Optimal Rotation Age in Fast Growing Plantations: A Dynamical Optimization Problem.

Forest plantations are economically and environmentally relevant, as they play a key role in timber production and carbon capture. It is expected that the future climate change scenario affects forest growth and modify the rotation age for timber production. However, mathematical models on the effect of climate change on the rotation age for timber production remain still limited. We aim to determine the optimal rotation age that maximizes the net economic benefit of timber volume in a negative scenario from the climatic point of view. For this purpose, a bioeconomic optimal control problem was formulated from a system of Ordinary Differential Equations (ODEs) governed by the state variables live biomass volume, intrinsic growth rate, and area affected by fire. Then, four control variables were associated to the system, representing forest management activities, which are felling, thinning, reforestation, and fire prevention. The existence of optimal control solutions was demonstrated, and the solutions of the optimal control problem were also characterized using Pontryagin's Maximum Principle. The solutions of the model were approximated numerically by the Forward-Backward Sweep method. To validate the model, two scenarios were considered: a realistic scenario that represents current forestry activities for the exotic species Pinus radiata D. Don, and a pessimistic scenario, which considers environmental conditions conducive to a higher occurrence of forest fires. The optimal solution that maximizes the net benefit of timber volume consists of a strategy that considers all four control variables simultaneously. For felling and thinning, regardless of the scenario considered, the optimal strategy is to spend on both activities depending on the amount of biomass in the field. Similarly, for reforestation, the optimal strategy is to spend as the forest is harvested. In the case of fire prevention, in the realistic scenario, the optimal strategy consists of reducing the expenses in fire prevention because the incidence of fires is lower, whereas in the pessimistic scenario, the opposite is true. It is concluded that the optimal rotation age that maximizes the net economic benefit of timber volume in P. radiata plantations is 24 and 19 years for the realistic and pessimistic scenarios, respectively. This corroborates that the presence of fires influences the determination of the optimal rotation age, and as a consequence, the net economic benefit.

Current perspectives on the use of artificial intelligence in critical patient safety.

Intensive Care Units (ICUs) have undergone enhancements in patient safety, and artificial intelligence (AI) emerges as a disruptive technology offering novel opportunities. While the published evidence is limited and presents methodological issues, certain areas show promise, such as decision support systems, detection of adverse events, and prescription error identification. The application of AI in safety may pursue predictive or diagnostic objectives. Implementing AI-based systems necessitates procedures to ensure secure assistance, addressing challenges including trust in such systems, biases, data quality, scalability, and ethical and confidentiality considerations. The development and application of AI demand thorough testing, encompassing retrospective data assessments, real-time validation with prospective cohorts, and efficacy demonstration in clinical trials. Algorithmic transparency and explainability are essential, with active involvement of clinical professionals being crucial in the implementation process.

Immunogenicity and safety in pigs of PHH-1V, a SARS-CoV-2 RBD fusion heterodimer vaccine candidate.

The continuing high global incidence of COVID-19 and the undervaccinated status of billions of persons strongly motivate the development of a new generation of efficacious vaccines. We have developed an adjuvanted vaccine candidate, PHH-1V, based on a protein comprising the receptor binding domain (RBD) of the Beta variant of SARS-CoV-2 fused in tandem with the equivalent domain of the Alpha variant, with its immunogenicity, safety and efficacy previously demonstrated in mouse models. In the present study, we immunized pigs with different doses of PHH-1V in a prime-and-boost scheme showing PHH-1V to exhibit an excellent safety profile in pigs and to produce a solid RBD-specific humoral response with neutralising antibodies to 7 distinct SARS-CoV-2 variants of concern, with the induction of a significant IFNγ+ T-cell response. We conclude that PHH-1V is safe and elicits a robust immune response to SARS-CoV-2 in pigs, a large animal preclinical model.

Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates.

SARS-CoV-2 emerged in December 2019 and quickly spread worldwide, continuously striking with an unpredictable evolution. Despite the success in vaccine production and mass vaccination programs, the situation is not still completely controlled, and therefore accessible second-generation vaccines are required to mitigate the pandemic. We previously developed an adjuvanted vaccine candidate coded PHH-1V, based on a heterodimer fusion protein comprising the RBD domain of two SARS-CoV-2 variants. Here, we report data on the efficacy, safety, and immunogenicity of PHH-1V in cynomolgus macaques. PHH-1V prime-boost vaccination induces high levels of RBD-specific IgG binding and neutralizing antibodies against several SARS-CoV-2 variants, as well as a balanced Th1/Th2 cellular immune response. Remarkably, PHH-1V vaccination prevents SARS-CoV-2 replication in the lower respiratory tract and significantly reduces viral load in the upper respiratory tract after an experimental infection. These results highlight the potential use of the PHH-1V vaccine in humans, currently undergoing Phase III clinical trials.

Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2.

Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralizing activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.

Experimental Characterization and Analysis of the In-Plane Elastic Properties and Interlaminar Fracture Toughness of a 3D-Printed Continuous Carbon Fiber-Reinforced Composite.

The use of continuous fiber as reinforcement in polymer additive manufacturing technologies enhances the mechanical performance of the manufactured parts. This is the case of the Carbon-Fiber reinforced PolyAmide (CF/PA) used by the MarkForged MarkTwo® 3D printer. However, the information available on the mechanical properties of this material is limited and with large variability. In this work, the in-plane mechanical properties and the interlaminar fracture toughness in modes I and II of Markforged's CF/PA are experimentally investigated. Two different standard specimens and end-tabs are considered for the in-plane properties. Monolithic CF/PA specimens without any additional reinforcement are used for the interlaminar fracture toughness characterization. Two different mode I specimen configurations are compared, and two different test types are considered for mode II. The results show that prismatic specimens with paper end-tabs are more appropriate for the characterization of the in-plane material properties. The use of thick specimens for mode I fracture toughness tests complicates the characterization and can lead to erroneous results. Contrary to what has been reported in the literature for the same material, fracture toughness in mode I is lower than for mode II, which agrees with the normal tendency of traditional composite materials.

Network Analysis of the Structure of the Core Symptoms and Clinical Correlates in Comorbid Schizophrenia and Gambling Disorder.

Few studies have analyzed the clinical profile of treatment-seeking patients with the comorbid presence of schizophrenia (SCZ) and gambling disorder (GD), which warrants new research to assess the network structure of this complex mental condition. The aim of this study was to explore the organization of the symptoms and other clinical correlates of SCZ with GD. Network analysis was applied to a sample of N = 179 SCZ patients (age range: 19-70 years, mean=39.5, SD=9.9) who met clinical criteria for gambling disorder-related problems. Variables included in the network were the core GD symptoms according to the DSM-5, psychotic and paranoid ideation levels, global psychological distress, GD severity measures (debts and illegal behavior related with gambling), substances (tobacco, alcohol, and illegal drugs), and personality profile. The nodes with the highest authority in the network (variables of highest relevance) were personality traits and psychological distress. Four empirical modules/clusters were identified, and linkage analysis identified the nodes with the highest closeness (bridge nodes) to be novelty seeking and reward dependence (these traits facilitate the transition between the modules). Identification of the variables with the highest centrality/linkage can be particularly useful for developing precise management plans to prevent and treat SCZ with GD. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-022-00983-y.

Leukocyte Subset Changes in Response to a 164-km Road Cycle Ride in a Hot Environment.

The purpose of this observational study was to determine the circulating leukocyte subset response to completing the 2013 Hotter'N Hell Hundred recreational 164-km road cycle event in a hot and humid environmental condition. Twenty-eight men and four women were included in this study. Whole blood samples were obtained 1-2 hours before (PRE) and immediately after (POST) the event. Electronic sizing/sorting and cytometry were used to determine complete blood counts (CBC) including neutrophil, monocyte, and lymphocyte subsets. The concentration of circulating total leukocytes (103·µL-1) increased 134% from PRE to POST with the greatest increase in neutrophils (319%, p<0.0001). Circulating monocytes (including macrophages) increased 24% (p=0.004) and circulating lymphocytes including B and T cells increased 53% (p<0.0001). No association was observed between rolling time or relative intensity and leukocyte subset. Completing the Hotter n' Hell Hundred (HHH), a 100 mile recreational cycling race in extreme (hot and humid) environmental conditions, induces a substantial increase in total leukocytes in circulation. The contribution of increases in specific immune cell subsets is not equal, with neutrophils increasing to greater than 4-fold starting values from PRE to POST race. It is likely that exercise in stressful environmental conditions affects the complement of circulating immune cells, although activational state and characterization of specific leukocyte subsets remains unclear. The observed increase in circulating cell sub-populations suggests that the circulating immune surveillance system may be acutely affected by exercise in hot and humid conditions.

Imaging of early inflammation in low-to-moderate carotid stenosis by 18-FDG-PET.

It is not clear if 18FDG-PET can be useful for detection of inflammation in low to moderate carotid stenosis. We studied 15 patients scheduled for endarterectomy with contralateral carotids with less than 50% stenosis. 18-FDG-PET was performed prior to CEA and 3 months following surgery. FDG-uptake values were calculated based on maximum standardized uptake value (SUV) and corresponding uptake ratios. We confirmed by CD68 macrophage staining that FDG accumulation corresponds to active inflammation (R=0.8 p less than 0.005). We found significant correlation between the FDG-uptake in the carotids scheduled for CEA and contralateral carotids with low to moderate stenosis (R=0.9 p less than 0.001). The FDG uptake ratio in the contralateral arteries remained stable on the follow-up imaging (1.15+/-0.2 vs. 1.14+/-0.1, R=0.7 p=0.006). We did not find correlation between FDG uptake and symptomatic or asymptomatic patients, degree of carotid stenosis and vascular risk factors. This is a prospective, preliminary in vivo study demonstrating that low to moderate carotid atherosclerosis can be detected using 18-FDG-PET imaging and highlights the truly systemic nature of atherosclerosis.

Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients.

Metalloproteinase 7 (MMP-7) plays an important role in tumor growth, invasion and dissemination, and is secreted to the media. Because of the close implication of MMP-7 in cancer biology, we sought to define the prognostic significance of serum levels of MMP-7 in metastatic colorectal cancer (CRC) and explore its possible impact in the daily clinical practice. MMP-7 expression was determined by enzyme-linked immunoabsorbent assay. We assessed serum MMP-7 levels in 87 healthy controls, 96 patients with nonmetastatic CRC and 120 patients with advanced CRC. Clinical information was gathered from patient files. Cox proportional hazards model was used to assess survival. MMP-7 and the variables associated with prognosis were entered and a backward elimination method was employed to adjust the model. Inclusion criteria was p /= 0.10. Advanced CRC patients have a significant higher mean serum MMP-7 levels (13.4 ng/ml) than those in nonmetastatic CRC (5.5 ng/ml; p < 0.001) and healthy controls (4.2 ng/ml; p < 0.001). In metastatic patients, after adjusting for other prognostic variables, MMP-7 (entered as a continuous variable) is associated with decreased survival (HR 1.016, IC 95% 1.002-1.031). Serum MMP-7 levels are significantly elevated in patients with advanced CRC. In conclusion, MMP-7 is an independent prognostic factor for survival in advanced CRC. In our sample, the risk of death associated to MMP-7 increase is much higher than the risk of death associated to lactate dehydrogenase elevation.

[Impact of the availability of an external nuclear medicine service in the application of sentinel lymph node biopsy in breast cancer surgery]. / Impacto de la disponibilidad de un servicio externo de medicina nuclear en la aplicación de la biopsia del ganglio centinela en cirugía del cáncer de mama.

INTRODUCTION: To perform sentinel lymph node biopsy (SLNB), nuclear medicine services that have previously undergone a validation phase are required. The aim of the present study was to analyze the possibility of performing this technique with a previously validated, external nuclear medicine service and to study its impact on the indication for radical axillary lymphadenectomy (RAL) and on length of postoperative hospital stay. PATIENTS AND METHODS: We performed a prospective study in a cohort of patients with breast cancer starting from the introduction of SLNB in our center, which was made possible by collaboration with an external nuclear medicine service that performed lymphoscintigraphy and sentinel node detection. Intraoperative detection was performed through a portable probe. The feasibility of the project and its clinical impact were analyzed, taking a reduction in the number of lymphadenectomies and length of hospital stay as endpoints. RESULTS: A total of 196 patients with 201 breast carcinomas were treated. The most frequent interventions were tumorectomy (TC) with SLNB in 124 patients (62%), and TC with SLNB and RAL in 62 patients (31%). Sentinel node visualization on lymphoscintigraphy was achieved in 187/201 carcinomas (93.1%) and sentinel nodes were detected during the intervention in 182/187 carcinomas (97.4%). Sentinel node detection in the internal mammary chain was achieved in 23/201 carcinomas (11.4%). RAL was avoided in 131 of the 201 carcinomas (65%). Days of postoperative hospital stay with or without RAL showed a mean difference of 1.8 days (3.1 vs. 1.3; P < .001). CONCLUSION: SLNB is feasible with the collaboration of an external nuclear medicine service. This technique avoids 65% of RAL and reduces length of postoperative stay by 1.8 days.

Impacto de la disponibilidad de un servicio externo de medicina nuclear en la aplicación de la biopsia del ganglio centinela en cirugía del cáncer de mama / Impact of the availability of an external nuclear medicine service in the application of sentinel lymph node biopsy in breast cancer surgery

Introducción. La realización de la técnica de la biopsia selectiva del ganglio centinela (BSGC) en el tratamiento del cáncer de mama requiere disponer de un servicio de medicina nuclear (SMN) y de la validación de su técnica. El objetivo del presente estudio es analizar la posibilidad de realizar esta técnica con un SMN externo ya validado, y estudiar su impacto en la indicación de la linfadenectomía axilar radical (LAR) y en la estancia postoperatoria. Pacientes y métodos. Estudio prospectivo en una cohorte de pacientes con cáncer de mama a partir de la implantación en nuestro centro de la técnica de la BSGC gracias a la colaboración de un SMN externo que realizaba la linfogammagrafía y la detección del ganglio centinela (GC), en tanto que su identificación intraoperatoria se llevaba a cabo mediante una sonda portátil. Se analiza la viabilidad del proyecto y su impacto clínico tomando como resultados finales la disminución del número de linfadenectomías y la estancia hospitalaria. Resultados. Se ha tratado a 196 pacientes, con 201 carcinomas de mama. Las intervenciones mayoritarias fueron la tumorectomía (TC) con BSGC en 124 casos (62%), y la TC con BSGC y LAR en 62 casos (31%). La visualización del GC en la linfogammagrafía se obtuvo en 187 de 201 casos (93,1%) y se ha detectado el GC durante la intervención en 182 de los 187 (97,4%) casos. La detección de GC en la cadena mamaria interna se ha producido en 23 de los 201 casos (11,4%). Se ha evitado la LAR en 131 de los 201 casos (65%). La diferencia de días de ingreso postoperatorio con o sin LAR fue de una media de 1,8 días (3,1 frente a 1,3; p < 0,001). Conclusiones. La técnica de BSGC ha sido factible con la colaboración de un SMN externo; se evitó el 65% de las LAR y disminuyó la estancia media en 1,8 días (AU)

Introduction. To perform sentinel lymph node biopsy (SLNB), nuclear medicine services that have previously undergone a validation phase are required. The aim of the present study was to analyze the possibility of performing this technique with a previously validated, external nuclear medicine service and to study its impact on the indication for radical axillary lymphadenectomy (RAL) and on length of postoperative hospital stay. Patients and methods. We performed a prospective study in a cohort of patients with breast cancer starting from the introduction of SLNB in our center, which was made possible by collaboration with an external nuclear medicine service that performed lymphoscintigraphy and sentinel node detection. Intraoperative detection was performed through a portable probe. The feasibility of the project and its clinical impact were analyzed, taking a reduction in the number of lymphadenectomies and length of hospital stay as endpoints. Results. A total of 196 patients with 201 breast carcinomas were treated. The most frequent interventions were tumorectomy (TC) with SLNB in 124 patients (62%), and TC with SLNB and RAL in 62 patients (31%). Sentinel node visualization on lymphoscintigraphy was achieved in 187/201 carcinomas (93.1 %) and sentinel nodes were detected during the intervention in 182/187 carcinomas (97.4%). Sentinel node detection in the internal mammary chain was achieved in 23/201 carcinomas (11.4%). RAL was avoided in 131 of the 201 carcinomas (65%). Days of postoperative hospital stay with or without RAL showed a mean difference of 1.8 days (3.1 vs. 1.3; P<.001). Conclusion. SLNB is feasible with the collaboration of an external nuclear medicine service. This technique avoids 65% of RAL and reduces length of postoperative stay by 1.8 days (AU)