Leonard Kaufman

Finding Groups in Data

An electrical signal transmission system, applicable to the transmission of signals from trackside hot box detector equipment for railroad locomotives and rolling stock, wherein a basic pulse train is transmitted whereof the pulses are of a selected first amplitude and represent a train axle count, and a spike pulse of greater selected amplitude is transmitted, occurring immediately after the axle count pulse to which it relates, whenever an overheated axle box is detected. To enable the signal receiving equipment to determine on which side of a train the overheated box is located, the spike pulses are of two different amplitudes corresponding, respectively, to opposite sides of the train.

An algorithm for the quadratic assignment problem using Bender's decomposition

Abstract A well known method used for solving quadratic assignment problems proceeds by the construction of an equivalent much larger linear assignment problem with many side constraints. The disadvantage of this method lies in the weakness of the bounds obtained by solving the linear problem. An alternate linearization has been suggested using a general method of Glover. In this paper the mixed integer program obtained by Glovers method is discussed and a solution using Benders decomposition is proposed.

Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation.

Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha were frequently measured during the first 30 days after allogeneic bone marrow transplantation (BMT) in 84 consecutive adult patients. Major transplant-related complications (MTCs) occurred in 33% of cases and included veno-occlusive liver disease, idiopathic pneumonia syndrome, severe endothelial leakage syndrome and >grade II acute graft-versus-host disease. Compared with patients having minor complications, those with MTCs developed higher levels at times of maximal clinical signs (all cytokines, P<0.001), between days 0–5 post-BMT (IL-6 and IL-8, P<0.05) and days 6–10 (L-6, P<0.001; IL-8 and TNF, P<0.01) post-BMT. We could not discriminate patterns of cytokine release that were specific for any subtype of MTC. Higher levels of IL-8 during days 0–5 were associated (P=0.044) with early (<40 days) death. Multivariate analysis including patient and transplant characteristics as well as post-BMT levels of C-reactive protein showed that high average levels of one or more of the cytokines within the first 10 days post-BMT were independently associated with MTC (Odds ratio: 2.3 [1.2–4.5], P=0.011). This study shows that systemic release of proinflammatory cytokines contributes to the development of MTC and provides a rationale for pre-emptive anti-inflammatory treatment in selected patients.

Inferior and Lateral Electrocardiographic Repolarization Abnormalities in Brugada Syndrome

Background—Repolarization abnormalities in the inferior-lateral leads in Brugada syndrome (BS) have not been systematically investigated. Methods and Results—280 patients (age, 41±18 years; 168 males) with BS were screened for inferior-lateral repolarization abnormalities. The repolarization abnormalities were classified either as early repolarization pattern or coved ≥2-mm Brugada pattern and as spontaneous or class I antiarrhythmic drug (AAD) induced. Thirty-two patients (11%) had inferior-lateral spontaneous early repolarization pattern. These patients were less likely to be asymptomatic at first presentation (13 of 32 versus 156 of 248 patients, P=0.02), and spontaneous type I ECG was more frequent among them (38% versus 21%, P=0.05). The spontaneous early repolarization pattern occurred more frequently among patients with BS than in 283 family members not having BS (11% versus 6%, P=0.03). Class I AAD administration provoked inferior-lateral coved Brugada pattern in 13 patients with BS. These patients had longer baseline PR intervals (206±48 versus 172±31 ms, P<0.001) and class I AAD–induced QRS interval prolongation (108 to 178 versus 102 ms to 131 ms, P<0.001). In 3 patients, the class I AAD–provoked coved Brugada pattern was only present in the inferior leads. Conclusions—Inferior-lateral early repolarization pattern occurs spontaneously relatively frequently in BS. These patients have a more severe phenotype. Class I AAD administration provokes inferior-lateral coved Brugada pattern in 4.6% of patients. We report for the first time 3 patients in whom the class I AAD–provoked coved Brugada pattern was only observed in the inferior leads.

Least median of squares: a robust method for outlier and model error detection in regression and calibration

Abstract The least median of squares method is a robust regression method, which means that it is not sensitive to outliers or other violations of the assumption of the usual normal model. This contrasts with the conventional regression method, which minimizes the sum of squares. It is demonstrated that the proposed method can be used to detect or correct for outliers or model errors in calibration applications and in comparing two procedures.

Differences in Baseline Lymphocyte Counts and Autoreactivity Are Associated With Differences in Outcome of Islet Cell Transplantation in Type 1 Diabetic Patients

OBJECTIVE The metabolic outcome of islet cell transplants in type 1 diabetic patients is variable. This retrospective analysis examines whether differences in recipient characteristics at the time of transplantation are correlated with inadequate graft function. RESEARCH DESIGN AND METHODS Thirty nonuremic C-peptide–negative type 1 diabetic patients had received an intraportal islet cell graft of comparable size under an ATG-tacrolimus–mycophenolate mofetil regimen. Baseline patient characteristics were compared with outcome parameters during the first 6 posttransplant months (i.e., plasma C-peptide, glycemic variability, and gain of insulin independence). Correlations in univariate analysis were further examined in a multivariate model. RESULTS Patients that did not become insulin independent exhibited significantly higher counts of B-cells as well as a T-cell autoreactivity against insulinoma-associated protein 2 (IA2) and/or GAD. In one of them, a liver biopsy during posttransplant year 2 showed B-cell accumulations near insulin-positive β-cell aggregates. Higher baseline total lymphocytes and T-cell autoreactivity were also correlated with lower plasma C-peptide levels and higher glycemic variability. CONCLUSIONS Higher total and B-cell counts and presence of T-cell autoreactivity at baseline are independently associated with lower graft function in type 1 diabetic patients receiving intraportal islet cells under ATG-tacrolimus–mycophenolate mofetil therapy. Prospective studies are needed to assess whether control of these characteristics can help increase the function of islet cell grafts during the first year posttransplantation.

Optimization by statistical linear discriminant analysis in analytical chemistry

Abstract The application of statistical linear discriminant analysis in analytical chemistry is discussed. In addition to a general discussion of the theory of the method, which is illustrated by some examples, its suitability for problem solving in analytical chemistry is demonstrated by a review of published applications. A more mathematical point of view is added as an appendix.

Fiberoptic examination of the nasal cavity and nasopharynx in children

In this prospective study, a flexible fiberoptic nasolaryngoscope with color video camera was used to examine the nasal cavity and nasopharynx in 180 pediatric patients. The relative size of the adenoid tissue was judged by endoscopy, which lead to a classification into 3 types according to the distance from the vomer to the adenoid tissue. The condition of the nasopharyngeal orifice of the Eustachian tube was also described and differentiated into 3 types relating to the condition of adenoid tissue. Assessment was performed by correlating these measurements with the tympanogram, lateral X-ray and clinical complaints. The authors conclude that: (1) fiberoptic examination allows direct visualization of the size and condition of the adenoid tissue, as well as of the condition of the nasopharyngeal orifice of the Eustachian tube. (2) The size of the adenoid tissue correlates very well with the nasal obstruction complaints as well as with the type of tympanogram. (3) The condition of the nasopharyngeal orifice of the Eustachian tube significantly corresponds with the type of tympanogram. (4) For the indication of adenoidectomy, fiberscopy gives more accurate information than standard X-ray. (5) With a correct choice of premedication and local anesthesia, it is a minor invasive technique which is very well tolerated by children. It is possible in all cases, provided it is performed by a skilled endoscopist and preceded by careful explanation to the child. (6) Finally, thanks to the possibility of direct visualization of the fiberscopic image via a monitor, it allows a better explanation of the indication for adenoidectomy to the childs parents.

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation

We monitored levels of C-reactive protein (CRP) in 96 consecutive adult allogeneic BMT patients (age 15–50 years) transplanted in our unit. Major transplant-related complications (MTC) occurred in 32% of cases and included: hepatic veno-occlusive disease, pneumonitis, severe endothelial leakage syndrome and >II acute GVHD. Transplant-related mortality (TRM) before day 100 post-BMT was 13.5%. Variables included in a stepwise logistic regression model were: gender, age, disease category, donor type, T cell depletion, TBI, use of growth factors, bacteremia, mean CRP-levels >50 mg/l between days 0 and 5 (CRP day 0–5) and >100 mg/l between days 6 and 10 (CRP day 6–10) post-BMT. Only high CRP-levels (for MTC and TRM) (P < 0.001) and donor-type (for TRM) (P = 0.02) were independent risk factors. The estimated probability for MTC was 73% (CRP day 6–10 >100 mg/l) vs 17% (CRP day 6–10 <100 mg/l). Using the same cut-off levels, the probabilities for TRM were 36.5% vs 1% in the identical sibling donor situation and 88% vs 12.5% in other donor-type transplants. We conclude that the degree of systemic inflammation, as reflected by CRP-levels, during the first 5–10 days after BMT identifies patients at risk of MTC and TRM. Our data may be useful in selecting patients for clinical trials involving pre-emptive anti-inflammatory treatment.

Monitoring of C-reactive protein after allogeneic bone marrow transplantation identifies patients at risk of severe transplant-related complications and mortality

Patterns of C-reactive protein (CRP) release were derived from frequent CRP measurements in a cohort of 66 consecutive patients receiving allogeneic bone marrow transplants (BMT) in our unit. Based on a retrospective study of clinical events occurring within the first 40 days after BMT, patients with major transplant-related complications (MTC+ group, n = 22) could be separated from those with fever or mild complications only (MTC− group, n = 44). Treatment-related mortality in the MTC+ group was significantly higher: 32 vs 0% (P < 0.001). major complications included veno-occlusive liver disease (vod), severe endothelial leakage syndrome (els), pneumonitis and acute gvhd >II. The severity of complications was reflected by the patterns of CRP release with continuously high levels preceding the maximal signs and symptoms of MTC. Univariate analysis showed that, among other variables (sex, age, disease status at transplant, ±TBI in the conditioning regimen, ± use of myeloid growth factors after BMT, time to reach PN >200/mm3), three factors were significantly associated with MTC: maximal levels of CRP during the post-transplant episode (CRPmax) (296.6 ± 91.8 vs 88.9 ± 55.8 mg/100 ml, P < 0.001), the use of unmanipulated graft (no t depletion) (46.9 vs 12.5%, P < 0.009) and the crp level on the day of bmt (crpo) (42.7 ± 55.4 vs 18.2 ± 19.5, P = 0.045). In multivariate analysis, using a stepwise logistic regression model including the same variables, CRPmax appeared to be the strongest independent variable (P < 0.001) and a reliable (94% accuracy) parameter to assess the risk of mtc. based on this model, crp levels of 200 and 300 mg/100 ml are associated with a risk of 48 and 94% of developing mtc, respectively. we conclude that crp monitoring after bmt identifies patients at risk of severe transplant-related complications and mortality.