Blending PEG-based polymers and their use in surface micro-patterning by the FIMIC method to obtain topographically smooth patterns of elasticity

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.We have designed and fabricated a library of polyethylene glycol (PEG)-based polymer blends, including blends of two PEG-based polymers that are liquid at room temperature where the optimisation of the blending method allows for the incorporation of higher molecular-weight PEG-based polymers which are solid at room temperature. The absence of a solvent in these blends makes them perfect candidates for use in our recently developed Fill-Molding in Capillaries (FIMIC) patterning method. As our FIMIC samples have shown to be not completely smooth (a small topography up to several nanometers has been seen previously), and this is likely to affect the cellular behaviour, we have improved our technique in order to obtain virtually smooth samples that exhibit a pattern of elasticity only. It is demonstrated that, by taking advantage of the differential swelling of the pattern components, we can level out the undesired topographic difference. In particular, by employing blends of materials, (1) the swelling degree of each component can be fine-tuned to even out any topography and (2) the use of the same blends in the sample, yet with varying cross-linker amounts, ensures the swelling degree and elasticity change without changing the surface chemistry significantly. Genuine, binary patterns of elasticity can thus be fabricated, which are a great asset to study cell migration phenomena in systematic detail.DFG, EXC 314, Unifying Concepts in Catalysi

Hybrid hierarchical patterns of gold nanoparticles and poly(ethylene glycol) microstructures

Hybrid surface micro-patterns composed of topographic structures of polyethylene glycol (PEG)-hydrogels and hierarchical lines of gold nanoparticles (Au NPs) were fabricated on silicon wafers. Micro-sized lines of Au NPs were first obtained on the surface of a silicon wafer via “micro-contact deprinting”, a method recently developed by our group. Topographic micro-patterns of PEG, of both low and high aspect ratio (AR up to 6), were then aligned on the pre-patterned surface via a procedure adapted from the soft lithographic method MIMIC (Micro-Molding in Capillaries), which is denoted as “adhesive embossing”. The result is a complex surface pattern consisting of alternating flat Au NP lines and thick PEG bars. Such patterns provide novel model surfaces for elucidating the interplay between (bio)chemical and physical cues on cell behavior

The efficacy of suppressive antibiotic treatment in patients managed non-operatively for periprosthetic joint infection and a draining sinus

Objectives: Patients with prosthetic joint infections (PJIs) not suitable for curative surgery may benefit from suppressive antibiotic therapy (SAT). However, the usefulness of SAT in cases with a draining sinus has never been investigated. Methods: A multicentre, retrospective observational cohort study was performed in which patients with a PJI and a sinus tract were eligible for inclusion if managed conservatively and if sufficient follow-up data were available (i.e. at least 2 years). SAT was defined as a period of > 6 months of oral antibiotic therapy. Results: SAT was initiated in 63 of 72 (87.5 %) included patients. Implant retention during follow-up was the same in patients receiving SAT vs. no SAT (79.4 % vs. 88.9 %; pCombining double low line0.68). In total, 27 % of patients using SAT experienced side effects. In addition, the occurrence of prosthetic loosening in initially fixed implants, the need for surgical debridement, or the occurrence of bacteremia during follow-up could not be fully prevented with the use of SAT, which still occurred in 42 %, 6.3 %, and 3.2 % of cases, respectively. However, the sinus tract tended to close more often (42 % vs. 13 %; pCombining double low line0.14), and a higher resolution of pain was observed (35 % vs. 14 %; pCombining double low line0.22) in patients receiving SAT. Conclusions: SAT is not able to fully prevent complications in patients with a draining sinus. However, it may be beneficial in a subset of patients, particularly in those with pain or the hindrance of a draining sinus. A future prospective study, including a higher number of patients not receiving SAT, is needed

Standardizing definitions and reporting guidelines for the infertility core outcome set : an international consensus development study

Acknowledgments We would like to thank the consensus development meeting participants and colleagues at the Cochrane Gynaecology and Fertility Group, University of Auckland, New Zealand. Funding This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data or manuscript preparation. Siladitya Bhattacharya was supported by the University of Auckland Foundation Seelye Travelling Fellowship. B.W.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548) This article has not been externally peer reviewed. This article has been published simultaneously in Fertility and SterilityPeer reviewedPublisher PD

Endometrial scratching in women undergoing IVF/ICSI : an individual participant data meta-analysis

Funding No specific funding was sought for this project. The sponsor of this project is the University Medical Center Utrecht (UMC Utrecht), Utrecht, the Netherlands. The sponsor was not involved in the study design, data interpretation, or writing of the manuscript.Peer reviewedPublisher PD

Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity

<p>Abstract</p> <p>Background</p> <p>Malaria parasite infectivity to mosquitoes has been measured in a variety of ways and setting, includind direct feeds of and/or membrane feeding blood collected from randomly selected or gametocytemic volunteers. <it>Anopheles gambiae s.l </it>is the main vector responsible of <it>Plasmodium falciparum </it>transmission in Bancoumana and represents about 90% of the laboratory findings, whereas <it>Plasmodium malariae </it>and <it>Plasmodium ovale </it>together represent only 10%.</p> <p>Materials and methods</p> <p>Between August 1996 and December 1998, direct and membrane feeding methods were compared for the infectivity of children and adolescent gametocyte carriers to anopheline mosquitoes in the village of Bancoumana in Mali. Gametocyte carriers were recruited twice a month through a screening of members of 30 families using Giemsa-stained thick blood smears. F1 generation mosquitoes issued from individual female wild mosquitoes from Bancoumana were reared in a controlled insectary conditions and fed 5% sugar solution in the laboratory in Bamako, until the feeding day when they are starved 12 hours before the feeding experiment. These F1 generation mosquitoes were divided in two groups, one group fed directly on gametocyte carriers and the other fed using membrane feeding method.</p> <p>Results</p> <p>Results from 372 <it>Plasmodium falciparum </it>gametocyte carriers showed that children aged 4–9 years were more infectious than adolescents (p = 0.039), especially during the rainy season. Data from 35 carriers showed that mosquitoes which were used for direct feeding were about 1.5 times more likely to feed (p < 0.001) and two times more likely to become infected, if they fed (p < 0.001), than were those which were used for membrane feeding. Overall, infectivity was about three-times higher for direct feeding than for membrane feeding (p < 0.001).</p> <p>Conclusion</p> <p>Although intensity of infectivity was lower for membrane feeding, it could be a surrogate to direct feeding for evaluating transmission-blocking activity of candidate malaria vaccines. An optimization of the method for future trials would involve using about three-times more mosquitoes than would be used for direct feeding.</p

Large-Vessel Vasculitis:Interobserver Agreement and Diagnostic Accuracy of (18)F-FDG-PET/CT

Introduction. F-18-FDG-PET visualises inflammation. Both atherosclerosis and giant cell arteritis cause vascular inflammation, but distinguishing the two may be difficult. The goal of this study was to assess interobserver agreement and diagnostic accuracy of F-18-FDG-PET for the detection of large artery involvement in giant cell arteritis (GCA). Methods. 31 F-18-FDG-PET/CT scans were selected from 2 databases. Four observers assessed vascularwall F-18-FDGuptake, initially without and subsequently with predefined observer criteria (i.e., vascular wall F-18-FDG uptake compared to liver or femoral artery F-18-FDG uptake). External validation was performed by two additional observers. Sensitivity and specificity of F-18-FDG-PET were determined by comparing scan results to a consensus diagnosis. Results. The highest interobserver agreement (kappa: 0.96 in initial study and 0.79 in external validation) was observed when vascular wall F-18-FDG uptake higher than liver uptake was used as a diagnostic criterion, although agreement was also good without predefined criteria (kappa: 0.68 and 0.85). Sensitivity and specificity were comparable for these methods. The criterion of vascular wall F-18-FDG uptake equal to liver F-18-FDG uptake had low specificity. Conclusion. Standardization of image assessment for vascular wall F-18-FDG uptake promotes observer agreement, enables comparative studies, and does not appear to result in loss of diagnostic accuracy compared to nonstandardized assessment

Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study

STUDY QUESTION:Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER:Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY:Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION:Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS:Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE:Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION:We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS:A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S):This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER:Core Outcome Measures in Effectiveness Trials Initiative: 1023.J M N Duffy, S Bhattacharya, S Bhattacharya, M Bofill, B Collura, C Curtis ... et al

Unification of New Zealand's local vertical datums: iterative gravimetric quasigeoid computations

New Zealand uses 13 separate local vertical datums (LVDs) based on normal-orthometric-corrected precise geodetic levelling from 12 different tide-gauges. We describe their unification using a regional gravimetric quasigeoid model and GPS-levelling data on each LVD. A novel application of iterative quasigeoid computation is used, where the LVD offsets computed from earlier models are used to apply additional gravity reductions from each LVD to that model. The solution converges after only three iterations yielding LVD offsets ranging from 0.24 m to 0.58 m with an average standard deviation of 0.08 m. The so-computed LVD offsets agree, within expected data errors, with geodetically levelled height differences at common benchmarks between adjacent LVDs. This shows that iterated quasigeoid models do have a role in vertical datum unification

A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma

Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is under-investigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (IG) and T-cell receptor (TR) rearrangements was performed in paired cHL diagnosis and recurrences of 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal IG rearrangements were detected by next-generation sequencing (NGS) in 69/120 (58%) diagnosis and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24/34 patients (71%). Clonally unrelated cHL was observed in 10/34 patients (29%) as determined by IG-NGS clonality assessment, and confirmed by the identification of predominantly mutually exclusive gene mutations in the paired cHL samples. In recurrences of &gt;2 years, ~60% of cHL patients for which the clonal relationship could be established showed a second primary cHL. Clonal TR gene rearrangements were identified in 14/125 samples (11%), and TCL-associated gene mutations were detected in 7/14 samples. Retrospective pathology review with integration of the molecular findings were consistent with an underlying TCL in 5 patients aged &gt;50 years. This study shows that cHL recurrences, especially after 2 years, sometimes represent a new primary cHL or TCL mimicking cHL, as uncovered by NGS-based IG/TR clonality testing and gene mutation analysis. Given the significant therapeutic consequences, molecular testing of a presumed relapse in cHL is crucial for subsequent appropriate treatment strategies adapted to the specific lymphoma presentation.</p