Morphology and Grain Texture in As-Deposited and Heat Treated Inconel 718 Structures Produced using Laser-Based Powder Bed Fusion

With increasing interest in the use of powder bed fusion (PBF) processes for additive manufacturing, understanding the relationship between as-deposited and heat treated states and the intrinsic anisotropy of fabricated parts has become critical for its successful application. This phenomenon has been studied and reported extensively for Inconel 718 parts fabricated using PBF for aerospace applications, but few reports exist on the morphology and grain texture of Inconel 718 parts fabricated for oil and gas applications, which have different demands. This work demonstrates that the anisotropy in Inconel 718 parts produced using laser-based PBF is not entirely removed by subsequent heat treatments, and it may be an artifact of the as-deposited grain structure, whose elongated grains may stretch through several melt pools. The as-built material is observed to exhibit some texturing, with (001) being the preferential growth direction. Despite some residual anisotropy, heat treatments are sufficient to provide material qualities that meet specification, even without the use of a HIP (hot isostatic pressing) step. It is hypothesized that similarly elongated grain structures may explain the anisotropy observed in other materials systems employed in PBF additive manufacturing processes.Mechanical Engineerin

A Preliminary Examination of Variability Due to Build Location and Powder Feedstock in Additive Manufacture of Inconel 718 using Laser-Based Powder Bed Fusion

The production of metallic parts by additive manufacturing (AM) is of significant interest to industry, but in the absence of standards, practical design considerations for manufacturing engineers are not widely known. Within the context of powder bed fusion (PBF), many unknowns persist regarding variations in part quality due to part location on the build plate, process consistency, feedstock supplier, and machine manufacturer. In this paper, we investigate the mechanical property variance across the build platform and document the successful use of feedstock powders obtained from several suppliers for the manufacture of Inconel 718 tensile and Charpy specimens, built on an EOS M280 laser-based powder bed fusion system. Particular emphasis is placed on describing the manufacturing process design challenges encountered even for simple geometries. While many advocate that complexity is free when using AM, we find that AM can lead to expensive build failures given the current state of manufacturing process knowledge and that design for additive manufacture is required for successful application of AM techniques.Mechanical Engineerin

Depression, antidepressant medications, and risk of Clostridium difficile infection

Abstract Background An ancillary finding in previous research has suggested that the use of antidepressant medications increases the risk of developing Clostridium difficile infection (CDI). Our objective was to evaluate whether depression or the use of anti-depressants altered the risk of developing CDI, using two distinct datasets and study designs. Methods In Study 1, we conducted a longitudinal investigation of a nationally representative sample of older Americans (n = 16,781), linking data from biennial interviews to physician and emergency department visits, stays in hospital and skilled nursing facilities, home health visits, and other outpatient visits. In Study 2, we completed a clinical investigation of hospitalized adults who were tested for C. difficile (n = 4047), with cases testing positive and controls testing negative. Antidepressant medication use prior to testing was ascertained. Results The population-based rate of CDI in older Americans was 282.9/100,000 person-years (95% confidence interval (CI)) 226.3 to 339.5) for individuals with depression and 197.1/100,000 person-years for those without depression (95% CI 168.0 to 226.1). The odds of CDI were 36% greater in persons with major depression (95% CI 1.06 to 1.74), 35% greater in individuals with depressive disorders (95% CI 1.05 to 1.73), 54% greater in those who were widowed (95% CI 1.21 to 1.95), and 25% lower in adults who did not live alone (95% CI 0.62 to 0.92). Self-reports of feeling sad or having emotional, nervous or psychiatric problems at baseline were also associated with the later development of CDI. Use of certain antidepressant medications during hospitalization was associated with altered risk of CDI. Conclusions Adults with depression and who take specific anti-depressants seem to be more likely to develop CDI. Older adults who are widowed or who live alone are also at greater risk of CDI.http://deepblue.lib.umich.edu/bitstream/2027.42/112859/1/12916_2012_Article_763.pd

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: A national observational study

Objective. To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk. Methods. Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF. Results. Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than-2.0 at 12 months compared to 16% of children without IVF (P = 0.011). Conclusion. The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months. © 2012, American College of Rheumatology

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma

Glucocorticoid-related changes in body mass index among children and adolescents with rheumatic diseases

Objective To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. Methods Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (\u3c0.2 mg/kg/day to a maximum of 7.5 mg/day), and moderate (between high and low) dosage. The impact of GC dosing, underlying diagnosis, pubertal status, physical activity, and disease activity on BMI Z scores and on percent body fat was assessed with longitudinal mixed-effects growth curve models. Results The GC starting dose was high in 59% and moderate in 39% of patients. The peak BMI Z score was +1.29 at 4 months with high-dose GCs and +0.69 at 4.2 months with moderate-dose GCs (P \u3c 0.001). Overall, 50% (95% confidence interval 41-59%) of the children returned to within +0.25 SD of their baseline BMI Z score. Oral GC dose over the preceding 3 months was the most significant determinant of BMI Z score and percent body fat. The proportion of days in receipt of GCs, disease activity, and a diagnosis of systemic-onset juvenile idiopathic arthritis were also associated with BMI Z scores. The correlation between changes in BMI and changes in percent body fat was 0.09. Conclusion In children with rheumatic diseases starting moderate and high doses of GCs, BMI Z scores peaked at 4 months, and only half returned to within +0.25 SD of their baseline BMI Z score after 18 months. Copyright © 2013 by the American College of Rheumatology

Proceedings of the Second Caldwell Conference, St. Catherines Island, Georgia, March 30-April 1, 2007

229 p. : ill. (some col.), maps (some col.) ; 26 cm. "Issued August 26, 2009." Includes bibliographical references (p. [213]-229).Archaeologists have long known that important changes took place in aboriginal ceramic assemblages of the northern Florida, Georgia, and South Carolina coast after the arrival of Europeans. New pottery designs emerged and aboriginal demographics became fluid. Catastrophic population loss occurred in some places, new groups formed in others, and movements of people occurred nearly everywhere. Although culturally and linguistically diverse, the native inhabitants of this region shared the unwelcome encounter with Spanish people and colonial institutions, beginning in the early decades of the 16th century and continuing into the 18th century. Spanish missions and military outposts were established at native communities throughout the area, and these sites have been studied by both archaeologists and historians for decades. As a consequence, the lower southeastern Atlantic coast offers one of the most intensively studied episodes of multicultural colonial engagement in America. The Second Caldwell Conference was organized to bring researchers working in South Carolina, Georgia, and Florida together to address and more precisely define aboriginal ceramic change throughout the region as a baseline for approaching a more broadly based anthropological perspective on the consequences of encounter. The scope of inquiry was restricted to late prehistoric and early historic (A.D. 1400-1700) aboriginal ceramic wares from Santa Elena (South Carolina) to St. Augustine (Florida). The primary objective was to more precisely establish the technology, form, and design of the archaeological ceramic evidence. Without devolving into semantic and/or taxonomic wrangles, we examined how well (or poorly) archaeological labels used throughout the region to identify pottery serve as reliable proxies for the physical examples of those ceramic traditions. We also attempted to define the time-space distribution of the various ceramic traditions and pottery types throughout the south Atlantic coast. Specifically, we asked: (1) Did the indigenous ceramic complexes change fundamentally with the arrival of the Spaniards? (2) Or did indigenous ceramic traditions essentially persist, and merely shifted geographically? The eight contributions of this volume examine, on a case-by-case basis, the most important aboriginal ceramic assemblages from Santa Elena southward to St. Augustine, across the region, contextualizing each assemblage with the relevant physical stratigraphy, radiocarbon dates, associations with Euro-American wares, and documentary evidence. We also attempt to situate the physical ceramic evidence from the northern Florida-Georgia-South Carolina coastline with the contemporary archaeological assemblages in the immediate interior. The volume concludes with an epilogue that summarizes the results and general contributions of the conference, relative to archaeological practice in the lower Atlantic coastal Southeast, and also to the larger cultural and methodological issues raised by these papers

The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study

<p>Abstract</p> <p>Background</p> <p>We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (<it>LRRK2</it>)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen <it>LRRK2 </it>mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of <it>LRRK2 </it>mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD.</p> <p>Methods</p> <p>A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different <it>LRRK2 </it>mutations. Penetrance was estimated in families of <it>LRRK2 </it>carriers with consideration of the inherent bias towards increased penetrance in a familial sample.</p> <p>Results</p> <p>Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 <it>LRRK2 </it>mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the <it>LRRK2 </it>mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-<it>LRRK2</it>-related PD families.</p> <p>Conclusion</p> <p>Lifetime penetrance of <it>LRRK2 </it>estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained <it>LRRK2 </it>cases, suggesting that inherited susceptibility factors may modify the penetrance of <it>LRRK2 </it>mutations. In addition, the presence of nine PD phenocopies in the <it>LRRK2 </it>families suggests that these susceptibility factors may also increase the risk of non-<it>LRRK2</it>-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for <it>LRRK2 </it>carriers are independent of the factors which increase PD prevalence in men.</p

Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis

10.2139/ssrn.15462511-2