John C. Kern

The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders.

The frequency of zinc deficiency, copper toxicity and low zinc/copper in children with autism spectrum disorders (ASDs) may indicate decrement in metallothionein system functioning. A retrospective review of plasma zinc, serum copper and zinc/copper was performed on data from 230 children with autistic disorder, pervasive developmental disorder-NOS and Asperger’s syndrome. The entire cohort’s mean zinc level was 77.2 μg dl−1, mean copper level was 131.5 μg dl−1, and mean Zn/Cu was 0.608, which was below the 0.7 cut-off of the lowest 2.5% of healthy children. The plasma zinc/serum copper ratio may be a biomarker of heavy metal, particularly mercury, toxicity in children with ASDs.

Inhibition of Alveolar Osteitis in Mandibular Tooth Extraction Sites Using Platelet-Rich Plasma

Alveolar osteitis (AO), also known as dry socket, continues to be a complication of tooth removal. Platelet-rich plasma (PRP) can be used to accelerate both soft and hard tissue healing. This paper is a retrospective review of the benefits of PRP in AO prevention. PRP was obtained from patients for use in the postremoval alveolar sockets of mandibular molar extraction sites. Statistical analysis of 904 extraction sites with and without PRP use was examined. PRP significantly reduced the incidence of AO by 62.1%, from 9.57% in patients not receiving PRP to 3.63% in patients who received PRP (P = .00043). PRP use had benefits in all subpopulations. The odds of AO occurring in patients not receiving PRP treatment following tooth extraction was 2.81 times greater than in patients receiving PRP treatment immediately following tooth extraction. Four statistically significant risk factors for AO were identified: complete impaction, oral contraceptive use, bruxism, and failure to administer PRP. The application of PRP can significantly reduce the incidence of AO even in patients with risk factors for AO, such as removal of impacted teeth, bruxism, and oral contraceptive use. PRP may be of benefit because it helps initiate clot formation, provides growth factors to facilitate the healing process, and contains concentrated white blood cells to inhibit infection. The use of PRP following tooth extraction is a simple, cost-effective technique that can be used to decrease the incidence of AO and therefore decrease postoperative pain.

Molecular speciated isotope dilution mass spectrometric methods for accurate, reproducible and direct quantification of reduced, oxidized and total glutathione in biological samples.

Novel protocols were developed to accurately quantify reduced (GSH), oxidized (GSSG) and total (tGSH) glutathione in biological samples using molecular speciated isotope dilution mass spectrometry (SIDMS). For GSH and GSSG measurement, the sample was spiked with isotopically enriched analogues of the analytes ((310)GSH and (616)GSSG), along with N-ethylmaleimide (NEM), and treated with acetonitrile to solubilize the endogenous analytes via protein precipitation and equilibrate them with the spikes. The supernatant was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the analytes were quantified with simultaneous tracking and correction for auto-oxidation of GSH to GSSG. For tGSH assay, a (310)GSH-spiked sample was treated with dithiothreitol (DTT) to convert disulfide-bonded glutathione to GSH. After removing the protein, the supernatant was analyzed by LC-MS/MS and the analyte was quantified by single-spiking isotope dilution mass spectrometry (IDMS). The mathematical relationships in IDMS and SIDMS quantifications are based on isotopic ratios and do not involve calibration curves. The protocols were validated using spike recovery tests and by analyzing synthetic standard solutions. Red blood cell (RBC) and saliva samples obtained from healthy subjects, and whole blood samples collected and shipped from a remote location were analyzed. The concentrations of tGSH in the RBC and whole blood samples were 2 orders of magnitude higher than those found in saliva. The fractions of GSSG were 0.2-2.2% (RBC and blood) and 15-47% (saliva) of the free glutathione (GSH + 2xGSSG) in the corresponding samples. Up to 3% GSH was auto-oxidized to GSSG during sample workup; the highest oxidations (>1%) were in the saliva samples.

Improved sample preparation of glyphosate and methylphosphonic acid by EPA method 6800A and time-of-flight mass spectrometry using novel solid-phase extraction

The employment of chemical weapons by rogue states and/or terrorist organizations is an ongoing concern in the United States. The quantitative analysis of nerve agents must be rapid and reliable for use in the private and public sectors. Current methods describe a tedious and time-consuming derivatization for gas chromatography-mass spectrometry and liquid chromatography in tandem with mass spectrometry. Two solid-phase extraction (SPE) techniques for the analysis of glyphosate and methylphosphonic acid are described with the utilization of isotopically enriched analytes for quantitation via atmospheric pressure chemical ionization-quadrupole time-of-flight mass spectrometry (APCI-Q-TOF-MS) that does not require derivatization. Solid-phase extraction-isotope dilution mass spectrometry (SPE-IDMS) involves pre-equilibration of a naturally occurring sample with an isotopically enriched standard. The second extraction method, i-Spike, involves loading an isotopically enriched standard onto the SPE column before the naturally occurring sample. The sample and the spike are then co-eluted from the column enabling precise and accurate quantitation via IDMS. The SPE methods in conjunction with IDMS eliminate concerns of incomplete elution, matrix and sorbent effects, and MS drift. For accurate quantitation with IDMS, the isotopic contribution of all atoms in the target molecule must be statistically taken into account. This paper describes two newly developed sample preparation techniques for the analysis of nerve agent surrogates in drinking water as well as statistical probability analysis for proper molecular IDMS. The methods described in this paper demonstrate accurate molecular IDMS using APCI-Q-TOF-MS with limits of quantitation as low as 0.400 mg/kg for glyphosate and 0.031 mg/kg for methylphosphonic acid.

Student Assistance Program Outcomes for Students at Risk for Suicide

Pennsylvania’s response to adolescent suicide is its Student Assistance Program (SAP). SAP has been funded for 27 years although no statewide outcome studies using case-level data have been conducted. This study used logistic regression to examine drug-/alcohol-related behaviors and suspensions of suicidal students who participated in SAP. Of the 46 services, 10 best predicted (p < .01) that these undesirable outcomes would cease. Although no study subjects died by suicide, 42 of 374,626 referred students did die by suicide. Suicidal students who did not participate had double the rate of suicide of suicidal participants of SAP. Students referred for other reasons also killed themselves. Further work must be done to assess all referred students for suicide risk, examine educational outcomes, monitor substance-related crimes and overdoses, and examine school-related factors postmortem. Evidence from this study can be used by researchers to plan future studies and by Pennsylvania’s school nurses when planning services.

Pig Data and Bayesian Inference on Multinomial Probabilities.

Bayesian inference on multinomial probabilities is conducted based on data collected from the game Pass the Pigs®. Prior information on these probabilities is readily available from the instruction manual, and is easily incorporated in a Dirichlet prior. Posterior analysis of the scoring probabilities quantifies the discrepancy between empirical and prior estimates, and yields posterior predictive simulations used to compare competing extreme strategies.

Mean serum-level of common organic pollutants is predictive of behavioral severity in children with autism spectrum disorders

Autism spectrum disorders (ASD), and their pathogenesis, are growing public health concerns. This study evaluated common organic pollutant serum-concentrations in children, as it related to behavioral severity determined by rating scales and the Autism Diagnostic Observation Schedule (ADOS). Thirty children, ages 2–9, with ASD and thirty controls matched by age, sex, and socioeconomic status were evaluated using direct blood serum sampling and ADOS. Pooling concentrations of all studied pollutants into a single variable yielded cohort-specific neurobehavioral relationships. Pooled serum-concentration correlated significantly with increasing behavioral severity on the ADOS in the ASD cohort (p = 0.011, r = 0.54), but not controls (p = 0.60, r = 0.11). Logistic regression significantly correlated mean pollutant serum-concentration with the probability of diagnosis of behaviorally severe autism, defined as ADOS >14, across all participants (odds ratio = 3.43 [95% confidence: 1.14–10.4], p = 0.0287). No specific analyte correlated with ADOS in either cohort. The ASD cohort displayed greater quantitative variance of analyte concentrations than controls (p = 0.006), suggesting a wide range of detoxification functioning in the ASD cohort. This study supports the hypothesis that environmental exposure to organic pollutants may play a significant role in the behavioral presentation of autism.

The Pitman Closeness of a Class of Scaled Estimators

Abstract Scaling is known to reduce the mean square error of unbiased estimators of the mean. Pitman closeness, like mean square error, is often used as a criterion for comparing competing estimators. Scaling is reexamined from the perspective of Pitman closeness. Scaling is found to offer not only reduced mean square error, but also, in many cases, an advantage in terms of Pitman closeness. However, these advantages accrue to a substantial degree only in experiments with low signal-to-noise ratio and very costly measurements.

Introduction to Regression Analysis

in a proportional font in a way that often results in ugly syntax like a < -sum(x) instead of a <sum(x). Also, compound statements such as function definitions are mostly not indented, and the output although properly formatted in a fixed width (“typewriter”) font, shows an extraneous space in lines like [1 ] 0.158. All the graphics—it is nice that there are many—have been imported as bitmaps (rather than “vector”) graphics, giving rise to unnecessary staircase effects (p. 30 and many more) or blurring (p. 264) with inferior quality. In summary, the book contains some very good concepts, but there are aspects which could have been elaborated more effectively as has been done in the given references carrying very similar titles.

Menopausal Symptom Relief with Acupuncture: Bayesian Analysis Using Piecewise Regression

ABSTRACT Due to the risk of recurrence, cancer-surviving menopausal women are urged to avoid traditional hormone therapy in their efforts to alleviate the symptoms of menopause. Here we consider the effectiveness of an alternative treatment for the relief of menopausal symptoms: acupuncture. We construct and apply a piecewise linear negative binomial regression model to the longitudinal frequency data collected from subjects randomly allocated to experimental groups. Bayesian inference on the parameters of this model—which include the knot locations of the piecewise regression curve—reveals intriguing differences between experimental groups.