The Acidity of a Carbon Nucleophile Dictates Enantioselectivity and Reactivity in Michael Additions to Aromatic and Aliphatic Enals via Iminium Activation

The Michael addition of activated methylenes to β-substituted α,β-unsaturated aldehydes (enals) via iminium catalysis takes place following reactivity and enantioselectivity patterns which depend on the electronic nature of the substituent in the β position (β-aryl or β-alkyl). Application of the same reaction conditions to both families of enals may result in erratic levels of asymmetric induction in the reactions of β-aryl enals or low reactivity with β-alkyl enals. A systematic analysis of this behavior using phenylacetic acid derivatives as case studies has led us to find a general trend: the different problems found for β-aryl and β-alkyl enals depend on the acidity of the nucleophile, and the outcome of the reaction for both types of enals can be improved substantially by careful choice of catalyst, solvent, and additive. Furthermore, this study has allowed us to understand subtle aspects of this transformation and has enabled the formulation of a general and reliable protocol to obtain high yields and enantioselectivities consistently, regardless of the acidity of the nucleophile and the nature of the substituent (aromatic or aliphatic) at the β positionWe thank CTQ-2009-12168, CAM (AVANCAT CS2009/PPQ-1634), UAM-CAM (CCG10-UAM/PPQ-5769), CTQ-2012-35957, CTQ2015-63997-C2-1-P, CTQ2016-78779-R and FOTOCARBON-CAM S2013/MIT-2841 for financial support. S.D. thanks the Comunidad Autónoma de Madrid (CAM), and E.R. and S.M. thank MICINN, for predoctoral fellowships. P.M. thanks MICINN for a Ramón y Cajal contract and the EU for a Marie Curie grant (CIG: HYPERCAT-30422

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Arylacetic acid derivatives as nucleophiles in iminium ion activation catalysis: synthetic applications and mechanistic insights

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 23-05-201

Diseño de una vivienda unifamiliar aislada

El trabajo final de grado trata de dar explicación la realización del diseño de una vivienda unifamiliar aislada según el estándar Passivhaus, realizando una memoria descriptiva, constructiva, cumplimiento del CTE y otros reglamentos, certificación energética y mediciones y presupuestos para evaluar el resultado de las soluciones adoptadas en el proyecto. Se ha realizado a la vez una parte teórica en la que se explican los conceptos básicos sobre el tema y de donde parten las soluciones escogidas para el diseño de la vivienda

Toward the discovery and development of PSMA targeted inhibitors for nuclear medicine applications

Background: The rising incidence rate of prostate cancer (PCa) has promoted the development of new diagnostic and therapeutic radiopharmaceuticals during the last decades. Promising im-provements have been achieved in clinical practice using prostate specific membrane antigen (PSMA) labeled agents, including specific antibodies and small molecular weight inhibitors. Focusing on molecular docking studies, this review aims to highlight the progress in the design of PSMA targeted agents for a potential use in nuclear medicine. Results: Although the first development of radiopharmaceuticals able to specifically recognize PSMA was exclusively oriented to macromolecule protein structure such as radiolabeled monoclonal antibodies and derivatives, the isolation of the crystal structure of PSMA served as the trigger for the synthesis and the further evaluation of a variety of low molecular weight inhibitors. Among the nuclear imaging probes and radiotherapeutics that have been developed and tested till today, labeled Glutamate-ureido inhibitors are the most prevalent PSMA-targeting agents for nuclear medicine applications. Conclusion: PSMA represents for researchers the most attractive target for the detection and treatment of patients affected by PCa using nuclear medicine modalities. [99mTc]MIP-1404 is considered the tracer of choice for SPECT imaging and [68Ga]PSMA-11 is the leading diagnostic for PET imaging by general consensus. [18F]DCFPyL and [18F]PSMA-1007 are clearly the emerging PET PSMA candidates for their great potential for a widespread commercial distribution. After paving the way with new imaging tools, academic and industrial R&Ds are now focusing on the development of PSMA inhibitors labeled with alpha or beta minus emitters for a theragnostic application

Adequate health literacy is associated with adherence to continuous positive airway pressure in adults with Obstructive Sleep Apnoea

Study Objectives: Obstructive sleep apnea (OSA) is a chronic disease with significant health implications and adequate adherence to continuous positive airway pressure (CPAP) is essential for effective treatment. In many chronic diseases, health literacy has been found to predict treatment adherence and outcomes. In this study, the aim was to determine the health literacy of a sleep clinic population and evaluate the association between health literacy and CPAP adherence.Methods: A prospective cohort study was undertaken, recruiting 104 consecutive patients with a variety of sleep diagnoses. The Short Form Rapid Estimate of Adult Literacy in Medicine (REALM-SF), a validated questionnaire, was administered to measure health literacy. In a sub-group of 91 patients prescribed CPAP for OSA, CPAP usage was measured, with adequate usage defined as greater than 4 h/night CPAP therapy.Results: Seventy-one percent of the sleep clinic cohort was found to have adequate health literacy, as measured by the REALM-SF. In those prescribed CPAP for OSA, inadequate health literacy was associated with a twofold increased risk for inadequate CPAP usage (adjusted odds ratio [OR] 2.9, 95% CI: 1.1 to 8.22, p = 0.045). There was a 1.7 h/night difference in median CPAP usage comparing those with adequate to inadequate health literacy (4.6 h vs. 6.3 h/night).Conclusions: The majority of this sleep disorders cohort had adequate health literacy as measured by the REALM-SF questionnaire. However, inadequate health literacy appears to be an independent predictor of treatment adherence and may represent a modifiable risk factor of poor treatment outcomes in OSA

Sentinel lymph node mapping in breast cancer: a critical reappraisal of the internal mammary chain issue

Although, like the axilla, the internal mammary nodes (IMNs) are a first-echelon nodal drainage site in breast cancer, the importance of their treatment has long been debated. Seminal randomized trials have failed to demonstrate a survival benefit from surgical IMN dissection, and several retrospective studies have shown that IMNs are rarely the first site of recurrence. However, the recent widespread adoption of sentinel lymph node (SLN) biopsy has stimulated a critical reappraisal of such early results. Furthermore, the higher proportion of screening-detected cancers, improved imaging and techniques (i.e., lymphoscintigraphy for radioguided SLN biopsy) make it possible to visualize lymphatic drainage to the IMNs. The virtually systematic application of adjuvant systemic and/or loco-regional radiotherapy encourages re-examination of the significance of IMN metastases. Moreover, randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic chemotherapy, which was not routinely administered in the earlier studies. However, the contribution from IMN treatment is unclear. Lymphoscintigraphic studies have shown that a significant proportion of breast cancers have primary drainage to the IMNs, including approximately 30% of medial tumors and 15% of lateral tumors. In the few studies where IMN biopsy was performed, 20% of sentinel IMNs were metastatic. The risk of IMN involvement is higher in patients with medial tumors and positive axillary nodes. IMN metastasis has prognostic significance, as recognized by its inclusion in the American Joint Committee on Cancer staging criteria, and seems to have similar prognostic importance as axillary nodal involvement. Although routine IMN evaluation might be indicated, it has not been routinely performed, perhaps because IMN drainage with lymphoscintigraphy is more difficult to demonstrate than axillary drainage. This difference is due to technical reasons and not the absence of lymphatics to the IMN. Recent anatomical studies have confirmed a model of breast lymphatic drainage that comprises superficial, deep and perforating systems. The superficial system drains to the axilla, usually to a lymph node posterior to the pectoralis minor muscle. The deep system drains to the axilla and also anastomoses with the perforating system which drains to the IMNs. The perforating system does not connect with the superficial system. The prevalence of IMN drainage tends to reflect the method of lymphoscintigraphy, where peritumoral (deep lymphatic system) injections have a much higher likelihood of IMN drainage than subareolar or subdermal (superficial lymphatic system) injections. The fused SPECT/CT images represent a further technical solution to increase the identification of IMNs and consequently can significantly reduce the false negative rate of sentinel lymph node biopsy. Before mature results from current and future randomized trials assessing the benefit of IMN irradiation become available, lymphoscintigraphy and IMNs biopsy may be used to guide decisions regarding systemic and local-regional treatment. However, even in patients with visualized primary IMN drainage, the potential benefit of treatment should be balanced against the risk of added morbidity

Randomized controlled trial on the efficacy of audio-visual health educational materials on CPAP adherence: the AHEAD trial

Study Objectives: Educational interventions have been proposed to improve continuous positive airway pressure (CPAP) adherence; however, studies to date have not demonstrated robust effectiveness, due to methodological issues. Furthermore, these educational interventions have not specifically targeted low health literacy communication techniques, which have been demonstrated to improve outcomes in numerous other chronic diseases. We hypothesized that the addition of low-cost audio-visual educational videos (EVs) to usual standard-of-care (SC) education would improve CPAP adherence in adults with obstructive sleep apnea (OSA) syndrome. Methods: At CPAP initiation, treatment-naïve adults with OSA syndrome were randomized to (1) usual SC or (2) SC + 5 EVs showing a patient’s journey, designed with low health literacy communication techniques to teach patients about OSA and CPAP therapy. The primary endpoint was CPAP usage at 2 months (hours/night) and secondary endpoints were CPAP usage at 12 months and percentage of patients with ≥ 4 hours/night use at 2 months and 12 months. Results: One hundred and ninety-five patients were randomized (SC 99, EV 96), with a mean age of 57 years (interquartile range [IQR] 44.1–64.8 years). There were no statistically significant differences in patient characteristics at baseline between the SC vs EV groups, with the diagnostic apnea-hypopnea index of 34 events/h (IQR 21–59 events/h) vs 30 events/h (IQR 20–50 events/h) and Epworth Sleepiness Scale score of 12.8 ± 6 vs 11.7 ± 5. At 2 months, there was no significant difference in hours of CPAP usage (SC: 3.45 hours/night [95% confidence interval (CI): 2.76 to 4.13] vs EV: 3.75 hours/night [95% CI: 3.14 to 4.37]) nor in proportion with adequate usage or overall commencement rate. However, at 12 months, there was a significant difference in hours of CPAP usage (SC: 2.50 hours/night [95% CI: 1.94 to 3.06] vs EV: 3.66 hours/night [95% CI: 2.92 to 4.40]). The probability of adequate CPAP usage at 12 months was higher in the intervention arm (odds ratio: 1.33; 95% CI: 1.04 to 1.7; P = .013). Patients with low education backgrounds benefitted substantially from the EV intervention compared with SC (mean difference at 12 months = 2.47 hours/night usage; 95% CI: 1.01 to 2.93; P < .01). Conclusions: Low health literacy–designed EVs improve CPAP adherence at 12 months compared with SC, with the greatest impact in patients with a low educational background. Clinical Trial Registration: Registry: Australian New Zealand Clinical Trials Registry; Name: Randomised controlled trial on the efficacy of audio-visual health educational materials on sleep health literacy and continuous positive airway pressure (CPAP) adherence in Sleep Clinic patients; URL: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12619000523101;</p

A Preliminary characterization of wools from italian native sheep breeds: opportunities for new productions and the development of rural areas

Italian sheep breeds, either local or native, produce about 14,000 tons of greasy wool per year included in the range of moderate to poor quality wools. In order to exploit neglected local textile resources, this study focused on a preliminary descriptive analysis of wools from some Italian native sheep breeds by measuring diameter and length of wool fibers. Variability emerging from data was described using multivariate techniques. A graphic description of different wools was provided by applying cluster analysis in order to distinguish wool characters by sheep breeds and clearly identify wool groups according to fiber variables