Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

The development of type-1 autoimmune hepatitis after chronic hepatitis C (HCV) clearance by direct-acting antivirals (DAA).

We present the case of a 72-year-old female in follow-up for chronic hepatitis due to hepatitis C virus (HCV) genotype 1b, with a liver stiffness measurement estimated by transient elastography in 2015 of 17 Kp and type 2 diabetes mellitus. She was treated daily with ledipasvir 90 mg and sofosbuvir 400 mg for 12 weeks. In March 2016, she achieved a sustained virological response (SVR) after 12 weeks and 24 weeks. She had a positive determination of antinuclear antibodies 7.9 in 2014.

Pliocene-Pleistocene ecological niche evolution shapes the phylogeography of a Mediterranean plant group.

Estimating species ability to adapt to environmental changes is crucial to understand their past and future response to climate change. The Mediterranean Basin has experienced remarkable climatic changes since the Miocene, which have greatly influenced the evolution of the Mediterranean flora. Here, we examine the evolutionary history and biogeographic patterns of two sedge sister species (Carex, Cyperaceae) restricted to the western Mediterranean Basin, but with Pliocene fossil record in central Europe. In particular, we estimated the evolution of climatic niches through time and its influence in lineage differentiation. We carried out a dated phylogenetic-phylogeographic study based on seven DNA regions (nDNA and ptDNA) and fingerprinting data (AFLPs), and modelled ecological niches and species distributions for the Pliocene, Pleistocene and present. Phylogenetic and divergence time analyses revealed that both species form a monophyletic lineage originated in the late Pliocene-early Pleistocene. We detected clear genetic differentiation between both species with distinct genetic clusters in disjunct areas, indicating the predominant role of geographic barriers limiting gene flow. We found a remarkable shift in the climatic requirements between Pliocene and extant populations, although the niche seems to have been relatively conserved since the Pleistocene split of both species. This study highlights how an integrative approach combining different data sources and analyses, including fossils, allows solid and robust inferences about the evolutionary history of a plant group since the Pliocene.

[Outcome of posterior anorectal myectomy for the treatment of idiopathic chronic constipation]. / Resultados de la miectomía anorrectal posterior en el tratamiento del estreñimiento crónico idiopático.

OBJECIVES: The aim of this study is to assess the outcome of surgery (Lynn's myectomy) in patients with chronic persistent constipation and failure of medical treatment. MATERIAL AND METHODS: Descriptive study of patients with severe chronic constipation treated by posterior anorectal myectomy (Lynn's technique). We report data from the last 15 years, with a minimum postoperative follow-up of one year. Patients included in the study suffered from a long-term constipation refractory to medical management. Data regarding contrast enema, anorectal manometry and rectal biopsy were recorded. The procedure's outcome is classified following clinical criteria: Asymptomatic: >3 bowel movements per week, with no soiling/incontinence and with no medical treatment; Improvement: >3 bowel movements per week, with no soiling/incontinence but using laxatives occasionally. RESULTS: Nineteen myectomies were performed (median age of 8.47 years). Median time of constipation before surgery was 7.89 years. Rectal biopsy findings: 10 with ganglion cells, 4 without ganglion cells and other abnormalities in 5. Anorectal manometry was performed in 6 patients, 4 presented rectoanal inhibitory reflex. Four patients were diagnosed of Hirschsprung's disease (1 was asymptomatic after myectomy, 2 needed further surgery and 1 was lost in follow-up). Of the remaining 15 patients, 8 were asymptomatic (53.3%), 4 experienced improvement (26.6%) and 1 without clinical changes is on pelvic floor physiotherapy. Two were lost in follow-up. There were no other postoperative complications after long term follow-up. CONCLUSIONS: Lynn's myectomy is an effective and safe procedure in patients suffering from persistent chronic constipation despite of medical treatment. It is also the definitive treatment for patients with ultrashort-segment Hirschsprung's disease.

OBJETIVO: Evaluar los resultados clínicos del tratamiento quirúrgico de pacientes con estreñimiento crónico incontrolable con tratamiento médico. MATERIAL Y METODOS: Estudio descriptivo de pacientes con estreñimiento crónico severo tratados mediante miectomía anorrectal posterior (técnica de Lynn). Se recogen los resultados de los últimos 15 años, con periodo de seguimiento postoperatorio mínimo de 1 año. Se incluyen pacientes con larga historia de estreñimiento, refractarios a tratamiento médico. Pruebas complementarias: enema opaco, manometría anorrectal y biopsias rectales. El resultado clínico de la técnica se clasifica según los siguientes criterios: Curación: >3 movimientos intestinales por semana, sin incontinencia/encopresis y sin necesidad de tratamiento médico; Mejoría: >3 movimientos intestinales por semana, sin incontinencia/encopresis y con necesidad de laxante. RESULTADOS: Se realizaron 19 miectomías (edad media de 8,47 años). Tiempo medio de estreñimiento previo de 7,89 años. Los hallazgos en la anatomía patológica fueron: presencia de células ganglionares en 10, ausencia de células ganglionares en 4 y otras alteraciones en 5. Manometría en 6 pacientes, 4 presentaron reflejo inhibitorio anal. Cuatro pacientes se diagnosticaron de enfermedad de Hirschsprung (uno se curó con la miectomía, dos precisaron cirugía correctora y uno no acudió a revisiones). En los 15 restantes, cumplieron criterios de curación 8 pacientes (53,3%), 4 mejoraron (26,6%), 1 sin mejoría sigue tratamiento fisioterápico. Dos pacientes no continuaron las revisiones. No se registró incontinencia fecal ni otras complicaciones. CONCLUSIONES: La miectomía de Lynn es un procedimiento eficaz y seguro para los pacientes con estreñimiento crónico severo refractario al tratamiento médico. También resulta el tratamiento definitivo en la enfermedad de Hirschsprung de segmento ultracorto.

Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study).

INTRODUCTION: Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer. METHODS: Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method). RESULTS: The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was ∼100%. The pathologic complete response was 50%. CONCLUSIONS: The combination allows the delivery of full-dose intensity, while efficacy seems promising.

Increased intraocular pressure secondary to retinal detachment.

Four clinical cases of patients with rhegmatogenous retinal detachment (RRD) associated with elevated intraocular pressure (IOP) are described. All the patients were men who came to the emergency service with floaters, all presented mild to moderate inflammation in the anterior chamber and increased intraocular pressure greater than 30 mmHg. All were diagnosed of RRD. This demonstrates that a RRD does not always present low IOP. In these cases of clinical retinal pathology and high IOP, we must carefully examine the anterior chamber and the fundus of the eye so that an associated retinal detachment does not remain unnoticed, and can be treated immediately. This association of elevated IOP and RRD is called as Schwartz-Matsuo Syndrome.1.

Effect of environmental and spatial factors on the phylogenetic and functional diversity of the Mediterranean tree communities of Europe.

The tree flora of the Mediterranean Basin contains an outstanding taxonomic richness and a high proportion of endemic taxa. Contrary to other regions of the Mediterranean biome, a comprehensive phylogenetic analysis of the relationship between phylogenetic diversity, trait diversity and environmental factors in a spatial ecological context is lacking. We inferred the first calibrated phylogeny of 203 native tree species occurring in the European Mediterranean Basin based on 12 DNA regions. Using a set of four functional traits, we computed phylogenetic diversity for all 10,042 grid cells of 10 × 10 km spatial resolution to completely cover Mediterranean Europe. Then, we tested the spatial influence of environmental factors on tree diversity. Our results suggest that the nature of the relationship between traits and phylogeny varies among the different studied traits and according to the evolutionary distance considered. Phylogenetic diversity and functional diversity of European Mediterranean trees correlated strongly with species richness. High values of these diversity indices were located in the north of the study area, at high altitude, and minimum temperature of the coldest month. In contrast, the two phylogenetic indices that were not correlated with species richness (Mean Phylogenetic Distance, Phylogenetic Species Variability) were located in the south of the study area and were positively correlated with high altitude, soil organic carbon stock and sand soil texture. Our study provides support for the use of phylogenies in conservation biology to assess ecosystem functioning, and provides insights for the implementation of sustainable forest ecosystem management.

A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

Open air mineral treatment operations and ambient air quality: assessment and source apportionment.

We present a methodology for evaluating and quantifying the impact of inhalable mineral dust resuspension close to a potentially important industrial point source, in this case an open air plant producing sand, flux and kaolin in the Capuchinos district of Alcañiz (Teruel, NE Spain). PM(10) levels at Capuchinos were initially high (42 µg m(-3) as the annual average with 91 exceedances of the EU daily limit value during 2007) but subsequently decreased (26 µg m(-3) with 16 exceedances in 2010) due to a reduced demand for minerals from the ceramic industry and construction sector during the first stages of the economic crisis. Back trajectory and local wind pattern analyses revealed only limited contribution from exotic PM sources such as African dust intrusions whereas there was clearly a strong link with the mineral stockpiles of the local industry. This link was reinforced by chemical and mineral speciation and source apportionment analysis which showed a dominance of mineral matter (sum of CO(3)(2-), SiO(2), Al(2)O(3), Ca, Fe, K, Mg, P, and Ti: mostly aluminosilicates) which in 2007 contributed 76% of the PM(10) mass (44 µg m(-3) on average). The contribution from Secondary Inorganic Aerosols (SIA, sum of SO(4)(2-), NO(3)(-) and NH(4)(+)) reached 8.4 µg m(-3), accounting for 14% of the PM(10) mass, similar to the amount of calcareous road dust estimated to be present (8 µg m(-3); 13%). Organic matter and elemental carbon contributed 5.3 µg m(-3) (9%) whereas marine aerosol (Na + Cl) levels were minor with an average concentration of 0.4 µg m(-3) (1% of the PM(10) mass). Finally, chemical and mineralogical analysis of stockpile samples and comparison with filter samples confirmed the local industry to be the major source of ambient PM(10) in the area.

Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force.

BACKGROUND: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. PATIENTS AND METHODS: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. RESULTS: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. CONCLUSIONS: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.

Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study.

BACKGROUND: In order to determine the feasibility of substituting pegylated liposomal doxorubicin (PLD) for doxorubicin in combination with cyclophosphamide and trastuzumab as adjuvant therapy, we conducted a phase II study of the combination as first-line therapy in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic breast cancer (MBC). METHODS: PLD 50 mg/m(2) and cyclophosphamide 600 mg/m(2) were administered every 4 weeks for six cycles; trastuzumab (4 mg/kg loading dose, then 2 mg/kg) was administered weekly for 24 weeks. The primary end point was objective response rate (ORR), and the secondary end points included time to progression (TTP), overall survival (OS), and safety. RESULTS: Among the 48 evaluable patients, ORR was 68.8% [95% confidence interval (CI) 55.69% to 81.91%], with 6 patients (12.5%) achieving a complete response and 27 (56.2%) a partial response. The median TTP was 12 months (95% CI 9-15.1 months), and the median OS was 34.2 months (95% CI 27.2-41.2 months). Febrile neutropenia was seen in three patients, grade 3 hand-foot syndrome in 29.2% of patients, and grade 3-4 mucositis in 22.9% of patients. Symptomatic congestive heart failure was not observed, and 16.7% of patients experienced grade 2 asymptomatic left ventricular systolic dysfunction. CONCLUSION: The combination of PLD-cyclophosphamide-concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.

Atypical symptoms of gastro-esophageal reflux during pregnancy.

BACKGROUND: Pregnancy is associated with an increased incidence of heartburn. However, there is no information for other symptoms related to gastro-esophageal reflux (GOR). AIM: to assess the prevalence of atypical symptoms of GOR during pregnancy, and to examine its association with typical GOR symptoms. METHODS: we report data for 263 women with a pregnancy of less than 12 weeks. They were interviewed at the end of each trimester of pregnancy and at 1-year post-partum, using the Gastro Esophageal Reflux Questionnaire (GERQ). In the first interview, information about symptoms in the year before pregnancy was also collected with GERQ. RESULTS: women suffered atypical GOR symptoms during pregnancy more frequently than in the year before: non-cardiac chest pain (NCCP) (9.1 vs. 1.9%), dysphagia (12.6 vs. 2.3%), globus (33.1 vs. 4.6%), cough (26.6 vs. 6.8%), belching (66.2 vs. 19.4%) and hiccups (19.0 vs. 8.4%). Atypical GOR symptoms in pregnancy showed an association with suffering the same symptom before pregnancy and NCCP, globus, belching and hiccups with suffering typical GOR symptoms in the first trimester. CONCLUSIONS: Atypical GOR symptoms are highly prevalent in pregnancy, and are associated with atypical symptoms before pregnancy and with typical symptoms of GOR in the first trimester.

Understanding the local and remote source contributions to ambient O3 during a pollution episode using a combination of experimental approaches in the Guadalquivir valley, southern Spain.

The Guadalquivir Valley is one of three major O3 hotspots in Spain. An airborne and surface measurement campaign was carried out from July 9th to 11th, 2019 to quantify the local/regional O3 contributions using experimental approaches. Air quality and meteorology data from surface measurements, a microlight aircraft, a helium balloon, and remote sensing data (TROPOMI-NO2-ESA) were used to obtain the 3D distribution of O3 and various tracer pollutants. O3 accumulation over 2.5 days started with inputs from oceanic air masses transported inland by sea breezes, which drew O3 and its precursors from a local/regional origin to the northeastern end of the basin. The orographic-meteorological setting of the valley caused vertical recirculation of the air masses inside the valley that caused the accumulation by increasing regional background O3 concentration by 25-30 ppb. Furthermore, possible Mediterranean O3 contributions and additional vertical recirculation through the entrainment zone of the convective boundary layer also contributed. Using particulate matter finer than 2.5 µm (PM2.5), ultrafine particles (UFP), and black carbon (BC) as tracers of local sources, we calculated that local contributions increased regional O3 levels by 20 ppb inside specific pollution plumes transported by the breeze into the valley, and by 10 ppb during midday when flying over an area with abundant agricultural burning during the morning. Air masses that crossed the southern boundaries of the Betic system at mid-altitude (400-1850 m a.s.l.) on July 10th and 11th may have provided additional O3. Meanwhile, a decreasing trend at high altitudes (3000-5000 m a.s.l.) was observed, signifying that the impact of stratospheric O3 intrusion decreased during the campaign.

The east-west-north colonization history of the Mediterranean and Europe by the coastal plant Carex extensa (Cyperaceae).

Coastal plants are ideal models for studying the colonization routes of species because of the simple linear distributions of these species. Carex extensa occurs mainly in salt marshes along the Mediterranean and European coasts. Variation in cpDNA sequences, amplified fragment length polymorphisms (AFLPs) and simple sequence repeats (SSRs) of 24 populations were analysed to reconstruct its colonization history. Phylogenetic relationships indicate that C. extensa together with the South American Carex vixdentata and the southern African Carex ecklonii form a monophyletic group of halophilic species. Analyses of divergence times suggest that early lineage diversification may have occurred between the late Miocene and the late Pliocene (Messinian crisis). Phylogenetic and network analyses of cpDNA variation revealed the monophyly of the species and an ancestral haplotype contained in populations of the eastern Mediterranean. The AFLP and SSR analyses support a pattern of variation compatible with these two lineages. These analyses also show higher levels of genetic diversity and differentiation in the eastern population group, which underwent an east-to-west Mediterranean colonization. Quaternary climatic oscillations appear to have been responsible for the split between these two lineages. Secondary contacts may have taken place in areas near the Ligurian Sea in agreement with the gene flow detected in Corsican populations. The AFLP and SSR data accord with the 'tabula rasa' hypothesis in which a recent and rapid colonization of northern Europe took place from the western Mediterranean after the Last Glacial Maximum. The unbalanced west-east vs. west-north colonization may be as a result of 'high density blocking' effect.

Heavy metal transport and evolution of atmospheric aerosols in the Antarctic region.

Suspended particulate matter (SPM) measurements and backward air mass trajectory analysis using the HYSPLIT model were performed to better understand the main sources and transport pathways of heavy metals in atmospheric aerosols reaching the Antarctic region. Field campaigns were carried out during the austral summer 2016-2017 at the "Gabriel de Castilla" Spanish Antarctic Research Station, located on Deception Island. Aerosols were deposited in an air filter through a low-volume sampler and chemically analysed using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The study of air masses and high enrichment factor values of several elements (Hf, Zr, As, Cu, Sn, Zn, Pb) together with their correlations (Hf/Zr, V/As, Ti/Mn and Cu/Sn) suggests a potentially significant role of three main sources in this area: remote maritime traffic, local petrol combustion (generators and/or tourist cruises), and remote/local crust. Additionally, the investigation of atmospheric flow patterns through backward trajectory analysis revealed that Hf/Zr correlation was related to a remote crustal origin, V/As to anthropogenic local pollution, Ti/Mn to terrestrial inputs on the island and Cu/Sn to remote anthropogenic sources. Overall, the present study demonstrates the existence of anthropogenic pollution at this remote site from distant as well as local sources following the Antarctic circumpolar wind pattern.

Electrochemically reduced graphene oxide on CoCr biomedical alloy: Characterization, macrophage biocompatibility and hemocompatibility in rats with graphene and graphene oxide.

Electrochemically reduced graphene oxide (ErGO) films on a biomedical grade CoCr alloy have been generated and characterized in order to study their possible application for use on joint prostheses. The electrodeposition process was performed by cyclic voltammetry. The characterization of the ErGO films on CoCr alloys by XPS revealed sp2 bonding and the presence of CO and CO residual groups in the graphene network. Biocompatibility studies were performed with mouse macrophages J774A.1 cell cultures measured by the ratio between lactate dehydrogenase and mitochondrial activities. An enhancement in the biocompatibility of the CoCr with the ErGO films was obtained, a result that became more evident as exposure time increased. Macrophages on the CoCr with the ErGO were well-distributed and conserved the characteristic cell shape. In addition, vimentin expression was unaltered in comparison with the control, results that indicated an improvement in the CoCr biocompatibility with the ErGO on the material surface. The in vivo response of graphene and graphene oxide was assessed by intraperitoneal injection in wistar rats. Red blood cells are one of the primary interaction sites so hemocompatibility tests were carried out. Rats inoculated with graphene and graphene oxide showed red blood cells of smaller size with a high content in hemoglobin.

Inhibitory effects of sucrose fatty acid esters on survival of Yersinia enterocolitica on eggshell surface and use of blue lake as indicator of bacterial penetration into eggs.

AIMS: To determine the effectiveness of sucrose monolaurate (SML) and sucrose monocaprate (SMC), alone and in combination with ethylenediaminetetraacetic acid (EDTA), propionic acid (PA) or citric acid (CA) in reducing mesophilic aerobic bacteria (MAB) and Yersinia enterocolitica O:9 populations on eggshells and their damage potential on the microstructure of shell cuticle. METHODS AND RESULTS: Uninoculated eggs and eggs submerged in a solution of Y. enterocolitica were immersed in solutions of the various treatments. MAB and Y. enterocolitica counts on the surface of the eggs were carried out before and after treatment. MAB counts decreased less than 2 logs on uninoculated eggshells irrespective of treatment and reductions of 3.2 and 3.0 logs of Y. enterocolitica were obtained with 1000 microg ml(-1) SML plus 0.1% CA or 1000 microg ml(-1) SML plus 600 microg ml(-1) EDTA solutions, respectively. Y. enterocolitica 2/O:9 was recovered from natural microflora. Use of blue lake staining revealed minimal damage to the shells from the washing treatments. CONCLUSIONS: SML and SMC at 1000 microg ml(-1) combined with CA or EDTA could be effective in reducing Y. enterocolitica on eggshells with a minimal risk of later bacterial recontamination. SIGNIFICANCE AND IMPACT OF THE STUDY: Eggs are a recognized vehicle for transmission of Y enterocolitica although a prevalence of only 2.7% was detected in this study. Washing eggs in solutions containing SML or SMC could eliminate Y. enterocolitica contamination of egg shells.