Treatment of Young Children with HIV Infection: Using Evidence to Inform Policymakers

PMCID: PMC3404108This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Hierarchical network meta-analysis models to address sparsity of events and differing treatment classifications with regard to adverse outcomes

This is the accepted version of the article, which has been published in final form at DOI: 10.1002/sim.6131.Meta-analysis for adverse events resulting from medical interventions has many challenges, in part due to small numbers of such events within primary studies. Furthermore, variability in drug dose, potential differences between drugs within the same pharmaceutical class and multiple indications for a specific treatment can all add to the complexity of the evidence base. This paper explores the use of synthesis methods, incorporating mixed treatment comparisons, to estimate the risk of adverse events for a medical intervention, while acknowledging and modelling the complexity of the structure of the evidence base. The motivating example was the effect on malignancy of three anti-tumour necrosis factor (anti-TNF) drugs (etanercept, adalimumab and infliximab) indicated to treat rheumatoid arthritis. Using data derived from 13 primary studies, a series of meta-analysis models of increasing complexity were applied. Models ranged from a straightforward comparison of anti-TNF against non-anti-TNF controls, to more complex models in which a treatment was defined by individual drug and its dose. Hierarchical models to allow 'borrowing strength' across treatment classes and dose levels, and models involving constraints on the impact of dose level, are described. These models provide a flexible approach to estimating sparse, often adverse, outcomes associated with interventions. Each model makes its own set of assumptions, and approaches to assessing goodness of fit of the various models will usually be extremely limited in their effectiveness, due to the sparse nature of the data. Both methodological and clinical considerations are required to fit realistically complex models in this area and to evaluate their appropriateness.Partially supported by a National Institute for Health Research Senior Investigator Awar

Canonical Generations and the British Left: The Narrative Construction of the Miners’ Strike 1984–85

‘Generations’ have been invoked to describe a variety of social and cultural relationships, and to understand the development of self-conscious group identity. Equally, the term can be an applied label and politically useful construct; generations can be retrospectively produced. Drawing on the concept of ‘canonical generations’ – those whose experiences come to epitomise an event of historic and symbolic importance – this article examines the narrative creation and functions of ‘generations’ as collective memory shapes and re-shapes the desire for social change. Building a case study of the canonical role of the miners’ strike of 1984–85 in the narrative history of the British left, it examines the selective appropriation and transmission of the past in the development of political consciousness. It foregrounds the autobiographical narratives of activists who, in examining and legitimising their own actions and prospects, (re)produce a ‘generation’ in order to create a relatable and useful historical understanding

The Role of Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Primary Staging of Newly Diagnosed Prostate Cancer: A Systematic Review of the Literature

Context Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT), in initial staging remains controversial. Objective To systematically review the studies of MRI and/or PET/CT in the staging of newly diagnosed PCa with respect to tumor (T), nodal (N), and metastatic (M) staging (TNM staging). Evidence acquisition We performed a systematic review of the literature using MEDLINE and Web of Science databases between 2012 and 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. Evidence synthesis A total of 139 studies (83 on T, 47 on N, and 24 on M status) were included. Ninety-nine (71%) were retrospective, 39 (28%) were prospective, and one was a randomized controlled trial (RCT). Most studies on T staging examined MRI, while PET/CT was used primarily for N and M staging. Sensitivity for the detection of extraprostatic extension, seminal vesicle invasion, or lymph node invasion ranged widely. When imaging was incorporated into existing risk tools, gain in accuracy was observed in some studies, although these findings have not been replicated. For M staging, most favorable results were reported for prostate-specific membrane antigen (PSMA) PET/CT, which demonstrated significantly better performance than conventional imaging. Conclusions A variety of studies on modern imaging techniques for TNM staging in newly diagnosed PCa exist. For T and N staging, reported sensitivity of imaging modalities such as MRI or PET/CT varied widely due to data heterogeneity, small sample size, and low event rates resulting in large confidence intervals and a high level of uncertainty. Therefore, uniformity in data presentation and standardization on this topic are needed. The most promising technique for M staging, which was evaluated recently in an RCT, is PSMA-PET/CT. Patient summary We performed a systematic review of currently available imaging modalities to stage newly diagnosed prostate cancer. With respect to local tumor and lymph node assessment, performance of imaging ranged widely. However, prostate-specific membrane antigen positron emission tomography/computed tomography showed favorable results for the detection of distant metastases

Calculating Unknown Eigenvalues with a Quantum Algorithm

Quantum algorithms are able to solve particular problems exponentially faster than conventional algorithms, when implemented on a quantum computer. However, all demonstrations to date have required already knowing the answer to construct the algorithm. We have implemented the complete quantum phase estimation algorithm for a single qubit unitary in which the answer is calculated by the algorithm. We use a new approach to implementing the controlled-unitary operations that lie at the heart of the majority of quantum algorithms that is more efficient and does not require the eigenvalues of the unitary to be known. These results point the way to efficient quantum simulations and quantum metrology applications in the near term, and to factoring large numbers in the longer term. This approach is architecture independent and thus can be used in other physical implementations

The Many Faces of Fear: Comparing the Pathways and Impacts of Nonconsumptive Predator Effects on Prey Populations

Background: Most ecological models assume that predator and prey populations interact solely through consumption: predators reduce prey densities by killing and consuming individual prey. However, predators can also reduce prey densities by forcing prey to adopt costly defensive strategies. Methodology/Principal Findings: We build on a simple Lotka-Volterra predator-prey model to provide a heuristic tool for distinguishing between the demographic effects of consumption (consumptive effects) and of anti-predator defenses (nonconsumptive effects), and for distinguishing among the multiple mechanisms by which anti-predator defenses might reduce prey population growth rates. We illustrate these alternative pathways for nonconsumptive effects with selected empirical examples, and use a meta-analysis of published literature to estimate the mean effect size of each pathway. Overall, predation risk tends to have a much larger impact on prey foraging behavior than measures of growth, survivorship, or fecundity. Conclusions/Significance: While our model provides a concise framework for understanding the many potential NCE pathways and their relationships to each other, our results confirm empirical research showing that prey are able to partially compensate for changes in energy income, mitigating the fitness effects of defensive changes in time budgets. Distinguishing the many facets of nonconsumptive effects raises some novel questions, and will help guide both empirica

Integrating evolution into ecological modelling: accommodating phenotypic changes in agent based models.

PMCID: PMC3733718This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Evolutionary change is a characteristic of living organisms and forms one of the ways in which species adapt to changed conditions. However, most ecological models do not incorporate this ubiquitous phenomenon. We have developed a model that takes a 'phenotypic gambit' approach and focuses on changes in the frequency of phenotypes (which differ in timing of breeding and fecundity) within a population, using, as an example, seasonal breeding. Fitness per phenotype calculated as the individual's contribution to population growth on an annual basis coincide with the population dynamics per phenotype. Simplified model variants were explored to examine whether the complexity included in the model is justified. Outputs from the spatially implicit model underestimated the number of individuals across all phenotypes. When no phenotype transitions are included (i.e. offspring always inherit their parent's phenotype) numbers of all individuals are always underestimated. We conclude that by using a phenotypic gambit approach evolutionary dynamics can be incorporated into individual based models, and that all that is required is an understanding of the probability of offspring inheriting the parental phenotype

Changing Pattern of Esophageal Cancer Incidence in New Mexico: A 30-Year Evaluation

The incidence of esophageal adenocarcinoma has increased over the last 30 years, especially in non-Hispanic whites (nHw). Recent work indicates an increase in Hispanic Americans (HA). It is important to understand the effect of ethnicity on cancer occurrence over a prolonged interval. We searched the New Mexico Tumor Registry for all cases of esophageal cancer from 1 January 1973 to 31 December 2002. Inclusion criteria were histologic diagnosis of adenocarcinoma or squamous cell carcinoma, ethnicity and gender. Incidence rates for both were compared among ethnic groups in 5-year intervals. Nine hundred eighty-eight patients met the criteria. Esophageal adenocarcinoma incidence rates/100,000 population increased significantly over 30 years; 1973–1977, 0.4 cases; 1978–1982, 0.4 cases; 1983–1987, 0.6 cases; 1988–1992, 1.2 cases, 1993–1997, 1.6 cases and 1998–2002, 2.2 cases; P < 0.001. Squamous cell carcinoma incidence rates remained unchanged during the interval. In nHw and HA, adenocarcinoma incidence rates increased significantly during the study period. In all minority groups, squamous cell carcinoma remained the major type. Esophageal adenocarcinoma incidence among nHw and HA increased from 1973 to 2002 in New Mexico. Squamous cell carcinoma remains predominant in minorities. Ethnicity may influence the histology or indicate an increased risk for certain types of esophageal cancer

Lost in reviews:Looking for the involvement of stakeholders, patients, public and other non-researcher contributors in realist reviews

The involvement of non‐researcher contributors (eg, stakeholders, patients and the public, decision and policy makers, experts, lay contributors) has taken a variety of forms within evidence syntheses. Realist reviews are a form of evidence synthesis that involves non‐researcher contributors yet this practice has received little attention. In particular, the role of patient and public involvement (PPI) has not been clearly documented. This review of reviews describes the ways in which contributor involvement, including PPI, is documented within healthcare realist reviews published over the last five years. A total of 448 papers published between 2014 and 2019 were screened, yielding 71 full‐text papers included in this review. Statements about contributor involvement were synthesized across each review using framework analysis. Three themes are described in this article including nomenclature, nature of involvement, and reporting impact.Papers indicate that contributor involvement in realist reviews refers to stakeholders, experts, or advisory groups (ie, professionals, clinicians, or academics). Patients and the public are occasionally subsumed into these groups and in doing so, the nature and impact of their involvement become challenging to identify and at times, is lost completely. Our review findings indicate a need for the realist review community to develop guidance to support researchers in their future collaboration with contributors, including patients and the public

Resurrecting melancholia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65798/1/j.1600-0447.2007.00958.x.pd