RESUMEN
Intellectual disability (ID) is associated with an increased risk of developing psychiatric disorders, suggesting a common underlying genetic factor. Importantly, altered signaling and/or expression of regulator of G protein signaling 6 (RGS6) is associated with ID and numerous psychiatric disorders. RGS6 is highly conserved and undergoes complex alternative mRNA splicing producing ~36 protein isoforms with high sequence similarity historically necessitating a global approach in functional studies. However, our recent analysis in mice revealed RGS6 is most highly expressed in CNS with RGS6L(+GGL) isoforms predominating. A previously reported genetic variant in intron 17 of RGS6 (c.1369-1G>C), associated with ID, may provide further clues into RGS6L(+GGL) isoform functional delineation. This variant was predicted to alter a highly conserved canonical 3' acceptor site creating an alternative branch point within exon 18 (included in a subset of RGS6L(+GGL) transcripts) and a frameshift forming an early stop codon. We previously identified this alternative splice site and demonstrated its use generates RGS6Lζ(+GGL) isoforms. Here, we show that the c.1369-1G>C variant disrupts the canonical, preferred (>90%) intron 17 splice site and leads to the exclusive use of the alternate exon 18 splice site, inducing disproportionate expression of a subset of isoforms, particularly RGS6Lζ(+GGL). Furthermore, RGS6 global knockout mice do not exhibit ID. Thus, ID caused by the c.1369-1G>C variant likely results from altered RGS6 isoform expression, rather than RGS6 isoform loss. In summary, these studies highlight the importance of proper RGS6 splicing and identify a previously unrecognized role of G protein signaling in ID.
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Catarata , Discapacidad Intelectual , Microcefalia , Proteínas RGS , Animales , Humanos , Ratones , Catarata/genética , Proteínas de Unión al GTP/genética , Discapacidad Intelectual/genética , Microcefalia/genética , Isoformas de Proteínas/genética , Proteínas RGS/genética , Proteínas RGS/metabolismo , Sitios de Empalme de ARNRESUMEN
To mitigate methane emission from urban natural gas distribution systems, it is crucial to understand local leak rates and occurrence rates. To explore urban methane emissions in cities outside the U.S., where significant emissions were found previously, mobile measurements were performed in 12 cities across eight countries. The surveyed cities range from medium size, like Groningen, NL, to large size, like Toronto, CA, and London, UK. Furthermore, this survey spanned across European regions from Barcelona, ES, to Bucharest, RO. The joint analysis of all data allows us to focus on general emission behavior for cities with different infrastructure and environmental conditions. We find that all cities have a spectrum of small, medium, and large methane sources in their domain. The emission rates found follow a heavy-tailed distribution, and the top 10% of emitters account for 60-80% of total emissions, which implies that strategic repair planning could help reduce emissions quickly. Furthermore, we compare our findings with inventory estimates for urban natural gas-related methane emissions from this sector in Europe. While cities with larger reported emissions were found to generally also have larger observed emissions, we find clear discrepancies between observation-based and inventory-based emission estimates for our 12 cities.
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Contaminantes Atmosféricos , Gas Natural , Ciudades , Gas Natural/análisis , Metano/análisis , Contaminantes Atmosféricos/análisis , LondresRESUMEN
A major challenge in evolutionary biology has been to explain the variation in multicellularity across the many independently evolved multicellular lineages, from slime moulds to vertebrates. Social evolution theory has highlighted the key role of relatedness in determining multicellular complexity and obligateness; however, there is a need to extend this to a broader perspective incorporating the role of the environment. In this paper, we formally test Bonner's 1998 hypothesis that the environment is crucial in determining the course of multicellular evolution, with aggregative multicellularity evolving more frequently on land and clonal multicellularity more frequently in water. Using a combination of scaling theory and phylogenetic comparative analyses, we describe multicellular organizational complexity across 139 species spanning 14 independent transitions to multicellularity and investigate the role of the environment in determining multicellular group formation and in imposing constraints on multicellular evolution. Our results, showing that the physical environment has impacted the way in which multicellular groups form, highlight that environmental conditions might have affected the major evolutionary transition to obligate multicellularity.
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Evolución Biológica , Animales , FilogeniaRESUMEN
OBJECTIVE: To investigate the demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma. DESIGN: A retrospective national population-based study. SETTING: UK 1995-2015. POPULATION: A total of 234 women with a diagnosis of gestational choriocarcinoma, in the absence of a prior molar pregnancy, managed at the UKs two gestational trophoblast centres in London and Sheffield. METHODS: Retrospective review of the patient's demographic and clinical data. Comparison with contemporary UK birth and pregnancy statistics. MAIN OUTCOMES: Incidence statistics for non-molar choriocarcinoma across the maternal age groups. Cure rates for patients by FIGO prognostic score group. RESULTS: Over the 21-year study period, there were 234 cases of non-molar gestational choriocarcinoma, giving an incidence of 1:66 775 relative to live births and 1:84 226 to viable pregnancies. For women aged under 20, the incidence relative to viable pregnancies was 1:223 494, for ages 30-34, 1:80 227, and for ages 40-45, 1:41 718. Treatment outcomes indicated an overall 94.4% cure rate. Divided by FIGO prognostic groups, the cure rates were low-risk group 100%, high-risk group 96% and ultra-high-risk group 80.5%. CONCLUSIONS: Non-molar gestational choriocarcinoma is a very rare diagnosis with little prior detailed information on the demographics and natural history. The data in this study give age-related incidence data based on a large national population study. The results also demonstrated the widely varying natural history of this rare malignancy and the marked correlation of disease incidence with rising maternal age. TWEETABLE ABSTRACT: National gestational choriocarcinoma database indicates a close association between increasing maternal age and incidence.
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Coriocarcinoma/epidemiología , Neoplasias Uterinas/epidemiología , Adolescente , Adulto , Distribución por Edad , Coriocarcinoma/complicaciones , Coriocarcinoma/secundario , Coriocarcinoma/terapia , Femenino , Número de Embarazos , Humanos , Incidencia , Nacimiento Vivo/epidemiología , Edad Materna , Persona de Mediana Edad , Embarazo , Complicaciones Neoplásicas del Embarazo/epidemiología , Complicaciones Neoplásicas del Embarazo/patología , Complicaciones Neoplásicas del Embarazo/terapia , Pronóstico , Factores de Riesgo , Resultado del Tratamiento , Reino Unido/epidemiología , Hemorragia Uterina/etiología , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapia , Adulto JovenRESUMEN
OBJECTIVE: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country. DESIGN: Historical cohort study. SETTING: Charing Cross Hospital, United Kingdom. POPULATION: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2). METHODS: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups. MAIN OUTCOME MEASURES: MTX resistance, recurrence rate and survival. RESULTS: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups. CONCLUSIONS: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered. TWEETABLE ABSTRACT: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.
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Coriocarcinoma , Resistencia a Antineoplásicos/efectos de los fármacos , Enfermedad Trofoblástica Gestacional , Neoplasias Pulmonares , Metotrexato , Adulto , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Coriocarcinoma/tratamiento farmacológico , Coriocarcinoma/patología , Estudios de Cohortes , Femenino , Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Enfermedad Trofoblástica Gestacional/patología , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Estadificación de Neoplasias , Países Bajos/epidemiología , Evaluación de Resultado en la Atención de Salud , Embarazo , Recurrencia , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Reino Unido/epidemiologíaRESUMEN
INTRODUCTION: Facilitating stroke survivors and their caregivers to lead a fulfilling life after stroke requires service providers to think about their different needs. Poor post stroke care may lead to unmet needs in stroke survivors and stroke caregivers. This may compromise them in leading their lives optimally after stroke. OBJECTIVES & METHODOLOGY: This systematic narrative review examines articles published from 1990 to 2017, generated from Ovid, MEDLINE, CINAHL, and PubMed. The search was also supplemented by an examination of reference lists for related articles via Scopus. We included 105 articles. FINDINGS: We found that the type of unmet needs in stroke survivors and the contributing factors were substantially different from their caregivers. The unmet needs in stroke survivors ranged from health-related needs to re-integration into the community; while the unmet needs in stroke caregivers ranged from information needs to support in caring for the stroke survivors and caring for themselves. Additionally, the unmet needs in both groups were associated with different factors. CONCLUSION: More research is required to understand the unmet needs of stroke survivors and stroke caregivers to improve the overall post-stroke care services.
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Cuidadores/psicología , Necesidades y Demandas de Servicios de Salud , Cuidados a Largo Plazo , Evaluación de Necesidades , Calidad de Vida , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/terapia , Sobrevivientes/psicología , Adaptación Psicológica , Anciano , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Alta del Paciente , Recuperación de la Función , Autocuidado , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/psicología , Resultado del TratamientoRESUMEN
The treatment of post-traumatic femoral deformity with circular frames can be difficult both for the patient and for the surgeon. Patients frequently suffer from residual knee stiffness, and the cumbersome location of the frame can even result in psychiatric problems such as depression and anxiety during their treatment. Here we describe a novel technique of constructing the Taylor spatial frame (TSF) eccentrically from the femur to allow the same level of comfort as a monolateral external fixator, while applying trigonometric principles to successfully retain the utility of the TSF prescription software. Deformity correction and fracture compression can therefore still be achieved in a controlled and predictable manner on an outpatient basis.
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Fijadores Externos , Fracturas del Fémur/complicaciones , Fracturas del Fémur/cirugía , Fijación de Fractura/métodos , Adulto , Femenino , Fijación de Fractura/instrumentación , Humanos , RecurrenciaRESUMEN
Understanding how and why cells cooperate to form multicellular organisms is a central aim of evolutionary biology. Multicellular groups can form through clonal development (where daughter cells stick to mother cells after division) or by aggregation (where cells aggregate to form groups). These different ways of forming groups directly affect relatedness between individual cells, which in turn can influence the degree of cooperation and conflict within the multicellular group. It is hard to study the evolution of multicellularity by focusing only on obligately multicellular organisms, like complex animals and plants, because the factors that favour multicellular cooperation cannot be disentangled, as cells cannot survive and reproduce independently. We support the use of Saccharomyces cerevisiae as an ideal model for studying the very first stages of the evolution of multicellularity. This is because it can form multicellular groups both clonally and through aggregation and uses a family of proteins called 'flocculins' that determine the way in which groups form, making it particularly amenable to laboratory experiments. We briefly review current knowledge about multicellularity in S. cerevisiae and then propose a framework for making predictions about the evolution of multicellular phenotypes in yeast based on social evolution theory. We finish by explaining how S. cerevisiae is a particularly useful experimental model for the analysis of open questions concerning multicellularity.
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Saccharomyces cerevisiae/fisiología , Evolución Biológica , FenotipoRESUMEN
PURPOSE: Prospective data are lacking on long-term morbidity of inguinal lymphadenectomy including the influence of extent of surgery, use of radiotherapy, and patient factors. The aim of this study is to evaluate the effects of these factors on patient outcome, quality of life (QOL), regional symptoms, and limb volumes after inguinal or ilio-inguinal lymphadenectomy for melanoma. METHODS: Analysis of the subgroup of patients with inguinal lymph node field relapse of melanoma, treated by inguinal or ilio-inguinal lymphadenectomy in the ANZMTG/TROG randomized trial of adjuvant radiotherapy versus observation. RESULTS: Sixty-nine patients, 46 having undergone inguinal and 23 ilio-inguinal lymphadenectomy, with median follow-up of 73 months were analyzed. Mean limb volume increased rapidly after surgery (7% by 3 months) and continued to increase for at least another 18 months. Patients with body mass index (BMI) ≥ 25 kg/m2 had greater limb volume increase than normal-weight patients (13.3% versus 6.9%, P = 0.030). QOL improved over the first 18 months, but despite initial improvement, regional symptoms persisted long term. Type of surgery (inguinal or ilio-inguinal lymphadenectomy) had no demonstrably significant effect on limb volume (9.9% versus 13.4%, P = 0.35), QOL (P = 0.68), or regional symptoms (P = 0.65). There was no difference in overall survival between inguinal and ilio-inguinal lymphadenectomy [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.40-1.40, P = 0.43]. CONCLUSIONS: Inguinal lymphadenectomy for melanoma is a potentially morbid procedure with significant increases in limb volume. Patients report reasonable QOL but may have ongoing regional symptoms. Overweight/obesity is associated with poorer QOL, increased limb volume, and regional symptoms.
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Ilion/cirugía , Conducto Inguinal/cirugía , Ganglios Linfáticos/cirugía , Melanoma/cirugía , Calidad de Vida , Adulto , Anciano , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Ilion/patología , Conducto Inguinal/patología , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Melanoma/patología , Persona de Mediana Edad , Morbilidad , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The non-operative management of splenic injury in children is recommended widely, and is possible in over 95 per cent of episodes. Practice appears to vary between centres. METHODS: The Trauma Audit and Research Network (TARN) database was interrogated to determine the management of isolated paediatric splenic injuries in hospitals in England and Wales. Rates of non-operative management, duration of hospital stay, readmission and mortality were recorded. Management in paediatric surgical hospitals was compared with that in adult hospitals. RESULTS: Between January 2000 and December 2015 there were 574 episodes. Children treated in a paediatric surgical hospital had a 95·7 per cent rate of non-operative management, compared with 75·5 per cent in an adult hospital (P < 0·001). Splenectomy was done in 2·3 per cent of children in hospitals with a paediatric surgeon and in 17·2 per cent of those treated in an adult hospital (P < 0·001). There was a significant difference in the rate of non-operative management in children of all ages. There was some improvement in non-operative management in adult hospitals in the later part of the study, but significant ongoing differences remained. CONCLUSION: The management of children with isolated splenic injury is different depending on where they are treated. The rate of non-operative management is lower in hospitals without a paediatric surgeon present.
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Bazo/lesiones , Heridas no Penetrantes/terapia , Adolescente , Niño , Preescolar , Inglaterra , Femenino , Disparidades en Atención de Salud , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Tiempo de Internación/estadística & datos numéricos , Masculino , Esplenectomía/estadística & datos numéricos , Centros Quirúrgicos/estadística & datos numéricos , GalesRESUMEN
A series of polyampholytes based on different molar ratios on N, N-dimethylaminopropyl methacrylamide (DMAPMA), acrylic acid (AA), and optionally, N- tert-butylacrylamide ( t-BuAAm), were prepared by free radical copolymerization, and tested as DMSO-free cryoprotective agents for 3T3 fibroblast cells by using a standard freeze-rethaw protocol. Polybetaines prepared by reaction of DMAPMA homo and copolymers with 1,3-propane sultone were used as additional controls. Results showed strong effects of copolymer composition, molecular weight, polymer and NaCl concentrations, on post-thaw cell viability. Binary (DMAPMA/AA) copolymers showed best post-thaw cell viability of 70% at a 30/70 mol % ratio of DMAPMA/AA, which increased to 90% upon introduction of 9 mol % t-BuAAm while maintaining the 30/70 mol % cation/anion ratio. The use of acrylamide linkages in DMAPMA ensures absence of hydrolytic loss of cationic side chains. These polyampholytes were found to decrease ice crystal size and to form a polymer-rich, ice-free layer around cells, reducing damage from intercellular ice crystals during both freezing and thawing steps. These polyampholytes also dehydrate cells during freezing, which helps protect cells from intracellular ice damage. While cell viability immediately after thawing was high, subsequent culturing revealed poor attachment and long-term viability, which is attributed to residual cell damage from intracellular ice formation. Addition of 2 wt % DMSO or 1% BSA to the polymer-based freeze medium was found to mitigate this damage and result in post-thaw viabilities matching those achieved with 10 wt % DMSO.
RESUMEN
Skin conditions are common in adolescence and impart considerable psychological burden. The Department of Health has identified the specialized needs of adolescents transitioning from paediatric to adult services as a priority, yet there are few dedicated transitional clinics in the UK providing appropriate psychosocial support. We have established a monthly Teenage and Young Adult (TYA) dermatology clinic dedicated to managing teenagers and young adults with skin disease alongside open-access psychological support. Demographic data and Teenagers' Quality of Life Index (T-QoL) measures were recorded for all patients in 2016. To evaluate patient experience, two online surveys were conducted. Statistically significant improvements in the T-QoL were recorded for patients with the most common skin condition (eczema) attending for repeat assessment by the psychologist. Patients reported high satisfaction rates in both patient experience surveys. These results demonstrate that specialized adolescent care both is well received and can improve outcomes for these patients.
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Servicios de Salud del Adolescente , Dermatología , Satisfacción del Paciente/estadística & datos numéricos , Psicoterapia , Calidad de Vida , Enfermedades de la Piel/psicología , Acné Vulgar , Adolescente , Niño , Eccema , Humanos , Psoriasis , Encuestas y Cuestionarios , Transición a la Atención de Adultos , Reino Unido , Adulto JovenRESUMEN
PURPOSE: This study aimed to compare support persons of haematological cancer survivors living in rural and urban areas in regard to the type, prevalence and factors associated with reporting unmet needs. METHODS: One thousand and four (792 urban and 193 rural) support persons of adults diagnosed with haematological cancer were recruited from five Australian state population-based cancer registries. Participants completed the Support Person Unmet Needs Survey (SPUNS) that assessed the level of unmet needs experienced over the past month across six domains. RESULTS: Overall, 66% of support persons had at least one 'moderate, high or very high' unmet need and 24% (n = 182) reported having multiple (i.e. 6 or more) 'high/very high' unmet needs in the past month. There were no significant differences between rural and urban support persons in the prevalence of multiple unmet needs or mean total unmet needs scores. There were however significant differences in the types of 'high/very high' unmet needs with support persons living in rural areas more likely to report finance-related unmet needs. Support persons who indicated they had difficulty paying bills had significantly higher odds of reporting multiple 'high/very high' unmet needs. CONCLUSIONS: This is the first large, population-based study to compare the unmet needs of support persons of haematological cancer survivors living in rural and urban areas. Findings confirm previous evidence that supporting a person diagnosed with haematological cancer correlates with a high level of unmet needs and highlight the importance of developing systemic strategies for assisting support persons, especially in regard to making financial assistance and travel subsidies known and readily accessible to those living in rural areas.
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Neoplasias Hematológicas/terapia , Australia/epidemiología , Estudios Transversales , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Población Rural , Encuestas y Cuestionarios , Sobrevivientes , Población UrbanaRESUMEN
Although single-center and cross-sectional studies have suggested a modest impact of liver donation on donor psychological well-being, few studies have assessed these outcomes prospectively among a large cohort. We conducted one of the largest, prospective, multicenter studies of psychological outcomes in living liver donors within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL-2) consortium. In total, 271 (91%) of 297 eligible donors were interviewed at least once before donation and at 3, 6, 12, and 24 mo after donation using validated measures. We found that living liver donors reported low rates of major depressive (0-3%), alcohol abuse (2-5%), and anxiety syndromes (2-3%) at any given assessment in their first 2 years after donation. Between 4.7% and 9.6% of donors reported impaired mental well-being at various time points. We identified significant predictors for donors' perceptions of being better people and experiencing psychological growth following donation, including age, sex, relationship to recipient, ambivalence and motivation regarding donation, and feeling that donation would make life more worthwhile. Our results highlight the need for close psychosocial monitoring for those donors whose recipients died (n=27); some of those donors experienced guilt and concerns about responsibility. Careful screening and targeted, data-driven follow-up hold promise for optimizing psychological outcomes following this procedure for potentially vulnerable donors.
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Trastorno Depresivo Mayor/psicología , Trasplante de Hígado/psicología , Donadores Vivos/psicología , Calidad de Vida , Adulto , Estudios Transversales , Trastorno Depresivo Mayor/epidemiología , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
Because results from single-center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2) consortium. Among other initiatives, A2ALL-2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated-measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one-third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out-of-pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.
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Trasplante de Hígado , Donadores Vivos/psicología , Factores Socioeconómicos , Obtención de Tejidos y Órganos/economía , Adulto , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Apoyo Social , Encuestas y CuestionariosRESUMEN
In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.
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Antineoplásicos/uso terapéutico , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/tratamiento farmacológico , Tomografía de Emisión de Positrones/normas , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tomografía Computarizada por Rayos X/normas , Antineoplásicos/efectos adversos , Consenso , Medios de Contraste/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Determinación de Punto Final , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) is increasingly being used for juxtarenal aortic aneurysms. The aim of this study was to review long-term results and assess the importance of changing stent-graft design on outcomes. METHODS: This was a retrospective review of all patients who underwent FEVAR within a single unit over 12 years (February 2003 to December 2015). Kaplan-Meier analysis of survival, and freedom from target vessel loss, aneurysm expansion, graft-related endoleak and secondary intervention was performed. Comparison between outcomes of less complex grafts (fewer than 3 fenestrations) and more complex grafts (3 or 4 fenestrations) was undertaken. RESULTS: Some 173 patients underwent FEVAR; median age was 76 (i.q.r. 70-79) years and 90·2 per cent were men. Median aneurysm diameter was 63 (59-71) mm and median follow-up was 34 (16-50) months. The adjusted primary technical operative success rate was 95·4 per cent. The in-hospital mortality rate was 5·2 per cent; there was no known aneurysm-related death during follow-up. Median survival was 7·1 (95 per cent c.i. 5·2 to 8·1) years and overall survival was 60·1 per cent (104 of 173). There was a trend towards an increasing number of fenestrations in the graft design over time. In-hospital mortality appeared higher when more complex stent-grafts were used (8 versus 2 per cent for stent-grafts with 3-4 versus fewer than 3 fenestrations; P = 0·059). Graft-related endoleaks were more common following deployment of stent-grafts with three or four fenestrations (12 of 90 versus 6 of 83; P < 0·001). CONCLUSION: Fenestrated endovascular aneurysm repair for juxtarenal aneurysm is associated with few aneurysm-related deaths in the long term. Significant numbers of secondary interventions are required, but the majority of these can be performed using an endovascular approach.
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Aneurisma de la Aorta Abdominal/cirugía , Procedimientos Endovasculares/métodos , Stents/tendencias , Cuidados Posteriores , Anciano , Aneurisma de la Aorta Abdominal/mortalidad , Prótesis Vascular/tendencias , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/mortalidad , Tiempo de Internación , Masculino , Tempo Operativo , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Diseño de Prótesis/mortalidad , Diseño de Prótesis/tendencias , Estudios Retrospectivos , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/metabolismo , Análisis de SupervivenciaRESUMEN
Health providers may not be aware of their patients' needs or preferences, and patients reluctant to raise their concerns. Consequently, the first step in ensuring quality of care is to ask the patient about the care that they would like. A cross-sectional sample of 244 medical oncology outpatients were surveyed about provider-asking behaviours across six dimensions of patient-centred care defined by the Institute of Medicine. Specifically, were patients asked by clinic staff at the treatment centre about their physical and emotional symptoms, information needs to enable decision-making, preferences for involvement in decision-making, involvement of family and friends, and appointment scheduling. Patients were significantly (Cochran's χ2 (9) = 122.541, P < 0.001) less likely to be asked about emotional symptoms (35% infrequently asked), preferences for the involvement of family and friends (25% infrequently asked), and preferences for involvement in medical decision-making (23% infrequently asked). Only a minority of patients were infrequently asked about their treatment-related information needs (8%), physical symptoms (13% pain, 14% fatigue) and preferences for appointment scheduling (13%). Younger age, not Australian born and greater educational qualifications were associated with being infrequently asked. Improvements to care delivery can be made if clinic staff were to more regularly elicit patient's emotional symptoms, and their preferences for the involvement of family/friends and participation in medical decision-making.
Asunto(s)
Neoplasias/terapia , Atención Dirigida al Paciente/normas , Calidad de la Atención de Salud/normas , Adolescente , Adulto , Anciano , Atención Ambulatoria/normas , Australia , Instituciones Oncológicas , Estudios Transversales , Atención a la Salud/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Participación del Paciente , Prioridad del Paciente , Apoyo Social , Adulto JovenRESUMEN
Esophageal replacement by colonic interposition is an uncommon procedure. This study sought to identify the frequency of this operation in England, identify techniques and associated problems, and also assess health-related quality of life (HR QOL) from the two largest centers performing this procedure. Hospital Episode Statistics were used to identify patients and centers undertaking colon interposition between March 2001 and March 2015. An online survey of UK consultants discussed methods and experience. HR QOL was assessed using the Short Form 36(SF-36v2) with additional gastrointestinal questions. Hospital Episode Statistics identified 328 interpositions (22 in pediatric hospitals). The two highest volume units did 42 and 45 operations, respectively. Thirty-four surgeons (79% response rate) replied to the survey. Fifty-two percent preferred to use the left colon with 81% preferring a substernal placement. The HR QOL survey was performed on 24 patients with a median of 3 years after surgery (ranging from 9 months to 10 years) from the two largest centers and a 56% response rate. Five patients had physical QOL scores above population average and 10 had mental scores above population average. All patients had early satiety, 20 described dysphagia, and 18 regularly took antireflux medication. There was an estimated mean loss of 13.1% body weight (10.6 kg) postoperatively and three patients still relied on a feeding tube for nutrition after an average of 3 years. Colon interposition results in an acceptable long-term QOL. Few centers regularly perform this operation, and centralizing to high-volume centers may lead to better outcomes.
Asunto(s)
Colon/cirugía , Colon/trasplante , Enfermedades del Esófago/cirugía , Esofagectomía/métodos , Esófago/cirugía , Calidad de Vida , Anciano , Anastomosis Quirúrgica/métodos , Niño , Preescolar , Inglaterra , Esofagectomía/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Auditoría Médica , Persona de Mediana Edad , Periodo Posoperatorio , Encuestas y CuestionariosRESUMEN
High flows of sulfur through wastewater treatment plants (WWTPs) may cause noxious gaseous emissions, corrosion of infrastructure, inhibit wastewater microbial communities, or contribute to acid rain if the biosolids or biogas is combusted. Yet, sulfur is an important agricultural nutrient and the direct application of biosolids to soils enables its beneficial re-use. Flows of sulfur throughout the biosolids processing of six WWTPs were investigated to identify how they were affected by biosolids processing configurations. The process of tracking sulfur flows through the sites also identified limitations in data availability and quality, highlighting future requirements for tracking substance flows. One site was investigated in more detail showing sulfur speciation throughout the plant and tracking sulfur flows in odour control systems in order to quantify outflows to air, land and ocean sinks. While the majority of sulfur from WWTPs is removed as sulfate in the secondary effluent, the sulfur content of biosolids is valuable as it can be directly returned to soils to combat the potential sulfur deficiencies. Biosolids processing configurations, which focus on maximising solids recovery, through high efficiency separation techniques in primary sedimentation tanks, thickeners and dewatering centrifuges retain more sulfur in the biosolids. However, variations in sulfur loads and concentrations entering the WWTPs affect sulfur recovery in the biosolids, suggesting industrial emitters, and chemical dosing of iron salts are responsible for differences in recovery between sites.