Experimental estimates of the photon background in a potential light-by-light scattering study

High power short pulse lasers provide a promising route to study the strong field effects of the quantum vacuum, for example by direct photon–photon scattering in the all-optical regime. Theoretical predictions based on realistic laser parameters achievable today or in the near future predict scattering of a few photons with colliding Petawatt laser pulses, requiring single photon sensitive detection schemes and very good spatio-temporal filtering and background suppression. In this article, we present experimental investigations of this photon background by employing only a single high power laser pulse tightly focused in residual gas of a vacuum chamber. The focal region was imaged onto a single-photon sensitive, time gated camera. As no detectable quantum vacuum signature was expected in our case, the setup allowed for characterization and first mitigation of background contributions. For the setup employed, scattering off surfaces of imperfect optics dominated below residual gas pressures of 1 × 10−4 mbar. Extrapolation of the findings to intensities relevant for photon–photon scattering studies is discussed

Correlation between cystatin-C, acute phase reactants, and retinopathy severity in diabetic patients

AIM: To evaluate correlation of cystatin-C (Cys-C) with severity of diabetic retinopathy (DR) and acute phase reactants, including erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP). METHODS: All diabetic patients who were referred for diabetic retinopathy (DR) screening during 1mo were enrolled. Demographic data were recorded. All patients have undergone full ophthalmic exam. At the same day, all patients were tested for hemoglobin A1c (HbA1c), ESR, hs-CRP, and Cys-C serum levels. RESULTS: Sixty seven diabetics were enrolled, including 19 (28.3) without retinopathy, 22 (32.8) non-proliferative retinopathy, and 26 (38.8) proliferative retinopathy patients. The mean age, sex distribution, mean duration of diabetes, prevalence of hypertension and dyslipidemia, smoking status and HbA1c levels were not significantly different among the three groups. The mean levels of Cys-C increase significantly as retinopathy progress $$1.1±0.48; 1.22±0.38; 1.71±0.92 (P=0.007), respectively$$. In multiple regression analysis, just Cys-C was significantly associated with severity of DR (P=0.025). CONCLUSIONS: This study revealed that serum levels of Cys-C increase while DR progress independently of acute phase reactants. Therefore, it could be used as an associated marker by primary care physicians to distinguish patients at higher risk of severe DR. Larger randomized studies are warranted to confirm findings. Reviewing physiological role of the Cys-C, we proposed that the Cys-C may be a protective response to catalytic stress rather than being a pathogenic factor in microangiopathies. Copyright 2018 by the IJO Press

BioDiVinE: A Framework for Parallel Analysis of Biological Models

In this paper a novel tool BioDiVinEfor parallel analysis of biological models is presented. The tool allows analysis of biological models specified in terms of a set of chemical reactions. Chemical reactions are transformed into a system of multi-affine differential equations. BioDiVinE employs techniques for finite discrete abstraction of the continuous state space. At that level, parallel analysis algorithms based on model checking are provided. In the paper, the key tool features are described and their application is demonstrated by means of a case study

Adjuvant drugs for peripheral nerve blocks: The role of nmda antagonists, neostigmine, epinephrine, and sodium bicarbonate

The potential for misuse, overdose, and chronic use has led researchers to look for other methods to decrease opioid consumption in patients with acute and chronic pain states. The use of peripheral nerve blocks for surgery has gained increasing popularity as it minimizes peripheral pain signals from the nociceptors of local tissue sustaining trauma and inflammation from surgery. The individualization of peripheral nerve blocks using adjuvant drugs has the potential to improve patient outcomes and reduce chronic pain. The major limitations of peripheral nerve blocks are their limited duration of action and dose-dependent adverse effects. Adjuvant drugs for peripheral nerve blocks show increasing potential as a solution for postoperative and chronic pain with their synergistic effects to increase the duration of action and decrease the required dosage of local anesthetic. N-methyl-d-aspartate (NMDA) receptor antagonists are a viable option for patients with opioid resistance and neuropathic pain due to their affinity to the neurotransmitter glutamate, which is released when patients experience a noxious stimulus. Neostigmine is a cholinesterase inhibitor that exerts its effect by competitively binding at the active site of acetylcholinesterase, which prevents the hydrolysis of acetylcholine and subsequently retaining acetylcholine at the nerve terminal. Epinephrine, also known as adrenaline, can potentially be used as an adjuvant to accelerate and prolong analgesic effects in digital nerve blocks. The theorized role of sodium bicarbonate in local anesthetic preparations is to increase the pH of the anesthetic. The resulting alkaline solution enables the anesthetic to more readily exist in its un-ionized form, which more efficiently crosses lipid membranes of peripheral nerves. However, more research is needed to show the efficacy of these adjuvants for nerve block prolongation as studies have been either mixed or have small sample sizes

Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which and Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly increased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homologous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4$^{+}$ T cell responses were detected in natalizumab-treated pwMS. This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, further demonstrating the role of EBV adaptive immune responses in MS development

Factors Associated with Physician Agreement on Verbal Autopsy of over 11500 Injury Deaths in India

Worldwide, injuries account for 9.8% of all deaths. The majority of these deaths occur in low- and middle-income countries where vital registration systems are often inadequate. Verbal autopsy (VA) is a tool used to ascertain cause of death in such settings. Validation studies for VA using hospital diagnosed causes of death as comparisons have shown that injury deaths can be reliably diagnosed by VA. However, no study has assessed the factors that may affect physicians' abilities to code specific causes of injury death using VA.This study used data from over 11 500 verbal autopsies of injury deaths from the Million Death Study (MDS) in which 6.3 million people in India were monitored from 2001–2003 for vital events. Deaths that occurred in the MDS were coded by two independent physicians. This study focused on whether physician agreement on the classification of injury deaths was affected by characteristics of the deceased and respondent. Agreement was analyzed using three primary methods: 1) kappa statistic; 2) sensitivity and specificity analysis using the final VA diagnosed category of injury death as gold standard; and 3) multivariate logistic regression using a conceptual hierarchical model. The overall agreement for all injury deaths was 77.9% with a kappa of 0.74 (99% CI 0.74–0.75). Deaths in the injury categories of “transport”, “falls”, “drowning” and “other unintentional injury” occurring outside the home were associated with greater physician agreement than those occurring at home. In contrast, self-inflicted injury deaths that occurred outside the home were associated with lower physician agreement.With few exceptions, most characteristics of the deceased and the respondent did not influence physician agreement on the classification of injury deaths. Physician training and continued adaptation of the VA tool should focus on the reasons these factors influenced physician agreement

Efficacy of acupuncture in the treatment of chronic abdominal pain

Context: Abdominal pain is a widespread complaint and is one of the common reasons leading patients to seek medical care, either in emergency situations or with their primary providers. While acute abdominal pain is a better defined, usually surgical condition, chronic abdominal pain requires longer, typically lifelong, therapy. Chronic abdominal pain may also present with acute flares and complications. Here we review seminal and novel evidence discussing the use of acupuncture in the treatment of abdominal pain, indications, and conditions that may benefit from this approach. Evidence Acquisition: Chronic abdominal pain is a common complaint causing significant morbidity and disability and has a hefty price tag attached. Recent studies show it may be prevalent in as much as 25 of the adult population. It is defined as three episodes of severe abdominal pain over the course of three months. Chronic abdominal pain could be the result of chronicity of acute pain or of chronic pain syndromes, most commonly IBD syndromes and IBS. While a plethora of treatments exists for both conditions, these treatments usually fall short of complete symptom control, and there is a need for complementary measures to curb disability and increase the quality of life in these patients. Acupuncture is a form of integrative medicine that has long been used in Chinese and traditional medicine, based on the rebalancing of the patient�s Qi, or Ying/Yang balance. It has been shown to be effective in treating several other conditions, and novel evidence may expand its use into other fields as well. Clinical trials studying acupuncture in chronic pain conditions have been promising, and recent evidence supports the use of abdominal pain in chronic abdominal pain conditions as well. Though not curative, acupuncture is a complementary approach that helps reduce symptoms and improved quality of life. Conclusions: Chronic abdominal pain is a widespread condition, mostly affected by the IBS and IBD spectrum. Etiologies are still being studied for these conditions, and while novel treatment approaches are absolute game changers for these patients, many continue to experience some level of symptoms and disability. Acupuncture may provide further alleviation of these symptoms in select patients, thus improving quality of life, reducing disability, and saving healthcare dollars. It is a largely safe and inexpensive method that may significantly contribute to the quality of life of selected patients. © 2021, Author(s)

Motility-related protein-1 (MRP-1/CD9) expression can predict disease-free survival in patients with squamous cell carcinoma of the head and neck

CD9 is a transmembrane protein that has been implicated in cell adhesion, motility and proliferation, and numerous studies have demonstrated the prognostic value of its expression in different solid tumours. The purpose of this study is to determine the predictive value of CD9 in squamous cell carcinoma (SCC) of the head and neck. A total of 153 cases were examined for CD9 expression using immunohistochemistry applied on formalin-fixed, paraffin-embedded tissue. Cases were stratified in two categories depending on CD9 expression, as positive (>/=50% positive cells) or reduced (<50%). In all, 108 cases were positive for CD9 (85 cases with membranous, and 23 with both membranous and cytoplasmic staining) and 45 reduced expression. Reduced CD9 expression was significantly associated with high grade (P=0.0007) and lower disease-free survival (DFS) (P=0.017). The latter retained its significance in the multivariate analysis. When the 23 cases with both membranous and cytoplasmic patterns were studied as a separate subgroup, there were significant associations between CD9 expression and tumour grade (P=0.025) (95% CI 11-68), tumour stage (P=0.08) (95% CI 3.5-86) and the occurrence of any failure (P=0.083) (95% CI -1.7-57). Immunohistochemical CD9 expression proved to be an independent prognostic factor in SCC of the head and neck, and it may detect patients at a high risk of recurrence. In addition, the cytoplasmic pattern seems to have an even more significant value. However, this finding is limited to the small number of cases with this pattern

Robust metrics for assessing the performance of different verbal autopsy cause assignment methods in validation studies

<p>Abstract</p> <p>Background</p> <p>Verbal autopsy (VA) is an important method for obtaining cause of death information in settings without vital registration and medical certification of causes of death. An array of methods, including physician review and computer-automated methods, have been proposed and used. Choosing the best method for VA requires the appropriate metrics for assessing performance. Currently used metrics such as sensitivity, specificity, and cause-specific mortality fraction (CSMF) errors do not provide a robust basis for comparison.</p> <p>Methods</p> <p>We use simple simulations of populations with three causes of death to demonstrate that most metrics used in VA validation studies are extremely sensitive to the CSMF composition of the test dataset. Simulations also demonstrate that an inferior method can appear to have better performance than an alternative due strictly to the CSMF composition of the test set.</p> <p>Results</p> <p>VA methods need to be evaluated across a set of test datasets with widely varying CSMF compositions. We propose two metrics for assessing the performance of a proposed VA method. For assessing how well a method does at individual cause of death assignment, we recommend the average chance-corrected concordance across causes. This metric is insensitive to the CSMF composition of the test sets and corrects for the degree to which a method will get the cause correct due strictly to chance. For the evaluation of CSMF estimation, we propose CSMF accuracy. CSMF accuracy is defined as one minus the sum of all absolute CSMF errors across causes divided by the maximum total error. It is scaled from zero to one and can generalize a method's CSMF estimation capability regardless of the number of causes. Performance of a VA method for CSMF estimation by cause can be assessed by examining the relationship across test datasets between the estimated CSMF and the true CSMF.</p> <p>Conclusions</p> <p>With an increasing range of VA methods available, it will be critical to objectively assess their performance in assigning cause of death. Chance-corrected concordance and CSMF accuracy assessed across a large number of test datasets with widely varying CSMF composition provide a robust strategy for this assessment.</p