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1.
Rev Fish Biol Fish ; 32(4): 1035-1061, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187439

RESUMO

Billfish species (families Istiophoridae and Xiphiidae) are caught in artisanal, recreational, and commercial fisheries throughout the Western Indian Ocean region. However, data and information on the interactions among these fisheries and the ecology of billfish in the WIO are not well understood. Using an in-depth analysis of peer-reviewed articles, grey literature, observation studies, and authors' insider knowledge, we summarize the current state of knowledge on billfish fisheries in 10 countries. To describe historical and current trends, we examined fisheries statistics from governmental and non-governmental agencies, sportfishing clubs' reports, diaries of sportfishing captains, and the catch and effort databases of the Indian Ocean Tuna Commission. We highlight two key points. First, billfish fisheries in the Western Indian Ocean are highly diverse, comprising two distinct segments-coastal and oceanic. However, data are poor for most countries with significant gaps in information especially for sport and artisanal fisheries. Second, the evidence assembled showed that billfish species have immense social, cultural, and economic value. Swordfish are targeted by both large-scale and semi-industrial fisheries, while other billfish species, particularly marlin, are highly sought after by sport fisheries in most countries. Our paper provides a comprehensive review of billfish fisheries and available information in the context of the WIO underscoring the need to strengthen data collection and reporting, citizen science, and collaborative sustainable development and management of billfish. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-022-09725-8.

2.
Artif Intell Med ; 117: 102111, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34127240

RESUMO

INTRODUCTION: Thanks to improvement of care, cancer has become a chronic condition. But due to the toxicity of treatment, the importance of supporting the quality of life (QoL) of cancer patients increases. Monitoring and managing QoL relies on data collected by the patient in his/her home environment, its integration, and its analysis, which supports personalization of cancer management recommendations. We review the state-of-the-art of computerized systems that employ AI and Data Science methods to monitor the health status and provide support to cancer patients managed at home. OBJECTIVE: Our main objective is to analyze the literature to identify open research challenges that a novel decision support system for cancer patients and clinicians will need to address, point to potential solutions, and provide a list of established best-practices to adopt. METHODS: We designed a review study, in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, analyzing studies retrieved from PubMed related to monitoring cancer patients in their home environments via sensors and self-reporting: what data is collected, what are the techniques used to collect data, semantically integrate it, infer the patient's state from it and deliver coaching/behavior change interventions. RESULTS: Starting from an initial corpus of 819 unique articles, a total of 180 papers were considered in the full-text analysis and 109 were finally included in the review. Our findings are organized and presented in four main sub-topics consisting of data collection, data integration, predictive modeling and patient coaching. CONCLUSION: Development of modern decision support systems for cancer needs to utilize best practices like the use of validated electronic questionnaires for quality-of-life assessment, adoption of appropriate information modeling standards supplemented by terminologies/ontologies, adherence to FAIR data principles, external validation, stratification of patients in subgroups for better predictive modeling, and adoption of formal behavior change theories. Open research challenges include supporting emotional and social dimensions of well-being, including PROs in predictive modeling, and providing better customization of behavioral interventions for the specific population of cancer patients.


Assuntos
Inteligência Artificial , Ciência de Dados , Neoplasias , Feminino , Humanos , Masculino , Neoplasias/terapia , Qualidade de Vida
3.
J Dent Res ; 100(8): 824-832, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33655783

RESUMO

Although a potential link between periodontitis and cardiorespiratory fitness might provide a reasonable explanation for effects of tooth-related alterations seen on cardiometabolic diseases, evidence is currently limited. Thus, we investigated the association between clinically assessed periodontitis and cardiopulmonary exercise testing (CPET). Data from 2 independent cross-sectional population-based studies (5-y follow-up of the Study of Health in Pomerania [SHIP-1; N = 1,639] and SHIP-Trend-0 [N = 2,439]) were analyzed. Participants received a half-mouth periodontal examination, and teeth were counted. CPET was based on symptom limited-exercise tests on a bicycle ergometer. Associations of periodontitis parameters with CPET parameters were analyzed by confounder-adjusted multivariable linear regression. In the total sample, mean pocket probing depth (PPD), mean clinical attachment levels, and number of teeth were consistently associated with peak oxygen uptake (peakVO2) and exercise duration in both studies, even after restriction to cardiorespiratory healthy participants. Statistically significant associations with oxygen uptake at anaerobic threshold (VO2@AT), slope of the efficiency of ventilation in removing carbon dioxide, and peak oxygen pulse (VÉ/VCO2 slope) occurred. Further, interactions with age were identified, such that mainly older individuals with higher levels of periodontal disease severity were associated with lower peakVO2. Restricted to never smokers, associations with mean clinical attachment levels and the number of teeth mostly diminished, while associations of mean PPD with peakVO2, VO2@AT, VÉ/VCO2 slope, and exercise duration in SHIP-1 and SHIP-Trend-0 were confirmed. In SHIP-1, mean peakVO2 was 1,895 mL/min in participants with a mean PPD of 1.6 mm and 1,809 mL/min in participants with a mean PPD of 3.7 mm. To conclude, only mean PPD reflecting current disease severity was consistently linked to cardiorespiratory fitness in 2 cross-sectional samples of the general population. If confirmed in well-designed large-scale longitudinal studies, the association between periodontitis and cardiorespiratory fitness might provide a biologically plausible mechanism linking periodontitis with cardiometabolic diseases.


Assuntos
Tolerância ao Exercício , Periodontite , Estudos Transversais , Teste de Esforço , Humanos , Consumo de Oxigênio , Periodontite/epidemiologia
5.
Pneumologie ; 75(4): 268-275, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32820488

RESUMO

OBJECTIVES: The assessment of pulmonary single-breath diffusing capacity is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance examinations of pulmonary diseases.The aim of this study was to establish reference equations for pulmonary single-breath diffusing capacity parameters in a representative adult-population across a wide age range and to compare the normative values from this sample with previous ones. METHODS: Diffusing capacity measurement was carried out in 3566 participants (1811 males) of a cross-sectional, population-based survey ("Study of Health in Pomerania - SHIP"). RESULTS: Individuals with cardiopulmonary disorders and current smoking habits were excluded, resulting in 1786 healthy individuals (923 males), aged 20 - 84 years. Prediction equations for both sexes were established by quantile regression analyses, taking into consideration the influence of age, height, weight and former smoking. CONCLUSION: The study provides a novel set of prediction equations for pulmonary single-breath diffusing capacity in an adult Caucasian population. The results are comparable to previously reported equations, underline their importance and draw attention to the need for up-to-date reference equations that adequately take into account both the subjects' origin, age, anthropometric characteristics and the equipment used.


Assuntos
Pneumopatias , Capacidade de Difusão Pulmonar , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fumar , Adulto Jovem
7.
Pneumologie ; 74(5): 263-293, 2020 May.
Artigo em Alemão | MEDLINE | ID: mdl-32227328

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since publication of the international IPF guideline in the year 2011 and Update 2018 several studies and technical advances occurred, which made a new assessment of the diagnostic process mandatory. In view of the antifibrotic drugs which have been approved for the treatment of IPF patients, the goal of this guideline is to foster early, confident and effective diagnosis of IPF. The guideline focusses on the typical clinical setting of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardised questionnaires, serologic testing and cellular analysis of bronchoalveolar lavage. High resolution computed tomography remains crucial in the diagnostic work-up. If it is necessary to obtain specimen for histology transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom bronchoscopic diagnosis did not provide the information needed. Despite considerable progress, IPF remains a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/terapia , Pulmão/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Biópsia , Humanos , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Doenças Pulmonares Intersticiais , Tomografia Computadorizada por Raios X
8.
Pneumologe (Berl) ; 17(3): 186-196, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-32206051

RESUMO

Complications of idiopathic pulmonary fibrosis (IPF) are responsible for a relevant proportion of the mortality. Most importantly, acute exacerbation leads to an in-hospital mortality of more than 50% with a mean survival time of only a few months. Therefore, consideration of complications in IPF is of great importance for understanding the disease and treatment planning. Furthermore, the evidence for pneumological rehabilitation in IPF has greatly increased. This resulted in specific recommendations by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) for improvement in physical capacity, quality of life and symptom control.

9.
Pneumologie ; 72(10): 687-731, 2018 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-30304755

RESUMO

This document replaces the DGP recommendations published in 1998 and 2013. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method and its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for blood gas analysis and right heart catheterization during exercise, walk tests, spiroergometry, and stress echocardiography. The correct use of different exercise tests is discussed for specific situations in respiratory medicine: exercise induced asthma, obesity, monitoring of rehabilitation or therapeutical interventions, preoperative risk stratification, and evaluation in occupational medicine.


Assuntos
Teste de Esforço/normas , Guias de Prática Clínica como Assunto , Pneumologia/normas , Testes de Função Respiratória/normas , Espirometria/normas , Alemanha , Humanos , Medicina do Trabalho
10.
Scand J Med Sci Sports ; 28(6): 1628-1635, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29345858

RESUMO

Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by bioelectrical impedance analysis. The suitability of the different markers as a normalization variable was evaluated by taking into account correlation coefficients (r) and intercept (α-coefficient) values from linear regression models. A combination of high r and low α values was considered as preferable for normalization purposes. BCM was the best normalization variable for VO2peak (r = .72; P ≤ .001; α-coefficient = 63.3 mL/min; 95% confidence interval [CI]: 3.48-123) followed by FFM (r = .63; P ≤ .001; α-coefficient = 19.6 mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a markedly higher intercept were found for TBW (r = .42; P ≤ .001; α-coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified as a poor normalization variable (r = .10; P ≤ .001; α-coefficient = 2133; 95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the different normalization variables. Our results suggest that BCM, followed by FFM, might be the most appropriate marker for the normalization of VO2peak when comparing CPF between subjects with different body shape.


Assuntos
Composição Corporal , Peso Corporal , Aptidão Cardiorrespiratória , Consumo de Oxigênio , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Leukemia ; 32(2): 303-312, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28751770

RESUMO

Targeted therapies are frequently combined with standard cytotoxic drugs to enhance clinical response. Targeting the B-cell lymphoma 2 (BCL-2) family of proteins is an attractive option to combat chemoresistance in leukemia. Preclinical and clinical studies indicate modest single-agent activity with selective BCL-2 inhibitors (for example, venetoclax). We show that venetoclax synergizes with cytarabine and idarubicin to increase antileukemic efficacy in a TP53-dependent manner. Although TP53 deficiency impaired sensitivity to combined venetoclax and chemotherapy, higher-dose idarubicin was able to suppress MCL1 and induce cell death independently of TP53. Consistent with an MCL1-specific effect, cell death from high-dose idarubicin was dependent on pro-apoptotic Bak. Combining higher-dose idarubicin with venetoclax was able to partially overcome resistance in Bak-deficient cells. Using inducible vectors and venetoclax to differentially target anti-apoptotic BCL-2 family members, BCL-2 and MCL1 emerged as critical and complementary proteins regulating cell survival in acute myeloid leukemia. Dual targeting of BCL-2 and MCL1, but not either alone, prolonged survival of leukemia-bearing mice. In conclusion, our findings support the further investigation of venetoclax in combination with standard chemotherapy, including intensified doses of idarubicin. Venetoclax should also be investigated in combination with direct inhibitors of MCL1 as a chemotherapy-free approach in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Sulfonamidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Idarubicina/farmacologia , Camundongos , Camundongos Endogâmicos NOD , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
12.
Sci Rep ; 7(1): 3998, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28638097

RESUMO

The design of efficient and robust pulse sequences is a fundamental requirement in quantum control. Numerical methods can be used for this purpose, but with relatively little insight into the control mechanism. Here, we show that the free rotation of a classical rigid body plays a fundamental role in the control of two-level quantum systems by means of external electromagnetic pulses. For a state to state transfer, we derive a family of control fields depending upon two free parameters, which allow us to adjust the efficiency, the time and the robustness of the control process. As an illustrative example, we consider the quantum analog of the tennis racket effect, which is a geometric property of any classical rigid body. This effect is demonstrated experimentally for the control of a spin 1/2 particle by using techniques of Nuclear Magnetic Resonance. We also show that the dynamics of a rigid body can be used to implement one-qubit quantum gates. In particular, non-adiabatic geometric quantum phase gates can be realized based on the Montgomery phase of a rigid body. The robustness issue of the gates is discussed.

13.
Pneumologie ; 71(8): 514-524, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-28505685

RESUMO

The increasing importance of intensive care medicine including mechanical ventilation has been accompanied by the demand of weaning opportunities for patients undergoing prolonged mechanical ventilation. Consequently, specialised clinical institutions, focusing on the weaning from mechanical ventilation, have been established since the 1980 s.The present article illustrates the structural development and results of such a specialised institution at the University Medicine Greifswald, using data of 616 patients collected within the past ten years (2006 - 2015). Across the years, a shift in the underlying disease leading to mechanical ventilation can be found, with rising numbers of patients suffering from pneumonia/sepsis and declining numbers of patients who underwent cardiac surgery in advance. The days with mechanical ventilation outside (p = 0.004) and within the investigated institution (p = 0.02) are significantly declining. The percentage of successfully weaned patients increased from 62.7 % (2006 - 2010) to 77.3 % (2011 - 2015), p < 0.001. Consecutively, the percentage of patients who remained mechanically ventilated decreased from 16.4 % to 9.6 % (p < 0.001) and the share of in-hospital deceased patients significantly declined from 20.9 % to 13.0 % (p < 0.001). Furthermore, the one-year-survival after hospital discharge in successful weaned patients was 72 percent. The present data, collected at the University Medicine Greifswald are quite comparable to data of other German institutions that are specialised on weaning from mechanical ventilation.


Assuntos
Unidades Hospitalares/organização & administração , Hospitais Universitários/organização & administração , Unidades de Terapia Intensiva/organização & administração , Assistência de Longa Duração/organização & administração , Pneumonia/terapia , Sepse/terapia , Desmame do Respirador/métodos , Idoso , Feminino , Alemanha , Unidades Hospitalares/tendências , Hospitais Universitários/tendências , Humanos , Unidades de Terapia Intensiva/tendências , Assistência de Longa Duração/tendências , Masculino , Pessoa de Meia-Idade , Pneumonia/mortalidade , Sepse/mortalidade , Taxa de Sobrevida/tendências , Desmame do Respirador/tendências
14.
Brachytherapy ; 16(2): 330-341, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28159553

RESUMO

PURPOSE: Androgen suppression combined with elective nodal and dose-escalated radiation therapy recently demonstrated an improved biochemical failure-free survival in men who received external beam radiation therapy (EBRT) plus a brachytherapy boost (BB) compared with dose-escalated external beam radiotherapy (DE-EBRT). We sought to analyze the factors predictive for use of EBRT + BB as compared with DE-EBRT and report resulting survival outcomes on a national level using a hospital-based registry. METHODS AND MATERIALS: We identified 113,719 men from the National Cancer Database from 2004 to 2013 with intermediate- or high-risk prostate cancer who were treated with EBRT + BB or DE-EBRT. We performed univariate and multivariate analyses of all available factors potentially predictive of receipt of treatment selection. Survival was evaluated in a multivariable model with propensity adjustment. RESULTS: For intermediate-risk patients, utilization of BB decreased from 33.1% (n = 1742) in 2004 to 12.5% (n = 766) in 2013 and for high-risk patients, utilization dropped from 27.6% (n = 879) to 10.8% (n = 479). Numerous factors predictive for use of BB were identified. Cox proportional hazards analysis was performed-adjusting for age, Charlson-Deyo comorbidity score, T stage, prostate-specific antigen, Gleason score, and sociodemographic factors-and demonstrated BB use was associated with a hazard ratio of 0.71 (95% confidence interval, 0.67-0.75; p < 0.0005) and 0.73 (95% confidence interval, 0.68-0.78; p < 0.0005) for intermediate- and high-risk patients, respectively. CONCLUSIONS: There has been a concerning decline in the utilization of BB for intermediate- and high-risk prostate cancer patients despite an association with improved on overall survival. Numerous factors predictive for use of BB have been identified.


Assuntos
Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Braquiterapia/estatística & dados numéricos , Braquiterapia/tendências , Quimioterapia Adjuvante , Bases de Dados Factuais , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Fatores Socioeconômicos , Análise de Sobrevida , Resultado do Tratamento
15.
Pneumologie ; 71(1): 17-35, 2017 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-28114706

RESUMO

Investigating reasons for differing life expectancy and prevalence of cardiovascular risk factors between old and new states of the Federal Republic of Germany an epidemiological study in Western Pomerania - the population-based project Study of Health in Pomerania (SHIP) - was planned.Prevalence and incidence of common risk factors, subclinical disorders and clinical diseases have been assessed since 1997 in five-year intervals. The third follow up (SHIP-3) was assessed between 2014 and 2016. In addition, an independent representative population sample was investigated between 2008 - 2012 (SHIP-TREND). Recently, the first follow up of this cohort has been started (SHIP-TREND-1). This paper reports the methodological approaches for detecting pneumological relevant morbidities in this population-based study. It aims to offer insights for potential cooperation with interested research groups.


Assuntos
Doenças Cardiovasculares/mortalidade , Nível de Saúde , Expectativa de Vida , Pneumopatias/mortalidade , Projetos de Pesquisa , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Pneumopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
16.
Psychometrika ; 82(1): 210-232, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27844271

RESUMO

This paper discusses the issue of differential item functioning (DIF) in international surveys. DIF is likely to occur in international surveys. What is needed is a statistical approach that takes DIF into account, while at the same time allowing for meaningful comparisons between countries. Some existing approaches are discussed and an alternative is provided. The core of this alternative approach is to define the construct as a large set of items, and to report in terms of summary statistics. Since the data are incomplete, measurement models are used to complete the incomplete data. For that purpose, different models can be used across countries. The method is illustrated with PISA's reading literacy data. The results indicate that this approach fits the data better than the current PISA methodology; however, the league tables are nearly identical. The implications for monitoring changes over time are discussed.


Assuntos
Avaliação Educacional , Internacionalidade , Alfabetização , Modelos Estatísticos , Inquéritos e Questionários , Canadá , Humanos , México , Psicometria , Leitura
17.
J Chem Phys ; 144(16): 164103, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27131527

RESUMO

Here we study the optimum efficiency of the excitation of maximum quantum (MaxQ) coherence using analytical and numerical methods based on optimal control theory. The theoretical limit of the achievable MaxQ amplitude and the minimum time to achieve this limit are explored for a set of model systems consisting of up to five coupled spins. In addition to arbitrary pulse shapes, two simple pulse sequence families of practical interest are considered in the optimizations. Compared to conventional approaches, substantial gains were found both in terms of the achieved MaxQ amplitude and in pulse sequence durations. For a model system, theoretically predicted gains of a factor of three compared to the conventional pulse sequence were experimentally demonstrated. Motivated by the numerical results, also two novel analytical transfer schemes were found: Compared to conventional approaches based on non-selective pulses and delays, double-quantum coherence in two-spin systems can be created twice as fast using isotropic mixing and hard spin-selective pulses. Also it is proved that in a chain of three weakly coupled spins with the same coupling constants, triple-quantum coherence can be created in a time-optimal fashion using so-called geodesic pulses.

18.
Clin Oncol (R Coll Radiol) ; 28(8): 513-21, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27146264

RESUMO

AIMS: Stage II testicular seminoma is highly curable with radiotherapy or multi-agent chemotherapy (MACT). These modalities have not been compared in a randomised manner. MATERIALS AND METHODS: Using the US National Cancer Data Base, we identified 2437 stage II seminoma patients (IIA = 960, IIB = 812, IIC = 665) treated with orchiectomy and either radiotherapy or MACT from 1998 to 2012. Factors affecting treatment modality (radiotherapy versus MACT) were studied using multivariable logistic regression. Propensity scores for treatment selection were incorporated into multivariable Cox regression analyses of overall survival. RESULTS: The median follow-up was 65 months (interquartile range 34-106). Rates of radiotherapy utilisation were: IIA = 78.1%, IIB = 54.4%, IIC = 4.2%. Rates of MACT utilisation were: IIA = 21.9%, IIB = 45.6%, IIC = 95.8%. For both IIA and IIB patients, later year of diagnosis, academic treatment facility and pathological confirmation of lymph node positivity were associated with increased utilisation of MACT. Also predictive for preferential utilisation of MACT were comorbidity score ≥ 1 and non-private insurance for IIA patients and T stage ≥ 2 for IIB patients. For IIA patients, survival was improved with radiotherapy compared with MACT with a 5 year survival of 99.0% (95% confidence interval 98.2-99.8) versus 93.0% (95% confidence interval 89.0-97.0). This advantage persisted on propensity-adjusted multivariate analysis (hazard ratio 0.28; 95% confidence interval 0.09-0.86; P = 0.027). For IIB patients, 5 year survival was 95.2% (95% confidence interval 92.8-97.6) for radiotherapy and 92.4% (95% confidence interval 89.2-95.6) for MACT (Log-rank P = 0.041), with no significant difference on multivariable analysis. CONCLUSIONS: Radiotherapy is associated with improved survival over MACT for IIA patients, with no significant survival difference for IIB patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/radioterapia , Radioterapia , Seminoma/tratamento farmacológico , Seminoma/radioterapia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/radioterapia , Adulto , Idoso , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/mortalidade , Orquiectomia , Modelos de Riscos Proporcionais , Seminoma/mortalidade , Neoplasias Testiculares/mortalidade
19.
Leukemia ; 30(7): 1531-41, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27055867

RESUMO

The BET (bromodomain and extraterminal domain) bromodomain-containing proteins, such as BRD4, are highly promising targets for treating lymphoid and myeloid malignancies. They act to modulate the expression of multiple genes that control diverse cellular processes including proliferation, survival and differentiation that are consequentially disrupted by small-molecule BET bromodomain inhibitors such as JQ1. By assessing the impact of these inhibitors on normal mouse hematopoietic cells or their transformed counterparts, we establish definitively that their cytotoxic action in vitro and in vivo relies predominantly on the activation of BAX/BAK-dependent mitochondrial (intrinsic) apoptosis. In large part, this is triggered by marked upregulation of the BH3-only protein BIM when the BET inhibitors suppress miR-17-92, a key post-transcriptional repressor of BIM expression. Thus, our study strongly suggests that mutations that permit the evasion of apoptosis (for example, BCL2 overexpression, BIM inactivation) are likely to blunt the activity of the BET bromodomain inhibitors and should be anticipated when therapy resistance develops. Strikingly, we also found that certain normal hematopoietic cells, especially those of lymphoid origin, are as prone to apoptosis induced by the BET inhibitors as their transformed counterparts, indicating that their susceptibility to BET inhibitors did not arise from oncogenic transformation.


Assuntos
Apoptose , Azepinas/farmacologia , Proteína 11 Semelhante a Bcl-2/fisiologia , Linfoma/patologia , MicroRNAs/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Triazóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas de Ciclo Celular , Linhagem Celular , Linhagem Celular Transformada , Modelos Animais de Doenças , Sistema Hematopoético/citologia , História Antiga , Humanos , Camundongos , Camundongos Transgênicos , Proteínas Nucleares/antagonistas & inibidores , RNA Longo não Codificante
20.
Physiol Genomics ; 48(1): 1-11, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26487704

RESUMO

Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n = 7,781, ages: 20-104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation, and the stress response. Ten genes were associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥ 60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age- and sex-specific gene expression signatures in blood for muscle strength.


Assuntos
Envelhecimento/fisiologia , Coração/fisiologia , Força Muscular/genética , RNA Mensageiro/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Ontologia Genética , Humanos , Joelho/fisiologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Caracteres Sexuais , Adulto Jovem
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