Marangoni driven turbulence in high energy surface melting processes

Experimental observations of high-energy surface melting processes, such as laser welding, have revealed unsteady, often violent, motion of the free surface of the melt pool. Surprisingly, no similar observations have been reported in numerical simulation studies of such flows. Moreover, the published simulation results fail to predict the post-solidification pool shape without adapting non-physical values for input parameters, suggesting the neglect of significant physics in the models employed. The experimentally observed violent flow surface instabilities, scaling analyses for the occurrence of turbulence in Marangoni driven flows, and the fact that in simulations transport coefficients generally have to be increased by an order of magnitude to match experimentally observed pool shapes, suggest the common assumption of laminar flow in the pool may not hold, and that the flow is actually turbulent. Here, we use direct numerical simulations (DNS) to investigate the role of turbulence in laser melting of a steel alloy with surface active elements. Our results reveal the presence of two competing vortices driven by thermocapillary forces towards a local surface tension maximum. The jet away from this location at the free surface, separating the two vortices, is found to be unstable and highly oscillatory, indeed leading to turbulence-like flow in the pool. The resulting additional heat transport, however, is insufficient to account for the observed differences in pool shapes between experiment and simulations

Therapeutisches Potential von Antileukoproteinase in einem Modell des akuten septischen Leberversagens

Beim akuten Leberversagen infolge septischen Schocks kommt der Interaktion von apoptotischem Zelluntergang und gesteigerter Leukozyten-Endothelzell-Interaktion mit Freisetzung proteolytischer Enzyme eine wesentliche Bedeutung zu. Ziel der vorliegenden In-vivo-Studie war es daher, die antiapoptotische und antiinflammatorische Wirkung rekombinant hergestellter Antileukoproteinase (ALP), einem physiologischen Inhibitor leukozytärer Serinproteasen, in einem murinen Modell des akuten Leberversagens zu evaluieren

Applicability of liquid biopsies to represent the mutational profile of tumor tissue from different cancer entities

Genetic investigation of tumor heterogeneity and clonal evolution in solid cancers could be assisted by the analysis of liquid biopsies. However, tumors of various entities might release different quantities of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) into the bloodstream, potentially limiting the diagnostic potential of liquid biopsy in distinct tumor histologies. Patients with advanced colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), and melanoma (MEL) were enrolled in the study, representing tumors with different metastatic patterns. Mutation profiles of cfDNA, CTCs, and tumor tissue were assessed by panel sequencing, targeting 327 cancer-related genes. In total, 30 tissue, 18 cfDNA, and 7 CTC samples from 18 patients were sequenced. Best concordance between the mutation profile of tissue and cfDNA was achieved in CRC and MEL, possibly due to the remarkable heterogeneity of HNSCC (63%, 55% and 11%, respectively). Concordance especially depended on the amount of cfDNA used for library preparation. While 21 of 27 (78%) tissue mutations were retrieved in high-input cfDNA samples (30-100 ng, N = 8), only 4 of 65 (6%) could be detected in low-input samples (<30 ng, N = 10). CTCs were detected in 13 of 18 patients (72%). However, downstream analysis was limited by poor DNA quality, allowing targeted sequencing of only seven CTC samples isolated from four patients. Only one CTC sample reflected the mutation profile of the respective tumor. Private mutations, which were detected in CTCs but not in tissue, suggested the presence of rare subclones. Our pilot study demonstrated superiority of cfDNA- compared to CTC-based mutation profiling. It was further shown that CTCs may serve as additional means to detect rare subclones possibly involved in treatment resistance. Both findings require validation in a larger patient cohort

Adrenal Dysfunction in Hemodynamically Unstable Patients in the Emergency Department

Objective: Adrenal failure, a treatable condition, can have catastrophic consequences if unrecognized in critically ill ED patients. The authors' objective was to prospectively study adrenal function in a case series of hemodynamically unstable (high-risk) patients from a large, urban ED over a 12-month period. Methods: In a prospective manner, critically ill adult patients presenting to the ED were enrolled when presenting with a mean arterial blood pressure ≤60 mm Hg requiring vasopressor therapy for more than one hour after receiving fluid resuscitation (central venous pressure of 12-15 mm Hg or a minimum of 40 mL/kg of crystalloid). Patients were excluded if presenting with hemorrhage, trauma, or AIDS, or if steroids were used within the previous six months. An adrenocorticotropic hormone (ACTH) stimulation test was performed and serum cortisol was measured. Treatment for adrenal insufficiency was not instituted. Results: A total of 57 consecutive patients were studied. Of these, eight (14%) had baseline serum cortisol concentrations of <20 Μg/dL (<552 nmol/L), which was considered adrenal insufficiency (AI). Three additional patients (5%) had subnormal 60-minute post-ACTH-stimulation cortisol responses (<30 Μg/dL) and a delta cortisol ≤9 Μg/dL, which is the difference between the baseline and 60-minute levels. This is functional hypoadrenalism (FH). There were no laboratory abnormalities that distinguished patients with AI or FH from those with preserved adrenal function (PAF). Rates of survival to discharge did not differ between the AI group (7 of 8) and PAF patients (21 of 46; p = 0.052). Conclusions: Adrenal dysfunction is common in high-risk ED patients. Overall, it has a frequency of 19% among a homogeneous population of hemodynamically unstable vasopressor-dependent patients. The effect of physiologic glucocorticoid replacement in this setting remains to be determined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71956/1/j.1553-2712.1999.tb00417.x.pd

Revealing internal flow behaviour in arc welding and additive manufacturing of metals

Internal flow behaviour during melt-pool-based metal manufacturing remains unclear and hinders progression to process optimisation. In this contribution, we present direct time-resolved imaging of melt pool flow dynamics from a high-energy synchrotron radiation experiment. We track internal flow streams during arc welding of steel and measure instantaneous flow velocities ranging from 0.1 m s−1 to 0.5 m s−1. When the temperature-dependent surface tension coefficient is negative, bulk turbulence is the main flow mechanism and the critical velocity for surface turbulence is below the limits identified in previous theoretical studies. When the alloy exhibits a positive temperature-dependent surface tension coefficient, surface turbulence occurs and derisory oxides can be entrapped within the subsequent solid as result of higher flow velocities. The widely used arc welding and the emerging arc additive manufacturing routes can be optimised by controlling internal melt flow through adjusting surface active elements

Use of flucinolone acetonide for patients with diabetic macular oedema:patient selection criteria and early outcomes in real world setting

Introduction: Fluocinolone acetonide slow release implant (Iluvien®) was approved in December 2013 in UK for treatment of eyes which are pseudophakic with DMO that is unresponsive to other available therapies. This approval was based on evidence from FAME trials which were conducted at a time when ranibizumab was not available. There is a paucity of data on implementation of guidance on selecting patients for this treatment modality and also on the real world outcome of fluocinolone therapy especially in those patients that have been unresponsive to ranibizumab therapy. Method: Retrospective study of consecutive patients treated with fluocinolone between January and August 2014 at three sites were included to evaluate selection criteria used, baseline characteristics and clinical outcomes at 3-month time point. Results: Twenty two pseudophakic eyes of 22 consecutive patients were included. Majority of patients had prior therapy with multiple intravitreal anti-VEGF injections. Four eyes had controlled glaucoma. At baseline mean VA and CRT were 50.7 letters and 631 μm respectively. After 3 months, 18 patients had improved CRT of which 15 of them also had improved VA. No adverse effects were noted. One additional patient required IOP lowering medication. Despite being unresponsive to multiple prior therapies including laser and anti-VEGF injections, switching to fluocinolone achieved treatment benefit. Conclusion: The patient level selection criteria proposed by NICE guidance on fluocinolone appeared to be implemented. This data from this study provides new evidence on early outcomes following fluocinolone therapy in eyes with DMO which had not responded to laser and other intravitreal agents

Osteopontin is a prognostic circulating biomarker in patients with neuroendocrine neoplasms

PURPOSE: Osteopontin (OPN), also called secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and which has been shown to be involved in tumorigenesis and metastasis in many malignancies. Its role in neuroendocrine neoplasms (NEN) remains to be established. The aim of the study was to analyze plasma concentrations of OPN in patients with NEN and to explore its diagnostic and prognostic value as a clinical biomarker. METHODS: OPN plasma concentrations were measured in a total of 38 patients with histologically proven NEN at three different time points during the course of disease and therapy (at the start of the study, after 3 and 12 months, respectively) as well as in healthy controls. Clinical and imaging data as well as concentrations of Chromogranin A (CgA) and Neuron Specific Enolase (NSE) were assessed. RESULTS: OPN levels were significantly higher in patients with NEN compared to healthy controls. High-grade tumors (grade 3) showed the highest OPN levels. OPN levels were neither different between male and female patients nor between different primary tumor sites. OPN correlated significantly with corresponding NSE levels, while there was no correlation with Chromogranin A. High OPN levels above a cutoff value of 200 ng/ml at initial analysis predicted a worsened prognosis with significantly shorter progression-free survival of patients with NEN, which also held true within the subgroup of well-differentiated G1/G2 tumors. CONCLUSION: Our data indicate that high baseline OPN levels in patients with NEN are predictive of an adverse outcome with shorter progression-free survival, even within the group of well differentiated G1/G2 tumors. Therefore, OPN may be used as a surrogate prognostic biomarker in patients with NEN

Heterogeneity of primary outcome measures used in clinical trials of treatments for intermediate, posterior, and panuveitis

BACKGROUND: Uveitis describes a heterogeneous group of conditions characterized by intraocular inflammation. Since most of the sight-threatening forms of uveitis are individually rare, there has been an increasing tendency for clinical trials to group distinct uveitis syndromes together despite clear variations in phenotype which may reflect real aetiological and pathogenetic differences. Furthermore this grouping of distinct syndromes, and the range of manifestations within each uveitis syndrome, leads to a wide range of possible outcome measures. In this study we wished to review the degree of consensus or otherwise in the choice of primary outcome measures for registered clinical trials related to uveitis. METHODS: Systematic review of data provided in clinical trial registries describing clinical trials dealing with medical treatment of intermediate, posterior, or panuveitis through 01 October 2013. We reviewed 15 on-line clinical trial registries approved by the International Committee of Medical Journal Editors. We identified all that met the following inclusion criteria: prospective, interventional design; target populations with intermediate, posterior or panuveitis; and one or more pre-specified outcome measures that were related to uveitis. Primary outcome measures were classified in terms of type (efficacy or safety or both; single, composite, or multiple); dimension (disease activity, disease damage, measured or patient-reported visual function); and domain (the specific study variable being measured). RESULTS: Of 195 registered uveitis studies, we identified 104 clinical trials that met inclusion criteria. There were 14 different domains used as primary outcome measures. Among clinical trials that utilized primary outcome measures of treatment efficacy (n = 94), 70 (74 %) used a measure of disease activity (vitreous haze in 40/70 [57 %]; macular oedema in 19/70 [27 %]) and 49 (70 %) used a measure of visual function (visual acuity in all cases). Multiple primary outcome measures were used in 23 (22 %) of 104 clinical trials. With regard to quality, in 12 (12 %) of 104 clinical trials, outcome measures were poorly defined. No clinical trial utilized a patient-reported study variable as primary outcome measure. CONCLUSIONS: This systematic review highlights the heterogeneity of outcome measures used in recent clinical trials for intermediate, posterior, and panuveitis. Current designs prioritize clinician-observed measures of disease activity and measurement of visual function as outcome measures. This apparent lack of consensus regarding outcome measures for the study of uveitis is a concern, as it prevents comparison of studies and meta-analyses, and weakens the evidence available to stake-holders, from patients to clinicians to regulators, regarding the efficacy and value of a given treatment