Potential ecological and socio-economic effects of a novel megaherbivore introduction: the hippopotamus in Colombia

Introduced species can have strong ecological, social and economic effects on their non-native environment. Introductions of megafaunal species are rare and may contribute to rewilding efforts, but they may also have pronounced socio-ecological effects because of their scale of influence. A recent introduction of the hippopotamus Hippopotamus amphibius into Colombia is a novel introduction of a megaherbivore onto a new continent, and raises questions about the future dynamics of the socio-ecological system into which it has been introduced. Here we synthesize current knowledge about the Colombian hippopotamus population, review the literature on the species to predict potential ecological and socio-economic effects of this introduction, and make recommendations for future study. Hippopotamuses can have high population growth rates (7–11%) and, on the current trajectory, we predict there could be 400–800 individuals in Colombia by 2050. The hippopotamus is an ecosystem engineer that can have profound effects on terrestrial and aquatic environments and could therefore affect the native biodiversity of the Magdalena River basin. Hippopotamuses are also aggressive and may pose a threat to the many inhabitants of the region who rely upon the Magdalena River for their livelihoods, although the species could provide economic benefits through tourism. Further research is needed to quantify the current and future size and distribution of this hippopotamus population and to predict the likely ecological, social and economic effects. This knowledge must be balanced with consideration of social and cultural concerns to develop appropriate management strategies for this novel introduction

Extraction of the antioxidant phytocomplex from wine-making by-products and sustainable loading in phospholipid vesicles specifically tailored for skin protection

The present study is aimed at valorizing grape pomace, one of the most abundant winery-making by-products of the Mediterranean area, through the extraction of the main bioactive compounds from the skin of grape pomace and using them to manufacture innovative nanoformulations capable of both avoiding skin damages and promoting skincare. The phytochemicals were recovered through maceration in hydroethanolic solution. Catechin, quercetin, fisetin and gallic acid, which are known for their antioxidant power, were detected as the main compounds of the extract. Liposomes and phospholipid vesicles modified with glycerol or Montanov 82® or a combination of both, were used as carriers for the extract. The vesicles were small (~183 nm), slightly polydispersed (PI ≥ 0.28), and highly negatively charged (~−50 mV). The extract was loaded in high amounts in all vesicles (~100%) irrespective of their composition. The antioxidant activity of the extract, measured by using the DPPH (2,2-Diphenyl-1-picrylhydrazyl) test, was 84 ± 1%, and slightly increased when loaded into the vesicles (~89%, P < 0.05). The grape pomace extract loaded vesicles were highly biocompatible and able to protect fibroblasts (3T3) from the oxidative stress induced by hydrogen peroxide

Incorporation of lippia citriodora microwave extract into total-green biogelatin-phospholipid vesicles to improve its antioxidant activity

Phytochemicals from Lippia citriodora leaves were extracted by applying an innovative technology based on the use of microwaves, which represents an alternative method to extract bioactive substances. The obtained extract was incorporated into phospholipid vesicles in order to promote the antioxidant effect of the bioactive molecules present in L. citriodora extract. The extract was analyzed by High Performance Liquid Chromatography coupled to Time-Of-Flight mass spectrometer by electrospray (HPLC-ESI-TOF-MS) and different phytochemicals were detected and quantified. The whole extract was incorporated in liposomes, glycerosomes (liposomes modified with glycerol) and propylene glycol-containing vesicles (PG-PEVs). Moreover, a biopolymer obtained from fish by-product, that is Thunnus albacares skin, was added to improve the bioactivity of the formulations. The in vitro biocompatibility and the antioxidant efficacy of the extract in solution or loaded in the vesicles were tested in primary mouse embryonic fibroblasts (3T3). The results showed the superior bioactivity of the vesicle formulations over the aqueous solution of the extract, which points to an interesting strategy for the treatment of skin disorders

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin

Single immune checkpoint blockade has shown limited activity in patients with neuroendocrine neoplasms (NENs). Here the authors report the results of a phase II clinical trial of durvalumab (anti-PD-L1) and tremelimumab (anti CTLA-4) in patients with advanced NENs of gastroenteropancreatic and lung origin. Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS

A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry

BACKGROUND: The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry. METHOD: TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain. RESULTS: Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p<0.0001). The 12-month cumulative incidence of venous rethrombosis was 7.1% (95% CI, 4.7-10.2) in stage IV vs 3.0% (95% CI, 0.9-7.1) in stages I-III. The 12-month cumulative incidence of major/clinically relevant bleeding was 9.6% (95% CI, 6.1-14.0) in the presence of risk factors. CONCLUSION: CAT continues to be a relevant problem in the era of immunotherapy and targeted therapies. The initial TESEO data highlight the evolution of CAT, with new agents and thrombotic risk factors

Seeds of Life in Space (SOLIS) VI. Chemical evolution of sulfuretted species along the outflows driven by the low-mass protostellar binary NGC1333-IRAS4A

Context: Low-mass protostars drive powerful molecular outflows that can be observed with millimetre and submillimetre telescopes. Various sulfuretted species are known to be bright in shocks and could be used to infer the physical and chemical conditions throughout the observed outflows. Aims: The evolution of sulfur chemistry is studied along the outflows driven by the NGC 1333-IRAS4A protobinary system located in the Perseus cloud to constrain the physical and chemical processes at work in shocks. Methods: We observed various transitions from OCS, CS, SO, and SO2 towards NGC 1333-IRAS4A in the 1.3, 2, and 3 mm bands using the IRAM NOrthern Extended Millimeter Array and we interpreted the observations through the use of the Paris-Durham shock model. Results: The targeted species clearly show different spatial emission along the two outflows driven by IRAS4A. OCS is brighter on small and large scales along the south outflow driven by IRAS4A1, whereas SO2 is detected rather along the outflow driven by IRAS4A2 that is extended along the north east–south west direction. SO is detected at extremely high radial velocity up to +25 km s−1 relative to the source velocity, clearly allowing us to distinguish the two outflows on small scales. Column density ratio maps estimated from a rotational diagram analysis allowed us to confirm a clear gradient of the OCS/SO2 column density ratio between the IRAS4A1 and IRAS4A2 outflows. Analysis assuming non Local Thermodynamic Equilibrium of four SO2 transitions towards several SiO emission peaks suggests that the observed gas should be associated with densities higher than 105 cm−3 and relatively warm (T > 100 K) temperatures in most cases. Conclusions: The observed chemical differentiation between the two outflows of the IRAS4A system could be explained by a different chemical history. The outflow driven by IRAS4A1 is likely younger and more enriched in species initially formed in interstellar ices, such as OCS, and recently sputtered into the shock gas. In contrast, the longer and likely older outflow triggered by IRAS4A2 is more enriched in species that have a gas phase origin, such as SO2

Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study

Background Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD), which constitutes a serious public health problem. Objective To investigate whether single nucleotide polymorphisms (SNPs) located in genes related to immune and inflammatory processes, could be associated with ESRD development. Design and methods A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. Results Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R) gene (OR: 0.66 (95%CI=0.46-0.95); p=0.025; overdominant model), rs4586 in chemokine (C-C motif) ligand 2 (CCL2) gene (OR: 0.70 (95%CI=0.54-0.90); p=0.005; additive model), rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4) (OR: 1.82 (95%CI=1.17-2.83); p=0.006; additive model) and rs7830 in the nitric oxide synthase 3 (NOS3) gene (OR: 1.31 (95%CI=1.01-1.71); p=0.043; additive model). After adjusting for multiple testing, results lost significance. Conclusion Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD.This work was supported by grants from Instituto de Salud Carlos III (Ref: PI08/0738 and PI11/00245) to SR and Junta de Castilla y Leon (Ref: GRS 234/A/08) to ET. 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Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients

A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia