A brief history of long memory: Hurst, Mandelbrot and the road to ARFIMA

Long memory plays an important role in many fields by determining the behaviour and predictability of systems; for instance, climate, hydrology, finance, networks and DNA sequencing. In particular, it is important to test if a process is exhibiting long memory since that impacts the accuracy and confidence with which one may predict future events on the basis of a small amount of historical data. A major force in the development and study of long memory was the late Benoit B. Mandelbrot. Here we discuss the original motivation of the development of long memory and Mandelbrot's influence on this fascinating field. We will also elucidate the sometimes contrasting approaches to long memory in different scientific communitiesComment: 40 page

Prediction of Critical Illness During Out-of-Hospital Emergency Care

CONTEXT: Early identification of nontrauma patients in need of critical care services in the emergency setting may improve triage decisions and facilitate regionalization of critical care. OBJECTIVES: To determine the out-of-hospital clinical predictors of critical illness and to characterize the performance of a simple score for out-of-hospital prediction of development of critical illness during hospitalization. DESIGN AND SETTING: Population-based cohort study of an emergency medical services (EMS) system in greater King County, Washington (excluding metropolitan Seattle), that transports to 16 receiving facilities. PATIENTS: Nontrauma, non-cardiac arrest adult patients transported to a hospital by King County EMS from 2002 through 2006. Eligible records with complete data (N = 144,913) were linked to hospital discharge data and randomly split into development (n = 87,266 [60%]) and validation (n = 57,647 [40%]) cohorts. MAIN OUTCOME MEASURE: Development of critical illness, defined as severe sepsis, delivery of mechanical ventilation, or death during hospitalization. RESULTS: Critical illness occurred during hospitalization in 5% of the development (n = 4835) and validation (n = 3121) cohorts. Multivariable predictors of critical illness included older age, lower systolic blood pressure, abnormal respiratory rate, lower Glasgow Coma Scale score, lower pulse oximetry, and nursing home residence during out-of-hospital care (P < .01 for all). When applying a summary critical illness prediction score to the validation cohort (range, 0-8), the area under the receiver operating characteristic curve was 0.77 (95% confidence interval [CI], 0.76-0.78), with satisfactory calibration slope (1.0). Using a score threshold of 4 or higher, sensitivity was 0.22 (95% CI, 0.20-0.23), specificity was 0.98 (95% CI, 0.98-0.98), positive likelihood ratio was 9.8 (95% CI, 8.9-10.6), and negative likelihood ratio was 0.80 (95% CI, 0.79- 0.82). A threshold of 1 or greater for critical illness improved sensitivity (0.98; 95% CI, 0.97-0.98) but reduced specificity (0.17; 95% CI, 0.17-0.17). CONCLUSIONS: In a population-based cohort, the score on a prediction rule using out-of-hospital factors was significantly associated with the development of critical illness during hospitalization. This score requires external validation in an independent populationPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85143/1/Seymour - JAMA-2010-747-54.pdf11

Automated imaging system for fast quantitation of neurons, cell morphology and neurite morphometry in vivo and in vitro

Producción CientíficaQuantitation of neurons using stereologic approaches reduces bias and systematic error, but is time-consuming and labor-intensive. Accurate methods for quantifying neurons in vitro are lacking; conventional methodologies are limited in reliability and application. The morphological properties of the soma and neurites are a key aspect of neuronal phenotype and function, but the assays commonly used in such evaluations are beset with several methodological drawbacks. Herein we describe automated techniques to quantify the number and morphology of neurons (or any cell type, e.g., astrocytes) and their processes with high speed and accuracy. Neuronal quantification from brain tissue using a motorized stage system yielded results that were statistically comparable to those generated by stereology. The approach was then adapted for in vitro neuron and neurite outgrowth quantification. To determine the utility of our methods, rotenone was used as a neurotoxicant leading to morphological changes in neurons and cell death, astrocytic activation, and loss of neurites. Importantly, our technique counted about 8 times as many neurons in less than 5-10% of the time taken by manual stereological analysis

Understanding uncertainty and bias to improve causal inference in health intervention research

Most research on health interventions aims to find evidence to support better causal inferences about those interventions. However, for decades, a majority of this research has been criticised for inadequate control of bias and overconfident conclusions that do not reflect the uncertainty. Yet, despite the need for improvement, clear signs of progress have not appeared, suggesting the need for new ideas on ways to reduce bias and improve the quality of research. With the aim of understanding why bias has been difficult to reduce, we first explore the concepts of causal inference, bias and uncertainty as they relate to health intervention research. We propose a useful definition of ‘a causal inference’ as: ‘a conclusion that the evidence available supports either the existence, or the non-existence, of a causal effect’. We used this definition in a methodological review that compared the statistical methods used in health intervention cohort studies with the strength of causal language expressed in each study’s conclusions. Studies that used simple instead of multivariable methods, or did not conduct a sensitivity analysis, were more likely to contain overconfident conclusions and potentially mislead readers. The review also examined how the strength of causal language can be judged, including an attempt to create an automatic rating algorithm that we ultimately deemed cannot succeed. This review also found that a third of the articles (94/288) used a propensity score method, highlighting the popularity of a method developed specifically for causal inference. On the other hand, 11% of the articles did not adjust for any confounders, relying on methods such as t-tests and chi-squared tests. This suggests that many researchers still lack an understanding of how likely it is that confounding affects their results. Drawing on knowledge from statistics, philosophy, linguistics, cognitive psychology, and all areas of health research, the central importance of how people think and make decisions is examined in relation to bias in research. This reveals the many hard-wired cognitive biases that, aside from confirmation bias, are mostly unknown to statisticians and researchers in health. This is partly because they mostly occur without conscious awareness, yet everyone is susceptible. But while the existence of biases such as overconfidence bias, anchoring, and failure to account for the base rate have been raised in the health research literature, we examine biases that have not been raised in health, or we discuss them from a different perspective. This includes a tendency of people to accept the first explanation that comes to mind (called take-the-first heuristic); how we tend to believe that other people are more susceptible to cognitive biases than we are (bias blind spot); a tendency to seek arguments that defend our beliefs, rather than seeking the objective truth (myside bias); a bias for causal explanations (various names including the causality heuristic); and our desire to avoid cognitive effort (many names including the ‘law of least mental effort’). This knowledge and understanding also suggest methods that might counter these biases and improve the quality of research. This includes any technique that encourages the consideration of alternative explanations of the results. We provide novel arguments for a number of methods that might help, such as the deliberate listing of alternative explanations, but also some novel ideas including a form of adversarial collaboration. Another method that encourages the researcher to consider alternative explanations is causal diagrams. However, we introduce them in a way that differs from the more formal presentation that is currently the norm, avoiding most of the terminology to focus instead on their use as an intuitive framework, helping the researcher to understand the biases that may lead to different conclusions. We also present a case study where we analysed the data for a pragmatic randomised controlled trial of a telemonitoring service. Considerable missing data hampered the forming of conclusions; however, this enabled an exploration of methods to better understand, reduce and communicate the uncertainty that remained after the analysis. Methods used included multiple imputation, causal diagrams, a listing of alternative explanations, and the parametric g-formula to handle bias from time-dependent confounding. Finally, we suggest strategies, resources and tools that may overcome some of the barriers to better control of bias and improvements in causal inference, based on the knowledge and ideas presented in this thesis. This includes a proposed online searchable causal diagram database, to make causal diagrams themselves easier to learn and use

Peptides as potent antimicrobials tethered to a solid surface: Implications for medical devices

Medical devices are an integral part of therapeutic management; despite their importance, they carry a significant risk of microbial infection. Bacterial attachment to a medical device is established by a single, multiplying organism, leading to subsequent biofilm formation. To date, no preventative measures have impacted the incidence of device-related infection. We report the bidirectional covalent coupling of an engineered cationic antimicrobial peptide (eCAP), WLBU2, to various biological surfaces is accomplished. These surfaces included (i) a carbohydrate-based gel matrix, (ii) a complex polymeric plastic bead, and (iii) a silica-calcium phosphate nanocomposite associated with bone reconstruction. WLBU2-conjugated surfaces are shown to retain potent antimicrobial activity related to bacterial surface adhesion. This study provides proof of principle that covalently coating laboratory and bone-regenerating materials with eCAPs has the potential for decreasing infection rates of implanted devices. These findings have important consequences to the patient management component of our current health care technology

An ancient spliceosomal intron in the ribosomal protein L7a gene (Rpl7a) of Giardia lamblia

BACKGROUND: Only one spliceosomal-type intron has previously been identified in the unicellular eukaryotic parasite, Giardia lamblia (a diplomonad). This intron is only 35 nucleotides in length and is unusual in possessing a non-canonical 5' intron boundary sequence, CT, instead of GT. RESULTS: We have identified a second spliceosomal-type intron in G. lamblia, in the ribosomal protein L7a gene (Rpl7a), that possesses a canonical GT 5' intron boundary sequence. A comparison of the two known Giardia intron sequences revealed extensive nucleotide identity at both the 5' and 3' intron boundaries, similar to the conserved sequence motifs recently identified at the boundaries of spliceosomal-type introns in Trichomonas vaginalis (a parabasalid). Based on these observations, we searched the partial G. lamblia genome sequence for these conserved features and identified a third spliceosomal intron, in an unassigned open reading frame. Our comprehensive analysis of the Rpl7a intron in other eukaryotic taxa demonstrates that it is evolutionarily conserved and is an ancient eukaryotic intron. CONCLUSION: An analysis of the phylogenetic distribution and properties of the Rpl7a intron suggests its utility as a phylogenetic marker to evaluate particular eukaryotic groupings. Additionally, analysis of the G. lamblia introns has provided further insight into some of the conserved and unique features possessed by the recently identified spliceosomal introns in related organisms such as T. vaginalis and Carpediemonas membranifera

The gender specification and cultural sensitivity of depression research with Black Americans: A multidimensional model

http://deepblue.lib.umich.edu/bitstream/2027.42/64287/1/Watkins_Johnson2008.pd

Sunproofed study protocol: A mixed-methods scoping study of sun safety policies in primary schools in Wales

BackgroundSkin cancer, including melanoma and non-melanoma (keratinocyte), is increasing in incidence in the UK. Accounting for half of all cancers in England and Wales, the disease significantly impacts overstretched dermatology services. Research suggests that 86% of melanoma is preventable with modified sun exposure. Educating children about sun safety in schools can help prevent skin cancer and is recommended by major health organisations. In England, teaching sun safety in primary schools is compulsory, while in Wales this is left to school discretion.AimsUnderstand how primary schools in Wales are responding to growing skin cancer rates and explore the effectiveness of sun safety policies in schools on knowledge and behaviour.MethodsSunproofed is a mixed-methods scoping study comprising 5 work packages (WP) using survey and routine electronic health record (EHR) data supplemented by qualitative case studies. Objective(s) are to: WP1: Discover if primary schools in Wales have sun safety policies; policy characteristics; determine factors that may influence their presence and identify areas where schools need support. WP2: Determine what EHR data is available regarding the incidence of sunburn in primary school children and the feasibility of using this data to evaluate the impact of sun safety policies. WP3: Understand the impact of sun safety policies on sun-safe knowledge and behaviour amongst children, parents, teachers, and school management; identify barriers and facilitators to schools implementing sun safety policies. WP4: Co-produce guidance regarding sun safety policies and best methods for implementation in schools. WP5: Disseminate guidance and findings widely to ensure impact and uptake.DiscussionSkin cancer rates are increasing in the UK, straining limited resources. Sunproofed has the potential to inform the development of future prevention activities, both in Wales and beyond. This could reduce the number of skin cancer cases in the future and keep people healthier for longer