Regression to the mean: treatment effect without the intervention

Regression to the mean (RTM) is a widespread statistical phenomenon. It is a group phenomenon that occurs whenever an extreme group is selected from a population based on the measurement of a particular variable. If a second measurement is then taken for the same group, the second mean will be closer to the population mean than the first measurement. This decrease (or increase) can be mistakenly attributed to a treatment effect; the conclusion can be drawn that an effect results from treatment when it in fact results from chance. Any intervention that is aimed at a group or characteristic that is very different from the average will appear to be successful because of RTM. It is therefore important that any genuine reductions because of the treatment are separated out from the effect of RTM. If the problem is ignored then this will lead to errors in the interpretation of results and, potentially, decisions made on the evidence of those results. This paper highlights the importance of the issue and its effects on many common clinical, public health and managerial decisions.     

Analysis of oxygen metabolism implies a neural origin for the negative BOLD response in human visual cortex

The sustained negative blood oxygenation level-dependent (BOLD) response in functional MRI is observed universally, but its interpretation is controversial. The origin of the negative response is of fundamental importance because it could provide a measurement of neural deactivation. However, a substantial component of the negative response may be due to a non-neural hemodynamic artifact. To distinguish these possibilities, we have measured evoked BOLD, cerebral blood flow (CBF), and oxygen metabolism responses to a fixed visual stimulus from two different baseline conditions. One is a normal resting baseline, and the other is a lower baseline induced by a sustained negative response. For both baseline conditions, CBF and oxygen metabolism responses reach the same peak amplitude. Consequently, evoked responses from the negative baseline are larger than those from the resting baseline. The larger metabolic response from negative baseline presumably reflects a greater neural response that is required to reach the same peak amplitude as that from resting baseline. Furthermore, the ratio of CBF to oxygen metabolism remains approximately the same from both baseline states (approximately 2:1). This tight coupling between hemodynamic and metabolic components implies that the magnitude of any hemodynamic artifact is inconsequential. We conclude that the negative response is a functionally significant index of neural deactivation in early visual cortex.     

The composition of a mucus glycoprotein from meconium of cystic fibrosis, healthy pre-term and full-term neonates

A high molecular mass mucus glycoprotein fraction (molecular mass greater than 1 million) which is a major component of meconium mucin, has been isolated from individual specimens collected from 20 healthy full-term infants, 19 premature infants and 19 infants with proven cystic fibrosis. The mucus glycoprotein fraction isolated from cystic fibrosis meconium had a significantly lower saccharide content than that isolated from specimens from healthy full-term infants but had a similar composition to that isolated from meconium of premature infants, gestational age 28-32 weeks. The composition of the glycoprotein fraction from the meconium of infants, gestational age 32-36 weeks, lay between that from cystic fibrosis and full-term. There is therefore a change or 'maturation' of epithelial mucin during gestation and it is hypothesised that the cystic fibrosis genetic lesion affects the maturation of epithelial secretion, resulting in the abnormal exocrine secretion associated with the disease.     

Scabies. How to find and stop the itch.

Scabies is a pruritic skin infestation caused by the itch mite Sarcoptes scabiei. Physical proximity allows the mite to move from one host to another. The diagnosis is made by identifying the mite or its eggs or excrement microscopically from a sample of skin scrapings. Treatment is achieved with topical application of a scabicide and elimination of the mite from the patient's surroundings.     

Filter learning: application to suppression of bony structures from chest radiographs

A novel framework for image filtering based on regression is presented. Regression is a supervised technique from pattern recognition theory in which a mapping from a number of input variables (features) to a continuous output variable is learned from a set of examples from which both input and output are known. We apply regression on a pixel level. A new, substantially different, image is estimated from an input image by computing a number of filtered input images (feature images) and mapping these to the desired output for every pixel in the image. The essential difference between conventional image filters and the proposed regression filter is that the latter filter is learned from training data. The total scheme consists of preprocessing, feature computation, feature extraction by a novel dimensionality reduction scheme designed specifically for regression, regression by k-nearest neighbor averaging, and (optionally) iterative application of the algorithm. The framework is applied to estimate the bone and soft-tissue components from standard frontal chest radiographs. As training material, radiographs with known soft-tissue and bone components, obtained by dual energy imaging, are used. The results show that good correlation with the true soft-tissue images can be obtained and that the scheme can be applied to images from a different source with good results. We show that bone structures are effectively enhanced and suppressed and that in most soft-tissue images local contrast of ribs decreases more than contrast between pulmonary nodules and their surrounding, making them relatively more pronounced.     

What is a pathogen?

The question 'what is a pathogen?' derives from pathogen-centered views of microbial pathogenesis that invoke microbial characteristics to explain virulence. However, virulence cannot be an independent microbial variable since it is only expressed in a susceptible host. Hence, the question 'what is a pathogen?' cannot be separated from the question 'what is a host?' Given that virulence is an outcome of the host-microbe interaction that is not invariant from host to host, neither the pathogen or the host can be defined independently. To sidestep this paradox, one can focus on the outcome of the interaction using host damage as the common denominator to define and explain the various outcomes that can result from the host-microbe interaction. Using this concept a pathogen is defined as a microbe capable of causing host damage.     

Adverse health-care events: Part 3. Learning the lessons

If the NHS is to achieve its goal of developing a safety culture, active learning from adverse events and near misses is crucial. This paper, the third in the series, will discuss how learning from adverse events is informing practice and promoting the development of a safety culture. It also discusses a number of case studies where learning has occurred from adverse events.     

肺动脉异常起源于升主动脉的病理分型

目的 肺动脉异常起源升主动脉的病理分型及胚胎发生机制探讨。方法 5例肺动脉异常起源于升主动脉，作心血管造影（ACG)及磁共振(MRI)检查。结果 5例病例中3例为右肺动脉异常起源于升主动脉；2例为左肺动脉异常起源于升主动脉，4例属近端型，1例远端型。结论 肺动脉异常起源于升主动脉为少见的先天性心脏病，病理分型有二种，一种右肺动脉异常起源于升主动脉，占肺动脉异常起源升主动脉的绝大部分；另一种为左肺动脉异常起源升主动脉，此种类型少见，又可根据肺动脉起源离主动脉瓣及无名动脉的距离分近端型及远端型二种亚型。二种类型的胚胎发生学的解释不尽相同。肺动脉异常起源于升主动脉以前称为半永存动脉干，从胚胎角度讲与永存动脉干不同，故目前不提倡用半永存动脉干这个术语。     

A model of evaluation exemplified by Swedish nursing education

In an historical perspective it can be seen that the target for educational evaluation in Swedish nursing education was changed from that of student to programme evaluation. Since education, however, is an interaction of student prerequisites and educational goal-directed influences, there is a need for a more general evaluation model. This should preferably incorporate both student and programme influences over time at different levels, from classroom to societal level. Such a model is presented here based on data from a Swedish longitudinal twin project (Fischbein, 1979). A discussion of the model is initiated from an example of a recent evaluation study made of nurse education in Sweden.     

Further Thoughts on Research Funding

A research-based department is developed from a specific intentional process. It requires a commitment of time and money from the leadership and desire from the faculty. Faculty need to be taught and mentored. Research funding is achieved only through a careful, deliberate plan.     

Assessment of forest degradation in Brazilian Amazon due to selective logging and fires using time series of fraction images derived from Landsat ETM+ images

A method has been developed to identify and map areas of forest degradation caused by either selective logging or fires in tropical humid ecosystems. Our study area is located in the Mato Grosso state of Brazil, in a region known as ‘Deforestation Arc’. Eight consecutive Landsat Enhanced Thematic Mapper Plus (ETM+) images were available over this study area during the dry season of 2002 (from June to October). The proposed method is based on multi-temporal image segmentation and classification of a data set of soil and shade fraction images derived from Landsat ETM+ imagery. Areas of selectively logged forest are identified and mapped from the soil fraction images, whereas burned forest areas are identified and mapped from the shade fraction images combined with a map of deforestation happening during 2002. The main benefit of this approach is the capability to discriminate selectively logged forest from burned forest, which is a very important issue for estimating carbon emissions from forest degradation.     

Referred muscle pain: Clinical and pathophysiologic aspects

Referred pain, that is, pain perceived in an area other than that in which the noxious stimulation takes place, is very frequent in the clinical setting. There are various forms of referred muscle pain from viscera and from somatic structures. Examples of the latter are referred pain from one muscle to another muscle (as in myofascial pain syndromes) and referred pain from joints (as in osteoarthritis of the knee). Whatever the origin of the symptom, a condition of secondary hyperalgesia very often takes place in the referred zones, together with trophic tissue changes. Referred muscle pain from viscera without hyperalgesia is explained on the basis of the convergence of visceral and somatic afferent fibers on the same central neurons. Referred muscle pain from viscera with hyperalgesia is not completely understood; it is hypothesized that it is due to both central (sensitization process) and peripheral (intervention of reflex arcs) mechanisms. Referred muscle pain from other muscles or from joints is not easily explained by the mechanism of “central convergence” in its original form, because in dorsal horn neurons there is little convergence from deep tissues. It has been proposed that convergent connections from deep tissues to dorsal horn neurons are not present from the beginning but are opened by nociceptive input from skeletal muscle, and referral to myotomes outside the lesion is due to a spread of central sensitization to adjacent spinal segments.     

Lack of association between hypermutation and antibiotic resistance development in Pseudomonas aeruginosa isolates from intensive care unit patients

Hypermutation is a common feature of Pseudomonas aeruginosa isolates from chronically infected cystic fibrosis patients that is linked with antibiotic resistance development. In this work, using a large collection of sequential P. aeruginosa isolates from ICU patients, we found that despite the fact that mutational antibiotic resistance development is a frequent outcome, the prevalence of hypermutable strains is low (found in isolates from only 1 of 103 patients) and there is no evidence of coselection of the hypermutable and antibiotic resistance phenotypes.     

A simplified method for estimating mean values of multiple specimens

Determination of the correct average content of a constituent in multiple specimens requires measurements of concentration and volume of each specimen. We have evaluated a simplified method by which the mean content is estimated from one concentration determination and the total volume of the specimens. The greatest possible deviation from the correct mean value can be estimated, and is shown in diagrams. It is demonstrated that a simplified method can often be used with little loss of accuracy. The method is exemplified by measurements of lipid and biliary acids in faeces from healthy subjects and from patients with Crohn's disease.     

Desorption out of an oil-water multilaminate membrane

Asymptotic solutions for desorption out of an oil-water niultilaminate are obtained by an analytical technique which requires simple assumptions about concentration profiles. Desorption from multilaminates is surprisingly similar to desorption from a single laminate with a reservoir, although nonsteady-state transport across a multilaminate is quite different from that across a single laminate. Applications to controlled release from liposomes and transport across skin are discussed.     

Neural system for updating object working memory from different sources: sensory stimuli or long-term memory

Working memory (WM) is the active maintenance of currently relevant information so that it is available for use. A crucial component of WM is the ability to update the contents when new information becomes more relevant than previously maintained information. New information can come from different sources, including from sensory stimuli (SS) or from long-term memory (LTM). Updating WM may involve a single neural system regardless of source, distinct systems for each source, or a common network with additional regions involved specifically in sensory or LTM processes. The current series of experiments indicates that a single fronto-parietal network (including supplementary motor area, parietal, left inferior frontal junction, middle frontal gyrus) is active in updating WM regardless of the source of information. Bilateral cuneus was more active during updating WM from LTM than updating from SS, but the activity in this region was attributable to recalling information from LTM regardless of whether that information was to be entered into WM for future use or not. No regions were found to be more active during updating from SS than updating from LTM. Functional connectivity analysis revealed that different regions within this common update network were differentially more correlated with visual processing regions when participants updated from SS, and more correlated with LTM processing regions when participants updated from the contents of LTM. These results suggest that a single neural mechanism is responsible for controlling the contents of WM regardless of whether that information originates from a sensory stimulus or from LTM. This network of regions involved in updating WM interacts with the rest of the brain differently depending on the source of newly relevant information.     

Attenuation estimations using envelope echo data: analysis and simulations

Previously we described a video signal analysis (VSA) method for measuring backscatter and attenuation from B-Mode image data. VSA computes depth-dependent ratios of the mean echo intensity from a sample to the mean echo intensity from a reference phantom imaged using identical scanner settings. The slope of a line-fit of this ratio (expressed in dB) versus depth is related to the attenuation of the sample. This paper investigates conditions for which the echo intensity ratio versus depth is independent of transducer pulsing characteristics and instrument settings, and depends only on the properties of the sample and the reference. A theoretical model is described for the echo signal power versus depth from a uniform medium containing scatterers. The model incorporates bandwidth, frequency and media attenuation. Results show that the sample-to-reference echo intensity ratio versus depth is a curve, the departure of which from a straight line is a function of the relative attenuation of the two media, the imaging system bandwidth and the initial frequency. The model also leads to a depth-dependent "effective frequency" determination in the VSA method. Model predictions are verified using RF signals computed by an acoustic pulse-echo simulation program.