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1.  Influence of calibration method on DPOAE measurements: I. Test performance 
Ear and hearing  2010;31(4):533-545.
Calibration errors in distortion-product otoacoustic emission (DPOAE) measurements due to standing waves cause unpredictable changes in stimulus and DPOAE response level. The purpose of this study was to assess the extent to which these errors affect DPOAE test performance. Standard calibration procedures use sound pressure level (SPL) to determine specified levels. Forward pressure level (FPL) is an alternate calibration method that is less susceptible to standing waves. However, FPL derivation requires prior cavity measurements, which have associated variability. In an attempt to address this variability, four FPL methods were compared with SPL: a reference calibration derived from 25 measurements prior to all data collection and a daily calibration measurement, both of which were made at body and room temperature.
Data were collected from 52 normal-hearing and 103 hearing-impaired subjects. DPOAEs were measured for f2 frequencies ranging from 2 to 8 kHz in half-octave steps, with L2 ranging from −20 to 70 dB SPL (5-dB steps),. At each f2, DPOAEs were measured in five calibration conditions: SPL, daily FPL at body temperature (daily body), daily FPL at room temperature (daily room), reference FPL at body temperature (ref body), and reference FPL at room temperature (ref room). Data were used to construct receiver operating characteristic (ROC) curves for each f2, calibration method and L2. From these curves, areas under the ROC curve (AROC) were estimated.
The results of this study are summarized by the following observations: (1) DPOAE test performance was sensitive to stimulus level, regardless of calibration method, with the best test performance observed for moderate stimulus-level conditions. (2) An effect of frequency was observed for all calibration methods, with the best test performance at 6 kHz and the worst performance at 8 kHz. (3) At clinically applicable stimulus levels, little difference in test performance among calibration methods was noted across frequencies, except at 8 kHz. At 8 kHz, FPL-based calibration methods provided superior performance compared with the standard SPL calibration. (4) A difference between FPL calibration methods was observed at 8 kHz, with the best test performance occurring for daily body calibrations.
With the exception of 8 kHz, there was little difference in test performance across calibration methods. At 8 kHz, AROCs and specificities for fixed sensitivities indicate that FPL-based calibration methods provide superior performance compared with the standard SPL calibration for clinically relevant levels. Temperature may have an impact on FPL calculations relative to DPOAE test performance. Although the differences in AROC among calibration procedures were not statistically significant, the present results indicate that standing-wave errors may impact DPOAE test performance and can be reduced by using FPL, although the largest effects were restricted to 8 kHz.
PMCID: PMC2896442  PMID: 20458246
2.  Measures to Summarize and Compare the Predictive Capacity of Markers 
The predictive capacity of a marker in a population can be described using the population distribution of risk (Huang et al. 2007; Pepe et al. 2008a; Stern 2008). Virtually all standard statistical summaries of predictability and discrimination can be derived from it (Gail and Pfeiffer 2005). The goal of this paper is to develop methods for making inference about risk prediction markers using summary measures derived from the risk distribution. We describe some new clinically motivated summary measures and give new interpretations to some existing statistical measures. Methods for estimating these summary measures are described along with distribution theory that facilitates construction of confidence intervals from data. We show how markers and, more generally, how risk prediction models, can be compared using clinically relevant measures of predictability. The methods are illustrated by application to markers of lung function and nutritional status for predicting subsequent onset of major pulmonary infection in children suffering from cystic fibrosis. Simulation studies show that methods for inference are valid for use in practice.
PMCID: PMC2827895  PMID: 20224632
3.  Influence of Calibration Method on DPOAE Measurements: II. Threshold Prediction 
Ear and hearing  2010;31(4):546-554.
Distortion-product otoacoustic emission (DPOAE) stimulus calibrations are typically performed in sound pressure level (SPL) prior to DPOAE measurements. These calibrations may yield unpredictable DPOAE response levels, presumably due to the presence of standing waves in the ear canal. Forward pressure level (FPL) has been proposed as an alternative method for stimulus calibration because it avoids complications due to standing waves. DPOAE thresholds following four FPL calibrations and one SPL calibration were compared to behavioral thresholds to determine which calibration results in data that yield the highest correlations between the two threshold estimates.
Fifty-two subjects with normal hearing and 103 subjects with hearing loss participated, with ages ranging from 11 to 75 years. These were the same individuals whose data were used to address the influence of calibration method on test performance in an accompanying paper (Burke et al., 2010). DPOAE input/output (I/O) functions were obtained at f2 frequencies of 2, 3, 4, 6, and 8 kHz with the primary frequency ratio fixed at f2/f1≈1.22. L1 was set according to the equation L1=0.4L2+39 (Kummer et al. 1998, 2000) with L2 levels ranging from −20 to 70 dB SPL and FPL in 5-dB steps. I/O functions were obtained at each frequency for each of five stimulus calibrations: SPL, daily FPL at room temperature, daily FPL at body temperature, reference FPL at room temperature, and reference FPL at body temperature. DPOAE thresholds were estimated using two methods. In the first, DPOAE threshold was taken as the lowest L2 for which DPOAE level is 3 dB or greater above the noise floor (SNR ≥ 3 dB). In a second method, a linear regression method first described by Boege & Janssen (2002) and later adapted by Gorga et al. (2003), all DPOAE levels in each I/O function are converted to linear pressure and extrapolated to 0 μPa, where the L2 is taken as threshold. Correlations of DPOAE thresholds with behavioral thresholds were obtained for each frequency, calibration method, and threshold-prediction method.
Correlations were greatest for frequencies of 3–6 kHz and lowest for 8 kHz, consistent with the previous frequency effects reported by Gorga et al. (2003). Calibration method made little difference in correlations between DPOAE and behavioral thresholds at any frequency. A small difference was noted in correlations for the two threshold-prediction methods, with the linear regression method yielding slightly higher correlations at all frequencies.
Little difference in threshold correlations was observed among the five calibration methods used to calibrate the stimuli prior to DPOAE measurements. These results were not anticipated given the known effects of standing waves on ear-canal estimates of SPL at the plane of the probe (Siegel, 1994; Siegel and Hirohata, 1994; Siegel, 2007; Driesbach and Siegel, 2001; Neely and Gorga, 1998; Scheperle et al., 2008). In addition, there was no effect of temperature (body vs. room) or timing (daily vs. reference) for FPL calibrations. It may be important to note that differences between SPL and FPL calibrations should not be seen if a standing wave does not occur at the plane of the probe at or near the frequency being tested. The frequencies 2–8 kHz were chosen because it was expected that effects from standing waves would occur between these frequencies due to the typical lengths of ear canals for the age group tested. Because measurements were taken at only five discrete frequencies in the interval, it is possible that standing waves were present but did not affect the specific test frequencies. In total, these results suggest that SPL calibrations may be adequate when attempting to predict pure-tone thresholds from DPOAEs, despite the fact that they are known to be susceptible to errors associated with standing waves.
PMCID: PMC2896427  PMID: 20458245
4.  Achondroplasia and hypochondroplasia. Comments on frequency, mutation rate, and radiological features in skull and spine. 
Journal of Medical Genetics  1979;16(2):140-146.
An attempt was made to ascertain all the dwarfs in the State of Victoria. The incidence of achondroplasia proved to be approximately 1 in 26,000 live births in the period 1969 to 1975 when ascertainment was nearly complete. This indicates a mutation rate of 1.93 X 10(-5) per generation in this locus. Paternal age was shown to influence mutation. Ascertainment in earlier years of the study was low despite the very great effort made to find all cases. Patients with hypochondroplasia were particularly difficult to find. However, 25 cases were found for study. Overlap between hypochondroplasia and achondroplasia was found in all features except the facial appearance (which was the basis of definition). Achondroplasia was more severe in all regards, but some individuals with hypochondroplasia were very short and some had extreme degrees of spinal canal stenosis. The classical measurements used to describe the skull changes in acondroplasia failed to distinguish this condition from hypochondroplasia. More efficient indices were devised, but visual assessment of the size of the facial region compared to that of the cranial valult proved more reliable than any index. The clinical distinction based upon facial appearance remains the arbitrary basis of definition.
PMCID: PMC1012739  PMID: 458831
5.  “Those Comments Last Forever”: Parents and Grandparents of Preschoolers Recount How They Became Aware of Their Own Body Weights as Children 
PLoS ONE  2014;9(11):e111974.
Parents' and grandparents' willingness to talk about children's body weights may be influenced by their own childhood experiences of body weight awareness and ‘weight talk’ in the family; however, little is known about how adults describe their recollected weight-related childhood experiences.
This paper examines how parents and grandparents of preschoolers describe the emergence of their own body weight awareness in childhood or adolescence. The analysis highlights the sources that participants identify as having instigated their body weight awareness, the feelings and experiences participants associate with the experience of becoming aware of their body weights, and their framings of potential links between childhood experiences and attitudes and practices in adulthood.
49 participants (22 parents, 27 grandparents, 70% women, 60% with overweight/obesity) from sixteen low-income families of children aged 3–5 years (50% girls, 56% with overweight/obesity) in the Pacific Northwest were interviewed. The interviews were videotaped, transcribed, and analyzed qualitatively.
Twenty-five participants (51%) said they became aware of their body weights in childhood or adolescence. Fourteen participants said their body weight awareness emerged through comments made by others, with the majority citing parents or peers. No participant described the emergence of body weight awareness in positive terms. Four participants directly linked their own negative experiences to the decision not to discuss body weight with their preschoolers. All four cited critical comments from their parents as instigating their own body weight awareness in childhood.
In most cases, participants associated their emergent awareness of body weight with overtly negative feelings or consequences; some participants said these negative experiences continued to affect them as adults. Since family-based childhood obesity interventions involve open discussion of children's body sizes, the results suggest that clinicians should reframe the discussion to deconstruct obesity stigma and emphasize inclusive, affirmative, and health-focused messages.
PMCID: PMC4230937  PMID: 25393236
6.  Effect of calibration method on distortion-product otoacoustic emission measurements at and around 4 kHz 
Ear and hearing  2013;34(6):10.1097/AUD.0b013e3182994f15.
Distortion-product otoacoustic emissions (DPOAEs) collected following sound pressure level (SPL) calibration are susceptible to standing waves that affect measurements at the plane of the probe microphone due to overlap of incident and reflected waves. These standing wave effects can be as large as 20 dB, and may affect frequencies both above and below 4 kHz. It has been shown that forward pressure level (FPL) calibration minimizes standing-wave effects by isolating the forward-propagating component of the stimulus. Yet, previous work has failed to demonstrate more than a small difference in test performance and behavioral-threshold prediction with DPOAEs following SPL and FPL calibration (Burke et al., 2010; Rogers et al., 2010; Kirby et al., 2011). One potential limitation in prior studies is that measurements were restricted to octave and interoctave frequencies; as a consequence, data were not necessarily collected at the standing-wave null frequency. In the present study, DPOAE responses were measured with f2 set to each subject’s standing-wave frequency in an effort to increase the possibility that differences in test performance and threshold prediction will be observed for SPL and FPL calibration methods.
Data were collected from 42 normal-hearing participants and 93 participants with hearing loss. DPOAEs were measured with f2 set to 4 kHz and at each individual’s notch frequency following SPL and FPL calibration. DPOAE input/output functions were obtained from −10 dB to 80 dB in 5-dB steps for each calibration/stimulus condition. Test performance was evaluated using clinical decision theory. Both area under receiver operating characteristic (AROC) curves for all stimulus levels and cumulative distributions when L2 = 50 dB (a level at which the best performance was observed regardless of calibration method) were used to evaluate the accuracy with which auditory status was determined. A bootstrap procedure was used to evaluate the significance of the differences in test performance between SPL and FPL calibrations. DPOAE predictions of behavioral threshold were evaluated by correlating actual behavioral thresholds and predicted thresholds using a multiple linear regression model.
(1) Larger DPOAE levels were measured following SPL calibration than following FPL calibration, which demonstrated the expected impact of standing waves. (2) For both FPL and SPL calibration, test performance was best for moderate stimulus levels. (3) Differences in test performance between calibration methods were evident at low and high stimulus levels. (4) There were small but statistically significant improvements in test performance following FPL calibration for clinically relevant conditions. (4) Calibration method had no effect on threshold prediction.
Standing waves following SPL calibration have an impact on DPOAE levels. Although the effect of calibration method on test performance was small, test performance was better following FPL calibration than following SPL calibration. There was no effect of calibration method on predictions of behavioral threshold.
PMCID: PMC3812541  PMID: 24165303
7.  A Supervised Approach to Predict the Hierarchical Structure of Conversation Threads for Comments 
The Scientific World Journal  2014;2014:479746.
User-generated texts such as comments in social media are rich sources of information. In general, the reply structure of comments is not publicly accessible on the web. Websites present comments as a list in chronological order. This way, some information is lost. A solution for this problem is to reconstruct the thread structure (RTS) automatically. RTS predicts a semantic tree for the reply structure, useful for understanding users' behaviours and facilitating follow of the actual conversation streams. This paper works on RTS task in blogs, online news agencies, and news websites. These types of websites cover various types of articles reflecting the real-world events. People with different views participate in arguments by writing comments. Comments express opinions, sentiments, or ideas about articles. The reply structure of threads in these types of websites is basically different from threads in the forums, chats, and emails. To perform RTS, we define a set of textual and nontextual features. Then, we use supervised learning to combine these features. The proposed method is evaluated on five different datasets. The accuracy of the proposed method is compared with baselines. The results reveal higher accuracy for our method in comparison with baselines in all datasets.
PMCID: PMC3942392  PMID: 24672323
The American economic review  2013;103(5):2003-2020.
Using historical census and survey data, Long and Ferrie (forthcoming) found a significant decline in social mobility in the United States from 1880 to 1973. We present two critiques of the Long-Ferrie study. First, the data quality of the Long-Ferrie study is more limiting than the authors acknowledge. Second, and more critically, they applied a method ill-suited for measuring social mobility of farmers in a comparative study between 1880 and 1973, a period in which the proportion of farmers dramatically declined in the U.S. We show that Long and Ferrie’s main conclusion is all driven by this misleading result for farmers.
PMCID: PMC3747841  PMID: 23970805
Social mobility; U.S. history; Census data
9.  Probe Microphone Measurements: 20 Years of Progress 
Trends in Amplification  2001;5(2):35-68.
Probe-microphone testing was conducted in the laboratory as early as the 1940s (e.g., the classic work of Wiener and Ross, reported in 1946), however, it was not until the late 1970s that a “dispenser friendly” system was available for testing hearing aids in the real ear. In this case, the term “dispenser friendly,” is used somewhat loosely. The 1970s equipment that I'm referring to was first described in a paper that was presented by Earl Harford, Ph.D. in September of 1979 at the International Ear Clinics' Symposium in Minneapolis. At this meeting, Earl reported on his clinical experiences of testing hearing aids in the real ear using a miniature (by 1979 standards) Knowles microphone. The microphone was coupled to an interfacing impedance matching system (developed by David Preves, Ph.D., who at the time worked at Starkey Laboratories) which could be used with existing hearing aid analyzer systems (see Harford, 1980 for review of this early work). Unlike today's probe tube microphone systems, this early method of clinical real-ear measurement involved putting the entire microphone (about 4mm by 5mm by 2mm) in the ear canal down by the eardrum of the patient. If you think cerumen is a problem with probe-mic measurements today, you should have seen the condition of this microphone after a day's work!
While this early instrumentation was a bit cumbersome, we quickly learned the advantages that probe-microphone measures provided in the fitting of hearing aids. We frequently ran into calibration and equalization problems, not to mention a yelp or two from the patient, but the resulting information was worth the trouble.
Help soon arrived. In the early 1980s, the first computerized probe-tube microphone system, the Rastronics CCI-10 (developed in Denmark by Steen Rasmussen), entered the U.S. market (Nielsen and Rasmussen, 1984). This system had a silicone tube attached to the microphone (the transmission of sound through this tube was part of the calibration process), which eliminated the need to place the microphone itself in the ear canal. By early 1985, three or four different manufactures had introduced this new type of computerized probe-microphone equipment, and this hearing aid verification procedure became part of the standard protocol for many audiology clinics. At his time, the POGO (Prescription Of Gain and Output) and Libby 1/3 prescriptive fitting methods were at the peak of their popularity, and a revised NAL (National Acoustic Laboratories) procedure was just being introduced. All three of these methods were based on functional gain, but insertion gain easily could be substituted, and therefore, manufacturers included calculation of these prescriptive targets as part of the probe-microphone equipment software. Audiologists, frustrated with the tedious and unreliable functional gain procedure they had been using, soon developed a fascination with matching real-ear results to prescriptive targets on a computer monitor.
In some ways, not a lot has changed since those early days of probe-microphone measurements. Most people who use this equipment simply run a gain curve for a couple inputs and see if it's close to prescriptive target—something that could be accomplished using the equipment from 1985. Contrary to the predictions of many, probe-mic measures have not become the “standard hearing aid verification procedure.” (Mueller and Strouse, 1995). There also has been little or no increase in the use of this equipment in recent years. In 1998, I reported on a survey that was conducted by The Hearing Journal regarding the use of probe-microphone measures (Mueller, 1998). We first looked at what percent of people dispensing hearing aids own (or have immediate access to) probe-microphone equipment. Our results showed that 23% of hearing instrument specialists and 75% of audiologists have this equipment. Among audiologists, ownership varied among work settings: 91% for hospitals/clinics, 73% for audiologists working for physicians, and 69% for audiologists in private practice. But more importantly, and a bit puzzling, was the finding that showed that nearly one half of the people who fit hearing aids and have access to this equipment, seldom or never use it.
I doubt that the use rate of probe-microphone equipment has changed much in the last three years, and if anything, I suspect it has gone down. Why do I say that? As programmable hearing aids have become the standard fitting in many clinics, it is tempting to become enamoured with the simulated gain curves on the fitting screen, somehow believing that this is what really is happening in the real ear. Additionally, some dispensers have been told that you can't do reliable probe-mic testing with modern hearing aids—this of course is not true, and we'll address this issue in the Frequently Asked Questions portion of this paper.
The infrequent use of probe-mic testing among dispensers is discouraging, and let's hope that probe-mic equipment does not suffer the fate of the rowing machine stored in your garage. A lot has changed over the years with the equipment itself, and there are also expanded clinical applications and procedures. We have new manufacturers, procedures, acronyms and noises. We have test procedures that allow us to accurately predict the output of a hearing aid in an infant's ear. We now have digital hearing aids, which provide us the opportunity to conduct real-ear measures of the effects of digital noise reduction, speech enhancement, adaptive feedback, expansion, and all the other features. Directional microphone hearing aids have grown in popularity and what better way to assess the real-ear directivity than with probe-mic measures? The array of assistive listening devices has expanded, and so has the role of the real-ear assessment of these products. And finally, with today's PC -based systems, we can program our hearing aids and simultaneously observe the resulting real-ear effects on the same fitting screen, or even conduct an automated target fitting using earcanal monitoring of the output. There have been a lot of changes, and we'll talk about all of them in this issue of Trends.
PMCID: PMC4168927  PMID: 25425897
10.  Risk Models to Predict Chronic Kidney Disease and Its Progression: A Systematic Review 
PLoS Medicine  2012;9(11):e1001344.
A systematic review of risk prediction models conducted by Justin Echouffo-Tcheugui and Andre Kengne examines the evidence base for prediction of chronic kidney disease risk and its progression, and suitability of such models for clinical use.
Chronic kidney disease (CKD) is common, and associated with increased risk of cardiovascular disease and end-stage renal disease, which are potentially preventable through early identification and treatment of individuals at risk. Although risk factors for occurrence and progression of CKD have been identified, their utility for CKD risk stratification through prediction models remains unclear. We critically assessed risk models to predict CKD and its progression, and evaluated their suitability for clinical use.
Methods and Findings
We systematically searched MEDLINE and Embase (1 January 1980 to 20 June 2012). Dual review was conducted to identify studies that reported on the development, validation, or impact assessment of a model constructed to predict the occurrence/presence of CKD or progression to advanced stages. Data were extracted on study characteristics, risk predictors, discrimination, calibration, and reclassification performance of models, as well as validation and impact analyses. We included 26 publications reporting on 30 CKD occurrence prediction risk scores and 17 CKD progression prediction risk scores. The vast majority of CKD risk models had acceptable-to-good discriminatory performance (area under the receiver operating characteristic curve>0.70) in the derivation sample. Calibration was less commonly assessed, but overall was found to be acceptable. Only eight CKD occurrence and five CKD progression risk models have been externally validated, displaying modest-to-acceptable discrimination. Whether novel biomarkers of CKD (circulatory or genetic) can improve prediction largely remains unclear, and impact studies of CKD prediction models have not yet been conducted. Limitations of risk models include the lack of ethnic diversity in derivation samples, and the scarcity of validation studies. The review is limited by the lack of an agreed-on system for rating prediction models, and the difficulty of assessing publication bias.
The development and clinical application of renal risk scores is in its infancy; however, the discriminatory performance of existing tools is acceptable. The effect of using these models in practice is still to be explored.
Please see later in the article for the Editors' Summary
Editors' Summary
Chronic kidney disease (CKD)—the gradual loss of kidney function—is increasingly common worldwide. In the US, for example, about 26 million adults have CKD, and millions more are at risk of developing the condition. Throughout life, small structures called nephrons inside the kidneys filter waste products and excess water from the blood to make urine. If the nephrons stop working because of injury or disease, the rate of blood filtration decreases, and dangerous amounts of waste products such as creatinine build up in the blood. Symptoms of CKD, which rarely occur until the disease is very advanced, include tiredness, swollen feet and ankles, puffiness around the eyes, and frequent urination, especially at night. There is no cure for CKD, but progression of the disease can be slowed by controlling high blood pressure and diabetes, both of which cause CKD, and by adopting a healthy lifestyle. The same interventions also reduce the chances of CKD developing in the first place.
Why Was This Study Done?
CKD is associated with an increased risk of end-stage renal disease, which is treated with dialysis or by kidney transplantation (renal replacement therapies), and of cardiovascular disease. These life-threatening complications are potentially preventable through early identification and treatment of CKD, but most people present with advanced disease. Early identification would be particularly useful in developing countries, where renal replacement therapies are not readily available and resources for treating cardiovascular problems are limited. One way to identify people at risk of a disease is to use a “risk model.” Risk models are constructed by testing the ability of different combinations of risk factors that are associated with a specific disease to identify those individuals in a “derivation sample” who have the disease. The model is then validated on an independent group of people. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the researchers critically assess the ability of existing CKD risk models to predict the occurrence of CKD and its progression, and evaluate their suitability for clinical use.
What Did the Researchers Do and Find?
The researchers identified 26 publications reporting on 30 risk models for CKD occurrence and 17 risk models for CKD progression that met their predefined criteria. The risk factors most commonly included in these models were age, sex, body mass index, diabetes status, systolic blood pressure, serum creatinine, protein in the urine, and serum albumin or total protein. Nearly all the models had acceptable-to-good discriminatory performance (a measure of how well a model separates people who have a disease from people who do not have the disease) in the derivation sample. Not all the models had been calibrated (assessed for whether the average predicted risk within a group matched the proportion that actually developed the disease), but in those that had been assessed calibration was good. Only eight CKD occurrence and five CKD progression risk models had been externally validated; discrimination in the validation samples was modest-to-acceptable. Finally, very few studies had assessed whether adding extra variables to CKD risk models (for example, genetic markers) improved prediction, and none had assessed the impact of adopting CKD risk models on the clinical care and outcomes of patients.
What Do These Findings Mean?
These findings suggest that the development and clinical application of CKD risk models is still in its infancy. Specifically, these findings indicate that the existing models need to be better calibrated and need to be externally validated in different populations (most of the models were tested only in predominantly white populations) before they are incorporated into guidelines. The impact of their use on clinical outcomes also needs to be assessed before their widespread use is recommended. Such research is worthwhile, however, because of the potential public health and clinical applications of well-designed risk models for CKD. Such models could be used to identify segments of the population that would benefit most from screening for CKD, for example. Moreover, risk communication to patients could motivate them to adopt a healthy lifestyle and to adhere to prescribed medications, and the use of models for predicting CKD progression could help clinicians tailor disease-modifying therapies to individual patient needs.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Maarten Taal
The US National Kidney and Urologic Diseases Information Clearinghouse provides information about all aspects of kidney disease; the US National Kidney Disease Education Program provides resources to help improve the understanding, detection, and management of kidney disease (in English and Spanish)
The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories
The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish)
The not-for-profit UK National Kidney Federation support and information for patients with kidney disease and for their carers, including a selection of patient experiences of kidney disease
World Kidney Day, a joint initiative between the International Society of Nephrology and the International Federation of Kidney Foundations, aims to raise awareness about kidneys and kidney disease
PMCID: PMC3502517  PMID: 23185136
11.  Cloak and DAG: A Response to the Comments on our Comment 
NeuroImage  2011;76:446-449.
Our original comment (Lindquist and Sobel 2011) made explicit the types of assumptions neuroimaging researchers are making when directed graphical models (DGM’s), which include certain types of structural equation models (SEM’s), are used to estimate causal effects. When these assumptions, which many researchers are not aware of, are not met, parameters of these models should not be interpreted as effects. Thus it is imperative that neuroimaging researchers interested in issues involving causation, for example, effective connectivity, consider the plausibility of these assumptions for their particular problem before using SEM’s. In cases where these additional assumptions are not met, researchers may be able to use other methods and/or design experimental studies where the use of unrealistic assumptions can be avoided. Pearl does not disagree with anything we stated. However, he takes exception to our use of potential outcomes notation, which is the standard notation used in the statistical literature on causal inference, and his comment is devoted to promoting his alternative conventions. Glymour’s comment is based on three claims that he inappropriately attributes to us. Glymour is also more optimistic than us about the potential of using directed graphical models (DGM’s) to discover causal relations in neuroimaging research; we briefly address this issue toward the end of our rejoinder.
PMCID: PMC4121662  PMID: 22119004
12.  How to discover modules in mind and brain: The curse of nonlinearity, and blessing of neuroimaging. A comment on Sternberg (2011) 
Cognitive Neuropsychology  2011;28(3-4):209-223.
Sternberg (2011) elegantly formalizes how certain sets of hypotheses, specifically modularity and pure or composite measures, imply certain patterns of behavioural and neuroimaging data. Experimentalists are often interested in the converse, however: whether certain patterns of data distinguish certain hypotheses, specifically whether more than one module is involved. In this case, there is a striking reversal of the relative value of the data patterns that Sternberg considers. Foremost, the example of additive effects of two factors on one composite measure becomes noninformative for this converse question. Indeed, as soon as one allows for nonlinear measurement functions and nonlinear module processes, even a cross-over interaction between two factors is noninformative in this respect. Rather, one requires more than one measure, from which certain data patterns do provide strong evidence for multiple modules, assuming only that the measurement functions are monotonic. If two measures are not monotonically related to each other across the levels of one or more experimental factors, then one has evidence for more than one module (i.e., more than one nonmonotonic transform). Two special cases of this are illustrated here: a “reversed association” between two measures across three levels of a single factor, and Sternberg's example of selective effects of two factors on two measures. Fortunately, functional neuroimaging methods normally do provide multiple measures over space (e.g., functional magnetic resonance imaging, fMRI) and/or time (e.g., electroencephalography, EEG). Thus to the extent that brain modules imply mind modules (i.e., separate processors imply separate processes), the performance data offered by functional neuroimaging are likely to be more powerful in revealing modules than are the single behavioural measures (such as accuracy or reaction time, RT) traditionally considered in psychology.
PMCID: PMC3330956  PMID: 21714750
Cognitive neuroscience; Cognitive psychology; functional magnetic resonance imaging; Electroencephalography; Dissociations
13.  Pharmacometrics and Systems Pharmacology Software Tutorials and Use: Comments and Guidelines for PSP Contributions 
In addition to methodological Tutorials,1 CPT:PSP has recently started to publish software Tutorials.2,3 Our readership and authors may be wondering what kind of format or product is expected, and the review of submissions we have already received prompted several discussions within the PSP Editorial Team. This editorial reflects on these discussions and summarizes their salient points. It aims at providing some details about the current vision of CPT:PSP for software tutorial articles. In addition, it brings some clarity on the topic of what role commercial software tutorials can have in CPT:PSP and how CPT:PSP tutorials differ from publications which describe the software itself, as those which can be found in other computer science journals. Finally, the discussion includes reproducibility considerations and the general use of commercial and noncommercial software in CPT:PSP publications. We hope our thoughts, and especially a stated requirement to publish user input to the software to aid in reproducibility, will help in guiding our authors and will stimulate healthy debate among our readers about the evolving nature of our science, how it can be facilitated using software and associated databases as a conduit, and what role this journal can play in fostering both the best modeling and simulation practices and the best scientific approaches to computational modeling, to bring the advantages of modeling and simulation to all regular practitioners, and not to just a (self) selected few.
PMCID: PMC3872531  PMID: 24352522
14.  Governance of Health Systems Comment on “A Network Based Theory of Health Systems and Cycles of Well-Being”  
Health systems research aims to understand the governance of health systems (i.e. how health systems function and perform and how their actors interact with each other). This can be achieved by applying innovative methodologies and concepts that are going to capture the complexity and dynamics of health systems when they are affected by shocks. The capacity of health systems to adapt to shocks (i.e. the resilience of health systems) is a new area of investigation. Social network analysis is a great avenue that can help measure the properties of systems and analyse the relationships between its actors and between the structure of a health system and the performance of a health system. A new conceptual framework is presented to define the governance of health systems using a resilience perspective.
PMCID: PMC3937924  PMID: 24596859
Health Systems; Social Network Analysis; Governance; Resilience
15.  Use of Sentiment Analysis for Capturing Patient Experience From Free-Text Comments Posted Online 
There are large amounts of unstructured, free-text information about quality of health care available on the Internet in blogs, social networks, and on physician rating websites that are not captured in a systematic way. New analytical techniques, such as sentiment analysis, may allow us to understand and use this information more effectively to improve the quality of health care.
We attempted to use machine learning to understand patients’ unstructured comments about their care. We used sentiment analysis techniques to categorize online free-text comments by patients as either positive or negative descriptions of their health care. We tried to automatically predict whether a patient would recommend a hospital, whether the hospital was clean, and whether they were treated with dignity from their free-text description, compared to the patient’s own quantitative rating of their care.
We applied machine learning techniques to all 6412 online comments about hospitals on the English National Health Service website in 2010 using Weka data-mining software. We also compared the results obtained from sentiment analysis with the paper-based national inpatient survey results at the hospital level using Spearman rank correlation for all 161 acute adult hospital trusts in England.
There was 81%, 84%, and 89% agreement between quantitative ratings of care and those derived from free-text comments using sentiment analysis for cleanliness, being treated with dignity, and overall recommendation of hospital respectively (kappa scores: .40–.74, P<.001 for all). We observed mild to moderate associations between our machine learning predictions and responses to the large patient survey for the three categories examined (Spearman rho 0.37-0.51, P<.001 for all).
The prediction accuracy that we have achieved using this machine learning process suggests that we are able to predict, from free-text, a reasonably accurate assessment of patients’ opinion about different performance aspects of a hospital and that these machine learning predictions are associated with results of more conventional surveys.
PMCID: PMC3841376  PMID: 24184993
Internet; patient experience; quality; machine learning
16.  Weight Comments by Family and Significant Others in Young Adulthood 
Body image  2010;8(1):12-19.
Weight teasing is common among adolescents, but less is known about the continuation of this experience during young adulthood. The present study uses survey data from a diverse sample of 2,287 young adults, who participated in a 10-year longitudinal study of weight-related issues to examine hurtful weight comments by family members or a significant other. Among young adults, 35.9% of females and 22.8% of males reported receiving hurtful weight-related comments by family members, and 21.2% of females and 23.8% of males with a significant other had received hurtful weight-related comments from this source. Hispanic and Asian young adults and overweight/obese young adults were more likely to report receiving comments than those in other groups. Weight teasing during adolescence predicted hurtful weight-related comments in young adulthood, with some differences by gender. Findings suggest that hurtful weight talk continues into young adulthood and is predicted by earlier weight teasing experiences.
PMCID: PMC3101896  PMID: 21163716
Weight teasing; romantic relationships; emerging adults; young adults
17.  Neoplecostomus doceensis: a new loricariid species (Teleostei, Siluriformes) from the rio Doce basin and comments about its putative origin 
ZooKeys  2014;115-127.
A new species of Neoplecostomus is described from the rio Doce basin representing the first species of this genus in the basin. The new species is distinguished from its congeners by having enlarged, fleshy folds between dentaries, two or three series of developed papillae anterior to premaxillary teeth and a adipose-fin membrane present, and by lacking enlarged odontodes along snout lateral margins in mature males, a well-developed dorsal-fin spinelet wider than dorsal-fin spine base, lower number of lateral-line figs and developed membrane on the dorsal portion of the first, second and third pelvic-fin branched rays. Additionally, we present a brief discussion of biogeographic scenarios that may explain the distribution of the new species in the rio Doce basin. We suggested that the ancestral lineage of the new species reached the rio Doce from the upper portions of rio Paraná drainages about 3.5 Mya (95% HPD: 1.6–5.5) indicating a colonization route of the N. doceensis ancestral lineage from the south end of Serra do Espinhaço, probably as a result of headwater capture processes between the upper rio Paraná and rio Doce basins.
PMCID: PMC4195942  PMID: 25317064
Brazilian shield; catfishes; freshwater; ichthyology; Neoplecostominae; Neotropical fishes; Ostariophysi
18.  Rhinolekos capetinga: a new cascudinho species (Loricariidae, Otothyrinae) from the rio Tocantins basin and comments on its ancestral dispersal route 
ZooKeys  2015;109-130.
The present study deals with the description of a new species of Rhinolekos. It can be distinguished from its congeners by having 31 vertebrae, the anterior portion of the compound supraneural-first dorsal-fin proximal radial contacting the neural spine of the 9th vertebra, the absence of transverse dark bands in the pectoral, pelvic and anal-fin rays, 24–28 plates in the dorsal series, the lack of odontodes on the ventral tip of the snout, the absence of accessory teeth, a greater prenasal length, a smaller head length, and by a greater snout length. Rhinolekos capetinga is restricted to the headwaters of the rio Tocantins and it is the first species of this genus in the Amazon basin. Additionally, we present a brief discussion of a biogeographic scenario that may explain the dispersal of the new species from the rio Paranaíba to the rio Tocantins basin. We suggest that the ancestral lineage of Rhinolekos capetinga reached the rio Tocantins from portions of the rio Paranaíba at the end of the Miocene, about 6.3 Mya (4.1–13.9 Mya 95% HPD), probably as a result of headwater capture processes among adjacent drainages.
PMCID: PMC4319103
Biodiversity; Freshwater; Neotropical fish; South America; Taxonomy
19.  Comments on the Eslicarbazepine Acetate Section of the Article ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’  
Pharmaceuticals  2010;3(12):3629-3632.
The recent review of Matthew D. Krasowski on ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’ is a useful foundation of comparative interpretations on our current knowledge about therapeutic drug monitoring. Within the review, the statement that therapeutic drug monitoring has a minimal role in the therapeutic use of eslicarbazepine acetate due to its relatively predictable pharmacokinetics reflects the existing body of evidence although some information such as eslicarbazepine acetate’s chemical structure, proportions of its metabolites, their pharmacokinetics and chiral method of plasma level measurement need to be revised. These critical characteristics differentiate the novel compound from former dibenzazepines such as carbamazepine and oxcarbazepine in its clinical effects and needs for therapeutic drug monitoring.
PMCID: PMC4034070
anticonvulsants; anti-epileptic drugs; drug monitoring; drug toxicity; epilepsy; seizures; carbamazepine; oxcarbazepine; eslicarbazepine acetate
20.  What does it take to demonstrate memory erasure? Theoretical comment on Norrholm et al (2008) 
Behavioral neuroscience  2008;122(5):1186-1190.
An issue of increasing interest in Pavlovian conditioning is to identify ways to facilitate the development and persistence of extinction. Both behavioral and molecular lines of evidence demonstrate that learning during extinction can be enhanced. Similar evidence has been offered to support the idea that extinction causes the original association to be unlearned, or erased. Differentiating between extinction and erasure accounts is extremely difficult and requires many assumptions about the fundamental nature of how memory storage maps into memory expression. In this issue of Behavioral Neuroscience, Norrholm, et al (2008) describe a study of extinction with humans that has the potential to serve as a translational bridge between rodent work and clinical applications. They find less recovery of a conditioned fear response when extinction occurs 10-min compared to 72-hr after conditioning; however, the recovery of subjects’ expectancies of the fearful stimulus is independent of when extinction occurred. These findings and others discussed here demonstrate some of the challenges in making inferences about memory erasure during extinction.
PMCID: PMC2559954  PMID: 18823175
Extinction; consolidation; reconsolidation; memory storage; memory erasure
21.  A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study 
PLoS Medicine  2014;11(1):e1001589.
Beth Payne and colleagues use a risk prediction model, the Pre-eclampsia Integrated Estimate of RiSk (miniPIERS) to help inform the clinical assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings.
Please see later in the article for the Editors' Summary
Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications.
Methods and Findings
From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735–0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658–0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability.
The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.
Please see later in the article for the Editors' Summary
Editors' Summary
Each year, ten million women develop pre-eclampsia or a related hypertensive (high blood pressure) disorder of pregnancy and 76,000 women die as a result. Globally, hypertensive disorders of pregnancy cause around 12% of maternal deaths—deaths of women during or shortly after pregnancy. The mildest of these disorders is gestational hypertension, high blood pressure that develops after 20 weeks of pregnancy. Gestational hypertension does not usually harm the mother or her unborn child and resolves after delivery but up to a quarter of women with this condition develop pre-eclampsia, a combination of hypertension and protein in the urine (proteinuria). Women with mild pre-eclampsia may not have any symptoms—the condition is detected during antenatal checks—but more severe pre-eclampsia can cause headaches, blurred vision, and other symptoms, and can lead to eclampsia (fits), multiple organ failure, and death of the mother and/or her baby. The only “cure” for pre-eclampsia is to deliver the baby as soon as possible but women are sometimes given antihypertensive drugs to lower their blood pressure or magnesium sulfate to prevent seizures.
Why Was This Study Done?
Women in low- and middle-income countries (LMICs) are more likely to develop complications of pre-eclampsia than women in high-income countries and most of the deaths associated with hypertensive disorders of pregnancy occur in LMICs. The high burden of illness and death in LMICs is thought to be primarily due to delays in triage (the identification of women who are or may become severely ill and who need specialist care) and delays in transporting these women to facilities where they can receive appropriate care. Because there is a shortage of health care workers who are adequately trained in the triage of suspected cases of hypertensive disorders of pregnancy in many LMICs, one way to improve the situation might be to design a simple tool to identify women at increased risk of complications or death from hypertensive disorders of pregnancy. Here, the researchers develop miniPIERS (Pre-eclampsia Integrated Estimate of RiSk), a clinical risk prediction model for adverse outcomes among women with hypertensive disorders of pregnancy suitable for use in community and primary health care facilities in LMICs.
What Did the Researchers Do and Find?
The researchers used data on candidate predictors of outcome that are easy to collect and/or measure in all health care settings and that are associated with pre-eclampsia from women admitted with any hypertensive disorder of pregnancy to participating centers in five LMICs to build a model to predict death or a serious complication such as organ damage within 48 hours of admission. The miniPIERS model included parity (whether the woman had been pregnant before), gestational age (length of pregnancy), headache/visual disturbances, chest pain/shortness of breath, vaginal bleeding with abdominal pain, systolic blood pressure, and proteinuria detected using a dipstick. The model was well-calibrated (the predicted risk of adverse outcomes agreed with the observed risk of adverse outcomes among the study participants), it had a good discriminatory ability (it could separate women who had a an adverse outcome from those who did not), and it designated women as being at high risk (25% or greater probability of an adverse outcome) with an accuracy of 85.5%. Importantly, external validation using data collected in fullPIERS, a study that developed a more complex clinical prediction model based on data from women attending tertiary hospitals in high-income countries, confirmed the predictive performance of miniPIERS.
What Do These Findings Mean?
These findings indicate that the miniPIERS model performs reasonably well as a tool to identify women at increased risk of adverse maternal outcomes associated with hypertensive disorders of pregnancy. Because miniPIERS only includes simple-to-measure personal characteristics, symptoms, and signs, it could potentially be used in resource-constrained settings to identify the women who would benefit most from interventions such as transportation to a higher level of care. However, further external validation of miniPIERS is needed using data collected from women living in LMICs before the model can be used during routine antenatal care. Moreover, the value of miniPIERS needs to be confirmed in implementation projects that examine whether its potential translates into clinical improvements. For now, though, the model could provide the basis for an education program to increase the knowledge of women, families, and community health care workers in LMICs about the signs and symptoms of hypertensive disorders of pregnancy.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization provides guidelines for the management of hypertensive disorders of pregnancy in low-resourced settings
The Maternal and Child Health Integrated Program provides information on pre-eclampsia and eclampsia targeted to low-resourced settings along with a tool-kit for LMIC providers
The US National Heart, Lung, and Blood Institute provides information about high blood pressure in pregnancy and a guide to lowering blood pressure in pregnancy
The UK National Health Service Choices website provides information about pre-eclampsia
The US not-for profit organization Preeclampsia Foundation provides information about all aspects of pre-eclampsia; its website includes some personal stories
The UK charity Healthtalkonline also provides personal stories about hypertensive disorders of pregnancy
MedlinePlus provides links to further information about high blood pressure and pregnancy (in English and Spanish); the MedlinePlus Encyclopedia has a video about pre-eclampsia (also in English and Spanish)
More information about miniPIERS and about fullPIERS is available
PMCID: PMC3897359  PMID: 24465185
22.  Are Alcohol Expectancies Associations? Comment on Moss and Albery (2009) 
Psychological bulletin  2010;136(1):12-20.
A. C. Moss and I. P. Albery (2009) presented a dual-process model of the alcohol-behavior link, integrating alcohol expectancy and alcohol myopia theory. Their integrative theory rests on a number of assumptions including, first, that alcohol expectancies are associations that can be activated automatically by an alcohol-relevant context, and second, that alcohol selectively reduces propositional reasoning. As a result, behavior comes under the control of associative processes after alcohol consumption. We agree with the second but not with the first assumption, based on theoretical and empirical arguments. Although in some cases expectancies may involve a simple association, they are propositional in nature. We demonstrate that this assertion is supported by existing literature cited in Moss and Albery. Moreover, six recent studies consistently demonstrated that under circumstances where executive control is impaired (either as a stable individual difference or under the acute influence of alcohol), associative processes, over and above expectancies, predict alcohol-related behavior. Taken together, the evidence strongly suggests a fundamental distinction between expectancies and associations in memory: effects of propositional expectancies and executive functions are impaired under the acute influence of alcohol but memory associations are not. This difference in perspective not only has theoretical implications, but also leads to different predictions regarding acute alcohol effects in society.
PMCID: PMC3468318  PMID: 20063922
Dual-Process Theories; Automatic and Controlled Processes; Acute Alcohol Effects
23.  Only Time will Tell: Cross-sectional Studies Offer no Solution to the Age-Brain-Cognition Triangle—Comment on Salthouse (2011) 
Psychological bulletin  2011;137(5):790-795.
Salthouse (2011) critically reviewed cross-sectional and longitudinal relations among adult age, brain structure, and cognition (ABC), and identified problems in interpretation of the extant literature. His review, however, misses several important points. First, there is enough disparity among the measures of brain structure and cognitive performance to question the uniformity of B and C vertices of the ABC triangle. Second, age differences and age changes in brain and cognition are often nonlinear. Third, variances and correlations among measures of brain and cognition frequently vary with age. Fourth, cross-sectional comparisons among competing models of ABC associations cannot disambiguate competing hypotheses about the structure and the range of directed and reciprocal relations between changes in brain and behavior. Based on these observations, we offer the following conclusions. First, individual differences among younger adults are not useful for understanding the aging of brain and behavior. Second, only multivariate longitudinal studies, age-comparative experimental interventions, and a combination of the two will deliver us from the predicaments of the ABC triangle described by Salthouse (2011). Mediation models of cross-sectional data represent age-related differences in target variables but fail to approximate time-dependent relations, and thus do not elucidate the dimensions and dynamics of cognitive aging.
PMCID: PMC3160731  PMID: 21859179
brain; aging; cognition; longitudinal; mediation
24.  National Poisons Information Services: report and comment 1980. 
The National Poisons Information Services (NPIS) covering the United Kingdom and the Republic of Ireland currently receive over 40,000 telephone inquiries a year. Over the years there has been little change in the proportion of inquiries related to each of the main categories of poisons (drugs, household, chemical, agricultural, animals, and plants). More detailed analysis, however, shows pronounced changes in the inquiries relating to specific types of poisoning, particularly with drugs. By monitoring these trends and assessing the risks of toxicity, the NPIS has an important role in informing the medical profession of the need for preventive measures and for improved methods of treatment. At present, the NPIS cannot make full use of the available data due to inadequate staffing and lack of computer facilities. It is argued that for a modest increase in funding a much more comprehensive service could be provided.
PMCID: PMC1505520  PMID: 6786585
25.  Green Paper on Bio–Preparedness–general comments–  
Journal of Medicine and Life  2010;3(4):430-432.
The Commission's Green Paper on Bio–preparedness represents an important signal that the European Commission is actively involved in, working on issues related to bio–preparedness across all Member States and the international Community. In 2006, the Commission held two seminars on European Bio Preparedness and a workshop on Transport and Traceability of Bio materials. The results and recommendations emerging from these discussions have been inserted in this Green Paper. The document intends to stimulate a debate within and between the Member States and to launch a process of consultation on how to reduce biological risks and to enhance preparedness and response. All the national authorities responsible for risk prevention and response, human, animal and plant health, customs, civil protection, law enforcement authorities, the military, bio–industry, epidemiological and health communities, academic institutions and bioresearch institutes are therefore called to be involved, to contribute and to improve the ability of the EU to prevent, respond to and recover from a biological incident or deliberate criminal activity.
PMCID: PMC3019068  PMID: 21254743

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