Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy:An analysis of health equity based on a randomised trial

Background: We have addressed health equity attained by fecal immunochemical testing (FIT) and primary colonoscopy (PCOL), respectively, in the randomised controlled screening trial SCREESCO conducted in Sweden. Methods: We analysed data on the individuals recruited between March 2014, and March 2020, within the study registered with ClinicalTrials.gov, NCT02078804. Swedish population registry data on educational level, household income, country of birth, and marital status were linked to each 60-year-old man and woman who had been randomised to two rounds of FIT 2 years apart (n = 60,123) or once-only PCOL (n = 30,390). Furthermore, we geo-coded each study individual to his/her residential area and assessed neighbourhood-level data on deprivation, proportion of non-Western immigrants, population density, and average distance to healthcare center for colonoscopy. We estimated adjusted associations of each covariate with the colonoscopy attendance proportion out of all invited to respective arms; ie, the preferred outcome for addressing health equity. In the FIT arm, the test uptake and the colonoscopy uptake among the test positives were considered as the secondary outcomes. Findings: We found a marked socioeconomic gradient in the colonoscopy attendance proportion in the PCOL arm (adjusted odds ratio [95% credibility interval] between the groups categorised in the highest vs. lowest national quartile for household income: 2.20 [2.01-2.42]) in parallel with the gradient in the test uptake of the FIT x 2 screening (2.08 [1.96-2.20]). The corresponding gradient in the colonoscopy attendance proportion out of all invited to FIT was less pronounced (1.29 [1.16-1.42]), due to higher proportions of FIT positives in socioeconomically disadvantaged groups. Interpretation: The unintended risk of exacerbating inequalities in health by organised colorectal cancer screening may be higher with a PCOL strategy than a FIT strategy, despite parallel socioeconomic gradients in uptake

Picropodophyllin causes mitotic arrest and catastrophe by depolymerizing microtubules via Insulin-like growth factor-1 receptor-independent mechanism

Picropodophyllin (PPP) is an anticancer drug undergoing clinical development in NSCLC. PPP has been shown to suppress IGF-1R signaling and to induce a G2/M cell cycle phase arrest but the exact mechanisms remain to be elucidated. The present study identified an IGF-1-independent mechanism of PPP leading to pro-metaphase arrest. The mitotic block was induced in human cancer cell lines and in an A549 xenograft mouse but did not occur in normal hepatocytes/mouse tissues. Cell cycle arrest by PPP occurred in vitro and in vivo accompanied by prominent CDK1 activation, and was IGF-1R-independent since it occurred also in IGF-1R-depleted and null cells. The tumor cells were not arrested in G2/M but in mitosis. Centrosome separation was prevented during mitotic entry, resulting in a monopolar mitotic spindle with subsequent prometaphase-arrest, independent of Plk1/Aurora A or Eg5, and leading to cell features of mitotic catastrophe. PPP also increased soluble tubulin and decreased spindle-associated tubulin within minutes, indicating that it interfered with microtubule dynamics. These results provide a novel IGF-1R-independent mechanism of antitumor effects of PPP

Genuine Counterfactual Communication with a Nanophotonic Processor

In standard communication information is carried by particles or waves. Counterintuitively, in counterfactual communication particles and information can travel in opposite directions. The quantum Zeno effect allows Bob to transmit a message to Alice by encoding information in particles he never interacts with. The first suggested protocol not only required thousands of ideal optical components, but also resulted in a so-called "weak trace" of the particles having travelled from Bob to Alice, calling the scalability and counterfactuality of previous proposals and experiments into question. Here we overcome these challenges, implementing a new protocol in a programmable nanophotonic processor, based on reconfigurable silicon-on-insulator waveguides that operate at telecom wavelengths. This, together with our telecom single-photon source and highly-efficient superconducting nanowire single-photon detectors, provides a versatile and stable platform for a high-fidelity implementation of genuinely trace-free counterfactual communication, allowing us to actively tune the number of steps in the Zeno measurement, and achieve a bit error probability below 1%, with neither post-selection nor a weak trace. Our demonstration shows how our programmable nanophotonic processor could be applied to more complex counterfactual tasks and quantum information protocols.Comment: 6 pages, 4 figure

Real-life experience with non-vitamin K antagonist oral anticoagulants versus warfarin in patients undergoing elective cardioversion of atrial fibrillation

Background Nonvitamin K antagonist oral anticoagulants (NOACs) are increasingly used in patients with atrial fibrillation (AF) undergoing elective cardioversion (ECV). The aim was to investigate the use of NOACs and warfarin in ECV in a real-life setting and to assess how the chosen regimen affected the delay to ECV and rate of complications. Methods Consecutive AF patients undergoing ECVs in the city hospitals of Helsinki between January 2015 and December 2016 were studied. Data on patient characteristics, delays to cardioversion, anticoagulation treatment, acute ( Results Nine hundred patients (59.2% men; mean age, 68.0 +/- 10.0) underwent 992 ECVs, of which 596 (60.0%) were performed using NOACs and 396 (40.0%) using warfarin. The mean CHA(2)DS(2)-VASc score was 2.5 (+/- 1.6). In patients without previous anticoagulation treatment, NOACs were associated with a shorter mean time to cardioversion than warfarin (51 versus. 68 days, respectively; p <.001). Six thromboembolic events (0.6%) occurred: 4 (0.7%) in NOAC-treated patients and 2 (0.5%) in warfarin-treated patients. Clinically relevant bleeding events occurred in seven patients (1.8%) receiving warfarin and three patients (0.5%) receiving NOACs. Anticoagulation treatment was altered for 99 patients (11.0%) during the study period, with the majority (88.2%) of changes from warfarin to NOACs. Conclusions In this real-life study, the rates of thromboembolic and bleeding complications were low in AF patients undergoing ECV. Patients receiving NOAC therapy had a shorter time to cardioversion and continued their anticoagulation therapy more often than patients on warfarin.Peer reviewe

S53P4 bioactive glass scaffolds induce BMP expression and integrative bone formation in a critical-sized diaphysis defect treated with a single-staged induced membrane technique

Surgical management of critical-sized diaphyseal defects involves multiple challenges, and up to 10% result in delayed or non-union. The two-staged induced membrane technique is successfully used to treat these defects, but it is limited by the need of several procedures and bone graft. Repeated procedures increase costs and morbidity, while grafts are subject to donor-site complications and scarce availability. To transform this two-staged technique into one graft-independent procedure, we developed amorphous porous scaffolds sintered from the clinically used bioactive glass S53P4. This work constitutes the first evaluation of such scaffolds in vivo in a critical-sized diaphyseal defect in the weight-bearing rabbit femur. We provide important knowledge and prospects for future development of sintered S53P4 scaffolds as a bone substitute. Critical-sized diaphysis defects are complicated by inherent sub-optimal healing conditions. The two staged induced membrane technique has been used to treat these challenging defects since the 1980 & rsquo;s. It involves temporary implantation of a membrane-inducing spacer and subsequent bone graft defect filling. A single-staged, graft-independent technique would reduce both socio-economic costs and patient morbidity. Our aim was to enable such single-staged approach through development of a strong bioactive glass scaffold that could replace both the spacer and the graft filling. We constructed amorphous porous scaffolds of the clinically used bioactive glass S53P4 and evaluated them in vivo using a critical sized defect model in the weight-bearing femur diaphysis of New Zealand White rabbits. S53P4 scaffolds and standard polymethylmethacrylate spacers were implanted for 2, 4, and 8 weeks. Induced membranes were confirmed histologically, and their osteostimulative activity was evaluated through RT-qPCR of bone morphogenic protein 2, 4, and 7 (BMPs). Bone formation and osseointegration were examined using histology, scanning electron microscopy, energy-dispersive X-ray analysis, and micro-computed tomography imaging. Scaffold integration, defect union and osteosynthesis were assessed manually and with X-ray projections. We demonstrated that S53P4 scaffolds induce osteostimulative membranes and produce osseointegrative new bone formation throughout the scaffolds. We also demonstrated successful stable scaffold integration with early defect union at 8 weeks postoperative in critical-sized segmental diaphyseal defects with implanted sintered amorphous S53P4 scaffolds. This study presents important considerations for future research and the potential of the S53P4 bioactive glass as a bone substitute in large diaphyseal defects. Statement of significance Surgical management of critical-sized diaphyseal defects involves multiple challenges, and up to 10% result in delayed or non-union. The two-staged induced membrane technique is successfully used to treat these defects, but it is limited by the need of several procedures and bone graft. Repeated procedures increase costs and morbidity, while grafts are subject to donor-site complications and scarce availability. To transform this two-staged technique into one graft-independent procedure, we developed amorphous porous scaffolds sintered from the clinically used bioactive glass S53P4. This work constitutes the first evaluation of such scaffolds in vivo in a critical-sized diaphyseal defect in the weight-bearing rabbit femur. We provide important knowledge and prospects for future development of sintered S53P4 scaffolds as a bone substitute. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )Peer reviewe

S53P4 bioactive glass scaffolds induce BMP expression and integrative bone formation in a critical-sized diaphysis defect treated with a single-stage d induce d membrane technique

Surgical management of critical-sized diaphyseal defects involves multiple challenges, and up to 10% result in delayed or non-union. The two-staged induced membrane technique is successfully used to treat these defects, but it is limited by the need of several procedures and bone graft. Repeated procedures increase costs and morbidity, while grafts are subject to donor-site complications and scarce availability. To transform this two-staged technique into one graft-independent procedure, we developed amorphous porous scaffolds sintered from the clinically used bioactive glass S53P4. This work constitutes the first evaluation of such scaffolds in vivo in a critical-sized diaphyseal defect in the weight-bearing rabbit femur. We provide important knowledge and prospects for future development of sintered S53P4 scaffolds as a bone substitute. Critical-sized diaphysis defects are complicated by inherent sub-optimal healing conditions. The two staged induced membrane technique has been used to treat these challenging defects since the 1980 & rsquo;s. It involves temporary implantation of a membrane-inducing spacer and subsequent bone graft defect filling. A single-staged, graft-independent technique would reduce both socio-economic costs and patient morbidity. Our aim was to enable such single-staged approach through development of a strong bioactive glass scaffold that could replace both the spacer and the graft filling. We constructed amorphous porous scaffolds of the clinically used bioactive glass S53P4 and evaluated them in vivo using a critical sized defect model in the weight-bearing femur diaphysis of New Zealand White rabbits. S53P4 scaffolds and standard polymethylmethacrylate spacers were implanted for 2, 4, and 8 weeks. Induced membranes were confirmed histologically, and their osteostimulative activity was evaluated through RT-qPCR of bone morphogenic protein 2, 4, and 7 (BMPs). Bone formation and osseointegration were examined using histology, scanning electron microscopy, energy-dispersive X-ray analysis, and micro-computed tomography imaging. Scaffold integration, defect union and osteosynthesis were assessed manually and with X-ray projections. We demonstrated that S53P4 scaffolds induce osteostimulative membranes and produce osseointegrative new bone formation throughout the scaffolds. We also demonstrated successful stable scaffold integration with early defect union at 8 weeks postoperative in critical-sized segmental diaphyseal defects with implanted sintered amorphous S53P4 scaffolds. This study presents important considerations for future research and the potential of the S53P4 bioactive glass as a bone substitute in large diaphyseal defects. Statement of significance Surgical management of critical-sized diaphyseal defects involves multiple challenges, and up to 10% result in delayed or non-union. The two-staged induced membrane technique is successfully used to treat these defects, but it is limited by the need of several procedures and bone graft. Repeated procedures increase costs and morbidity, while grafts are subject to donor-site complications and scarce availability. To transform this two-staged technique into one graft-independent procedure, we developed amorphous porous scaffolds sintered from the clinically used bioactive glass S53P4. This work constitutes the first evaluation of such scaffolds in vivo in a critical-sized diaphyseal defect in the weight-bearing rabbit femur. We provide important knowledge and prospects for future development of sintered S53P4 scaffolds as a bone substitute. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )Peer reviewe

Floral and environmental gradients on a Late Cretaceous landscape

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116378/1/ecm201282123.pd

Water absorption and hydrothermal performance of PHBV/sisal biocomposites

The performance of biocomposites of poly(hydroxybutyrate-co-valerate) (PHBV) and sisal fibre subjected to hydrothermal tests at different temperatures above the glass transition of PHBV (TH = 26, 36 and 46 °C) was evaluated in this study. The influences of both the fibre content and presence of coupling agent were focused. The water absorption capability and water diffusion rate were considered for a statistical factorial analysis. Afterwards, the physico-chemical properties of water-saturated biocomposites were assessed by Fourier-Transform Infrared Analysis, Size Exclusion Chromatography, Differential Scanning Calorimetry and Scanning Electron Microscopy. It was found that the water diffusion rate increased with both temperature and percentage of fibre, whereas the amount of absorbed water was only influenced by fibre content. The use of coupling agent was only relevant at the initial stages of the hydrothermal test, giving an increase in the diffusion rate. Although the chemical structure and thermal properties of water-saturated biocomposites remained practically intact, the physical performance was considerably affected, due to the swelling of fibres, which internally blew-up the PHBV matrix, provoking cracks and fibre detachment