circadian fluctuations of 7.3 (3.3) mm Hg. Mean sitting IOP was 15.1 (3.9) mm Hg (range 8-26), with circadian fluctuations of 5.4 (3.1) mm Hg. Mean CCT was 534 (39) microm (range 443-637 microm) with circadian fluctuations of 16.5 (6.2) microm (range 6-31 microm). Both the within patient and within time point fluctuations in CCT were statistically significant (p<0.0001, ANOVA). CONCLUSIONS: The authors found considerable fluctuations in 24 hour IOP. The circadian fluctuations in CCT were small and, although statistically significant, did not seem to interfere with the circadian IOP assessment

A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer

The Tn antigen is a well-known tumor-associated carbohydrate determinant, often incorporated in glycopeptides to develop cancer vaccines. Herein, four copies of a conformationally constrained mimetic of the antigen TnThr (GalNAc-Thr) were conjugated to the adjuvant CRM197, a protein licensed for human use. The resulting vaccine candidate, mime[4]CRM elicited a robust immune response in a triple-negative breast cancer mouse model, correlated with high frequency of CD4+ T cells and low frequency of M2-type macrophages, which reduces tumor progression and lung metastasis growth. Mime[4]CRM-mediated activation of human dendritic cells is reported, and the proliferation of mime[4]CRM-specific T cells, in cancer tissue and peripheral blood of patients with breast cancer, is demonstrated. The locked conformation of the TnThr mimetic and a proper presentation on the surface of CRM197 may explain the binding of the conjugate to the anti-Tn antibody Tn218 and its efficacy to fight cancer cells in mice

Blood component therapy and coagulopathy in trauma: A systematic review of the literature from the trauma update group

Background Traumatic coagulopathy is thought to increase mortality and its treatment to reduce preventable deaths. However, there is still uncertainty in this field, and available literature results may have been overestimated. Methods We searched the MEDLINE database using the PubMed platform. We formulated four queries investigating the prognostic weight of traumatic coagulopathy defined according to conventional laboratory testing, and the effectiveness in reducing mortality of three different treatments aimed at contrasting coagulopathy (high fresh frozen plasma/packed red blood cells ratios, fibrinogen, and tranexamic acid administration). Randomized controlled trials were selected along with observational studies that used a multivariable approach to adjust for confounding. Strict criteria were adopted for quality assessment based on a two-step approach. First, we rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Then, this rating was downgraded if other three criteria were not met: high reporting quality according to shared standards, absence of internal methodological and statistical issues not detailed by the GRADE system, and absence of external validity issues. Results With few exceptions, the GRADE rating, reporting and methodological quality of observational studies was "very low", with frequent external validity issues. The only two randomized trials retrieved were, instead, of high quality. Only weak evidence was found for a relation between coagulopathy and mortality. Very weak evidence was found supporting the use of fibrinogen administration to reduce mortality in trauma. On the other hand, we found high evidence that the use of 1:1 vs. 1:2 high fresh frozen plasma/packed red blood cells ratios failed to obtain a 12% mortality reduction. This does not exclude lower mortality rates, which have not been investigated. The use of tranexamic acid in trauma was supported by "high" quality evidence according to the GRADE classification but was downgraded to "moderate" for external validity issues. Conclusions Tranexamic acid is effective in reducing mortality in trauma. The other transfusion practices we investigated have been inadequately studied in the literature, as well as the independent association between mortality and coagulopathy measured with traditional laboratory testing. Overall, in this field of research literature quality is poor

Vascular risk factors in glaucoma: the results of a national survey

Background The role of vascular risk factors in glaucoma is still being debated. To assess the importance of vascular risk factors in patients with primary open-angle glaucoma (POAG), data from the medical history of 2,879 POAG patients and 973 age-matched controls were collected and analyzed. Methods Design: observational survey. Setting: 35 Italian academic centers. Study population: POAG patients and age-matched controls. In order to reduce bias consecutive patients were included. Observation procedures: data concerning vascular risk factors were collected for all patients with a detailed questionnaire. A complete ophthalmological examination with assessment of intraocular pressure (IOP), visual field, optic disc, and systemic blood pressure was performed. Main outcome measures: the ESH-ESC (European Society of Hypertension-European Society of Cardiology) guidelines were used to calculate the level of cardiovascular risk. Crude and adjusted estimates of the odds ratios (OR) were calculated for all cardiovascular risk factors in POAG and controls. Results The study included 2,879 POAG patients and 973 controls. POAG cases had a significantly higher systolic and diastolic blood pressure (p=0.001) and systolic perfusion pressure (p=0.02) as compared with controls. Also mean IOP was significantly higher in the POAG group (p=0.01), while diastolic perfusion pressure was not significantly different in the two groups. Myopia was more prevalent in the POAG group (23 vs 18%, p=0.005) as well as a positive family history for glaucoma (26 vs 12%, p= 0.004). POAG patients tended to have a higher cardiovascular risk than controls: 63% of glaucoma cases vs 55% of controls (OR: 1.38, p=0.005) had a “high” or “very high” cardiovascular risk. Conclusions The level of cardiovascular risk was significantly higher in glaucoma patients than in controls

Blood component therapy and coagulopathy in trauma: A systematic review of the literature from the trauma update group

Background Traumatic coagulopathy is thought to increase mortality and its treatment to reduce preventable deaths. However, there is still uncertainty in this field, and available literature results may have been overestimated. Methods We searched the MEDLINE database using the PubMed platform. We formulated four queries investigating the prognostic weight of traumatic coagulopathy defined according to conventional laboratory testing, and the effectiveness in reducing mortality of three different treatments aimed at contrasting coagulopathy (high fresh frozen plasma/packed red blood cells ratios, fibrinogen, and tranexamic acid administration). Randomized controlled trials were selected along with observational studies that used a multivariable approach to adjust for confounding. Strict criteria were adopted for quality assessment based on a two-step approach. First, we rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Then, this rating was downgraded if other three criteria were not met: high reporting quality according to shared standards, absence of internal methodological and statistical issues not detailed by the GRADE system, and absence of external validity issues. Results With few exceptions, the GRADE rating, reporting and methodological quality of observational studies was "very low", with frequent external validity issues. The only two randomized trials retrieved were, instead, of high quality. Only weak evidence was found for a relation between coagulopathy and mortality. Very weak evidence was found supporting the use of fibrinogen administration to reduce mortality in trauma. On the other hand, we found high evidence that the use of 1:1 vs. 1:2 high fresh frozen plasma/packed red blood cells ratios failed to obtain a 12% mortality reduction. This does not exclude lower mortality rates, which have not been investigated. The use of tranexamic acid in trauma was supported by "high" quality evidence according to the GRADE classification but was downgraded to "moderate" for external validity issues. Conclusions Tranexamic acid is effective in reducing mortality in trauma. The other transfusion practices we investigated have been inadequately studied in the literature, as well as the independent association between mortality and coagulopathy measured with traditional laboratory testing. Overall, in this field of research literature quality is poor

Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): A Prospective Longitudinal Observational Study

BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20 000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management