Some commentaries on confidence intervals of the mean in a Normal population

In this paper, a study on the length of confidence intervals of the mean in a Normal population when the variance is either known or unknown is carried out. It is also proved that ignoring the population variance always leads to a worse interval than when such a variance is taken into accoun

The duration of intervals on the oral cancer care pathway and implications for survival: a systematic review and meta-analysis

This work was supported by the Spanish Association Against Cancer [Asociación Española contra el Cáncer, PROYE20023SANC “High resolution study of social inequalities in cancer (HiReSIC)”], the Cancer Epidemiological Surveillance Subprogram of the CIBER of Epidemiology and Public Health and the Health Institute Carlos III (VICA), and the Health Institute Carlos III (PI18/01593 “Multilevel population-based study of socioeconomic inequalities in the geographical distribution of cancer incidence, mortality and net survival”). DP was supported by a Juan de la Cierva Fellowship from the Ministry of Science and the National Research Agency of Spain (MCIN/AEI, JC2019- 039691-I, http://doi.org/10.13039/501100011033, Accessed October 4, 2021). The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2023.1183244/full#supplementary-materialIntroduction: Previous studies measuring intervals on the oral cancer care pathway have been heterogenous, showing mixed results with regard to patient outcomes. The aims of this research were (1) to calculate pooled meta-analytic estimates for the duration of the patient, diagnostic and treatment intervals in oral cancer, considering the income level of the country, and (2) to review the evidence on the relationship of these three intervals with tumor stage at diagnosis and survival. Materials and methods: We conducted a systematic review with meta-analysis following PRISMA 2020 guidelines (pre-registered protocol CRD42020200752). Following the Aarhus statement, studies were eligible if they reported data on the length of the patient (first symptom to first presentation to a healthcare professional), diagnostic (first presentation to diagnosis), or treatment (diagnosis to start of treatment) intervals in adult patients diagnosed with primary oral cancer. The risk of bias was assessed with the Aarhus checklist. Results: Twenty-eight studies reporting on 30,845 patients met the inclusion criteria. The pooled median duration of the patient interval was 47 days (95% CI = 31–73), k = 18, of the diagnosis interval 35 days (95% CI = 21–38),k = 11, and of the treatment interval 30 days (95% CI = 23–53), k = 19. In lower-income countries, the patient and treatment intervals were significantly longer, and longer patient intervals were related to later stage at diagnosis. In studies with a lower risk of bias from high-income countries, longer treatment intervals were associated with lower survival rates. Conclusion: Interval duration on the oral cancer care pathway is influenced by the socio-economic context and may have implications for patient outcomes.Asociación Española contra el Cáncer, PROYE20023SANCCancer Epidemiological Surveillance Subprogram of the CIBER of Epidemiology and Public HealthHealth Institute Carlos III (VICA)Health Institute Carlos III: PI18/01593MCIN/AEI, JC2019-039691-

Organocatalytically Generated Donor − Acceptor Cyclopropanes in Domino Reactions. One-Step Enantioselective Synthesis of Pyrrolo[1,2 ‑ a ]quinolines

An easy and straightforward procedure has been developed for the synthesis of highly enantioenriched pyrrolo-[1,2-a]quinolines through a one-pot process that comprises a domino cyclopropane ring opening/aza-Michael/aldol reaction followed by acid-promoted lactamization. The key feature of the synthetic approach relies on the ability of conveniently functionalized cyclopropaneacetaldehydes to undergo organocatalytic activation by a chiral secondary amine that enables the catalytic generation of a donor acceptor cyclopropane. This intermediate has the potential to undergo a ring opening that generates an electrophilic alpha,beta-unsaturated iminium ion that subsequently reacts through the already mentioned domino sequence and in which stereochemical information is very efficiently transferred from the amine catalyst to the final products. Moreover, one of the alkoxycarbonyl moieties can be easily removed by standard hydrolysis/decarboxylation, providing access to the target adducts as single stereoisomers.This research was supported by the Spanish MINECO (FEDER-CTQ2014-52107-P), the Basque Government (Grupos IT328-10), and UPV/EHU (fellowship to E.S. and UFI QOSYC 11/22). Membership in the COST action CM1407 (NatChemDrugs) is also acknowledged

Catalytic Generation of Donor-Acceptor Cyclopropanes under N-Heterocyclic Carbene Activation and their Stereoselective Reaction with Alkylideneoxindoles

Formylcyclopropanes undergo activation in the presence of an N-heterocyclic carbene catalyst generating a donor-acceptor cyclopropane intermediate with the ability to undergo ring-opening followed by formal [4+2] cycloaddition with alkylideneoxindoles. This enables the direct enantio- and diastereoselective synthesis of tetrahydropyrano[ 2,3-b]indoles through the use of a chiral NHC catalyst. Keywords: asymmetricSpanish MINECO(FEDER-CTQ2014-52107), Basque Government (Grupos IT908-16), UPV/EHU (EHUA 16/10 and UFIQOSYC11/22) for financial support. L. P. and E. S.-D

Organocatalytic Enantioselective Vinylcyclopropane-Cyclopentene (VCP-CP) Rearrangement

We have demonstrated that the catalytic and enantioselective vinylcyclopropane-cyclopentene rearrangement can be carried out on (vinylcyclopropyl)acetaldehydes through activation via enamine intermediates. The reaction makes use of racemic starting materials that, upon ring opening facilitated by the catalytic generation of a donor-acceptor cyclopropane, deliver an acyclic iminium ion/dienolate intermediate in which all stereochemical information has been deleted. The final cyclization step forms the rearrangement product, showing that chirality transfer from the catalyst to the final compound is highly effective and leads to the stereocontrolled formation of a variety of structurally different cyclopentenes.Grants PID2019-104090RB-100 and PID2020-118422GB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future” are gratefully acknowledged together with the Basque Government (Grupos IT1558-22) and the Government of Aragón (Grupos Consolidados, E34-20R and a fellowship to M. P.). G. G. also thanks the Spanish Ministerio de Universidades for an FPU grant. The authors thankfully acknowledge the resources from the supercomputers “Memento” and “Cierzo”, technical expertise and assistance provided by BIFI-ZCAM (Universidad de Zaragoza, Spain)

Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study

We would like to thank M Luisa Puertas-Martin and Isabel Manzano-Jimenez, nurses at the Unit of Mammary Pathology, General Surgery Service, San Cecilio University Hospital (Granada), without whose enthusiasm the enrolment of participants in Granada would still be stalled. We are indebted to all the women taking part in the study.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Trial registration ClinicalTrials.gov NCT03885648, 03/25/2019. Retrospectively registered.Background Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. Methods We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. Discussion: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease.This work is funded by grants PI-0538-2017 (Junta de Andalucía, Spain, to LF) and Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP) of the Institute of Health Carlos III -supported by European Regional Development Fund/FEDER (FIS-PI16/01812) (to MFF)

Sleep time estimated by an actigraphy watch correlates with CSF tau in cognitively unimpaired elders: the modulatory role of APOE

There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer’s Disease core biomarkers (amyloid-β-42 and –40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the APOE ε4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the APOE ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that APOE modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes.This work was supported by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitario, PI08/0139, PI12/02288, PI16/01652, and PI20/01011), the JPND (DEMTEST PI11/03028), the CIBERNED, and the Siemens Healthineer

Clinical Factors, Preventive Behaviours and Temporal Outcomes Associated with COVID-19 Infection in Health Professionals at a Spanish Hospital

The authors thank K. Shashok for improving the use of English in the manuscript.The novel coronavirus disease (COVID-19) outbreak has quickly spread around the world, with Spain being one of the most severely affected countries. Healthcare professionals are an important risk group given their exposure. The aims of this study were to determine the prevalence of symptoms, main concerns as patients, preventive behaviours of healthcare professionals, and the different temporal outcomes associated with the negativization of PCR results. A total of 238 professionals were analysed and follow-up was conducted from 11 March to 21 April 2020 through clinical records, in-depth surveys, and telephone interviews. Symptoms, concerns, and preventive measures were documented, and temporal outcomes (start and end of symptoms, first positive PCR, and negativization of PCR) were analysed through survival analyses. A high prevalence of gastrointestinal symptoms (especially in women and older professionals), fever, cough, and fatigue were reported. The main concern was contagion in the work and home environment. Professionals (especially men) reported low use of face masks before the pandemic. Our analysis indicates that the median times for the negativization of PCR testing to confirm the resolution of infection is 15 days after the end of symptoms, or 25 days after the first positive PCR test. Our results suggest that these times are longer for women and for professionals aged ≥55 years, therefore follow-up strategies should be optimized in light of both variables. This is the first study we are aware of to report factors associated with the time to negativization of PCR results. We present the first rigorous estimates of time outcomes and hope that these data can be valuable to continue feeding the prediction models that are currently being developed. Similar studies are required to corroborate our results.Chair of Teaching and Research in Family Medicine SEMERGEN-UGR. University of Granad

Integración de recursos electrónicos en las bibliotecas del Consorcio de Bibliotecas Universitarias de Andaluzas (CBUA)

En los últimos años, el presupuesto en recursos electrónicos ha ido creciendo paulatinamente en las Bibliotecas Universitarias y como consecuencia las inversiones en este tipo de materiales han ido aumentando, convirtiéndose hoy día la Biblioteca Universitaria en una gran factoría virtual. El Consorcio de Bibliotecas Universitarias Andaluzas (CBUA) que asume entre sus políticas el desarrollo de proyectos para la mejora de la calidad de los servicios a través de la cooperación, consciente de esta situación, acomete el plan de dotar a las Bibliotecas del Consorcio de tecnologías centradas en el usuario, para hacer más accesibles las colecciones de recursos electrónicos y poder competir en la Europa del conocimiento con parámetros de calidad. Se presenta el proyecto que está llevando a cabo el Grupo de Trabajo de MAP y ERM del CBUA, de implementación y puesta en marcha de herramientas, para el acceso, integración y gestión de los recursos electrónicos en las Bibliotecas Universitarias Andaluzas, para un mejor uso de las colecciones digitales contratadas, que redundará en la calidad y mejora de los servicios prestados. Se enumeran las fases del proyecto, los objetivos operativos, las líneas de acción, las acciones realizadas, la documentación generada, la difusión y formación en las nuevas herramientas y la repercusión que está teniendo en las Bibliotecas del CBU