Integrated Platform for Testing MEMS Mechanical Properties at the Wafer Scale by the IMaP Methodology

Extracts basic mechanical properties such as Young's modulus and cantilever curvature

Endoscopic and surgical treatment outcomes of colitis-associated advanced colorectal neoplasia:a multicenter cohort study

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia or colorectal cancer). The authors aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD, and (2) identify factors associated with treatment choice. MATERIAL AND METHODS: In this retrospective multicenter cohort study, the authors used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic advanced neoplasia (AN) between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine &amp; Gray's subdistribution hazard models were used to assess adjusted subdistribution hazard ratios for metachronous neoplasia and associations with treatment choice. RESULTS: The authors included 189 patients (high-grade dysplasia n =81; colorectal cancer n =108). Patients were treated with proctocolectomy ( n =33), (sub)total colectomy ( n =45), partial colectomy ( n =56) and endoscopic resection ( n =38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn's disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n =22, partial colectomy n =8, endoscopic resection n =13). The authors found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (adjusted subdistribution hazard ratios 4.16, 95% CI 1.64-10.54, P &lt;0.01) compared with (sub)total colectomy. CONCLUSION: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance.</p

Endoscopic and surgical treatment outcomes of colitis-associated advanced colorectal neoplasia:a multicenter cohort study

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia or colorectal cancer). The authors aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD, and (2) identify factors associated with treatment choice.MATERIAL AND METHODS: In this retrospective multicenter cohort study, the authors used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic advanced neoplasia (AN) between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine &amp; Gray's subdistribution hazard models were used to assess adjusted subdistribution hazard ratios for metachronous neoplasia and associations with treatment choice.RESULTS: The authors included 189 patients (high-grade dysplasia n =81; colorectal cancer n =108). Patients were treated with proctocolectomy ( n =33), (sub)total colectomy ( n =45), partial colectomy ( n =56) and endoscopic resection ( n =38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn's disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n =22, partial colectomy n =8, endoscopic resection n =13). The authors found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (adjusted subdistribution hazard ratios 4.16, 95% CI 1.64-10.54, P &lt;0.01) compared with (sub)total colectomy.CONCLUSION: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance.</p

Hydrodynamic effects on coalescence.

The goal of this project was to design, build and test novel diagnostics to probe the effect of hydrodynamic forces on coalescence dynamics. Our investigation focused on how a drop coalesces onto a flat surface which is analogous to two drops coalescing, but more amenable to precise experimental measurements. We designed and built a flow cell to create an axisymmetric compression flow which brings a drop onto a flat surface. A computer-controlled system manipulates the flow to steer the drop and maintain a symmetric flow. Particle image velocimetry was performed to confirm that the control system was delivering a well conditioned flow. To examine the dynamics of the coalescence, we implemented an interferometry capability to measure the drainage of the thin film between the drop and the surface during the coalescence process. A semi-automated analysis routine was developed which converts the dynamic interferogram series into drop shape evolution data

On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

In this study, an integrated approach is developed for the formation, identification and biological characterization of electrochemical conversion products of p38α mitogen-activated protein kinase inhibitors. This work demonstrates the hyphenation of an electrochemical reaction cell with a continuous-flow bioaffinity assay and parallel LC-HR-MS. Competition of the formed products with a tracer (SKF-86002) that shows fluorescence enhancement in the orthosteric binding site of the p38α kinase is the readout for bioaffinity. Parallel HR-MSn experiments provided information on the identity of binders and non-binders. Finally, the data produced with this on-line system were compared to electrochemical conversion products generated off-line. The electrochemical conversion of 1-{6-chloro-5-[(2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazine-1-carbonyl]-3aH-indol-3-yl}-2-morpholinoethane-1,2-dione resulted in eight products, three of which showed bioaffinity in the continuous-flow p38α bioaffinity assay used. Electrochemical conversion of BIRB796 resulted, amongst others, in the formation of the reactive quinoneimine structure and its corresponding hydroquinone. Both products were detected in the p38α bioaffinity assay, which indicates binding to the p38α kinase

PROGNOSTIC IMPLICATION OF THE MITRAL VALVE TENTING GEOMETRY IN PATIENTS WITH DILATED CARDIOMYOPATHY: TRANSTHORACIC REAL-TIME 3D ECHOCARDIOGRAPHIC STUDY

BACKGROUND: The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of phospholamban R14del mutation carriers. METHODS AND RESULTS: Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 1.4-2.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, whereas for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively. CONCLUSIONS: Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is, therefore, advised from adolescence onwards

A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering

To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome. In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin response, following up associations with p < 1 × 10(-4) (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in ABCG2, LPA and APOE. No new SNPs were found associated with statin response. The GRS was associated with reduced statin response: 0.0394 mmol/l per allele (95% CI: 0.0171-0.0617, p = 5.37 × 10(-4)). The GRS was associated with statin response, but the small effect size (˜2% of the average low-density lipoprotein cholesterol reduction) limits applicabilit

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

High fidelity frictional models for MEMS.

The primary goals of the present study are to: (1) determine how and why MEMS-scale friction differs from friction on the macro-scale, and (2) to begin to develop a capability to perform finite element simulations of MEMS materials and components that accurately predicts response in the presence of adhesion and friction. Regarding the first goal, a newly developed nanotractor actuator was used to measure friction between molecular monolayer-coated, polysilicon surfaces. Amontons law does indeed apply over a wide range of forces. However, at low loads, which are of relevance to MEMS, there is an important adhesive contribution to the normal load that cannot be neglected. More importantly, we found that at short sliding distances, the concept of a coefficient of friction is not relevant; rather, one must invoke the notion of 'pre-sliding tangential deflections' (PSTD). Results of a simple 2-D model suggests that PSTD is a cascade of small-scale slips with a roughly constant number of contacts equilibrating the applied normal load. Regarding the second goal, an Adhesion Model and a Junction Model have been implemented in PRESTO, Sandia's transient dynamics, finite element code to enable asperity-level simulations. The Junction Model includes a tangential shear traction that opposes the relative tangential motion of contacting surfaces. An atomic force microscope (AFM)-based method was used to measure nano-scale, single asperity friction forces as a function of normal force. This data is used to determine Junction Model parameters. An illustrative simulation demonstrates the use of the Junction Model in conjunction with a mesh generated directly from an atomic force microscope (AFM) image to directly predict frictional response of a sliding asperity. Also with regards to the second goal, grid-level, homogenized models were studied. One would like to perform a finite element analysis of a MEMS component assuming nominally flat surfaces and to include the effect of roughness in such an analysis by using a homogenized contact and friction models. AFM measurements were made to determine statistical information on polysilicon surfaces with different roughnesses, and this data was used as input to a homogenized, multi-asperity contact model (the classical Greenwood and Williamson model). Extensions of the Greenwood and Williamson model are also discussed: one incorporates the effect of adhesion while the other modifies the theory so that it applies to the case of relatively few contacting asperities