Insights on the climatic evolution at the pre-Jaramillo to Jaramillo transition in Europe using mineralogical analysis of the Quibas palaeontological site (Early Pleistocene, southern Iberian Peninsula)

© The Authors, 2023. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (for details please see http://creativecommons.org/licenses/by/4.0/), which permits use, copy, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source. This document is the Published version of a Published Work that appeared in final form in Spanish Journal of Palaeontology. To access the final edited and published work see https://doi.org/10.7203/sjp.27562The palaeontological site of Quibas is a karst outcrop with an age between 1.1 and 0.9 Ma (late Early Pleistocene). It represents the unique continuous sequence of terrestrial vertebrates of pre-Jaramillo to Jaramillo age in Europe. It is formed by two main structures: Quibas-Sima (divided into units QS-1 to QS-7) and Quibas-Cueva (QC-1– QC-6). In this work, we analyse the mineralogical composition of the sediments that form the stratigraphic units of Quibas-Sima using X-ray diffraction analysis, electrical conductivity, ion chromatography and optical emission spectrometry, to evaluate climatic trends in the sequence. Preliminary results indicate that there is an increase in the proportions of carbonates, gypsum and halite from QS-2 towards QS-4 and QS-5 (1.07–0.99 Ma), suggesting a progressive decrease in precipitation in south-eastern Iberian Peninsula a million years ago. Our data are consistent with the onset of a glacial phase, which is supported by the progressive disappearance of taxa related to forests and water bodies in Quibas-Sima, such as the flying squirrel Hylopetes sp. and the semiaquatic shrew Neomys sp., in favour of the appearance of taxa linked to open areas such as the Montpellier snake (Malpolon monspessulanus) and the snub-nosed viper (Vipera latastei). El yacimiento paleontológico de Quibas es un afloramiento kárstico con una edad comprendida entre 1,1 y 0,9 Ma (Pleistoceno Inferior tardío). Representa la única secuencia continua de vertebrados terrestres de edad pre-Jaramillo a Jaramillo de Europa. Está formado por dos estructuras principales: Quibas-Sima (dividida en las unidades QS-1 a QS-7) y Quibas-Cueva (QC-1 a QC-6). En este trabajo se estudia la composición mineralógica de los sedimentos que conforman las unidades estratigráficas de QuibasSima, a través e análisis de difracción de rayos X, conductividad eléctrica, cromatografía iónica y espectrometría de emisión óptica por plasma de argón, con el objetivo de evaluar tendencias paleoclimáticas en la secuencia. Los resultados preliminares indican que hay un aumento en las proporciones de carbonatos, yesos y halita desde QS-2 hacia QS-4 y QS-5 (1,07–0,99 Ma), lo que sugiere una progresiva disminución de las precipitaciones en el sureste peninsular hace un millón de años. Los datos son consistentes con el inicio de una fase glaciar, lo cual viene apoyado por la desaparición progresiva en Quibas-Sima de taxones afines a bosques y cursos de agua estables como la ardilla voladora Hylopetes sp. y el musgaño Neomys sp., en favor de la aparición de taxones ligados a espacios abiertos como la culebra bastarda (Malpolon monspessulanus) y la víbora hocicuda (Vipera latastei)

Current approaches to soft contact lens handling training - Global perspectives

Purpose All neophyte contact lens wearers require training on how to handle contact lenses. Currently, almost no published information exists describing the most common approaches used by those involved in such training in soft contact lens wearers. This study aimed to gather information on the approaches taken by those conducting this training worldwide. Methods An online survey was created in English and translated to Spanish and distributed internationally via social media, conference attendees, and professional contacts. The anonymous survey included information on workplace setting of respondents, information about the typical approaches used for application and removal of soft contact lenses, length of the appointment, and success rate with their approach. Survey responses were received between May 2021 and April 2022. Results A total of 511 individuals completed the survey and responses were received from 31 countries with 48.7% from the UK. The most common approach taught for application was to have the patient hold the upper eyelashes (84.7%) and to hold the lower eyelid with the same hand as the lens (89.4%). Lenses were applied directly to the cornea by 57.7% of the respondents. The most common approach taught for lens removal was to drag the lens inferiorly from the cornea prior to removal (49.3%). Most respondents did not use videos to aid the teaching appointment (62.0%); however, they felt that their approach was successful in most cases (90). Application and removal training sessions lasted a median of 30 min and contact lenses were typically dispensed after the instructor witnessing successful application and removal three times. Conclusion Various methods are adopted globally for training of application and removal of soft contact lenses, with many advising a patient-specific approach is required for success. The results of this survey provide novel insights into soft contact lens handling training in clinical practice

Automatic Filtering and Substantiation of Drug Safety Signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America

Background: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. Methods: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. Results: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. Conclusion: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.Radium Hospital Foundation (Oslo, Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, Helse Sør-Øst (Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, the French Association Recherche contre le Cancer (ARC) in the analysis, and interpretation of data, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (Gefluc) in the analysis, and interpretation of data, the Association Nationale de la Recherche et de la Technologie (ANRT, CIFRE PhD fellowship to H.T.) in the analysis, and interpretation of data and by the OpenHealth Institute in the analysis, and interpretation of data. Barretos Cancer Hospital received financial support by FINEP-CT-INFRA (02/2010)info:eu-repo/semantics/publishedVersio

Intense pulsed light-based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops

Background: Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40% to 59% of these patients worldwide. The current study was aimed at evaluating the potential clinical benefit of an intense pulsed light (IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments. To our knowledge, this is the first series analyzing the therapeutic effect of this treatment option in this type of patients. Methods: This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye symptomatology. All patients received four sessions of IPL treatment using the Optima IPL system (Lumenis, Yokneam, Israel) adjusted to the official optimized Lumenis setting. Changes in symptomatology, corneal staining, conjunctival hyperemia, non-invasive break-up time (NIBUT), tear osmolarity, tear meniscus height (TMH), meiboscore and meibomian gland expressibility was analyzed after treatment. Results: Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires [ocular surface disease index (OSDI), standard patient evaluation of eye dryness (SPEED) and symptom assessment questionnaire in dry eye (SANDE)] as well as with the visual analogue scale (P < 0.001). Mean change in OSDI was − 15.0 ± 11.3. A significant reduction was found after treatment in the corneal staining score (P < 0.001). A significant reduction was found in tear film meniscus height (P = 0.012), as well as in tear film osmolarity (P = 0.001). A significant reduction was also found in meibomian gland expressibility (P = 0.003), changing the percentage of grade 3 eyes from 44.4% before IPL to 17.2% after treatment. Conclusions: IPL therapy combined with meibomian gland expression (MGX) seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments, with an additional improvement in clinical signs, such as tear osmolarity and corneal staining

Efficacy and safety of a soft contact lens to control myopia progression

Clinical relevance: The control of myopia progression is currently considered an evidence-based therapeutic need. Background: To determine the efficacy and safety of the Esencia lens, a new soft contact lens (SCL) designed to slow down myopia progression in paediatric patients. Methods: This study was a randomised, parallel, double-masked clinical trial. Seventy myopic (−0.50 to −8.75 D) boys and girls, 7–15 years of age, were randomised and allocated to one of two groups: (i) study (n = 36) or (ii) control (n = 34). Study group patients were given the Esencia lens, a progressive multifocal and reverse geometry SCL. Control group patients were given conventional SCLs. Efficacy measurements (change in cycloplegic autorefraction and axial length) were measured at baseline and at the six-month intervals over a 12- month period. Visual performance measurements were corneal power, comfort, quality of vision and contact lens fitting. Safety measures included detection of adverse events. Results: Mean changes in cycloplegic autorefraction after 12 months were −0.28 ± 0.35 D for study and −0.57 ± 0.52 D for control group patients (p = 0.02). A significantly lower increase in axial length was found in the study group (0.13 ± 0.12 mm) compared to control (0.22 ± 0.14 mm) patients (p = 0.03). Compared to control group patients, there was less myopia progression in the study group: 51 and 41 per cent in terms of cycloplegic autorefraction and axial length, respectively. No significant differences between groups for change in corneal power, comfort, vision quality and contact lens fitting were found (p > 0.05). Regarding safety, there were no serious and/or unexpected adverse events during the study. Conclusions: The Esencia lens seems to be efficacious in slowing down progression of myopia in children compared to traditional SCLs in the short term, with comparable safety features and visual outcomes

Easyton® transpalpebral versus Perkins applanation tonometry in different populations

Objective To compare intraocular pressure (IOP) measurements obtained using the new transpalpebral Easyton® tonometer and Perkins applanation tonometer (PAT) in three different clinical populations. Methods The participants of this prospective study were 84 subjects divided into the groups: 22 healthy children (G1), 42 healthy adults (G2), and 20 adult patients with primary open angle glaucoma (G3). The data recorded in 84 eyes of these subjects were age, sex, gender, central corneal thickness (CCT), and axial length (AL). In all eyes, IOP was determined in the same examination room by the same experienced examiner using Easyton® and PAT in random order. Results Mean differences in IOP readings between Easyton® and PAT were 0.45 ± 1.97 (p = 0.295), − 0.15 ± 2.13 (p = 0.654), − 1.65 ± 3.22 (p = 0.033), and − 0.018 ± 2.50 mmHg (p = 0.500) in the groups G1, G2, G3, and whole sample (G4), respectively. Correlations between Easyton® and PAT IOP values were 0.668 (p = 0.001) for G1, 0.463 (p = 0.002) for G2, 0.680 (p < 0.001) for G3, and 0.605 (p < 0.001) for G4. Moderate to good agreement between the two tonometers was found in all groups according to intraclass correlation coefficients, which were 0.794 (p < 0.001) for G1, 0.632 (p < 0.001) for G2, 0.809 (p < 0.001) for G3, and 0.740 (p < 0.001) for G4. The lower and upper limits of agreement between the devices were − 5.1 and 4.7 mmHg, respectively, in the complete group. No correlation was noted between CCT or AL and the Easyton® IOP measurements. Conclusion IOP measurements obtained with Easyton® and PAT show an acceptable level of agreement mainly in healthy individuals, recommending it for IOP screening in children and in patients in which PAT measurement may be impared as patients with hemifacial spasms, corneal irregularities, or reduced mobility. It is not recommended for glaucoma patients follow-up