Exposure assessment models for elemental components of particulate matter in an urban environment: A comparison of regression and random forest approaches.

Exposure assessment for elemental components of particulate matter (PM) using land use modeling is a complex problem due to the high spatial and temporal variations in pollutant concentrations at the local scale. Land use regression (LUR) models may fail to capture complex interactions and non-linear relationships between pollutant concentrations and land use variables. The increasing availability of big spatial data and machine learning methods present an opportunity for improvement in PM exposure assessment models. In this manuscript, our objective was to develop a novel land use random forest (LURF) model and compare its accuracy and precision to a LUR model for elemental components of PM in the urban city of Cincinnati, Ohio. PM smaller than 2.5 µm (PM2.5) and eleven elemental components were measured at 24 sampling stations from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). Over 50 different predictors associated with transportation, physical features, community socioeconomic characteristics, greenspace, land cover, and emission point sources were used to construct LUR and LURF models. Cross validation was used to quantify and compare model performance. LURF and LUR models were created for aluminum (Al), copper (Cu), iron (Fe), potassium (K), manganese (Mn), nickel (Ni), lead (Pb), sulfur (S), silicon (Si), vanadium (V), zinc (Zn), and total PM2.5 in the CCAAPS study area. LURF utilized a more diverse and greater number of predictors than LUR and LURF models for Al, K, Mn, Pb, Si, Zn, TRAP, and PM2.5 all showed a decrease in fractional predictive error of at least 5% compared to their LUR models. LURF models for Al, Cu, Fe, K, Mn, Pb, Si, Zn, TRAP, and PM2.5 all had a cross validated fractional predictive error less than 30%. Furthermore, LUR models showed a differential exposure assessment bias and had a higher prediction error variance. Random forest and other machine learning methods may provide more accurate exposure assessment.

Analysis of Personal and Home Characteristics Associated with the Elemental Composition of PM2.5 in Indoor, Outdoor, and Personal Air in the RIOPA Study.

The complex mixture of chemicals and elements that constitute particulate matter (PM*) varies by season and geographic location because source contributors differ over time and place. The composition of PM having an aerodynamic diameter < 2.5 µm (PM2.5) is hypothesized to be responsible, in part, for its toxicity. Epidemiologic studies have identified specific components and sources of PM2.5 that are associated with adverse health outcomes. The majority of these studies use measures of outdoor concentrations obtained from one or a few central monitoring sites as a surrogate for measures of personal exposure. Personal PM2.5 (and its elemental composition), however, may be different from the PM2.5 measured at stationary outdoor sites. The objectives of this study were (1) to describe the relationships between the concentrations of various elements in indoor, outdoor, and personal PM2.5 samples, (2) to identify groups of individuals with similar exposures to mixtures of elements in personal PM2.5 and to examine personal and home characteristics of these groups, and (3) to evaluate whether concentrations of elements from outdoor PM2.5 samples are appropriate surrogates for personal exposure to PM2.5 and its elements and whether indoor PM2.5 concentrations and information about home characteristics improve the prediction of personal exposure. The objectives of the study were addressed using data collected as part of the Relationships of Indoor, Outdoor, and Personal Air (RIOPA) study. The RIOPA study has previously measured the mass concentrations of PM2.5 and its elemental constituents during 48-hour concurrent indoor, outdoor (directly outside the home), and personal samplings in three urban areas (Los Angeles, California; Houston, Texas; and Elizabeth, New Jersey). The resulting data and information about personal and home characteristics (including air-conditioning use, nearby emission sources, time spent indoors, census-tract geography, air-exchange rates, and other information) for each RIOPA participant were downloaded from the RIOPA study database. We performed three sets of analyses to address the study aims. First, we conducted descriptive analyses to describe the relationships between elemental concentrations in the concurrently gathered indoor, outdoor, and personal air samples. We assessed the correlation between personal exposure and indoor concentrations as well as personal exposure and outdoor concentrations of each element and calculated ratios between them. In addition, we performed principal component analysis (PCA) and calculated principal component scores (PCSs) to examine the heterogeneity of the elemental composition and then tested whether the mixture of elements in indoor, outdoor, and personal PM2.5 was significantly different within each study site and across study sites. Secondly, we performed model-based clustering analysis to group RIOPA participants with similar exposures to mixtures of elements in personal PM2.5. We examined the association between cluster membership and the concentrations of elements in indoor and outdoor PM2.5 samples and personal and home characteristics. Finally, we developed a series of linear regression models and random forest models to examine the association between personal exposure to elements in PM2.5 and (1) outdoor measurements, (2) outdoor and indoor measurements, and (3) outdoor and indoor measurements and home characteristics. As we developed each model, the improvement in prediction of personal exposure when including additional information was assessed. Personal exposures to PM2.5 and to most elements were significantly correlated with both indoor and outdoor concentrations, although concentrations in personal samples frequently exceeded those of indoor and outdoor samples. In general, for most PM2.5 elements indoor concentrations were more highly correlated with personal exposure than were outdoor concentrations. PCA showed that the mixture of elements in indoor, outdoor, and personal PM2.5 varied significantly across sample types within each study site and also across study sites within each sample type. Using model-based clustering, we identified seven clusters of RIOPA participants whose personal PM2.5 samples had similar patterns of elemental composition. Using this approach, subsets of RIOPA participants were identified whose personal exposures to PM2.5 (and its elements) were significantly higher than their indoor and outdoor concentrations (and vice versa). The results of linear and random forest regression models were consistent with our correlation analyses and demonstrated that (1) indoor concentrations were more significantly associated with personal exposure than were outdoor concentrations and (2) participant reports of time spent at their home significantly modified many of the associations between indoor and personal concentrations. In linear regression models, the inclusion of indoor concentrations significantly improved the prediction of personal exposures to Ba, Ca, Cl, Cu, K, Sn, Sr, V, and Zn compared with the use of outdoor elemental concentrations alone. Including additional information on personal and home characteristics improved the prediction for only one element, Pb. Our results support the use of outdoor monitoring sites as surrogates of personal exposure for a limited number of individual elements associated with long-range transport and with a few local or indoor sources. Based on our PCA and clustering analyses, we concluded that the overall elemental composition of PM2.5 obtained at outdoor monitoring sites may not accurately represent the elemental composition of personal PM2.5. Although the data used in these analyses compared outdoor PM2.5 composition collected at the home with indoor and personal samples, our results imply that studies examining the complete elemental composition of PM2.5 should be cautious about using data from central outdoor monitoring sites because of the potential for exposure misclassification. The inclusion of personal and home characteristics only marginally improved the prediction of personal exposure for a small number of elements in PM2.5. We concluded that the additional cost and burden of indoor and personal sampling may be justified for studies examining elements because neither outdoor monitoring nor questionnaire data on home and personal characteristics were able to represent adequately the overall elemental composition of personal PM2.5.

Evolution of MRI changes in Rasmussen's encephalitis.

PURPOSE: We studied the MRI findings in 16 patients with Rasmussen's encephalitis (RE), further analysed serial MRI changes in 11 of them and correlated it with clinical features. METHODOLOGY: The diagnosis of RE was based on the European consensus statement (Brain, 128, 2005, 454). Details related to demographical, clinical, MRI observations were analysed. RESULTS: Forty MRIs of brain of 16 patients were reviewed. Eleven patients had undergone serial brain MRIs ranging from two to five occasions. All the patients had unihemispheric focal cortical atrophy, predominantly in the perisylvian region (n = 13). Other features were white matter signal changes (n = 14), and ipsilateral caudate (n = 6) and putamen (n = 4) atrophy. Signal alterations in putamen and caudate were noted in four each. In all the 11 patients with serial MRI, there was progression of cerebral atrophy and a trend towards increase in MRI staging. The MRI signal changes remained same in five patients, resolved in three patients, differential change in two patients and increased in one patient. Diffusion-weighted imaging showed facilitated diffusion (n = 5), and MR spectroscopy showed reduced N-acetyl-aspartate and elevated lactate (n = 2). CONCLUSIONS: Pattern recognition of MRI findings and the changes in serial MRI might serve as a surrogate marker of disease viz. unihemispheric progressive focal cortical atrophy and signal changes predominantly in the perisylvian distribution and caudate followed by putamen involvement. This might assist in understanding and monitoring of the disease progression.

Evolving strategies in mechanobiology to more effectively treat damaged musculoskeletal tissues.

In this paper, we had four primary objectives. (1) We reviewed a brief history of the Lissner award and the individual for whom it is named, H.R. Lissner. We examined the type (musculoskeletal, cardiovascular, and other) and scale (organism to molecular) of research performed by prior Lissner awardees using a hierarchical paradigm adopted at the 2007 Biomechanics Summit of the US National Committee on Biomechanics. (2) We compared the research conducted by the Lissner award winners working in the musculoskeletal (MS) field with the evolution of our MS research and showed similar trends in scale over the past 35 years. (3) We discussed our evolving mechanobiology strategies for treating musculoskeletal injuries by accounting for clinical, biomechanical, and biological considerations. These strategies included studies to determine the function of the anterior cruciate ligament and its graft replacements as well as novel methods to enhance soft tissue healing using tissue engineering, functional tissue engineering, and, more recently, fundamental tissue engineering approaches. (4) We concluded with thoughts about future directions, suggesting grand challenges still facing bioengineers as well as the immense opportunities for young investigators working in musculoskeletal research. Hopefully, these retrospective and prospective analyses will be useful as the ASME Bioengineering Division charts future research directions.

Economic recession and headache-related hospital admissions.

Incidence of headaches across different regions and its relationship to unemployment rates in the United States before and during an economic recession was evaluated. Years 2008 and 2009 were determined as recessionary period. Headache-related admissions, particularly the uncomplicated headaches, increased significantly during recession. Proportion of women with headaches has increased and the age group of 25-54 years was the most affected during the recession. The hospital charges have increased even though the average length and charge of stay decreased. These findings are consistent with our understanding of effects of stress and unemployment on psychological and physical health.

Antiresorptive and anti-angiogenic drug therapy in the pediatric population with reference to medication-related osteonecrosis of the jaw.

The objective of this study was to identify the prevalence of osteonecrosis of the jaw in a pediatric population with systemic therapeutic exposure to an antiresorptive, anti-angiogenic, and/or immunomodulating drug (ARAID), and in particular in the subgroup of patients who had undergone invasive dental treatment. This was a retrospective cohort study performed at a single center. The investigation included pediatric patients who had undergone systemic therapy with ARAIDs and who began receiving ARAID therapy at ≤16 years of age. The study included 482 patients who received ARAIDs between January 2011 and January 2021. The most common medication class was bisphosphonates (45.0%), followed by mTOR inhibitors (30.1%) and anti-angiogenics (17.8%). No diagnosis of osteonecrosis of the jaw was observed. From this population, 26 patients were noted to have undergone invasive dental treatment. The duration from treatment to the invasive procedure ranged from 0 to 5.9 years. Medication-related osteonecrosis of the jaw is extremely rare among the pediatric population - much less common when compared to the adult population. Prospective cohort studies and continued evaluation will help determine the incidence and prevalence of medication-related osteonecrosis of the jaw in pediatric patients.

Disorientation effects, circulating small ribonucleic acid, and genetic susceptibility on static postural stability.

Background: Motion Sickness increases risk of performance deficits and safety of flight concerns. The etiology of motion sickness is poorly understood. Here, we attempted to quantify the physiological effects of motion sickness on static balance and determine the genetic predictors associated with these effects. Methods: 16 subjects underwent a disorientation stimulus to induce motion sickness. Motion sickness susceptibility was identified using the Motion Sickness Susceptibility Questionnaire. Postural balance outcomes were measured using two tasks, and small ribonucleic acid profiles were assessed with blood draws before motion sickness stimulus. Differences in postural sway before and after the stimulus as well as effect modification of susceptibility were assessed. A random forest followed by regression tree analysis was constructed for each postural sway variable to determine top genetic and covariate predictors. Findings: Significant differences existed in mean postural balance responses between before and after stimulus. Individuals with longer stimulus survival experienced a greater (but insignificant) perception of sway, even if not displaying increased sway for all conditions. Circulation small ribonucleic acids were differentially expressed between individuals with long and short stimulus survival, many of these microRNA have purported targets in genes related to vestibular disorders. Interpretation: We found motion sickness produces transient motor dysfunction in a healthy military population. Small ribonucleic acids were differentially expressed between subjects with long and short stimulus survival times.

Identification of microbial agents in culture-negative brain abscess samples by 16S/18S rRNA gene PCR and sequencing.

Despite clinical suspicion of an infection, brain abscess samples are often culture-negative in routine microbiological testing. Direct PCR of such samples enables the identification of microbes that may be fastidious, non-viable, or unculturable. Brain abscess samples (n = 217) from neurosurgical patients were subjected to broad range 16S rRNA gene PCR and sequencing for bacteria. All these samples and seven formalin-fixed paraffin-embedded tissue (FFPE) samples were subjected to species-specific 18S rRNA PCR for neurotropic free-living amoeba that harbour pathogenic bacteria. The concordance between smear and/or culture and PCR was 69%. One-third of the samples were smear- and culture-negative for bacterial agents. However, 88% of these culture-negative samples showed the presence of bacterial 16S rRNA by PCR. Sanger sequencing of 27 selected samples showed anaerobic/fastidious gram negative bacteria (GNB, 38%), facultative Streptococci (35%), and aerobic GNB (27%). Targeted metagenomics sequencing of three samples showed multiple bacterial species, including anaerobic and non-culturable bacteria. One FFPE tissue revealed the presence of Acanthamoeba 18S rRNA. None of the frozen brain abscess samples tested was positive for 18S rRNA of Acanthamoeba or Balamuthia mandrillaris. The microbial 16/18S rRNA PCR and sequencing outperformed culture in detecting anaerobes, facultative Streptococci and FLA in brain abscess samples. Genetic analyses of 16S/18S sequences, either through Sanger or metagenomic sequencing, will be an essential diagnostic technology to be included for diagnosing culture-negative brain abscess samples. Characterizing the microbiome of culture-negative brain abscess samples by molecular methods could enable detection and/or treatment of the source of infection.

Effects of Heat Exposure from Live-Burn Fire Training on Postural Stability of Firefighters.

Firefighters perform physically intensive jobs in suboptimal environments, making it even more important for them to maintain good functional postural balance or stability. As part of their training, firefighters are required to perform physically demanding tasks under high stress and high heat environments. These demanding tasks lead to increased physical fatigue which can then result in poor performance and/or postural instability. The objectives of this study were to 1) investigate the effect of live-firefighting training-induced heat stress on static postural balance, and 2) investigate the association between commonly monitored physiological responses (core body temperature, heart rate, oxygen saturation and blood pressure) and measures of static postural balance. Twenty-six firefighters (mean ± SD: age 36.0 years ±5.2, weight 216 lbs. ± 34, BMI 29.7 ± 4.2) participated in live firefighting training while performing following tasks: search and rescue, hose advancement, and backup. Prior to heat exposure (PRE) and following each scenario (POST1, POST2, POST3), firefighters' postural balance was assessed with a wearable 3-D inertial sensor system quantifying time dependent changes in linear acceleration (LIN ACC) and angular velocity (AV) about three orthogonal axes [Anterior-Posterior (AP), Medial-Lateral (ML), and vertical (V)] during one foot balance tests for 30 seconds under eyes open and eyes closed conditions. The outcome variables from 3-D wearable sensors were used to create 3-D Phase-Plane based postural stability metrics. Physiological measurement of core body temperature (CBT) (measured with a radio pill) as well as perception of heat increased significantly during the live fire-training exercise. In addition, firefighters also perceived an increase in physical fatigue and respiratory distress. Angular combined stability parameters (ACSP), RMS angular velocity around ML axis were significantly correlated with CBT. In the multivariate analysis adjusted for the scenarios, height and weight of the firefighters, these measures of static postural balance were significantly associated with CBT. As per the model results, static postural balance, as indicated by ACSP, worsened with an increase in CBT. Future studies should place sensors at body extremities along with close to center of mass to capture the kinematic movements more comprehensively influencing postural balance.

Molecular and biotechnological aspects of microbial proteases.

Proteases represent the class of enzymes which occupy a pivotal position with respect to their physiological roles as well as their commercial applications. They perform both degradative and synthetic functions. Since they are physiologically necessary for living organisms, proteases occur ubiquitously in a wide diversity of sources such as plants, animals, and microorganisms. Microbes are an attractive source of proteases owing to the limited space required for their cultivation and their ready susceptibility to genetic manipulation. Proteases are divided into exo- and endopeptidases based on their action at or away from the termini, respectively. They are also classified as serine proteases, aspartic proteases, cysteine proteases, and metalloproteases depending on the nature of the functional group at the active site. Proteases play a critical role in many physiological and pathophysiological processes. Based on their classification, four different types of catalytic mechanisms are operative. Proteases find extensive applications in the food and dairy industries. Alkaline proteases hold a great potential for application in the detergent and leather industries due to the increasing trend to develop environmentally friendly technologies. There is a renaissance of interest in using proteolytic enzymes as targets for developing therapeutic agents. Protease genes from several bacteria, fungi, and viruses have been cloned and sequenced with the prime aims of (i) overproduction of the enzyme by gene amplification, (ii) delineation of the role of the enzyme in pathogenecity, and (iii) alteration in enzyme properties to suit its commercial application. Protein engineering techniques have been exploited to obtain proteases which show unique specificity and/or enhanced stability at high temperature or pH or in the presence of detergents and to understand the structure-function relationships of the enzyme. Protein sequences of acidic, alkaline, and neutral proteases from diverse origins have been analyzed with the aim of studying their evolutionary relationships. Despite the extensive research on several aspects of proteases, there is a paucity of knowledge about the roles that govern the diverse specificity of these enzymes. Deciphering these secrets would enable us to exploit proteases for their applications in biotechnology.

Clinical, electrophysiological, imaging, pathological and therapeutic observations among 18 patients with Rasmussen's encephalitis.

We studied the clinical, electrophysiological, imaging and pathological features of 18 patients with Rasmussen's encephalitis (RE). This descriptive study included 18 patients (six males, 12 females) with RE who were evaluated for demographic and phenotypic details, electroencephalogram (EEG) results, MRI results, pathological features, virological markers and outcome. Radiological staging as per Bien et al. and pathological staging in accordance with Robitaille et al. were performed. Simple partial seizures were the most common initial manifestation. During the disease course, epilepsia partialis continua (EPC) developed in 15/18 (83.3%) and hemiparesis in 17/18 (94.4%) patients. EEG revealed hemispheric slowing (100%), interictal epileptiform discharges (100%) and ictal pattern (44.4%). Brain MRI revealed unihemispheric focal cortical atrophy (100%), white matter changes (88.2%), basal ganglia-ipsilateral caudate and putamen involvement (50.0%) and progression of atrophy on serial MRI (100%). Unusual presentations in this series included late onset (n=1), and isolated lingual EPC (n=1). Diagnostic biopsies in two patients revealed Robitaille stage 3 disease. The six hemispherotomy specimens showed stage 2 disease in one, stage 3 in three and stage 4 in two cases. Heterogeneity in disease stage in the different neuroanatomical regions and within the same cortical segment reflected progression of immune-mediated damage. Immunomodulation provided only temporary benefit. Patients who underwent functional hemispherotomy had reduction in seizure frequency and improved quality of life. The clinical, EEG and MRI findings are in accordance with the established literature. MRI staging was concordant with Robitaille pathological staging. Immunomodulation did result in transient reduction in seizure frequency while surgery in six produced reasonable benefit.

Purification, kinetic characterization and involvement of tryptophan residue at the NADPH binding site of xylose reductase from Neurospora crassa.

Xylose reductase (XR) from Neurospora crassa was purified to homogeneity and was found to be specific to NADPH (nicotinamide adenine dinucleotide phosphate). The purified enzyme showed M(r) of 60 and 29 kDa by gel filtration and SDS-PAGE indicating the presence of two subunits. The kinetic mechanism of xylose reductase is 'iso-ordered bi bi'. Inactivation of XR by N-bromosuccinimide (NBS) was found to be biphasic with second-order rate constants of 2.5 x 10(2) and 80 M-1S-1 for the fast (kf) and slow phase (ks), respectively. NADPH protected 90% of XR activity against inhibition by NBS. The fluorescence and circular dichroism (CD) studies revealed that inactivation was not due to gross conformational change in the enzyme. Analysis of the modified Stern-Volmer plot indicated that 49% of the tryptophanyl fluorescence was available for quenching which was completely abolished in the presence of NADPH confirming the involvement of tryptophan at the coenzyme binding site. Experimental evidence presented here serves to implicate the involvement of a tryptophan residue at the low-affinity NADPH binding site and the nature of this site has been assessed by using the hydrophobic probe ANS.

Hyperglycemia-induced activation of human erythrocyte aldose reductase and alterations in kinetic properties.

Incubation of human erythrocytes with varying concentrations of glucose resulted in a several-fold increase in aldose reductase (alditol:NADP+ 1-oxidoreductase, EC 1.1.1.21) activity as determined by the rate of NADPH oxidation and the rate of sorbitol formation. As compared to aldose reductase from human erythrocytes not incubated with glucose (native enzyme), aldose reductase from 30 mM glucose-incubated erythrocytes (activated enzyme) exhibited altered kinetic and inhibition properties. Native enzyme showed biphasic kinetics with substrates (glucose and glyceraldehyde), was strongly inhibited by 15 microM ADP, 1,3-diphosphoglycerate, 2,3-diphosphoglycerate and 3-phosphoglycerate, and aldose reductase inhibitors such as sorbinil and alrestatin. The activated enzyme, on the other hand, exhibited monophasic kinetics, low Km for substrates, was not inhibited by the phosphorylated intermediates, and was less susceptible to inhibition by aldose reductase inhibitors. In erythrocytes of the diabetic subjects, we have found an excellent correlation between aldose reductase activity and plasma glucose levels and have observed that whenever the blood glucose level was higher than 15 mM, all of the erythrocyte aldose reductase was present in the activated form and exhibited properties similar to those observed with aldose reductase obtained from 30 mM glucose-incubated erythrocytes.

Significance of the N-6/N-3 ratio for insulin action in diabetes.

This report supplies supportive data for the hypothesis that a high n-6/n-3 dietary fat ratio is a potent, negative variable in NIDDM. Further work is necessary to critically evaluate this hypothesis.

Vasopressin and oxytocin content of human fetal brain at different stages of gestation.

Pituitaries from 38 human fetuses and 5 microdissected hypothalamic areas from each of 14 fetuses were assayed for vasopressin and oxytocin. The fetuses were between 15 and 34 weeks of gestation. Vasopressin and oxytocin were found in all the pituitary glands and all the hypothalamic areas studied. A trend of increasing content of both hormones was found in the pituitary gland towards the end of gestation with a marked increase in vasopressin/oxytocin ratio. The human fetus synthesizes oxytocin and vasopressin at least from 15 weeks of gestation and the presence of both hormones in the hypothalamus is not limited to the supraoptic and paraventricular nuclei.

Juvenile tricuspid stenosis and rheumatic tricuspid valve disease: an echocardiographic study.

Tricuspid valve involvement is not uncommon in patients with rheumatic heart disease and is frequently missed on routine clinical examination. We prospectively studied the echocardiographic profile of tricuspid valve disease in 788 consecutive patients with rheumatic heart disease. Out of these patients 9% (70) had tricuspid valve disease and 55.7% (39) of these were of < or = 20 years of age. Of these 60% were females and 40% were males. Their ages ranged from 9 to 64 years (mean 24.2+/-13.6 years). Of these patients, 50% had tricuspid stenosis with or without tricuspid regurgitation whereas 50% had isolated tricuspid regurgitation. Isolated tricuspid stenosis was present in 7.4% of these cases. All patients had associated mitral stenosis. Severe mitral stenosis was present more commonly in patients with juvenile tricuspid stenosis compared to older patients (94.1% vs. 55.6%, P<0.005). Mitral regurgitation was present more commonly in juvenile age group patients compared to older patients (53.8% vs. 25.8%, P<0.01). A combination of mitral, aortic and tricuspid stenosis was present in five cases and four of these were in the juvenile age group. Left ventricular enlargement and dysfunction were present in 28.6 and 14.3% patients, respectively, and the majority of these patients were in the juvenile age group (P<0.05). We conclude that rheumatic tricuspid valve disease occurs early in the course of the disease and progresses faster in India and is always associated with mitral stenosis. Juvenile tricuspid stenosis is more commonly associated with severe mitral stenosis, mitral regurgitation, left ventricular enlargement and dysfunction as compared with older patients.

Clinical and echocardiographic predictors of left atrial clot and spontaneous echo contrast in patients with severe rheumatic mitral stenosis: a prospective study in 200 patients by transesophageal echocardiography.

The objective of this study was to prospectively investigate various clinical and echocardiographic variables to predict the left atrial and left atrial appendage clot and spontaneous echo contrast in patients with severe rheumatic mitral stenosis. We studied 200 consecutive patients (112 males and 88 females; mean age 29.6+/-9.6 years). Left atrial clot and spontaneous echo contrast were present in 26 and 53.5% of cases, respectively. There were no significant differences in the mitral valve area, mean transmitral diastolic gradient and left ventricular ejection fraction between patients with and without clot. Patients with clot were older (34.4+/-11.4 vs. 28.2+/-8.5 years, P<0.001), had longer duration of symptoms (41. 4+/-36.0 vs. 28.8+/-22.9 months, P<0.001), more frequent atrial fibrillation and spontaneous echo contrast (69.2 vs. 16.9%, P<0. 00001 and 76.9 vs. 45.3%, P<0.00001, respectively) and larger left atrial area and diameter (41.0+/-12.7 vs. 29.9+/-7.4 cm(2), P<0.00001 and 53.9+/-8.3 vs. 47.6+/-7.4 mm, P<0.0001, respectively) as compared to patients without clot. Similarly patients with spontaneous echo contrast were older (31+/-10.4 vs. 27.8+/-8.3 years, P<0.01), had more frequent atrial fibrillation (48.6 vs. 9.7%, P<0.0001), left atrial clot (37.4 vs. 12.9%, P<0.0001), larger left atrial area and diameter (37.6+/-11.2 vs. 28.1+/-6.7 cm(2), P<0.00001 and 52.2+/-8.3 vs. 45.9+/-6.5 mm, P<0.00001, respectively) and smaller mitral valve area (0.77+/-0.14 vs. 0.84+/-0.13 cm(2), P<0.01) as compared to patients without spontaneous echo contrast. There were no significant differences in the mean transmitral diastolic gradient and left ventricular ejection fraction. On multiple regression and discriminant function analysis, atrial fibrillation and left atrial area were independent predictors of left atrial clot formation. In a subgroup of patients with sinus rhythm, larger left atrial area and presence of spontaneous echo contrast were significantly associated with the presence of clot in left atrium and appendage. We conclude that in patients with severe mitral stenosis, the presence of atrial fibrillation and in the subgroup of the patients with sinus rhythm the presence of large left atrium (> or =40 cm(2)) and spontaneous echo contrast were associated with higher risk of clot formation in the left atrium and might be benefited by prophylactic anticoagulation.

Primary hypothyroidism in chronic renal failure.

Serum thyroid hormone concentrations have been measured in 8 patients with chronic renal failure (CRF) who are currently enrolled on a chronic hemodialysis program. Three of these patients were diagnosed to be suffering from coexistent primary hypothyroidism whereas the other 5 were considered euthyroid. There was a variable decline in serum thyroid hormone levels in both groups. However, the serum TSH response to TRH was normal or blunted in the euthyroid group but was characteristically brisk in subjects with CRF and coexistent primary hypothyroidism. The TRH test may be useful in the diagnosis of primary hypothyroidism coexistent with CRF.

Craniospinal and spinal enterogenous cysts--report of three cases.

We report three cases of enterogenous cyst, one craniospinal and two spinal manifesting with features of spinal cord compression. In one the cyst was intramedullary in location and in the other two it was intradural, extramedullary. The unusual clinical presentation, location and magnetic resonance imaging (MRI) characteristics are discussed. None of the three patients had any vertebral anomaly or other congenital malformation. All patients had excellent outcome following surgery.

A result on a 2 x 2 survival experiment.

Lifetime data classified according to categorical variables under the proportionality of the hazard functions of response variables for various treatment combinations is assumed. The proposed model is a combination of Cox's proportional hazards model and ANOVA model. The existence of a solution to the marginal likelihood function is examined for the case of 2 x 2 two-way classification. We provide an easily verifiable condition for the existence of a unique estimate.