The desert wolf-spider genus Xenoctenus: two endemic species from the Brazilian Caatinga, and a redescription of the type-species, X. unguiculatus (Araneae: Xenoctenidae).

The Caatinga is a nucleus of seasonally dry tropical forest (SDTF) known as a hotspot of diversification and endemism. Despite its importance, this biome is still insufficiently sampled, resulting in extensive knowledge gaps regarding its species richness and composition. In this study we report two species of Xenoctenidae that are endemic to, and widely distributed in the Caatinga. We redescribe and illustrate Odo vittatus (Mello-Leito, 1936), the only xenoctenid species previously known from the Caatinga. We transfer this species to Xenoctenus Mello-Leito,1938, a genus currently known from six species restricted to Argentina, Bolivia, and Colombia. We also newly describe the male of Xenoctenus vittatus comb. nov. and provide new records of this species, which was hitherto known only from the type-locality, throughout the Caatinga and nearby semiarid vegetation formations. We also describe and illustrate a new species, Xenoctenus kaatinga sp. nov., based on males and female specimens collected throughout the Caatinga. Additionally, we propose diagnostic characters for Xenoctenus and redescribe the type-species, X. unguiculatus.

Copulatory mechanics of ghost spiders reveals a new self-bracing mechanism in entelegyne spiders.

Spiders evolved a distinctive sperm transfer system, with the male copulatory organs located on the tarsus of the pedipalps. In entelegyne spiders, these organs are usually very complex and consist of various sclerites that not only allow the transfer of the sperm themselves but also provide a mechanical interlock between the male and female genitalia. This interlocking can also involve elements that are not part of the copulatory organ such as the retrolateral tibial apophysis (RTA)-a characteristic of the most diverse group of spiders (RTA clade). The RTA is frequently used for primary locking i.e., the first mechanical engagement between male and female genitalia. Despite its functional importance, some diverse spider lineages have lost the RTA, but evolved an apophysis on the femur instead. It can be hypothesized that this femoral apophysis is a functional surrogate of the RTA during primary locking or possibly serves another function, such as self-bracing, which involves mechanical interaction between male genital structures themselves to stabilize the inserted pedipalp. We tested these hypotheses using ghost spiders of the genus Josa (Anyphaenidae). Our micro-computed tomography data of cryofixed mating pairs show that the primary locking occurs through elements of the copulatory organ itself and that the femoral apophysis does not contact the female genitalia, but hooks to a projection of the copulatory bulb, representing a newly documented self-bracing mechanism for entelegyne spiders. Additionally, we show that the femoral self-bracing apophysis is rather uniform within the genus Josa. This is in contrast to the male genital structures that interact with the female, indicating that the male genital structures of Josa are subject to different selective regimes.

Health and well-being of the Portuguese citizens: impacts of the COVID-19.

BACKGROUND: COVID-19 pandemic placed unprecedented pressure on societies and healthcare systems around the world. Over the last years, measures imposed in almost all countries dealing with the pandemic sent the entire world into an extensive crisis and thus into a deep global recession. Since the outbreak began, many European countries have faced three/four waves of pandemic. Portugal has mainly dealt with three waves (March/April'2020; October/November'2020; January/February'2021), the third being the deadliest one. The purpose of this article is to provide evidence on the impact of the COVID-19 on health-related quality of life (HRQol) and well-being (W-B) of Portuguese citizens. It aims to (i) characterize these outcomes during the COVID-19 pandemic; (ii) compare them to pre-COVID-19 Portuguese population; and (iii) identify the social determinants that may affect these outcomes during the COVID-19 pandemic. METHODS: This study used data from a survey that collected data on HRQoL, W-B, satisfaction with life, economic and labour impacts, access to healthcare, mental and physical health, amongst others. The survey was implemented by telephone to a representative random sample of 1,255 respondents from the general adult Portuguese population, stratified by sex, age group and region. Data was collected during the end of the second national lockdown. For comparison purposes, we have also used two other representative databases from the general Portuguese population: (i) data from before the pandemic (n = 1,006); and (ii) data from a survey conducted during the first lockdown, (n = 904). RESULTS: Looking at health and access to healthcare, 4% of citizens had their surgeries postponed or cancelled because of COVID-19, more than a quarter had medical appointments or complementary exams postponed or cancelled, with 7% over 65 years old with surgeries cancelled or postponed and 32% medical appointments. COVID-19 pandemic also impacted negatively on the HRQoL of citizens, especially in the first lockdown. Half of the respondents reported feeling nervous, anxious, or on edge, about 45% of citizens felt sad or depressed. Sleeping problems were reported for almost 39% of citizens, and loneliness is reported by 29% of citizens. For about 70-85% of citizens, these feelings were more so than before the pandemic. Citizens with fair/strong economic stability were the most economically affected by the pandemic. CONCLUSIONS: We provided evidence on the impact of COVID-19 on health and W-B of Portuguese citizens. Their health was worse than before the pandemic and the access to healthcare was highly affected.

New trends in sugarcane fertilization: Implications for NH3 volatilization, N2O emissions and crop yields.

Recycling nutrients helps to reduce the environmental impact of agriculture and contributes to alleviating the effects of global climate change. A recent trend in sugarcane cultivation is the application of concentrated vinasse (CV) combined with fertilizers into an organo-mineral formulation to improve logistics, reduce costs and foster the circular economy. However, the implications of the application of such organo-mineral formulation in sugarcane fields are unclear. In this study, we evaluated the effects of the organo-mineral formulation containing granular urea (UR), and a nitrification inhibitor (NI) on crop yields, NH3 volatilization, and N2O emissions. Field experiments were conducted during two fertilization seasons, dry and wet, and the treatments were: control; UR; UR + NI; CV; CV + UR; and CV + UR + NI. CV was applied at 7 m3 ha-1. The treatments (except control and CV) were balanced to receive the same amount of N and K. Compared with UR, the organo-mineral formulation of CV + UR decreased NH3 volatilization losses from 7% to 4% in the dry season and from 3.5% to 0.5% in the wet season. Conversely, compared with UR, N2O emissions increased significantly (p ≤ 0.05) in CV + UR in the wet season from 1% to 2% of applied N. In the dry season, no differences were observed. The addition of NI was effective in mitigating N2O emissions in both seasons. Emission reductions ranged from 43 to 48% in the dry season and from 71 to 84%, in the wet season. Fertilization with UR or the organo-mineral formulation influenced sugarcane yield only in the dry season, with the highest yield in CV + UR. NI did not affect crop yield. In general, emission intensities (kg CO2eq Mg-1 of stalk) were highest in CV + UR. We conclude that the organo-mineral formulation reduced NH3 losses and increased N2O emissions compared with regular solid fertilizer and that NI was effective for mitigating N2O emissions.

EQ-5D-5L Portuguese population norms.

OBJECTIVES: The EQ-5D-5L is a generic preference-based quality-of-life measure for which the corresponding Portuguese population value set was only recently developed. This study sought to establish EQ-5D-5L population norms for Portugal and to identify significant relationships with sociodemographic variables. METHODS: The research was based on a representative sample of Portugal's general population (n = 1006) aged 18 or older. The sample was stratified by gender, age group, and geographical region. The respondents were interviewed by telephone and asked to value their own state of health using both the EQ-5D-5L description system and the EuroQol-Visual Analogue Scale (EQ VAS). RESULTS: The estimated mean EQ-5D-5L index for Portugal's general population is 0.887 (standard error [SE] = 0.0051), and the EQ VAS score was estimated as 76.0 (SE = 0.640). One-third of the population reported being in the best health state (11111). Women, individuals 70 years old or more and people with low education or a chronic disease reported a lower EQ-5D-5L index score (p < 0.001). Residents in the Azores and the Algarve reported higher health utility scores. CONCLUSIONS: The EQ-5D-5L Portuguese population norms obtained can be used as reference scores. These norms are consistent with other countries' population norms. The findings facilitate clinical, economic, and policy decision-making processes and provide a fuller understanding of the Portuguese population's health-related quality of life.

Chemoimmunotherapy Administration Protocol Design for the Treatment of Leukemia through Mathematical Modeling and In Silico Experimentation.

Cancer with all its more than 200 variants continues to be a major health problem around the world with nearly 10 million deaths recorded in 2020, and leukemia accounted for more than 300,000 cases according to the Global Cancer Observatory. Although new treatment strategies are currently being developed in several ongoing clinical trials, the high complexity of cancer evolution and its survival mechanisms remain as an open problem that needs to be addressed to further enhanced the application of therapies. In this work, we aim to explore cancer growth, particularly chronic lymphocytic leukemia, under the combined application of CAR-T cells and chlorambucil as a nonlinear dynamical system in the form of first-order Ordinary Differential Equations. Therefore, by means of nonlinear theories, sufficient conditions are established for the eradication of leukemia cells, as well as necessary conditions for the long-term persistence of both CAR-T and cancer cells. Persistence conditions are important in treatment protocol design as these provide a threshold below which the dose will not be enough to produce a cytotoxic effect in the tumour population. In silico experimentations allowed us to design therapy administration protocols to ensure the complete eradication of leukemia cells in the system under study when considering only the infusion of CAR-T cells and for the combined application of chemoimmunotherapy. All results are illustrated through numerical simulations. Further, equations to estimate cytotoxicity of chlorambucil and CAR-T cells to leukemia cancer cells were formulated and thoroughly discussed with a 95% confidence interval for the parameters involved in each formula.

Community dynamics of soil-borne fungal communities along elevation gradients in neotropical and palaeotropical forests.

Because of their steep gradients in abiotic and biotic factors, mountains offer an ideal setting to illuminate the mechanisms that underlie patterns of species distributions and community assembly. We compared the composition of taxonomically and functionally diverse fungal communities in soils along five elevational gradients in mountains of the Neo- and Palaeotropics (northern Argentina, southern Brazil, Panama, Malaysian Borneo and Papua New Guinea). Both the richness and composition of soil fungal communities reflect environmental factors, particularly temperature and soil pH, with some shared patterns among neotropical and palaeotropical regions. Community dynamics are characterized by replacement of species along elevation gradients, implying a relatively narrow elevation range for most fungi, which appears to be driven by contrasting environmental preferences among both functional and taxonomic groups. For functional groups dependent on symbioses with plants (especially ectomycorrhizal fungi), the distribution of host plants drives richness and community composition, resulting in important differences in elevational patterns between neotropical and palaeotropical montane communities. The pronounced compositional and functional turnover along elevation gradients implies that tropical montane forest fungi will be sensitive to climate change, resulting in shifts in composition and functionality over time.

Personalized Immunotherapy Treatment Strategies for a Dynamical System of Chronic Myelogenous Leukemia.

This paper is devoted to exploring personalized applications of cellular immunotherapy as a control strategy for the treatment of chronic myelogenous leukemia described by a dynamical system of three first-order ordinary differential equations. The latter was achieved by applying both the Localization of Compact Invariant Sets and Lyapunov's stability theory. Combination of these two approaches allows us to establish sufficient conditions on the immunotherapy treatment parameter to ensure the complete eradication of the leukemia cancer cells. These conditions are given in terms of the system parameters and by performing several in silico experimentations, we formulated a protocol for the therapy application that completely eradicates the leukemia cancer cells population for different initial tumour concentrations. The formulated protocol does not dangerously increase the effector T cells population. Further, complete eradication is considered when solutions go below a finite critical value below which cancer cells cannot longer persist; i.e., one cancer cell. Numerical simulations are consistent with our analytical results.

Analysing indoor mycobiomes through a large-scale citizen science study in Norway.

In the built environment, fungi can cause important deterioration of building materials and have adverse health effects on occupants. Increased knowledge about indoor mycobiomes from different regions of the world, and their main environmental determinants, will enable improved indoor air quality management and identification of health risks. This is the first citizen science study of indoor mycobiomes at a large geographical scale in Europe, including 271 houses from Norway and 807 dust samples from three house compartments: outside of the building, living room and bathroom. The fungal community composition determined by DNA metabarcoding was clearly different between indoor and outdoor samples, but there were no significant differences between the two indoor compartments. The 32 selected variables, related to the outdoor environment, building features and occupant characteristics, accounted for 15% of the overall variation in community composition, with the house compartment as the key factor (7.6%). Next, climate was the main driver of the dust mycobiomes (4.2%), while building and occupant variables had significant but minor influences (1.4% and 1.1%, respectively). The house-dust mycobiomes were dominated by ascomycetes (⁓70%) with Capnodiales and Eurotiales as the most abundant orders. Compared to the outdoor samples, the indoor mycobiomes showed higher species richness, which is probably due to the mixture of fungi from outdoor and indoor sources. The main indoor indicator fungi belonged to two ecological groups with allergenic potential: xerophilic moulds and skin-associated yeasts. Our results suggest that citizen science is a successful approach for unravelling the built microbiome at large geographical scales.

Tundra Type Drives Distinct Trajectories of Functional and Taxonomic Composition of Arctic Fungal Communities in Response to Climate Change - Results From Long-Term Experimental Summer Warming and Increased Snow Depth.

The arctic tundra is undergoing climate-driven changes and there are serious concerns related to the future of arctic biodiversity and altered ecological processes under possible climate change scenarios. Arctic land surface temperatures and precipitation are predicted to increase further, likely causing major transformation in terrestrial ecosystems. As a response to increasing temperatures, shifts in vegetation and soil fungal communities have already been observed. Little is known, however, how long-term experimental warming coupled with increased snow depth influence the trajectories of soil fungal communities in different tundra types. We compared edaphic variables and fungal community composition in experimental plots simulating the expected increase in summer warming and winter snow depth, based on DNA metabarcoding data. Fungal communities in the sampled dry and moist acidic tundra communities differed greatly, with tundra type explaining ca. one-third of compositional variation. Furthermore, dry and moist tundra appear to have different trajectories in response to climate change. Specifically, while both warming and increased snow depth had significant effects on fungal community composition and edaphic variables in dry tundra, the effect of increased snow was greater. However, in moist tundra, fungal communities mainly were affected by summer warming, while increased snow depth had a smaller effect and only on some functional groups. In dry tundra, microorganisms generally are limited by moisture in the summer and extremely low temperatures in winter, which is in agreement with the stronger effect of increased snow depth relative to warming. On the contrary, moist tundra soils generally are saturated with water, remain cold year-round and show relatively small seasonal fluctuations in temperature. The greater observed effect of warming on fungi in moist tundra may be explained by the narrower temperature optimum compared to those in dry tundra.

Soil depth matters: shift in composition and inter-kingdom co-occurrence patterns of microorganisms in forest soils.

Soil depth represents a strong physiochemical gradient that greatly affects soil-dwelling microorganisms. Fungal communities are typically structured by soil depth, but how other microorganisms are structured is less known. Here, we tested whether depth-dependent variation in soil chemistry affects the distribution and co-occurrence patterns of soil microbial communities. This was investigated by DNA metabarcoding in conjunction with network analyses of bacteria, fungi, as well as other micro-eukaryotes, sampled in four different soil depths in Norwegian birch forests. Strong compositional turnover in microbial assemblages with soil depth was detected for all organismal groups. Significantly greater microbial diversity and fungal biomass appeared in the nutrient-rich organic layer, with sharp decrease towards the less nutrient-rich mineral zones. The proportions of copiotrophic bacteria, Arthropoda and Apicomplexa were markedly higher in the organic layer, while patterns were opposite for oligotrophic bacteria, Cercozoa, Ascomycota and ectomycorrhizal fungi. Network analyses indicated more intensive inter-kingdom co-occurrence patterns in the upper mineral layer (0-5 cm) compared to the above organic and the lower mineral soil, signifying substantial influence of soil depth on biotic interactions. This study supports the view that different microbial groups are adapted to different forest soil strata, with varying level of interactions along the depth gradient.

Quality of life under the COVID-19 quarantine.

BACKGROUND: COVID-19 has spread rapidly throughout the world, causing thousands of illnesses and deaths. To fight this pandemic, almost all governments and health authorities have focused on prevention. In March or April, most countries' officials imposed home quarantine and lockdown measures nationwide. PURPOSE: This study sought to assess health-related quality of life (HRQoL) and anxiety levels among people in Portugal under mandatory home quarantine due to the COVID-19 pandemic. The results were compared to the general Portuguese population's HRQoL before the COVID-19 outbreak. This research also aimed to understand the factors that can influence the respondents' HRQoL. METHODS: A sample of Portugal's population quarantined at home (n = 904) filled in an online survey comprising the Generalized Anxiety Disorder 7-item and the EQ-5D-5L and other questions about sociodemographic characteristics, feelings, duties and activities during the quarantine. The sample was weighted to mirror the general population's gender, age and education. Descriptive analyses and correlation coefficients were used to evaluation the respondents' anxiety and HRQoL. Generalised linear models were estimated to identify determinants of HRQoL during the COVID-19 quarantine. RESULTS: The results show that individuals quarantined at home reported higher anxiety and lower HRQoL levels and that people with more anxiety tended to have a lower HRQoL. Females and elderly individuals experienced the highest levels of anxiety and poorest HRQoL. In addition, HRQoL during the quarantine can be explained by various occupational and attitudinal variables, as well as sociodemographic variables. CONCLUSION: Individuals' mental health should be taken into consideration during pandemics or other emergency situations. Anxiety and other factors can decrease people's HRQoL, in conjunction with the pandemic's social and economic consequences.

Neurocognitive evaluation using the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment Test (MoCA) in an HIV-2 population.

OBJECTIVES: We aimed to characterize neurocognitive impairment (NI) in an HIV-2 population using an observational cross-sectional study in four Portuguese hospitals. METHODS: Adult HIV-2-infected patients were included. Montreal Cognitive Assessment Test (MoCA) and International HIV Dementia Scale (IHDS) scales were applied for screening of NI. Patient Health Questionnaire-9 (PHQ-9) and Instrumental Activities of Daily Living (IADL) scales were used for assessment of depression and functionality. A multivariate analysis was performed to assess for risk factors for NI. RESULTS: Eighty-one patients were included, 50.6% of African origin (n = 41) and 49.4% of Portuguese origin (n = 40). The MoCA scale showed alterations in 81.5% of patients (100% of migrants vs. 62.5% of non-migrants, P < 0.001) and the IHDS scale showed alterations in 42%. Both scales were altered simultaneously in 35.8%. Variables independently associated with NI were age [odds ratio (OR) = 0.885] and migrant status (OR = 9.150). CONCLUSIONS: Neurocognitive impairment (both scales altered) was present in 35.8%, which is comparable to what is described for HIV-1. The MoCA performed worse in the migrant population and might not be applicable in this setting.

Outcomes in non-ST-segment elevation myocardial infarction patients according to heart failure at admission: Insights from a large trial with systematic early invasive strategy.

BACKGROUND: Previous studies published before the era of systematic early invasive strategy have reported a higher mortality in non-ST-segment elevation myocardial infarction patients with heart failure. The aim of our study was to compare the clinical characteristics, outcomes and causes of death of patients according to their heart failure status at admission in a large non-ST-segment elevation myocardial infarction population with planned early invasive management. METHODS: We performed a post-hoc analysis of the Treatment of Acute Coronary Syndrome with Otamixaban randomised trial which included non-ST-segment elevation myocardial infarction patients with systematic coronary angiography within 72 h. Patients were categorised according to presence or absence of heart failure (Killip grade ≥2) at admission. RESULTS: A total of 13,172 patients were enrolled, of whom 944 (7.2%) had heart failure. At day 30, death occurred in 213 patients (1.6%) and cardiovascular death was the dominant cause of death in both groups ((with vs without heart failure) 78.8% vs 78.4%, p = 0.94). At six months, death occurred in 90/944 (9.5%) patients with heart failure and 258/12228 patients without heart failure (2.1%) (p < 0.001). After adjustment on Global Registry of Acute Coronary Events risk score, heart failure was an independent predictor of all-cause mortality at day 30 (odds ratio: 1.58; 95% confidence interval, 1.06-2.36, p = 0.02) and at day 180 (odds ratio: 1.77; 95% confidence interval, 1.3-2.42, p < 0.001) as well as of ischaemic complications (cardiovascular death, myocardial infarction, stent thrombosis or stroke at day 30 (odds ratio: 1.28; 95% confidence interval, 1.01-1.62, p = 0.04). CONCLUSION: Non-ST-segment elevation myocardial infarction patients with heart failure at admission still have worse outcomes than those without heart failure, even with systematic early invasive strategy. Further efforts are needed to improve the prognosis of these high risk patients.

Estimation of maximum temperature and thermal crosstalk between two active elements in a PIC: development of a thermal equivalent circuit.

The operating temperature plays a key role in the performance and lifetime of photonic integrated circuits (PICs). Miniaturization and increasing heat dissipation promote thermal crosstalk effects and pose additional challenges to the PIC designer. The European Photonics Industry Consortium recommends thermal modeling during design phase. However, a fully numerical optimization of a particular layout requires an unrealistically large number of simulations. Here, we propose a compromise approach: a set of carefully chosen simulations are performed with a multi-physics software. The obtained results are used to derive a linearized equivalent thermal circuit that can be used to maximize the power levels and to minimize the distance between the chosen components while guaranteeing the absence of a thermal crosstalk. For simplification, this model is derived considering a PIC with only two active components. Other parameters are varied, such as the material of the holder (silicon or diamond) and the layer of epoxy that is used to attach the PIC to the holder. The obtained circuit is used to determine the maximum dissipated power or the minimum distance between the components while keeping some predetermined specifications. The model can be extended to contain more elements or to include transient analysis of the temperature distribution.

Outcomes in non-ST-segment elevation myocardial infarction patients according to heart failure at admission: Insights from a large trial with systematic early invasive strategy.

BACKGROUND: Previous studies published before the era of systematic early invasive strategy have reported a higher mortality in non-ST-segment elevation myocardial infarction patients with heart failure. The aim of our study was to compare the clinical characteristics, outcomes and causes of death of patients according to their heart failure status at admission in a large non-ST-segment elevation myocardial infarction population with planned early invasive management. METHODS: We performed a post-hoc analysis of the Treatment of Acute Coronary Syndrome with Otamixaban randomised trial which included non-ST-segment elevation myocardial infarction patients with systematic coronary angiography within 72 h. Patients were categorised according to presence or absence of heart failure (Killip grade ≥2) at admission. RESULTS: A total of 13,172 patients were enrolled, of whom 944 (7.2%) had heart failure. At day 30, death occurred in 213 patients (1.6%) and cardiovascular death was the dominant cause of death in both groups ((with vs without heart failure) 78.8% vs 78.4%, p = 0.94). At six months, death occurred in 90/944 (9.5%) patients with heart failure and 258/12228 patients without heart failure (2.1%) (p < 0.001). After adjustment on Global Registry of Acute Coronary Events risk score, heart failure was an independent predictor of all-cause mortality at day 30 (odds ratio: 1.58; 95% confidence interval, 1.06-2.36, p = 0.02) and at day 180 (odds ratio: 1.77; 95% confidence interval, 1.3-2.42, p < 0.001) as well as of ischaemic complications (cardiovascular death, myocardial infarction, stent thrombosis or stroke at day 30 (odds ratio: 1.28; 95% confidence interval, 1.01-1.62, p = 0.04). CONCLUSION: Non-ST-segment elevation myocardial infarction patients with heart failure at admission still have worse outcomes than those without heart failure, even with systematic early invasive strategy. Further efforts are needed to improve the prognosis of these high risk patients.

Copulatory mechanics in the wolf spider Agalenocosa pirity reveals a hidden diversity of locking systems in Lycosidae (Araneae).

Genital traits are among the fastest to evolve, and the processes that drive their evolution are intensively studied. Spiders are characterized by complex genitalia, but the functional role of the different structures during genital coupling is largely unknown. Members of one of the largest spider groups, the retrolateral tibial apophysis (RTA) clade, are characterized by a RTA on the male palp, which is thought to play a crucial role during genital coupling. However, the RTA was lost in several families including the species-rich wolf spiders (Lycosidae) leading to the hypothesis that the genital coupling is achieved by alternative mechanisms. Here, we investigate the genital interactions during copulation in the wolf spider Agalenocosa pirity (Zoicinae) on cryofixed mating pairs using electron, optical and X-ray microscopy and compare our findings with other lycosids and entelegyne spiders. We found an unprecedented coupling mechanism for lycosid spiders involving the palea and a membranous cuticle folding adjacent to the epigynal plate. Additionally, we show an uncommon coupling between the median apophysis and the contralateral genital opening, and confirmed that the terminal apophysis acts as functional conductor, as previously hypothesized for males of Zoicinae. Phylogenetic mapping of RTA indicated that the basal tibial process found in Agalenocosa is a secondary acquisition rather than a modified RTA.

Tumor Clearance Analysis on a Cancer Chemo-Immunotherapy Mathematical Model.

Mathematical models may allow us to improve our knowledge on tumor evolution and to better comprehend the dynamics between cancer, the immune system and the application of treatments such as chemotherapy and immunotherapy in both short and long term. In this paper, we solve the tumor clearance problem for a six-dimensional mathematical model that describes tumor evolution under immune response and chemo-immunotherapy treatments. First, by means of the localization of compact invariant sets method, we determine lower and upper bounds for all cells populations considered by the model and we use these results to establish sufficient conditions for the existence of a bounded positively invariant domain in the nonnegative orthant by applying LaSalle's invariance principle. Then, by exploiting a candidate Lyapunov function we determine sufficient conditions on the chemotherapy treatment to ensure tumor clearance. Further, we investigate the local stability of the tumor-free equilibrium point and compute conditions for asymptotic stability and tumor persistence. All conditions are given by inequalities in terms of the system parameters, and we perform numerical simulations with different values on the chemotherapy treatment to illustrate our results. Finally, we discuss the biological implications of our work.

A hybrid modelling approach for eliciting health state preferences: the Portuguese EQ-5D-5L value set.

BACKGROUND: The EQ-5D is a generic preference-based quality of life measure considered useful for supporting clinical and policy decisions by providing utility values that can easily be converted into quality-adjusted life years to be integrated in cost-utility economic evaluations. Although the three-level classification system of the EuroQol questionnaire (EQ-5D-3L) is still the most popular preference-based instrument used worldwide, several studies reported a ceiling effect on this version, especially in healthy and/or young individuals. In 2009, the EuroQol Group introduced a five-level EQ-5D, which expands the descriptive system from three to five levels within the same five dimensions. For this version to be used in health economic evaluation, societal values need to be assigned to the 3125 health states generated by this instrument. OBJECTIVES: The aims of this study were to elicit the EQ-5D-5L health state preferences from the general Portuguese population and to derive the Portuguese value set for the EQ-5D-5L. METHODS: A representative sample of the Portuguese general population aged above 18 years was stratified by age and gender (n = 1451). Between October 2015 and July 2016, 28 interviewers carried out a series of 1-h-long computer-assisted personal interviews following the EuroQol Valuation Technology protocol. Each interview included the valuation of ten health states using the composite time trade-off (cTTO) and seven pairs of discrete choice experiments (DCEs). A standardized tool for quality control was used to assess the quality of the data as well as direct supervision and cross-examination of 10% of the global sample size. Data from both cTTO and DCE valuation tasks were modelled using a censored heteroskedastic hybrid model. RESULTS: Interviewers complied with the quality control protocol in providing high-quality valuation data. The hybrid econometric model had consistent and significant parameters. The derived societal values for the Portuguese population ranged from - 0.603 to 1. CONCLUSION: This study provided the Portuguese value set for the EQ-5D-5L on the basis of a hybrid econometric model using cTTO and DCE data. These results represent the preferences of the Portuguese population and are recommended to inform health decision-making in Portugal.