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The analog Hawking radiation (HR) emanating from a sonic black hole horizon formed in a cigar-shaped Bose-Einstein condensate (BEC) at finite temperature is investigated. In particular, we study the effect of HR on a dark (topological) soliton. We show that, due to thermal fluctuations, the dark soliton in the BEC displays a nonlinear Brownian motion resulting in a specific asymmetric diffusion. Based on numerical simulations we argue that the analog HR formed in the BEC can be detected indirectly through measurement of the dark soliton diffusion. Keywords: Analog Hawking radiation, Solitons, Bose-Einstein condensation

Could a conformal Galileon be describing a gauge mode of a broader diffeomorphism invariant theory? We answer this question affirmatively in 3D by using a coset construction for a nonlinearly realized conformal symmetry. In particular, we show that the conformal Galileon emerges as a Stückelberg field of a local Weyl symmetry. The coset construction gives us a diffeomorphism and Weyl invariant 3D theory containing first, second, and third powers of the curvatures, their couplings to certain tensors made of the Galileon and its derivatives, and the conformal Galileon terms. In a theory with a boundary additional surface terms are required for the boundary Weyl anomaly cancellation. When gravity is switched off, the theory reduces to the conformal Galileon plus a boundary term. On the other hand, it reduces to a generalization of “New Massive Gravity” by A. Sinha, if the Weyl symmetry is gauge-fixed in a particular way. Last but not least, there exists a parameter space for which the theory has no propagating ghosts. Thus we show by an explicit construction that “New Massive Gravity” (and its generalization) is a unique scalar ghost free low energy effective field theory non-linearly realizing conformal symmetry in 3D.

Mast cells (MCs) are well-known for their role in IgE-mediated cutaneous anaphylactic responses, but their regulatory functions in the skin are still under intense scrutiny. Using a Red MC and Basophil reporter (RMB) mouse allowing red fluorescent detection and diphtheria toxin mediated depletion of MCs, we investigated the interaction of MCs, Foxp3+ regulatory T lymphocytes (Tregs) and Langerhans cells (LCs) during passive cutaneous anaphylaxis (PCA) responses. Using intravital imaging we show that MCs are sessile at homeostasis and during PCA. Breeding RMB mice with Langerin-eGFP mice revealed that dermal MCs do not interact with epidermal-localized LCs, the latter showing constant sprouting of their dendrites at homeostasis and during PCA. When bred with Foxp3-eGFP mice, we found that, although a few Foxp3+ Tregs are present at homeostasis, many Tregs transiently infiltrated the skin during PCA. While their velocity during PCA was not altered, Tregs increased the duration of their contact time with MCs compared to PCA-control mice. Antibody-mediated depletion of Tregs had no effect on the intensity of PCA. Hence, the observed increase in Treg numbers and contact time with MCs, regardless of an effect on the intensity of PCA responses, suggests an anti-inflammatory role dedicated to prevent further MC activation.

In this essay, I apply Lowe’s theory of rational agency to God’s causal activity. I argue that Lowe’s account fits well the traditional notions that God acts in the world for reasons. In contrast to Lowe’s analysis of human causal agency, I argue that in the divine case, reasons for acting are not constituted by needs. They are constituted by God’s desires or plans. The fit between Lowe’s account of causal agency and the contours of divine causal agency motivate an argument in favor of Lowe’s theory. Any philosopher who is a theist ought to think Lowe’s account is likely to be true.

We demonstrate 1.7–18 µm mid-infrared coherent supercontinuum generation by means of the full transmission window of a unique dispersion-engineered step-index Ge-Se-Te fiber. Our study thus opens the entire molecular fingerprint region to future chalcogenide fiber platforms.

Amino acid transporters play a vital role in metabolism and nutrient signaling pathways. Typically, transport activity is investigated using single substrates and competing amounts of other amino acids. We used GC-MS and LC-MS for metabolic screening of Xenopus laevis oocytes expressing various human amino acid transporters incubated in complex media to establish their comprehensive substrate profiles. For most transporters, amino acid selectivity matched reported substrate profiles. However, we could not detect substantial accumulation of cationic amino acids by SNAT4 and ATB0,+ in contrast to previous reports. In addition, comparative substrate profiles of two related sodium neutral amino acid transporters known as SNAT1 and SNAT2, revealed the latter as a significant leucine accumulator. As a consequence, SNAT2, but not SNAT1, was shown to be an effective activator of the eukaryotic cellular growth regulator mTORC1. We propose, that metabolomic profiling of membrane transporters in Xenopus laevis oocytes can be used to test their substrate specificity and role in intracellular signaling pathways.

The purpose of this case report is to report the long-term outcome following shoulder hemiarthroplasty in a patient with dwarfism. A 60-year old female with pseudoachondroplasia dwarfism presented 17 years post-operative with a Subjective Shoulder Value of 90% and minimal pain. Custom designed implants were critical for surgical success. Preoperative planning with a CT scan was important in assessing glenoid dysplasia and determining the feasibility of glenoid resurfacing. The emergence of 3D CT virtual preoperative planning tools can further assist in the recognition of deformity to determine if custom designed implants are needed. Shoulder arthroplasty in dwarfism can lead to excellent long-term outcomes.

Introduction Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT.Methods and analysis DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0–2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0–2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment.Ethics and dissemination The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal.Trial registration number NCT03969511.

The cerebellum, or “little brain”, is often overlooked in studies of brain metabolism in favour of the cortex. Despite this, anomalies in cerebellar amino acid homeostasis in a range of disorders have been reported. Amino acid homeostasis is central to metabolism, providing recycling of carbon backbones and ammonia between cell types. Here, we examined the role of cerebellar amino acid transporters in the cycling of glutamine and alanine in guinea pig cerebellar slices by inhibiting amino acid transporters and examining the resultant metabolism of [1-13C]d-glucose and [1,2-13C]acetate by NMR spectroscopy and LCMS. While the lack of specific inhibitors of each transporter makes interpretation difficult, by viewing results from experiments with multiple inhibitors we can draw inferences about the major cell types and transporters involved. In cerebellum, glutamine and alanine transfer is dominated by system A, blockade of which has maximum effect on metabolism, with contributions from System N. Inhibition of neural system A isoform SNAT1 by MeAIB resulted in greatly decreased metabolite pools and reduced net fluxes but showed little effect on fluxes from [1,2-13C]acetate unlike inhibition of SNAT3 and other glutamine transporters by histidine where net fluxes from [1,2-13C]acetate are reduced by ~50%. We interpret the data as further evidence of not one but several glutamate/glutamine exchange pools. The impact of amino acid transport inhibition demonstrates that the cerebellum has tightly coupled cells and that glutamate/glutamine, as well as alanine cycling, play a major role in that part of the brain.

This essay might be construed as something of a missive in the vein of Kropotkin’s “An Appeal to the Young,” from old radicals who accomplished little, to young radicals who must accomplish much. We intend our remarks as preliminary, for it will be the young who will re-make the world, and in the process they will learn much to teach their descendants. This essay draws on both Marxist and anarchist currents in its formulation of revolutionary medicine for the current situation. Marx is necessary for his analysis of capitalism, his historical materialism, for his labor theory of value, for his formulation of history as the history of class struggle, for his emphasis on praxis. Anarchism is necessary for its hatred of capitalism, emphasis on freedom, its defiance of authority, and its radical democracy.

To mimic Alzheimer’s disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that the neuroprotective effects of ETAS®50, a standardized extract of Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to the inhibition of the apoptosis cascade through an enhancement of the stress-response proteins: heat shock proteins (HSPs). APP-overexpressing mice (double-transgenic APP and PS1 mouse strains with a 129s6 background), ages 6-8 weeks old, and weighing 20-24 grams were successfully bred in our laboratory. The animals were divided into 5 groups. APP-overexpressing mice and wild-type (WT) mice were pretreated with ETAS®50 powder (50% elemental ETAS and 50% destrin) at 200 mg/kg and 1000 mg/kg body weight. Saline, the vehicle for ETAS®50, was administered in APP-overexpressing mice and WT mice. ETAS®50 and saline were administered by gavage daily for 1 month. Cognitive assessments, using the Morris Water Maze, demonstrated that memory was recovered following ETAS®50 treatment as compared to nontreated APP mice. At euthanization, the brain was removed and HSPs, amyloid β, tau proteins, and caspase-3 were evaluated through immunofluorescence staining with the appropriate antibodies. Our data indicate that APP mice have cognitive impairment along with elevated amyloid β, tau proteins, and caspase-3. ETAS®50 restored cognitive function in these transgenic mice, increased both HSP70 and HSP27, and attenuated pathogenic level of amyloid β, tau proteins, and caspsase-3 leading to neuroprotection. Our results were confirmed with a significant increase in HSP70 gene expression in the hippocampus.

IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or without proliferative renal damage and compared to a healthy control group.MethodologyThis retrospective study was performed on SLE patients’ sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer >6 U/ml).ResultsThe cohort was composed of 100 SLE patients with proliferative LN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (>10 U/ml) by the automated technique, three sera were found “ambivalent” (>7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies.ConclusionAnti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.

Biceps tenotomy is a common procedure performed in arthroscopic shoulder surgery. Numerous studies have demonstrated the effectiveness of both biceps tenotomy and tenodesis to relieve pain and restore function for the diagnoses of bicipital tenosynovitis, SLAP tears, rotator interval pulley lesions, and failed SLAP repairs. It is also frequently performed as a concomitant procedure with arthroscopic rotator cuff repair. We report a technique to improve the efficiency of arthroscopic bicep tenotomy using a biceps squeeze maneuver. This is a simple method of manually squeezing the biceps muscle belly while performing the arthroscopic biceps tenotomy. This shortens and tensions the intra-articular portion of the tendon to facilitate a more safe and efficient procedure.

Objective: Mechanical retrieval of thrombotic material from acute ischemic stroke patients provides a unique entry point for translational research investigations. Here, we resolved the proteomes of cardioembolic and atherothrombotic cerebrovascular human thrombi and applied an artificial intelligence routine to examine protein signatures between the two selected groups.Methods: We specifically used n = 32 cardioembolic and n = 28 atherothrombotic diagnosed thrombi from patients suffering from acute stroke and treated by mechanical thrombectomy. Thrombi proteins were successfully separated by gel-electrophoresis. For each thrombi, peptide samples were analyzed by nano-flow liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) to obtain specific proteomes. Relative protein quantification was performed using a label-free LFQ algorithm and all dataset were analyzed using a support-vector-machine (SVM) learning method. Data are available via ProteomeXchange with identifier PXD020398. Clinical data were also analyzed using SVM, alone or in combination with the proteomes.Results: A total of 2,455 proteins were identified by nano-LC-MS/MS in the samples analyzed, with 438 proteins constantly detected in all samples. SVM analysis of LFQ proteomic data delivered combinations of three proteins achieving a maximum of 88.3% for correct classification of the cardioembolic and atherothrombotic samples in our cohort. The coagulation factor XIII appeared in all of the SVM protein trios, associating with cardioembolic thrombi. A combined SVM analysis of the LFQ proteome and clinical data did not deliver a better discriminatory score as compared to the proteome only.Conclusion: Our results advance the portrayal of the human cerebrovascular thrombi proteome. The exploratory SVM analysis outlined sets of proteins for a proof-of-principle characterization of our cohort cardioembolic and atherothrombotic samples. The integrated analysis proposed herein could be further developed and retested on a larger patients population to better understand stroke origin and the associated cerebrovascular pathophysiology.

Background: The prevention of radiation-induced liver disease (RILD) is very significant in ensuring a safe radiation treatment and high quality of life. Aims and Objectives: The purpose of this study is to investigate the correlation of physical and biological effective dose (BED) metrics with liver toxicity from hypo-fractionated liver radiotherapy. Materials and Methods: 41 hypo-fractionated patients in 2 groups were evaluated for classic radiation-induced liver disease (RILD) and chronic RILD, respectively. Patients were graded for effective toxicity (post-treatment minus pre-treatment) using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Physical dose (PD) distributions were converted to BED. The V10Gy, V15Gy, V20Gy, V25Gy and V30Gy physical dose-volume metrics were used in the analysis together with their respective BED-converted metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3. All levels were normalized to their respective patient normal liver volumes (NLV) and evaluated for correlation to RILD. Results were measured quantitatively using R2 regression analysis. Results: The classic RILD group had median follow-up time of 1.9 months and the average PD-NLV normalized V10Gy, V15Gy, V20Gy, V25Gy and V30Gy metrics per grade were plotted against RILD yielding R2 correlations of 0.84, 0.72, 0.73, 0.65 and 0.70, respectively while the BED-volume metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3 resulted in correlation values of 0.84, 0.74, 0.66, 0.78 and 0.74, respectively. BED compared to PD showed a statistically significant (p=.03) increase in R2 for the classic RILD group. Chronic RILD group had median follow-up time of 12.3 months and the average PD-NLV normalized V10Gy, V15Gy, V20Gy, V25Gy and V30Gy metrics per grade were plotted against RILD grade yielding R2 correlations of 0.48, 0.92, 0.88, 0.90 and 0.99 while the BED-volume metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3 resulted in correlation values of 0.43, 0.94, 0.99, 0.21 and 0.00, respectively. Conclusion: The strong correlations of the V10Gy and V15Gy PD-volume metrics as well as the V16.7Gy3(BED of V10Gy) to both classic and chronic RILD imply the appropriateness of the current 15Gy evaluation level for liver toxicity with hypo-fractionated treatments.

The Crewther–Broadhurst–Kataev (CBK) relation connects the Bjorken function for deep-inelastic sum rules (or the Gross–Llewellyn Smith function) with the Adler function for electron–positron annihilation in QCD; it has been checked to hold up to four loops in perturbation theory. Here we study non-perturbative terms in the CBK relation using a holographic dual theory that is believed to capture properties of QCD. We show that for the large invariant momenta the perturbative CBK relation is exactly satisfied. For the small momenta non-perturbative corrections enter the relation and we calculate their significant effects. We also give an exact holographic expression for the Bjorken function, as well as for the entire three-point axial-vector–vector correlation function, and check their consistency in the conformal limit.

Abstract Background Squamous cell carcinoma of the head and neck (HNSCC) represents an array of disease processes with a generally unfavorable prognosis. Inflammation plays an important role in tumor development and response to therapy. We performed a retrospective analysis of HNSCC patients to explore the relationship of the lymphocyte and neutrophil counts, the neutrophil-to-lymphocyte ratio (NLR) overall survival (OS), cancer-specific survival (CSS), local control (LC) and distant control (DC). Materials/methods All patients received definitive treatment for cancers of the oropharynx or larynx between 2006–2015. Neutrophil and lymphocyte counts were collected pre-, during-, and post-treatment. The correlations of patient, tumor, and biological factors to OS, CSS, LC and DC were assessed. Results 196 patients met our inclusion criteria; 171 patients were Stage III or IV. Median follow-up was 2.7 years. A higher neutrophil count at all treatment time points was predictive of poor OS with the pre-treatment neutrophil count and overall neutrophil nadir additionally predictive of DC. Higher pre-treatment and overall NLR correlated to worse OS and DC, respectively. Conclusion A higher pre-treatment neutrophil count correlates to poor OS, CSS and DC. Lymphocyte counts were not found to impact survival or tumor control. Higher pre-treatment NLR is prognostic of poor OS.

Abstract Bullous Pemphigoid (BP) is an inflammatory rare autoimmune bullous dermatosis, which outcome cannot be predicted through clinical investigations. Eosinophils are the main immune infiltrated cells in BP. However, the release of Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN), and Eosinophil Cationic Protein (ECP) upon eosinophil activation has still not been evaluated with respect to BP development. MBP, EDN and ECP were measured by ELISA in serum (n = 61) and blister fluid (n = 20) of patients with BP at baseline, and in serum after 2 months of treatment (n = 41). Eosinophil activation in BP patients was illustrated at baseline by significantly higher MBP, EDN and ECP serum concentrations as compared with control subjects (n = 20), but without distinction according to disease severity or outcome. EDN and ECP values were even higher in the blister fluids (P

A certain class of nonlocal theories eliminates an arbitrary cosmological constant (CC) from a universe that can be perceived as our world. Dark energy then cannot be explained by a CC; it could however be due to massive gravity. We calculate the new corrections, which originate from the nonlocal terms that eliminate the CC, to the decoupling limit Lagrangian of massive gravity. The new nonlocal terms also have internal field space Galilean symmetry and are referred here as “nonlocal Galileons.” We then study a self-accelerated solution and show that the new nonlocal terms change the perturbative stability analysis. In particular, small fluctuations are now stable and non-superluminal for some simple parameter choices, whereas for the same choices the pure massive gravity fluctuations are unstable. We also study stable spherically symmetric solutions on this background.

Contemporary arthroscopic double-row suture anchor rotator cuff repairs have superior biomechanics compared with prior iterations. Numerous techniques have been described, but consensus regarding value has yet to be established. We describe an effective and easily reproducible technique: the arthroscopic “Montgolfier double-row” repair technique. This knotless construct has an evenly distributed, load-sharing, radially oriented suture limb configuration much like the envelope cables of a Montgolfier hot-air balloon, its namesake. Other advantages include the ability to apply manual, progressive and calculated tension on each suture limb and easy intraoperative modification depending on tear size, shape, and delamination, as well as tissue tension and quality. Future studies are needed to validate the biomechanics and clinical outcomes of this technique.

Introduction: Preoperative axillary nerve palsy is a contraindication to reverse total shoulder arthroplasty (rTSA) due to the theoretical risk of higher dislocation rates and poor functional outcomes. Treatment of fracture-dislocations of the proximal humerus with rTSA is particularly challenging, as these injuries commonly present with concomitant neurologic and soft tissue injury. The aim of the current study was to determine the efficacy of rTSA for this fracture pattern in geriatric patients presenting with occult or profound neurologic injury. Methods: A retrospective case series of all shoulder arthroplasty procedures for proximal humerus fractures from February 2006 to February 2018 was performed. Inclusion criteria were patients aged greater than 65 years at the time of surgery, fracture-dislocations of the proximal humerus, and treatment with rTSA. Patients with preoperative nerve injuries were compared to patients without overt neurologic dysfunction. Forward elevation, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), Visual Analog Scale (VAS), and Subjective Shoulder Value (SSV) were obtained at final follow-up. Results: Forty-six rTSA for acute fracture were performed during the study period, 16 patients met the inclusion criteria and 5 (31%) presented with overt preoperative nerve injuries. At mean 3.1 years follow up, there were no postoperative complications including dislocations and final forward elevation was similar between study groups. Patients with overt nerve palsy had higher QuickDASH and VAS scores with lower SSV and self-rated satisfaction. Discussion: In the majority of patients with or without overt nerve injury, rTSA reliably restored overhead function and led to good or excellent patient-rated treatment outcomes. Overt nerve palsy did not lead to higher complication rates, including dislocation. Despite greater disability and less satisfaction, complete or partial nerve recovery can be expected in the majority of patients. Conclusion: Nerve injury following proximal humeral fracture dislocation may not be an absolute contraindication to rTSA.

Background: DNA extracellular traps (ETs), released by neutrophils (NETs), or eosinophils (EETs), play a pathogenic role in several autoimmune disorders. However, to date, NETs have never been investigated in bullous pemphigoid (BP) with respect to clinical and immunological activities, both at baseline and at time of relapse which have been characterized with specific IL-17 and IL-23 patterns.Objective: We sought to assess whether ETs were associated with BP as well as the relative contribution of IL-17 axis cytokines to NET induction.Methods: Skin biopsy specimens were obtained from 11 patients with BP. Immuno-detection of neutrophils and eosinophils combined to DNA staining allowed us to investigate the in-situ presence of NETs and EETs using confocal scanning microscopy. NETs release was evaluated ex vivo by stimulating polymorphonuclear cells from BP patients with BP biological fluids in presence of IL-17A and IL-23 or of glucocorticoids.Results: At baseline, ETs were observed in BP lesions at the site of dermal-epidermal cleavage. Despite an important infiltrate of eosinophils, ETs were essentially associated with neutrophils in situ and were not related to BP clinical activity at diagnosis. In situ observation of NETs was associated in 6 among 8 patients with serum capacity of NET induction. Notably both blister fluid and sera from BP patients at diagnosis and at time of relapse could induce NET formation ex vivo. In contrast, a longitudinal investigation showed a decrease of NET formation with time of treatment in patients undergoing remission. Mimicking relapse, complementation of sera from BP patients with ongoing remission with either IL-17A or IL-23 increased NET formation. Conversely, IL-17A inhibited NET formation induced by serum from BP patients with relapse supplemented or not with IL-23. Finally, glucocorticoids also inhibited NET formation ex vivo in BP.Conclusion: NET formation is an associated phenomenon with BP. Furthermore, we showed that IL-23 favored NET formation, whereas the effects of IL-17A are environment dependent. Indeed, IL-17A displayed a protective effect on NET formation when associated with IL-23, showing for the first-time differential effects of these two cytokines in BP.

Since 1982 all infants born within the East Anglian Regional Health Authority have been screened for cystic fibrosis. Between April 1985 and April 1992 infants identified in this way have been entered into a randomised prospective controlled trial of antibiotic prophylaxis. Approximately half the infants received continuous oral flucloxacillin and the remainder received antibiotics when clinically indicated. Infants underwent tests of respiratory function at 3-4 months and at 1 year of age. Measurements of thoracic gas volume and airway conductance were made with an infant whole body plethysmograph, and maximum expiratory flow by the 'squeeze' technique. A total of 73 tests was performed of 42 infants. To facilitate comparisons, measurements were expressed as scores. The mean values of the scores for the two groups of infants fell within normal limits. There was no difference between the treatment groups at either age. A reduction in airways conductance was observed between the two tests. [ABSTRACT FROM AUTHOR]

Background and Purpose: Endovascular treatment of tandem occlusions is an emerging option. We describe our multicenter experience with endovascular management of atherosclerotic tandem occlusions in the anterior circulation, particularly the technical aspects and complications in comparison to isolated intracranial occlusions.Materials and Methods: Consecutive patients with tandem occlusions due to atherosclerotic causes who underwent mechanical thrombectomy at two major stroke centers between January 2010 and September 2015 were reviewed. Clinical data, procedural aspects, recanalization rates, complication rates, and clinical outcome were analyzed and compared to findings in patients with isolated intracranial occlusions.Results: One hundred and twenty-one patients with tandem occlusions and 456 patients with isolated intracranial occlusions (carotid-T/M1) were included. Mean intervention time was faster (33 min vs. 57 min, p < 0.001) and recanalization success was higher (TICI 2b/3 83.6 vs. 70.2%, p = 0.002) in patients with isolated occlusions. No difference was seen in clinical outcome and complications, except for a higher rate of asymptomatic hemorrhage in the tandem group (29.8 vs. 17.1%, p = 0.003). Choice of recanalization approach (antegrade vs. retrograde) in the tandem group made no difference, except for a trend toward less distal emboli using the retrograde approach (4.0 vs. 13.0%, p = 0.082). Stenting of the extracranial internal carotid artery (ICA) was performed in 81%, PTA alone in 7.4%, and deferred stenting in 11.6%. Rate of stent/ICA occlusion within 7 days was 10.3% after stenting and 33.3% after PTA (p = 0.127). In the tandem group, age (p = 0.034), National Institutes of Health Stroke Scale score (NIHSS) at admission (p = 0.002), recanalization rate (p < 0.001), complications (p = 0.016), and symptomatic intracranial hemorrhage (sICH) (p = 0.001) were associated with poor outcome, whereas extracranial treatment modality and stent/ICA occlusion within 7 days did not affect outcome.Conclusion: Endovascular treatment of tandem occlusions is technically feasible, achieves recanalization rates and rates of good clinical outcome comparable to those in patients with isolated intracranial occlusions. Following acute ICA stenting, the risk of stent occlusion and sICH appeared to be low, but was associated with an increased rate of asymptomatic ICH.

Recent evidences indicate an important role of tissue inflammatory responses by innate immune cells in allograft acceptance and survival. Here we investigated the role of mast cells (MC) in an acute male to female skin allograft rejection model using red MC and basophil (RMB) mice enabling conditional MC depletion. Kinetic analysis showed that MCs markedly accelerate skin rejection. They induced an early inflammatory response through degranulation and boosted local synthesis of KC, MIP-2, and TNF. This enhanced early neutrophil infiltration compared to a female-female graft-associated repair response. The uncontrolled neutrophil influx accelerated rejection as antibody-mediated depletion of neutrophils delayed skin rejection. Administration of cromolyn, a MC stabilizer and to a lesser extent ketotifen, a histamine type I receptor antagonist, and absence of MCPT4 chymase also delayed graft rejection. Together our data indicate that mediators contained in secretory granules of MC promote an inflammatory response with enhanced neutrophil infiltration that accelerate graft rejection.

Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by anti-BP180 and anti-BP230 autoantibodies (AAbs). Mucous membrane involvement is an uncommon clinical feature of BP which may evoke epidermolysis bullosa acquisita, another skin autoimmune disease characterized by anti-type VII collagen AAbs. We therefore evaluated the presence of anti-type VII collagen AAbs in the serum of BP patients with and without mucosal lesions at time of diagnosis and under therapy. Anti-BP180, anti-BP230, and anti-type VII collagen AAbs were measured by ELISA in the serum of unselected patients fulfilling clinical and histo/immunopathological BP criteria at baseline (n = 71) and at time of relapse (n = 24). At baseline, anti-type VII collagen AAbs were detected in 2 out of 24 patients with BP presenting with mucosal involvement, but not in patients without mucosal lesions (n = 47). At the time of relapse, 10 out of 24 BP patients either displayed a significant induction or increase of concentrations of anti-type VII collagen AAbs (P

Bullous pemphigoid (BP) is the most common autoimmune bullous disease and typically affects the elderly. Binding of specific autoantibodies to BP180/230 hemidesmosomal components induces an inflammatory response leading to skin blister formation. Unusual manifestations of BP include additional mucous membrane involvement, without pathophysiological knowledge associated to the formation of these lesions. We here performed a prospective study on series of consecutive BP patients with (n = 77) and without (n = 18) mucosal involvements at baseline to further investigate why some BP patients display mucosal lesion and other not. Analysis of disease activity showed that BP patients with mucosal involvement displayed a higher total BP Disease Area Index (BPDAI) score (P = 0.008), but also higher skin and blister/erosion BPDAI scores (P = 0.02 and P = 0.001, respectively). By contrast, the erythema/urticaria BPDAI score was identical between the two groups of patients. The erythema/urticaria BPDAI score, but not the blister/erosion BPDAI score, was correlated with the serum concentration of anti-BP180 NC16A autoantibodies in patients with mucosal involvement. In multivariate analysis, the absence of anti-BP230 autoantibody was the only factor independently associated with mucosal involvement (OR 7.8; 95% CI, 3.1–19.6) (P

Xylem sap circulates under either positive or negative hydraulic pressure in plants. Negative hydraulic pressure (i.e., tension) is the most common situation when transpiration is high, and several devices have been developed to quantify it accurately (e.g., Scholander pressure chamber, psychrometers). However, a proper measurement of positive xylem sap pressures may be critical when pressure is generated by the root system, allowing vessels to be refilled. Here, we describe two different methods to monitor positive xylem bulk pressure: the pressure gauge which can only be set onto a rootstock or a side branch and the point pressure sensor, which can allow measurements from a functioning plant without detopping or cutting.

Some time ago, Tseytlin has made an original and unusual proposal for an action that eliminates an arbitrary cosmological constant. The form of the proposed action, however, is strongly modified by gravity loop effects, ruining its benefit. Here I discuss an embedding of Tseytlin's action into a broader context, that enables to control the loop effects. The broader context is another universe, with its own metric and dynamics, but only globally connected to ours. One possible Lagrangian for the other universe is that of unbroken AdS supergravity. A vacuum energy in our universe does not produce any curvature for us, but instead increases or decreases the AdS curvature in the other universe. I comment on how to introduce the accelerated expansion in this framework in a technically natural way, and consider the case where this is done by the self-accelerated solutions of massive gravity and its extensions.

Background: The epidemiology and management of skin infections in nursing homes has not been adequately described. We reviewed the characteristics, diagnosis and treatment of skin infections among residents of nursing homes to identify opportunities to improve antibiotic use. Methods: A retrospective study involving 12 nursing homes in the Denver metropolitan area. For residents at participating nursing homes diagnosed with a skin infection between July 1, 2013 and June 30, 2014, clinical and demographic information was collected through manual chart review.Results: Of 100 cases included in the study, the most common infections were non-purulent cellulitis (n=55), wound infection (n=27), infected ulcer (n=8), and cutaneous abscess (n=7). In 26 cases, previously published minimum clinical criteria for initiating antibiotics (Loeb criteria) were not met. Most antibiotics (n=52) were initiated as a telephone order following a call from a nurse, and 41 patients were not evaluated by a provider within 48 hours after initiation of antibiotics. Nearly all patients (n=95) were treated with oral antibiotics alone. The median treatment duration was 7 days (interquartile range [IQR] 7-10); 43 patients received treatment courses of ≥ 10 days.Conclusions: Most newly diagnosed skin infections in nursing homes were non-purulent infections treated with oral antibiotics. Antibiotics were initiated by telephone in over half of cases, and lack of a clinical evaluation within 48 hours after starting antibiotics was common. Improved diagnosis through more timely clinical evaluations and decreasing length of therapy are important opportunities for antibiotic stewardship in nursing homes.

Internet-facilitated interventions may offer numerous advantages in reaching the large numbers of military service men and women exposed to traumatic events. The Internet is now a primary source of health-related information for consumers and research has shown the effectiveness of web-based interventions in addressing a range of mental health problems.Clinicians can learn how to bring Internet education and intervention into routine care, to help clients better understand mental health issues and learn skills for self-management of problems.The Afterdeployment.org (AD) Internet site can be used by health care professionals serving U.S. military personnel returning from Iraq and Afghanistan, and their families. The site currently addresses 18 key domains of functioning, including post-traumatic stress, sleep, anger, alcohol and drugs, and military sexual trauma. It provides an extensive amount of client and family education that is suitable for immediate use by clients and providers, as well as the kinds of interactive workshop content and self-assessment tools that have been shown to be helpful in other treatment contexts. AD can be utilized in clinical practice in a variety of ways: as an adjunct to treatment for PTSD, to supplement existing treatments for a range of post-deployment problems, or as the primary focus of treatment for a client.AD represents a kind of service that is likely to become increasingly available in coming years and that is important for mental health providers to actively explore as a tool for extending their reach, improving their efficiency, and improving quality of care.For the abstract or full text in other languages, please see Supplementary files under Reading Tools online.

Mid-infrared supercontinuum generation from 1.5 to 4.5 µm with sub-nanojoule femtosecond pump pulses is demonstrated by using a short segment of dispersion-engineered step-index tellurite fiber with very low OH content. Distinct group-velocity dispersion regimes in a simple design of step-index tellurite fiber are also reported, which allows to choose the nonlinear pulse propagation regime according to the required tailoring of the supercontinuum source. Numerical simulations based on the generalized nonlinear Schrödinger equation are used to determine optimized fiber parameters before experimental demonstrations. We also analyse the coherence properties of the resulting supercontinuum sources.

This article presents a series of guidelines both for researchers in search of software to be used in linguistic analysis and for programmers designing such software. A description of the intended audience and the types of software under consideration and a review of some relevant literature are followed by a discussion of several important considerations in evaluations of a project’s software requirements. The main section of the article then presents a series of guidelines or desiderata, grouped thematically, for the design of software for linguistic analysis. These describe goals and principles of interest both to programmers designing software and to researchers deciding on requirements or evaluating tools. The article closes with an exhortation to researchers and developers to communicate closely during the software design process and to understand the compromises that are necessary.

BACKGROUND AND PURPOSE:Approximately 30% of strokes are cryptogenic despite an exhaustive in-hospital work-up. Analysis of clot composition following endovascular treatment could provide insight into stroke etiology. T-cells already have been shown to be a major component of vulnerable atherosclerotic carotid lesions. We therefore hypothesize that T-cell content in intracranial thrombi may also be a biomarker of atherothrombotic origin. MATERIALS AND METHODS:We histopathologically investigated 54 consecutive thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fibrin-dominant, erythrocyte-dominant or mixed pattern. We then performed quantitative analysis of CD3+ cells on immunohistochemically-stained thrombi and compared T-cell content between "atherothrombotic", "cardioembolism" and "other causes" stroke subtypes. RESULTS:Fourteen (26%) thrombi were defined as fibrin-dominant, 15 (28%) as erythrocyte-dominant, 25 (46%) as mixed. The stroke cause was defined as "atherothrombotic" in 10 (18.5%), "cardioembolism" in 25 (46.3%), and "other causes" in 19 (35.2%). Number of T-cells was significantly higher in thrombi from the "atherothrombotic" group (53.60 ± 28.78) than in the other causes (21.77 ± 18.31; p

Los circuitos integrados bioinformadores bioluminiscentes (CIBB) son dispositivos que constan de una célula viva modificada por ingeniería genética para responder a un inductor determinado con luminiscencia, la cual es captada por un chip y convertida en una señal cuantificable. Se utilizaron inicialmente en la detección de agentes contaminantes, físicos o químicos, pero en la actualidad se realizan ensayos clínicos, en los cuales se utilizan linfocitos B para la detección de microorganismos patógenos y en la evaluación de la efectividad del tratamiento instaurado. Se plantea su posible uso en la detección precoz de células cancerosas y para monitorizar los niveles sanguíneos de sustancias útiles en el diagnóstico clínico.

Es evidente el impacto de la nanotecnología en la medicina. El desarrollo de nuevas herramientas para combatir microorganismos muestra lo prometedor de los avances en este campo. La fabricación de nanodispositivos inteligentes permitiría el diagnóstico temprano de lesiones celulares así como acceder a terapéuticas de alta efectividad y especificidad, que incluyen el control y reparación del DNA. A la par de estos avances es necesario profundizar en la reflexión bioética de la comunidad científica.

Studying texts by Lydia Maria Child, Sarah Grimke, and Margaret Fuller, this article seeks to recover the early phases of a dialogue that moved marriage away from an institution grounded in ideas of unification and toward a concept of marriage grounded in liberal ideas about equality. It seeks to situate the “marriage question” within both the rhetoric of American antebellum reform and of liberal religious thought. Rather than concluding that these early texts facilitated a movement toward a contractarian ideal of marriage this article concludes that Child, Grimke, and Fuller, sought to discredit unification as an organizing idea for marriage and replace it with a definition that placed a spiritual commitment to equality between the partners as the animating core of the idea of marriage.

Shape change of the left atrium (LA) and LA appendage in atrial fibrillation (AF) patients is hypothesized to be linked to AF pathology and to play a role in thrombogenesis; however, many aspects of shape variation in the heart are poorly understood. To date, studies of the LA shape in AF have been limited to empirical observation and summary metrics, such as volume and its likeness to a sphere. This paper describes a more comprehensive approach to the study of the LA shape through the use of computationally derived statistical shape models. We describe practical approaches that we have developed to extract shape parameters automatically from the three-dimensional MR images of the patient. From these images and our techniques, we can produce a more comprehensive description of LA geometric variability than that has been previously possible. We present the methodology and results from two examples of specific analyses using shape models: (1) we describe statistically significant group differences between the normal control and AF patient populations ( n = 137) and (2) we describe characteristic shapes of the LA appendage that are associated with the risk of thrombogenesis determined by transesophageal echocardiography ( n = 203).

Background: Polypharmacy has been identified as a quality indicator, but no studies have been reported about the epidemiology of polypharmacy among hospital patients at discharge. Methods: Records of 142 family medicine patients aged ≥65 years who were discharged from the hospital during the period November 2008 to October 2009 were extracted. Forty-six of these patients were readmitted within 30 days and the remaining 96 not readmitted within 30 days. Polypharmacy was measured as >16 medications at dismissal. Independent variables related to person (use of medical care in the 12 months prior to hospitalization, number of high-risk diagnoses, and demographic characteristics), place (living situation at admission and disposition location), and time (month of admission). Chronic obstructive pulmonary disease, cancer, diabetes mellitus, congestive heart failure, and coronary artery disease were diagnoses determined to be high-risk. Results: Mean number of medications at dismissal was 13.5 and 23.2% of patients were prescribed more than 16 medications. No interactions were found between readmission status and any of the independent variables. Use of medical services in the previous year was not related to polypharmacy and no seasonal pattern was detected. Two or more high-risk diagnoses were independently related to polypharmacy (odds ratio [OR] = 4.75, confidence interval [CI] = 1.0-11.2, P = .00). Being discharged to a location with personal health services such as home care or a skilled nursing facility was also related to polypharmacy (OR = 3.07, CI = 1.3-7.2, P = .01). Conclusion: Drug reviews intended to reduce the rate of polypharmacy among discharged persons aged ≥65 years can be targeted at patients who have 2 or more high-risk diagnoses and at those discharged to receive personal health services either at home or in a convalescence facility.

In terahertz (THz) materials science, imaging by scanning prevails when low power THz sources are used. However, the application of array detectors operating with high power THz sources is increasingly reported. We compare the imaging properties of four different array detectors that are able to record THz radiation directly. Two micro-bolometer arrays are designed for infrared imaging in the 8–14 μm wavelength range, but are based on different absorber materials (i) vanadium oxide; (ii) amorphous silicon; (iii) a micro-bolometer array optimized for recording THz radiation based on silicon nitride; and (iv) a pyroelectric array detector for THz beam profile measurements. THz wavelengths of 96.5 μm, 118.8 μm, and 393.6 μm from a powerful far infrared laser were used to assess the technical performance in terms of signal to noise ratio, detector response and detectivity. The usefulness of the detectors for beam profiling and digital holography is assessed. Finally, the potential and limitation for real-time digital holography are discussed.

Plants depend on the combined action of a shoot-root-soil system to maintain their anchorage to the soil. Mechanical failure of any component of this system results in lodging, a permanent and irreversible inability to maintain vertical orientation. Models of anchorage in grass crops identify the compressive strength of roots near the soil surface as key determinant of resistance to lodging. Indeed, studies of disparate grasses report a ring of thickened, sclerenchyma cells surrounding the root cortex, present only at the base of nodal roots. Here, in the investigation of the development and regulation of this agronomically important trait, we show that development of these cells is uncoupled from the maturation of other secondary cell wall-fortified cells, and that cortical sclerenchyma wall thickening is stimulated by mechanical forces transduced from the shoot to the root. We also show that exogenous application of gibberellic acid stimulates thickening of lignified cell types in the root, including cortical sclerenchyma, but is not sufficient to establish sclerenchyma identity in cortex cells. Leveraging the ability to manipulate cortex development via mechanical stimulus, we show that cortical sclerenchyma development alters root mechanical properties and improves resistance to lodging. We describe transcriptome changes associated with cortical sclerenchyma development under both ambient and mechanically stimulated conditions and identify SECONDARY WALL NAC7 as a putative regulator of mechanically responsive cortex cell wall development at the root base., Competing Interests: CONFLICT OF INTEREST None

Purpose of the Review: Current global information on incidence, prevalence, and mortality of type 1 diabetes (T1D) is limited, particularly in low- and middle-income countries. To address this gap in evidence, JDRF, Life for a Child, International Society for Pediatric and Adolescent Diabetes, and International Diabetes Federation have developed the T1D Index, which uses a Markov mathematical model, and machine learning and all available data to provide global estimates of the burden on T1D. This review assesses the methodology, limitations, current findings, and future directions of the Index., Recent Findings: Global prevalence was estimated at 8.4 million in 2021, with 1.5 million <20 years (y). T1D prevalence varied from 1.5 to 534 per 100,000, with T1D accounting for <0.1-17.8% of all diabetes in different countries. A total of 35,000 young people <25 y are estimated to have died at clinical onset of T1D from non-diagnosis. An estimated 435,000 people <25 y were receiving "minimal care." Health-adjusted life years (HALYs) lost for individuals diagnosed with T1D at age 10 y in 2021 ranged from 14 to 55 y. These results show that interventions to reduce deaths from non-diagnosis, and improve access to at least an intermediate care level, are needed to reduce projected life years lost. The results have significant uncertainties due to incomplete data across the required inputs. Obtaining recent incidence, prevalence, and mortality data, as well as addressing data quality issues, misdiagnoses, and the lack of adult data, is essential for maintaining and improving accuracy. The index will be updated regularly as new data become available., (© 2023. The Author(s).)