Exact procedures for solving the discrete ordered median problem

The Discrete Ordered Median Problem (DOMP) generalizes classical discrete location problems, such as the N-median, N-center and Uncapacitated Facility Location problems. It was introduced by Nickel [S. Nickel. Discrete Ordered Weber problems. In B. Fleischmann, R. Lasch, U. Derigs, W. Domschke, and U. Rieder, editors, Operations Research Proceedings 2000, pages 71–76. Springer, 2001], who formulated it as both a nonlinear and a linear integer program. We propose an alternative integer linear programming formulation for the DOMP, discuss relationships between both integer linear programming formulations, and show how properties of optimal solutions can be used to strengthen these formulations. Moreover, we present a specific branch and bound procedure to solve the DOMP more efficiently. We test the integer linear programming formulations and this branch and bound method computationally on randomly generated test problems.Ministerio de Ciencia y Tecnologí

The Origin of Kinematically Persistent Planes of Satellites as Driven by the Early Evolution of the Cosmic Web in ΛCDM

Kinematically persistent planes (KPPs) of satellites are fixed sets of satellites co-orbiting around their host galaxy, whose orbital poles are conserved and clustered across long cosmic time intervals. They play the role of “skeletons,” ensuring the long-term durability of positional planes. We explore the physical processes behind their formation in terms of the dynamics of the local cosmic web (CW), characterized via the so-called Lagrangian volumes (LVs) built up around two zoom-in, cosmological hydro-simulations of Milky Way–mass disk galaxy + satellites systems, where three KPPs have been identified. By analyzing the LV deformations in terms of the reduced tensor of inertia (TOI), we find an outstanding alignment between the LV principal directions and the KPP satellites’ orbital poles. The most compressive local mass flows (along the eˆ3 eigenvector) are strong at early times, feeding the so-called eˆ3 -structure, while the smallest TOI axis rapidly decreases. The eˆ3 -structure collapse marks the end of this regime and is the timescale for the establishment of satellite orbital pole clustering when the Universe is ≲4 Gyr old. KPP protosatellites aligned with eˆ3 are those whose orbital poles are either aligned from early times or have been successfully bent at eˆ3 -structure collapse. KPP satellites associated with eˆ1 tend to have early trajectories already parallel to eˆ3 . We show that KPPs can arise as a result of the ΛCDM-predicted large-scale dynamics acting on particular sets of protosatellites, the same dynamics that shape the local CW environment

Microbiological Characterization of the Biofilms Colonizing Bioplastics in Natural Marine Conditions: A Comparison between PHBV and PLA

Biodegradable polymers offer a potential solution to marine pollution caused by plastic waste. The marine biofilms that formed on the surfaces of poly(lactide acid) (PLA) and poly(3- hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were studied. Bioplastics were exposed for 6 months to marine conditions in the Mediterranean Sea, and the biofilms that formed on their surfaces were assessed. The presence of specific PLA and PHBV degraders was also studied. PHBV showed extensive areas with microbial accumulations and this led to higher microbial surface densities than PLA (4.75 vs. 5.16 log CFU/cm2 ). Both polymers’ surfaces showed a wide variety of microbial structures, including bacteria, fungi, unicellular algae and choanoflagellates. A high bacterial diversity was observed, with differences between the two polymers, particularly at the phylum level, with over 70% of bacteria affiliated to three phyla. Differences in metagenome functions were also detected, revealing a higher presence of proteins involved in PHBV biodegradation in PHBV biofilms. Four bacterial isolates belonging to the Proteobacteria class were identified as PHBV degraders, demonstrating the presence of species involved in the biodegradation of this polymer in seawater. No PLA degraders were detected, confirming its low biodegradability in marine environments. This was a pilot study to establish a baseline for further studies aimed at comprehending the marine biodegradation of biopolymers

Spilled ink blots the mind: A reply to Merrit et al. (2018) on subjectivity and bone surface modifications

Categorical variables identifying microscopic features of cut marks produce high accuracy in discrimination of bone surface modifications, but are vulnerable to variable degrees of inter-analyst subjectivity. Metric analyses of cut mark width and depth are presented by Merritt et al. (2018) as a more objective method of identifying cut marks. However, this uni(bi)variate method has shown very high rates of mark classification error when structurally similar marks are compared. Furthermore, within-sample comparison carried out via subsampling shows that different datasets of metric values, obtained with the same type of tool and raw material, are subject to such a high degree of variability that significant differences of homogeneous subsamples are repeatedly obtained, thus preventing any useful analogs to be made. Additionally, this much higher stochastic variability depends on limited knowledge of the contextual processes that intervene in cut mark metric properties, as well as on a mismatch between theoretical premises on the immanent-configurational process-trace dynamics and their confusion during experimental praxis. The selection of specific contextual variables and disregard of others, in addition to the combination of different tool types and raw materials, distorts the resulting cut mark properties. This indicates that even when attempting to use exclusively metric numeric variables, subjectivity is a conditioning factor in analyzing and interpreting cut marks

COVID-19 in patients with haematologic malignancies: Effect of RNAemia on clinical outcome in vaccinated patients

Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19.This study was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases ( REIPI RD16/0016/0009 ); co‐financed by European Development Regional Fund ‘A way to achieve Europe’, Operative Program Intelligence Growth 2014‐2020; and supported by the grant PI21/01569 from the Instituto de Salud Carlos III and the grant IM22/INF/13 from the CIBERINFEC, Instituto de Salud Carlos III, Spain. RA-M, LM, JMC, EC, JS-C and MA-G ( CB21/13/00006 ) and ZRP-B, and PP-P ( CB21/13/00012 ) were also supported by CIBERINFEC – Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU. JM-E was supported by a predoctoral health research training contracts from the Instituto de Salud Carlos III ( FI22/00025 ). JS-C is a researcher belonging to the program ‘Nicolás Monardes’ (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain.Peer reviewe

Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation

[Background & Aims] Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transplants performed with postmortem NRP vs. super-rapid recovery (SRR), the current standard for cDCD.[Methods] This was an observational cohort study including all cDCD liver transplants performed in Spain between June 2012 and December 2016, with follow-up ending in December 2017. Each donor hospital determined whether organ recovery was performed using NRP or SRR. The propensity scores technique based on the inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups; logistic and Cox regression models were used for binary and time-to-event outcomes.[Results] During the study period, there were 95 cDCD liver transplants performed with postmortem NRP and 117 with SRR. The median donor age was 56 years (interquartile range 45–65 years). After IPTW analysis, baseline covariates were balanced, with all absolute standardised differences <0.15. IPTW-adjusted risks were significantly improved among NRP livers for overall biliary complications (odds ratio 0.14; 95% CI 0.06–0.35, p <0.001), ischaemic type biliary lesions (odds ratio 0.11; 95% CI 0.02–0.57; p = 0.008), and graft loss (hazard ratio 0.39; 95% CI 0.20–0.78; p = 0.008).[Conclusions] The use of postmortem NRP in cDCD liver transplantation appears to reduce postoperative biliary complications, ischaemic type biliary lesions and graft loss, and allows for the transplantation of livers even from cDCD donors of advanced age.[Lay summary] This is a propensity-matched nationwide observational cohort study performed using livers recovered from donors undergoing cardiac arrest provoked by the intentional withdrawal of life support (controlled donation after circulatory death, cDCD). Approximately half of the livers were recovered after a period of postmortem in situ normothermic regional perfusion, which restored warm oxygenated blood to the abdominal organs, whereas the remainder were recovered after rapid preservation with a cold solution. The study results suggest that the use of postmortem normothermic regional perfusion helps reduce rates of post-transplant biliary complications and graft loss and allows for the successful transplantation of livers from older cDCD donors.Peer reviewe

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio