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Desde hace un tiempo China viene compitiendo con Estados Unidos por una posición dominante en el mundo. La competencia es, sobre todo económica, aunque implica, por supuesto, aspectos también políticos, sociales y militares. Una de las regiones más disputadas es, sin duda, América Latina, en la que Estados Unidos pierde cada vez más terreno y China se posiciona como el mayor socio comercial. En este contexto, los países latinoamericanos han tenido que reconfigurar sus políticas exteriores para poder satisfacer sus expectativas de la mano de quien le ofrezca mejores posibilidades. Perú no ha sido una excepción y, de hecho, se ha acercado en los últimos años más a China como principal socio comercial, aunque no ha soltado la mano de Estados Unidos del todo. El presente artículo explora cómo se ha reconfigurado la política exterior peruana de cara a la competencia entre China y Estados Unidos

Aim of this study was to analyze the distribution and characteristics of runs of homozygosity in Bos taurus taurus and Bos taurus indicus breeds, as well as their crosses, farmed all around the world. With this aim in view, we used single-nucleotide polymorphisms (SNP) genotypes for 3,263 cattle belonging to 204 different breeds. After quality control, 23,311 SNPs were retained for the analysis. Animals were divided into seven different groups: 1) continental taurus, 2) temperate taurus, 3) temperate indicus, 4) temperate composite, 5) tropical taurus, 6) tropical indicus, and 7) tropical composite. The climatic zones were created according to the latitude of the breeds’ country of origin: i) continental, latitude ≥ 45°; ii) temperate, 45°< Latitude >23.26°; iii) tropics, latitude ≤ 23.26°. Runs of homozygosity were computed as 15 SNPs spanning in at least 2 Mb; number of ROH per animal (nROH), average ROH length (meanMb), and ROH-based inbreeding coefficients (FROH) were also computed. Temperate indicus showed the largest nROH, whereas Temperate taurus the lowest value. Moreover, the largest meanMb was observed for Temperate taurus, whereas the lowest value for Tropics indicus. Temperate indicus breeds showed the largest FROH values. Genes mapped in the identified ROH were reported to be associated with the environmental adaptation, disease resistance, coat color determinism, and production traits. Results of the present study confirmed that runs of homozygosity could be used to identify genomic signatures due to both artificial and natural selection.

The secreted products of the metastasis suppressor geneKiSS1-derived peptide levels in liquid biopsies from 60 NSCLC patients were assayed by ELISA. Preclinical experiments were carried out using quantitative real time polymerase chain reaction (qRT-PCR), ELISA, annexin V-binding and caspase activation assays.We compared KiSS1 release in 3 different matrices (serum, plasma and urine) and the highest levels were detectable in serum (range, 0-4.5 ng/mL). We observed increased levels of seric KiSS1 in NSCLC patients as compared to healthy donors. KiSS1 serum concentrations, after surgical procedure and/or adjuvant therapy. We observed differences among disease stages in urine samples. In preclinical models,Our results showing a peculiar modulation of KiSS1 levels in liquid biopsies of NSCLC patients and a regulation of cisplatin-induced apoptosis by KiSS1-derived peptides support an involvement of KiSS1 in cell response to treatment and highlight its promising features as a potential biomarker in NSCLC.

The adoption of quantitative risk assessments (QRA) for land-slide management decision-making has increased over the last few decades, particularly when projects threaten sensitive built environments and heritage sites. The QRA process provides a quantitative estimate of the level of risk that can then be evaluated against adopted criteria for decision-making purposes regarding the need for prevention and mitigation. Although the QRA process provides for considerations of uncertainty in landslide hazard (occurrence probability, volumes, velocities, runout distances, etc.) and consequence (e.g. quantity and vulnerability of exposed population and infrastructure); The uncertainty associated with quantification in the QRA process is seldom understood or quantified. This presentation shares the outcome of a research project where the uncertainties associated with the QRA process were quantified in order to gain an understanding of the reliability in landslide QRA. The results are evaluated in terms of typical ranges within common risk tolerability criteria. The knowledge gained on this project was used to develop a simplified approach to consider uncertainty in QRA for practical purposes, which is illustrated for a section of highway exposed to rock fall hazards in Canmore, Alberta, Canada. The QRA was selected to inform decision-making for the selection of rock fall protection strategies at a location where environmental concerns, tourism activities, and economic activities are of significant value for the public. This significantly increased the complexity of the decision-making process, and therefore required a robust, clear approach for balancing public socio-economic expectations and safety. In the QRA process, uncertainty was associated with hazard and consequence quantification. The work elicited the plausible ranges for the input variables for risk calculation. The expected and the range in risk were calculated for the current conditions and considering the implementation of the mitigation option. The individual risk to highway users was considered low because of the limited exposure of any particular individual. The calculated current total risk (probability of fatality) was 2.9 × 10−4 with a plausible range between 2.0 × 10−5 and 5.5 × 10−3. The residual total risk considering implementation of the slope protection was calculated between 9.0 × 10−4 and 2.9 × 10−6, with an expected value of 4.5 × 10−5.The risk levels considering implementation of the mitigation options were evaluated against criteria previously used in Canada. These were considered an adequate balance between project costs, public safety, environmental concerns, tourism, and economic activities.

Background: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. Objective: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DIIr), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines. Methods: This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders. Results: Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DIIr were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index. Conclusions: Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements.

Landslides are common across Canada and they pose hazards to human safety, economic activities, and the environment. Robust risk management strategies are necessary for sustainable development. A slope risk management framework has been adopted by the geotechnical community for approximately four decades allowing a systematic, consistent and transparent framework for managing risks. Implementing this framework is associated with uncertainties embedded in our estimates of risk. This paper presents a brief summary of the sources and categories of uncertainty in geotechnical slope engineering and focuses on two topics: 1) estimates of uncertainty in risk calculations; and 2) temporal changes in landslide likelihood as a function of weather and steps towards estimating landslide risk changes with climate change. The paper argues that a quantitative risk assessment should not focus on the final risk calculation, but the overall knowledge gained. This allows comprehensive documentation of sources of uncertainty and how they impact geotechnical and risk assessments. Furthermore, the paper outlines approaches to define quantitative correlations between rock fall occurrences and weather, which can be leveraged to estimate changes in rock fall risk with climate change. The paper corresponds to, and expands on, the 2021 Canadian Geotechnical Colloquium.

Descriptive statistics of the primary and secondary endpoint measurements.

Boxplot reflecting the distribution of 15-PGDH expression at baseline (T0) and at six months (T2) according to the Aperio ScanScope Cytoplasm Algorithm V2. Each box indicates the 25th and 75th percentiles of the distribution. The horizontal line inside the box indicates the median and the whiskers indicate the extreme measured values; the mean value is represented by a black diamond.

Panel A-1: COX-2 IHC performed on normal FAP biopsies collected before the dietary intervention (T0) and after six months of diet (T2). Panel A-2: COX-2 IHC performed on adenoma FAP biopsies at T0 and T2. Panel B-1: COX-2 IHC performed on normal colon mucosa collected from surgery for sporadic colon cancer. Panel B-2: 15-PGDH IHC performed on normal colon mucosa collected from surgery for sporadic colon cancer.

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BACKGROUND: To examine the associations of animal and plant protein intake with all-cause, cardiovascular and cancer mortality risk in middle-aged Italian men and women with substantially lower animal protein intake than North Americans. METHODS AND RESULTS: Food consumption was assessed by validated Epic semiquantitative FFQs. Multivariable Cox models stratified by center, age, and sex, and adjusted for confounders, estimated associations of animal and plant protein consumption with mortality for all causes, cardiovascular disease, and cancer. After a median follow-up of 15.2 years, 2,449 deaths were identified in 45,009 participants. No significant association between intake of total, animal or plant protein and mortality was found in the fully adjusted models. Substitution of plant protein for animal protein was inversely associated with cardiovascular mortality (HR, 0.47; 95% CI, 0.24–0.92) only in people with at least 1 unhealthy lifestyle risk factor and poor adherence to a Mediterranean diet. Participants in the highest quintile group of animal protein intake had higher glucose, total and LDL cholesterol levels than those in the lowest quintile. In contrast, higher plant protein intake was negatively associated with fasting insulin and cholesterol, despite higher BMI, physical inactivity and starch consumption. CONCLUSIONS: Replacing plant protein for animal protein was associated with lower cardiovascular mortality among individuals with unhealthy lifestyle risk factors. High animal but not plant protein intake is associated with impaired fasting glucose and hypercholesterolemia, despite lower calorie and carbohydrate intake, suggesting that protein source plays crucial roles in modulating cardiometabolic health independently of body weight.

Displacement monitoring is a critical control for risks associated with potentially sudden slope failures. Instrument measurements are, however, obscured by the presence of scatter. Data filtering methods aim to reduce the scatter and therefore enhance the performance of early warning systems (EWSs). The effectiveness of EWSs depends on the lag time between the onset of acceleration and its detection by the monitoring system such that a timely warning is issued for the implementation of consequence mitigation strategies. This paper evaluates the performance of three filtering methods (simple moving average, Gaussian-weighted moving average, and Savitzky–Golay) and considers their comparative advantages and disadvantages. The evaluation utilized six levels of randomly generated scatter on synthetic data, as well as high-frequency global navigation satellite system (GNSS) displacement measurements at the Ten-mile landslide in British Columbia, Canada. The simple moving average method exhibited significant disadvantages compared to the Gaussian-weighted moving average and Savitzky–Golay approaches. This paper presents a framework to evaluate the adequacy of different algorithms for minimizing monitoring data scatter.

Canada’s rail transportation network is a critical part of Canada’s integrated supply chain which connects industries, consumers, and resource sectors to ports on the Atlantic and Pacific coasts. One transportation activity that is essential to most industries, especially oil and manufacturing, is the rail transport of dangerous goods (DG). Although rail transportation of DG is beneficial to Canada’s economy, not paying attention to the safe transportation of these types of goods can have irreparable effects on the economy, human lives, and the environment. Recent rail accidents, such as Lake Wabamun in 2005 and Lac-Mégantic in 2013, have shown that there is still room to increase the safety of transportation of DG by rail through improving railways’ safety management systems (SMS). As a result, investigations to increase the safety of rail transportation of DG have been started. This work is part of these initiatives focusing on enhancing railways’ SMS, particularly DG main-track train derailments. The current study applied detailed root cause analysis (RCA), the bow tie analysis (BTA), and incident databases to identify the main causes and consequences of these types of accidents (2007–2017). Then, the relationship between these factors and gaps in SMS elements were identified and the frequency of each factor was investigated. The results showed that the main gaps are related to process and equipment integrity, incident investigation, and company standards, codes, and regulations. Furthermore, some useful recommendations are presented to improve the management of each SMS element and reduce these gaps.

The aim of this pilot study was to clarify the acceptability and clinical efficacy of an oxygen-enriched oil-based gel for treatment of angular cheilitis.A class IIb medical preparation, packaged in appropriate syringes, was tested. Patients were instructed how to use the gel for 10 days: finger rub application (3 times daily) on the dried lesion after meals, without eating, drinking, or speaking for at least 30 min thereafter. The Wilcoxon signed-rank test was used to assess whether there were any differences in the distributions of reported pain and lesion dimension. A microbiological examination was also performed with oral swabs; chi-squared test was used to compare the difference in the presence of microorganisms before and after treatment.Thirty patients were treated. A significant improvement in reported outcome and a significant reduction in the initially measured largest dimension of the lesion were observed after use of the clinical protocol. Additionally, a significant reduction in the pathogen count was found.Even if with limitations, data showed that this medical preparation facilitated prompt recovery from reported pain, without adverse reactions. Further work with a larger study population, and possibly a randomized control medication, will be needed.

Background Breast Cancer (BC) is a leading public-health issue affecting women on a global scale, accounting for about 500,000 new cases every year in Europe. Thanks to the widespread implementation of screening programs and the improvement in therapies, women with BC live longer but they also are more likely to experience an increased risk of other diseases, including second primary cancer, cardiovascular, and metabolic diseases. Reasons for this increased risk include genetics, shared risk factors, and adverse effects from BC treatment. Methods To analyse the risk of myocardial infarction (MI) and stroke in women with BC considering the potential side effects of treatments, we used data from the Piedmont Longitudinal Study, an administrative cohort based on the record-linkage among census data and several health-administrative databases to include than 4 million inhabitants of an Italian region. Results Among 1,342,333 women ranging from 30 to 75 years old 19,203 had a BC diagnosis in the follow-up period, of whom 206 experienced a subsequent MI and 203 a stroke. Women with BC showed an increased risk for MI (HR: 1.20; 95%CI: 1.05–1.38) and for stroke (HR: 1.58; 95%CI: 1.38–1.82). Chemotherapy seemed to be the major risk factor for MI in BC women, while no different risk by therapy was found for stroke. Conclusion The results of this study supported the hypothesis about the toxic effect of therapies, suggesting both clinicians to routinely and actively screen for these treatment-related toxicities in women with BC and researchers to prioritize personalized treatments in order to minimize potentially devastating side effects.

BackgroundObservational studies have shown that women with an early menopause are at higher risk of stroke compared to women with a later menopause. However, associations with stroke subtypes are inconsistent and the causality is unclear. Therefore, we conducted a large-scale analysis to investigate the observational association between age at menopause and different types of stroke accompanied by a Mendelian Randomization analysis to evaluate causality.MethodsWe analyzed data of the UK Biobank and EPIC-CVD study. Postmenopausal women without a history of stroke at baseline were eligible for inclusion. The study endpoints were total stroke and stroke subtypes (i.e., ischemic stroke, hemorrhagic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage). We investigated the observational association between age at menopause and risk of stroke using Cox-regression analysis in each study separately before combining effect sizes using random-effects meta-analysis. Cox-regression analyses were progressively adjusted for (1) age, (2) smoking status, body mass index, glycated hemoglobin, total cholesterol, and hypertension, and (3) ever use of hormone replacement therapy and age at menarche. We used two-sample Mendelian Randomization analysis to study whether there is a causal relationship between genetically proxied age at menopause and risk of stroke.ResultsA total of 204,244 women were included (7,883 from EPIC-CVD [5,292 from the sub-cohort]; 196,361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD 5.8) and pooled mean age at menopause was 47.8 years (SD 6.2). Natural menopause occurred in 77.6% of all women. Over a median follow-up of 12.6 years (IQR 11.8, 13.3), 6,770 women experienced a stroke. In multivariable adjusted observational analyses, the pooled hazard ratios per five years younger age at menopause were 1.09 (95% CI: 1.07, 1.12) for stroke, 1.09 (1.06, 1.13) for ischemic stroke, 1.10 (1.04, 1.16) for hemorrhagic stroke, 1.14 (1.08, 1.20) for intracerebral hemorrhage, and 1.00 (0.84, 1.20) for subarachnoid hemorrhage. The Mendelian Randomization analysis found no evidence for a causal relationship between genetically proxied age at menopause and risk of any type of stroke.ConclusionsEarlier age at menopause is associated with, but not causally related to the risk of stroke.Clinical PerspectiveWhat is new?This analysis involves over 200,000 postmenopausal women and more than 6,000 incident stroke cases and investigates the observational association between age at menopause and various subtypes of stroke. Furthermore, a Mendelian Randomization analysis was conducted to study whether associations are causal or not.Earlier age at menopause was statistically significantly associated with a higher risk of stroke and its subtypes ischemic stroke, hemorrhagic stroke, and intracerebral hemorrhage. We found no statistically significant relationship between earlier or later age at menopause and risk of subarachnoid hemorrhage.The Mendelian Randomization analysis suggested no causal effect of genetically proxied age at menopause and risk of any type of stroke.What are the clinical implications?Women with earlier age at menopause are at higher risk of stroke. The underlying reasons need to be further investigated.Our analysis suggested that earlier menopauseper sedoes not cause stroke. For prevention and adequate treatment of stroke in women, a better understanding of the specific role of menopause and the mechanistic background that leads to higher risk of stroke is needed.

Supplemental material, sj-pdf-1-trr-10.1177_03611981231176549 for Assessing the Risks Associated with the Canadian Railway System Using a Safety Risk Model Approach by Nafiseh Esmaeeli, Fereshteh Sattari, Lianne Lefsrud and Renato Macciotta in Transportation Research Record

IntroductionThe ability to return to work after a cancer diagnosis is a key aspect of cancer survivorship and quality of life. Studies have reported a significant risk of income loss for cancer survivors; however, there is limited evidence of the Italian context.MethodsThe Work Histories Italian Panel (WHIP)-Salute database was used to select a cohort of incident cases of colorectal cancer (CRC) among workers in the private sector, based on hospital discharges. A propensity score matching was used to find a balanced control group for several confounders. Ordinary least square and logistic regressions were used to estimate the effect of a CRC diagnosis on annual income and the probability of switching from a full-time contract to a part-time one considering 3 years after the diagnosis.ResultsOverall, we identified 925 CRC incident cases from 2006 until 2012. Our results confirm a statistically significant reduction in survivors’ income compared with controls. This reduction was greater in the first year and then tend to decrease, with an average income loss over 3 years of about €12 000. Stratified analyses by sex and position confirmed the overall trend while indicating a strong effect modification. Regarding the switching from full-time to part-time employment, the results were never significant.ConclusionIncome loss does not seem to be related to an increase in part-time contracts, but rather to survivors’ reduced work capacity following the invasive treatments. Further research is needed to investigate the complex dynamics behind this association.

Supplemental material, sj-pdf-1-trr-10.1177_03611981231176549 for Assessing the Risks Associated with the Canadian Railway System Using a Safety Risk Model Approach by Nafiseh Esmaeeli, Fereshteh Sattari, Lianne Lefsrud and Renato Macciotta in Transportation Research Record

The relationship between chronic rhinosinusitis, asthma and allergic rhinitis is well known, but only recently has the scientific community started to evaluate these as different manifestations of a common pathogenic phenomenon, considering them as a unified airway disease.Twenty-two patients with chronic rhinosinusitis treated with endoscopic sinus surgery (ESS) were included in the study. Sino-nasal assessment questionnaire (SNAQ) investigating subjective evaluation of sino-nasal state was administered to patients, while objective evaluations included nasal endoscopy, sinonasal CT, skin prick tests, nasal cytology, spirometry, bronchodilator responsiveness testing and sputum eosinophil count. All tests were performed before surgery. Two months after surgery, SNAQ questionnaire, nasal endoscopy, spirometry and bronchodilator responsiveness testing were repeated.All patients had significant improvement of subjective status: mean SNAQ score decreased in all from 99.31 to 16.04. Mean Forced Expiratory Volume in the 1ESS achieved a beneficial effect on upper and lower airway status in patients with chronic rhinosinusitis with or without lower airway diseases.Studio prospettico pilota sugli effetti della ESS sulla performance delle vie aeree superiori e inferiori.La relazione tra rinosinusite cronica, asma e rinite allergica è ben nota, ma solo recentemente la comunità scientifica ha iniziato a considerarle come manifestazioni differenti di un comune evento patogenetico.In questo studio sono stati arruolati 22 pazienti con rinosinusite cronica trattati con chirurgia endoscopica dei seni paranasali (ESS), sottoposti prima dell’intervento chirurgico a Sino-nasal assesment questionnaire (SNAQ) per valutare la sintomatologia soggettiva, endoscopia nasale, TC dei seni paranasali, prick test cutanei, citologia nasale, spirometria con valutazione del volume espiratorio massimo nel 1 secondo (FEVTutti i pazienti hanno presentato un miglioramento significativo dei parametri soggettivi (riduzione della media del SNAQ da 99,31 a 16,04), e di quelli oggettivi (media del FEVLa chirurgia dei seni paranasali ha dimostrato di apportare benefici sia alle alte che alle basse vie aeree in pazienti con rinosinusite cronica, associata o meno a disturbi delle basse vie aeree.

This work was funded by the French National Cancer Institute (grant number 2015-166). Mathilde His' work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk (DOI 10.22025/2019.10.105.00004); C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143, MR/N003284/1, MC-UU_12015/1 and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (UK). The funders were not involved in designing the study; collecting, analyzing, or interpreting the data; or writing or submitting the manuscript for publication., Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2). Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786). Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34: 2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed. Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated., Institut National du Cancer (INCA) France 2015-166, International Agency for Research on Cancer - Fondation ARC, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/N003284/1 MC-UU_12015/1 MC_UU_00006/1 MR/M012190/1

The aim of this study was to test the feasibility of genomic selection in the Italian Mediterranean water buffalo, which is farmed mainly in the south Italy for milk, and mozzarella, production. A total of 498 animals were genotyped at 49,164 loci. Test day records (80,417) of milk (MY), fat (FY) and protein (PY) yields from 4127 cows, born between 1975 and 2009, were analysed in a three-trait model. Cows born in 2008 and 2009 with phenotypes and genotypes were selected as validation animals (n = 50). Variance components (VC) were estimated with BLUP and ssGBLUP. Heritabilities for BLUP were 0.25 ? 0.02 (MY), 0.16 ? 0.01 (FY) and 0.25 ? 0.01 (PY). Breeding values were computed using BLUP and ssGBLUP, using VC estimated from BLUP. ssGBLUP was applied in five scenarios, each with a different number of genotypes available: (A) bulls (35); (B) validation cows (50); (C) bulls and validation cows (85); (D) all genotyped cows (463); (E) all genotypes (498). Model validation was performed using the LR method: correlation, accuracy, dispersion, and bias statistics were calculated. Average correlations were 0.71 ? 0.02 and 0.82 ? 0.01 for BLUP and ssGBLUP-E, respectively. Accuracies were also higher in ssGBLUP-E (0.75 ? 0.03) compared to BLUP (0.57 ? 0.03). The best dispersions (i.e. closer to 1) were found for ssGBLUP-C. The use of genotypes only for the 35 bulls did not change the validation values compared to BLUP. Results of the present study, even if based on small number of animals, showed that the inclusion of genotypes of females can improve breeding values accuracy in the Italian Buffalo.HighlightsThe genotypes of males did not improve the predictions.Genotypes of females improve breeding values accuracy.Slight increase in prediction accuracy with weighted ssGBLUP.

The effects of inbreeding in livestock species breeds have been well documented and they have a negative impact on profitability. The objective of this study was to evaluate the levels of inbreeding in Sarda (SAR, n= 785) and Valle del Belice (VdB, n= 473) dairy sheep breeds and their impact on milk production traits. Two inbreeding coefficients (F) were estimated: using pedigree (FPED), or runs of homozygosity (ROH; FROH) at different minimum ROH lengths and different ROH classes. After the quality control, 38,779 single nucleotide polymorphisms remained for further analyses. A mixed-linear model was used to evaluate the impact of inbreeding coefficients on production traits within each breed. VdB showed higher inbreeding coefficients compared to SAR, with both breeds showing lower estimates as the minimum ROH length increased. Significant inbreeding depression was found only for milk yield, with a loss of around 7g/day (for SAR) and 9g/day (VdB) for a 1% increase of FROH. The present study confirms how the use of genomic information can be used to manage intra-breed diversity and to calculate the effects of inbreeding on phenotypic traits.

The inbreeding coefficient is an important parameter for livestock management. Small ruminant breeders and associations mainly rely on pedigree information, but genomic tools are gaining relevance, overcoming possible pedigree inconsistencies. This study investigates the relationship between pedigree-based and genomic inbreeding in two goat and four sheep dairy breeds. Pedigree and genomic data (medium-density SNPchip) were obtained for 3107 goats and 2511 sheep. We estimated pedigree depth (number of fully traced generations, FullGen) and inbreeding (FPED), as well as two genomic inbreeding indexes, using runs of the homozygosity (FROH) and genomic relationship matrix (FGRM). The correlation between the inbreeding coefficients was assessed. A linear regression model (LRM) was fitted for estimating FPED from FROH. After quality control on genomic data, we retained 5085 animals. Mean inbreeding values were low, with higher FROH than FPED and FGRM. Breed differences can partially depend on different managements. The correlation between FPED and FROH was the highest and directly related to pedigree depth. The best LRM was chosen for FullGen ≥4 and ≥6 for goats and sheep, respectively; after excluding animals with extreme residuals, a new refined regression equation was calculated. Since massive genotyping is not affordable to small ruminant breeders, it is important to understand the distinction and relationship between differently calculated inbreeding coefficients, also in view of the introduction of genomic enhanced breeding values. Our study highlights the importance of accurate pedigree information and, especially if not obtainable, of calculating genomic-based inbreeding coefficients. A better estimation of animals’ relatedness contributes to improve animal breeding and conservation.

The Thompson River valley is one of the most important transportation corridors in western Canada as it hosts two important railways. This valley has experienced several historical landslide events, many of them along a 10 km section south of the town of Ashcroft. Six of these landslides, showing varying states of activity, were selected for analysis in this paper, as these have the potential for the biggest impact on the railways. The subsurface interpretation of these landslides is combined with satellite InSAR data from May 2015 to May 2017 to enhance the current understanding of the landslide kinematics. Two InSAR orientations are combined geometrically with the assumption that the horizontal component of landslide movement is parallel to the slope azimuth, which provides a practicable approach to approximate landslide displacement vectors. The results classify these landslides as very slow-moving. The maximum velocities recorded are 29, 35, 26, 64, 18, and 52 mm/year for the Goddard, North, South, South extension, Barnard, and Redhill landslides, respectively. All landslides except the Redhill landslide show near-horizontal movements near the toe, with increasing vertical components as measurements approach the back scarp. This confirms that kinematics include rotational and compound mechanisms.

Lipoprotein lipase (LPL) is a key enzyme for lipid metabolism, playing a fundamental role in the composition of fat in adipose tissue and milk. The LPL gene has been seldom investigated in dairy ruminants and barely studied in river buffalo (Bubalus bubalis). The aim of this work was to explore the genetic diversity of LPL and its promoter and to identify functional mutations, using a combined approach based on sequencing, dual-color electrophoretic mobility shift assay, and quantitative PCR. Thirteen consensus sequences for transcription factors were found in the promoter. Eleven SNP were detected, and the attention was focused on the SNP with potential functional effects: g.-446A>G, because the presence of G created a consensus motif for the transcription factor Sp1, and g.107A>G, which was the only exonic SNP. We developed PCR-RFLP methods for genotyping the 2 SNP and calculated the allele frequencies. A strong linkage disequilibrium (D' = 1; r2 = 0.903) was found between the 2 SNP. The dual-color electrophoretic mobility shift assay demonstrated that only genotype g.-446GG allowed the binding of the Sp1 transcription factor, resulting in overexpression of the gene (~2.5 fold), as confirmed by the quantitative PCR results. Haploinsufficiency is proposed as a regulation mechanism. This study adds further knowledge on the structure of the LPL gene and its expression in river buffalo, with potential effects on milk qualitative and quantitative production.

International audience; The COVID-19 pandemic introduced changes in people’s lives that affected their mental health. Our study aimed to explore the level of psychological distress in the academic population during the lockdown period and investigate its association with the new working or studying conditions. The study sample included 9364 students and 2159 employees from five Italian universities from the study IO CONTO 2020. We applied linear regression models to investigate the association between home learning or remote working conditions and psychological distress, separately for students and employees. Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS). In both students and employees, higher levels of distress were significantly associated with study/work–family conflicts, concerns about their future careers, and inadequacy of equipment; in employees, higher levels of distress were significantly associated with a lack of clarity on work objectives. Our results are in line with previous research on the impact of spaces and equipment in remote working/studying from home. Moreover, the study contributes to deepening the association between well-being and telework–family conflict, which in the literature is still equivocal. Practical implications require academic governance to promote sustainable environments both in remote and hybrid work conditions, by referring to a specific management by objectives approach.

Genomic information allows for a more accurate calculation of relationships among animals than the pedigree information, leading to an increase in accuracy of breeding values. Here, we used pedigree‐based and single‐step genomic approaches to estimate variance components and breeding values for β‐hydroxybutyrate milk content (BHB). Additionally, we performed a genome‐wide association study (GWAS) to depict its genetic architecture. BHB concentrations within the first 90 days of lactation, estimated from milk medium infrared spectra, were available for 30,461 cows (70,984 records). Genotypes at 42,152 loci were available for 9,123 animals. Low heritabilities were found for BHB using pedigree‐based (0.09 ± 0.01) and genomic (0.10 ± 0.01) approaches. Genetic correlation between BHB and milk traits ranged from −0.27 ± 0.06 (BHB and protein percentage) to 0.13 ± 0.07 (BHB and fat‐to‐protein ratio) using pedigree and from −0.26 ± 0.05 (BHB and protein percentage) to 0.13 ± 0.06 (BHB and fat‐to‐protein ratio) using genomics. Breeding values were validated for 344 genotyped cows using linear regression method. The genomic EBV (GEBV) had greater accuracy (0.51 vs. 0.45) and regression coefficient (0.98 vs. 0.95) compared to EBV. The correlation between two subsequent evaluations, without and with phenotypes for validation cows, was 0.85 for GEBV and 0.82 for EBV. Predictive ability (correlation between (G)EBV and adjusted phenotypes) was greater when genomic information was used (0.38) than in the pedigree‐based approach (0.31). Validation statistics in the pairwise two‐trait models (milk yield, fat and protein percentage, urea, fat/protein ratio, lactose and logarithmic transformation of somatic cells count) were very similar to the ones highlighted for the single‐trait model. The GWAS allowed discovering four significant markers located on BTA20 (57.5–58.2 Mb), where the ANKH gene is mapped. This gene has been associated with lactose, alpha‐lactalbumin and BHB. Results of this study confirmed the usefulness of genomic information to provide more accurate variance components and breeding values, and important insights about the genomic determination of BHB milk content.

Oral lichen planus (OLP) is a chronic immune disease. In this paper, we evaluated the overall characters, clinical presentation, and outcome of gingival lesions in OLP Italian patients.A retrospective cohort study was accomplished: a total of 1319 charts were investigated, of whom 922 were female (69.9%): 617 patients (46.8%) manifested white lesions and 702 red ones (53.2%). While most patients had several oral sites of involvement, the gingiva was the unique location in 103 cases. Symptoms were reported in 480 patients (36.4%): 286 patients with erosive OLP, 103 with atrophic form, and 91 with a white form. Long-lasting surveillance showed that only 40 patients (3.03%) had a total clinical signs remission. Regarding OLP medical treatment provided, patients attending less frequently a dental office underwent more often a specific therapy.To the best of our knowledge, this is the biggest collections of patients with gingival OLP ever described; exclusive gingival lesions are, however, rare and unlikely to undergo a malignant transformation. Moreover, gum lesions seemed to anticipate the appearance of oral lesions and a higher rate of OLP therapy was observed in patients with less frequent dental check-ups and oral hygiene instructions.

The inbreeding coefficient is an important parameter for livestock management. Small ruminant breeders and associations mainly rely on pedigree information, but genomic tools are gaining relevance, overcoming possible pedigree inconsistencies. This study investigates the relationship between pedigree-based and genomic inbreeding in two goat and four sheep dairy breeds. Pedigree and genomic data (medium-density SNPchip) were obtained for 3107 goats and 2511 sheep. We estimated pedigree depth (number of fully traced generations, FullGen) and inbreeding (F

At the very beginning of the European spread of SARS-CoV-2, Piedmont was one of the most affected regions in Italy, with a strong impact on healthcare organizations. In this study, we evaluated the characteristics and outcomes of the COVID-19 patients in an entire region during the first three pandemic waves, identifying similarities and differences in the SARS-CoV-2 epidemic’s timeline. We collected the health-administrative data of all the Piedmont COVID-19 patients infected during the first three pandemic waves (1 March 2020–15 April 2020; 15 October 2020–15 December 2020; 1 March 2021–15 April 2021, respectively). We compared differences among the waves in subjects positive for SARS-CoV-2 and in patients admitted to ICU. Overall, 18.621 subjects tested positive during the first wave (405 patients/day), 144.350 (2366.4 patients/day) in the second, and 81.823 (1778.8 patients/day) in the third. In the second and third waves, we observed a reduction in median age, comorbidity burden, mortality in outpatients, inpatients, and patients admitted to ICU, in intubation, invasive ventilation and tracheostomy, and a parallel increase in the use of CPAP. Our study confirmed a trend towards younger and healthier patients over time but also showed an independent effect of the period on mortality and ICU admission. The appearance of new viral variants, the starting of vaccination, and organizational improvements in tracking, outpatients and inpatients management could have influenced these trends.

Background Since 2011 Italy has faced an extraordinary increase in migrants arrivals, mainly from the Mediterranean route, one of the world’s most dangerous journeys. The purpose of the present article is to provide a comprehensive picture of the migrants' health status in the "T. Fenoglio" centre, Settimo Torinese (Turin, Italy). Methods A retrospective cross-sectional study was conducted using data collected from June 2016 to May 2018 on adult migrants (over 18 years old) from Africa, Middle East and South East Asia (Bangladesh, Cambodia, India, Nepal). Data was collected through the migrants' medical records. Descriptive statistics were performed on socio-demographic variables. The diagnosed diseases were anonymously registered and classified according to the International Classification of Primary Care (ICPC-2). Conditional Inference Trees were used to perform a descriptive analysis of the sample and to detect the covariates with the strongest association with the variables Disease on arrival, Disease after arrival, ICPC on arrival and ICPC after arrival. Results Analyzed observations were 9 857. 81.8% were men, median age was 23 (Interquartile range: 20.0–27.4). 70.3% of the sample came from Sub-Saharan Africa. 2 365 individuals (24%) arrived at the centre with at least one disease. On arrival, skin (27.71%), respiratory (14.46%), digestive (14.73%) and generic diseases (20.88%) were the most frequent. During the stay respiratory diseases were the most common (25.70%). The highest probability of arriving with a disease occurred in 2018 and during the period September–November 2016, in particular for people from the Horn of Africa. During this period and also in the first half of 2017, skin diseases were the most reported. In seasons with lower prevalence of diseases on arrival the most common disease code was generic for both men and women (usually fever or trauma). Conclusions This study provides information on the diverse diseases that affect the asylum seekers population. In our sample, the Horn of Africa was the most troubled area of arrival, with severe conditions frequently reported regarding skin diseases, in particular scabies. 2018 was the most critical year, especially for migrants from the Horn of Africa and Sub-Saharan Africa. During the stay at the camp, the prevalence of respiratory diseases increased. However, skin diseases remained the main issue for people from the Horn of Africa. Overall, the most reported diseases in the sample were dermatological, respiratory, digestive and generic diseases, both on arrival and during the stay. A better understanding of the health status of asylum seekers is an important factor to determine a more efficient reception and integration process and a better allocation of economic resources in the context of migrants' health care.

Milkability is a trait related to the milking efficiency of an animal, and it is a component of the herd profitability. Due to its economic importance, milkability is currently included in the selection index of the Italian Simmental cattle breed with a weight of 7.5%. This lowly heritable trait is measured on a subjective scale from 1 to 3 (1 = slow, 3 = fast), and genetic evaluations are performed by pedigree-based BLUP. Genomic information is now available for some animals in the Italian Simmental population, and its inclusion in the genetic evaluation system could increase accuracy of breeding values and genetic progress for milkability. The aim of this study was to test the feasibility and advantages of having a genomic evaluation for this trait in the Italian Simmental population. Phenotypes were available for 131,308 cows. A total of 9,526 animals had genotypes for 42,152 loci; among the genotyped animals, 2,455 were cows with phenotypes, and the other were their relatives. The youngest cows with both phenotypes and genotypes (n = 900) were identified as selection candidates. Variance components and heritability were estimated using pedigree information, whereas genetic and genomic evaluations were carried out using BLUP and single-step genomic BLUP (ssGBLUP), respectively. In addition, a weighted ssGBLUP was assessed using genomic regions from a genome-wide association study. Evaluation models were validated using theoretical and realized accuracies. The estimated heritability for milkability was 0.12 ± 0.01. The mean theoretical accuracies for selection candidates were 0.43 ± 0.08 (BLUP) and 0.53 ± 0.06 (ssGBLUP). The mean realized accuracies based on linear regression statistics were 0.29 (BLUP) and 0.40 (ssGBLUP). No genomic regions were significantly associated with milkability, thus no improvements in accuracy were observed when using weighted ssGBLUP. Results indicated that genomic information could improve the accuracy of breeding values and increase genetic progress for milkability in Italian Simmental.

Fatty acid (FA) profile is one of the most important aspects of the nutritional properties of milk. The FA content in milk is affected by several factors such as diet, physiology, environment, and genetics. Recently, principal component analysis (PCA) and multivariate factor analysis (MFA) have been used to summarize the complex correlation pattern of the milk FA profile by extracting a reduced number of new variables. In this work, the milk FA profile of a sample of 993 Sarda breed ewes was analyzed with PCA and MFA to compare the ability of these 2 multivariate statistical techniques in investigating the possible existence of latent substructures, and in studying the influence of physiological and environmental effects on the new extracted variables. Individual scores of PCA and MFA were analyzed with a mixed model that included the fixed effects of parity, days in milking, lambing month, number of lambs born, altitude of flock location, and the random effect of flock nested within altitude. Both techniques detected the same number of latent variables (9) explaining 80% of the total variance. In general, PCA structures were difficult to interpret, with only 4 principal components being associated with a clear meaning. Principal component 1 in particular was the easiest to interpret and agreed with the interpretation of the first factor, with both being associated with the FA of mammary origin. On the other hand, MFA was able to identify a clear structure for all the extracted latent variables, confirming the ability of this technique to group FA according to their function or metabolic origin. Key pathways of the milk FA metabolism were identified as mammary gland de novo synthesis, ruminal biohydrogenation, desaturation performed by stearoyl-coenzyme A desaturase enzyme, and rumen microbial activity, confirming previous findings in sheep and in other species. In general, the new extracted variables were mainly affected by physiological factors as days in milk, parity, and lambing month; the number of lambs born had no effect on the new variables, and altitude influenced only one principal component and factor. Both techniques were able to summarize a larger amount of the original variance into a reduced number of variables. Moreover, factor analysis confirmed its ability to identify latent common factors clearly related to FA metabolic pathways.

R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 216 any-stage chemonaïve DLBCL patients candidate to R-CHOP were enrolled. The median age of the 185 eligible patients was 59.2 years, 49.7% were women and 45.4% were stage I–II patients. According to the Revised International Prognostic Index (R-IPI), 14.1%, 56.8% and 29.2% were in the very good, good and poor prognosis groups, respectively. Of the patients, 85.9% produced a complete response. Highly significant associations (i.e., p < 5 × 10−8) were found between progression-free survival (PFS) and six SNPs (i.e., rs116665727, rs1607795, rs75614943, rs77241831, rs117500207, rs78466241). Additionally, five SNPs (i.e., rs74832512, rs117500207, rs35789195, rs11721010, rs12356569) were highly associated with overall survival (OS). Wild-type patients showed a prolonged PFS or OS compared with patients carrying deleterious alleles (p < 0.001). No association with the adequate significant threshold was observed between SNPs and the objective response or toxicity. In the future, these SNPs, alone or in combination, after a proper validation in an independent cohort, could contribute to improving the prediction of R-CHOP response.