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1.
J Public Health Manag Pract ; 28(Suppl 1): S101-S110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34797267

RESUMO

CONTEXT: The New York City (NYC) Test & Trace Corps (Test & Trace), under New York City Health + Hospitals (NYC H+H), set out to provide universal access to COVID-19 testing. Test & Trace partnered with numerous organizations to direct mobile COVID-19 testing from concept through implementation to reduce COVID-19-related health inequities. PROGRAM: Test & Trace employs a community-informed mobile COVID-19 testing model to deliver testing to the hardest-hit, underserved communities. Community partners, uniquely knowledgeable of the residents they serve, are engaged as decision makers and operational partners in mobile COVID-19 testing delivery. IMPLEMENTATION: Through several mobile testing methods, community partners choose testing locations and tailor outreach to their community. Test & Trace assumes logistical responsibility for mobile testing but defers critical programmatic decisions and community engagement to partners. Integral to the success of this program is responsive, bidirectional communication. EVALUATION: During the reporting period of December 1, 2020, to April 30, 2021, Test & Trace's community-informed mobile COVID-19 testing model provided testing to 150351 unique patients and processed 274083 tests in total. The available outcomes data and qualitative feedback provided by community partners illustrate that this intervention, combined with robust governmental investment, successfully ensured that NYC-identified, low-resource neighborhoods had greater access to COVID-19 testing. DISCUSSION: Making community partners decision makers reduced inequities in access to testing for communities of color. In addition, the model has served as the framework for Test & Trace's community-informed mobile COVID-19 vaccination program, operated in concert with NYC's Vaccine Command Center, and is a foundation for addressing health inequities at scale, including during public health crises.


Assuntos
COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Humanos , Características de Residência , SARS-CoV-2
2.
J Phys Chem A ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793148

RESUMO

Ultrafast hole transfer from solvent radical cations produced by radiolysis with ∼10 ps, 9 MeV electron pulses to solutes in tetrahydrofuran (THF) was investigated. Because of rapid fragmentation of initially produced THF+•, solute radical cations are not expected and have not previously been reported. When 9,9-dihexyl-2,7-dibromofluorene (Br2F) at 5 to 1000 mM was used, Br2F+• with radiation chemical yields up to G = 2.23/100 eV absorbed was observed. While more than half of this was the result of direct solute ionization, the results highlight the importance of capturing holes from THF+• prior to solvation and fragmentation. The observed data show a time-resolution limited (15 ps) rise in transient absorption of Br2F+•, identical in form to reports of presolvated or dry electron capture in water and a few organic liquids, including THF. The results were thus interpreted with a similar formalism, finding C37 = 1.7 M, the concentration at which 37% of holes escape capture. The yield of solvent hole capture can be accounted for by the formation of solvent holes adjacent to solute molecules reacting faster than they can fragment; however, mechanisms such as delocalized holes or rapid hopping may play a role. Low temperature results find over two times more capture, supporting the speculation that if THF+• was longer lived, the yield of capture in under 15 ps would have been at least 2 times larger at 1 M Br2F, possibly capturing nearly all available holes from the solvent.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34808255

RESUMO

PURPOSE: To determine if prophylactic gabapentin usage in patients undergoing definitive concurrent chemoradiotherapy (chemoRT) for oropharyngeal cancer (OPC) improves treatment-related oral mucositis pain, opioid use, and feeding tube (FT) placement. METHODS AND MATERIALS: This double-blind, randomized phase III study for patients with locally advanced OPC undergoing chemoRT randomly allocated patients to prophylactic gabapentin (600 mg thrice daily) or placebo. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores over the entire treatment period (baseline to 6 weeks post-RT follow-up) with higher scores indicating worse outcomes. Opioid requirements, FT placement, and other patient-reported QOL metrics (Functional Assessment of Cancer Therapy-Head and Neck [FACT-HN] and Patient-Reported Outcomes of Common Terminology Criteria for Adverse Events [PRO-CTCAE]) were assessed. Lower scores suggested poorer quality of life (QOL) with the FACT-HN questionnaire, and higher scores suggested worse outcomes with the PRO-CTCAE questionnaire. Questionnaires were administered at baseline, weekly during RT, and at 6-week post-RT follow-up. Repeated measures analysis of variance were used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon-rank sum tests were used to compare averages for the other secondary endpoints. A p-value less than .05 was considered statistically significant. RESULTS: Treatment arms were well-balanced overall, including T and N staging and dosimetric variables. There were 58 patients analyzed. No significant difference was found in PROMS scores (mean 29.1, Standard Deviation [SD] 22.5, vs 20.1, SD 16.8, for gabapentin vs placebo, respectively, p = .11). The FACT-HN functional well-being index had a significant decrease in scores from baseline to follow-up in the gabapentin arm (median -6, interquartile range [IQR] -10.0 to -0.5, vs -1, IQR -5.5 to 3.0, p = .03). PRO-CTCAE scores increased significantly at follow-up for gabapentin (median 6.5, IQR 3.5 to 11.8, vs 1, IQR -2.0 to 6.0, p = .01). There was no significant difference in average or change in opioid use. FT placement was significantly higher in the gabapentin arm (62.1% vs 20.7%, p < .01). CONCLUSIONS: This study suggests that prophylactic gabapentin is not effective in improving treatment-related oral mucositis symptoms in a select population of patients with OPC undergoing definitive chemoRT.

4.
Phys Chem Chem Phys ; 23(43): 24589-24597, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34710211

RESUMO

Specialized extractant ligands - such as tri-butyl phosphate (TBP), N,N-di-(2-ethylhexyl)butyramide (DEHBA), and N,N-di-2-ethylhexylisobutryamide (DEHiBA) - have been developed for the recovery of uranium from used nuclear fuel by reprocessing solvent extraction technologies. These ligands must function in the presence of an intense multi-component radiation field, and thus it is critical that their radiolytic behaviour be thoroughly evaluated. This is especially true for their metal complexes, where there is negligible information on the influence of complexation on radiolytic reactivity, despite the prevalence of metal complexes in used nuclear fuel reprocessing solvent systems. Here we present a kinetic investigation into the effect of uranyl (UO22+) complexation on the reaction kinetics of the dodecane radical cation (RH˙+) with TBP, DEHBA, and DEHiBA. Complexation had negligible effect on the reaction of RH˙+ with TBP, for which a second-order rate coefficient (k) of (1.3 ± 0.1) × 1010 M-1 s-1 was measured. For DEHBA and DEHiBA, UO22+ complexation afforded an increase in their respective rate coefficients: k(RH˙+ + [UO2(NO3)2(DEHBA)2]) = (2.5 ± 0.1) × 1010 M-1 s-1 and k(RH˙+ + [UO2(NO3)2(DEHiBA)2]) = (1.6 ± 0.1) × 1010 M-1 s-1. This enhancement with complexation is indicative of an alternative RH˙+ reaction pathway, which is more readily accessible for [UO2(NO3)2(DEHBA)2] as it exhibited a much larger kinetic enhancement than [UO2(NO3)2(DEHiBA)2], 2.6× vs. 1.4×, respectively. Complementary quantum mechanical calculations suggests that the difference in reaction kinetic enhancement between TBP and DEHBA/DEHiBA is attributed to a combination of reaction pathway (electron/hole transfer vs. proton transfer) energetics and electron density distribution, wherein attendant nitrate counter anions effectively 'shield' TBP from RH˙+ electron transfer processes.

5.
Health Technol Assess ; 25(53): 1-52, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34505829

RESUMO

BACKGROUND: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. OBJECTIVES: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. DESIGN: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. SETTING: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. RESULTS: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. CONCLUSIONS: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. LIMITATIONS: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. FUTURE WORK: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. FUNDING: Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council-National Institute for Health Research Methodology Research programme.


Assuntos
Efeito Placebo , Humanos , Projetos de Pesquisa
6.
Bone Joint J ; 103-B(9): 1464-1471, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34465159

RESUMO

AIMS: Cauda equina syndrome (CES) can be associated with chronic severe lower back pain and long-term autonomic dysfunction. This study assesses the recently defined core outcome set for CES in a cohort of patients using validated questionnaires. METHODS: Between January 2005 and December 2019, 82 patients underwent surgical decompression for acute CES secondary to massive lumbar disc prolapse at our hospital. After review of their records, patients were included if they presented with the clinical and radiological features of CES, then classified as CES incomplete (CESI) or with painless urinary retention (CESR) in accordance with guidelines published by the British Association of Spinal Surgeons. Patients provided written consent and completed a series of questionnaires. RESULTS: In total, 61 of 82 patients returned a completed survey. Their mean age at presentation was 43 years (20 to 77; SD 12.7), and the mean duration of follow-up 58.2 months (11 to 182; SD 45.3). Autonomic dysfunction was frequent: 33% of patients reported bladder dysfunction, and 10% required a urinary catheter. There was a 38% and 53% incidence of bowel and sexual dysfunction, respectively: 47% of patients reported genital numbness. A total of 67% reported significant back pain: 44% required further investigation and 10% further intervention for the management of lower back pain. Quality of life was lower than expected when corrected for age and sex. Half the patients reported moderate or worse depression, and 40% of patients of working age could no longer work due to problems attributable to CES. Urinary and faecal incontinence, catheter use, sexual dysfunction, and genital numbness were significantly more common in patients with CESR. CONCLUSION: This study reports the long-term outcome of patients with CES and is the first to use validated patient-reported outcome measures to assess the CES Core Outcome Set. Persistent severe back pain and on-going autonomic dysfunction were frequently reported at a mean follow-up of five years. Cite this article: Bone Joint J 2021;103-B(9):1464-1471.


Assuntos
Doenças do Sistema Nervoso Autônomo/epidemiologia , Síndrome da Cauda Equina/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Descompressão Cirúrgica , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Tempo para o Tratamento
7.
J Soc Psychol ; 161(6): 753-778, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34392801

RESUMO

In a 2003 study, we examined five antecedents of school shootings - a history of rejection, acute rejection experience, history of psychological problems, fascination with death or violence, and fascination with guns. In three studies, the current project examined the role of these factors in 57 K-12 shootings, 24 college/university shootings, and 77 mass shootings that occurred since the original study. Over half of all shooters had a history of psychological problems. More K-12 shooters than college or mass shooters displayed a history of rejection. However, more mass than school shooters had experienced an acute rejection, such as a workplace firing. The characteristics identified in the original study appeared as common antecedent conditions of not only K-12 shootings but college/university and mass shootings as well. These results identify problems that can be addressed to minimize the occurrence of school and mass shootings.


Assuntos
Armas de Fogo , Ferimentos por Arma de Fogo , Humanos , Instituições Acadêmicas , Universidades , Violência
8.
Pilot Feasibility Stud ; 7(1): 157, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404479

RESUMO

BACKGROUND: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to improved postoperative outcomes. The aim of this study was to develop and pilot a specialist diabetes team-led intervention to improve surgical outcomes in people with diabetes. DESIGN: Open pilot feasibility study SETTING: Diabetes and cardiothoracic surgery departments, University Hospital Southampton NHS Foundation Trust PARTICIPANTS: Seventeen people with diabetes undergoing cardiothoracic surgery INTERVENTION: Following two rapid literature reviews, a prototype intervention was developed based on a previously used nurse-led outpatient intervention and tested. PRIMARY OUTCOME: Feasibility and acceptability of delivering the intervention SECONDARY OUTCOMES: Biomedical data were collected at baseline and prior to surgery. We assessed how the intervention was used. In depth qualitative interviews with participants and healthcare professionals were used to explore perceptions and experiences of the intervention and how it might be improved. RESULTS: Thirteen of the 17 people recruited completed the study and underwent cardiothoracic surgery. All components of the OCTOPuS intervention were used, but not all parts were used for all participants. Minor changes were made to the intervention as a result of feedback from the participants and healthcare professionals. Median (IQR) HbA1c was 10 mmol/mol (3, 13) lower prior to surgery than at baseline. CONCLUSION: This study has shown that it is possible to develop a clinical pathway to improve diabetes management prior to admission. The clinical and cost-effectiveness of this intervention will now be tested in a multicentre randomised controlled trial in cardiothoracic centres across the UK. TRIAL REGISTRATION: ISRCTN; ISRCTN10170306 . Registered 10 May 2018.

9.
World J Pediatr Congenit Heart Surg ; 12(5): E1-E18, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34304616

RESUMO

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

10.
Cardiol Young ; 31(7): 1057-1188, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34323211

RESUMO

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.


Assuntos
Cardiopatias Congênitas , Classificação Internacional de Doenças , Criança , Feminino , Humanos , Sistema de Registros , Sociedades Médicas , Organização Mundial da Saúde
11.
Nat Commun ; 12(1): 4491, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301950

RESUMO

Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)-a complex chaperoning the selection of branch and 3' splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.


Assuntos
DNA/genética , Íntrons/genética , Piranos/metabolismo , Ribonucleoproteína Nuclear Pequena U2/metabolismo , Compostos de Espiro/metabolismo , Spliceossomos/metabolismo , Microscopia Crioeletrônica , Cristalografia por Raios X , DNA/química , DNA/metabolismo , Humanos , Lactonas/química , Lactonas/metabolismo , Modelos Moleculares , Conformação de Ácido Nucleico , Ligação Proteica , Conformação Proteica , Piranos/química , Pironas/química , Pironas/metabolismo , Ribonucleoproteína Nuclear Pequena U2/química , Compostos de Espiro/química , Spliceossomos/ultraestrutura
12.
Dalton Trans ; 50(31): 10853-10859, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34296716

RESUMO

Insight into the effects of radiolytic processes on the actinides is critical for advancing our understanding of their solution chemistry because the behaviour of these elements cannot be easily separated from the influence of their inherent radiation field. However, minimal information exists on the radiation-induced redox behaviour of curium (Cm), a key trivalent transuranic element present in used nuclear fuel and frequently used as an alpha radiation source. Here we present a kinetic study on the aqueous redox reactions of Cm(iii) with radicals generated through the radiolysis of aqueous media. In particular, we probe reaction kinetics in nitric acid solutions that are used as the aqueous phase component of used nuclear fuel reprocessing solvent systems. Second-order rate coefficients (k) were measured for the reaction of Cm(iii) with the hydrated electron (eaq-, k = (1.25 ± 0.03) × 1010 M-1 s-1), hydrogen atom (H˙, k = (5.16 ± 0.37) × 108 M-1 s-1), hydroxyl radical (˙OH, k = (1.69 ± 0.24) × 109 M-1 s-1), and nitrate radical (NO3˙, k = (4.83 ± 0.09) × 107 M-1 s-1). Furthermore, the first-ever Cm(ii) absorption spectrum (300-700 nm) is also reported. These kinetic data dispel the status quo notion of Cm(iii) possessing little to no redox chemistry in aqueous solution, and suggest that the resulting Cm(ii) and Cm(iv) transients could exist in irradiated aqueous solutions and be available to undergo subsequent redox chemistry with other solutes.

13.
BMJ Open ; 11(6): e050919, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108175

RESUMO

INTRODUCTION: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to better postoperative outcomes. We previously demonstrated the feasibility of delivering the Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) intervention, an outpatient intervention delivered by diabetes healthcare professionals for people with suboptimally managed diabetes over 8-12 weeks before elective cardiac surgery. The present study will assess the clinical and cost-effectiveness of the intervention in cardiothoracic centres across the UK. METHODS AND ANALYSIS: A multicentre, parallel group, single-blinded 1:1 individually randomised trial comparing time from surgery until clinically fit for discharge in adults with suboptimally managed type 1 diabetes or type 2 diabetes undergoing elective surgery between the OCTOPuS intervention and usual care (primary endpoint). Secondary endpoints will include actual time from surgery to discharge from hospital; days alive and either out of hospital or judged as clinically fit for discharge; mortality; time on intensive therapy unit (ITU)/ventilator; infections; acute myocardial infarction; change in weight; effect on postoperative renal function and incidence of acute kidney injury; change in HbA1c; frequency and severity of self-reported hypoglycaemia; operations permanently cancelled for suboptimal glycaemic levels; cost-effectiveness; psychosocial questionnaires. The target sample size will be 426 recruited across approximately 15 sites. The primary analysis will be conducted on an intention-to-treat population. A two-sided p value of 0.05 or less will be used to declare statistical significance for all analyses and results will be presented with 95% CIs. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Hampshire A Research Ethics Committee (20/SC/0271). Results will be disseminated through conferences, scientific journals, newsletters, magazines and social media. TRIAL REGISTRATION NUMBER: ISRCTN10170306.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Octopodiformes , Adulto , Animais , Humanos , Estudos Multicêntricos como Assunto , Pacientes Ambulatoriais , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Inorg Chem ; 60(10): 7372-7380, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33904730

RESUMO

A series of (cyclopentadienyl)cobalt(III) half-sandwich complexes (1-4) supported by bidentate bis(phosphino)amine ligands was synthesized and characterized by NMR spectroscopy, X-ray crystallography, and cyclic voltammetry. The CoIII-hydride complex 4-H bearing the bis(cyclohexylphosphine) ligand derivative was successfully isolated via protonation of the neutral reduced CoI complex 5 with a weak acid. Experimental and computational methods were used to determine the thermodynamic hydride accepting ability of these CoIII centers and to evaluate their reactivity toward the oxidation of formate. We find that the hydride accepting ability of 1-4 ranges from 71 to 74 kcal/mol in acetonitrile, which should favor a highly exergonic reaction with formate through direct hydride transfer. Formate oxidation was demonstrated at elevated temperatures in the presence of stoichiometric quantities of 4, generating carbon dioxide and the CoIII-hydride complex 4-H in 72% yield.

15.
Opt Express ; 29(2): 2049-2064, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33726406

RESUMO

X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a compact system (total length <1 m). The detection of very small refractive angles (∼50 nrad) at an interferometer design energy of 19 keV was enabled by combining small period X-ray gratings (1.0, 1.5 and 3.0 µm) and a single-photon counting X-ray detector (75 µm pixel size). The performance of the X-ray interferometer was fully characterized in terms of angular sensitivity and spatial resolution. Finally, the potential of laboratory X-ray phase contrast for biomedical imaging is demonstrated by obtaining high resolution X-ray phase tomographies of a mouse embryo embedded in solid paraffin and a formalin-fixed full-thickness sample of human left ventricle in water with a spatial resolution of 21.5 µm.


Assuntos
Embrião de Mamíferos/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Interferometria/instrumentação , Microscopia de Contraste de Fase/instrumentação , Tomografia Computadorizada por Raios X/métodos , Animais , Desenho de Equipamento , Humanos , Processamento de Imagem Assistida por Computador/métodos , Camundongos , Inclusão em Parafina
16.
Cureus ; 13(2): e13505, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33786214

RESUMO

Objective To determine the impact of different adjuvant strategies on outcomes in women with early-stage uterine serous carcinoma (USC). Methods Our retrospective database for women with endometrial carcinoma was queried for women with 2009 International Federation of Gynecology and Obstetrics (FIGO) stages I-II USC who underwent surgical staging between January 1991 and April 2019 followed by adjuvant management (observation, radiation therapy (RT), chemotherapy (CT), or combined modality treatment (CRT)). Chi-square tests were performed to compare differences in outcome by type of adjuvant management. Recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were assessed by Kaplan-Meier and log-rank tests. Univariate and multivariate analyses (MVA) were performed to identify statistically significant predictors of survival endpoints. Results We identified 171 women who met our inclusion criteria. The median follow-up time was 70.5 months. Seventy-five percent of the study cohort was FIGO stage IA, 13% were stage IB, and 12% were stage II. All women underwent pelvic lymph node dissection with a median number of dissected lymph nodes of 14. Omentectomy was performed in 64% of patients. Adjuvant RT was utilized in 56% of women (65 patients received vaginal brachytherapy alone, 10 patients received pelvic RT, and 21 patients received a combination of both). The most commonly used chemotherapy regimen was carboplatin and paclitaxel with a median number of cycles of six. A total of 44% of the cohort received CRT, 12% received RT alone, 19% received chemo alone, and 25% were observed. Five-year RFS was 73% for those who received CRT, 84% for those who received RT alone, 68% for those who received CT alone, and 55% for those who were observed (p=0.13). Five-year DSS was 81%, 94%, 71%, and 60%, respectively (p=0.02). Five-year OS was 76%, 70%, 60%, and 56%, respectively (p=0.11). On MVA of OS and DSS, a higher percentage of myometrial invasion, the presence of lower uterine segment involvement, positive peritoneal cytology, and receipt of chemotherapy alone/observation were independent predictors of worse outcomes. The sole independent predictor of worse RFS on MVA was the presence of positive peritoneal cytology. Conclusion In this cohort of women with early-stage USC who underwent surgical staging, adjuvant radiation treatment with or without chemotherapy was associated with improved survival endpoints and trended toward improved recurrence rates.

17.
BMJ Open ; 11(3): e043323, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664076

RESUMO

OBJECTIVE: To review comparisons of the effectiveness of endovascular stent grafting (ESG) against open surgical repair (OSR) for treatment of chronic arch or descending thoracic aortic aneurysms (TAA). DESIGN: Systematic review and meta-analysis DATA SOURCES: MEDLINE, EMBASE, CENTRAL, WHO International Clinical Trials Routine data collection, current controlled trials, clinical trials and the NIHR portfolio were searched from January 1994 to March 2020. ELIGIBILITY CRITERIA FOR SELECTIVE STUDIES: All identified studies that compared ESG and OSR, including randomised controlled trials (RCTs), quasi-randomised and non-RCTs, comparative cohort studies and case-control studies matched on main outcomes were sought. Participants had to receive elective treatments for arch/descending (TAA). Studies were excluded where other thoracic aortic conditions (eg, rupture or dissection) were reported, unless results for patients receiving elective treatment for arch/descending TAA reported separately. DATA EXTRACTION AND SYNTHESIS: Data were extracted by one reviewer and checked by another. Risk of Bias was assessed using the ROBINS-I tool. Meta-analysis was conducted using random effects. Where meta-analysis not appropriate, results were reported narratively. RESULTS: Five comparative cohort studies met inclusion criteria, reporting 3955 ESG and 21 197 OSR patients. Meta-analysis of unadjusted short-term (30 day) all-cause mortality favoured ESG (OR 0.75; 95% CI 0.55 to 1.03)). Heterogeneity identified between larger and smaller studies. Sensitivity analysis of four studies including only descending TAA showed no statistical significance (OR 0.73, 95% CI 0.45 to 1.18)), moderate heterogeneity. Meta-analysis of adjusted short-term all-cause mortality favoured ESG (OR 0.71, 95% CI 0.51 to 0.98)), no heterogeneity. Longer-term (beyond 30 days) survival from all-cause mortality favoured OSR in larger studies and ESG in smaller studies. Freedom from reintervention in the longer-term favoured OSR. Studies reporting short-term non-fatal complications suggest fewer events following ESG. CONCLUSIONS: There is limited and increasingly dated evidence on the comparison of ESG and OSR for treatment of arch/descending TAA. PROSPERO REGISTRATION NUMBER: CRD42017054565.


Assuntos
Aneurisma da Aorta Abdominal , Aneurisma da Aorta Torácica , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Procedimentos Cirúrgicos Eletivos , Humanos , Stents , Resultado do Tratamento
18.
Inorg Chem ; 60(7): 4996-5004, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33764048

RESUMO

Reaction of 1 equiv of KN(SiMe3)2 with 9-fluorenone results in the formation of (Me3Si)N═C13H8 (1) in high yield after work-up. Addition of 1 equiv of phenol to 1 results in rapid desilylation and formation of 9-fluorenone imine, HN═C13H8 (2). Subsequent reaction of 2 with 1 equiv of LiNiPr2 results in deprotonation and formation of [Li(Et2O)]4[N═C13H8]4 (3) in good yield. Reaction of 1 equiv of KN(SiMe3)2 with 2-adamantanone for 7 days at room temperature results in the formation of (Me3Si)N═C10H14 (4) in good yield. Dissolution of 4 in neat MeOH results in rapid desilylation concomitant with formation of 2-adamantanone imine, HN═C10H14 (5). Subsequent reaction of 5 with 1 equiv of LiNiPr2 results in formation of [Li(THF)]4[N═C10H14]4 (6). Both 3 and 6 were characterized by X-ray crystallography. Finally, reaction of CrCl3 with 3.5 equiv of 6 results in formation of the [Cr2]6+ dimer, [Li][Cr2(N═C10H14)7] (7), which can be isolated in modest yield after work-up. Complex 7 features a Cr-Cr bond length of 2.653(2) Å. Additionally, solid-state magnetic susceptibility measurements reveal strong antiferromagnetic coupling between the two Cr centers, with J = -200 cm-1.

19.
Toxicol Appl Pharmacol ; 417: 115463, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33631232

RESUMO

By extending our Paraquat (PQ) work to include primates we have implemented a modelling and simulation strategy that has enabled PQ pharmacokinetic data to be integrated into a single physiologically based pharmacokinetic (PBPK) model that enables more confident extrapolation to humans. Because available data suggested there might be differences in PQ kinetics between primates and non-primates, a radiolabelled study was conducted to characterize pharmacokinetics and excretion in Cynomolgus monkeys. Following single intravenous doses of 0.01 or 0.1 mg paraquat dichloride/kg bw, plasma PQ concentration-time profiles were dose-proportional. Excretion up to 48 h (predominantly urinary) was 82.9%, with ca. 10% remaining unexcreted. In vitro blood binding was similar across Cynomolgus monkeys, humans and rat. Our PBPK model for the rat, mouse and dog, employing a single set of PQ-specific parameters, was scaled to Cynomolgus monkeys and well represented the measured plasma concentration-time profiles over 14 days. Addition of a cartilage compartment to the model better captured the percent remaining in the monkeys at 48 h, whilst having negligible effect on model predictions for the other species. The PBPK model performed well for all four species, demonstrating there is little difference in PQ kinetics between non-primates and primates enabling a more confident extrapolation to humans. Scaling of the PBPK model to humans, with addition of a human-specific dermal submodel based on in vitro human dermal absorption data, provides a valuable tool that could be employed in defining internal dosimetry to complement human health risk assessments.


Assuntos
Herbicidas/farmacocinética , Modelos Biológicos , Paraquat/farmacocinética , Animais , Simulação por Computador , Herbicidas/administração & dosagem , Herbicidas/sangue , Herbicidas/toxicidade , Humanos , Infusões Intravenosas , Eliminação Intestinal , Macaca fascicularis , Paraquat/administração & dosagem , Paraquat/sangue , Paraquat/toxicidade , Ratos , Eliminação Renal , Medição de Risco , Absorção Cutânea , Especificidade da Espécie , Distribuição Tecidual , Toxicocinética
20.
Toxicol Appl Pharmacol ; 417: 115462, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33631233

RESUMO

Paraquat dichloride (PQ) is a non-selective herbicide which has been the subject of numerous toxicology studies over more than 50 years. This paper describes the development of a physiologically-based pharmacokinetic (PBPK) model of PQ kinetics for the rat, mouse and dog, firstly to aid the interpretation of studies in which no kinetic measurements were made, and secondly to enable the future extension of the model to humans. Existing pharmacokinetic data were used to develop a model for the rat and mouse. Simulations with this preliminary model were then used to identify key data gaps and to design a new blood binding study to reduce uncertainty in critical aspects of the model. The new data provided evidence to support the model structure, and its predictive performance was then assessed against dog and rat datasets not used in model development. The PQ-specific model parameters are the same for all three species, with only the physiological parameters varying between species. This consistency across species provides a strong basis for extrapolation to other species, as demonstrated here for the dog. The model enables a wide range of PQ data to be linked together to provide a broad understanding of PQ pharmacokinetics in rodents and the dog, showing that the key aspects of PQ kinetics in these species are understood and adequately encapsulated within the model.


Assuntos
Herbicidas/farmacocinética , Modelos Biológicos , Paraquat/farmacocinética , Animais , Simulação por Computador , Cães , Herbicidas/sangue , Herbicidas/toxicidade , Eliminação Intestinal , Camundongos , Paraquat/sangue , Paraquat/toxicidade , Ligação Proteica , Ratos , Eliminação Renal , Medição de Risco , Especificidade da Espécie , Distribuição Tecidual , Toxicocinética
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