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Methods. Table showing methods. (DOCX 16Â kb)

Summary of survival probabilities for patients with SMA Type I in the United States. Table showing summary of survival probabilities for patients with SMA Type I in the United States. (DOCX 20Â kb)

Summary of survival probabilities for patients with SMA Type II in the United States. Table showing summary of survival probabilities for patients with SMA Type II in the United States. (DOCX 14Â kb)

Supplementary information. Table S1. Estimated measures of association of household ownership of a latrine in use with prevalence of Ascaris lumbricoides infection, using conditional logistic regression and mixed regression with and without individual sampling weights. Table S2. Number of clusters (n) contributing to each stratum-specific analysis out of the total number of clusters within that stratum of community sanitation usage (N) and correlation between cluster-specific odds ratios of association of household ownership of a latrine in use with prevalence of Ascaris lumbricoides infection and respective sampling weight by strata of community sanitation usage. (DOCX 24Â kb)

Summary of contemporary published estimates of SMA birth prevalence. Table showing summary of contemporary published estimates of SMA birth prevalence. (DOCX 23Â kb)

We show how simple and effective metaheuristics can be developed for the number partitioning problem using the “problem space” approach [1]. In a previous application of local search to number partitioning [2], it was found that the performance of simulated annealing used in conjunction with “swap neighborhoods” was disappointing relative to the differencing heuristic of Karmarkar and Karp [3]. Using problem space neighborhoods as an alternative to swapping, we empirically demonstrate several orders of magnitude improvement over the differencing algorithm, albeit with greater computation time. This improvement in performance comes as little surprise since a modified version of the differencing heuristic is explicitly embedded in the problem space algorithm.

We propose a novel approach to the prediction of vehicle driving comfort that allows the comfort issue to be integrated into the design process. Whereas current practice relies on building prototype driving configurations and asking a number of subjects to assess comfort, our approach will enable the design engineer to obtain predicted comfort ratings on the basis of readily available design parameters, thus avoiding the expensive and time-consuming step of building a prototype for every proposed design. We describe our approach, which focuses on the contribution to comfort from the design parameters of the entire driving configuration, and the results of using a neural network to construct a relationship between these parameters and our empirical findings on subject comfort.

A key aspect of neural network application is determining how to select the network architecture, and how to use the data to optimize performance and to facilitate proper evaluation. Ontogenic (evolutionary) networks address these problems by leaving the user with minimal parameter selection and decision making, and utilizing available data more fully. We explain and illustrate this idea by comparing the classification performance for backpropagation and an ontogenic neural network. The ontogenic network is shown to have significant advantages in classification accuracy, speed, and utilization of data; furthermore, it does not require the user to determine the number of hidden units or any learning rate parameters, which avoids the trial and error approach necessary for both backpropagation and radial basis functions. In previous tests, ontogenic nets showed the ability to match backpropagation's results in a fraction of the training time. In addition, one of those problems demonstrated a further advantage of the network: by refraining from responding to patterns lying outside of the region on which it was trained, the network does not attempt to extrapolate and may signal that training and test sets lack adequate compatibility. Two new test problems arising out of a beam vibration minimization application in smart structures show the ability of the network to find solutions to low dimensional complex mappings for classifications which pose great difficulty for backpropagation.

Material handling and the provision of supporting resources, particularly tools, in flexible manufacturing systems (FMSs) can constrain production. To improve the productivity for an existing FMS, we first developed a simulation model that included constraints arising from material handling and tool management. Detailed simulations of the FMS showed that a simple set of heuristic rules could produce several alternative schedules of nearly optimum performance. They also showed that when the flow of tooling was considered the FMS was operating near or over capacity. The goal of the study—to generate slack production time for the manufacture of additional parts—was unachievable. Clearly companies must consider the constraints arising from material handling and the flow of supporting resources in scheduling, yet these constraints have seldom been considered in simulations of FMSs.

To the editor: As more effective therapies become routinely used to treat multiple myeloma,[1][1] standardized methods (such as flow cytometry) to determine the presence/absence of minimal residual disease (MRD) will likely play an increasingly important role in the clinical, research, and

Estimating the effects of continuous chronic disease risk factors on mortality is an area that generates confusion and controversy. The frequently observed U-shaped or J-shaped relationships between the risk factors and mortality are often in contrast with presumed monotone relationships. Therefore, some investigators suggest that subjects dying during the first k years of follow-up (where k is some positive number less than the total length of follow-up) be excluded from statistical analyses. The rationale for this approach is that subjects dying during the first k years of follow-up are likely to have some pre-existing occult disease that confounds the relationship between the risk factors and mortality. Excluding such subjects purportedly reduces bias due to this confounding. The purpose of this study was to test the effects of excluding subjects who die during the first k years of follow-up on the reduction of bias under a variety of situations.Using body mass index (BMI; kg/m2) as an example, we conducted Monte Carlo simulations to investigate such effects.Results suggest that under the conditions investigated, the method of excluding early deaths does not reliably or substantially reduce bias due to confounding introduced by occult disease.Excluding subjects dying during the first k years of follow-up may not be a judicious strategy for handling confounding due to occult disease. Investigators are encouraged to develop alternative methods.

e19506 Background: The European Myeloma Network has reported that plasma cell (PC) enumeration by flow cytometry (FC) varies depending on quality of aspirate pull and field biopsied. We conducted a prospective study to evaluate PC site variation content in the core biopsy (CB), PC viability (V) and proportion of monoclonal PCs based on immunophenotypic characteristics, anticoagulant use, and aspirate (A) pull sequence in SMM and MM treatment-naïve patients. Methods: Untreated SMM (n=5) and MM (n=5) patients underwent bilateral bone marrow (BM) A and CB. Bilateral first-pull A were anticoagulated with ethylenediaminetetraacetic acid (EDTA). The second-pull A were anticoagulated with heparin. CB were performed after obtaining all A. The first pull A was sent for morphology and FC evaluation, and the second-pull for FC. CB infiltration by PC was assessed by CD138 immunohistochemistry (IHC). Analysis of PC by FC used CD markers: 19, 45, 20, 38, 138, 27, 28, 19, 81, 126, 200 and 117. V was measured by FC using 7-amino-actinomycin D exclusion. We used the two-tailed Wilcoxon signed rank test to determine the significance of the difference between paired values. Results: The mean difference in estimated percentage of PC infiltration between the right and left CB was 0.033 +/- 0.017 (p=0.25). Phenotypic analysis of PCs by FC showed similar expression of CD markers. PC V was significantly lower in samples anticoagulated with EDTA when compared to heparin (p0.05). Conclusions: Based on IHC and FC, our results suggest that in untreated patients with SMM or MM there are no major differences in the estimated number or immunophenotypic characteristics and distribution of PC in marrow samples obtained from two distant bone sites. These observations have implications for current diagnostic and treatment of MM and its precursor disease. More advanced molecular profiling may find biological variation in bone marrow tumor PC extracted from different locations.

8597 Background: Presently, there is no reliable biomarker for predicting clinical progression from smoldering (SMM) to symptomatic MM for individual patients. To improve our understanding on the pathogenesis from SMM to MM, we conducted a screening study of circulating cytokines using peripheral blood (PB) and bone marrow supernatant (BM) collected from treatment naïve SMM and MM patients as well as healthy donors as controls. Methods: PB samples from 14 SMM and 38 MM patients and 7 controls and BM obtained from 17 MM patients and 9 controls were assayed in duplicates using ultra-sensitive Human TH1/TH2 10-plex multi-spot plate and multi-array plate for interleukin-(IL)-6. Two-tailed Mann-Whitney test was used for statistical analysis. Results: PB of SMM patients (vs controls) had increased levels of several cytokines, including IL-8 (p=0.008) and IFN-gamma (p=0.002). In PB, MM patients (compared to SMM patient and controls) had increased levels of IL-6 (p=0.006 and 0.001, respectively), IL-8 (p=0.0001 and 0.008), IL-10 (p=0.02 and 0.02), TNF-alpha (p=0.01 and 0.009), and IFN-gamma (p=0.01 and 0.02). Analysis of BM revealed a similar profile with increased levels of IL-2, IL-6, IL-8, and TNF-alpha in MM patients compared with controls (p=0.007, p=0.0003, p=0.0001 and p=0.0008). Conclusions: We found significantly increased levels of key cytokines associated with progressive disease state (controls→SMM→MM). Patterns of cytokines were similar in BM and PB, suggesting that serum based cytokines may have a future role as biomarkers for disease progression, and could potentially be assessed as novel targets for treatment.

An enhanced oil recovery project is being proposed in response to the US Department of Energy`s Near Term Class 2 Oil Program for shallow shelf carbonate reservoirs. Productivity problems associated with a shallow shelf carbonate reservoir will be addressed by integrating high resolution 3-D seismic data, reservoir characterization techniques, and 3-D reservoir simulation. The purpose of the study is to yield results which will preserve access to existing well bores by identifying additional reserves. The general approach will be to shoot a 3-D seismic survey designed specifically for imaging the Grayburg/San Andres interval. The data will then be processed and interpreted using state of the art techniques aimed at identifying porosity, permeability barriers and their zones within the reservoir. A technical team will integrate existing geological data with the geophysical results of the seismic survey for detailed reservoir characterization. These results will be used in a 3-D reservoir simulation model to delineate flow units. A field demonstration of infill drilling and water flood development will follow. The authors expect the results of this study to demonstrate a methodology for reservoir characterization which is feasible for the independent operator. Furthermore, it will provide one of the first public demonstrations of the enhancement of reservoir characterization using high resolution 3-D seismic data. Additionally, it will showcase the improvement of water flood development by using an integrated multi-disciplinary approach, and the addition of otherwise unrecovered reserves by selective infill drilling. This report has four sections: summary of preliminary data; plots and maps; well production data; and well data.

A tutorial survey directed to the practicing engineer who is interested in computerized techniques for static and dynamic structural analysis. The discussion is directed to the general questions which occur in the application of computer aided analysis. Consideration is given to structural modeling, input preparation procedures, solutions algorithms, numerical errors, and output interpretation. The emphasis is on large general purpose programs and on establishing a definition of the current state of the art.

Genital herpes was studied in two social groups. Among Caucasians of the upper socioeconomic class with symptomatic primary genital herpes, 78 per cent lacked antibodies to either herpesvirus type 1 or type 2 in their initial serum samples. Among Negroes of the lower socioeconomic class attending a venereal disease clinic, only 29 per cent of persons with primary genital herpes initially lacked antibodies to either type of herpesvirus, and, among women of this group, asymptomatic infections occurred. The antibody response to herpesvirus type 2 among individuals with genital herpes was similar in both social groups. The occurrence of genital herpes among 14 of 18 (78 per cent) female sex contacts of males with genital herpes indicates that the virus is venereally transmitted.

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Dover, N. H., Feb. 28, 1906. To the Editor: —In a pamphlet sent out by the manufacturers of Argyrol I find the following statement: "Argyrol is the only silver salt that does not permanently stain the conjunctiva. It may be used with safety by patients themselves, as often as required." Last week a patient appeared in my office who had been using a 10 per cent, solution of Argyrol in the left eye for nearly a year. It was originally prescribed by a competent oculist, but, of course, with the intention that it should only be used for a short time. I took pains to hunt up the original prescription to be sure that it was Argyrol. In this case the bulbar conjunctiva, the caruncle, and the lining of the lid were as badly stained as from the prolonged use of a solution of nitrate of silver.

Patient. —Mr. J. G., aged 42, was sent to me Dec. 21, 1905, for treatment of his left eye. He gave the following history: History. —Seven years ago, while striking with a stone chisel, a bit of steel flew from the tool and struck him with great force in the left eye. He went to an infirmary where "they found the hole, but could not find the bit of steel." After six weeks of inflammation the eye quieted down, and in six months after the injury the sight was reduced to perception of light only. From that time he had occasional attacks of irritation with blurring of the sound eye, but nothing to amount to anything until the night before he appeared for treatment. He spent that night, as he graphically expressed it, "on my hands and knees in bed, shrieking with pain." Examination. —I found a marked irido-cyclitis and

A 14-month-old girl with chorioretinitis, patent ductus arteriosus, short digits with deformed nails, and growth and developmental retardation is described. Bullous lesions were present at birth and bouts of fever and vesicular skin lesions recurred periodically. Herpesvirus was cultured from the vesicular lesions and the patient's antibody response indicated infection with herpesvirus type II. It is postulated that the infection occurred in utero, produced the anomalies, and persisted to cause the recurring episodes of illness.

That medicine is an all-absorbing profession is a trite saying. If we were to bring two doctors into this room, the one from the coast of Maine, the other from the coast of California, the chances are more than even that they would be talking medicine within ten minutes. The one would brag a bit over a cure he had effected when recovery seemed impossible, and when even Dame Nature herself was wringing her hands in despair; the other would shake his head gravely over the mistaken diagnosis of a brother practitioner, a diagnosis that should have been as plain as the nose on one's face, and which was instantly made by the narrator when called in consultation. These little preliminaries settled, both would begin to discuss cases in which the patients obstinately refused to be cured in spite of diagnostic skill, or scientific treatment. In order that medical men