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1.
Artículo en Inglés | MEDLINE | ID: mdl-38369906

RESUMEN

There is high demand for specialist mental health services for children and young people in the UK. Non-mental health nurses are well-placed to assess the mental health needs and risks of children and young people to maximise opportunities for early intervention and relieve the pressure on child and adolescent mental health services. This article provides an overview of a service development project to develop a web-based application (app) to support non-mental health nurses when assessing the mental health needs and risks of children and young people. The article describes the development, testing and evaluation process, which involved consultation with children and young people as well as interviews, focus groups and an online survey with a range of professionals working with children and young people. Overall, the findings suggest that the app is appropriate for use by non-mental health nurses in terms of quality, functionality and acceptability.

2.
Chem Mater ; 36(1): 501-513, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38222936

RESUMEN

Quantum spin liquids are highly entangled magnetic states with exotic properties. The S = 1/2 square-lattice Heisenberg model is one of the foundational models in frustrated magnetism with a predicted, but never observed, quantum spin liquid state. Isostructural double perovskites Sr2CuTeO6 and Sr2CuWO6 are physical realizations of this model but have distinctly different types of magnetic order and interactions due to a d10/d0 effect. Long-range magnetic order is suppressed in the solid solution Sr2CuTe1-xWxO6 in a wide region of x = 0.05-0.6, where the ground state has been proposed to be a disorder-induced spin liquid. Here, we present a comprehensive neutron scattering study of this system. We show using polarized neutron scattering that the spin liquid-like x = 0.2 and x = 0.5 samples have distinctly different local spin correlations, which suggests that they have different ground states. Low-temperature neutron diffraction measurements of the magnetically ordered W-rich samples reveal magnetic phase separation, which suggests that the previously ignored interlayer coupling between the square planes plays a role in the suppression of magnetic order at x ≈ 0.6. These results highlight the complex magnetism of Sr2CuTe1-xWxO6 and hint at a new quantum critical point between 0.2 < x < 0.4.

4.
Antimicrob Agents Chemother ; 67(12): e0091623, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38014945

RESUMEN

Rezafungin is a chemically and metabolically stable echinocandin with a longer half-life than other echinocandins, allowing for a once-weekly intravenous infusion versus a daily infusion. Rezafungin is approved in the US for the treatment of candidemia and/or invasive candidiasis and is in development for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp. in immunosuppressed patients. A population pharmacokinetic (PPK) model was developed using data from five Phase 1, one Phase 2, and one Phase 3 study. The model found to best describe the available data was a three-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V23), intercompartmental clearance 1, and intercompartmental clearance 2. The variability model included correlated interindividual variability in CL, V1, and V23 and a proportional residual variability model. The following statistically significant covariates were identified: albumin concentrations on V23; body surface area (BSA) on CL, V1, and V23; and disease state on CL and V1. Disease states were defined as patients from the Phase 2 and Phase 3 studies and hepatically impaired subjects. Covariates of BSA, disease state, or albumin, included in the final model, were not associated with clinically meaningful changes in PK, nor were any other patient factors, indicating that a common dose regimen is adequate for all adult patients. Target attainment simulations were performed to estimate the probability of achieving PK/pharmacodynamic targets across the range of minimum inhibitory concentration values for six species of Candida.


Asunto(s)
Candidemia , Candidiasis Invasiva , Adulto , Humanos , Candidemia/tratamiento farmacológico , Antifúngicos/farmacología , Equinocandinas/farmacología , Candidiasis Invasiva/tratamiento farmacológico , Candida , Albúminas/uso terapéutico
5.
Microbiol Spectr ; 11(3): e0133923, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37154682

RESUMEN

Rezafungin is a novel once-weekly echinocandin for intravenous injection currently in development for the treatment of Candida infections and the prevention of Candida, Aspergillus, and Pneumocystis infections in allogeneic blood and marrow transplant recipients. While in vitro data indicated that rezafungin exposure was unlikely to be affected by commonly prescribed medicines, interactions resulting in the altered systemic exposure of some drugs coadministered with rezafungin could not be excluded. Two phase 1 open label crossover studies, conducted in healthy subjects, examined drug interactions between rezafungin and multiple drug probe cytochrome P450 (CYP) substrates and/or transporter proteins, immunosuppressants, and cancer therapies. Statistical analysis compared the outcomes for drugs coadministered with rezafungin to those for the drugs administered alone. The geometric mean ratio was reported, and a default 90% confidence interval (CI) no-effect equivalence range of 80 to 125% was used for the maximal plasma concentration (Cmax), the area under the curve from time zero to the final sampling time point (AUC0-t), and the AUC from time zero to infinity (AUC0-∞). Most probes and concomitant drugs were within the equivalence range. For tacrolimus, ibrutinib, mycophenolic acid, and venetoclax, the AUC or Cmax was reduced (10 to 19%), with lower bounds of the 90% CI values falling outside the no-effect range. The rosuvastatin AUC and Cmax and the repaglinide AUC0-∞ were increased (12 to 16%), with the 90% CI being marginally above the upper bound. Overall, the in vitro and in vivo data demonstrated a low drug interaction potential with rezafungin via CYP substrate/transporter pathways and commonly prescribed comedications, suggesting that coadministration was unlikely to result in clinically significant effects. Treatment-emergent adverse events were typically mild, and rezafungin was generally well tolerated. IMPORTANCE Antifungal agents used to treat life-threatening infections are often associated with severe drug-drug interactions (DDIs) that may limit their usefulness. Rezafungin, a newly approved once-weekly echinocandin, has been shown to be free of DDIs based on extensive nonclinical and clinical testing described in this study.


Asunto(s)
Candidiasis , Equinocandinas , Humanos , Antifúngicos/efectos adversos , Candida , Candidiasis/tratamiento farmacológico , Interacciones Farmacológicas , Equinocandinas/efectos adversos , Ensayos Clínicos Fase I como Asunto , Estudios Cruzados
6.
Phys Chem Chem Phys ; 25(13): 9282-9293, 2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-36919868

RESUMEN

High-entropy order-disorder phase transitions can be used for efficient and eco-friendly barocaloric solid-state cooling. Here the barocaloric effect is reported in an archetypal plastic crystal, adamantane. Adamantane has a colossal isothermally reversible entropy change of 106 J K-1 kg-1. Extremely low hysteresis means that this can be accessed at pressure differences less than 200 bar. Configurational entropy can only account for about 40% of the total entropy change; the remainder is due to vibrational effects. Using neutron spectroscopy and supercell lattice dynamics calculations, it is found that this vibrational entropy change is mainly caused by softening in the high-entropy phase of acoustic modes that correspond to molecular rotations. We attribute this difference in the dynamics to the contrast between an 'interlocked' state in the low-entropy phase and sphere-like behaviour in the high-entropy phase. Although adamantane is a simple van der Waals solid with near-spherical molecules, this approach can be leveraged for the design of more complex barocaloric molecular crystals. Moreover, this study shows that supercell lattice dynamics calculations can accurately map the effect of orientational disorder on the phonon spectrum, paving the way for studying the vibrational entropy, thermal conductivity, and other thermodynamic effects in more complex materials.

7.
Sci Bull (Beijing) ; 67(1): 38-44, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36545957

RESUMEN

We report thermodynamic and neutron scattering measurements of the triangular-lattice quantum Ising magnet TmMgGaO4 in longitudinal magnetic fields. Our experiments reveal a quasi-plateau state induced by quantum fluctuations. This state exhibits an unconventional non-monotonic field and temperature dependence of the magnetic order and excitation gap. In the high field regime where the quantum fluctuations are largely suppressed, we observed a disordered state with coherent magnon-like excitations despite the suppression of the spin excitation intensity. Through detailed semi-classical calculations, we are able to understand these behaviors quantitatively from the subtle competition between quantum fluctuations and frustrated Ising interactions.

8.
Eur Urol Oncol ; 5(4): 412-419, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35450835

RESUMEN

BACKGROUND: Bacteria play a suspected role in the development of several cancer types, and associations between the presence of particular bacteria and prostate cancer have been reported. OBJECTIVE: To provide improved characterisation of the prostate and urine microbiome and to investigate the prognostic potential of the bacteria present. DESIGN, SETTING, AND PARTICIPANTS: Microbiome profiles were interrogated in sample collections of patient urine (sediment microscopy: n = 318, 16S ribosomal amplicon sequencing: n = 46; and extracellular vesicle RNA-seq: n = 40) and cancer tissue (n = 204). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Microbiomes were assessed using anaerobic culture, population-level 16S analysis, RNA-seq, and whole genome DNA sequencing. RESULTS AND LIMITATIONS: We demonstrate an association between the presence of bacteria in urine sediments and higher D'Amico risk prostate cancer (discovery, n = 215 patients, p < 0.001; validation, n = 103, p < 0.001, χ2 test for trend). Characterisation of the bacterial community led to the (1) identification of four novel bacteria (Porphyromonas sp. nov., Varibaculum sp. nov., Peptoniphilus sp. nov., and Fenollaria sp. nov.) that were frequently found in patient urine, and (2) definition of a patient subgroup associated with metastasis development (p = 0.015, log-rank test). The presence of five specific anaerobic genera, which includes three of the novel isolates, was associated with cancer risk group, in urine sediment (p = 0.045, log-rank test), urine extracellular vesicles (p = 0.039), and cancer tissue (p = 0.035), with a meta-analysis hazard ratio for disease progression of 2.60 (95% confidence interval: 1.39-4.85; p = 0.003; Cox regression). A limitation is that functional links to cancer development are not yet established. CONCLUSIONS: This study characterises prostate and urine microbiomes, and indicates that specific anaerobic bacteria genera have prognostic potential. PATIENT SUMMARY: In this study, we investigated the presence of bacteria in patient urine and the prostate. We identified four novel bacteria and suggest a potential prognostic utility for the microbiome in prostate cancer.


Asunto(s)
Microbiota , Neoplasias de la Próstata , Bacterias/genética , Humanos , Masculino , Microbiota/genética , Próstata/patología , Neoplasias de la Próstata/patología , ARN Ribosómico 16S/genética
9.
Phys Rev Lett ; 127(14): 147205, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34652174

RESUMEN

We report neutron scattering measurements of the spinel oxide LiGaCr_{4}O_{8}, in which magnetic ions Cr^{3+} form a breathing pyrochlore lattice. Our experiments reveal the coexistence of a nearly dispersionless resonance mode and dispersive spin-wave excitations in the magnetically ordered state, which can be quantitatively described by a quantum spin model of hexagonal loops and linear spin-wave theory with the same set of exchange parameters, respectively. Comparison to other Cr spinel oxides reveals a linear relationship between the resonance energy and lattice constant across all these materials, which is in agreement with our hexagonal loop calculations. Our results suggest a unified picture for spin resonances in Cr spinel oxides.

10.
Science ; 373(6558): 1017-1022, 2021 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-34446603

RESUMEN

The thermal conductivity of crystalline materials cannot be arbitrarily low, as the intrinsic limit depends on the phonon dispersion. We used complementary strategies to suppress the contribution of the longitudinal and transverse phonons to heat transport in layered materials that contain different types of intrinsic chemical interfaces. BiOCl and Bi2O2Se encapsulate these design principles for longitudinal and transverse modes, respectively, and the bulk superlattice material Bi4O4SeCl2 combines these effects by ordering both interface types within its unit cell to reach an extremely low thermal conductivity of 0.1 watts per kelvin per meter at room temperature along its stacking direction. This value comes within a factor of four of the thermal conductivity of air. We demonstrated that chemical control of the spatial arrangement of distinct interfaces can synergically modify vibrational modes to minimize thermal conductivity.

11.
Front Neurosci ; 15: 664525, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34220424

RESUMEN

We retrospectively examined the relationship between blood biomarkers, in particular the historical mean phenylalanine to tyrosine (Phe:Tyr) ratio, and cerebral glucose metabolism. We hypothesized that the historical mean Phe:Tyr ratio would be more predictive of cerebral glucose metabolism than the phenylalanine (Phe) level alone. We performed a retrospective case series analysis involving 11 adult classical phenylketonuria/hyperphenylalaninemia patients under the care of an Inherited Metabolic & Neuropsychiatry Clinic who had complained of memory problems, collating casenote data from blood biochemistry, and clinical [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET). The Phe:Tyr ratio was calculated for individual blood samples and summarized as historical mean Phe:Tyr ratio (Phe:Tyr) and historical standard deviation in Phe:Tyr ratio (SD-Phe:Tyr), for each patient. Visual analyses of [18F]FDG PET revealed heterogeneous patterns of glucose hypometabolism for eight patients. [18F]FDG PET standardized uptake was negatively correlated with Phe in a large cluster with peak localized to right superior parietal gyrus. Even larger clusters of negative correlation that encompassed most of the brain, with frontal peaks, were observed with Phe:Tyr, and SD-Phe:Tyr. Our case series analysis provides further evidence for the association between blood biomarkers, and cerebral glucose hypometabolism. Mean historical blood Phe:Tyr ratio, and its standard deviation over time, appear to be more indicative of global cerebral glucose metabolism in patients with memory problems than Phe.

12.
BMJ Open ; 11(2): e041947, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33526500

RESUMEN

OBJECTIVE: To explore the relationship between symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM). The hypothesis predicated that there would be no significant differences between the group's symptom experience. DESIGN: A quasiexperimental design. Structural equation modelling (SEM) and invariance testing. PARTICIPANTS: Males (M) and females (F) >16 with a confirmed diagnosis of CFS/ME or FM by a general practitioner or specialist. CFS/ME (n=101, F: n=86, M: n=15, mean (M) age M=45.5 years). FM (n=107, F: n=95, M: n=12, M=47.2 years). OUTCOME MEASURES: Diagnostic criteria: the American Centers for Disease Control and Prevention (CDC) for CFS/ME and the American College of Rheumatology (ACR) criteria for FM. Additional symptom questionnaires measuring: pain, sleep quality, fatigue, quality of life, anxiety and depression, locus of control and self-esteem. RESULTS: Invariance was confirmed with the exception of the American CDC Symptom Inventory, Fibromyalgia Impact Questionnaire and Hospital Anxiety and Depression Scale (p<0.05) based on five questions. Consequently, it was erroneous to conclude differences. Therefore, the Syndrome Model was created. SEM could not have tested the ACR previously, as it comprised a single data point. Thus, it was combined with these three questionnaires, increasing the data points, to create this new measurable model. Results confirmed no significant differences between groups (p=0.07 (p<0.05)). CONCLUSION: Participants responded in a similar manner to the questionnaire, confirming the same symptom experience. It is important to consider this in context with differing criteria and management guidelines, as this may influence diagnosis and the trajectory of patient's management. With the biomedical cause currently unclear, it is the symptom experience and the impact on quality of life that is important. These findings are meaningful for patients, clinicians and policy development and support the requirement for future research.


Asunto(s)
Síndrome de Fatiga Crónica , Fibromialgia , Ansiedad , Síndrome de Fatiga Crónica/diagnóstico , Femenino , Fibromialgia/complicaciones , Fibromialgia/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios
13.
Br J Pain ; 15(1): 26-39, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33633851

RESUMEN

INTRODUCTION: Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and fibromyalgia (FM) are both debilitating syndromes with complex polysymptomatology. Early research infers that a relationship may exist even though the diagnosis provided may influence the management trajectory. In the absence of a diagnostic test and treatment, this study aims to confirm the symptoms and their severity, which may infer a relationship and influence future research. METHOD: A quasi-experimental design was utilised, using Internet-based self-assessment questionnaires focusing on nine symptom areas: criteria, pain, sleep, fatigue, anxiety and depression, health-related quality of life, self-esteem and locus of control. The questionnaires used for data collection are as follows: the American Centre for Disease Control and Prevention Symptom Inventory for CFS/ME (American CDC Symptom Inventory); the American College of Rheumatology (ACR) Criteria for FM; Fibromyalgia Impact Questionnaire (FIQ); McGill Pain Questionnaire (MPQ); Multidimensional Fatigue Inventory (MFI); Pittsburgh Sleep Quality Index (PSQI); Health-Related Quality of Life SF-36 V2 (HRQoL SF-36 V2); Hospital Anxiety and Depression Scale (HADS); Multidimensional Health Locus of Control (MHLOC) and the Rosenberg Self-Esteem Scale (RSES). SETTING AND PARTICIPANTS: Participants were recruited from two distinct community groups, namely CFS/ME (n = 101) and FM (n = 107). Participants were male and female aged 17 (CFS/ME mean age 45.5 years; FM mean age 47.2 years). RESULTS: All participants in the CFS/ME and FM groups satisfied the requirements of their individual criteria. Results confirmed that both groups experienced the debilitating symptoms measured, with the exception of anxiety and depression, impacting on their quality of life. Results suggest a relationship between CFS/ME and FM, indicating the requirement for future research.

14.
Phys Ther Sport ; 47: 173-177, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33310584

RESUMEN

OBJECTIVES: To compare the change in supraspinatus tendon thickness (STT) following a high volume (HV) and high intensity (HI) swimming practice in shoulders of elite swimmers. DESIGN: Cohort Study. SETTING: Non-clinical, state swim team training facility. PARTICIPANTS: A convenience sample of eight non-injured state and national level swimmers from a regional swim team were recruited for this study. MAIN OUTCOME MEASURES: Ultrasound measures of STT were collected in response to the two swimming practice sessions. Measures were taken prior to each swim practice; immediately after practice; 6-hours post practice and 24-hours post practice. RESULTS: A significant increase in STT resulted from both the HI and HV (p < 0.05) practice immediately post practice. For the HI practice, the STT remained significantly thicker than pre-practice measures at the 6-hour post practice test (p < 0.05) however no longer significant 24-hours post practice. The difference in the change in STT between the HI and HV practice was significantly different immediately post practice and 6-hours post practice (p < 0.05) however no longer significant 24-hour post practice. CONCLUSION: Ultrasound measures of STT following different swimming volumes and intensities may provide information on shoulder tendon loads.


Asunto(s)
Acondicionamiento Físico Humano/fisiología , Manguito de los Rotadores/anatomía & histología , Natación/fisiología , Adolescente , Estudios de Cohortes , Femenino , Humanos , Masculino , Manguito de los Rotadores/diagnóstico por imagen , Hombro/diagnóstico por imagen , Dolor de Hombro/fisiopatología , Ultrasonografía
15.
Front Psychiatry ; 11: 357, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32477174

RESUMEN

INTRODUCTION: Forensic mental health nurses working at the forefront of services can intermittently face enduring and somewhat harrowing or stressful situations. Enclosed is an example of the use of mechanical restraints (Soft Restraint Kit) for a two month period. Staff experience of working under such circumstances is an under reported area. METHODS: The experience of nursing a patient under extreme conditions was captured through use of a qualitative study, using semi structured interviews with a purposive sample of (n = 10) staff nurses and nursing assistants in a high-security hospital. RESULTS: Thematic analysis was undertaken generating four themes: sense of responsibility, aptitude, enablers/inhibitors, and consequence. Conclusions suggest that Soft Restraint Kits provide a useful method of containment, although prolonged use presents considerable challenges for staff. The importance of preparation and training cannot be underestimated and continued support and supervision are absolutely essential.

16.
Scand J Med Sci Sports ; 30(8): 1442-1448, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32278323

RESUMEN

OBJECTIVES: To assess if swimming practice results in changes in supraspinatus tendon thickness, acromiohumeral distance, and occupational ratio in shoulders of elite swimmers with and without a history of shoulder pain. DESIGN: Case-Control study. METHODS: A convenience sample of fifty elite swimmers (14-22 years) were recruited for this study. Groups were defined by the presence (history of pain, N = 37) or absence (pain free, N = 63) of significant interfering shoulder pain within the previous 6 months. The current study analyzed supraspinatus tendon thickness, acromiohumeral distance, and the occupational ratio, through the use of ultrasound. Measures were taken prior to swim practice; immediately after practice; and 6 hours post-practice. RESULTS: No statistically significant difference in supraspinatus tendon thickness, acromiohumeral distance or ratio between shoulders with and without a history of pain were found at rest. Following a swimming practice, both shoulders with and without a history of pain had a significant increase in tendon thickness (0.27 & 0.17 mm; P ≤ .001 & <.001). The increase in thickness was significantly greater in the history of pain shoulders compared to pain-free shoulders (P = .003). At 6-hour post-practice, the history of pain shoulders was still significantly thicker than their pre-practice (rested) levels (P = .007). Despite changes in tendon thickness, the occupational ratio remained non-significant between groups. CONCLUSION: Shoulders with a history of pain show an altered response to swimming practice. The results of the current study have implications for training load and injury management. It should prompt investigation into how the tendon reacts under varying load conditions.


Asunto(s)
Traumatismos en Atletas/fisiopatología , Lesiones del Manguito de los Rotadores/fisiopatología , Dolor de Hombro/fisiopatología , Natación/fisiología , Traumatismos de los Tendones/fisiopatología , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Ultrasonografía , Adulto Joven
17.
Int Psychogeriatr ; 32(3): 347-358, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31762434

RESUMEN

OBJECTIVES: One-on-one structured Montessori-based activities conducted with people with dementia can improve agitation and enhance engagement. These activities may however not always be implemented by nursing home staff. Family members may present an untapped resource for enabling these activities. This study aimed to evaluate the impact of the Montessori activities implemented by family members on visitation experiences with people who have dementia. DESIGN: Cluster-randomized crossover design. SETTING: General and psychogeriatric nursing homes in the state of Victoria, Australia. PARTICIPANTS: Forty participants (20 residents and 20 carers) were recruited. INTERVENTION: During visits, family members interacted with their relative either through engaging in Montessori-based activities or reading a newspaper (the control condition) for four 30-minute sessions over 2 weeks. MEASUREMENTS: Residents' predominant affect and engagement were rated for each 30-second interval using the Philadelphia Geriatric Center Affect Rating Scale and the Menorah Park Engagement Scale. The Pearlin Mastery Scale was used to rate carers satisfaction with visits. The 15-item Mutuality Scale measured the carers quality of their relationship with the resident. Carers' mood and overall quality of life were measured using the Center for Epidemiological Studies Depression Scale and Carer-QoL questionnaires, respectively. RESULTS: Linear regressions within the generalized estimating equations approach assessed residents' and carers' outcomes. Relative to the control condition, the Montessori condition resulted in more positive engagement (b = 13.0, 95%CI 6.3-19.7, p < 0.001) and affect (b = 0.4, 95%CI 0.2-0.6, p < 0.001) for the residents and higher satisfaction with visits for carers (b = 1.7, 95%CI 0.45-3.00, p = 0.008). No correction was applied to p-values for multiple comparisons. CONCLUSION: This study strengthens the evidence base for the use of the Montessori programs in increasing well-being in nursing home residents. The findings also provide evidence that family members are an additional valuable resource in implementing structured activities such as the Montessori program with residents.


Asunto(s)
Control de la Conducta/métodos , Síntomas Conductuales/terapia , Demencia/terapia , Familia/psicología , Agitación Psicomotora/terapia , Anciano , Síntomas Conductuales/psicología , Botswana , Cuidadores/psicología , Estudios Cruzados , Demencia/psicología , Femenino , Hogares para Ancianos , Humanos , Masculino , Casas de Salud , Evaluación de Procesos y Resultados en Atención de Salud , Agitación Psicomotora/complicaciones , Agitación Psicomotora/psicología , Calidad de Vida , Encuestas y Cuestionarios
18.
J Pharmacol Exp Ther ; 371(1): 202-207, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31371481

RESUMEN

Fenebrutinib (GDC-0853) is an orally administered small molecule inhibitor of Bruton's tyrosine kinase being investigated for treatment of rheumatoid arthritis in patients with inadequate responses to methotrexate (MTX). This study interrogated the potential for pharmacokinetic drug interactions between fenebrutinib and MTX. Eighteen healthy male subjects were enrolled in the study. They received a single oral dose of MTX (7.5 mg) on day 1 followed by a 13-day washout period. Subsequently, on days 15-20 the participants received 200 mg of fenebrutinib twice daily. On day 21, they received a 7.5 mg dose of MTX and a 200 mg dose of fenebrutinib under fasting conditions. The geometric mean ratios of MTX area under the plasma concentration-time curve (AUC) and C max on day 21 relative to day 1 (90% confidence interval [CI]) were 0.96 (0.88-1.04) and 1.05 (0.94-1.18), respectively. The geometric mean ratios of fenebrutinib AUC and C max for day 21 relative to day 20 (90% CI) were 1.03 (0.95-1.11) and 1.02 (0.90-1.15), respectively. The combination treatment was well tolerated, with an adverse event profile similar to that reported in other MTX trials. These results indicate that there is no clinically significant pharmacokinetic interaction between fenebrutinib and MTX.


Asunto(s)
Antirreumáticos/farmacocinética , Metotrexato/farmacocinética , Piperazinas/farmacocinética , Inhibidores de Proteínas Quinasas/farmacocinética , Piridonas/farmacocinética , Adulto , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Interacciones Farmacológicas , Humanos , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Piridonas/administración & dosificación , Piridonas/efectos adversos
19.
BJU Int ; 124(4): 609-620, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31106513

RESUMEN

OBJECTIVES: To develop a risk classifier using urine-derived extracellular vesicle (EV)-RNA capable of providing diagnostic information on disease status prior to biopsy, and prognostic information for men on active surveillance (AS). PATIENTS AND METHODS: Post-digital rectal examination urine-derived EV-RNA expression profiles (n = 535, multiple centres) were interrogated with a curated NanoString panel. A LASSO-based continuation ratio model was built to generate four prostate urine risk (PUR) signatures for predicting the probability of normal tissue (PUR-1), D'Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer. This model was applied to a test cohort (n = 177) for diagnostic evaluation, and to an AS sub-cohort (n = 87) for prognostic evaluation. RESULTS: Each PUR signature was significantly associated with its corresponding clinical category (P < 0.001). PUR-4 status predicted the presence of clinically significant intermediate- or high-risk disease (area under the curve = 0.77, 95% confidence interval [CI] 0.70-0.84). Application of PUR provided a net benefit over current clinical practice. In an AS sub-cohort (n = 87), groups defined by PUR status and proportion of PUR-4 had a significant association with time to progression (interquartile range hazard ratio [HR] 2.86, 95% CI 1.83-4.47; P < 0.001). PUR-4, when used continuously, dichotomized patient groups with differential progression rates of 10% and 60% 5 years after urine collection (HR 8.23, 95% CI 3.26-20.81; P < 0.001). CONCLUSION: Urine-derived EV-RNA can provide diagnostic information on aggressive prostate cancer prior to biopsy, and prognostic information for men on AS. PUR represents a new and versatile biomarker that could result in substantial alterations to current treatment of patients with prostate cancer.

20.
Chem Sci ; 10(2): 480-489, 2019 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-30713645

RESUMEN

The relative amounts of hydrogen retained by a range of supported palladium catalysts have been investigated by a combination of electron microscopy and spectroscopic techniques, including incoherent inelastic neutron scattering. Contrary to expectation, the hydrogen capacity is not determined solely by the metal particle size, but it is a complex interaction between the particle size and its state of aggregation. The nature of the support is not only integral to the amount of hydrogen held by the catalyst, it also causes a marked difference in the rate of release of stored hydrogen from palladium. It is more difficult to fully dehydrogenate palladium on/in the porous activated carbon than on the non-porous carbon black based catalyst. The type of support also results in differences in the form of the residual hydrogen: whether it is α- or ß-hydride phase, subsurface or in the threefold surface site. Our data on the supported catalysts reinforces what has only been seen previously with palladium black and our computational study provides confirmation of the empirical assignments. We also report the first vibrational spectroscopic study of hydrogen adsorbed at the surface of ß-PdH and have observed for the first time hydrogen in the on-top site. This has enabled the relative proportion of bulk- to surface-H occupation in calculated model and in industrial nanoparticles to be estimated.

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