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The role of 3D printing in the biomedical field is growing. In this context, photocrosslink-based 3D printing procedures for resorbable polymers stand out. Despite much work, more ...studies are needed on photocuring stereochemistry, new resin additives, new polymers and resin components. As part of these studies it is vital to present the logic used to optimize the amount of each resin constituent and how that effects printing process parameters.
The present manuscript aims to analyze the effects of poly(propylene fumarate) (PPF) resin components and their effect on 3D printing process parameters. Diethyl fumarate (DEF), bisacylphosphine oxide (BAPO), Irgacure 784, 2-hydroxy-4-methoxybenzophenone (HMB) and, for the first time, in biomedical 3D printing, ethyl acetate (EA), were the resin components under investigation in this study. Regarding printing process parameters, Exposure Time, Voxel Depth, and Overcuring Depth were the parameters studied. Taguchi Design of Experiments was used to search for the effect of varying these resin constituent concentrations and 3D printing parameters on the curing behavior of 3D printable PPF resins.
Our results indicate that resins with higher polymer cross-link density, especially those with a higher content of PPF, are able to be printed at higher voxel depth and with greater success (i.e., high yield). High voxel depth, as long as it does not sacrifice required resolution, is desirable as it speeds printing. Nevertheless, the overall process is governed by the correct setup of the voxel depth in relation to overcuring depth. In regards to resin biocompatibility, it was observed that EA is more effective than DEF, the material we had previously relied on. Our preliminary in vitro cytotoxicity tests indicate that the use of EA does not reduce scaffold biocompatibility as measured by standard cytotoxicity testing (i.e., ISO 10993-5). We demonstrate a workpath for resin constituent concentration optimization through thin film tests and photocrosslinkable process optimization.
We report here the results of a study of photo-crosslinkable polymer resin component optimization for the 3D printing of resorbable poly(propylene fumarate) (PPF) scaffolds. Resin additives are initially optimized for PPF thin film printing. Once those parameters have been optimized the 3D printing process parameters for PPF objects with complex, porous shapes can be optimized. The design of experiments to optimize both polymer thin films and complex porous resorbable polymer scaffolds is important as a guess and check, or in some cases a systematic method, are very likely to be too time consuming to accomplish. Previously unstudied resin components and process parameters are reported.
BACKGROUND AND PURPOSE—Flow diversion has emerged as an important tool for the management of intracranial aneurysms. The purpose of this study was to compare flow diversion and traditional ...embolization strategies in terms of safety, efficacy, and clinical outcomes in patients with unruptured, large saccular aneurysms (≥10 mm).
METHODS—Forty patients treated with the Pipeline Embolization Device (PED) were matched in a 1:3 fashion with 120 patients treated with coiling based on patient age and aneurysm size. Fusiform and anterior communicating artery aneurysms were eliminated from the analysis. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared.
RESULTS—There were no differences between the 2 groups in terms of patient age, sex, aneurysm size, and aneurysm location. The rate of procedure-related complications did not differ between the PED (7.5%) and the coil group (7.5%; P=1). At the latest follow-up, a significantly higher proportion of aneurysms treated with PED (86%) achieved complete obliteration compared with coiled aneurysms (41%; P<0.001). In multivariable analysis, coiling was an independent predictor of nonocclusion. Retreatment was necessary in fewer patients in the PED group (2.8%) than the coil group (37%; P<0.001). A similar proportion of patients attained a favorable outcome (modified Rankin Scale, 0–2) in the PED group (92%) and in the coil group (94%; P=0.8).
CONCLUSIONS—The PED provides higher aneurysm occlusion rates than coiling, with no additional morbidity and similar clinical outcomes. These findings suggest that the PED might be a preferred treatment option for large unruptured saccular aneurysms.
Abstract The Maipo River catchment is one of Chile’s most polluted basins. In recent decades, discharges of untreated sewage and organic matter have caused eutrophication and water quality ...degradation. We employed the indigenous silverfish species Basilichthys microlepidotus as a model organism to investigate the process of adaptation and selection on genes influenced by pollution. Using variation at single nucleotide polymorphisms (SNPs), we determined the temporal stability of the population structure patterns previously identified in this species by varying SNPs. We also examined local adaptation to pollution-selected genes. Using the genotypes of 7684 loci in 180 individuals, we identified 429 and 700 loci that may be undergoing selection. We detected these loci using the FSTHET and ARLEQUIN outlier detection software, respectively. Both software packages simultaneously identified a total of 250 loci. B. microlepidotus ' population structure did not change over time at contaminated or unpolluted sites. In addition, our analysis found: (i) selection of genes associated with pollution, consistent with observations in other organisms; (ii) identification of candidate genes that are functionally linked to the same biological processes, molecular functions and/or cellular components that previously showed differential expression in the same populations; and (iii) a candidate gene with differential expression and a non-synonymous substitution.
► This paper introduces a workforce scheduling problem with customer-oriented services. ► The objective is to minimize the required workers, balance workloads and satisfy demands. ► A network based ...approach is proposed to model this problem. ► Two different approaches are tested; an exact method and a heuristic approach. ► The approaches are tested on real instances increasing the coverage by up to 68%.
This paper introduces the multi-activity combined timetabling and crew scheduling problem. The goal of this problem is to schedule the minimum number of workers required in order to successfully visit a set of customers characterized by services needed matched against schedule availability. Two solution strategies are proposed. The first is based on mathematical programming whilst the second uses a heuristic procedure in order to reduce computational time. The proposed model combines timetabling with crew scheduling decisions in one mixed integer programming model which considers multiple activities. The algorithms are tested on randomly generated and real instances provided by the Health to School Initiative, a program based at Bogotá’s local Health Department. The results show that the Initiative can increase its coverage by up to 68% using the proposed heuristic approach as a planning process tool.
Over the past 5 years, breakthroughs in the delivery of systemic therapy have transformed advanced hepatocellular carcinoma, a disease with a typical life expectancy of 6 months following diagnosis,1 ...into an oncological indication in which more effective therapies and optimal sequencing have extended patients' survival to contemporary estimates ranging from 16 to 22 months in randomised trials2 and in routine practice.3 Although PD-1 pathway inhibition did not show superior efficacy over sorafenib,4 its use in combination with VEGF5 and CTLA-46 inhibitors has led to the approval of novel standards of care in advanced disease, making long-term survival an achievable aim in some patients. Taken together, these results show us that the cost of synergistic efficacy from ICI–TKI combinations might reside in a potential treatment-related deterioration in quality of life. The results from the LEAP-002 study, which had a median overall survival of 19·0 (95% CI 17·2–21·7) in patients treated with lenvatinib, provide credible evidence that TKI monotherapy remains a reasonable contemporary treatment option for some patients.14 The increasingly complex therapeutic allocation dominated by parallel reporting of multiple phase 3 trials against sorafenib advocates for the continued adoption of worldwide multidisciplinary standards of care in routine clinical practice to promote the truly individualised management of patients with hepatocellular carcinoma.
Agriculture is now facing the ‘perfect storm’ of climate change, increasing costs of fertilizer and rising food demands from a larger and wealthier human population. These factors point to a global ...food deficit unless the efficiency and resilience of crop production is increased. The intensification of agriculture has focused on improving production under optimized conditions, with significant agronomic inputs. Furthermore, the intensive cultivation of a limited number of crops has drastically narrowed the number of plant species humans rely on. A new agricultural paradigm is required, reducing dependence on high inputs and increasing crop diversity, yield stability and environmental resilience. Genomics offers unprecedented opportunities to increase crop yield, quality and stability of production through advanced breeding strategies, enhancing the resilience of major crops to climate variability, and increasing the productivity and range of minor crops to diversify the food supply. Here we review the state of the art of genomic‐assisted breeding for the most important staples that feed the world, and how to use and adapt such genomic tools to accelerate development of both major and minor crops with desired traits that enhance adaptation to, or mitigate the effects of climate change.
Carrion's disease affects small Andean communities in Peru, Colombia and Ecuador and is characterized by two distinct disease manifestations: an abrupt acute bacteraemic illness (Oroya fever) and an ...indolent cutaneous eruptive condition (verruga Peruana). Case fatality rates of untreated acute disease can exceed 80% during outbreaks. Despite being an ancient disease that has affected populations since pre-Inca times, research in this area has been limited and diagnostic and treatment guidelines are based on very low evidence reports. The apparently limited geographical distribution and ecology of Bartonella bacilliformis may present an opportunity for disease elimination if a clear understanding of the epidemiology and optimal case and outbreak management can be gained.
All available databases were searched for English and Spanish language articles on Carrion's disease. In addition, experts in the field were consulted for recent un-published work and conference papers. The highest level evidence studies in the fields of diagnostics, treatment, vector control and epidemiology were critically reviewed and allocated a level of evidence, using the Oxford Centre for Evidence-Based Medicine (CEBM) guidelines.
A total of 44 studies were considered to be of sufficient quality to be included in the analysis. The majority of these were level 4 or 5 (low quality) evidence and based on small sample sizes. Few studies had been carried out in endemic areas.
Current approaches to the diagnosis and management of Carrion's disease are based on small retrospective or observational studies and expert opinion. Few studies take a public health perspective or examine vector control and prevention. High quality studies performed in endemic areas are required to define optimal diagnostic and treatment strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cigarette smoke (CS) inhalation triggers oxidative stress and inflammation, leading to accelerated lung aging, apoptosis, and emphysema, as well as systemic pathologies. Metformin is beneficial for ...protecting against aging-related diseases.
We sought to investigate whether metformin may ameliorate CS-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD).
Mice were exposed chronically to CS and fed metformin-enriched chow for the second half of exposure. Lung, kidney, and muscle pathologies, lung proteostasis, endoplasmic reticulum (ER) stress, mitochondrial function, and mediators of metformin effects
and/or
were studied. We evaluated the association of metformin use with indices of emphysema progression over 5 years of follow-up among the COPDGene (Genetic Epidemiology of COPD) study participants. The association of metformin use with the percentage of emphysema and adjusted lung density was estimated by using a linear mixed model.
Metformin protected against CS-induced pulmonary inflammation and airspace enlargement; small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism
and
; and ER stress. The AMPK (AMP-activated protein kinase) pathway was central to metformin's protective action. Within COPDGene, participants receiving metformin compared with those not receiving it had a slower progression of emphysema (-0.92%; 95% confidence interval CI, -1.7% to -0.14%;
= 0.02) and a slower adjusted lung density decrease (2.2 g/L; 95% CI, 0.43 to 4.0 g/L;
= 0.01).
Metformin protected against CS-induced lung, renal, and muscle injury; mitochondrial dysfunction; and unfolded protein responses and ER stress in mice. In humans, metformin use was associated with lesser emphysema progression over time. Our results provide a rationale for clinical trials testing the efficacy of metformin in limiting emphysema progression and its systemic consequences.
The use of muon tomography in geoscience projects has been continuously increasing over the past few years. This led to a variety of applications that often use custom-tailored solutions for data ...acquisition and processing. The respective know-how is splintered and mainly available in a semi-published state in various physics departments that developed these methods. This complicates the design of new studies and the decision whether muon tomography is a suitable tool and feasible for a specific geoscientific question. In this study we review the current state of how muon tomography has been applied in the field of geosciences with the goal of equipping interested geoscientists with the basic knowledge on the physical basics that constitute muon tomography. After an explanation of how muons are produced, how they traverse matter and how they are recorded, a showcase is made of recent applications. These studies show the variety of how muon tomography can be applied in experiments, such that interested readers may implement this technology for their own research. Finally, we provide a guide to best practice to help interested geoscientists decide if and how muon tomography could be implemented in their own research. We believe that through a better mutual understanding, new interdisciplinary collaborations can be initiated that advance the whole field of muon tomography.
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