Response Surface Modeling of Rim Phase Shift Masks

The use of statistically designed experiments provide an efficient method of investigating a lithographic process. Lithographic simulators have also been used as a tool in the investigation of these processes. This paper provides a general methodology for conducting designed experiments in which a computer simulator is the tool used as the data collection device. The rim shifter is a phase shifting technique that was investigated. Response surfaces measuring depth of focus were generated from simulated data. The resolution and depth of focus capabilities of this phase shift technique were also measured by both experimental and simulated data

Response Surface Modelling Utilizing Lithographic Process Simulation

A method of incorporating statistically designed fractional factorial experiments into lithographic process simulation software (PROL1TH/2) has been used to determine input factor interrelationships inherent within a lithographic process. Rotatable Box-Behnken designs with 3 centerpoints were utilized for the experiment. The response surface methodology (RSM) approach was used to analyze the influence of independent factors on a dependant response, and optimize each process. A method of steepest ascent was utilized to produce first-order models, which were verified by lack of fit testing. As optimum operating points were approached, a second-order model was fitted and analyzed. A series of experiments studying the effects of prebake, exposure, post-exposure bake, and development on critical dimension and profile in PROLITH/2 produced response surfaces relating each main factor effect as well as non-linear and interaction effects. Additionally, experiments were conducted to study effects of numerical aperture, coherence, feature size, defocus, and flare on aerial image contrast. Process optimization for the target response value as well as process latitude as it relates to all factors simultaneously was then possible through use of the response surface

Glucagon like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24-hours following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness

Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

Glucagon-like peptide 1 (GLP-1) is a growth factor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a clinical trial in PD patients showed promising first results. Liraglutide and lixisenatide are two newer GLP-1 mimetics which have a longer biological half-life than exendin-4. We previously showed that these drugs have neuroprotective properties in an animal model of Alzheimer's disease. Here we demonstrate the neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20mg/kg i.p.) for 7days, and drugs were injected once-daily for 14days i.p. When comparing exendin-4 (10nmol/kg), liraglutide (25nmol/kg) and lixisenatide (10nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen. Both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro-apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The results demonstrate that in this study, both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of PD

The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics

In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept

Survival after chemotherapy and/or radiotherapy versus self-expanding metal stent insertion in the setting of inoperable esophageal cancer: a case-control study

<p>Abstract</p> <p>Background</p> <p>Our aim was to compare survival of the various treatment modality groups of chemotherapy and/or radiotherapy in relation to SEMS (self-expanding metal stents) in a retrospective case-control study. We have made the hypothesis that the administration of combined chemoradiotherapy improves survival in inoperable esophageal cancer patients.</p> <p>Methods</p> <p>All patients were confirmed histologically as having surgically non- resectable esophageal carcinoma. Included were patients with squamous cell carcinoma, undifferentiated carcinoma as well as Siewert type I--but not type II - esophagogastric junctional adenocarcinoma. The decision to proceed with palliative treatments was taken within the context of a multidisciplinary team meeting and full expert review based on patient's wish, co-morbid disease, clinical metastases, distant metastases, M1 nodal metastases, T4-tumor airway, aorta, main stem bronchi, cardiac invasion, and peritoneal disease. Patients not fit enough to tolerate a radical course of definitive chemo- and/or radiation therapy were referred for self-expanding metal stent insertion. Our approach to deal with potential confounders was to match subjects according to their clinical characteristics (contraindications for surgery) and tumor stage according to diagnostic work-up in four groups: SEMS group (A), Chemotherapy group (B), Radiotherapy group (C), and Chemoradiotherapy group (D).</p> <p>Results</p> <p>Esophagectomy was contraindicated in 155 (35.5%) out of 437 patients presenting with esophageal cancer to the Department of General and Abdominal Surgery of the University Hospital of Mainz, Germany, between November 1997 and November 2007. There were 133 males and 22 females with a median age of 64.3 (43-88) years. Out of 155 patients, 123 were assigned to four groups: SEMS group (A) n = 26, Chemotherapy group (B) n = 12, Radiotherapy group (C) n = 23 and Chemoradiotherapy group (D) n = 62. Mean patient survival for the 4 groups was as follows: Group A: 6.92 ± 8.4 months; Group B: 7.75 ± 6.6 months; Group C: 8.56 ± 9.5 months, and Group D: 13.53 ± 14.7 months. Significant differences in overall survival were associated with tumor histology (<it>P </it>= 0.027), tumor localization (<it>P </it>= 0.019), and type of therapy (<it>P </it>= 0.005), respectively, in univariate analysis. Treatment modality (<it>P </it>= 0.043) was the only independent predictor of survival in multivariate analysis. The difference in overall survival between Group A and Group D was highly significant (<it>P </it>< 0.01) and in favor of Group D. As concerns Group D versus Group B and Group D versus Group C there was a trend towards a difference in overall survival in favor of Group D (<it>P </it>= 0.069 and <it>P </it>= 0.059, respectively).</p> <p>Conclusions</p> <p>The prognosis of inoperable esophageal cancer seems to be highly dependent on the suitability of the induction of patient-specific therapeutic measures and is significantly better, when chemoradiotherapy is applied.</p

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome. Am J Physiol Endocrinol Metab 315: E1087–E1097, 2018. First published August 21, 2018; doi:10.1152/ajpendo.00058.2018.—A 2-day workshop organized by the National Institutes of Health and U.S. Department of Agriculture included 16 presentations focused on the role of diet in alterations of the gastrointestinal microbiome, primarily that of the colon. Although thousands of research projects have been funded by U.S. federal agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority addresses dietary effects, and a small subset is described in sufficient detail to allow reproduction of a study. Whereas there are standards being developed for many aspects of microbiome studies, such as sample collection, nucleic acid extraction, data handling, etc., none has been proposed for the dietary component; thus this workshop focused on the latter specific point. It is important to foster rigor in design and reproducibility of published studies to maintain high quality and enable designs that can be compared in systematic reviews. Speakers addressed the influence of the structure of the fermentable carbohydrate on the microbiota and the variables to consider in design of studies using animals, in vitro models, and human subjects. For all types of studies, strengths and weaknesses of various designs were highlighted, and for human studies, comparisons between controlled feeding and observational designs were discussed. Because of the lack of published, best-diet formulations for specific research questions, the main recommendation is to describe dietary ingredients and treatments in as much detail as possible to allow reproduction by other scientists

Evaluation of POSSUM scoring system in patients with gastric cancer undergoing D2-gastrectomy

BACKGROUND: Risk adjustment and stratification play an important role in quality assurance and in clinical research. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a patient risk prediction model based on 12 patient characteristics and 6 characteristics of the surgery performed. However, because the POSSUM was developed for quality assessment in general surgical units, its performance within specific subgroups still requires evaluation. The aim of the present study was to assess the accuracy of POSSUM in predicting mortality and morbidity in patients with gastric cancer undergoing D2-gastrectomy. METHODS: 137 patients with gastric cancer undergoing gastrectomy were included in this study. Detailed, standardized risk assessments and thorough documentation of the post-operative courses were performed prospectively, and the POSSUM scores were then calculated. RESULTS: The 30- and 90- day mortality rates were 3.6% (n = 5) and 5.8% (n = 8), respectively. 65.7% (n = 90) of patients had normal postoperative courses without major complications, 14.6% (n = 20) had moderate and 13.9% (n = 19) had severe complications. The number of mortalities predicted by the POSSUM-Mortality Risk Score (R1) was double the actual number of mortalities occurring in the median and high-risk groups, and was more than eight times the actual number of mortalities occurring in the low-risk group (R1 < 20%). However, the calculated R1 predicted rather well in terms of severe morbidity or post-operative death in each risk group: in predicted low risk patients the actual occurrence rate (AR) of severe morbidity or post-operative death was 14%, for predicted medium risk patients the AR was 23%, and for predicted high risk patients the AR was 50% (p < 0.05). The POSSUM-Morbidity Risk Score (R2) overestimated the risk of morbidity. CONCLUSION: The POSSUM Score may be beneficial and can be used for assessment of the peri- and post-operative courses of patients with gastric carcinoma undergoing D2-gastrectomy. However, none of the scores examined here are useful for preoperative prediction of postoperative course