The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD ...(cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients’ outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty‐seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty‐seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1‐year death‐censored kidney survival was 91%, and delayed graft function rate was 27%. The 1‐year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved.
Abdominal normothermic regional perfusion with premortem interventions represents an advance to increase the number and quality of grafts recovered in controlled donation after circulatory death.
Despite the tremendous potential of Toll‐like receptor 4 (TLR4) agonists in vaccines, their efficacy as monotherapy to treat cancer has been limited. Only some lipopolysaccharides (LPS) isolated from ...particular bacterial strains or structures like monophosphoryl lipid A (MPLA) derived from lipooligosaccharide (LOS), avoid toxic overactivation of innate immune responses while retaining adequate immunogenicity to act as adjuvants. Here, different LOS structures are incorporated into nanoparticle‐filled phospholipid micelles for efficient vaccine delivery and more potent cancer immunotherapy. The structurally unique LOS of the plant pathogen Xcc is incorporated into phospholipid micelles encapsulating iron oxide nanoparticles, producing stable pathogen‐mimicking nanostructures suitable for targeting antigen presenting cells in the lymph nodes. The antigen is conjugated via a hydrazone bond, enabling rapid, easy‐to‐monitor and high‐yield antigen ligation at low concentrations. The protective effect of these constructs is investigated against a highly aggressive model for tumor immunotherapy. The results show that the nanovaccines lead to a higher‐level antigen‐specific cytotoxic T lymphocyte (CTL) effector and memory responses, which when combined with abrogation of the immunosuppressive programmed death‐ligand 1 (PD‐L1), provide 100% long‐term protection against repeated tumor challenge. This nanovaccine platform in combination with checkpoint inhibition of PD‐L1 represents a promising approach to improve the cancer immunotherapy of TLR4 agonists.
A cancer vaccine platform based on pathogen‐mimicking Toll‐like receptor (TLR4) agonist‐functionalized magnetite containing nanostructures and chemoselective covalent conjugation of antigen by aniline‐catalyzed hydrazone ligation is designed and developed. Vaccination with these nanovaccines in combination with the abrogation of tumor cell programmed death‐ligand 1 (PD‐L1) expression confers complete protection against multiple melanoma challenges.
The relationship between lean management and resilience in the supply chain, whether negative or positive, is still not clear from the existing literature. This paper aims to investigate the ...relationship and links between lean and resilient supply chain (SC) practices and their impact on SC performance. To achieve this objective, the aerospace manufacturing sector (AMS) is chosen as the study sector because of the importance of both paradigms. Interpretive Structural Modeling (ISM) approach is used in order to identify linkages among various lean and resilience practices and SC performance metrics through a single systemic framework. ISM is an interactive learning process based on graph theory where experts' knowledge is extracted and converted into a powerful well-structured model. For that purpose, a heterogeneous panel of experts in the AMS was formed, providing a complete view of all SC levels in the sector. The final ISM model revealed that lean SC practices act as drivers for resilient SC practices, since implementing the former in isolation could lead to a more vulnerable SC. The findings also show that lean SC practices lead to a higher performance improvement than resilient SC practices. This is due to the fact that resilient SC practices do not exert influence over all SC performance metrics as it occurs with lean SC practices. In addition, several managerial implications regarding the most convenient practices in terms of the company's objectives are drawn from this study.
For establishing the true effect of different response categories in patients with multiple myeloma (MM) treated with autologous stem cell transplantation, we evaluated, after a median follow-up of ...153 months, 344 patients with MM who received a transplant between 1989 and 1998. Overall survival (OS) at 12 years was 35% in complete response (CR) patients, 22% in near complete response (nCR), 16% in very good partial response (VGPR), and 16% in partial response (PR) groups. Significant differences in OS and progression-free survival were found between CR and nCR groups (P = .01 and P = .002, respectively), between CR and VGPR groups (P = .0001 and P = .003), or between CR and PR groups (P = .003 and P = < 10−5); no differences were observed between the nCR and VGPR groups (P = .2 and P = .9) or between these groups and the PR group (P = .1 and P = .8). A landmark study found a plateau phase in OS after 11 years; 35% patients in the CR group and 11% in the nCR+VGPR+PR group are alive at 17 years; 2 cases had relapsed in the nCR+VGPR+PR group. In conclusion, MM achieving CR after autologous stem cell transplantation is a central prognostic factor. The relapse rate is low in patients with > 11 years of follow-up, possibly signifying a cure for patients in CR.
The startle response is composed by a set of reflex behaviors intended to prepare the organism to face a potentially relevant stimulus. This response can be modulated by several factors as, for ...example, repeated presentations of the stimulus (startle habituation), or by previous presentation of a weak stimulus (Prepulse Inhibition PPI). Both phenomena appear disrupted in schizophrenia that is thought to reflect an alteration in dopaminergic and glutamatergic neurotransmission. In this paper we analyze whether the reported deficits are indicating a transient effect restricted to the acute phase of the disease, or if it reflects a more general biomarker or endophenotype of the disorder. To this end, we measured startle responses in the same set of thirteen schizophrenia patients with a cross-sectional design at two periods: 5 days after hospital admission and 3 months after discharge. The results showed that both startle habituation and PPI were impaired in the schizophrenia patients at the acute stage as compared to a control group composed by 13 healthy participants, and that PPI but not startle habituation remained disrupted when registered 3 months after the discharge. These data point to the consideration of PPI, but not startle habituation, as a schizophrenia biomarker.
•We study a bi-objective parallel machine scheduling problem.•Setups need additional resources, such as workers.•We propose a new multi-objective algorithm.•We consider the minimization of the ...makespan and the number of additional resources.
We present a bi-objective parallel machine scheduling problem with machine and job sequence dependent setup times, with the additional consideration of resources needed during setups. The availability of such resources is limited. This models many practical situations where setup times imply, for example, cleaning and/or the reconfiguration of productive equipment. These setups are performed by personnel, who are of course limited in number. The objectives considered are the minimization of the makespan and the minimization of the number of resources. Fewer available resources reduce production costs but inevitably increase the makespan. On the contrary, a greater number of resources increase costs but allow for more setups to be done in parallel and a reduced makespan. An algorithm based on iterated greedy approaches is proposed to search for the Pareto front of the problem. This algorithm is compared with state-of-the art methods adapted to the problem. Computational experiments, supported by statistical analyses, indicate that the proposed approach outperforms all other tested procedures.
The physiology of hemostasis Sierra, Cristina; Moreno, Maite; García-Ruiz, Juan C
Blood coagulation & fibrinolysis,
2022-Jan-01, 2022-01-00, 20220101, Letnik:
33, Številka:
Suppl 1
Journal Article
Recenzirano
The breakdown of vascular integrity triggers a series of reactions, initially involving a vasoconstriction phenomenon that reduces blood loss and leads to platelet plug formation under changing flow ...conditions. Once the platelet plug has formed, the coagulation system is activated in order to allow the formation of fibrin, which anchors the platelet plug to the vessel breach. Finally, once the damage has resolved, the fibrin is eliminated through fibrinolysis. This article explains all these regulatory mechanisms.
Summary
The Latin American (LA) population has similarities with the Spanish population which makes its integration into Spanish society easier. Objective: to analyze the attitude toward organ ...donation among Latin American citizens residing in Spain, to determine the psychosocial variables which affect this attitude, and to examine the correlation between donation rates of LA citizens in Spain and in their countries of origin. A random sample of LA residents in Spain was taken and stratified according to the respondent's nationality (n = 1.314), in the year 2010. Attitude was assessed using a validated questionnaire (PCID‐DTO Dr Rios). The survey was self‐administered and completed anonymously. Statistical analysis: Student's t‐test, the χ2 test, and logistic regression analysis. There was a 94% completion rate (n = 1.237). Attitude toward donation was favorable in 60% of cases (n = 745), 12% (n = 145) were against, and 28% (n = 347) were undecided. The following variables were associated with attitude toward donation: sex (P = 0.038), level of formal education (P < 0.001), country of origin (P = 0.002), attitude toward the donation of a family member's organs (P < 0.001), having discussed donation with the family (P < 0.001), carrying out prosocial activities (P = 0.025), attitude toward cremation of the body (P < 0.001), attitude toward burial of the body (P < 0.001), attitude toward having an autopsy carried out (P < 0.001), previous experience of the organ donation and transplantation process (P < 0.001), fear of mutilation after donation (P < 0.001), knowledge that the Church has a positive attitude toward organ donation and transplantation (P < 0.001), knowledge of one's partner's attitude toward organ donation (P < 0.001), and a belief that one might need a transplant in the future (P < 0.001). The donation rates in this population group in Spain are higher than those recorded in their countries of origin (55.76 vs. <10 pmp; P < 0.001). The attitude toward organ donation among LA citizens residing in Spain is slightly worse than that reported in the native Spanish population and is determined by many psychosocial factors. The donation rates of LA citizens in Spain are higher than those in their countries of origin.
Plancha-type stoves have been widely disseminated in Mexico and Central America, but the contribution of fugitive emissions from these stoves to indoor air concentrations has been poorly quantified. ...In this study, fugitive emissions were measured for four plancha-type cookstoves most disseminated in Mexico (Patsari, ONIL, Ecostufa, and Mera-Mera). In controlled testing, fugitive emissions from plancha-type chimney stoves (n = 15 for each stove) were on average 5 ± 3% for PM2.5 and 1 ± 1% for CO, much lower than defaults in WHO Guidelines (25 ± 10%). Using a Monte Carlo single zone model with locally measured parameters, average kitchen concentrations resulting from fugitive emissions were 15 ± 9 μg/m3 for PM2.5 and 0.06 ± 0.04 mg/m3 for CO. On the basis of these models, plancha-type stoves meet benchmarks for WHO Air Quality Guidelines (AQG) Interim Target I for PM2.5 and the 24 h AQG for CO, respectively, with on average 97% of homes meeting the guideline for PM2.5. Similarly, all four plancha-type stoves were ISO IWA Tier 4 for indoor emissions of CO and Tier 3 for indoor emissions of PM2.5. Three-dimensional computational fluid dynamics (CFD) analysis was used to estimate neighborhood pollution impacts of upstream chimney emissions. When chimney emissions were included as background concentrations combined with indoor contributions from fugitive emissions, plancha-type stoves would still meet the WHO AQG Annual Interim Target I for PM2.5 and the 24 h AQG for CO for the scenario modeled in this study.
Atherosclerosis is a chronic inflammatory disease, but data on arterial inflammation at early stages is limited.
The purpose of this study was to characterize vascular inflammation by hybrid ...18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI).
Carotid, aortic, and ilio-femoral 18F-FDG PET/MRI was performed in 755 individuals (age 40 to 54 years; 83.7% men) with known plaques detected by 2-/3-dimensional vascular ultrasound and/or coronary calcification in the PESA (Progression of Early Subclinical Atherosclerosis) study. The authors evaluated the presence, distribution, and number of arterial inflammatory foci (increased 18F-FDG uptake) and plaques with or without inflammation (coincident 18F-FDG uptake).
Arterial inflammation was present in 48.2% of individuals (24.4% femorals, 19.3% aorta, 15.8% carotids, and 9.3% iliacs) and plaques in 90.1% (73.9% femorals, 55.8% iliacs, and 53.1% carotids). 18F-FDG arterial uptakes and plaques significantly increased with cardiovascular risk factors (p < 0.01). Coincident 18F-FDG uptakes were present in 287 of 2,605 (11%) plaques, and most uptakes were detected in plaque-free arterial segments (459 of 746; 61.5%). Plaque burden, defined by plaque presence, number, and volume, was significantly higher in individuals with arterial inflammation than in those without (p < 0.01). The number of plaques and 18F-FDG uptakes showed a positive albeit weak correlation (r = 0.25; p < 0.001).
Arterial inflammation is highly prevalent in middle-aged individuals with known subclinical atherosclerosis. Large-scale multiterritorial PET/MRI allows characterization of atherosclerosis-related arterial inflammation and demonstrates 18F-FDG uptake in plaque-free arterial segments and, less frequently, within plaques. These findings suggest an arterial inflammatory state at early stages of atherosclerosis. (Progression of Early Subclinical Atherosclerosis PESA; NCT01410318)
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