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2.
Eur J Haematol ; 110(6): 715-724, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36941654

RESUMO

INTRODUCTION: A high CD4/CD8 T cell ratio in hematopoietic stem cell transplant (HSCT) allografts was observed to predict graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) but has not been comparatively examined in settings of various GVHD-prophylaxis regimens. METHODS: This retrospective monocentric study included all consecutive HSCT performed with peripheral blood stem cells between January 2000 and June 2021. The impact of the graft CD4/CD8 ratio was analyzed in three cohorts with different GVHD-prophylaxis platforms. RESULTS: In the cyclosporine/mycophenolate-mofetil (CSA/MMF) cohort (n = 294, HLA-matched HSCT), a high (>75th percentile) CD4/CD8 ratio was associated with increased overall mortality (HR: 1.56; p = .01), increased NRM (HR: 1.85; p = .01) and GVHD-associated mortality (HR: 2.13; p = .005). In the post-transplant cyclophosphamide (PTCy)/tacrolimus/MMF cohort (n = 113, haploidentical-related or mismatched-unrelated HSCT), a high CD4/CD8 ratio was associated with increased overall mortality (HR 2.07; p = .04) and aGVHD3-4 (HR: 2.24; p = .02). By contrast, in the CSA/methotrexate (CSA/MTX) cohort (n = 185, HLA-matched HSCT) the CD4/CD8 ratio had no significant impact on any of the investigated endpoints. CONCLUSION: A high CD4/CD8 ratio in the allograft has an adverse impact on GVHD and survival in CSA/MMF- and PTCy-based HSCT, while MTX-based prophylaxis may largely alleviate this important risk factor.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Aloenxertos , Linfócitos T CD8-Positivos , Ciclofosfamida/efeitos adversos , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Estudos Retrospectivos , Linfócitos T CD4-Positivos
3.
BMC Musculoskelet Disord ; 24(1): 500, 2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37330489

RESUMO

BACKGROUND: Segmental bone transport is a common technique for treating large segmental bone defects. However, a docking site procedure is often necessary in segmental bone transport. To date, no prognostic factors for the need of docking site procedure have been reported. Thus, the decision is often made at random, based on the surgeon's subjective judgment and experience. The aim of this study was to identify prognostic factors for the need of docking site operation. METHODS: Patients with segmental bone transport in lower extremity bone defects were included regardless of age, aetiology, and defect size. We excluded patients undergoing treatments that were not yet completed, and those who discontinued therapy by any reason. The need for docking site operation was modelled with logistical and linear regression as well as univariate analysis of variances (ANOVA). Receiver operating characteristics (ROC) curve analysis was also performed. RESULTS: Twenty-seven patients from age 12 to 74 years (mean age: 39.07 ± 18.20 years) were included. The mean defect size was 76.39 ± 41.10 mm. The duration of transport (days) showed a significant influence (p = 0.049, 95%CI: 1.00-1.02) on the need for docking site operation. No other significant influences were detected. CONCLUSION: A link between the duration of transport and the need for docking site operation was detected. Our data showed that if a threshold of about 188 days is exceeded, docking surgery should be considered.


Assuntos
Osteogênese por Distração , Fraturas da Tíbia , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Criança , Adolescente , Idoso , Osteogênese por Distração/métodos , Resultado do Tratamento , Extremidade Inferior/cirurgia , Estudos Retrospectivos , Tíbia/cirurgia , Fraturas da Tíbia/cirurgia
4.
Tech Coloproctol ; 26(8): 665-675, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35593971

RESUMO

BACKGROUND: The occurrence of postoperative complications and anastomotic leakage are major drivers of mortality in the immediate phase after colorectal cancer surgery. We trained prediction models for calculating patients' individual risk of complications based only on preoperatively available data in a multidisciplinary team setting. Knowing prior to surgery the probability of developing a complication could aid in improving informed decision-making by surgeon and patient and individualize surgical treatment trajectories. METHODS: All patients over 18 years of age undergoing any resection for colorectal cancer between January 1, 2014 and December 31, 2019 from the nationwide Danish Colorectal Cancer Group database were included. Data from the database were converted into Observational Medical Outcomes Partnership Common Data Model maintained by the Observation Health Data Science and Informatics initiative. Multiple machine learning models were trained to predict postoperative complications of Clavien-Dindo grade ≥ 3B and anastomotic leakage within 30 days after surgery. RESULTS: Between 2014 and 2019, 23,907 patients underwent resection for colorectal cancer in Denmark. A Clavien-Dindo complication grade ≥ 3B occurred in 2,958 patients (12.4%). Of 17,190 patients that received an anastomosis, 929 experienced anastomotic leakage (5.4%). Among the compared machine learning models, Lasso Logistic Regression performed best. The predictive model for complications had an area under the receiver operating characteristic curve (AUROC) of 0.704 (95%CI 0.683-0.724) and an AUROC of 0.690 (95%CI 0.655-0.724) for anastomotic leakage. CONCLUSIONS: The prediction of postoperative complications based only on preoperative variables using a national quality assurance colorectal cancer database shows promise for calculating patient's individual risk. Future work will focus on assessing the value of adding laboratory parameters and drug exposure as candidate predictors. Furthermore, we plan to assess the external validity of our proposed model.


Assuntos
Fístula Anastomótica , Neoplasias Colorretais , Adolescente , Adulto , Fístula Anastomótica/etiologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Humanos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
5.
Unfallchirurg ; 125(5): 371-380, 2022 May.
Artigo em Alemão | MEDLINE | ID: mdl-35348803

RESUMO

The 3D printing technology is a relatively new procedure with a high potential, especially in the field of shoulder surgery. The 3D printing procedures are increasingly being developed and also gaining new users. Principally, 3D printing procedures can be applied preoperatively in planning the surgical procedure, patient clarification and in teaching; however, the technology is increasing being used intraoperatively. In addition to intraoperative visualization of the models, 3D printing permits the use of individual and specific instruments and implants. This allows the precise transfer of the preoperative planning to the surgical procedure. Inaccuracies are mainly caused by soft tissues. The 3D printing can be beneficial in the fields of arthroplasty, shoulder instability as well as orthopedic trauma. The literature shows promising results in relation to duration of surgery, blood loss and clinical results of the procedure. On the other hand, it is still unclear which indications warrant the use of 3D printing. Other aspects that raise questions are the time of planning, the production time and the additional cost that the use of 3D printing entails. Nonetheless, 3D printing represents a meaningful enhancement of the portfolio of surgeons, which becomes highly beneficial and useful in complex situations. Furthermore, this procedure enables a certain amount of flexibility when reacting to certain circumstances.


Assuntos
Instabilidade Articular , Articulação do Ombro , Cirurgia Assistida por Computador , Humanos , Impressão Tridimensional , Ombro , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Cirurgia Assistida por Computador/métodos
6.
Bull Environ Contam Toxicol ; 100(5): 603-608, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29532132

RESUMO

Military ranges are unlike many waste sites because the contaminants, both energetics and metals, are heterogeneously distributed in soil during explosive detonation or ballistic impact and cannot be readily characterized using conventional grab sampling. The Incremental Sampling Methodology (ISM) has been successful for characterization of energetic contamination in soils, but no published ISM processing studies for soils with small arms range metals such as Pb, Cu, Sb, and Zn exists. This study evaluated several ISM sample-processing steps: (1) field splitting to reduce the sample mass shipped to the analytical laboratory, (2) necessity of milling, and (3) processing a larger subsample mass for digestion in lieu of milling. Cone-and-quartering and rotary sectorial splitting techniques yielded poor precision and positively skewed distributions. Hence, an increase in digestion mass from 2 to 10 g was evaluated with milled and unmilled samples. Unmilled samples yielded results with the largest variability regardless of aliquot mass.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/análise , Poluentes do Solo/análise , Militares , Solo/química , Armas
7.
Bull Environ Contam Toxicol ; 100(1): 155-161, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29270645

RESUMO

This study compares conventional grab sampling to incremental sampling methodology (ISM) to characterize metal contamination at a military small-arms-range. Grab sample results had large variances, positively skewed non-normal distributions, extreme outliers, and poor agreement between duplicate samples even when samples were co-located within tens of centimeters of each other. The extreme outliers strongly influenced the grab sample means for the primary contaminants lead (Pb) and antinomy (Sb). In contrast, median and mean metal concentrations were similar for the ISM samples. ISM significantly reduced measurement uncertainty of estimates of the mean, increasing data quality (e.g., for environmental risk assessments) with fewer samples (e.g., decreasing total project costs). Based on Monte Carlo resampling simulations, grab sampling resulted in highly variable means and upper confidence limits of the mean relative to ISM.


Assuntos
Monitoramento Ambiental/métodos , Metais/análise , Poluentes do Solo/análise , Solo/química , Medição de Risco
8.
Bull Environ Contam Toxicol ; 100(1): 147-154, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29299633

RESUMO

Research shows grab sampling is inadequate for evaluating military ranges contaminated with energetics because of their highly heterogeneous distribution. Similar studies assessing the heterogeneous distribution of metals at small-arms ranges (SAR) are lacking. To address this we evaluated whether grab sampling provides appropriate data for performing risk analysis at metal-contaminated SARs characterized with 30-48 grab samples. We evaluated the extractable metal content of Cu, Pb, Sb, and Zn of the field data using a Monte Carlo random resampling with replacement (bootstrapping) simulation approach. Results indicate the 95% confidence interval of the mean for Pb (432 mg/kg) at one site was 200-700 mg/kg with a data range of 5-4500 mg/kg. Considering the U.S. Environmental Protection Agency screening level for lead is 400 mg/kg, the necessity of cleanup at this site is unclear. Resampling based on populations of 7 and 15 samples, a sample size more realistic for the area yielded high false negative rates.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/análise , Poluentes do Solo/análise , Armas , Recuperação e Remediação Ambiental , Solo
9.
Unfallchirurg ; 120(11): 950-960, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-29143065

RESUMO

Cartilage defects in adult patients are so far incurable. Fresh osteochondral allograft (OCA) transplantation is based on the insertion of mature, living, mechanically sound hyaline cartilage into an osteochondral defect where it undergoes osseointegration. Intact hyaline cartilage of OCA does not cause immune reactions in the recipient. Many reports show that small OCA have good osseointegration and show good long-term results. These observations have been incorporated into the development of the fresh large (> 10 cm2) osteochondral shell allograft transplantation (FLOCSAT) concept, which is based on the following principles: 1) the thickness of the osseous layer should be kept as thin as possible (target < 6-8 mm) so that the transplant remains stable and fixable. This results in reduced segments of vascularization, simplified ossification and reduced immunogenic bone volume. 2) The bone surface is processed and enlarged (oscillating saw: pie crust technique, drill holes) and areas of sclerosis are simultaneously broken off. 3) Cell reduction and washing out of the bony layer with a pulsatile jet lavage. 4) Prevention of impaction and dessication: cartilage with its living chondrocytes are very sensitive to mechanical contusion and dessication. When introducing the transplant, the tissue must therefore be continually moistened and the pressure acting on the cartilage must be controlled. 5) Stable fixation: extensive uniplanar osteochondral transplants cannot be inserted by the press-fit method; therefore, fixation is carried out with small implants. In this publication we demonstrate how severe and complex posttraumatic or degenerative delayed problems can be solved using FLOCSAT.


Assuntos
Artroplastia de Substituição , Cartilagem Articular , Osseointegração , Adulto , Transplante Ósseo , Cartilagem , Condrócitos , Humanos , Transplante Homólogo
10.
Unfallchirurg ; 120(3): 199-204, 2017 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-28138766

RESUMO

Tendinopathy in the region of the knee joint is a common pathological disorder. People active in sports, in particular, have a high probability of suffering from tendinopathy. Despite its high clinical relevance, the level of evidence of therapy options for tendinopathy in the knee region differs greatly. This review gives an overview of current evidence levels for therapy options in tendinopathy of the quadriceps, patellar and pes anserinus insertion tendons as well as of the distal iliotibial tract tendon. The treatment with platelet-rich plasma showed a significantly better outcome when used correctly and treatment with shock waves, operative treatment and sclerotherapy have also shown positive effects. Treatment with corticosteroid injections and with oral non-steroidal anti-inflammatory drugs (NSAID) showed positive short-term effects (follow-up ±4 weeks). No reasonable data are available for the treatment of tendinopathy in the knee region by acupuncture, fascial therapy or cryotherapy. The use of kinesio taping showed no significant relief from complaints compared with standard conservative treatment. The use of multimodal therapy without evidence is, therefore, particularly common in elite athletes.


Assuntos
Corticosteroides/administração & dosagem , Traumatismos do Joelho/terapia , Modalidades de Fisioterapia , Escleroterapia/métodos , Tendinopatia/terapia , Tenotomia/métodos , Terapia por Ultrassom/métodos , Anti-Inflamatórios/administração & dosagem , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/terapia , Transfusão de Componentes Sanguíneos/métodos , Terapia Combinada/métodos , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos , Traumatismos do Joelho/diagnóstico , Plasma Rico em Plaquetas , Tendinopatia/diagnóstico , Resultado do Tratamento
11.
Unfallchirurg ; 120(11): 932-949, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-29138892

RESUMO

Cartilage defects in adult patients do not heal well. Fresh osteochondral allograft (OCA) transplantation is based on mature, living, mechanically sound hyaline cartilage attached to a bone interface, which is brought into an osteochondral defect, where it becomes osseointegrated. According to current knowledge, intact hyaline cartilage tissue is immune privileged and does not, in contrast to bone, meniscus or ligaments, cause an immune reaction. The technique has the unique advantage of transplanting viable, mature and mechanically stable hyaline cartilage into the affected area. An OCA is the only biological surgical technique for chondral and osteochondral lesions after failed cell-based techniques or autologous osteochondral transplantation.Fresh osteochondral allografts with mainly small cylindrical transplants show survival of 20 years and more. Based on this experience the FLOCSAT (fresh large [> 10 cm2] osteochondral shell allograft transplantation) concept with the thinnest possible (< 6-8 mm) bone thickness has been developed. Cells survive in special media at 4 °C for 4 weeks or more and are transplanted with a minimum of 70% living cells in a live/dead assay and cell density > 200 cells/mm2.FLOCSATs can replace parts or entire joints as uniplanar or multiplanar(n-planar)-FLOCSAT, as unipolar, bipolar or tripolar(n-polar)-FLOCSAT, and in combination with meniscus and/or ligaments (nMnL)-FLOCSAT (n number of structures).The FLOCSAT concept was applied successfully to knee, ankle and elbow joints. All transplants showed sound osseointegration. Cartilage failure was the reason for unsuccessful outcome. Challenges remain regarding graft availability, precise size matching, complex logistics, demanding surgical technique in complex geometries, and open questions in immunology and chimerism.


Assuntos
Cartilagem Articular , Articulação do Joelho , Transplante Homólogo , Adulto , Aloenxertos , Transplante Ósseo , Humanos , Articulação do Joelho/cirurgia
12.
Persoonia ; 38: 38-57, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29151626

RESUMO

Based on molecular and morphological data we investigated the taxonomy and phylogeny of the ectomycorrhizal genus Tricholoma in northern Europe. Our phylogenetic tree confirmed the presence of at least 72 well circumscribed species within the region. Of these, three species, viz. T. boreosulphurescens, T. bryogenum and T. ilkkae are described as new to science, based on morphological, distributional, ecological and molecular data. Several other terminal branches represent putative cryptic taxa nested within classical species or species groups. Molecular type studies and/or designation of sequenced neotypes are needed in these groups, before the taxonomy can be settled. In general our phylogenetic analysis supported previous suprageneric classification systems, but with some substantial changes. Most notably, T. virgatum and allies were found to belong to sect. Tricholoma rather than sect. Atrosquamosa, while T. focale was found to be clearly nested in sect. Genuina rather than in sect. Caligata. In total, ten sections are accepted, with five species remaining unassigned. The combination of morphological and molecular data showed pileus colour, pileipellis structure, presence of clamp connections and spore size to be rather conservative characters within accepted sections, while the presence of a distinct ring, and especially host selection were highly variable within these.

13.
J Phys Chem A ; 118(1): 13-20, 2014 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-24372396

RESUMO

Chemical magnetometers are radical pair systems such as solutions of pyrene and N,N-dimethylaniline (Py-DMA) that show magnetic field effects in their spin dynamics and their fluorescence. We investigate the existence and decay of quantum entanglement in free geminate Py-DMA radical pairs and discuss how entanglement can be assessed in these systems. We provide an entanglement witness and propose possible observables for experimentally estimating entanglement in radical pair systems with isotropic hyperfine couplings. As an application, we analyze how the field dependence of the entanglement lifetime in Py-DMA could in principle be used for magnetometry and illustrate the propagation of measurement errors in this approach.

14.
J Chromatogr A ; 1721: 464803, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38547680

RESUMO

Rapid bioanalysis is beneficial to many applications. However, how 'rapid' a method is, or could be, is often an unanswered question. In this statistical review, the authors have assessed multiple pre-analytical (i.e. sample preparation), and analytical method parameters specifically for liquid chromatography to assist researchers in developing and validating 'rapid' bioanalytical methods. We restricted the search to urine and plasma matrices only. Data were extracted from over 2,000 recent studies and evaluated to assess how these parameters affected the 'on-instrument' analysis time. In addition to methods using ultra-violet (UV) detection, there were a large number of mass spectrometric (MS) methods, allowing additional review of the differences between high- and low-resolution MS on analysis time. We observed that most (N = 922, 70 %) methods used 5 or 10 cm columns, and that whilst uptake of ultra-high performance (U)HPLC columns was good, the use of sub-5 cm columns and/or flow rates in excess of 1 mL/min was incredibly rare (N = 25, 3 %). The detector of choice for quantitative (U)HPLC-MS remains the triple quadrupole, although a number of groups report the use of high-resolution MS for such methods.


Assuntos
Plasma , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos
15.
Int J Obes (Lond) ; 37(2): 175-81, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22349573

RESUMO

CONTEXT: Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in ß-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus. OBJECTIVE: To determine the influence of a functional UCP2 promoter polymorphism (-866G>A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes. DESIGN: We genotyped UCP2 rs659366 in a total of 17 636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations. RESULTS: We found no consistent associations between the UCP2 -866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12 984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826-0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800-0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15 107 individuals showed no association. The -866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05). CONCLUSIONS: The UCP2 -866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Resistência à Insulina , Canais Iônicos/sangue , Proteínas Mitocondriais/sangue , Obesidade/sangue , Polimorfismo de Nucleotídeo Único , População Branca/genética , Alelos , Animais , Glicemia/metabolismo , Estudos de Casos e Controles , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Resistência à Insulina/genética , Canais Iônicos/genética , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Obesidade/epidemiologia , Obesidade/genética , Regiões Promotoras Genéticas , Proteína Desacopladora 2
16.
Unfallchirurgie (Heidelb) ; 126(3): 175-183, 2023 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-36746799

RESUMO

BACKGROUND: Interdisciplinary case conferences are well-established in the field of oncology in order to provide the best possible treatment for patients with complex disease patterns which overlap several disciplines. METHODS: After studying the available literature the aims, indications, frequency, patient enrolment and documentation modalities, disciplines necessary to create the reconstruction plan and evaluation parameters of the board, were agreed in an interdisciplinary discussion among colleagues. The utilization of the extremity board and demographic features of the cases presented in the extremity board within the first 6 months were subsequently descriptively analyzed. RESULTS: The agreed primary aim of an extremity board is the timely and transparent preparation of a high-quality holistic reconstruction plan for optimized treatment of a challenging patient collective with complex injuries of the extremities. Decisive interfaces of an extremity board are the participation of interdisciplinary disciplines, established enrolment and documentation modalities and a longitudinal analysis of parameters of the acute medical treatment, the long-term function and quality of life of those affected. The patient collective so far mostly includes men under 40 years old with traumatic soft tissue defects and combined injuries. On average, reconstruction plans for 1-2 patients were approved in an interdisciplinary team per session. CONCLUSION: The extremity board serves as a platform for coordinated planning of treatment for patients with complex injuries. The limited personnel and time resources represent the greatest challenge for the successful implementation. The extremity board enables a high degree of interdisciplinary networking. The digital registration and documentation modality within the internal hospital documentation system is of utmost relevance. The preparation of the reconstruction plan is of decisive importance for the qualitative success of treatment and the restoration of function. The longitudinal analysis of appropriate parameters is imperative to measure the quality of treatment.


Assuntos
Procedimentos de Cirurgia Plástica , Qualidade de Vida , Masculino , Humanos , Adulto , Extremidades/lesões
17.
J Neurol Sci ; 428: 117585, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371243

RESUMO

This study analyzed the topography of acute ischemic stroke in the posterior cerebral artery (PCA) territory. We studied 84 patients with unilateral ischemic PCA stroke. Patients were classified according to lesion levels as cortico-subcortical (superficial), combined (cortical and mesodiencephalic) or isolated thalamic. To receive a lesion map, data from acute MR and CT imaging were normalized and labelled automatically by mapping to stereotaxic anatomical atlases. Cortical lesions accounted for 41.7%, combined for 36.9%, and isolated thalamic lesions for 21.4%. The maximum overlay of ischemia and, thus, highest occurrence of PCA ischemic stroke was found in the ventral and medial occipito-temporal cortex and adjacent white matter association tracts. Dorsal and peripheral segments of the occipito-temporo-parietal region were only rarely lesioned. This configuration was similar in both hemispheres. Consistent with this lesion pattern, visual field defects (VFD) were the most frequent signs, followed by sensorimotor signs, dizziness and sopor, cognitive and oculomotor deficits, and ataxia. The three vascular subgroups differed not only by their anatomical lesion profile and lesion load, but also by their clinical manifestation; although patients with combined and thalamic lesions were sigificantly younger, they were more disabled than participants with cortical lesions. VFD were only found in cortical and combined, and oculomotor deficits only in mesodiencephalic lesions. White matter lesions were common in the cortico-subcortical and the combined group. Basal occipito-temporal and calcarine regions, and neighbouring white matter tracts have the highest risk of ischemia in acute PCA stroke.


Assuntos
Isquemia Encefálica , Infarto da Artéria Cerebral Posterior , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Humanos , Infarto da Artéria Cerebral Posterior/complicações , Infarto da Artéria Cerebral Posterior/diagnóstico por imagem , Artéria Cerebral Posterior , Acidente Vascular Cerebral/diagnóstico por imagem , Tálamo
18.
Quantum Mach Intell ; 2(2): 13, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33184611

RESUMO

In recent years, the interest in leveraging quantum effects for enhancing machine learning tasks has significantly increased. Many algorithms speeding up supervised and unsupervised learning were established. The first framework in which ways to exploit quantum resources specifically for the broader context of reinforcement learning were found is projective simulation. Projective simulation presents an agent-based reinforcement learning approach designed in a manner which may support quantum walk-based speedups. Although classical variants of projective simulation have been benchmarked against common reinforcement learning algorithms, very few formal theoretical analyses have been provided for its performance in standard learning scenarios. In this paper, we provide a detailed formal discussion of the properties of this model. Specifically, we prove that one version of the projective simulation model, understood as a reinforcement learning approach, converges to optimal behavior in a large class of Markov decision processes. This proof shows that a physically inspired approach to reinforcement learning can guarantee to converge.

19.
Diabetologia ; 52(10): 2122-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19669124

RESUMO

AIMS/HYPOTHESIS: An association between elevated fasting plasma glucose and the common rs560887 G allele in the G6PC2/ABCB11 locus has been reported. In Danes we aimed to examine rs560887 in relation to plasma glucose and serum insulin responses following oral and i.v. glucose loads and in relation to hepatic glucose production during a hyperinsulinaemic-euglycaemic clamp. Furthermore, we examined rs560887 for association with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT), type 2 diabetes and components of the metabolic syndrome. METHODS: rs560887 was genotyped in the Inter99 cohort (n = 5,899), in 366 young, healthy Danes, in non-diabetic relatives of type 2 diabetic patients (n = 196), and in young and elderly twins (n = 159). Participants underwent an OGTT, an IVGTT or a 2 h hyperinsulinaemic-euglycaemic clamp. RESULTS: The rs560887 G allele associated with elevated fasting plasma glucose (p = 2 x 10(-14)) but not with plasma glucose levels at 30 min (p = 0.9) or 120 min (p = 0.9) during an OGTT. G allele carriers had elevated levels of serum insulin at 30 min during an OGTT (p = 1 x 10(-4)) and relatives of type 2 diabetes patients carrying the G allele had an increased acute insulin response (p = 4 x 10(-4)) during an IVGTT. Among elderly twins, G allele carriers had higher basal hepatic glucose production (p = 0.04). Finally, the G allele associated with the risk of having IFG (OR 1.26, 95% CI 1.08-1.47, p = 0.002), but not with IGT (OR 0.94, 95% CI 0.82-1.08, p = 0.4) or type 2 diabetes (OR 0.93, 95% CI 0.84-1.04, p = 0.2). CONCLUSIONS/INTERPRETATION: The common rs560887 G allele in the G6PC2/ABCB11 locus is associated with increased fasting glycaemia and increased risk of IFG, associations that may be partly related to an increased basal hepatic glucose production rate.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Glicemia/genética , Jejum/sangue , Glucose-6-Fosfatase/genética , Glucose/biossíntese , Insulina/metabolismo , Fígado/metabolismo , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Adulto , Feminino , Genótipo , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade
20.
Br J Dermatol ; 160(2): 284-96, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18945296

RESUMO

BACKGROUND: Interleukin (IL)-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interestingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the aetiology of psoriasis is unknown. OBJECTIVES: In this study, we investigate the effects both of blocking IL-20 signalling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin. METHODS: We employed the human skin xenograft transplantation model in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immuno-deficient mice. The transplanted mice were treated with anti-IL-20 antibodies or recombinant human IL-20. RESULTS: We demonstrate that blocking IL-20 signalling with anti-IL-20 antibodies induces psoriasis resolution and inhibits psoriasis induction. We also demonstrate that continuous IL-20 infusion, together with injection of additional nonactivated leucocytes, promotes induction of psoriasis in nonlesional skin from patients with psoriasis. CONCLUSIONS: The results suggest that IL-20 plays a critical role in the induction and maintenance of psoriasis, and IL-20 is suggested as a new possible specific target in psoriasis treatment.


Assuntos
Interleucinas/fisiologia , Psoríase/etiologia , Transdução de Sinais/imunologia , Transplante de Pele , Adulto , Idoso , Animais , Especificidade de Anticorpos/imunologia , Proliferação de Células , Humanos , Interleucinas/antagonistas & inibidores , Interleucinas/imunologia , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Psoríase/imunologia , Proteínas Recombinantes/imunologia , Indução de Remissão , Transplante Heterólogo
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