To investigate the null hypothesis that an objective, noninvasive technique of measuring cardiorespiratory reserve, does not improve the preoperative assessment of patient risk of postoperative ...complications, when compared with a standard questionnaire-based assessment of functional capacity.
Postoperative complications may be increased in patients with reduced cardiorespiratory function. Activity questionnaires are subjective, whereas cardiopulmonary exercise testing (CPET) provides an objective definition of cardiorespiratory reserve. The use of preoperative CPET to predict postoperative complications is not fully defined.
CPET and an algorithm-based activity assessment (Veterans Activity Questionnaire Index VASI) were performed on consecutive patients (n = 171) with low subjective functional capacity (metabolic equivalent score METS < 7), being assessed for major surgery. A morbidity survey determined postoperative day 7 complications. Logistic regression defined independent predictors of complication group. Receiver-operating curve (ROC) analysis defined the predictive value of CPET to outcome. P < 0.05 value demonstrated significance.
Objective cardiorespiratory reserve did not differ between operated (n = 116) and nonoperated patients (n = 55). Median complication rate on postoperative day 7 was 1. Patients with >1 complication had an increase in hospital LOS compared to the group with < or =1 complication (26 vs. 10 days; P < 0.001). Anaerobic threshold (AT) was higher in the group with < or =1 complication (11.9 vs. 9.1 mL/kg/min; P = 0.001) and demonstrated high accuracy (AUC = 0.85), sensitivity (88%), and specificity (79%), at an optimum AT of 10.1 mL/kg/min (defined by the furthest left point on the ROC curve). AT, VASI, and surgical reintervention were independent predictors of complication group. Preoperative AT significantly improved outcome prediction when compared with the use of VASI alone.
An objective measure of cardiorespiratory reserve was an independent predictor of a major surgical group with increased postoperative complications and hospital LOS. AT measurement significantly improved outcome prediction compared with an algorithm-based activity assessment.
The science of networks has revolutionised research into the dynamics of interacting elements. It could be argued that epidemiology in particular has embraced the potential of network theory more ...than any other discipline. Here we review the growing body of research concerning the spread of infectious diseases on networks, focusing on the interplay between network theory and epidemiology. The review is split into four main sections, which examine: the types of network relevant to epidemiology; the multitude of ways these networks can be characterised; the statistical methods that can be applied to infer the epidemiological parameters on a realised network; and finally simulation and analytical methods to determine epidemic dynamics on a given network. Given the breadth of areas covered and the ever-expanding number of publications, a comprehensive review of all work is impossible. Instead, we provide a personalised overview into the areas of network epidemiology that have seen the greatest progress in recent years or have the greatest potential to provide novel insights. As such, considerable importance is placed on analytical approaches and statistical methods which are both rapidly expanding fields. Throughout this review we restrict our attention to epidemiological issues.
To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an ...effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that
, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of
cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone.
function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively.
is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation and, with miR-488-3p, represent novel targets for the modulation of complex I activity.
Wildlife managers routinely seek to establish sustainable limits of sport harvest or other regulated forms of take while confronted with considerable uncertainty. A growing body of ecological ...research focuses on methods to describe and account for uncertainty in management decision-making and to prioritize research and monitoring investments to reduce the most influential uncertainties. We used simulation methods incorporating measures of demographic uncertainty to evaluate risk of overharvest and prioritize information needs for North American sea ducks (Tribe Mergini). Sea ducks are popular game birds in North America, yet they are poorly monitored and their population dynamics are poorly understood relative to other North American waterfowl. There have been few attempts to assess the sustainability of harvest of North American sea ducks, and no formal harvest strategy exists in the U.S. or Canada to guide management. The popularity of sea duck hunting, extended hunting opportunity for some populations (i.e., special seasons and/or bag limits), and population declines have led to concern about potential overharvest. We used Monte Carlo simulation to contrast estimates of allowable harvest and observed harvest and assess risk of overharvest for 7 populations of North American sea ducks: the American subspecies of common eider (Somateria mollissima dresseri), eastern and western populations of black scoter (Melanitta americana) and surf scoter (M. perspicillata), and continental populations of white-winged scoter (M. fusca) and long-tailed duck (Clangula hyemalis). We combined information from empirical studies and the opinions of experts through formal elicitation to create probability distributions reflecting uncertainty in the individual demographic parameters used in this assessment. Estimates of maximum growth (rmax), and therefore of allowable harvest, were highly uncertain for all populations. Long-tailed duck and American common eider appeared to be at high risk of overharvest (i.e., observed harvest < allowable harvest in 5-7% and 19-26% of simulations, respectively depending on the functional form of density dependence), whereas the other populations appeared to be at moderate risk to low risk (observed harvest < allowable harvest in 22-68% of simulations, again conditional on the form of density dependence). We also evaluated the sensitivity of the difference between allowable and observed harvest estimates to uncertainty in individual demographic parameters to prioritize information needs. We found that uncertainty in overall fecundity had more influence on comparisons of allowable and observed harvest than adult survival or observed harvest for all species except long-tailed duck. Although adult survival was characterized by less uncertainty than individual components of fecundity, it was identified as a high priority information need given the sensitivity of growth rate and allowable harvest to this parameter. Uncertainty about population size was influential in the comparison of observed and allowable harvest for 5 of the 6 populations where it factored into the assessment. While this assessment highlights a high degree of uncertainty in allowable harvest, it provides a framework for integration of improved data from future research and monitoring. It could also serve as the basis for harvest strategy development as management objectives and regulatory alternatives are specified by the management community.
The phenotype and function of cells enriched in tumor-propagating activity and their relationship to the phenotypic architecture in multiple myeloma (MM) are controversial. Here, in a cohort of 30 ...patients, we show that MM composes 4 hierarchically organized, clonally related subpopulations, which, although phenotypically distinct, share the same oncogenic chromosomal abnormalities as well as immunoglobulin heavy chain complementarity region 3 area sequence. Assessed in xenograft assays, myeloma-propagating activity is the exclusive property of a population characterized by its ability for bidirectional transition between the dominant CD19−CD138+ plasma cell (PC) and a low frequency CD19−CD138− subpopulation (termed Pre-PC); in addition, Pre-PCs are more quiescent and unlike PCs, are primarily localized at extramedullary sites. As shown by gene expression profiling, compared with PCs, Pre-PCs are enriched in epigenetic regulators, suggesting that epigenetic plasticity underpins the phenotypic diversification of myeloma-propagating cells. Prospective assessment in paired, pretreatment, and posttreatment bone marrow samples shows that Pre-PCs are up to 300-fold more drug-resistant than PCs. Thus, clinical drug resistance in MM is linked to reversible, bidirectional phenotypic transition of myeloma-propagating cells. These novel biologic insights have important clinical implications in relation to assessment of minimal residual disease and development of alternative therapeutic strategies in MM.
•CD19−CD138+ and CD19−CD138− myeloma cells represent interconvertible phenotypic and functional states and share myeloma-propagating activity.•Nongenetic, including epigenetic, diversification of myeloma-propagating cells is linked to clinical drug resistance.
The congenital dyserythropoietic anemias are a heterogeneous group of rare disorders primarily affecting erythropoiesis with characteristic morphological abnormalities and a block in erythroid ...maturation. Mutations in the CDAN1 gene, which encodes Codanin-1, underlie the majority of congenital dyserythropoietic anemia type I cases. However, no likely pathogenic CDAN1 mutation has been detected in approximately 20% of cases, suggesting the presence of at least one other locus. We used whole genome sequencing and segregation analysis to identify a homozygous T to A transversion (c.533T>A), predicted to lead to a p.L178Q missense substitution in C15ORF41, a gene of unknown function, in a consanguineous pedigree of Middle-Eastern origin. Sequencing C15ORF41 in other CDAN1 mutation-negative congenital dyserythropoietic anemia type I pedigrees identified a homozygous transition (c.281A>G), predicted to lead to a p.Y94C substitution, in two further pedigrees of SouthEast Asian origin. The haplotype surrounding the c.281A>G change suggests a founder effect for this mutation in Pakistan. Detailed sequence similarity searches indicate that C15ORF41 encodes a novel restriction endonuclease that is a member of the Holliday junction resolvase family of proteins.
The use of closed-suction drainage systems after total joint replacement is a common practice. The theoretical advantages for the use of drains is a reduction in the occurrence of wound hematomas and ...infection. The aim of this meta-analysis was to determine, on the basis of the evidence from randomized controlled trials, the advantages and adverse effects of surgical drains.
All randomized trials, as far as we know, that compared patients managed with closed-suction drainage systems and those managed without a drain following elective hip and knee arthroplasty were considered. The trials were identified with use of searches of the Cochrane Collaboration with no restriction on languages or source. Two authors independently extracted the data, and the methods of all identified trials were assessed.
Eighteen studies involving 3495 patients with 3689 wounds were included in the analysis. The pooled results indicated that there was no significant difference between the wounds treated with a drain and those treated without a drain with respect to the occurrence of wound infection (relative risk, 0.73; 95% confidence interval, 0.47 to 1.14), wound hematoma (relative risk, 1.73; 95% confidence interval, 0.74 to 4.07), or reoperations for wound complications (relative risk, 0.52; 95% confidence interval, 0.13 to 1.99). A drained wound was associated with a significantly greater need for transfusion (relative risk, 1.43; 95% confidence interval, 1.19 to 1.72). Reinforcement of wound dressings was required more frequently in the group managed without drains. No difference between the groups was seen with respect to limb-swelling, venous thrombosis, or hospital stay.
Studies to date have indicated that closed suction drainage increases the transfusion requirements after elective hip and knee arthroplasty and has no major benefits. Further randomized trials with use of larger numbers of patients with full reporting of outcomes are indicated before the absence of any benefit, particularly for the outcome of wound infection, can be proved.
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