Nanostructured Mg-ZK50 Sheets Fabricated for Potential Use for Biomedical Applications

Magnesium (Mg) alloys are widely used in biomedical applications thanks to their combination of exceptional mechanical properties, biocompatibility, and biodegradability. Mg-ZK alloy series; for instance, ZK40, ZK60 and ZK61; is an example of the most commonly used Mg bio-alloy. Zirconium (Zr) acts as a grain refiner when added to Mg, which manipulates the material structure by producing a refined internal structure and enhancing its properties. In addition, when Zinc (Zn) is added to a Mg-Zr alloy, strength is improved. Therefore, given the favorable properties of ZK alloys in biomedical applications, the current research aimed for the fabrication and the evaluation of a new ZK alloy with a new composition; ZK50, as a potential biomaterial for biomedical applications. Three stages were implemented in order to achieve the objective of this study. In the first stage, ball milling process was used to synthesize nanostructured Mg-ZK50 alloy from elemental powders (Mg, Zr, and Zn). The produced powders (BM) were studied using SEM, XRD and TEM to determine the internal structure refinement as well as the phase development due to milling. In the second stage, Powder-in-Tube (PIT) rolling process followed by annealing was applied to produce consolidated thin sheets from the BM powders. Accordingly, in the third stage, the effect of annealing on the internal structure, mechanical properties, corrosion behavior and cytotoxicity was evaluated. The mechanical milling of the elemental powders produced a nanostructured alloyed powder after 45 hrs of milling with a crystallite size of 8.83 nm, which is considered the finest internal structure for Mg and Mg based alloys to date. Afterwards, nanostructured thin sheets were successfully produced using PIT at 300 °C with 67% reduction percent. The modulus of the sheets was found matching to that of human bones. It is worthy to note that annealing was found to have a detrimental effect on the corrosion behavior of the alloy. However, a hydroxyapatite layer was formed which indicated that the produced sheets induced osteoinductivity of the bone. Moreover, cytotoxicity of the sheets was not affected by the sheets and all the produced sheets showed an acceptable toxicity level within the cells. In conclusion, the produced Mg-ZK50 nanostructured alloyed sheets are considered a new potential biomaterial for orthopedic implants that induces osteoinductivity and prevent stress shielding

Effective Organizational Culture Strategies for a Firm Operating in Foreign Countries

Organizational culture is a significant driver of success for firms, especially for those considering expansion to foreign countries. The purpose of this single case study was to explore effective cultural-oriented strategies that senior business leaders use to align the organization\u27s culture with foreign countries\u27 cultures to improve organizational performance in foreign countries. The target population was 8 current and former senior managers of a firm operating in 16 countries. Data were collected via a mix of videoconference and face-to-face interviews and the firm\u27s archival documents, the financial statements, the HR policy, and the internal control policy. The conceptual framework that grounded this study was Perlmutter and Hofstede\u27s theory of cultural dimensions, including the ethnocentric, polycentric, and geocentric model. Data analysis was conducted using Yin\u27s 5-step model, and 5 themes emerged from the data: general characteristics of the chosen organization culture, communication, adjustment to foreign environments, organizational and national cultures, and issues with employees. The implications for positive social change include the potential to enhance a firm\u27s social responsibility and social acceptance in international markets for the benefit of the firm, its employees, and the local societies

An Automated Fully-Computational Framework to Construct Printability Maps for Additively Manufactured Metal Alloys

In additive manufacturing, the optimal processing conditions need to be determined to fabricate porosity-free parts. For this purpose, the design space for an arbitrary alloy needs to be scoped and analyzed to identify the areas of defects for different laser power-scan speed combinations and can be visualized using a printability map. Constructing printability maps is typically a costly process due to the involvement of experiments, which restricts their application in high-throughput product design. To reduce the cost and effort of constructing printability maps, a fully computational framework is introduced in this work. The framework combines CALPHAD models and a reduced-order model to predict material properties. THen, an analytical thermal model, known as the Eagar-Tsai model, utilizes some of these materials' properties to calculate the melt pool geometry during the AM processes. In the end, printability maps are constructed using material properties, melt pool dimensions, and commonly used criteria for lack of fusion, balling, and keyholing defects. To validate the framework and its general application to laser powder-bed fusion alloys, five common additive manufacturing alloys are analyzed. Furthermore, NiTi-based alloys at three different compositions are evaluated to show the further extension of the framework to alloy systems at different compositions. The defect regions in these printability maps are validated with corresponding experimental observations to compare and benchmark the defect criteria and find the optimal criterion set with the maximum accuracy for each unique material composition. Furthermore, printability maps for NiTi that are obtained from our framework are used in conjunction with process maps resulting from a multi-model framework to guide the fabrication of defect-free additive manufactured parts with tailorable properties and performance.Comment: 18 Figures, 35 page

High-throughput Alloy and Process Design for Metal Additive Manufacturing

Designing alloys for additive manufacturing (AM) presents significant opportunities. Still, the chemical composition and processing conditions required for printability (ie., their suitability for fabrication via AM) are challenging to explore using solely experimental means. In this work, we develop a high-throughput (HTP) computational framework to guide the search for highly printable alloys and appropriate processing parameters. The framework uses material properties from state-of-the-art databases, processing parameters, and simulated melt pool profiles to predict process-induced defects, such as lack-of-fusion, keyholing, and balling. We accelerate the printability assessment using a deep learning surrogate for a thermal model, enabling a 1,000-fold acceleration in assessing the printability of a given alloy at no loss in accuracy when compared with conventional physics-based thermal models. We verify and validate the framework by constructing printability maps for the CoCrFeMnNi Cantor alloy system and comparing our predictions to an exhaustive 'in-house' database. The framework enables the systematic investigation of the printability of a wide range of alloys in the broader Co-Cr-Fe-Mn-Ni HEA system. We identified the most promising alloys that were suitable for high-temperature applications and had the narrowest solidification ranges, and that was the least susceptible to balling, hot-cracking, and the formation of macroscopic printing defects. A new metric for the global printability of an alloy is constructed and is further used for the ranking of candidate alloys. The proposed framework is expected to be integrated into ICME approaches to accelerate the discovery and optimization of novel high-performance, printable alloys.Comment: 46 pages, 20 figure

Selective Down-Regulation of Nuclear Poly(ADP-Ribose) Glycohydrolase

The formation of ADP-ribose polymers on target proteins by poly(ADP-ribose) polymerases serves a variety of cell signaling functions. In addition, extensive activation of poly(ADP-ribose) polymerase-1 (PARP-1) is a dominant cause of cell death in ischemia-reperfusion, trauma, and other conditions. Poly(ADP-ribose) glycohydrolase (PARG) degrades the ADP-ribose polymers formed on acceptor proteins by PARP-1 and other PARP family members. PARG exists as multiple isoforms with differing subcellular localizations, but the functional significance of these isoforms is uncertain.Primary mouse astrocytes were treated with an antisense phosphorodiamidate morpholino oligonucleotide (PMO) targeted to exon 1 of full-length PARG to suppress expression of this nuclear-specific PARG isoform. The antisense-treated cells showed down-regulation of both nuclear PARG immunoreactivity and nuclear PARG enzymatic activity, without significant alteration in cytoplasmic PARG activity. When treated with the genotoxic agent MNNG to induced PARP-1 activation, the antisense-treated cells showed a delayed rate of nuclear PAR degradation, reduced nuclear condensation, and reduced cell death.These results support a preferentially nuclear localization for full-length PARG, and suggest a key role for this isoform in the PARP-1 cell death pathway

Standardization and international multicenter validation of a PulseNet pulsed-field gel electrophoresis protocol for subtyping Shigella flexneri isolates

Fil: Pichel, Mariana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Brengi, Silvina P. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Cooper, Kara L. F. Centers for Disease Control and Prevention; Estados Unidos.Fil: Ribot, Efrain M. Centers for Disease Control and Prevention; Georgia.Fil: Al-Busaidy, Suleiman. Central Public Health Laboratory; Omán.Fil: Araya, Pamela. Instituto de Salud Pública de Chile; Chile.Fil: Fernández, Jorge. Instituto de Salud Pública de Chile; Chile.Fil: Vaz, Tania Ibelli. Instituto Adolfo Lutz; Brazil.Fil: Kam, Kai Man. Public Health Laboratory Centre; Japón.Fil: Morcos, Myriam. Regional Center at the U.S. Naval Medical Research Unit #3 (NAMRU-3). Global Disease Detection (GDD); Egipto.Fil: Nielsen, Eva M. Statens Serum Institut; Dinamarca.Fil: Nadon, Celine. National Microbiology Laboratory; Canadá.Fil: Pimentel, Guillermo. Regional Center at the U.S. Naval Medical Research Unit #3 (NAMRU-3). Global Disease Detection (GDD); Egipto.Fil: Pérez-Gutiérrez, Enrique. PAHO/WHO. Health Surveillance; Panamá.Fil: Gerner-Smidt, Peter. Centers for Disease Control and Prevention; Georgia.Fil: Binsztein, Norma. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Shigella flexneri is one of the agents most frequently linked to diarrheal illness in developing countries and often causes outbreaks in settings with poor hygiene or sanitary conditions. Travel is one of the means by which S. flexneri can be imported into developed countries, where this pathogen is not commonly seen. A robust and discriminatory subtyping method is needed for the surveillance of S. flexneri locally and regionally, and to aid in the detection and investigation of outbreaks. The PulseNet International network utilizes standardized pulsedfield gel electrophoresis (PFGE) protocols to carry out laboratory-based surveillance of foodborne pathogens in combination with epidemiologic data. A multicenter validation was carried out in nine PulseNet laboratories located in North and South America, Europe, and Asia, and it demonstrated that a new protocol is highly robust and reproducible for subtyping of S. flexneri. This protocol, already approved for PulseNet laboratories, applies NotI and XbaI as primary and secondary restriction enzymes, respectively, under electrophoresis conditions of initial switch time of 5 s to final switch time of 35 s, at 6 volts/cm

Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib). As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .)

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020