Studies into the synthesis of primary phosphines for the preparation of macrocycles by template methods

This thesis is focused in the synthesis of phosphine-based macrocycles by template methods. Furthermore, it explores some alternative methods for the synthesis of known and unknown polydentate primary phosphine compounds necessary for the preparation of new macrocycles. Following this new procedure the novel tripodal primary phosphine cis, cis-1,3,5-triphosphinomethylcyclohexane (2.15) has been prepared in good yields as well as the reported bis(2-phosphinoethyl)amine (PNP, 3.4). Mono-alkylation of 3.4 allowed the preparation of the asymmetric 2-(allylphosphino)-N-(2-phosphinoethyl)ethanamine ligand (3.16) in low yields. Whilst ligands 2.15 and 3.16 failed to form well-defined facially coordinated molybdenum(O) and chromium(O) complexes respectively, 3.4 formed octahedral complexes with Cr(0) and Fe(II) metals, {/ac-Cr(CO)3(PNP)}, 3.8 and {n5-C5H4(SiMe3)}Fe(PNP) PF6, 3.10. Different attempts have been made to cyclise the facially coordinated chromium complex 3.8, however all of them have failed. The synthesis of 3.8 and 3.10 has been confirmed by X-ray diffraction. The synthesis of a new Mn(I) 9-membered tribenzanulated I1 triphosphamacrocycle complex Mn(CO)3{(C6H4F)PC 6H4PHC6H4PHC6H4} OTf, 4.10 has been successfully synthesised by sequential introduction of 1,2-diphosphinobenzene and tris(2-fluorophenyl)phosphine on a manganese(I) complex and subsequent addition of /-BuOK. Alkylation of the two secondary phosphorus of 4.10 with Mel allowed the isolation of the more stable manganese complex II Mn(CO)3{(C6H4F)PC6H 4P(CH3)C6H4P(CH3)C 6H4} OTf/I 4.12. The liberation of the phosphine trioxide macrocycle, {(C6H4F)J>(0)C6H4P(0)(CH 3)C6H4(0)(CH3)C6H4 } 4.14 from the metal has been achieved using 4-methylmorpholine N-oxide in excess. In addition, the X-ray crystal structures of the non-cyclised precursor intermediate Mn(CO)3{(C6H4F)3P}{C 6H4(PH2)2-o} OTf 4.9 and the half cyclised intermediate (I Mn(CO)3{(C6H4F)2PC 6H4PHC6H4PH2} OTf 4.11 as well as the final macrocycle 4.12 have also been established.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Studies into the synthesis of primary phosphines for the preparation of macrocycles by template methods.

This thesis is focused in the synthesis of phosphine-based macrocycles by template methods. Furthermore, it explores some alternative methods for the synthesis of known and unknown polydentate primary phosphine compounds necessary for the preparation of new macrocycles. Following this new procedure the novel tripodal primary phosphine cis, cis-1,3,5-triphosphinomethylcyclohexane (2.15) has been prepared in good yields as well as the reported bis(2-phosphinoethyl)amine (PNP, 3.4). Mono-alkylation of 3.4 allowed the preparation of the asymmetric 2-(allylphosphino)-N-(2-phosphinoethyl)ethanamine ligand (3.16) in low yields. Whilst ligands 2.15 and 3.16 failed to form well-defined facially coordinated molybdenum(0) and chromium(0) complexes respectively, 3.4 formed octahedral complexes with Cr(0) and Fe(II) metals, [{fac-Cr(CO)3(PNP)}, 3.8] and [[{n5-C5H4(SiMe3)}Fe(PNP)]PF6, 3.10]. Different attempts have been made to cyclise the facially coordinated chromium complex 3.8, however all of them have failed. The synthesis of 3.8 and 3.10 has been confirmed by X-ray diffraction. The synthesis of a new Mn(I) 9-membered tribenzanulated triphosphamacrocycle complex [Mn(CO)3{(C6H4F)PC6H4PHC6H4PHC6H4}]OTf, 4.10 has been successfully synthesised by sequential introduction of 1,2-diphosphinobenzene and tris(2-fluorophenyl)phosphine on a manganese(I) complex and subsequent addition of t-BuOK. Alkylation of the two secondary phosphorus of 4.10 with Mel allowed the isolation of the more stable manganese complex [Mn(CO)3{(C6H4F)PC6H4P(CH3)6H4P(CH3)C6H4}]OTf/I 4.12. The liberation of the phosphine trioxide macrocycle, {(C6H4F)P(0)C6H4P(0)(CH3)C6H4(0)(CH3)C6H4} 4.14 from the metal has been achieved using 4-methylmorpholine N-oxide in excess. In addition, the X-ray crystal structures of the non-cyclised precursor intermediate [Mn(CO)3{(C6H4F)3P}{C6H4(PH2)2-o}] OTf 4.9 and the half cyclised intermediate [Mn(CO)3{(C6H4F)2PC 6H4PHC6H4PH2}] OTf 4.11 as well as the final macrocycle 4.12 have also been established

Enquesta sobre necessitats de tecnologies sanitàries per a l’abordatge de la COVID-19

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Tecnologies sanitàries; Avaluació; Detecció de necessitatsCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Tecnologías sanitarias; Evaluación; Detección de necesidadesCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Health technologies; Assessment; Needs detectionAmb la finalitat de poder identificar i prioritzar la valoració d’aquelles iniciatives innovadores en el marc del Grup de treball interinstitucional en innovació tecnològica per a la crisi de la COVID-19, es va plantejar conèixer les necessitats del sistema públic de salut quant a tecnologies sanitàries (no farmacològiques) per a la COVID-19. En aquest sentit, es volien conèixer les necessitats pel que fa a la provisió dels centres, les necessitats no cobertes (sense cap solució existent en el mercat), així com les necessitats d’avaluació de tecnologies ja existents des de l’inici de la pandèmia.Con la finalidad de poder identificar y priorizar la valoración de aquellas iniciativas innovadoras en el marco del Grupo de trabajo interinstitucional en innovación tecnológica para la crisis de la COVID-19, se planteó conocer las necesidades del sistema público de salud en cuanto a tecnologías sanitarias (no farmacológicas) para la COVID-19. En este sentido, se querían conocer las necesidades en cuanto a la provisión de los centros, las necesidades no cubiertas (sin ninguna solución existente en el mercado), así como las necesidades de evaluación de tecnologías ya existentes desde el inicio de la pandemia.In order to identify and prioritise the assessment of innovative initiatives within the framework of the Inter-institutional Working Group on Technological Innovation for the COVID-19 crisis, the aim was to ascertain the needs of the public health system in terms of health technologies (non-pharmacological) for COVID-19. In this regard, we wanted to identify the supply needs of the centres, the unmet needs (with no existing solution on the market), as well as the needs for assessment of technologies already in existence since the start of the pandemic

A Method to Compare the Delivery of Psychiatric Care for People with Treatment-Resistant Schizophrenia

Esquizofrènia resistent al tractament; Tecnologies de la informació i la comunicació (TIC); Serveis de salut mentalEsquizofrenia resistente al tratamiento; Tecnologías de la información y la comunicación (TIC); Servicios de salud mentalTreatment-resistant schizophrenia; Information and communication technologies (ICT); Mental health servicesIntroduction: Community services are gaining ground when it comes to attention to patients with psychiatric diseases. Regarding patients with treatment-resistant schizophrenia (TRS), the use of information and communication technology (ICT) could help to shift the focus from hospital-centered attention to community services. This study compares the differences in mental health services provided for patients with TRS in Budapest (Hungary), Tel-Aviv (Israel) and Catalonia (Spain) by means of a method for the quick appraisal of gaps among the three places, for a potential implementation of the same ICT tool in these regions. Methods: An adapted version of the Description and Standardised Evaluation of Services and Directories in Europe for Long Term Care (DESDE-LTC) instrument was made by researchers in Semmelweis University (Budapest, Hungary), Gertner Institute (Tel-Aviv, Israel) and Hospital de la Santa Creu I Sant Pau and Parc Sanitari Sant Joan de Déu (Catalonia, Spain). Results: Two types of outpatient care services were available in the three regions. Only one type of day-care facility was common in the whole study area. Two residential care services, one for acute and the other for non-acute patients were available in every region. Finally, two self-care and volunteer-care facilities were available in the three places. Conclusion: Although the availability of services was different in each region, most of the services provided were sufficiently similar to allow the implementation of the same ICT solution in the three places.This work has been supported by the Horizon 2020 Framework Programme of the European Union (grant number 643552). This research was also funded by ONA CORPORATION

Innovació tecnològica sanitària per la crisi de la COVID-19

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Innovació tecnològica; AvaluacióCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Innovación tecnológica; EvaluaciónCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Technological innovation; EvaluationLa crisi de salut pública per la COVID-19 durant la primera onada va posar el sistema sanitari sota el risc de desproveïment d'equips per tractar malalts crítics així com d'altres dispositius i materials necessaris per a la protecció del personal assistencial. Davant d’aquesta situació van sorgir múltiples iniciatives innovadores per donar resposta a les necessitats sobrevingudes. Per tal de donar resposta d’una forma ràpida i coordinada a les necessitats d’incorporació de tecnologies amb garanties, s’ha promogut a Catalunya, juntament amb la Fundació TIC Salut Social la creació d'un Grup de treball transversal inter-institucional que ha treballat de forma col·laborativa amb membres de l'àmbit de la innovació, l’avaluació, la regulació, la planificació operativa i la provisió assistencial. La finalitat d'aquest Grup de treball ha estat establir un procés d'actuació coordinat i sinèrgic per a l’anàlisi de les necessitats, la detecció de la innovació, la valoració i priorització de les iniciatives, el seu acompanyament en el desenvolupament i regulació i, finalment, si escau, l’avaluació de la seva aplicació per a la presa de decisions. S’ha obtingut informació de les iniciatives fonamentalment a través de formularis de recollida de dades, que han facilitat la seva caracterització. En aquest informe es recullen les iniciatives tractades fins a 31 de juliol de 2020 classificades segons la seva tipologia

m-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study

Mental disorder; Schizophrenia; Treatment-resistantTrastorno mental; Esquizofrenia; Resistentencia al tratamientoMalaltia mental; Esquizofrènia; Resistència al tractamentBackground: In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. Objective: The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. Methods: A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. Results: This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients' acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients' satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. Conclusions: The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS.This work has been supported by the Horizon 2020 Framework Programme of the European Union (grant 643552) and partly funded by CERCA (Centres de Recerca de Catalunya) Programme/Generalitat de Catalunya

Speech-based support system to supervise chronic obstructive pulmonary disease patient status

Chronic obstructive pulmonary disease; Prosody; Speech analysisMalaltia pulmonar obstructiva crònica; Prosòdia; Anàlisi de la parlaEnfermedad pulmonar obstructiva crónica; Prosodia; Análisi del hablaPatients with chronic obstructive pulmonary disease (COPD) suffer from voice changes with respect to the healthy population. However, two issues remain to be studied: how long-term speech elements such as prosody are affected; and whether physical effort and medication also affect the speech of patients with COPD, and if so, how an automatic speech-based detection system of COPD measurements can be influenced by these changes. The aim of the current study is to address both issues. To this end, long read speech from COPD and control groups was recorded, and the following experiments were performed: (a) a statistical analysis over the study and control groups to analyse the effects of physical effort and medication on speech; and (b) an automatic classification experiment to analyse how different recording conditions can affect the performance of a COPD detection system. The results obtained show that speech—especially prosodic features—is affected by physical effort and inhaled medication in both groups, though in opposite ways; and that the recording condition has a relevant role when designing an automatic COPD detection system. The current work takes a step forward in the understanding of speech in patients with COPD, and in turn, in the research on its automatic detection to help professionals supervising patient status.This research has been funded by GlaxoSmithKline, S.A. The first author has been funded by the Agencia Estatal de Investigación (AEI), Ministerio de Ciencia, Innovación y Universidades and the Fondo Social Europeo (FSE) under grant RYC-2015-17239 (AEI/FSE, UE)

Measuring the Digital Skills of Catalan Health Care Professionals as a Key Step Toward a Strategic Training Plan: Digital Competence Test Validation Study

Salut digital; eSalut; Competències digitals; Tecnologia de la informació i la comunicació; CapacitacióSalud digital; eSalud; Competencias digitales; Tecnología de la información y la comunicación; CapacitaciónDigital health; eHealth; Digital competences; Information and communication technology; TrainingBackground: despite Catalonia being an advanced region in terms of digital health adoption, the “Forum for Professional Dialogue” identified the need to improve information and communication technology (ICT) competences as one of the present and future challenges for health care professionals (HPs). Objective: we aimed to validate the digital competence test developed ad hoc for this study and to measure the digital competence level of Catalan HPs to establish their current level as the baseline for designing a strategic training plan. Methods: an exploratory observational study was conducted based on a voluntary survey where sociodemographic, professional and digital tool knowledge, digital tool use, and training needs data were collected and based on the score obtained from a digital competence test developed ad hoc. The digital competence test consisted of 2 “real-life scenarios” with 7 and 11 questions. Results: in total, 803 HPs, of whom 612 (76.2%) were women, completed the survey between June 28 and July 16, 2021. Most participants self-rated their digital competence level as either intermediate (384/803, 47.8%) or basic (357/803, 44.5%). The mean score in the digital competence test was 22.6 (SD 4.3). Therefore, most participants displayed a basic level of digital competence. The internal consistency of the digital competence test was 0.66, and the discrimination index of all questions was ≥0.2 for all items except for 1 question. Conclusions: this exploratory study highlights the need to improve the digital competence of HPs working in Catalonia, with special effort being made to provide training according to the specific needs of the different HP profiles. The results have informed the Health Plan for Catalonia 2021-2025 and lay the foundations for the development and deployment of a framework program for the digital competences of HPs. The developed digital competence test shows acceptable consistency for the objective pursued, although improvements are needed to fine-tune its accuracy

Healthcare System Digital Transformation across Four European Countries: A Multiple-Case Study

Multiple-case study; Digital transformation; Digital healthEstudio de casos múltiples; Transformación digital; Salud digitalEstudi de casos múltiples; Transformació digital; Salut digitalDigitization has become involved in every aspect of life, including the healthcare sector with its healthcare professionals (HCPs), citizens (patients and their families), and services. This complex process is supported by policies: however, to date, no policy analysis on healthcare digitalization has been conducted in European countries to identify the main goals of digital transformation and its practical implementation. This research aimed to describe and compare the digital health policies across four European countries; namely, their priorities, their implementation in practice, and the digital competencies expected by HCPs. A multiple-case study was performed. Participants were the members of the Digital EducationaL programme invoLVing hEalth profEssionals (DELIVER), a project funded by the European Union under the Erasmus+ programme, involving three countries (Denmark, Italy, and Slovenia) and one autonomous region (Catalonia—Spain). Data were collected using two approaches: (a) a written interview with open-ended questions involving the members of the DELIVER project as key informants; and (b) a policy-document analysis. Interviews were analysed using the textual narrative synthesis and the word cloud policy analysis was conducted according to the Ready, Extract, Analyse and Distil approach. Results showed that all countries had established recent policies at the national level to address the development of digital health and specific governmental bodies were addressing the implementation of the digital transformation with specific ramifications at the regional and local levels. The words “health” and “care” characterized the policy documents of Denmark and Italy (309 and 56 times, 114 and 24 times, respectively), while “development” and “digital” (497 and 478 times, respectively) were common in the Slovenia document. The most used words in the Catalonia policy document were “data” and “system” (570 and 523 times, respectively). The HCP competencies expected are not clearly delineated among countries, and there is no formal plan for their development at the undergraduate, postgraduate, and continuing educational levels. Mutual understanding and exchange of good practices between countries may facilitate the digitalization processes; moreover, concrete actions in the context of HCP migration across Europe for employment purposes, as well as in the context of citizens’ migration for healthcare-seeking purposes are needed to consider the differences emerged across the countries