A Surgical Complexity Factor for Clefts of Primary and Secondary Palates.

The surgical treatment of patients with cleft lip and palate depends on the characteristics of the affected anatomical structures (palate, lip and nose). The objective of this work was to develop a quantified classification for these clefts, to represent their surgical complexity. This work was developed with the team of surgeons of the SUMA Cleft Leadership Center (CLC) Smile Train Mexico. The method of Multiple-Criteria Decision Analysis was applied using the Analytic Hierarchy Approach. A surgical complexity factor associated with each cleft was defined and it was validated in a sample of fifty patients treated at the SUMA-CLC.Clinical Relevance- A quantitative classification that represents the surgical complexity of clefts provides an objective unified criteria for planning the surgical treatment of patients, as well as having standardized procedures for the surgical treatment of patients.

Effects of cholesterol on CCK-1 receptors and caveolin-3 proteins recycling in human gallbladder muscle.

The contraction of gallbladders (GBs) with cholesterol stones is impaired due to high cholesterol concentrations in caveolae compared with GBs with pigment stones. The reduced contraction is caused by a lower cholecystokinin (CCK)-8 binding to CCK-1 receptors (CCK-1R) due to caveolar sequestration of receptors. We aimed to examine the mechanism of cholesterol-induced sequestration of receptors. Muscle cells from human and guinea pig GBs were studied. Antibodies were used to examine CCK-1R, antigens of early and recycling endosomes, and total (CAV-3) and phosphorylated caveolar-3 protein (pCAV-3) by Western blots. Contraction was measured in muscle cells transfected with CAV3 mRNA or clathrin heavy-chain small-interfering RNA (siRNA). CCK-1R returned back to the bulk plasma membrane (PM) 30 min after CCK-8 recycled by endosomes, peaking at 5 min in early endosomes and at 20 min in recycling endosomes. Pretreatment with cholesterol-rich liposomes inhibited the transfer of CCK-1R and of CAV-3 in the endosomes by blocking CAV-3 phosphorylation. 4-Amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (inhibitor of tyrosine kinase) reproduced these effects by blocking pCAV-3 formation, increasing CAV-3 and CCK-1R sequestration in the caveolae and impairing CCK-8-induced contraction. CAV-3 siRNA reduced CAV-3 protein expression, decreased CCK-8-induced contraction, and accumulated CCK-1R in the caveolae. Abnormal concentrations of caveolar cholesterol had no effect on met-enkephalin that stimulates a delta-opioid receptor that internalizes through clathrin. We found that impaired muscle contraction in GBs with cholesterol stones is due to high caveolar levels of cholesterol that inhibits pCAV-3 generation. Caveolar cholesterol increases the caveolar sequestration of CAV-3 and CCK-1R caused by their reduced recycling to the PM.

Differential effect with septal and apical RV pacing on ventricular activation in patients with left bundle branch block assessed by non-invasive electrical imaging and in silico modelling.

PURPOSE: It is uncertain whether right ventricular (RV) lead position in cardiac resynchronization therapy impacts response. There has been little detailed analysis of the activation patterns in RV septal pacing (RVSP), especially in the CRT population. We compare left bundle branch block (LBBB) activation patterns with RV pacing (RVP) within the same patients with further comparison between RV apical pacing (RVAP) and RVSP. METHODS: Body surface mapping was undertaken in 14 LBBB patients after CRT implantation. Nine patients had RVAP, 5 patients had RVSP. Activation parameters included left ventricular total activation time (LVtat), biventricular total activation time (VVtat), interventricular electrical synchronicity (VVsync), and dispersion of left ventricular activation times (LVdisp). The direction of activation wave front was also compared in each patient (wave front angle (WFA)). In silico computer modelling was applied to assess the effect of RVAP and RVSP in order to validate the clinical results. RESULTS: Patients were aged 64.6 ± 12.2 years, 12 were male, 8 were ischemic. Baseline QRS durations were 157 ± 18 ms. There was no difference in VVtat between RVP and LBBB but a longer LVtat in RVP (102.8 ± 19.6 vs. 87.4 ± 21.1 ms, p = 0.046). VVsync was significantly greater in LBBB (45.1 ± 20.2 vs. 35.9 ± 17.1 ms, p = 0.01) but LVdisp was greater in RVP (33.4 ± 5.9 vs. 27.6 ± 6.9 ms, p = 0.025). WFA did rotate clockwise with RVP vs. LBBB (82.5 ± 25.2 vs. 62.1 ± 31.7 op = 0.026). None of the measurements were different to LBBB with RVSP; however, the differences were preserved with RVAP for VVsync, LVdisp, and WFA. In silico modelling corroborated these results. CONCLUSIONS: RVAP activation differs from LBBB where RVSP appears similar. TRIAL REGISTRATION: (ClinicalTrials.gov identifier: NCT01831518).

A rule-based method for predicting the electrical activation of the heart with cardiac resynchronization therapy from non-invasive clinical data.

BACKGROUND: Cardiac Resynchronization Therapy (CRT) is one of the few effective treatments for heart failure patients with ventricular dyssynchrony. The pacing location of the left ventricle is indicated as a determinant of CRT outcome. OBJECTIVE: Patient specific computational models allow the activation pattern following CRT implant to be predicted and this may be used to optimize CRT lead placement. METHODS: In this study, the effects of heterogeneous cardiac substrate (scar, fast endocardial conduction, slow septal conduction, functional block) on accurately predicting the electrical activation of the LV epicardium were tested to determine the minimal detail required to create a rule based model of cardiac electrophysiology. Non-invasive clinical data (CT or CMR images and 12 lead ECG) from eighteen patients from two centers were used to investigate the models. RESULTS: Validation with invasive electro-anatomical mapping data identified that computer models with fast endocardial conduction were able to predict the electrical activation with a mean distance errors of 9.2 ±â€¯0.5 mm (CMR data) or (CT data) 7.5 ±â€¯0.7 mm. CONCLUSION: This study identified a simple rule-based fast endocardial conduction model, built using non-invasive clinical data that can be used to rapidly and robustly predict the electrical activation of the heart. Pre-procedural prediction of the latest electrically activating region to identify the optimal LV pacing site could potentially be a useful clinical planning tool for CRT procedures.

Effect of cholecystokinin and the octapeptide of cholecystokinin on the feline sphincter of Oddi and gallbladder. Mechanisms of action.

We studied the effect of cholecystokinin (CCK) and the octapeptide of cholecystokinin (OP-CCK) on the feline gallbladder and sphinecter of Oddi. Both CCK caused a dose-dependent gallbladder contraction and sphincter of Oddi relaxation. The half-maximal responses of the sphincter of Oddi were 6 ng/kg for OP-CCK and 0.15 Ivy-dog U/kg for CCK, which were lower than those of the gallbladder with 28 ng/kg and 0.32 Ivy-dog U/kg, respectively. The effect of OP-CCK on the gallbladder was partially blocked by tetrodotoxin (P < 0.02), hexamethonium alone (P < 0.05), or a combination of hexamethonium and atropine (P < 0.01). The gallbladder response to CCK was not blocked by either atropine alone (P < 0.60) or adrenergic antagonists (P > 0.40). The sphincter of Oddi response to OP-CCK was blocked by tetrodotoxin (P < 0.001) but it was not blocked by cholinergic (P < 0.20) or adrenergic antagonists (P < 0.60). After complete denervation with tetrodotoxin, OP-CCK caused sphincter of Oddi contraction. These findings indicate that there are two excitatory receptors for CCK in the gallbladder, one at the cholinergic neurons and the other at the level of the gallbladder muscle. There are also two receptors for CCK in the sphincter of Oddi, one that is inhibitory, and present at the noncholinergic, nonadrenergic neurons, and the other, excitatory, at the circular muscle.

Neural control of the sphincter of Oddi. A physiological role of 5-hydroxytryptamine in the regulation of basal sphincter of Oddi motor activity in the cat.

The effect of 5-hydroxytryptamine (5-HT) on the sphincter of Oddi (SO) was studied in the cat. The SO had two motor responses to 5-HT: the most common was an initial contraction followed by a more prolonged relaxation, and the other was an exclusive relaxation. Tetrodotoxin did not impair the magnitude of the net contraction induced by 5-HT, but it completely blocked the relaxation. Methysergide partially inhibited the SO contraction in response to submaximal doses of 5-HT (5-20 micrograms/kg). Atropine decreased the SO excitatory response to all doses of 5-HT. The combination of atropine and methysergide completely antagonized the 5-HT excitatory effect, which changed the SO biphasic response to an exclusive relaxation. After tetrodotoxin, the effect of 5-HT was almost completely antagonized by methysergide alone. The SO contraction and relaxation caused by 5-HT were almost completely blocked by 5-HT tachyphylaxis. In contrast, a 5-HT depletion with reserpine enhanced the sensitivity of the SO to 5-HT, responding to doses a thousand times smaller than in control animals. Hexamethonium, phentolamine, propranolol, and 5-methoxy-N,N-dimethyltryptamine did not antagonize the 5-HT-induced contraction or relaxation. These findings indicate that 5-HT caused SO contraction by stimulating postganglionic cholinergic neurons and the smooth muscle directly and caused relaxation by stimulating postganglionic, noncholinergic, nonadrenergic inhibitory neurons. 5-HT blockade or depletion resulted in a significant reduction in basal tonic pressures and in the amplitude of phasic contractions, which suggested that serotonergic neurons may play a physiologic role in the regulation of basal SO motor activity.

Pressure tension, and force of closure of the human lower esophageal sphincter and esophagus.

The mechanical characteristics of the circular muscle of the human lower esophageal sphincter and esophagus were studied in subjects with competent and incompetent sphincters. Pressure-diameter curves were constructed by producing various degrees of circumferential stretch with pressure-measuring probes of increasing diameter. The circumferential membrane tension (force of closure) and the circumferential stress (muscle tension) of the circular muscle layer were also calculated from these data. The pressure-diameter curves of competent and incompetent sphincters were different in magnitude and shape. Incompetent sphincters had lower pressures at all diameters, with pressure gradually increasing with larger probe diameter. In contrast for competent sphincters the pressure was highest near closure, with an initial decline and then an increase in pressure with increasing probe diameter. Both shape and magnitude of pressure-diameter curves of competent and incompetent sphincters were interchangeable when manipulated by pharmacologic agents. Urecholine increased the pressures and changed the incompetent pressure-diameter curve to the levels of the competent sphincter; conversely. Pro-Banthine decreased pressures and changed the shape of the competent pressure-diameter curve to the levels of the incompetent sphincter. Force of closure and circular muscle tension curves of competent and incompetent sphincters were similar in shape but were higher at all diameters for competent sphincters. Force of closure and circular muscle tension increased with larger probe diameter. However, the diameter of optimal tension development was larger than the largest probe used and certainly far from closure. Fundoplication increased the magnitude and changed the shape of the incompetent pressure-diameter curve to one similar to a competent curve. This pressure change was associated with an increase in the force of closure, suggesting that fundopliation modified the length-force of closure characteristics of the incompetent spincter.

Vasoactive intestinal polypeptide. A neurotransmitter for lower esophageal sphincter relaxation.

The effect of rabbit vasoactive intestinal polypeptide (VIP) antiserum on in vitro relaxation of the lower esophageal sphincter (LES) was studied in 10 cats. The stomach and esophagus were opened along the lesser curvature of the stomach and stripped of mucosa. Consecutive strips were cut and mounted in a 2.5-ml muscle chamber. They were perfused with Tyrode's solution and oxygenated continuously. After equilibration for 1 h, perfusion was stopped and one strip from the lower esophageal sphincter region was incubated in solution that contained 12-25 parts of VIP antiserum per 1,000 to Tyrode's solution, while a second strip was incubated in a solution of normal rabbit serum at the same concentration. A third strip was maintained in Tyrode's solution for the duration of the experiment. After a 1-h incubation, the strips were stimulated with 6-s square wave trains of 0.1-, 0.2-, 0.4-, and 0.8-ms pulses at 1, 2, and 5 Hz. These stimulation parameters produced LES relaxation that was completely blocked by tetrodotoxin but not by atropine or phentolamine. The strips incubated in Tyrode's solution or in normal serum relaxed reliably and consistently at all levels of stimulation. In the antiserum-treated strips, LES relaxation in response to all stimuli was significantly inhibited. Strips treated with normal serum were relaxed in a dose-dependent fashion by 10(-7) and 10(-6) M VIP, whereas the antiserum inhibited the relaxation induced by 10(-7) M, but not by 10(-6) M, VIP. Stimulation with two successive 15-min trains of electrical pulses (2 ms, 5 Hz) separated by 30 min of rest released increasing amounts of VIP into the bathing solution. VIP released during the second train of electrical stimulation was significantly (P less than 0.05) greater than in control conditions. In the cat LES, VIP antiserum inhibits the relaxation induced by exogenous VIP or by electric stimulation of nonadrenergic, noncholinergic inhibitory nerves at a level that causes the release of VIP. These findings are consistent with the hypothesis that VIP may be an inhibitory neurotransmitter responsible for LES relaxation.

A multicenter placebo-controlled clinical trial of oral metoclopramide in diabetic gastroparesis.

Metoclopramide tablets were compared with placebo in the treatment of gastrointestinal symptoms in 40 patients with diabetic gastroparesis. Results of a 3-wk double-blind study indicate that metoclopramide at a dosage of one 10-mg tablet four times daily reduced nausea, vomiting, fullness, and early satiety and improved meal tolerance better than placebo. Statistically significant differences were noted for nausea and postprandial fullness. Mean gastric emptying assessed by radionuclide scintigraphy was significantly improved in the metoclopramide-treated group when compared with their baseline result. Metoclopramide is an effective agent for improving the upper gastrointestinal motor function in diabetic patients with gastroparesis.

Signal transduction pathways in esophageal and lower esophageal sphincter circular muscle.

Esophageal reflux is a common condition that affects children and 1 in 10 adults, and if untreated may result in chronic esophagitis, aspiration pneumonia, esophageal strictures, and Barrett's esophagus, a premalignant condition. Although esophagitis is a multifactorial disease that may depend on transient lower esophageal sphincter (LES) relaxation, speed of esophageal clearance, mucosal resistance, and other factors, impairment of LES pressure is a common finding in patients complaining of chronic heartburn. Our data suggest that esophageal and LES circular muscle utilize distinct Ca2+ sources, phospholipid pools, and signal transduction pathways to contract in response to acetylcholine (ACh): (1) In esophageal muscle ACh-induced contraction requires influx of extracellular Ca2+ and may be linked to phosphatidylcholine metabolism, production of diacylglycerol (DAG) and arachidonic acid, and activation of a protein kinase C (PKC)-dependent pathway. (2) In LES muscle ACh-induced contraction utilizes intracellular Ca2+ release arising from metabolism of phosphatidylinositol (PI), and a calmodulin-myosin light chain kinase-dependent pathway. Resting LES tone, on the other hand, may be due to relatively low basal PI hydrolysis resulting in submaximal levels of inositol triphosphate (IP3)-induced calcium release and interaction with DAG to activate PKC. (3) After induction of experimental esophagitis, basal levels of PI hydrolysis and intracellular calcium stores are substantially reduced, resulting in a reduction of resting tone. In addition the signal transduction pathway responsible for LES contraction in response to ACh changes from one that depends on IP3 production, calcium release, and calmodulin activation to one that relies on influx of extracellular calcium and activation of PKC.

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study.

INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. AIM: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS: Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n = 138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. RESULTS: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. CONCLUSIONS: These results show that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.

Residential air exchange rates for use in indoor air and exposure modeling studies.

Data on air exchange rates are important inputs to indoor air quality models. Indoor air models, in turn, are incorporated into the structure of total human exposure models. Fragmentary data on residential ventilation rates are available in various governmental reports, journal articles, and contractor reports. Most of the published papers present data on only a few homes to answer very specialized questions, and none of these publications summarize the ventilation rates of a large population of homes across the United States. Brookhaven National Laboratory (BNL) has conducted more than 4000 residential perfluorocarbon tracer (PFT) measurements and brought them together into a large data base from about 100 studies in the United States and elsewhere. This paper analyzes the BNL PFT data base to generate frequency distributions and summary statistics for different regions of the United States, different seasons, and different levels within the homes. The data analyses suggest that residential ventilation rates are similar in the northeastern and northwestern states but higher in the southwestern states. Winter and fall ventilation rates are similar, but the rates are slightly higher in spring, and much higher in summer. Multi-level residences have higher air exchange rates than single-level residences. Although the BNL data are not a representative sample of homes in the United States, these analyses give insight into the range of air exchange rates found in the United States under a great variety of conditions and are intended for use by developers of models of indoor air quality and total human exposure.

The National Human Activity Pattern Survey (NHAPS): a resource for assessing exposure to environmental pollutants.

Because human activities impact the timing, location, and degree of pollutant exposure, they play a key role in explaining exposure variation. This fact has motivated the collection of activity pattern data for their specific use in exposure assessments. The largest of these recent efforts is the National Human Activity Pattern Survey (NHAPS), a 2-year probability-based telephone survey (n=9386) of exposure-related human activities in the United States (U.S.) sponsored by the U.S. Environmental Protection Agency (EPA). The primary purpose of NHAPS was to provide comprehensive and current exposure information over broad geographical and temporal scales, particularly for use in probabilistic population exposure models. NHAPS was conducted on a virtually daily basis from late September 1992 through September 1994 by the University of Maryland's Survey Research Center using a computer-assisted telephone interview instrument (CATI) to collect 24-h retrospective diaries and answers to a number of personal and exposure-related questions from each respondent. The resulting diary records contain beginning and ending times for each distinct combination of location and activity occurring on the diary day (i.e., each microenvironment). Between 340 and 1713 respondents of all ages were interviewed in each of the 10 EPA regions across the 48 contiguous states. Interviews were completed in 63% of the households contacted. NHAPS respondents reported spending an average of 87% of their time in enclosed buildings and about 6% of their time in enclosed vehicles. These proportions are fairly constant across the various regions of the U.S. and Canada and for the California population between the late 1980s, when the California Air Resources Board (CARB) sponsored a state-wide activity pattern study, and the mid-1990s, when NHAPS was conducted. However, the number of people exposed to environmental tobacco smoke (ETS) in California seems to have decreased over the same time period, where exposure is determined by the reported time spent with a smoker. In both California and the entire nation, the most time spent exposed to ETS was reported to take place in residential locations.

Cellular dysplasia in acquired cystic renal disease: comparison of histomorphometrically gauged nuclear parameters in normal kidneys, renal cell carcinomas and acquired cystic kidneys.

Nuclear parameters were assessed by computer-assisted image analysis in the cells of abnormal epithelial formations in the acquired cystic kidneys of two dialysis patients, the proximal and distal tubules of a normal kidney and two well differentiated renal cell carcinomas. One acquired cystic kidney contained many small clear celled foci and am 0.9 cm-size clear celled lesion and the second one a papillary microadenoma. The clear celled lesion was cytologically indistinguishable from the carcinomas. The histomorphometrically gauged nuclear parameters were maximal and minimal ferret diameters, averaged ferret diameter, aspect ratio, shape factor, area, volume and specific length and width. Statistical evaluation evidenced that the nuclear area, volume, aspect ration and shape factor allowed for the distinction between benign and malignant epithelial structures. The medians of the nuclear parameters of atrophic tubules, cysts, clear celled foci, papillary adenoma and clear celled lesion in the two acquired cystic kidneys deviation from those of normal renal tubules and in, increasing order of disparity, approached those of the carcinomas.

Modeling indoor air concentrations near emission sources in imperfectly mixed rooms.

Assessments of exposure to indoor air pollutants usually employ spatially well-mixed models which assume homogeneous concentrations throughout a building or room. However, practical experience and experimental data indicate that concentrations are not uniform in rooms containing point sources of emissions; concentrations tend to be greater in close proximity to the source than they are further from it. This phenomenon could account for the observation that "personal air" monitors frequently yield higher concentrations than nearby microenvironmental monitors (i.e., the so-called "personal cloud" effect). In this project, we systematically studied the concentrations of a tracer gas at various distances from its emission source in a controlled-environment, room-size chamber under a variety of ventilation conditions. Measured concentrations in the proximity of the source deviated significantly above the predictions of a conventional well-mixed single-compartment mass balance model. The deviation was found to be a function of distance from the source and total room air flow rate. At typical air flow rates, the average concentration at arm's length (approximately 0.4 meters) from the source exceeds the theoretical well-mixed concentration by a ratio of about 2:1. However, this ratio is not constant; the monitored concentration appears to vary randomly from near the theoretical value to several times above it. Concentration data were fitted to a two-compartment model with the source located in a small virtual compartment within the room compartment. These two compartments were linked with a stochastic air transfer rate parameter. The resulting model provides a more realistic simulation of exposure concentrations than does the well-mixed model for assessing exposure to emissions from active sources. Parameter values are presented for using the enhanced model in a variety of typical situations.

Histologic analysis of the periprosthetic tissues of long-term surviving cemented total hip arthroplasties.

Qualitative and semiquantitative features of the interfacial membranes of five long-term (> 16 years) surviving cemented total hip arthroplasties (four revision cases and one autopsy case) were compared with those of thirty short-term surviving (< 15 years) cemented hip prostheses. Cement granulomas, micron-sized polyethylene particles-induced giant-celled granulomas, sheets of submicron-sized polyethylene particles-laden macrophages, and aggregated, metallic particles-laden macrophages were scattered in the fibrous tissue of all interfacial membranes. Quantitatively, characteristics of the interfacial membranes of the two groups differed from one another. The dominant species of prosthetic debris in the interfacial membranes of the short-term surviving joint replacements was derived from the polyethylene acetabular socket, and, correspondingly, giant-celled granulomas and macrophagic sheets predominated. Metallic particles and the macrophagic reaction thereto dominated in the interfacial membranes of the long-term surviving arthroplasties, and large cement and polyethylene chunks typically were incorporated in the fibrous tissue of the membranes without an accompanying macrophagic response. In long-term surviving hip arthroplasties, metallic particles may be at least as important as polymeric detritus in stimulating the formation of the bone-resorbing, granulomatous interfacial membrane, which is the hallmark of aseptically loosened arthroplasties. Differences in mechanical settings may account for unlike modes and rates of generation of prosthetic breakdown products, explaining the disparate survivorship of different patients' artificial joints.

The histologic features of the interfacial membrane of intramedullary nails.

Thirty-six interfacial membranes collected at the time of removal of intramedullary L316 stainless steel nails were studied histologically. The membranes consisted of bland fibrous tissue in a minority of cases. Most often, the nails were enclosed within a synovial-like membrane. Palisading macrophages and fibroblasts abutted on the metallic surface of the nails. Foreign body giant-celled granulomas were scattered in the midzone of the membranes, mono- and polykaryonic macrophages having phagocytozed small metallic particles, necrotic bony debris, and, sometimes, lipidic compounds. Aggregates of hemosiderin-containing macrophages occasionally marked the sites of previous hemorrhages. When present in the retrieved specimen, the bone underlying the membrane was undergoing remodeling. Interfacial motion, consequent on dissimilar stiffness of the bone and nail, as well as deposition of metallic and bony debris, are likely responsible for the formation of the synovial-like interfacial membrane.

A review of signals used in sleep analysis.

This article presents a review of signals used for measuring physiology and activity during sleep and techniques for extracting information from these signals. We examine both clinical needs and biomedical signal processing approaches across a range of sensor types. Issues with recording and analysing the signals are discussed, together with their applicability to various clinical disorders. Both univariate and data fusion (exploiting the diverse characteristics of the primary recorded signals) approaches are discussed, together with a comparison of automated methods for analysing sleep.