The effects of machining process variables and tooling characterisation on the surface generation: modelling, simulation and application promise

The paper presents a novel approach for modelling and simulation of the surface generation in the machining process. The approach, by integrating dynamic cutting force model, regenerative vibration model, machining system response model and tool profile model, models the complex surface generation process. Matlab Simulink is used to interactively perform the simulation in a user-friendly, effective and efficient manner. The effects of machining variables and tooling characteristics on the surface generation are investigated through simulations. CNC turning trials have been carried out to evaluate and validate the approach and simulations presented. The proposed approach contributes to comprehensive and better understanding of the machining system, and is promising for industrial applications with particular reference to the optimisation of the machining process based on the product/component surface functionality requirements

Multi-scale simulation of the nano-metric cutting process

Molecular dynamics (MD) simulation and the finite element (FE) method are two popular numerical techniques for the simulation of machining processes. The two methods have their own strengths and limitations. MD simulation can cover the phenomena occurring at nano-metric scale but is limited by the computational cost and capacity, whilst the FE method is suitable for modelling meso- to macro-scale machining and for simulating macro-parameters, such as the temperature in a cutting zone, the stress/strain distribution and cutting forces, etc. With the successful application of multi-scale simulations in many research fields, the application of simulation to the machining processes is emerging, particularly in relation to machined surface generation and integrity formation, i.e. the machined surface roughness, residual stress, micro-hardness, microstructure and fatigue. Based on the quasi-continuum (QC) method, the multi-scale simulation of nano-metric cutting has been proposed. Cutting simulations are performed on single-crystal aluminium to investigate the chip formation, generation and propagation of the material dislocation during the cutting process. In addition, the effect of the tool rake angle on the cutting force and internal stress under the workpiece surface is investigated: The cutting force and internal stress in the workpiece material decrease with the increase of the rake angle. Finally, to ease multi-scale modelling and its simulation steps and to increase their speed, a computationally efficient MATLAB-based programme has been developed, which facilitates the geometrical modelling of cutting, the simulation conditions, the implementation of simulation and the analysis of results within a unified integrated virtual-simulation environment

Ti alloy with enhanced machinability in UAT turning

Metastable β-titanium alloys such as Ti 15V 3Al 3Cr 3Sn are of great technological interest thanks to their high fatigue strength-to-density ratio. However, their high hardness and poor machinability increase machining costs. Additionally, formation of undesirable long chips increases the machining time. To address those issues, a metastable β-titanium alloy (Ti 15V 3Al 3Cr 2Zr 0.9La) with enhanced machinability was developed to produce short chips even at low cutting speeds. A hybrid ultrasonically assisted machining technique, known to reduce cutting forces, was employed in this study. Cutting force components and surface quality of the finished work-pieces were analyzed for a range of cutting speeds in comparison with those for more traditional Ti 15V 3Al 3Cr 3Sn. The novel alloy demonstrated slightly improved machining characteristics at higher cutting speeds and is now ready for industrial applications

Simple Nudges for Better Password Creation

Recent security breaches have highlighted the consequences of reusing passwords across online accounts. Recent guidance on password policies by the UK government recommend an emphasis on password length over an extended character set for generating secure but memorable passwords without cognitive overload. This paper explores the role of three nudges in creating website-specific passwords: financial incentive (present vs absent), length instruction (long password vs no instruction) and stimulus (picture present vs not present). Mechanical Turk workers were asked to create a password in one of these conditions and the resulting passwords were evaluated based on character length, resistance to automated guessing attacks, and time taken to create the password. We found that users created longer passwords when asked to do so or when given a financial incentive and these longer passwords were harder to guess than passwords created with no instruction. Using a picture nudge to support password creation did not lead to passwords that were either longer or more resistant to attacks but did lead to account-specific passwords

Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum

The ASBMT Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data on cases posted in the CCF from 1/29/2014 to 3/18/2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) autologous HCT and in 16 (12%) the type of transplant (auto vs. allo) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (AML; n = 23, 17%) and multiple myeloma (MM; n = 20, 15%). When compared with the US transplant activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were overrepresented in the CCF while myeloma was underrepresented (P < 0.001). A total of 259 topics were addressed in the CCF with a median of two topics/case (range 1-6). Particularly common topics included whether transplant was indicated (n = 57, 41%), conditioning regimen choice (n = 44, 32%), and post-HCT complications after day 100 (n = 43, 31%). The ASBMT CCF is a successful tool for collaborative discussion of complex cases in the HCT community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives

Performance measures for upper gastrointestinal endoscopy:A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

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Impaired Hepatitis C Virus-Specific T Cell Responses and Recurrent Hepatitis C Virus in HIV Coinfection

BACKGROUND: Hepatitis C virus (HCV)-specific T cell responses are critical for spontaneous resolution of HCV viremia. Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection. METHODS AND FINDINGS: We measured T cell responsiveness by lymphoproliferation and interferon-γ ELISPOT in a large cohort of HCV-infected individuals with and without HIV infection. Among 47 HCV/HIV-1-coinfected individuals, spontaneous control of HCV was associated with more frequent HCV-specific lymphoproliferative (LP) responses (35%) compared to coinfected persons who exhibited chronic HCV viremia (7%, p = 0.016), but less frequent compared to HCV controllers who were not HIV infected (86%, p = 0.003). Preservation of HCV-specific LP responses in coinfected individuals was associated with a higher nadir CD4 count (r (2) = 0.45, p < 0.001) and the presence and magnitude of the HCV-specific CD8(+) T cell interferon-γ response (p = 0.0014). During long-term follow-up, recurrence of HCV viremia occurred in six of 25 coinfected individuals with prior control of HCV, but in 0 of 16 HIV-1-negative HCV controllers (p = 0.03, log rank test). In these six individuals with recurrent HCV viremia, the magnitude of HCV viremia following recurrence inversely correlated with the CD4 count at time of breakthrough (r = −0.94, p = 0.017). CONCLUSIONS: These results indicate that HIV infection impairs the immune response to HCV—including in persons who have cleared HCV infection—and that HIV-1-infected individuals with spontaneous control of HCV remain at significant risk for a second episode of HCV viremia. These findings highlight the need for repeat viral RNA testing of apparent controllers of HCV infection in the setting of HIV-1 coinfection and provide a possible explanation for the higher rate of HCV persistence observed in this population

Protic Ionic Liquids Used as Metal-Forming Green Lubricants for Aluminum: Effect of Anion Chain Length

Among the applications for protic ionic liquids (PILs), lubrication is one of the newest and the most promising. In this work, ammonium-based protic ionic liquids were tested as lubricant fluids for aluminum-steel contacts. PILs were synthesized with 2-hydroxyethylamine (2HEA) and a carboxylic acid (formic and pentanoic), aiming to understand the effect of two different anion chain lengths on the lubricant behavior. The synthesized PILs were characterized by RMN, FTIR and TGA. Wear tests, conducted using a ball-on-plate configuration, showed that the increase of the anion carbon chain length in the PIL structure reduced significantly the coefficient of friction value. Besides, after the wear tests, the PILs structural integrity was not affected. In the same way, bending under tension (BUT) tests evidenced that the performance for stamping conditions of the PIL with the longest anion carbon chain was similar to that of the commercial lubricant. Since, both formed a uniform tribofilm, developed the same lubrication regime and the drawing forces values were close and constant. Hence, the ionic liquid obtained with 2HEA and pentanoic acid (2HEAPe) is as suitable as the commercial lubricant for metal forming processes

ASBMT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells

Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment of patients up to age 25 years with relapsed or refractory B cell acute lymphoblastic leukemia years "?>and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique toxicities of cytokine release syndrome (CRS) and neurologic toxicity. The assessment and grading of these toxicities vary considerably across clinical trials and across institutions, making it difficult to compare the safety of different products and hindering the ability to develop optimal strategies for management of these toxicities. Moreover, some aspects of these grading systems can be challenging to implement across centers. Therefore, in an effort to harmonize the definitions and grading systems for CRS and neurotoxicity, experts from all aspects of the field met on June 20 and 21, 2018, at a meeting supported by the American Society for Blood and Marrow Transplantation (ASBMT) in Arlington, VA. Here we report the consensus recommendations of that group and propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting

Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies

The field of primary immunodeficiencies (PIDs) is one of several in the area of clinical immunology that has not been static, but rather has shown exponential growth due to enhanced physician, scientist and patient education and awareness, leading to identification of new diseases, new molecular diagnoses of existing clinical phenotypes, broadening of the spectrum of clinical and phenotypic presentations associated with a single or related gene defects, increased bioinformatics resources, and utilization of advanced diagnostic technology and methodology for disease diagnosis and management resulting in improved outcomes and survival. There are currently over 200 PIDs with at least 170 associated genetic defects identified, with several of these being reported in recent years. The enormous clinical and immunological heterogeneity in the PIDs makes diagnosis challenging, but there is no doubt that early and accurate diagnosis facilitates prompt intervention leading to decreased morbidity and mortality. Diagnosis of PIDs often requires correlation of data obtained from clinical and radiological findings with laboratory immunological analyses and genetic testing. The field of laboratory diagnostic immunology is also rapidly burgeoning, both in terms of novel technologies and applications, and knowledge of human immunology. Over the years, the classification of PIDs has been primarily based on the immunological defect(s) ("immunophenotype") with the relatively recent addition of genotype, though there are clinical classifications as well. There can be substantial overlap in terms of the broad immunophenotype and clinical features between PIDs, and therefore, it is relevant to refine, at a cellular and molecular level, unique immunological defects that allow for a specific and accurate diagnosis. The diagnostic testing armamentarium for PID includes flow cytometry - phenotyping and functional, cellular and molecular assays, protein analysis, and mutation identification by gene sequencing. The complexity and diversity of the laboratory diagnosis of PIDs necessitates many of the above-mentioned tests being performed in highly specialized reference laboratories. Despite these restrictions, there remains an urgent need for improved standardization and optimization of phenotypic and functional flow cytometry and protein-specific assays. A key component in the interpretation of immunological assays is the comparison of patient data to that obtained in a statistically-robust manner from age and gender-matched healthy donors. This review highlights a few of the laboratory assays available for the diagnostic work-up of broad categories of PIDs, based on immunophenotyping, followed by examples of disease-specific testing