Serial concatenation of a block code and a 2D convolutional code (2019). Multidimensional Systems and Signal Processing, 30, 1113–1127.

María Victoria Herranz (University Miguel Hernández of Elche), Diego Napp (Universidade de Aveiro) and Carmen Perea (University Miguel Hernández of Elche).

Abstract. In this paper we study two different concatenation schemes of twodimensional (2D) convolutional codes. We consider Fornasini–Marchesini state space representation of 2D linear systems to describe our concatenated codes. Also we present upper and lower bounds on the distance of the proposed concatenated codes.

Keywords. 2D convolutional code; Concatenated convolutional code; Marchesini– Fornasini 2D model; Minimum distance; Free distance

Long-Term Outcome After Conventional Two-Stage Hepatectomy Versus Tourniquet-ALPPS in Colorectal Liver Metastases: A Propensity Score Matching Analysis (2019). World Journal of Surgery, 1-9.

Ricardo Robles-Campos (Virgen de La Arrixaca Clinic, University Hospital), Roberto Brusadin (Virgen de La Arrixaca Clinic, University Hospital), Asunción López-Conesa (Virgen de La Arrixaca Clinic, University Hospital), Víctor López-López (Virgen de La Arrixaca Clinic, University Hospital), Álvaro Navarro-Barrios (Virgen de La Arrixaca Clinic, University Hospital), José J. López-Espín (Miguel Hernández University of Elche), Julio Arévalo-Pérez (Memorial Sloan Kettering Cancer Center of New York) and Pascual Parrilla (Virgen de La Arrixaca Clinic, University Hospital).

Abstract. To compare the overall survival (OS) and disease-free survival (DFS) of Tourniquet-ALPPS (TALPPS) and conventional two-stage hepatectomy (TSH) in patients with colorectal liver metastases (CRLM). A retrospective study from a prospectively collected database was performed between October 2000 and July 2016. TSH was performed before September 2011, after which time T-ALPPS became the technique of choice. A propensity score matching (PSM) was performed based on a 1:1 ratio with consideration of the following variables: number and size of metastases, bilobar disease presence, and chemotherapy received. Thirty-four patients received T-ALPPS; 41 patients received TSH. After PSM, 21 patients remained in each group, with 100% resectability in the T-ALPPS group and 90.5% resectability in the TSH group. The median OS for TSH was 41 months; for T-ALPPS, the median OS was 36 months (P = 0.925). The median DFS was 16 months in the TSH group; the median DFS was 9 months in the T-ALPPS group (P = 0.930). The 1-, 3-, and 5-year OS for TSH was 81%, 66.7%, and 23.8% vs. 76.2%, 57.1%, and 22.9% for T-ALPPS, respectively. The 1-, 3-, and 5-year DFS for TSH was 66.7%, 9.5%, and 5% vs. 44.6%, 11.1%, and 11.1% for T-ALPPS, respectively. The volume increase with T-ALPPS was superior to that with TSH (68% vs. 39%; P = 0.018). There were no differences in morbidity and mortality after stages 1 and 2. T-ALPPS produces a similar outcome to TSH, indicating that it could be a safe and effective alternative for curative hepatectomy for all patients.

Pharmacogenetics and prediction of adverse events in prescription opioid use disorder patients (2019). Basic & Clinical Pharmacology & Toxicology, 124, 439-448.

Javier Muriel (Alicante Institute for Health and Biomedical Research), César Margarit (Alicante-General Hospital), Jordi Barrachina (Occupational Observatory, Miguel Hernández University of Elche), Pura Ballester (Alicante Institute for Health and Biomedical Research), Andrea Flor (Alicante-General Hospital), Domingo Morales (Miguel Hernández University of Elche), José F. Horga (Alicante-General Hospital), Eduardo Fernández (Miguel Hernández University of Elche) and Ana M. Peiró (Alicante-General Hospital).

Abstract. The threats involved in the long‐term opioid treatment of chronic non‐cancer pain (CNCP) have increased notably. Strategies to identify at‐risk patients are important because there is no clear evidence showing which screening or deprescription programmes are appropriate. Our aim was to evaluate the evidence provided by pharmacogenetics applied to predict an analgesic toxicity profile in prescription opioid use disorder (POUD) patients participating in an opioid deprescription programme. Pharmacogenetic markers were analysed in an observational, prospective deprescription programme for POUD patients (n = 88) treated for CNCP. It consisted of monitoring visits (baseline, follow‐up and final), opioid rotation or discontinuation and the recording of adverse events and suspected adverse drug reactions (ADRs). Variants in OPRM1 (A118G), ABCB1 (C3435T), COMT (G472A), OPRD1 (T921C) and ARRB2 (C8622T) genes were tested by real‐time PCR. Ethics committee approved the study. Wild‐type OPRM1‐AA genotype carriers reported a significantly higher number of adverse events than OPRM1‐AG/GG (median [p25 75], 7 [5‐11] vs 5 [3‐9]), particularly gastrointestinal system events (90% vs 63%) such as nausea (33% vs 0%). Suspected ADRs (affecting 17% of the patients) were three times higher in males than in females (30% vs 11%). The deprescription programme was effective and safe, and it achieved a significant progressive reduction in the morphine equivalent daily dose, strong opioids and other analgesics’ use, without causing any changes in pain intensity or opiate abstinence syndrome. OPRM1 gene polymorphisms could identify the risk of gastrointestinal adverse events in POUD patients. Deprescription programmes including pharmacogenetic analysis should be considered during the follow‐up of this population.

Keywords. Adverse events; Chronic pain; Opioid use disorder; Pharmacogenetics; Prescription opioids

Improved polyhedral descriptions and exact procedures for a broad class of uncapacitated p-hub median problems (2019). Transportation Research Part B: Methodological, 123, 38-63.

Ángel Corberán (University of Valencia), Mercedes Landete (University Miguel Hernández of Elche), Juanjo Peiró (University of Valencia) and Francisco Saldanha-da-Gama (University of Lisboa).

Abstract. This work focuses on a broad class of uncapacitated p -hub median problems that includes non-stop services and setup costs for the network structures. In order to capture both the single and the multiple allocation patterns as well as any intermediate case of interest, we consider the so-called r -allocation pattern with r denoting the maximum number of hubs a terminal can be allocated to. We start by revisiting an optimization model recently pro- posed for the problem. For that model, we introduce several families of valid inequalities as well as optimality cuts. Moreover, we consider a relaxation of the model that contains several sets of set packing constraints. This motivates a polyhedral study that we perform and that leads to the identification of many families of facets and other valid inequalities to the relaxed problem that, in turn, provide valid inequalities for the original model. Some of these families are too large for being handled directly. For those cases, separation algo- rithms are also presented. Finally, we gather all the above elements in a branch-and-cut procedure that we devise and implement for tackling the problem. The methodological developments proposed are tested computationally using data generated from the well- known AP data set.

Keywords. Hub location; Non-stop services; Set packing polytope; Branch and cut

Microeconomic education, strategic incentives, and gender: An oligopoly classroom experiment with social interaction (2019). International Review of Economics Education, 30, 1-11.

José Antonio García-Martínez (University Miguel Hernández of Elche), Carlos Gutiérrez-Hita (University Miguel Hernández of Elche) and Joaquín Sánchez-Soriano (University Miguel Hernández of Elche).

Abstract. In an oligopoly classroom experiment we study the extent to which microeconomic education, strategic incentives, and gender affect students’ profits. In our setting, students may interact in the classroom (indeed, everywhere) prior to submitting quantity bids to a virtual market. As students could submit a quantity bid over a week-long period, information exchange among students was expected to take place (as it did). This makes this experiment very useful as a pedagogical tool. Students were divided into markets. We first apply a treatment in which students’ incentives only depend on their own market performance. In the second treatment students’ incentives not only depend on their own market performance but also on performance in other markets. First, it is observed that gender does not affect the results. Second, significant education effects are found. Indeed, students’ profits differ as students reach a higher level of microeconomics education. Finally, cumulative profits depend on the treatment applied: under the first treatment students are more competitive, whereas under the second treatment students partially cooperate. Moreover, this result is related to the level of education in microeconomics.

Keywords. Classroom experiments; Microeconomic education; Gender; Strategic incentives; Quantity-setting oligopoly

Clinical relevance of monitoring serum adalimumab levels in axial spondyloarthritis (2019). Rheumatology International, 39 (5), 841-849.

José Miguel Senabre Gallego (Marina Baixa Hospital of Villajoyosa, Alicante), José Rosas (Marina Baixa Hospital of Villajoyosa, Alicante), Mariana Marco-Mingot (Marina Baixa Hospital of Villajoyosa, Alicante), José Alberto García-Gómez (General Hospital University of Elche), Gregorio Santos-Soler (Marina Baixa Hospital of Villajoyosa, Alicante), Esteban Salas-Heredia (Marina Baixa Hospital of Villajoyosa, Alicante), Ana Pons-Bas (Marina Baixa Hospital of Villajoyosa, Alicante), Xavier Barber-Vallés (University Miguel Hernández of Elche), José Antonio Bernal‑Vidal (Marina Baixa Hospital of Villajoyosa, Alicante), Catalina Cano-Pérez (Marina Baixa Hospital of Villajoyosa, Alicante), Mario García-Carrasco (Autonomous University of Puebla, Mexico), Emilio Flores-Pardo (University Miguel Hernández of Elche) and AIRE-MB Group (Association of Spanish Rheumatology).

Abstract. Our aim was to assess the relationship between serum adalimumab levels, anti-drug antibodies (ADA) and disease activity in patients with axial spondylarthritis (SpA). We have carried out a single-centre cross-sectional study. adalimumab and ADA levels were analysed with ELISA and correlated with SpA activity using BASDAI and ASDAS scores. Adalimumab cut-off value was calculated to discriminate inactive disease/low disease activity (BASDAI < 4; ASDAS < 2.1) from moderate/high disease activity (BASDAI ≥ 4; ASDAS ≥ 2.1), using a receiver operating characteristic (ROC) curve. Up to January 2016, 51 consecutive patients were included. The median (range) age was 46.6 (18–68) and 47.1% were women. ADA prevalence was 27.5%, with none detected in the 21.6% receiving concomitant disease-modifying antirheumatic drugs (DMARDs) (p = 0.021). Adalimumab level was normal (> 3 mg/l) in 36 patients (70.6%), all without ADA. Fifteen patients (29.4%) had subtherapeutic adalimumab levels (< 3 mg/l), with ADA in 14 (93%). Median adalimumab (mg/l) was significantly higher in patients with inactive disease/low disease activity: BASDAI < 4 vs ≥ 4: 9.5 vs 2.6 (p < 0.01); ASDAS-CRP < 2.1 vs ≥ 2.1: 9.3 vs 0.3 (p < 0.001); ASDAS-ESR < 2.1 vs ≥ 2.1: 9.9 vs 3.0 (p < 0.001), and this finding was consistent with the result of the multivariate model. Patients with inactive disease/low disease activity presented significantly lower ADA levels. The adalimumab level cut-offs and area under the curve (AUC) obtained in the ROC curves were: ASDAS-CRP (< 2.1) 4.6 mg/l (AUC 81.2%; 95% CI 67.5–94.9; p < 0.001); ASDAS-ESR (< 2.1) 7.7 mg/l (AUC 82.4%; 95% CI 69.3–95.5; p < 0.001); BASDAI (< 4) 6.4 mg/l (AUC 73.5%; 95% CI 58.6–88.3; p < 0.01). In conclusion, presence of ADA in axial SpA patients treated with adalimumab was associated with lower serum drug levels. ADA levels were lower and adalimumab levels were higher in patients with inactive disease/low disease activity based on BASDAI and ASDAS indices. Concomitant treatment with MTX reduces de likelihood of finding ADA. Serum adalimumab levels above 4.6 mg/l are recommended to avoid compromising efficacy.

Keywords. Spondylarthritis; Adalimumab; Antibody formation; Enzyme-linked immunosorbent assay; ROC curve; Treatment outcome