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AIMS: Patient-reported outcomes measures (PROMs) are an increasingly recognised end point of radiotherapy studies. We hypothesised that the baseline PROMs score is the strongest predictor for acute and late scores after treatment. We assessed the strength of association of baseline MD Anderson Symptom Inventory (MDASI) scores, alongside other known factors for patient- or clinician-reported toxicity, with acute (6-week) and late (12-month) scores in head and neck cancer (HNC) patients following (chemo)radiotherapy. MATERIALS AND METHODS: This was a retrospective analysis of longitudinal MDASI scores for 247 patients receiving (chemo)radiotherapy for HNC via multivariable linear regression. The factors investigated were: baseline symptom score, age, sex, concurrent chemotherapy, disease stage, radiotherapy fractionation, prior definitive surgery and performance status. Patients with a baseline score >4 in any item were defined as symptomatic in that category. RESULTS: Patients rated symptomatic for an MDASI item pre-treatment on average reported statistically (P < 0.0005) and clinically (>-1.5) significant reductions in scores 6 weeks and 12 months after (chemo)radiotherapy for all considered sub-items except taste, dryness of mouth and problems with teeth. Conversely patients asymptomatic at baseline reported a worsening of scores at both time points. Other investigated factors showed little association with changes in MDASI scores following treatment. CONCLUSIONS: Our data show that baseline MDASI scores are strongly associated with patient-reported toxicity 6 weeks and 12 months after (chemo)radiotherapy for HNC. Patients who are symptomatic at baseline can experience an early and durable benefit from treatment. This finding can inform discussions with patients before therapy and has implications for use of PROMs scores for the assessment of toxicity in randomised trials.
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Neoplasias de Cabeza y Cuello , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Medición de Resultados Informados por el Paciente , Estudios RetrospectivosRESUMEN
AIMS: Careful management of a patient's nutritional status during and after treatment for head and neck squamous cell cancers (HNSCC) is crucial for optimal outcomes. The aim of this study was to develop a model for stratifying a patient's risk of requiring reactive enteral feeding through a nasogastric tube during radiotherapy for HNSCC, based on clinical and treatment-related factors. MATERIALS AND METHODS: A cohort of consecutive patients treated with definitive (chemo)radiotherapy for HNSCC between January 2016 and January 2018 was identified in the institutional electronic database for retrospective analysis. Patients requiring enteral feeding pretreatment were excluded. Clinical and treatment data were obtained from prospectively recorded electronic clinical notes and planning software. RESULTS: Baseline patient characteristics and tumour-related parameters were captured for 225 patients. Based on the results of the univariate analysis and using a stepwise backwards selection process, clinical and dosimetric variables were selected to optimise a clinically predictive multivariate model, fitted using logistic regression. The parameters found to affect the probability, P, of requiring a nasogastric feeding tube for >4 weeks in our clinical multivariate model were: tumour site, tumour stage (early T0/1/2 stage versus advanced T3/T4 stage), chemotherapy drug (none versus any drug) and mean dose to the contralateral parotid gland. A scoring model using the regression coefficients of the selected variables in the clinical multivariate model achieved an area under the curve (AUC) of 0.745 (95% confidence interval 0.678-0.812), indicating good discriminative performance. Internal validation of the model involved splitting the dataset 80:20 into training and test datasets 10 times and assessing differences in AUC of the model fitted to these. CONCLUSIONS: We developed an easy-to-use prediction model based on both clinical and dosimetric parameters, which, once externally validated, can lead to more personalised treatment planning and inform clinical decision-making on the appropriateness of prophylactic versus reactive enteral feeding.
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Nutrición Enteral , Neoplasias de Cabeza y Cuello , Quimioradioterapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Intubación Gastrointestinal , Estudios RetrospectivosRESUMEN
PURPOSE: For oropharynx squamous cell carcinoma (OPSCC) this study aimed to: (i) compare 5-year overall survival (OS) stratification by AJCC/UICC TNM versions 7 (TNMv7) and 8 (TNMv8), (ii) determine whether changes to T and N stage groupings improve prognostication and (iii) develop and validate a model incorporating additional clinical characteristics to improve 5-year OS prediction. MATERIAL AND METHODS: All OPSCC treated with curative-intent at our institution between 2011 and 2017 were included. The primary endpoint was 5-year OS. Survival curves were produced for TNMv7 and TNMv8. A three-way interaction between T, N stage and p16 status was evaluated for improved prognostication. Cox proportional hazards modelling was used to derive a new predictive model. RESULTS: Of 750 OPSCC cases, 574 (77%) were p16-positive. TNMv8 was more prognostic than TNMv7 (concordance probability estimate [CPE]⯱â¯SEâ¯=â¯0.72⯱â¯0.02 vs 0.53⯱â¯0.02). For p16-positive disease, TNMv8 discriminated stages II vs I (HR 2.32, 95% CI 1.47-3.67) and III vs II (HR 1.75, 95% CI 1.13-2.72). For p16-negative disease, TNMv7 and TNMv8 demonstrated poor hazard discrimination. Different T, N stage and p16-status combinations did not improve prognostication after adjusting for other factors (CPEâ¯=â¯0.79 vs 0.79, pâ¯=â¯0.998). A model for p16-positive and p16-negative OPSCC including additional clinical characteristics improved 5-year OS prediction beyond TNMv8 (c-index 0.76⯱â¯0.02). CONCLUSIONS: TNMv8 is superior to TNMv7 for p16-positive OPSCC, but both performed poorly for p16-negative disease. A novel model incorporating additional clinical characteristics improved 5-year OS prediction for both p16-positive and p16-negative disease.
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Neoplasias Orofaríngeas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , PronósticoRESUMEN
INTRODUCTION: Auto contouring models help consistently define volumes and reduce clinical workload. This study aimed to evaluate the cross acquisition of a Magnetic Resonance (MR) deep learning auto contouring model for organ at risk (OAR) delineation in head and neck radiotherapy. METHODS: Two auto contouring models were evaluated using deep learning contouring expert (DLCExpert) for OAR delineation: a CT model (modelCT) and an MR model (modelMRI). Models were trained to generate auto contours for the bilateral parotid glands and submandibular glands. Auto-contours for modelMRI were trained on diagnostic images and tested on 10 diagnostic, 10 MR radiotherapy planning (RTP), eight MR-Linac (MRL) scans and, by modelCT, on 10 CT planning scans. Goodness of fit scores, dice similarity coefficient (DSC) and distance to agreement (DTA) were calculated for comparison. RESULTS: ModelMRI contours improved the mean DSC and DTA compared with manual contours for the bilateral parotid glands and submandibular glands on the diagnostic and RTP MRs compared with the MRL sequence. There were statistically significant differences seen for modelMRI compared to modelCT for the left parotid (mean DTA 2.3 v 2.8 mm), right parotid (mean DTA 1.9 v 2.7 mm), left submandibular gland (mean DTA 2.2 v 2.4 mm) and right submandibular gland (mean DTA 1.6 v 3.2 mm). CONCLUSION: A deep learning MR auto-contouring model shows promise for OAR auto-contouring with statistically improved performance vs a CT based model. Performance is affected by the method of MR acquisition and further work is needed to improve its use with MRL images.
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Aprendizaje Profundo , Neoplasias de Cabeza y Cuello , Cabeza , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Espectroscopía de Resonancia Magnética , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
AIM: To determine the feasibility of semi-quantitative haemodynamic parameters derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to assess liver fibrosis. MATERIALS AND METHODS: Seventy-five patients with Child's A classification (males/females=24/51; average age, 58 years; range, 30-80 years) received DCE-MRI 3 days prior to hepatectomy. Semi-quantitative haemodynamic parameters, including the wash-in slope, wash-out slope, and time-to-peak, were calculated from DCE-MRI data. Liver fibrosis of the resected non-tumour liver was graded pathologically from F0 (no fibrosis) to F6 (cirrhosis) in the regions corresponding to those assessed by DCE-MRI. RESULTS: The wash-out slope showed higher interobserver and intra-observer reliabilities than the wash-in slope and time-to-peak. There was a significant positive correlation between the wash-out slope and pathological grade of fibrosis (Spearman's correlation coefficient: r=0.5331, p<0.0001). The area under the receiver operating characteristic curve was 0.8066 when using the wash-out slope to differentiate cirrhosis (grade F6) from non-cirrhosis (grades F0-5). Using the cut-off point that maximised specificity, the sensitivity was 62.07%, specificity was 91.30%, positive predictive value was 81.81%, negative predictive value was 79.25%, and accuracy was 80%. CONCLUSIONS: The wash-out slope derived from DCE-MRI might be potentially useful in assessing liver cirrhosis in patients with Child's A classification before hepatectomy.
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Hepatectomía , Cirrosis Hepática/patología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Medios de Contraste , Estudios de Factibilidad , Femenino , Humanos , Cirrosis Hepática/cirugía , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Cuidados Preoperatorios/métodosRESUMEN
A dynamic metal-organic framework that consists of d-champhorate-based homochiral protuberant-grid-type networks can successively participate in gate-opening and closing processes for many cycles, which were triggered by the stimuli of the adsorption and desorption of CO2 to highly and specifically recognize CO2 over N2 and H2 with a high CO2 uptake of 90 mg g-1 under 35 bar at 298 K. It is highly thermally stable and the structure remains intact at least for ten reversible gate-opening and -closing processes. Thus, it is a potential candidate for industrial CO2 capture and facile release.
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AIMS: Treatment for head and neck cancers using definitive radiotherapy, with or without chemotherapy, is associated with significant acute toxicity. Our aim was to assess 90 day mortality after radical radiotherapy. A further aim was to identify patient, tumour or treatment factors associated with early death after treatment and whether these could be used to predict outcomes. MATERIALS AND METHODS: In total, 1116 patients with squamous cell pharyngeal and larynx cancer between January 2011 and December 2015 were included. Patients with T1 larynx cancer were excluded. Patients were treated using radical radiotherapy, with or without chemotherapy. Ninety day mortality was calculated using survival of less than 135 days from the planned start date for radical radiotherapy, to include early deaths during and up to 90 days after treatment. RESULTS: Overall, 90 day mortality was 4.7%. Among the subgroup of patients treated with concurrent platinum chemotherapy, the 90 day mortality rate was 0.4%. Overall survival at 1, 3 and 5 years was 84%, 62% and 53%, respectively. Factors associated with a higher risk of early death included performance status > 1, haemoglobin <100 g/l, weight < 60 kg, age > 80 years and presence of multiple comorbidities. CONCLUSION: We report excellent crude overall survival rates among our radically treated cohort of head and neck cancer patients. Several factors were associated with an increased risk of death within 90 days of completion of radical head and neck radiotherapy. Given the potential severe acute effects and the impact on patient quality of life associated with radical head and neck radiotherapy, this information is helpful to inform treatment-related discussions with patients.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Muerte , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Análisis de SupervivenciaRESUMEN
AIM: To determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: This was a phase 2, open-label, randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab (combination) vs cetuximab monotherapy (control) in cetuximab-naïve patients with R/M SCCHN who progressed on 1 cytotoxic regimen. Crossover to combination was permitted after progression. RESULTS: Objective response rate in both arms was 5.7% (95% CI 1.2-15.7%) by independent assessment. Disease control was 37.7% for patients on combination (24.8-52.1%) and 43.4% on control (29.8-57.7%). Neither independent nor investigator assessments showed significant differences between study arms. Median progression-free survival was 1.5 months (1.3-2.6) for patients on combination, and 1.9 months (1.5-2.9) on control. The most frequent adverse events in the combination arm were rash (29.6%), acneiform dermatitis (22.2%), and injection site reactions (20.4%). Grade 3/4 dyspnea and hypokalemia were more frequent with cetuximab monotherapy (7.5% and 5.7% vs 1.9% each, respectively), and grade 3/4 respiratory failure and disease progression were more frequent with combination (5.6% each vs 1.9% each). CONCLUSION: EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cetuximab , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oligonucleótidos/administración & dosificación , Oligonucleótidos/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
Human diseases of impaired ribosome biogenesis resulting from disruption of rRNA biosynthesis or loss of ribosomal components are collectively described as 'ribosomopathies'. Treacher Collins syndrome (TCS), a representative human ribosomopathy with craniofacial abnormalities, is attributed to mutations in the tcof1 gene that has a homologous gene called nopp140. Previous studies demonstrated that the dao-5 (dauer and aged animal overexpression gene 5) of Caenorhabditis elegans is a member of nopp140 gene family and plays a role in nucleogenesis in the early embryo. Here, we established a C. elegans model for studying Nopp140-associated ribosomopathy. A null dao-5 mutant ok542 with a semi-infertile phenotype showed a delay in gonadogenesis, as well as a higher incidence of germline apoptosis. These phenotypes in dao-5(ok542) are likely resulted from inefficient rDNA transcription that was observed by run-on analyses and chromatin immunoprecipitation (ChIP) assays measuring the RNA Pol I occupancy on the rDNA promoter. ChIP assays further showed that the modifications of acetylated histone 4 (H4Ac) and dimethylation at the lysine 9 of histone 3 (H3K9me2) around the rDNA promoter were altered in dao-5 mutants compared with the N2 wild type. In addition, activated CEP-1 (a C. elegans p53 homolog) activity was also linked to the loss of DAO-5 in terms of the transcriptional upregulation of two CEP-1 downstream effectors, EGL-1 and CED-13. We propose that the dao-5 mutant of C. elegans can be a valuable model for studying human Nopp140-associated ribosomopathy at the cellular and molecular levels.
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Apoptosis , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , ADN Ribosómico/genética , Proteínas de Unión al ADN/genética , Células Germinativas/citología , Mutación/genética , Transcripción Genética , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/citología , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/metabolismo , Nucléolo Celular/metabolismo , Cromatina/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Secuencia Conservada , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Genes de Helminto , Células Germinativas/metabolismo , Gónadas/anomalías , Gónadas/metabolismo , Histonas/metabolismo , Humanos , Modelos Biológicos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas/genética , Estructura Terciaria de Proteína , ARN Polimerasa I/metabolismo , Activación Transcripcional , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: Radiotherapy for T1 glottic cancer is commonly delivered using a lateral parallel opposed pair of megavoltage photon fields. There is increasing reported evidence of cerebrovascular events due to radiation-induced carotid stenosis. An alternative field arrangement is to use an anterior oblique technique. This study compares the carotid dosimetry between the two techniques and reviews the evidence for the risk of radiation-induced vascular events. METHODS: The radiotherapy plans of 10 patients with T1 glottic cancer treated with an anterior oblique technique were examined for carotid dose. Alternative plans were then created using a parallel opposed pair of fields and the dose to the carotids compared. All patients received 50 Gy in 16 fractions treating once daily, for 5 days in a week. RESULTS: The average of the mean dose to the carotids with the anterior oblique technique was 21 Gy compared with 37 Gy using the lateral parallel opposed pair arrangement (p < 0.0001). CONCLUSION: An anterior oblique field arrangement for the treatment of T1 glottic cancer results in a significantly lower radiation dose to the carotid arteries, which may be clinically important in terms of reducing the risk of cerebrovascular events in long-term survivors. ADVANCES IN KNOWLEDGE: Although the anterior oblique technique for treating early glottic cancers is well described, and it is predictable that the dose received by the carotid arteries should be lower with this technique, to our knowledge this is the first study to quantify that reduction in dose with a series of patients.
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Arterias Carótidas/efectos de la radiación , Glotis/efectos de la radiación , Neoplasias Laríngeas/radioterapia , Femenino , Humanos , Masculino , Radiometría , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
AIMS: Nasopharyngeal cancer (NPC) is relatively uncommon, especially in the Western world. We report our single institution experience of 20 years of data in 128 patients with NPC, including responses to different treatment modalities and outcomes by histological subtype. MATERIALS AND METHODS: NPC patients presenting from 1992 to 2005 were located on the cancer registry database. Demographic data included age, gender, length of presenting symptoms and stage. World Health Organization classification (2005) was used for histological subtyping. The date of recurrence and survival outcomes were analysed using Kaplan-Meier curves. RESULTS: Presentation data were analysed from 128 patients; the survival analysis included 123 patients. The median age at presentation was 57.7 years. Stage III and IV presentation rates were 34 and 38%, respectively. The most common presenting symptom was a palpable neck lump (55%) and the median duration of symptoms was 16 weeks. Forty-eight patients received radiotherapy alone and 75 received chemoradiotherapy. The median overall survival in chemoradiotherapy patients was 80.3 months versus 28.5 months with radiotherapy alone (P = 0.003). A significant difference was also seen with recurrence-free survival (RFS) (P = 0.017). Type 1 keratinising carcinoma had a significantly worse overall survival (P = 0.04) and a similar but non-statistically significant trend was seen for RFS (P = 0.051). The multivariate analysis for overall survival showed that histological subtype (hazard ratio 2.7, 95% confidence interval 1.3-5.5, P = 0.034), age (hazard ratio 2.3, 95% confidence interval 1.1-4.9, P = 0.018) and N stage (hazard ratio 3.7, 95% confidence interval 1.4-9.4, P = 0.024) were prognostic factors. CONCLUSIONS: We present the first large-scale, single-centre retrospective review of NPC in a UK-based population. Demographic data were similar to that in other Western populations, with a significantly worse survival outcome in the keratinising group. Further prospective study of outcome in Western populations accounting for newer radiotherapy techniques such as intensity-modulated radiotherapy and dose escalation, particularly in the keratinising population who were more likely to present with an isolated local recurrence, is recommended.
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Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The aims of this cross-sectional, case-controlled, observational study were to examine attitudes toward menstruation in female patients with schizophrenia or schizoaffective disorder and in a control group, and to explore the associations between attitudes toward menstruation and psychopathology, menstrual regularity during antipsychotic treatment, and menstrual distress symptoms. METHODS: Fifty-eight patients treated with anti-psychotic medications for at least the previous 6 months were placed in irregular (irregular menstrual cycle) (n = 31) and regular (regular menstrual cycle) (n = 27) groups. Sixty-two, age-matched, healthy female participants with regular menstrual cycles were enrolled as a control group. Psychopathology was assessed by psychiatrists using the Positive and Negative Syndrome Scale (PANSS). The Menstrual Attitude Questionnaire (MAQ) was used to assess attitudes toward menstruation, and symptom checklists based on the Moos Menstruation Distress Questionnaire (MMDQ) were used to assess menstrual distress symptoms. RESULTS: Patients with psychotic disorders (both irregular and regular groups) had more negative attitudes toward menstruation than the control group. In the Schizophrenia group, there was no association between the severity of psychotic symptoms and their influence on attitudes toward menstruation. Moreover, regular menstrual cycles during antipsychotic treatment and fewer menstrual distress symptoms were the two main predictors for more positive attitudes toward menstruation in the patient group. CONCLUSION: This is one of the first studies to explore the relationship between psychotic symptoms and attitudes toward menstruation. The findings provide more support for the assumption that attitudes toward menstruation are derived from a woman's perception of her bodily experience rather than a psychiatric disorder.
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Actitud , Trastornos de la Menstruación/psicología , Menstruación/psicología , Trastornos Psicóticos/psicología , Psicología del Esquizofrénico , Adolescente , Adulto , Antipsicóticos/uso terapéutico , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: A solvent/detergent (S/D) treatment in a medical device has been developed for pathogen reduction of plasma for transfusion. Impact of S/D on bacterial growth and on the capacity of complement to kill bacteria has been investigated in this study. STUDY DESIGN AND METHODS: A pool of apheresis plasma from four donors was spiked with eight transfusion-relevant bacteria. Plasma was treated with 1% tri(n-butyl) phosphate and 1% Triton X-45 at 31°C for 90 min and then extracted by oil at 31°C for 70 min. Decomplemented plasma and Phosphate Buffer Saline were used as controls. Bacterial count was determined in samples taken immediately after spiking, or after S/D and oil treatment. Similar experiments were conducted using three individual recovered plasma donations. Bacteria growth inhibition tests were performed using discs soaked with plasma samples whether containing the S/D agents or not. RESULTS: The mean reduction factors of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae due to complement during S/D treatment were >8·75, 4·71, and 4·18 log in pooled plasma and >7·42, 2·24 and >6·08 log in individual plasmas, respectively. Bacillus cereus and Bacillus subtilis were inactivated by S/D (>7·04 and 1·60 log in pooled, and >6·06 and 2·39 in individual plasmas, respectively). Staphylococcus aureus, Staphylococcus epidermidis and Enterobacter cloacae did not multiply during S/D treatment of plasma. Growth inhibition tests revealed an inhibition of three gram-negative bacteria by complement and all gram-positive by S/D. CONCLUSION: The S/D treatment of plasma does not alter the bactericidal activity of complement, and inactivates some gram-positive bacteria.
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Bacterias/efectos de los fármacos , Detergentes/farmacología , Plasma/efectos de los fármacos , Reacción a la Transfusión , Bacterias/crecimiento & desarrollo , Transfusión Sanguínea/normas , Proteínas del Sistema Complemento , Bacterias Gramnegativas , Humanos , Plasma/microbiología , Solventes/químicaRESUMEN
AIM: The aim of this study was to determine whether gadolinium-enhanced T1-weighted magnetic resonance (MR) sequence is beneficial in the preoperative assessment of tumour and nodal staging in patients with primary rectal cancer. METHOD: Eighty-eight patients with primary rectal cancer underwent preoperative MR imaging, followed by surgical resection. Two radiologists independently reviewed (i) T2-weighted MR images (T2WI); (ii) gadolinium-enhanced T1-weighted MR images (T1 + Gd); (iii) MR combined with T2WI and T1 + Gd for the prediction of tumour and nodal stage compared with histopathologic findings as the end point. Differences in the diagnostic performance of T2WI only, T1 + Gd image only and combined T2WI and T1 + Gd MR images were analyzed by comparing areas under receiver operating characteristic curves (Az) for each reader. Interobserver agreement was also calculated. RESULTS: There was no significant difference in the Az values of T2WI only, T1 + Gd image only and combined T2WI and T1 + Gd images for the prediction of tumour staging (Az of T2WI, T1 + Gd and combined MR images for reader 1, 0.80, 0.76 and 0.85; reader 2, 0.83, 0.82 and 0.87) and nodal staging (Az for reader 1, 0.73, 0.73 and 0.81; reader 2, 0.79, 0.80 and 0.83). Interobserver agreement for the prediction of tumour staging was moderate to substantial, while only fair agreement was noted for the prediction of nodal staging. CONCLUSION: Gadolinium-enhanced T1-weighted MRI did not increase the diagnostic yield for tumour and nodal staging, and may be omitted in the MR protocol for preoperative assessment of primary rectal cancer.
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Medios de Contraste , Gadolinio , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética/métodos , Estadificación de Neoplasias/métodos , Neoplasias del Recto/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Cuidados Preoperatorios , Curva ROC , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/cirugía , Estudios RetrospectivosRESUMEN
DNA double-strand breaks (DSBs) are considered the most important type of DNA damage inflicted by ionizing radiation. The molecular mechanisms of DSB repair by nonhomologous end joining (NHEJ) have not been well studied in live mammalian cells, due in part to the lack of suitable chromosomal repair assays. We previously introduced a novel plasmid-based assay to monitor NHEJ of site-directed chromosomal I-SceI breaks. In the current study, we expanded the analysis of chromosomal NHEJ products in murine fibroblasts to focus on the error-prone rejoining of DSBs with noncomplementary ends, which may serve as a model for radiation damage repair. We found that noncomplementary ends were efficiently repaired using microhomologies of 1-2 nucleotides (nt) present in the single-stranded overhangs, thereby keeping repair-associated end degradation to a minimum (2-3 nt). Microhomology-mediated end joining was disrupted by Wortmannin, a known inhibitor of DNA-PKcs. However, Wortmannin did not significantly impair the proficiency of end joining. In contrast to noncomplementary ends, the rejoining of cohesive ends showed only a minor dependence on microhomologies but produced fivefold larger deletions than the repair of noncomplementary ends. Together, these data suggest the presence of several distinct NHEJ mechanisms in live cells, which are characterized by the degree of sequence deletion and microhomology use. Our NHEJ assay should prove a useful system to further elucidate the genetic determinants and molecular mechanisms of site-directed DSBs in living cells.
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Rotura Cromosómica/fisiología , Daño del ADN/genética , Reparación del ADN/genética , Reparación del ADN/efectos de la radiación , ADN/genética , ADN/efectos de la radiación , Fibroblastos/efectos de la radiación , Animales , Células Cultivadas , Análisis Mutacional de ADN/métodos , Ratones , Mutagénesis Sitio-Dirigida , Homología de Secuencia de Ácido NucleicoRESUMEN
Thoracic radiotherapy has an established role in the management of limited-disease small-cell lung cancer (LD SCLC). However, essential questions relating to the optimisation of thoracic radiotherapy remain unanswered, including volume of irradiation, optimal total dose, fractionation, timing and sequencing of radiation. This review highlights the need for well-designed multi-national trials aimed at the optimisation and standardisation of radiotherapy for LD SCLC.
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Carcinoma de Células Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radioterapia/métodos , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos , Dosificación Radioterapéutica , Factores de TiempoRESUMEN
We compute numerically the zero-temperature defect energy DeltaE of the vector spin glass in the limit of an infinite number of spin components m , for a range of dimensions 2< or d < or =5 . Fitting to DeltaE approximately L(theta) , where L is the system size, we obtain: theta similar to-1.54 (d=2) , theta similar to-1.04 (d=3) , theta similar to -0.67 (d=4) , and theta similar to -0.37 (d=5) . These results show that the lower critical dimension dl (the dimension where theta changes sign) is significantly higher for m=infinity than for finite m (where 2< dl <3 ).
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cabello/crecimiento & desarrollo , Hipertricosis/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Alopecia/prevención & control , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Proliferación Celular/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Gefitinib , Cabello/efectos de los fármacos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To survey UK urologists and radiation oncologists in the evaluation and treatment of localised prostate cancer in the adjuvant and salvage setting. METHODS: Postal questionnaires were mailed to 292 urologists and 98 radiation oncologists in the UK. RESULTS: In all, 188 (48%) questionnaires were returned. In total, 72/128 (56%) of the urologist respondents and 58/60 (97%) of the oncologist respondents perform routine radical prostate treatment. Among 43 (60%) of the urologist, 40 (69%) recommended adjuvant treatment, which could be radiotherapy, hormonal treatment or combined hormonal and radiation treatment. There is no significant difference between the modality of treatment recommended. The poor prognostic factors that would influence the decision to offer adjuvant treatment include a detectable postoperative PSA, seminal vesicle involvement, positive margins, Gleason score>8 and pathological T3. With regard to the choice of hormonal treatment, most urologists preferred antiandrogens, whereas most oncologists prefer lutienising hormone releasing hormone (LHRH) analogue (P=0.03). Regarding salvage treatment, there is a wide variation in the PSA threshold and number of PSA rises before initiation of investigations and treatment. Significantly more urologists recommended salvage radiotherapy (P=0.02), whereas oncologists recommended combined hormonal radiation therapy (P=0.03). There is a wide variation of practice regarding the duration of hormonal treatment, the type of investigations initiated, range of radiotherapy doses and treatment volumes. CONCLUSION: There is a wide variation in practice among UK clinicians.
Asunto(s)
Quimioterapia Adyuvante/métodos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/terapia , Hormona Liberadora de Gonadotropina/análogos & derivados , Humanos , Masculino , Pronóstico , Próstata/patología , Antígeno Prostático Específico/metabolismo , Radioterapia/métodos , Terapia Recuperativa , Sensibilidad y Especificidad , Encuestas y Cuestionarios , Factores de Tiempo , Reino UnidoRESUMEN
We consider spin glass models in which the number of spin components m is infinite. In the formulation of the problem appropriate for numerical calculations proposed by several authors, we show that the order parameter defined by the long-distance limit of the correlation functions is actually zero and there is only "quasi-long-range order" below the transition temperature. Nonetheless, there can be a finite temperature phase transition where the decay of correlations changes from exponential to power law. We also show that the spin glass transition temperature is zero in three dimensions so power-law behavior only occurs at T=0 in this case. We also argue that the order of limits, m-->infinity and N-->infinity is important, where N is the number of spins.