Sacrificial Materials for the Fabrication of Complex Geometries with LENS

Mechanical Engineerin

Thermal Behavior in the Lens Process

Direct laser metal deposition processing is a promising manufacturing technology which could significantly impact the length oftime between initial concept and finished part. For adoption ofthis technology in the manufacturing environment, further understanding is required to ensure robust components with appropriate properties are routinelyfabricated. This requires a complete understanding ofthe thermal history.during part fabrication and control ofthis behavior. This paper will describe our research to understand the thermal behavior for the Laser Engineered Net Shaping (LENS) process!, where a component is fabricated by focusing a laser beam onto a substrate to create a molten pool in which powder particles are simultaneously injected to build each layer. The substrate is moved beneath the l~ser beam to deposit a thin cross section, thereby creating the desired geometry for each layer. After deposition of each layer, the powder delivery nozzle and focusing lens assembly is incremented in the positive Z-direction, thereby building a three dimensional component layer additively. It is important to control the thermal behavior to reproducibly fabricate parts. The ultimate intent is to monitor the thermal signatures and to incorporate sensors and feedback algorithms to control part fabrication. With appropriate control, the geometric properties (accuracy, surface finish, low warpage) as well as the materials' properties (e.g. strength, ductility) of a component can be dialed into the part through the fabrication parameters. Thermal monitoring techniques will be described, and their particular benefits highlighted. Preliminary details in correlating thermal behavior with processing results will be discussed.Mechanical Engineerin

Adherence to and acceptability of artemether-lumefantrine as first-line anti-malarial treatment: evidence from a rural community in Tanzania

\ud \ud Controlled clinical trials have shown that a six-dose regimen of artemether-lumefantrine (AL) therapy for uncomplicated Plasmodium falciparum malaria results in cure rates >95% with good tolerability. A prospective study was carried out to document the adherence to and acceptability of AL administration. This was undertaken in the context of the ALIVE study, a prospective, community-based, observational study in a rural, malaria-endemic area of Tanzania. Following microscopic confirmation of P. falciparum infection, the first AL dose was taken under supervision, with the subsequent five doses taken unsupervised at home. Patients were randomized to receive a home-based assessment close to the scheduled time for one of the unsupervised doses, but were blinded to which follow-up visit they had been allocated. A structured questionnaire was administered by trained staff and AL consumption was confirmed by inspection of blister packs. A total of 552 patients were recruited of whom 352 (63.8%) were <13 years old. The randomization process allocated 112, 109, 110, 100 and 111 patients to a follow-up visit after doses 2, 3, 4, 5 and 6, respectively. For dose 2, 92.0% of patients (103/112) correctly took AL at 8 +/- 1 hours after dose 1. The remaining doses were taken within four hours of the correct time in 87-95% of cases. Nine patients (1.7%) missed one dose. Blister packs were available for inspection in 548 of cases (99.3%) and confirmed patient-reported data that the previous dose had been administered. Nearly all patients took AL with water (549/552 [99.5%]). Two patients (0.4%) took the drug with food. The dosing pictogram and clustering of tablets within the blister packs was considered helpful by 91.8% and 100.0% of patients, respectively. Overall, 87.1% of patients (481/552) found AL easier to take/administer than sulphadoxine-pyrimethamine (SP) and 87.7% (484/552) believed that AL was more effective than SP. Factors contributing to adherence were likely to be helpful packaging, pictorial dosing instructions and patients' conviction that AL is effective. Adherence to the dosing regimen and timing of AL administration was very good.\u

Near Net Shape production of metal components using LENS

Rapid Prototyping and Near Net Shape manufacturing technologies are the subject of considerable attention and development efforts. At Sandia National Laboratories, one such effort is LENS (Laser Engineered Net Shaping). The LENS process utilizes a stream of powder and a focused Nd YAG laser to build near net shape fully dense metal parts. In this process, a 3-D solid model is sliced, then an X-Y table is rastered under the beam to build each slice. The laser 1 powder head is incremented upward with each slice and the deposition process is controlled via shuttering of the laser. At present, this process is capable of producing fully dense metal parts of iron, nickel and titanium alloys including tool steels and aluminides. Tungsten components have also been produced. A unique aspect of this process is the ability to produce components wherein the composition varies at differing locations in the part. Such compositional variations may be accomplished in either a stepped or graded fashion. In this paper, the details of the process will be described. The deposition mechanism will be characterized and microstructures and their associated properties will be discussed. Examples of parts which have been produced will be shown and issues regarding dimensional control and surface finish will be addressed

Incidence of angioedema after initiation of angiotensin-converting enzyme inhibitors in adults with heart failure

Background: Angioedema, a potentially life-threatening adverse event associated with angiotensin-converting enzyme inhibitor (ACEI) use, occurs more often among Black patients than non-Black patients. Specific angioedema incidence rates (IRs) among heart failure (HF) patients initiating an ACEI are limited. Objectives: To provide estimates of angioedema incidence among HF patients initiating an ACEI, particularly among Black patients. Methods: We conducted a retrospective cohort study among adult (≥18 years) patients with HF who initiated ACEI use at 5 health care delivery systems within the Cardiovascular Research Network between July 2015 and May 2019. We required patients to have ≥12 months of continuous medical and prescription drug coverage and no ACEI dispensings in the 1 year before treatment initiation. Our primary outcome was serious angioedema, defined as a primary or secondary diagnosis of ICD-9 code 995.1 (‘Angioneurotic edema not elsewhere classified’) or ICD-10 codes in the T78.3 series (‘Angioneurotic edema’) during hospitalization. Our secondary out-come was ‘any angioedema’, which included serious angioedema and non-serious angioedema that was diagnosed in the outpatient setting. We followed patients from ACEI initiation until first angioedema diagnosis or a censoring event (treatment discontinuation, initiation of another renin-angiotensin-aldosterone system blocking agent, disenrollment, death, or end of 365-day follow-up or study). We calculated crude IRs and exact 95% confidence intervals (CI) for angioedema among HF patients initiating an ACEI. Results: We identified 14 ,241 ACEI users, of which 6,156 (43 .2%)were women and 2,105 (15%) were self-reported Black. Mean age was 70 ± 14 years. We observed 6 serious angioedema events overall (IR: 0.8/1,000 person-years (PYs), 95% CI: 0.3-1.7), with 2 events occurring among Black patients (IR: 1.8/1,000 PYs, 95%CI: 0.2-6.5) and 4 events among non-Black patients (IR: 0.6/1,000PYs, 95% CI: 0.2-1.5). We observed 43 angioedema events overall (IR: 5.4/1,000 PYs, 95% CI: 3.9-7.3), with 21 events occurring among Black patients (IR: 19/1,000 PYs, 95% CI: 11.8-29.1) and 22 events among non-Black patients (IR: 3.2/1,000 PYs, 95%CI: 2.0-4.9). Conclusions: Our estimate of angioedema incidence among HF patients who initiated an ACEI (5.4 events/1,000 PYs) is slightly higher than a previously published estimate (3.3/1,000 PYs) among a similarly-defined population identified through administrative claims data. Similar to prior reports, we found a higher incidence of angioedema, both serious and non-serious, among Black ACEI users than among non-black ACEI users

Information security: Listening to the perspective of organisational insiders

Aligned with the strategy-as-practice research tradition, this article investigates how organisational insiders understand and perceive their surrounding information security practices, how they interpret them, and how they turn such interpretations into strategic actions. The study takes a qualitative case study approach, and participants are employees at the Research & Development department of a multinational original brand manufacturer. The article makes an important contribution to organisational information security management. It addresses the behaviour of organisational insiders – a group whose role in the prevention, response and mitigation of information security incidents is critical. The article identifies a set of organisational insiders’ perceived components of effective information security practices (organisational mission statement; common understanding of information security; awareness of threats; knowledge of information security incidents, routines and policy; relationships between employees; circulation of stories; role of punishment provisions; and training), based on which more successful information security strategies can be developed

Experience of safety monitoring in the context of a prospective observational study of artemether-lumefantrine in rural Tanzania: lessons learned for pharmacovigilance reporting

<p>Abstract</p> <p>Objectives</p> <p>To identify and implement strategies that help meet safety monitoring requirements in the context of an observational study for artemether-lumefantrine (AL) administered as first-line treatment for uncomplicated malaria in rural Tanzania.</p> <p>Methods</p> <p>Pharmacovigilance procedures were developed through collaboration between the investigating bodies, the relevant regulatory authority and the manufacturer of AL. Training and refresher sessions on the pharmacovigilance system were provided for healthcare workers from local health facilities and field recorders of the Ifakara Health Demographic Surveillance System (IHDSS). Three distinct channels for identification of adverse events (AEs) and serious adverse events (SAEs) were identified and implemented. Passive reporting took place through IHDSS and health care facilities, starting in October 2007. The third channel was through solicited reporting that was included in the context of a survey on AL as part of the ALIVE (<b>A</b>rtemether-<b>L</b>umefantrine <b>I</b>n <b>V</b>ulnerable patients: <b>E</b>xploring health impact) study (conducted only in March-April 2008).</p> <p>Results</p> <p>Training was provided for 40 healthcare providers (with refresher training 18 months later) and for six field recorders. During the period 1^stSeptember 2007 to 31^stMarch 2010, 67 AEs were reported including 52 under AL, five under sulphadoxine-pyrimethamine, one under metakelfin, two after antibiotics; the remaining seven were due to anti-pyretic or anti-parasite medications. Twenty patients experienced SAEs; in 16 cases, a relation to AL was suspected. Six of the 20 cases were reported within 24 hours of occurrence.</p> <p>Discussion</p> <p>Safety monitoring and reporting is possible even in settings with weak health infrastructure. Reporting can be enhanced by regular and appropriate training of healthcare providers. SMS text alerts provide a practical solution to communication challenges.</p> <p>Conclusion</p> <p>Experience gained in this setting could help to improve spontaneous reporting of AEs and SAEs to health authorities or marketing authorization holders.</p

Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment

The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer. © 1999 Cancer Research Campaig