Formability study and forming path optimization in single-point incremental forming process

Incremental sheet metal forming is becoming a popular approach for forming intricate shapes especially for rapid prototyping and small batch production of sheet metals. In this work, the formability of Aluminium sheet metal in a single-point incremental forming (SPIF) has been investigated numerically and the effect of the feed rate, the vertical feed (pitch) and the spindle revolution on the formability have been studied. Parameters study results built a base for enhancing SPIF process and presenting two approaches to optimize forming path. In these approaches, variation of vertical pitch has been considered and the effects of this parameter on the strain distribution and formability have been studied. It is found that these methods normalize the strain distribution and improve the formability. Finite element method (FEM) with the aid of design of experiments (DOE) technique is used for predicting the parameters effects and optimizing forming path. Experiments are also carried out to verify the validity of numerical results

Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer (vol 313, pg 1347, 2015)

Heli Nevanlinna ja Kristiina Aittomäki ovat CIMBA Consortium -työryhmän jäseniä.IMPORTANCE Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES Breast and ovarian cancer risks. RESULTS Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317(12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682(6%) with ovarian cancer, 272(2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% Cl, 1.22-1.74; P = 2 x 10(-6)), c.4328 to c.4945 (BCCR2; RH R = 1.34; 95% Cl, 1.01-1.78; P =.04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% Cl, 1.22-1.55; P = 6 x 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% Cl, 0.56-0.70; P = 9 x 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% Cl, 1.06-2.78; P =.03), c.772 to c.1806 (BCCRI; RHR = 1.63; 95% Cl, 1.10-2.40; P =.01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% Cl, 1.69-3.16; P =.00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% Cl, 0.44-0.60; P = 6 x 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% Cl, 0.41-0.80; P =.001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.Peer reviewe

A Novel Role for the NLRC4 Inflammasome in Mucosal Defenses against the Fungal Pathogen Candida albicans

Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1β production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell recruitment to infected tissues, as well as protects against systemic dissemination of infection. Deficiency in either NLRC4 or NLRP3 results in severely attenuated pro-inflammatory and antimicrobial peptide responses in the oral cavity. Using bone marrow chimeric mouse models, we show that, in contrast to NLRP3 which limits the severity of infection when present in either the hematopoietic or stromal compartments, NLRC4 plays an important role in limiting mucosal candidiasis when functioning at the level of the mucosal stroma. Collectively, these studies reveal the tissue specific roles of the NLRP3 and NLRC4 inflammasome in innate immune responses against mucosal Candida infection

Large Prospective Study of Ovarian Cancer Screening in High-Risk Women: CA125 Cut-Point Defined by Menopausal Status

Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, while the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols

Dutch guideline on total hip prosthesis

Contains fulltext : 97840.pdf (publisher's version ) (Open Access

Effects of a Perioperative Smoking Cessation Intervention on Postoperative Complications A Randomized Trial

Objective: To determine whether an intervention with smoking cessation starting 4 weeks before general and orthopedic surgery would reduce the frequency of postoperative complications.Summary Background Data: Complications are a major concern after elective surgery and smokers have an increased risk. There is insufficient evidence concerning how the duration of preoperative smoking intervention affects postoperative complications.Methods: A randomized controlled trial, conducted between February 2004 and December 2006 at 4 university-affiliated hospitals in the Stockholm region, Sweden. The outcome assessment was blinded. The follow-up period for the primary outcome was 30 days. Eligibility criteria were active daily smokers, aged 18 to 79 years. Of the 238 patients assessed, 76 refused participating, and 117 men and women undergoing surgery for primary hernia repair, laparoscopic cholecystectomy, or a hip or knee prosthesis were enrolled.Intervention: Smoking cessation therapy with individual counseling and nicotine substitution started 4 weeks before surgery and continued 4 weeks postoperatively. The control group received standard care. The main outcome measure was frequency of any postoperative complication.Results: An intention-to-treat analysis showed that the overall complication rate in the control group was 41%, and in the intervention group, it was 21% (P = 0.03). Relative risk reduction for the primary outcome of any postoperative complication was 49% and number needed to treat was 5 (95% CI, 3–40). An analysis per protocol showed that abstainers had fewer complications (15%) than those who continued to smoke or only reduced smoking (35%), although this difference was not statistically significant.Conclusion: Perioperative smoking cessation seems to be an effective tool to reduce postoperative complications even if it is introduced as late as 4 weeks before surgery

Bewertung von Methoden zur Beurteilung von Rissen in Rohrleitungen

Bei zerstoerungsfreien Pruefungen von in Deutschland betriebenen Kernkraftwerken wurden einige Faelle von Rissbildungen festgestellt, die sowohl von der Rissart als auch vom Umfang der Befunde nicht erwartet worden waren, beispielsweise Risse in austenitischen Rohrleitungen von Siedewasserreaktoren, verursacht durch Spannungsrisskorrosion. Nach derzeitiger Praxis wird fuer die Beurteilung von Befunden haeufig auf auslaendische Regelwerke (z.B. ASME-Code) zurueckgegriffen, da im KTA-Regelwerk leicht und schnell handhabbare diesbezuegliche Festlegungen fehlen. Sowohl in der Bundesrepublik als auch im Ausland liegen umfangreiche experimentelle und methodische Untersuchungen vor, die fuer die Beurteilung von Befunden im Prinzip nutzbar sind. Gemaess der Aufgabe des Vorhabens wurden aus den angesprochenen Untersuchungen in den Arbeitsfeldern a. bruchmechanische Experimente an Rohrbauteilen mit Rissen, b. aufgefundene Rissformen und Rissursachen, c. geeignete vereinfachte Methoden zur Bewertung von Rissen, d. Vorkommnisse mit tolerierten Rissbefunden, e. aktuelle Risswachstumsmodelle bewertende Zusammenstellungen der Grundlagen erarbeitet. Auf dieser Basis wurden schliesslich Empfehlungen fuer eine moeglichst einheitliche Handhabung der Befundbewertung ausgearbeitet, die den entsprechenden Gremien (RSK, KTA) zur weiteren Beratung zugeleitet werden koennen. Aus der Prueferfahrung mit den unerwarteten Rissbefunden wurden von den entsprechenden Institutionen Empfehlungen fuer die zukuenftige Pruefpraxis abgeleitet, die teilweise bereits Eingang in das KTA-Regelwerk gefunden haben. (orig.)Non-destructive examinations performed on piping of nuclear power plants in Germany had sometimes revealed cracks that have been expected neither with respect to their nature nor to their extent (e.g., cracks in austentic piping of boiling water reactors). At present the assessment of findings at the occasion of such examinations is based on foreign design codes (e.g. ASME-Code) since in German codes (KTA-Regelwerk) no quickly usable directions are provided for such cases. In both Germany and foreign countries several experiments and theoretical analyses exist that can be used for the assessment of findings at non-destructive examinations. On the basis of these data the foundations of procedures in the following spheres of work have been reviewed and assessed: a. Fracture mechanics experiments on cracked piping elements, b. the nature of cracks detected and their causes, c. practicable simplified methods for the assessment of cracks, d. occurrences of cracks that have been left after inspection, e. crack growth models used at present. On the basis of these investigations recommendations are given that allow a standardised assessment procedure of findings of non-destructive examinations. These recommendations can be submitted to corresponding bodies, e.g. RSK, KTA for further discussion and to give recommendations to the regulators. From the experience gained with the unexpected findings of non-destructive examinations, some recommendations were given by the corresponding institutions for the practice of future examinations practice, that in part have been implemented already into the KTA safety standards. (orig.)SIGLEAvailable from TIB Hannover: RO 3190(2001-577) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman