Enantioselective Synthesis of Dialkylated N-Heterocycles by Palladium-Catalyzed Allylic Alkylation

The enantioselective synthesis of α-disubstituted N-heterocyclic carbonyl compounds has been accomplished using palladium-catalyzed allylic alkylation. These catalytic conditions enable access to various heterocycles, such as morpholinone, thiomorpholinone, oxazolidin-4-one, 1,2-oxazepan-3-one, 1,3-oxazinan-4-one, and structurally related lactams, all bearing fully substituted α-positions. Broad functional group tolerance was explored at the α-position in the morpholinone series. We demonstrate the utility of this method by performing various transformations on our useful products to readily access a number of enantioenriched compounds

Glacioeustatic control on the origin and cessation of the Messinian salinity crisis.

The desiccation of the Mediterranean during the Messinian salinity crisis (MSC) is one of the most intriguing geological events of recent Earth history. However, the timing of its onset and end, as well as themechanisms involved remain controversial.We present a novel approach to these questions by examining theMSC fromthe Atlantic, but close to theGibraltar Arc, analysing the completeMessinian record of theMontemayor-1 core of theGuadalquivir Basin (SWSpain). Flexural backstripping analysis shows a tectonic uplift trend that would have reduced the depth of the Rifian Corridors considerably. Nonetheless, the rate of tectonic upliftwas insufficient to account for the close up of the corridors. At 5.97 Ma, a global cooling and associated glacioeustatic sea-level drop, estimated in 60 m, is observed. Thiswould have been sufficient to restrict the Rifian Corridors and to trigger theMSC. The later flooding of the Mediterranean occurred during a sea-level rise associated with global warming during a stable tectonic period. We postulate a two-step flooding event: 1) A glacioeustatic sea-level rise during interglacial stage TG 11 (5.52 Ma) led to subtropical Atlantic waters entering the west-central Mediterranean through pathways south of the Gibraltar Strait, probably the Rifian Corridors. 2) A global sea-level drop at 5.4 Ma, thatmight have favoured intensification of regressive fluvial erosion in the Gibraltar threshold, along with the subsequent global sea-level rise would have generated the Gibraltar Strait leading to complete Mediterranean refilling during the earliest Pliocene

Direct specific isotopic analysis of compounds released by pyrolysis (Py-CSIA): Novel applications in paleoenvironmental studies

Poster J.03 presentado en el The 40th International Symposium on Capillary Chromatography and 13th GCxGC Symposium May 29-June 03, (2016) Riva del Garda Fierecongressi, Riva del Garda, Italyisotopic analysis (Py-CSIA) and analytical pyrolysis (Py-GC/MS) opens new windows of information and is particularly useful to study solid materials that are not soluble and therefore not amenable by conventional GC/MS techniques. Py-CSIA is a rather novel hyphenated technique that combines the chromatographic separation of compounds released by pyrolysis (Py-GC) with an isotope ratio mass spectrometer (IRMS). The technique allows the measurement of stable isotope proportions i.e., δ13C, δ15N and δ2H, δ18O in specific compounds released by pyrolysis. The sample preparation is minimized and a molecular fingerprinting of the material is achieved.N

The role of neo-tectonics in the sedimentary infilling and geomorphological evolution of the Guadalquivir estuary (Gulf of Cadiz, SW Spain) during the Holocene.

Spain) has yielded new evidence regarding the sedimentary infilling and geomorphological evolution of the Guadalquivir estuary during the Holocene. The sedimentation and geomorphological disposition have been strongly conditioned by neotectonic activity along a set of SW-NE alignments, interrupted by other alignments that follow E-W and NW-SE directions. The most conspicuous of the SW-NE alignments is the Torre Carbonero-Marilópez Fault (TCMF). South of this fault, the estuary experienced a marked subsidence from about 4000 to 2000 cal. yr BP through a series of sedimentary sequences of retrogradation and aggradationwithin the context of relative sea-level rise. From c. 2000 cal. yr BP to the present the subsidence has remained relatively dormant, with progradation of the littoral systems and infilling of the marshland progressing within a context of sea-level stability. Our results reveal that neotectonic activity is a critical factor thatmust also be reckonedwith in any attempt to understand the Holocene geomorphological evolution in the Guadalquivir estuary

SilvAdapt.Net: A Site-Based Network of Adaptive Forest Management Related to Climate Change in Spain

[EN] Adaptive forest management (AFM) is an urgent need because of the uncertainty regarding how changes in the climate will affect the structure, composition and function of forests during the next decades. Current research initiatives for the long-term monitoring of impacts of silviculture are scattered and not integrated into research networks, with the consequent losses of opportunities and capacity for action. To increase the scientific and practical impacts of these experiences, it is necessary to establish logical frameworks that harmonize the information and help us to define the most appropriate treatments. In this context, a number of research groups in Spain have produced research achievements and know-how during the last decades that can allow for the improvement in AFM. These groups address the issue of AFM from different fields, such as ecophysiology, ecohydrology and forest ecology, thus resulting in valuable but dispersed expertise. The main objective of this work is to introduce a comprehensive strategy aimed to study the implementation of AFM in Spain. As a first step, a network of 34 experimental sites managed by 14 different research groups is proposed and justified. As a second step, the most important AFM impacts on Mediterranean pines, as one of the most extended natural and planted forest types in Spain, are presented. Finally, open questions dealing with key aspects when attempting to implement an AFM framework are discussed. This study is expected to contribute to better outlining the procedures and steps needed to implement regional frameworks for AFM.A.J. Molina is beneficiary of an "APOSTD" fellowship (APOSTD/2019/111) funded by the Generalitat Valenciana. M. Moreno-de las Heras is beneficiary of a Serra Hunter fellowship (UB-LE-9055) funded by the Generalitat de Catalunya. F.J. Ruiz-Gomez is supported by a postdoctoral fellowship of the Junta de Andalucia (Sevilla, Spain), and the European Social Fund 2014-2020 Program (DOC_0055). The authors received national and international funding through the following projects: SILVADAPT.NET (RED2018-102719-T), ESPECTRAMED (CGL2017-86161-R), Life-FOREST CO2 (LIFE14 CCM/ES/001271), ALTERACLIM (CGL2015-69773-C2-1-P), INERTIA (PID2019-111332RB-C22-BDV), CEHYRFO-MED (CGL2017-86839-C3-2-R), DEHESACLIM (IB16185), RESILIENTFORESTS (LIFE17 CCA/ES/000063), Rhysotto (PID2019-106583RB-I00), AGL2017-83828C2-2-R, RTI2018-096884-B-C31, ESPAS (CGL2015-65569-R), and caRRRascal (RTI2018-095037-B-I00).Molina Herrera, A.; Navarro Cerrillo, R.; Pérez-Romero, J.; Alejano, R.; Bellot, JF.; Blanco, JA.; Camarero, JJ.... (2021). SilvAdapt.Net: A Site-Based Network of Adaptive Forest Management Related to Climate Change in Spain. Forests. 12(12):1-27. https://doi.org/10.3390/f12121807127121

Paclitaxel Plus Cetuximab as Induction Chemotherapy for Patients With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma Unfit for Cisplatin-Based Chemotherapy

ObjectivesInduction chemotherapy (ICT) followed by definitive treatment is an accepted non-surgical approach for locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, ICT remains a challenge for cisplatin-unfit patients. We evaluated paclitaxel and cetuximab (P-C) as ICT in a cohort of LA-HNSCC patients unfit for cisplatin. Materials and MethodsThis is a retrospective analysis of patients with newly diagnosed LA-HNSCC considered unfit for cisplatin-based chemotherapy (age >70 and/or ECOG >= 2 and/or comorbidities) treated with weekly P-C followed by definitive radiotherapy and cetuximab (RT-C) between 2010 and 2017. Toxicity and objective response rate (ORR) to ICT and RT-C were collected. Median overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox regression analysis was performed to determine baseline predictors of OS and PFS. ResultsA total of 57 patients were included. Grade 3-4 toxicity rate to ICT was 54.4%, and there was a death deemed treatment-related (G5). P-C achieved an ORR of 66.7%, including 12.3% of complete responses (CR). After P-C, 45 patients (78.9%) continued with concomitant RT-C. Twenty-six patients (45.6%) achieved a CR after definitive treatment. With a median follow-up of 21.7 months (range 1.2-94.6), median OS and PFS were 22.9 months and 10.7 months, respectively. The estimated 2-year OS and PFS rates were 48.9% and 33.7%, respectively. Disease stage had a negative impact on OS (stage IVb vs. III-IVa: HR = 2.55 [1.08-6.04], p = 0.03), with a trend towards worse PFS (HR = 1.92 [0.91-4.05], p = 0.09). Primary tumor in the larynx was associated with improved PFS but not OS (HR = 0.45 [0.22-0.92], p = 0.03, and HR = 0.69 [0.32-1.54], p = 0.37, respectively). ConclusionP-C was a well-tolerated and active ICT regimen in this cohort of LA-HNSCC patients unfit for cisplatin-based chemotherapy. P-C might represent a valid ICT option for unfit patients and may aid patient selection for definitive treatment

Familial component of early-onset colorectal cancer: opportunity for prevention

[Background]: Individuals with a non-syndromic family history of colorectal cancer are known to have an increased risk. There is an opportunity to prevent early-onset colorectal cancer (age less than 50 years) (EOCRC) in this population. The aim was to explore the proportion of EOCRC that is preventable due to family history of colorectal cancer. [Methods]: This was a retrospective multicentre European study of patients with non-hereditary EOCRC. The impact of the European Society of Gastrointestinal Endoscopy (ESGE), U.S. Multi-Society Task Force (USMSTF), and National Comprehensive Cancer Network (NCCN) guidelines on prevention and early diagnosis was compared. Colorectal cancer was defined as potentially preventable if surveillance colonoscopy would have been performed at least 5 years before the age of diagnosis of colorectal cancer, and diagnosed early if colonoscopy was undertaken between 1 and 4 years before the diagnosis. [Results]: Some 903 patients with EOCRC were included. Criteria for familial colorectal cancer risk in ESGE, USMSTF, and NCCN guidelines were met in 6.3, 9.4, and 30.4 per cent of patients respectively. Based on ESGE, USMSTF, and NCCN guidelines, colorectal cancer could potentially have been prevented in 41, 55, and 30.3 per cent of patients, and diagnosed earlier in 11, 14, and 21.1 per cent respectively. In ESGE guidelines, if surveillance had started 10 years before the youngest relative, there would be a significant increase in prevention (41 versus 55 per cent; P = 0.010). [Conclusion]: ESGE, USMSTF, and NCCN criteria for familial colorectal cancer were met in 6.3, 9.4, and 30.4 per cent of patients with EOCRC respectively. In these patients, early detection and/or prevention could be achieved in 52, 70, and 51.4 per cent respectively. Early and accurate identification of familial colorectal cancer risk and increase in the uptake of early colonoscopy are key to decreasing familial EOCRC.This study was funded by Instituto de Salud Carlos III through project PI20/0974 to J.P and PI19/01867 to F.B. (co-funded by European Regional Development Fund ‘A way to make Europe’); and Agència de Gestió d’Ajuts Universitaris i de Recerca (Generalitat de Catalunya, GRC 2017SGR653). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas is funded by the Instituto de Salud Carlos III

Effectiveness of telephone monitoring in primary care to detect pneumonia and associated risk factors in patients with SARS-CoV-2

Improved technology facilitates the acceptance of telemedicine. The aim was to analyze the effectiveness of telephone follow-up to detect severe SARS-CoV-2 cases that progressed to pneumonia. A prospective cohort study with 2-week telephone follow-up was carried out March 1 to May 4, 2020, in a primary healthcare center in Barcelona. Individuals aged =15 years with symptoms of SARS-CoV-2 were included. Outpatients with non-severe disease were called on days 2, 4, 7, 10 and 14 after diagnosis; patients with risk factors for pneumonia received daily calls through day 5 and then the regularly scheduled calls. Patients hospitalized due to pneumonia received calls on days 1, 3, 7 and 14 post-discharge. Of the 453 included patients, 435 (96%) were first attended to at a primary healthcare center. The 14-day follow-up was completed in 430 patients (99%), with 1798 calls performed. Of the 99 cases of pneumonia detected (incidence rate 20.8%), one-third appeared 7 to 10 days after onset of SARS-CoV-2 symptoms. Ten deaths due to pneumonia were recorded. Telephone follow-up by a primary healthcare center was effective to detect SARS-CoV-2 pneumonias and to monitor related complications. Thus, telephone appointments between a patient and their health care practitioner benefit both health outcomes and convenience. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

The presence of both HLA-DRB1[*]04:01 and HLA-B[*]15:01 increases the susceptibility to cranial and extracranial giant cell arteritis.

Objectives: To determine if patients with the predominant extracranial large-vessel-vasculitis (LVV) pattern of giant cell arteritis (GCA) have a distinctive HLA-B association, different from that reported in biopsy-proven cranial GCA patients. In a further step we assessed if the combination of HLA-B and HLA-DRB1 alleles confers an increased risk for GCA susceptibility, either for the cranial and extracranial LVV phenotypes. Methods: A total of 184 patients with biopsy-proven cranial GCA, 105 with LVV-GCA and 486 healthy controls were included in our study. We compared HLA-B phenotype frequencies between the three groups. Results: HLA-B*15 phenotype was significantly increased in patients with classic cranial GCA compared to controls (14.7% versus 5.8%, respectively; p<0.01; OR [95% CI] =2.81 [1.54-5.11]). It was mainly due to the HLA-B*15:01 allele (12.5% versus 4.0%, respectively; p<0.01; OR [95% CI] =3.51 [1.77-6.99]) and remained statistically significant after Bonferroni correction. Similar HLA-B*15 association was observed in patients with the LVV-GCA (11.4% versus 5.8%, p=0.04, OR [95% CI] =2.11 [1.04-4.30]). This association was also mainly due to the HLA-B*15:01 allele (10.5% versus 4.0%, respectively; p=0.0054; OR [95% CI] =2.88 [1.19-6.59]). Noteworthy, the presence of HLA-B*15:01 together with HLA-DRB1*04:01 led to an increased risk of developing both cranial and extracranial LVV-GCA. Conclusions: Susceptibility to GCA is strongly related to the HLA region, regardless of the clinical phenotype of expression of the disease.This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from ‘‘Instituto de Salud Carlos III’’ (ISCIII) (Spain). However, this research did not receive any specific grant from funding agencies in the commercial or not-for-profit sectors