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Hollow-profile structures are significantly more stable than structures made using open profiles, which is the main reason for their use in truss and truss-like structures. The node intersections of such structures requires three-dimensional curved welded joints. Small and medium-sized enterprises usually weld tubular frame and truss structures manually, which is highly time-consuming and cost-intensive. In addition, this method requires personnel with corresponding qualifications to carry out the work as the welders need to adapt to constantly changing conditions in weld preparation and welding position, which obviously requires intensive training. Replacing this manual activity by mechanised welding processes would provide great relief to welders. [ABSTRACT FROM AUTHOR]

Ideas for the improvement of education in welding are close linked with the development of personal computer worldwide. Based on IIW guidelines it was a challenge to transform the new quality of computer- based technologies into programs to educate different players in welding. Computer-based training for engineer wars the starting point of these activities in 2003. Until now roughly 1000 engineers were educated first by self study on computer and then using Internet-learning platform. In case of training of welders we followed a different way. Learning from training methods of high sophisticated sportsmen a virtual welding training system (VWTS) using real small arc was developed. Welder were trained step by step but with permanent instructions from the computer control unit to correct the practice. In addition there is a permanent changing between training by VWTS and real welding in a welding cabin. [ABSTRACT FROM AUTHOR]

The aim of investigation of hybrid laser-arc welding lies in accumulation of knowledges about this process applicable to producing of pipe joints. Number of aspects are considered, such as tolerances, effect of environment, mobility of equipment and procedure in irregularities of position. The main attention is paid to investigation of effect of laser welding with large penetration depth in making of high-quality joint in root face of 6-10 mm. Performed is a comparison of different positions of laser beam and arc, which can be used in hybrid welding with different types of preparation for welding. Procedure of production of pipe joints lies in downhill welding of two vertical welds, that is standard practice for pipeline construction and significantly reduces degree of freedom in positioning of laser beam and arc, necessary for obtaining technological optimum parameters during joint formation. Weld bead is elongated by means of continuous movement of torch, that allows made the first pass using hybrid welding and cover pass by arc for one welding cycle in order to obtain closed seam profile in joints of up to 12 mm thickness. Besides, the latter process provides positive effect on mechanical properties of the weld metal. 3 Ref., 4 Tables, 8 Figures. [ABSTRACT FROM AUTHOR]

The health care settings of today are rapidly evolving in form and function, challenging nurse executives to adopt, adapt, and develop new ways to lead and find professional fulfillment in their roles. The organizational design of many health care settings has changed from a functional to a matrix structure to facilitate more effective and efficient operations. While the structures and reporting relationship of contemporary nurse executives may have changed significantly, the primary responsibility of championing the advancement of the profession of nursing remains essential. The mastery of change management methods is critical for the nurse executive to successfully lead in today's dynamic health care settings. A well-developed and actualized nursing professional practice model is a foundational tool for the nurse executive to employ to advance the profession of nursing in any health care setting or structure. This article describes how a nurse executive used change management methods and principles to lead the development of a new network-wide unifying nursing professional practice model in a highly matrixed health care setting., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Dissolution testing is an important physiochemical test for the development of solid oral dosage forms, tablets, and capsules. As a quality control test, the dissolution test is used for assessment of drug product quality and is specified for batch release and regulatory stability studies. In vitro dissolution test results can often be correlated with the biopharmaceutical behavior of a product.This article provides a summary of views from major global agencies (Europe, Japan, United States), pharmacopoeias, academia, and industry. Based on available guidance and literature, this article summarizes highlights for development and validation of a suitable dissolution method, setting appropriate specifications, in vitro-in vivo comparison, and how to obtain a biowaiver., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Except for meeting the individual palliative need, the benefit of breast surgery in primary metastatic breast cancer (PMBC), also known as de novo metastatic breast cancer, on long-term outcomes remains controversial. Twenty-four hundred and one patients with metastatic breast cancer, enrolled between 2000 and 2011 in two prospective non-interventional studies on targeted therapy, were screened with respect to this question., Methods: One study investigated trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in addition to mainly first-line chemotherapy. The other observed bevacizumab added to chemotherapy as first-line treatment for mostly HER2-negative disease., Results: Five-hundred and seventy (24%) patients presented with PMBC, and valid information on resection of the primary tumour was available for 568 women. Out of these, 426 (75%) underwent local resection. The latter group was characterised by less overall metastatic burden and a lower proportion of T4 tumours. No major differences were observed with respect to age, hormone receptor and HER2 status, visceral disease and performance status. Numerically, the surgery group showed a slightly favourable progression-free survival (PFS, medians: 13.6 versus 11.8 months; P = 0.18) and overall survival (OS, 34.1 versus 31.7; P = 0.23). However, in multivariable analysis, including all other univariably significant parameters, no trend for better outcome after surgery remained detectable, neither for PFS (hazard ratio 0.99; P = 0.92) nor for OS (0.95; P = 0.71)., Conclusions: Our findings suggest no major survival benefit for local resection in the overall PMBC population treated with modern targeted therapies. However, further analyses are warranted to define specific risk groups, which may benefit from surgical removal of the primary., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Trastuzumab is part of the standard treatment in patients with human epidermal growth factor receptor 2-positive early breast cancer in addition to (neo)adjuvant chemotherapy. This German prospective noninterventional study, which included major patient cohorts underrepresented in the pivotal randomized studies, examined the generalizability of the results of those studies., Patients and Methods: Between 2006 and 2012, 4,027 patients were enrolled and treated with trastuzumab; they were unselected regarding age or concomitant/sequential adjuvant chemotherapy. Long-term outcome data were obtained in yearly intervals. All analyses were descriptive in nature., Results: Among 3,940 evaluable patients, 26% were elderly (older than 65 years of age). More than half of the population had pN0 tumor stage. Ninety-four percent received chemotherapy: 78% as adjuvant treatment and 14% as neoadjuvant treatment, 2% both. Anthracyclines were administered in 87% and taxanes in 66%. Trastuzumab was stopped prematurely in 9% (because of cardiotoxicity in 3.5%). Recurrence-free survival was 90.0% (95% confidence interval [CI], 88.9%-91.1%) and 82.8% (95% CI, 81.2%-84.4%) after 3 and 5 years, respectively. The corresponding figures for overall survival were 96.8% (95% CI, 96.1%-97.6%) and 90.0% (95% CI, 88.6%-91.4%). Pathological primary tumor size, lymph node involvement, and hormone receptor status had the greatest independent effect on recurrence risk. Cardiac function toxicity of National Cancer Institute common toxicity criteria grade ≥2 and ≥3 was observed in 2.5% and less than 1% of patients, respectively., Conclusion: The maturing follow-up data seem to confirm the beneficial results of trastuzumab treatment for early breast cancer from the randomized studies. Moreover, these findings support use of trastuzumab-based therapy in patients groups less commonly included in the phase III trials (e.g., elderly patients and those with stage I disease). The Oncologist 2017;22:131-138 Implications for Practice: On the basis of the results of large pivotal phase III studies, the inclusion of trastuzumab in adjuvant treatment regimens for human epidermal growth factor receptor 2-positive breast cancer is standard of care. However, in these trials, elderly patients, those with comorbidities, and/or those with contraindications or refusal of cytotoxic chemotherapy are typically underrepresented. This study provides data on observed treatment options, outcomes, and risks in a wider, unselected patient population (including more than 1,000 patients with stage I disease), treated routinely in several institutions of varying size and location across Germany., (© AlphaMed Press 2017.)

Alzheimer disease (AD) is the most common form of dementia and characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles consisting of hyperphosphorylated tau, atrophy, and progressive neurodegeneration. While the familial, early onset form of AD is known to be caused by specific mutations in genes encoding presenilin 1, presenilin 2, or amyloid-β protein precursor, the underlying mechanisms leading to the development of sporadic AD are still not known. The major risk factors are, however, aging and APOE ε4. Here we review the latest evidence for the involvement of malfunctioning insulin signaling, dysfunction of mitochondria-associated membranes, cerebrovascular changes, increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic dysfunction in early stages of AD. We focus on whether the changes in these processes precede or succeed the earliest symptoms in AD patients, i.e., minimal cognitive impairment. Since changes in Aβ processing are probably a key event in AD we also highlight the relationship of the above mentioned processes with the formation, secretion, aggregation, and toxicity of Aβ. Based on our literature findings we propose a model in which insulin dysfunction, pathological cerebrovascular changes, dysfunction of mitochondria-associated membranes, and/or synaptic changes are likely to interact with each other, thereby initiating and facilitating the development of AD pathology by accelerating the production and deposition of Aβ. Increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic loss follow these events, but still occur very early in AD.

Aberrant DNA methylation patterns have been linked to molecular and cellular alterations in the aging brain. Caloric restriction (CR) and upregulation of antioxidants have been proposed as interventions to prevent or delay age-related brain pathology. Previously, we have shown in large cohorts of aging mice, that age-related increases in DNA methyltransferase 3a (Dnmt3a) immunoreactivity in the mouse hippocampus were attenuated by CR, but not by overexpression of superoxide dismutase 1 (SOD1). Here, we investigated age-related alterations of 5-methylcytidine (5-mC), a marker of DNA methylation levels, in a hippocampal subregion-specific manner. Examination of 5-mC immunoreactivity in 12- and 24-month-old wild type (WT) mice on control diet, mice overexpressing SOD1 on control diet, wild type mice on CR, and SOD1 mice on CR, indicated an age-related increase in 5-mC immunoreactivity in the hippocampal dentate gyrus, CA3, and CA1-2 regions, which was prevented by CR but not by SOD1 overexpression. Moreover, positive correlations between 5-mC and Dnmt3a immunoreactivity were observed in the CA3 and CA1-2. These findings suggest a crucial role for DNA methylation in hippocampal aging and in the mediation of the beneficial effects of CR on aging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aberrations in epigenetic marks have been associated with aging of the brain while caloric restriction (CR) and upregulation of endogenous antioxidants have been suggested as tools to attenuate the aging process. We have recently observed age-related increases in levels of 5-methylcytidine (5-mC) and DNA methyltransferase 3a (Dnmt3a) in the mouse hippocampus. Most of those age-related changes in these epigenetically relevant markers were prevented by CR but not by transgenic overexpression of the endogenous antioxidant superoxide dismutase 1 (SOD1). As recent work has suggested a distinct role for hydroxymethylation in epigenetic regulation of gene expression in the brain, the current study investigated age-related changes of 5-hydroxymethylcytosine (5-hmC) in the mouse hippocampus, and furthermore tested whether CR and transgenic upregulation of SOD1 affected any age-related changes in 5-hmC. Immunohistochemical analyses of 5-hmC in 12- and 24-month-old wild-type and transgenic mice overexpressing SOD1, which were kept under either a control or a calorie restricted diet, revealed an increase of 5-hmC immunoreactivity occurring with aging in the hippocampal dentate gyrus, CA3 and CA1-2 regions. Moreover, CR, but not overexpression of SOD1, prevented the age-related increase in the CA3 region. These findings indicate that the aging process in mice is connected with changes in epigenetic machinery in the hippocampus and suggest that CR acts by influencing epigenetic regulation.

The qualification process for ensuring that a paddle or basket apparatus is suitable for its intended use is a highly debated and controversial topic. Different instrument qualification and suitability methods have been proposed by the pharmacopeias and regulatory bodies. In an effort to internationally harmonize dissolution apparatus suitability requirements, the International Pharmaceutical Federation's (FIP) Dissolution/Drug Release Special Interest Group (SIG) reviewed current instrument suitability requirements listed in the US, European, and Japanese pharmacopeias and the International Conference on Harmonization (ICH) Topic Q4B on harmonization of pharmacopoeial methods, in its Annex 7, Dissolution Test General. In addition, the SIG reviewed the Food and Drug Administration (FDA) Draft Guidance for Industry, "The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2-Current Good Manufacturing Practice (CGMP)" and the related ASTM Standard E2503-07. Based on this review and several in-depth discussions, the FIP Dissolution/Drug Release SIG recommends that the qualification of a dissolution test instrument should be performed following the calibration requirements as indicated in the FDA (draft) guidance. If additional system performance information is desired, a performance verification test using US Pharmacopeia Reference Standard tablet or an established in-house reference product can be conducted. Any strict requirement on the use of a specific performance verification test tablet is not recommended at this time.

A novel assay for factor XIII is described that utilizes exclusively small synthetic peptides as substrates for the cross-linking reaction catalyzed by activated factor XIII (FXIIIa). The acyl donor substrate (selection peptide) is immobilized on a microplate via biotin while the acyl acceptor substrate (detection peptide) is labeled with the fluorochrome Oregon green to allow sensitive detection without the need for secondary enzyme systems for signal amplification. Starting with an amino acid sequence from the fibrin gamma-chain (GQQHHLGGAKQAGDV) as a prototype peptide, the influence of amino acid exchanges were investigated with respect to their impact on the FXIIIa-catalyzed reaction. It was found that FXIIIa readily accepts a broad range of substrate peptides, with a proline neighboring the essential lysine having the most detrimental effect. The assay appears to be valuable for the molecular characterization of factor XIII and may be used for a deeper investigation into the substrate requirements of this final enzyme of wound repair, and eventually also for the characterization of other transglutaminases.

In a large Czochralski-grown Si(1-x)Ge(x) (0.02

The time and frequency of wet and dry root canal instrumentation of teeth with apical periodontitis were compared. The importance of negative microbiological culture for the success rate and for the number of treatment appointments was determined. According to the microbiological and clinical results wet instrumentation is the more effective treatment. Microbiological testing is not requested for routine use.