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Growth alterations have been described in patients operated on for oral clefts. The purpose of this work was to analyze the craniofacial and palate morphology and dimensions of young adults operated on for oral clefts in early childhood in Spain. Eighty-three patients from eight different hospitals were divided into four groups based on their type of cleft: cleft lip (CL, n = 6), unilateral cleft lip and palate (UCLP, n = 37), bilateral cleft lip and palate (BCLP, n = 16), and cleft palate only (CPO, n = 24). A control group was formed of 71 individuals. Three-dimensional (3D) digital models were obtained from all groups with an intraoral scanner, together with cephalometries and frontal, lateral, and submental facial photographs. Measurements were obtained and analyzed statistically. Our results showed craniofacial alterations in the BCLP, UCLP, and CPO groups with an influence on the palate, maxilla, and mandible and a direct impact on facial appearance. This effect was more severe in the BCLP group. Measurements in the CL group were similar to those in the control group. Cleft characteristics and cleft type seem to be the main determining factors of long-term craniofacial growth alterations in these patients. Prospective research is needed to clearly delineate the effects of different treatments on the craniofacial appearance of adult cleft patients.

Neochlorogenic acid, a less-studied isomer of chlorogenic acid, has been seen to posses antioxidant, antifungal, anti-inflammatory and anticarcinogenic effects, which makes it an interesting candidate for incorporation in functional foods. However, its poor solubility in water and susceptibility to oxidation make such a task difficult. To overcome that, its encapsulation in cyclodextrins (CDs) is proposed. The fluorescence of neochlorogenic acid in different pH conditions was analyzed, and caffeic acid was proved to be the fluorescent moiety in the molecule. An encapsulation model whereby the ligand poses two potential complexation sites (caffeic and D-(-)-quinic moieties), showed that α-CD and HP-β-CD formed the best inclusion complexes with neochlorogenic acid, followed by M-β-CD, β-CD and γ-CD. Molecular docking with the two best CDs gave better scores for α-CD, despite HP-β-CD providing stabilization through H-bonds. The encapsulation of chlorogenic acid led to a similar CD order and scores, although constants were higher for α-CD, β-CD and M-β-CD, lower for HP-β-CD, and negligible for γ-CD. The protonation state affected these results leading to a different order of CD preference. The solubility and the susceptibility to oxidation of neochlorogenic acid improved after complexation with α-CD and HP-β-CD, while the antioxidant activity of both isomers was maintained.

Endometrial Cancer (EC) is one of the most common malignancies in women in developed countries. Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) and Copy Number High (CNH). The goal of this study was to develop a method to classify tumors in any of the four EC prognostic groups using affordable molecular techniques. Ninety-six Formalin-Fixed Paraffin-embedded (FFPE) samples were sequenced following a NGS TruSeq Custom Amplicon low input (Illumina) protocol interrogating a multi-gene panel. MSI analysis was performed by fragment analysis using eight specific microsatellite markers. A Random Forest classification algorithm (RFA), considering NGS results, was developed to stratify EC patients into different prognostic groups. Our approach correctly classifies the EC patients into the four TCGA prognostic biotypes. The RFA assigned the samples to the CNH and CNL groups with an accuracy of 0.9753 (p

Very few data exist on when a particular thrombopoietin-receptor agonist (TPO-RA) is favored in clinical practice for the treatment of patients with immune thrombocytopenia (ITP), about novel risk factors for vascular events (VE) with these drugs, nor about predictive factors for therapy free responses (TFR). We conducted an observational, retrospective, long-term follow-up multicenter study from November 2016 to January 2018 of 121 adult ITP patients initiating TPO-RA between January 2012 to December 2014. Data reflected that a platelet count ≤25 × 109/l at the time when the TPO-RA was initiated was associated with a 2.8 higher probability of receiving romiplostim vs. eltrombopag (P = 0.010). VE on TPO-RA was related to previous neoplasia in patients over 65 years (50% vs. 2.2%, P vs. 33%, P = 0.001). Receiving romiplostim as first TPO-RA with no subsequent TPO-RA switching was associated with a 50% likelihood of TFR after 2.9 years of therapy (3.3 years in chronic ITP patients). These real-world data help deciphering some areas of uncertainty, and offer insight into some of the most relevant challenges of ITP which may help clinicians make appropriate treatment decisions in the management of adult ITP patients with TPO-RA.

The mediating and moderating associations of cardiorespiratory fitness (CRF) and handgrip strength on the association between dietary patterns and several health outcomes have been previously studied. For instance, handgrip strength has been found as a moderator of the relationship between excess weight and cardiometabolic risk factors in young adults. Similarly, CRF has been shown as a mediator of the association between diet and obesity in children. However, to our knowledge, the role of CRF and handgrip strength on the association between sugar-sweetened beverage (SSB) consumption and adiposity is still unclear. The aim of this study was to determine whether CRF and handgrip strength moderate the association between SSB consumption and adiposity in a population-based sample of Spanish schoolchildren. This cross-sectional study involved 475 schoolchildren (52.0% girls), aged 8–12, from ten schools in Cuenca (Spain). Adiposity was determined as body fat (in kg), which was measured using a bioimpedance analysis system. Data on SSB consumption were gathered by using the Children’s Eating Habits Questionnaire, which was completed by parents. The CRF level was determined by the 20-m Shuttle Run test and Nevill’s curvilinear allometric model. Handgrip strength was determined using a digital dynamometer with adjustable grip. For each unit (in ml/kg/min) of CRF increased, the association between SSB consumption and adiposity was moderated (B = − 0.09, CI 95% − 0.14 to − 0.04). This significant moderation was also found for each 0.01 unit of increased normalized handgrip strength (B = − 0.07; CI 95% − 0.11 to − 0.02). Similarly, the Johnson-Neymann technique established three different regions. The first region shows that the association of SSB consumption on adiposity in participants who had levels of CRF 57.4 ml/kg/min (for CRF level) and > 0.58 (for normalized handgrip strength), indicating that the association between SSB consumption and adiposity was lower and statistically significant in children above these moderator values. Our results showed that certain levels of CRF and normalized handgrip strength moderate the association between SSB consumption and adiposity in a sample of Spanish schoolchildren. It might be possible that higher physical fitness level in childhood may contribute to reducing the association between SSB consumption and adiposity.

The endocannabinoid system (ECS), a signalling network with immunomodulatory properties, is a potential therapeutic target in multiple sclerosis (MS). Dimethyl fumarate (DMF) is an approved drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its therapeutic effects could imply the ECS. With the aim of studying if DMF can modulate the ECS, the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) were determined by liquid chromatography-mass spectrometry in peripheral blood mononuclear cells from 21 healthy donors (HD) and 32 MS patients at baseline and after 12 and 24 months of DMF treatment. MS patients presented lower levels of 2-AG and PEA compared to HD. 2-AG increased at 24 months, reaching HD levels. AEA and PEA remained stable at 12 and 24 months. OEA increased at 12 months and returned to initial levels at 24 months. Patients who achieved no evidence of disease activity (NEDA3) presented the same modulation over time as EDA3 patients. PEA was modulated differentially between females and males. Our results show that the ECS is dysregulated in MS patients. The increase in 2-AG and OEA during DMF treatment suggests a possible role of DMF in ECS modulation.

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.

The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p p p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22–11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37–15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia.

Is terrorism just another form of criminal activity, as many nations’ justice systems assume? We offer an initial answer using face-to-face interviews and structured surveys in thirty-five Spanish prisons. Recent theories of extreme sacrifice inform this direct observational and comparative study. Islamist terrorists display levels of self-sacrifice for their primary reference group similar to that of Latino gangs, but greater willingness to sacrifice for primary values than other inmates (non-radical Muslims, Latino gangs, and delinquent bands). This disposition is motivated by stronger perceived injustice, discrimination, and a visceral commitment to such values (risk/radicalization factors). Nevertheless, state authorities, prison staff, and families are (protective/de-radicalization) factors apt to reduce willingness to sacrifice and keep foreign fighters, now being released in large numbers, from returning to terrorism.

The aim of this study was to determine whether handgrip strength attenuates the negative relationship between age and olfactory function in a representative US population sample 40 years old and over. A cross-sectional study was performed with 2861 adults from the US National Health and Nutrition Examination Survey NHANES (2013–2014). An 8-item odor identification test was applied to determine olfactory function. Muscle strength was determined through a handgrip dynamometer (defined as the sum of the largest handgrip strength reading from right and left hands). Moderation analysis was performed to test whether the association between age and olfactory impairment was moderated by handgrip strength. Moderation analysis highlighted two regions of significance: the first region was found at < 56.6 kg, indicating that the adverse influence of age on olfactory function may be greater for the participants in this area; the second region was found at ≥ 56.6 kg, indicating that the negative impact of age on olfactory function disappeared for adults who were above this estimate point. In conclusion, handgrip strength, a general indicator of muscle strength, moderates the relationship between age and olfactory ability in a US adult population aged 40 years and older. Our findings are clinically relevant, since they emphasize the importance of muscular fitness in adulthood and old age by diminishing the deleterious effect of aging on olfactory performance. A.G.-H. is a Miguel Servet Fellow (Instituto de Salud Carlos III-FSE – CP18/0150). R.R.-V. is funded in part by a Postdoctoral Fellowship Resolution ID 420/2019 of the Universidad Pública de Navarra.

The pH–CO2–HCO3− system is a ubiquitous biological regulator with important functional implications for reproduction. Knowledge of the physiological values of its components is relevant for reproductive biology and the optimization of Assisted Reproductive Technologies (ARTs). However, in situ measurements of these parameters in the uterus are scarce or null. This study describes a non-invasive method for in situ time-lapse recording of pH and CO2 within the uterus of non-anesthetized sows. Animals were at three different reproductive conditions, estrous with no insemination and two hours after insemination, and diestrous. From pH and CO2 data, HCO3− concentration was estimated. The non-invasive approach to the porcine uterus with novel optical probes allowed the obtaining of in situ physiological values of pH, CO2, and HCO3−. Variable oscillatory patterns of pH, CO2 and HCO3− were found independently of the estrous condition. Insemination did not immediately change the levels of uterine pH, CO2 (%) and HCO3− concentration, but all the values were affected by the estrous cycle decreasing significantly at diestrous condition. This study contributes to a better understanding of the in vivo regulation of the pH-CO2-HCO3− system in the uterus and may help to optimize the protocols of sperm treatment for in vitro fertilization.

It is necessary to identify suitable alternative crops to ensure the nutritional demands of a growing global population. The genome of Moringa oleifera, a fast-growing drought-tolerant orphan crop with highly valuable agronomical, nutritional and pharmaceutical properties, has recently been reported. We model here gene family evolution in Moringa as compared with ten other flowering plant species. Despite the reduced number of genes in the compact Moringa genome, 101 gene families, grouping 957 genes, were found as significantly expanded. Expanded families were highly enriched for chloroplastidic and photosynthetic functions. Indeed, almost half of the genes belonging to Moringa expanded families grouped with their Arabidopsis thaliana plastid encoded orthologs. Microsynteny analysis together with modeling the distribution of synonymous substitutions rates, supported most plastid duplicated genes originated recently through a burst of simultaneous insertions of large regions of plastid DNA into the nuclear genome. These, together with abundant short insertions of plastid DNA, contributed to the occurrence of massive amounts of plastid DNA in the Moringa nuclear genome, representing 4.71%, the largest reported so far. Our study provides key genetic resources for future breeding programs and highlights the potential of plastid DNA to impact the structure and function of nuclear genes and genomes.

Càncer; Biologia molecular; Oncologia Cancer; Molecular biology; Oncology Cáncer; Biología molecular; Oncología The poly (ADP-Ribose) polymerase (PARP) inhibitor olaparib has shown antitumor activity in patients with ovarian or breast cancer with or without BRCA1/2 mutations. Lurbinectedin is an ecteinascidin that generates DNA double-strand breaks. We hypothesized that the combination of olaparib and lurbinectedin maximizes the DNA damage increasing the efficacy. A 3 + 3 dose-escalation study examined olaparib tablets with lurbinectedin every 21 days. The purpose of this phase I study is to determine the dose-limiting toxicities (DLTs) of the combination, to investigate the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), efficacy, pharmacokinetics, in addition to genotyping and translational studies. In total, 20 patients with ovarian and endometrial cancers were included. The most common adverse events were asthenia, nausea, vomiting, constipation, abdominal pain, neutropenia, anemia. DLT grade 4 neutropenia was observed in two patients in dose level (DL) 5, DL4 was defined as the MTD, and the RP2D was lurbinectedin 1.5 mg/m2 + olaparib 250 mg twice a day (BID). Mutational analysis revealed a median of 2 mutations/case, 53% of patients with mutations in the homologous recombination (HR) pathway. None of the patients reached a complete or partial response; however, 60% of stable disease was achieved. In conclusion, olaparib in combination with lurbinectedin was well tolerated with a disease control rate of 60%. These results deserve further evaluation of the combination in a phase II trial. This trial was sponsored by AstraZeneca and PharmaMar, including supply of study drugs.

The controls that affect the structure and timing of terminations are still poorly understood. We studied a tufa deposit from the Iberian Peninsula that covers Termination II (T-II) and whose chronology was synchronized to speleothem records. We used the same chronology to synchronize ocean sediments from the North Atlantic to correlate major climate events in a common timescale. We identify two stages within T-II. The first stage started with the increase of boreal summer integrated solar insolation, and during this stage three millennial climate oscillations were recorded. These oscillations resulted from complex ocean–atmosphere interactions in the Nordic seas, caused by the progressive decay of Northern Hemisphere ice-sheets. The second stage commenced after a glacial outburst that caused the collapse of the Thermohaline Circulation, a massive Heinrich event, and the onset of the Bipolar Seesaw Mechanism (BSM) that eventually permitted the completion of T-II. The pace of the millennial oscillations during the first stage of T-II controlled the onset of the second stage, when the termination became a non-reversible and global phenomenon that accelerated the deglaciation. During the last the two terminations, the BSM was triggered by different detailed climate interactions, which suggests the occurrence of different modes of terminations., The Junta de Comunidades de Castilla-La Mancha provided the permissions to sample in Trabaque Canyon. Tis research received funding from the European Community under the Marie Curie IEF of the FP7/2007-2013 (Grant agreement no. 219891: PROCAVET project, awarded to D.D.-V.). Publication was supported by the Open Access Publication Fund of the University of Zagreb Faculty of Agriculture

Streptococcus agalactiae (GBS) remains the leading cause of meningitis and neonatal sepsis in the world, and causes disease in pregnant and puerperal women. This is a retrospective study of GBS infections on women of childbearing age living in Comunitat Valenciana, Spain (years 2009-2014) and GBS colonization rate on pregnant women attending Hospital La Fe (years 2013-2015) according to their origin. An aggregated total of 6,641,960 women exposed during the study period had an average GBS isolation rate of 5.19 parts per thousand (5.14-5.25 parts per thousand), geographical group rates being: Western Europe (2.2 parts per thousand), North America (2.1 parts per thousand), Australia (3.7 parts per thousand), Spain (4.6 parts per thousand), Latin America II (4.5 parts per thousand), Eastern Europe (5.3 parts per thousand), Asia (6.7 parts per thousand), Latin America I (7.7 parts per thousand), Middle East (7.9 parts per thousand), Indian Subcontinent (17.2 parts per thousand), North Africa (17.8 parts per thousand), Sub-Saharan Africa (22.7 parts per thousand). The 4532 pregnant women studied had an average GBS colonization rate of 12.47% (11.51-13.43) and geographical group rates varied similar to geographical isolation rates. Low GDP and high temperatures of the birth country were associated with higher colonization rates. Thus, differences in GBS colonization depend on the country of origin; Africa and the Indian subcontinent presented the highest, while Western Europe and North America had the lowest. This variability portrays a geographical pattern influenced by temperature and GDP.

Pyrazinamide (PZA) is an antibiotic used in first- and second-line tuberculosis treatment regimens. Approximately 50% of multidrug-resistant tuberculosis and over 90% of extensively drug-resistant tuberculosis strains are also PZA resistant. Despite the key role played by PZA, its mechanisms of action are not yet fully understood. It has been postulated that pyrazinoic acid (POA), the hydrolyzed product of PZA, could inhibit trans-translation by binding to Ribosomal protein S1 (RpsA) and competing with tmRNA, the natural cofactor of RpsA. Subsequent data, however, indicate that these early findings resulted from experimental artifact. Hence, in this study we assess the capacity of POA to compete with tmRNA for RpsA. We evaluated RpsA wild type (WT), RpsA ∆A438, and RpsA ∆A438 variants with truncations towards the carboxy terminal end. Interactions were measured using Nuclear Magnetic Resonance spectroscopy (NMR), Isothermal Titration Calorimetry (ITC), Microscale Thermophoresis (MST), and Electrophoretic Mobility Shift Assay (EMSA). We found no measurable binding between POA and RpsA (WT or variants). This suggests that RpsA may not be involved in the mechanism of action of PZA in Mycobacterium tuberculosis, as previously thought. Interactions observed between tmRNA and RpsA WT, RpsA ∆A438, and each of the truncated variants of RpsA ∆A438, are reported.

Even though Pure Shift NMR methods have conveniently been used in the assessment of crowded spectra, they are not commonly applied to the analysis of metabolomics data. This paper exploits the recently published SAPPHIRE-PSYCHE methodology in the context of plant metabolome. We compare single pulse, PSYCHE, and SAPPHIRE-PSYCHE spectra obtained from aqueous extracts of Physalis peruviana fruits. STOCSY analysis with simplified SAPPHIRE-PSYCHE spectra of six types of Cape gooseberry was carried out and the results attained compared with classical STOCSY data. PLS coefficients analysis combined with 1D-STOCSY was performed in an effort to simplify biomarker identification. Several of the most compromised proton NMR signals associated with critical constituents of the plant mixture, such as amino acids, organic acids, and sugars, were more cleanly depicted and their inter and intra correlation better reveled by the Pure Shift methods. The simplified data allowed the identification of glutamic acid, a metabolite not observed in previous studies of Cape gooseberry due to heavy overlap of its NMR signals. Overall, the results attained indicated that Ultra-Clean Pure Shift spectra increase the performance of metabolomics data analysis such as STOCSY and multivariate coefficients analysis, and therefore represent a feasible and convenient additional tool available to metabolomics.

For a wide range of cells, from bacteria to mammals, locomotion movements are a crucial systemic behavior for cellular life. Despite its importance in a plethora of fundamental physiological processes and human pathologies, how unicellular organisms efficiently regulate their locomotion system is an unresolved question. Here, to understand the dynamic characteristics of the locomotion movements and to quantitatively study the role of the nucleus in the migration of Amoeba proteus we have analyzed the movement trajectories of enucleated and non-enucleated amoebas on flat two-dimensional (2D) surfaces using advanced non-linear physical-mathematical tools and computational methods. Our analysis shows that both non-enucleated and enucleated amoebas display the same kind of dynamic migration structure characterized by highly organized data sequences, super-diffusion, non-trivial long-range positive correlations, persistent dynamics with trend-reinforcing behavior, and move-step fluctuations with scale invariant properties. Our results suggest that the presence of the nucleus does not significantly affect the locomotion of amoeba in 2D environments., We would like to thank José González Romero and José Miguel Pérez Pérez from the Institute of Parasitology and Biomedicine “López-Neyra” for their technical assistance, as well as the technical support provided by SGIker of UPV/EHU, European funding (ERDF and ESF), the Basque Government funding (IT1974-16, KK-2018/00090), and by the UPV/EHU and Basque Center of Applied Mathematics (US18/21).

Highly mobile mammalian carnivores are expected to have the capability to maintain high levels of gene flow across large geographic scales. Nonetheless, surprising levels of genetic structure have been found in many such populations. We combined genetic and spatial behavioural information from wolves (Canis lupus) in the Iberian Peninsula (Western Europe) during the last two decades to present a particular case of low dispersal levels in a large carnivore population persisting in human-dominated landscapes. We found an exceptionally reticulated pattern of cryptic population structure emerging at two hierarchical levels, in which four or eleven meaningful genetic clusters can be recognized, respectively. These clusters were characterized by moderate-high levels of differentiation (average pairwise FST = 0.09–0.19), low levels of admixture and varying degrees of genetic diversity. The number of dispersers identified among the 11 clusters was very low (

Scientific Reports 7: Article number: 41875; published online: 03 February 2017; updated: 11 May 2018 This Article contains typographical errors in the Acknowledgements section. “This work was supported by grants from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness, PI12/00959, PI13/01741, RETICS RD012/0005/004 and RD012/0021, co-funded by FEDER) and Junta de Castilla y León (Excellence Group GR100, Ministry of Health, BIO/SA87/13 and IES095U14) and Fundación Mutua Madrileña (IX Call for Grants and Aids for Medical Research).

Successful coexistence between large carnivores and humans is conditional upon effective mitigation of the impact of these species on humans, such as through livestock depredation. It is therefore essential for conservation practitioners, carnivore managing authorities, or livestock owners to know the effectiveness of interventions intended to reduce livestock predation by large carnivores. We reviewed the scientific literature (1990-2016), searching for evidence of the effectiveness of interventions. We found experimental and quasi-experimental studies were rare within the field, and only 21 studies applied a case-control study design (3.7% of reviewed publications). We used a relative risk ratio to evaluate the studied interventions: changing livestock type, keeping livestock in enclosures, guarding or livestock guarding dogs, predator removal, using shock collars on carnivores, sterilizing carnivores, and using visual or auditory deterrents to frighten carnivores. Although there was a general lack of scientific evidence of the effectiveness of any of these interventions, some interventions reduced the risk of depredation whereas other interventions did not result in reduced depredation. We urge managers and stakeholders to move towards an evidence-based large carnivore management practice and researchers to conduct studies of intervention effectiveness with a randomized case-control design combined with systematic reviewing to evaluate the evidence.

Decision-makers in wildlife policy require reliable population size estimates to justify interventions, to build acceptance and support in their decisions and, ultimately, to build trust in managing authorities. Traditional capture-recapture approaches present two main shortcomings, namely, the uncertainty in defining the effective sampling area, and the spatially-induced heterogeneity in encounter probabilities. These limitations are overcome using spatially explicit capture-recapture approaches (SCR). Using wolves as case study, and non-invasive DNA monitoring (faeces), we implemented a SCR with a Poisson observation model in a single survey to estimate wolf density and population size, and identify the locations of individual activity centres, in NW Iberia over 4,378 km. During the breeding period, posterior mean wolf density was 2.55 wolves/100 km (95%BCI = 1.87-3.51), and the posterior mean population size was 111.6 ± 18.8 wolves (95%BCI = 81.8-153.6). From simulation studies, addressing different scenarios of non-independence and spatial aggregation of individuals, we only found a slight underestimation in population size estimates, supporting the reliability of SCR for social species. The strategy used here (DNA monitoring combined with SCR) may be a cost-effective way to generate reliable population estimates for large carnivores at regional scales, especially for endangered species or populations under game management., J.V.L.B. was supported by a Ramon & Cajal research contract (RYC-2015-18932) from the Spanish Ministry of Economy, Industry and Competitiveness. R.G. was supported by research contract (IF/00564/2012) from the Portuguese Foundation for Science and Technology (FCT). Tis work was partially supported by the project PTDC/BIA-EVF/2460/2014 (FCT).

Successful coexistence between large carnivores and humans is conditional upon effective mitigation of the impact of these species on humans, such as through livestock depredation. It is therefore essential for conservation practitioners, carnivore managing authorities, or livestock owners to know the effectiveness of interventions intended to reduce livestock predation by large carnivores. We reviewed the scientific literature (1990–2016), searching for evidence of the effectiveness of interventions. We found experimental and quasi-experimental studies were rare within the field, and only 21 studies applied a case-control study design (3.7% of reviewed publications). We used a relative risk ratio to evaluate the studied interventions: changing livestock type, keeping livestock in enclosures, guarding or livestock guarding dogs, predator removal, using shock collars on carnivores, sterilizing carnivores, and using visual or auditory deterrents to frighten carnivores. Although there was a general lack of scientific evidence of the effectiveness of any of these interventions, some interventions reduced the risk of depredation whereas other interventions did not result in reduced depredation. We urge managers and stakeholders to move towards an evidence-based large carnivore management practice and researchers to conduct studies of intervention effectiveness with a randomized case-control design combined with systematic reviewing to evaluate the evidence.

Scientific Reports 6: Article number: 20552; published online: 03 February 2016; updated: 28 March 2017 This corrigendum aims to correct errors detected in the outputs of the Extended Data Tables from our article Scientific Reports 6, 20552 (2016). A mistake occurred due to a failure in the conversion of the variable “species” from integer to a categorical (factor) variable.

Understanding the dynamics of wolf-dog hybridization and delineating evidence-based conservation strategies requires information on the spatial extent of wolf-dog hybridization in real-time, which remains largely unknown. We collected 332 wolf-like scats over ca. 5,000km2 in the NW Iberian Peninsula to evaluate wolf-dog hybridization at population level in a single breeding/pup-rearing season. Mitochondrial DNA (MtDNA) and 18 ancestry informative markers were used for species and individual identification, and to detect wolf-dog hybrids. Genetic relatedness was assessed between hybrids and wolves. We identified 130 genotypes, including 67 wolves and 7 hybrids. Three of the hybrids were backcrosses to dog whereas the others were backcrosses to wolf, the latter accounting for a 5.6% rate of introgression into the wolf population. Our results show a previously undocumented scenario of multiple and widespread wolf-dog hybridization events at the population level. However, there is a clear maintenance of wolf genetic identity, as evidenced by the sharp genetic identification of pure individuals, suggesting the resilience of wolf populations to a small amount of hybridization. We consider that real-time population level assessments of hybridization provide a new perspective into the debate on wolf conservation, with particular focus on current management guidelines applied in wolf-dog hybridization events.

Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage., This work was supported by grants from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness, PI12/00959, PI13/01741, RETICS RD012/0005/004 and RD012/0021, co-funded by FEDER) and Junta de Castilla y León (Excellence Group GR100, Ministry of Health, BIO/SA87/13 and IES095U14) and Fundación Mutua Madrileña (IX Call for Grants and Aids for Medical Research).

Obtaining reliable estimates of the structure of carnivore communities is of paramount importance because of their ecological roles, ecosystem services and impact on biodiversity conservation, but they are still scarce. This information is key for carnivore management: to build support for and acceptance of management decisions and policies it is crucial that those decisions are based on robust and high quality information. Here, we combined camera and live-trapping surveys, as well as telemetry data, with spatially-explicit Bayesian models to show the usefulness of an integrated multi-method and multi-model approach to monitor carnivore community structures. Our methods account for imperfect detection and effectively deal with species with non-recognizable individuals. In our Mediterranean study system, the terrestrial carnivore community was dominated by red foxes (0.410 individuals/km2); Egyptian mongooses, feral cats and stone martens were similarly abundant (0.252, 0.249 and 0.240 individuals/km2, respectively), whereas badgers and common genets were the least common (0.130 and 0.087 individuals/km2, respectively). The precision of density estimates improved by incorporating multiple covariates, device operation, and accounting for the removal of individuals. The approach presented here has substantial implications for decision-making since it allows, for instance, the evaluation, in a standard and comparable way, of community responses to interventions., We are in debt to the staff of the Regional Government of Extremadura, and the Spanish Ministry of Agriculture, Food and Environment, for their collaboration and the logistical support they provided. J.V.L.B. was supported by a ‘Juan de la Cierva’ research contract (JCI-2012-13066) from the Spanish Ministry of Economy and Competitiveness.