Viral load kinetics and the clinical consequences of cytomegalovirus in kidney transplantation

BackgroundDespite advances in clinical management, cytomegalovirus (CMV) infection remains a serious complication and an important cause of morbidity and mortality following kidney transplantation. Here, we explore the importance of viral load kinetics as predictors of risk and potential guides to therapy to reduce transplant failure in a large longitudinal Genome Canada Transplant Consortium (GCTC) kidney transplant cohort.MethodsWe examined the relationship between CMV infection rates and clinical characteristics, CMV viral load kinetics, and graft and patient outcomes in 2510 sequential kidney transplant recipients in the British Columbia Transplant Program. Transplants were performed between January 1, 2008, and December 31, 2018, were managed according to a standard protocol, and were followed until December 31, 2019, representing over 3.4 million days of care.ResultsLongitudinal CMV testing was performed in 2464 patients, of whom 434 (17.6%) developed a first episode of CMV viremia at a median of 120 (range: 9–3906) days post-transplant. Of these patients, 93 (21.4%) had CMV viremia only and 341 (78.6%) had CMV viremia with clinical complications, of whom 21 (4.8%) had resulting hospitalization. A total of 279 (11.3%) patients died and 177 (7.2%) patients lost their graft during the 12 years of follow-up. Patients with CMV infection were at significantly greater risk of graft loss (p=0.0041) and death (p=0.0056) than those without. Peak viral load ranged from 2.9 to 7.0 (median: 3.5) log10 IU/mL, the duration of viremia from 2 to 100 (15) days, and the viral load area under the curve from 9.4 to 579.8 (59.7) log10 IU/mL × days. All three parameters were closely inter-related and were significantly increased in patients with more severe clinical disease or with graft loss (p=0.001). Duration of the first CMV viremic episode greater than 15 days or a peak viral load ≥4.0 log10 IU/mL offered simple predictors of clinical risk with a 3-fold risk of transplant failure.ConclusionViral load kinetics are closely related to CMV severity and to graft loss following kidney transplantation and provide a simple index of risk which may be valuable in guiding trials and treatment to prevent transplant failure

White Blood Cell Differentials Enrich Whole Blood Expression Data in the Context of Acute Cardiac Allograft Rejection

Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) ≤ 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data***

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Os dividendos como estratégia de investimentos em ações

Na Teoria de Finanças, o papel dos dividendos nas cotações é um tema controverso, uma vez que há diferentes teorias que abordam sua relevância para o valor das ações e, em conseqüência, para a riqueza dos acionistas. Além disso, as descobertas empíricas que originaram a Hipótese de Mercado Eficiente de Capitais (HME) não apenas contradizem a Análise Técnica, mas também impõem um desafio à declarada habilidade superior da Análise Fundamentalista em gerar retornos superiores, com base em fatores ou variáveis contábeis, financeiros e econômicos, tais como o dividend yield (retorno em dividendos). A fim de se verificar a relação entre dividend yields e as taxas de retornos das ações, bem como a viabilidade de uma estratégia baseada em dividend yields históricos de "bater" o mercado, foram construídas, mensalmente, durante o período que vai do Plano Real em julho de 1994 a dezembro de 1999, três diferentes carteiras (alto, baixo e zero). Seus riscos, retornos e indicadores de desempenho ajustados ao risco foram calculados e comparados entre si e com seu paradigma (benchmark), o Índice da Bolsa de Valores de São Paulo - Ibovespa. A evidência empírica é incapaz de sugerir que as ações de altos dividend yield tendem a possuir maiores ou menores taxas de retorno do que as ações de baixo ou zero yield. Ademais, as evidências sugerem que não é possível demonstrar, usando o método empírico aplicado, uma clara associação entre dividend yield e taxas de retorno das ações.In Finance Theory, the role of dividends in stock prices is a controversial issue, considering the different theories that exist on their relevance for stock value and, consequently, for shareholders' wealth. Furthermore, empirical findings that have originated the Efficient Market Hypothesis (EMH) not only contradict Technical Analysis, but also pose a challenge to the Fundamental Analysis' supposedly superior ability to generate higher returns based on accounting, financial and economic factors or variables such as the dividend yield. In order to assess the relationship between dividend yields and stocks returns as well as the viability of a strategy based on historic dividend yield to "beat" the market, with reference to the period from the beginning of the Real Plan in July 1994 until December 1999, three different yield portfolios (high, low and zero) were formed on a monthly basis.Their risks, returns and risk-adjusted portfolio performance measurements were calculated, and then compared both among themselves and to the benchmark (São Paulo Stock Exchange Index - Ibovespa). Empirical evidence is unable to suggest either that stocks with a high dividend yield tend to have higher or lower returns than those with a low or zero yield. Moreover, the evidences suggest that, using the applied empirical method, no clear association between dividend yield and stock returns can be demonstrated

New parts for old: an odyssey in medicine

Item consists of a digitized copy of a video recording of a Vancouver Institute lecture given by Paul Keown on January 28, 1989. Original video recording available in the University Archives (UBC VT 169).Medicine, Faculty ofMedicine, Department ofUnreviewedFacult

Association between transplant glomerulopathy and graft outcomes following kidney transplantation: A meta-analysis.

Transplant glomerulopathy (TG), a morphological lesion associated with confluent mechanisms of endothelial injury of renal allografts, may provide a viable predictor of graft failure. This systematic literature review and meta-analysis were performed according to the PRISMA statement to examine evidence describing the association between TG and graft loss or failure and time to these events. The literature review was conducted using the Scopus, EBSCO, and Cochrane Library search engines. Hazard ratios, median survival times, and 95% confidence intervals (CIs) were estimated to evaluate graft survival in the total population and prespecified subgroups. Meta-regression analysis assessed heterogeneity. Twenty-one publications comprising 6,783 patients were eligible for data extraction and inclusion in the meta-analysis. Studies were highly heterogeneous (I2 = 67.3%). The combined hazard ratio of graft loss or failure from random-effects meta-analysis was 3.11 (95% CI 2.44-3.96) in patients with TG compared with those without. Median graft survival in patients with TG was 3.25 (95% CI 0.94-11.21) years-15 years shorter than in those without TG (18.82 [95% CI 10.03-35.32] years). The effect of time from transplantation to biopsy on graft outcomes did not reach statistical significance (p = 0.116). TG was associated with a threefold increase in the risk of graft loss or failure and a 15-year loss in graft survival, indicating viability as a surrogate measure for both clinical practice and studies designed to prevent or reverse antibody-mediated rejection