Immune status and the efficacy of adjuvant radiotherapy for patients with localized Merkel cell carcinoma of the head and neck.

PURPOSE: Immunosuppressed (IS) patients are at increased risk for developing Merkel cell carcinoma (MCC) with worsened outcomes compared to immunocompetent (IC) patients. We sought to determine the effects of immune status on the efficacy of adjuvant RT regarding OS for patients with stage I, II or III (localized) MCC of the head and neck. METHODS/PATIENTS: The National Cancer Database was queried for patients with resected, localized MCC of the head and neck with known immune status. Kaplan-Meier methods were used to describe OS. Log-rank tests, multivariable Cox regression models and interaction effect testing were used to compare OS by subgroup categorized by patient and treatment factors including immune status and adjuvant RT receipt. RESULTS: A total of 892 (89.6%) IC and 104 (10.4%) IS patients with MCC of the head and neck were included. Adjuvant RT was associated with improved 3-year OS rate for both IS patients (49.4% vs. 35.5%, p = 0.0467) and stage I/II IC patients (72.4% vs. 62.9%, p = 0.0092). Adjuvant RT was associated with decreased hazard of death (HR 0.77, 95% CI 0.62-0.95). Interaction effect testing did not demonstrate a difference in the efficacy of adjuvant RT on OS between IC and IS status (p = 0.157). CONCLUSIONS: In this NCDB analysis, adjuvant RT was associated with decreased hazard of death for patients with localized MCC of the head and neck regardless of immune status and should be considered for both IS and IC patients.

Reduction and Increase in Thermal Conductivity of Si Irradiated with Ga+ via Focused Ion Beam.

Focused ion beam (FIB) technology has become a valuable tool for the microelectronics industry and for the fabrication and preparation of samples at the micro/nanoscale. Its effects on the thermal transport properties of Si, however, are not well understood nor do experimental data exist. This paper presents a carefully designed set of experiments for the determination of the thermal conductivity of Si samples irradiated by Ga+ FIB. Generally, the thermal conductivity decreases with increasing ion dose. For doses of >1016 (Ga+/cm2), a reversal of the trend was observed due to recrystallization of Si. This report provides insight on the thermal transport considerations relevant to engineering of Si nanostructures and interfaces fabricated or prepared by FIB.

Covariance Partition Priors: A Bayesian Approach to Simultaneous Covariance Estimation for Longitudinal Data.

The estimation of the covariance matrix is a key concern in the analysis of longitudinal data. When data consists of multiple groups, it is often assumed the covariance matrices are either equal across groups or are completely distinct. We seek methodology to allow borrowing of strength across potentially similar groups to improve estimation. To that end, we introduce a covariance partition prior which proposes a partition of the groups at each measurement time. Groups in the same set of the partition share dependence parameters for the distribution of the current measurement given the preceding ones, and the sequence of partitions is modeled as a Markov chain to encourage similar structure at nearby measurement times. This approach additionally encourages a lower-dimensional structure of the covariance matrices by shrinking the parameters of the Cholesky decomposition toward zero. We demonstrate the performance of our model through two simulation studies and the analysis of data from a depression study. This article includes Supplementary Material available online.

Bayesian methods for nonignorable dropout in joint models in smoking cessation studies.

Inference on data with missingness can be challenging, particularly if the knowledge that a measurement was unobserved provides information about its distribution. Our work is motivated by the Commit to Quit II study, a smoking cessation trial that measured smoking status and weight change as weekly outcomes. It is expected that dropout in this study was informative and that patients with missed measurements are more likely to be smoking, even after conditioning on their observed smoking and weight history. We jointly model the categorical smoking status and continuous weight change outcomes by assuming normal latent variables for cessation and by extending the usual pattern mixture model to the bivariate case. The model includes a novel approach to sharing information across patterns through a Bayesian shrinkage framework to improve estimation stability for sparsely observed patterns. To accommodate the presumed informativeness of the missing data in a parsimonious manner, we model the unidentified components of the model under a non-future dependence assumption and specify departures from missing at random through sensitivity parameters, whose distributions are elicited from a subject-matter expert.

Sparsity Inducing Prior Distributions for Correlation Matrices of Longitudinal Data.

For longitudinal data, the modeling of a correlation matrix R can be a difficult statistical task due to both the positive definite and the unit diagonal constraints. Because the number of parameters increases quadratically in the dimension, it is often useful to consider a sparse parameterization. We introduce a pair of prior distributions on the set of correlation matrices for longitudinal data through the partial autocorrelations (PACs), each of which vary independently over [-1,1]. The first prior shrinks each of the PACs toward zero with increasingly aggressive shrinkage in lag. The second prior (a selection prior) is a mixture of a zero point mass and a continuous component for each PAC, allowing for a sparse representation. The structure implied under our priors is readily interpretable for time-ordered responses because each zero PAC implies a conditional independence relationship in the distribution of the data. Selection priors on the PACs provide a computationally attractive alternative to selection on the elements of R or R-1 for ordered data. These priors allow for data-dependent shrinkage/selection under an intuitive parameterization in an unconstrained setting. The proposed priors are compared to standard methods through a simulation study and a multivariate probit data example. Supplemental materials for this article (appendix, data, and R code) are available online.

Characterization of a Pasteurella haemolytica A1 mutant deficient in production of three membrane lipoproteins.

OBJECTIVE: To determine whether a Pasteurella haemolytica A1 mutant that is unable to produce membrane lipoproteins has reduced susceptibility to complement-mediated killing, and to characterize the mutant strain. SAMPLE POPULATION: 12 sera from cattle resistant to P haemolytica challenge exposure after vaccination with P haemolytica or its antigens, or after natural exposure. PROCEDURES: Complement-mediated killing assays were performed, using wild-type and mutant strains and, as antibody source, various immune sera from cattle that were resistant to P haemolytica challenge exposure. Antibody response to whole-cell antigens produced by mutant and wild-type strains, production of outer membrane proteins and iron-regulated outer membrane proteins by the 2 strains, and growth of the 2 strains in various media were analyzed. RESULTS: Compared with wild-type P haemolytica, the lipoprotein mutant strain had increased susceptibility to bovine complement-mediated killing. Aside from the lipoproteins that are not produced by the mutant, immunoblot analysis did not reveal differences between immunoreactive antigens that are produced by the 2 strains. Some iron-regulated, outer membrane proteins, which usually are only produced by P haemolytica under iron-deficient conditions, were produced constitutively by the mutant. The mutant grew to a lower final cell density and at a lower rate under conditions likely to reflect those encountered in vivo. CONCLUSIONS: Lack of 3 membrane lipoproteins resulted in enhanced susceptibility to bovine complement-mediated killing. Site-specific mutagenesis of genes encoding P haemolytica membrane lipoproteins alters production of iron-regulated outer membrane proteins by P haemolytica. Growth characteristics of the mutant suggested that it may have reduced capacity for survival in vivo.

Effects of brain endogenous insulin on neurofilament and MAPK in fetal rat neuron cell cultures.

We demonstrated the 'de novo' synthesis of insulin within the fetal nervous system in vivo and in vitro. We undertook this study to show a role for brain endogenous insulin within the fetal brain. We used neuron cell cultures (NCC) from 19 days gestational age fetal rat brains incubated in an insulin free/serum free defined medium. The neurons showed the presence of preproinsulin I and II mRNA using polymerase chain reaction and insulin immunoreaction employing peroxidase anti-peroxidase and radioimmunoassay techniques. Using an anti-pan neurofilament antibody (that recognizes non-phosphorylated neurofilaments) neurofilament immunoreaction (NFI) was observed within the neuron body, dendrites and axon. Either insulin antibody or isoproterenol treatment induced the neurites to retract and most of the neurons become round, with NFI confined to the neuron body. The antibody treatments induced the neurons to become hypertrophic and vacuolated. With PD98059 treatment NFI was only observed within the neuron body. The addition of insulin reversed the effects of isoproterenol and PD98059, but not those of the insulin antibody. Treatment with wortmannin had no effect. Western blot analysis showed that the basal level of mitogen activated protein kinase (MAPK) phosphorylation was inhibited by the treatment of the NCC with isoproterenol or trypsin, but was significantly increased by treatment with exogenous insulin, demonstrating that brain endogenous insulin phosphorylated MAPK (p<0.05). Thus, brain endogenous insulin promotes neurite outgrowth, probably via MAPK and by stimulating neurofilament distribution via this mechanism participates in neuron differentiation.

Air contamination in umbilical cord blood gas sampling.

OBJECTIVE: Our purpose was to determine the effect of air contamination and the length of time before assay on umbilical cord blood gases at delivery. STUDY DESIGN: Umbilical venous cord blood gases (0.5 ml) were drawn from 21 patients at delivery in 1 and 3 ml heparinized syringes with varying amounts of air contamination (none, 0.5 ml air admitted and removed from the syringe, and 0.5 ml of air retained). In an additional 15 patients the 0.5 ml sample was contaminated with 0.1, 0.2, 0.3, 0.4, and 0.5 ml of air. RESULTS: Air contamination had no effect on pH, PCO2, or bicarbonate but did increase the PO2 when the residual air was > 37.5% in a 3 ml syringe. No changes occurred in a 1 ml syringe. Time from drawing the blood to assay did not significantly alter the results. CONCLUSION: Umbilical cord blood gases are best drawn in 1 ml heparinized syringes. Only if the residual air contamination exceeds 37.5% will PO2 increase. The level of air contamination will not alter the evaluation of fetal-neonatal acidosis.

Does greater usage of a health plan reduce satisfaction?

As health care providers assess the future of managed care, the satisfaction of individual purchasers becomes an important issue. Do they become disenchanted after heavier use of managed care plans--and if so, does that contrast with purchasers of indemnity plans? The authors explore such issues.

Respiratory effects of spinal immobilization in children.

STUDY OBJECTIVE: To assess the restrictive effects of two spinal immobilization strapping techniques on the respiratory capacity of normal, healthy children. DESIGN: Prospective study with each subject serving as his own control. PARTICIPANTS: Fifty-one healthy children 6 to 15 years old. INTERVENTIONS: Participants' forced vital capacity (FVC) measurements were first obtained with children standing and lying supine and then in full spinal immobilization using two different strapping configurations, cross straps and lateral straps. Straps were tightened to allow one hand to fit snugly between the strap and child. MEASUREMENTS AND MAIN RESULTS: Supine FVC was less than upright FVC (P less than .001). FVC in spinal immobilization ranged from 41% to 96% of supine FVC (80 +/- 9%). There was no difference in FVCs between strapping techniques (P = .83). CONCLUSION: Spinal immobilization significantly reduced respiratory capacity as measured by FVC in healthy patients 6 to 15 years old. There is no significant benefit of one strapping technique over the other.

Exophiala pisciphila. A study of its development.

Exophiala pisciphila is a dematiaceous fungus that belongs to a group of fungi known as the 'black yeasts'. It was isolated from the skin lesions of a smooth dogfish, Mustelus canis Mitchill, that had been born in the shark exhibit tank of the New York Aquarium. The different stages of development of this fungus were studied by light microscopy and scanning electron microscopy to illustrate the morphology and surface structures of conidia and mycelium. The list of marine and fresh water fish, which have been infected by Exophiala spp. and Exophiala-like fungi has been up-dated. Potato Dextrose Agar and Malt Agar proved to be the best growth media, while Corn Meal Agar proved to be the best medium for studying the morphological features of the conidia and mycelial development of E. pisciphila, which exhibited polymorphic conidiogenesis.

Chemoprophylaxis of recurrent otitis media using trimethoprim/sulfamethoxazole.

This study was undertaken during the late fall, winter, and early spring months to determine the efficacy of daily trimethoprim/sulfamethoxazole (TMP/SMX) administration in the prevention of recurrent acute otitis media (RAOM) in a specific high-risk pediatric population. Twenty-one ambulatory patients, 10 in the study group and 11 in the control group, were selected from a medical university clinic and a local private practice. The study group receiving prophylactic therapy for six months suffered no recurrences, as compared with eight children suffering one recurrence each in the control group that was treated only acutely. The results were significant at p less than 0.005 with df = 1, determined by the Fischer's exact test and the chi-square method using Yates's correction factor. These data indicated that a mean dose of TMP/SMX 6.8/34 mg/kg/d divided into twice daily doses and given for six months was safe and effective in controlling RAOM infections in a high-risk pediatric population.

Neuroleptic drug use in a family-practice center.

A three-year retrospective review of neuroleptic drug use at the Family Practice Center of the Medical University of South Carolina was conducted. The charts of 73 patients who had taken neuroleptic agents were reviewed for compliance with the most recent guidelines established by the National Institute of Mental Health (NIMH). Information retrieved included: age, sex, number of clinic visits, diagnosis, neuroleptic agent used, dosages, duration of therapy, concomitant psychotropics, antiparkinson agents, and extrapyramidal side effects. Neuroleptic drug use was considered inappropriate for 26% of the patients' diagnoses. Twenty percent of the dosage regimens were outside the ranges recommended by NIMH. Almost 15% of the medications used consisted of th fixed-combination products of perphenazine and amitriptyline hydrochloride, and 77% of these prescriptions were for dosages below the recommended amounts. Polypsychopharmacy was a common problem, with 36% of the patients receiving one or more psychotropic drugs with a neuroleptic agent. Nineteen patients (26%) had been prescribed an inappropriate psychotropic combination. Nine patients (12%) had received antiparkinson agents. Eight patients (11%) had documented extrapyramidal side effects. Neuroleptic drug use was found to be suboptimal. Various deficiencies were documented particularly in the use of fixed-combination products and because of the problems associated with polypsychopharmacy.