Jeffrey R. Wilson

Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles

The role of intracranial atherosclerosis in Alzheimer’s disease (AD) has been a subject of debate since the first decade of the last century. The initial “vascular hypothesis” of AD was rejected after a series of mid-twentieth century gross anatomical postmortem studies that showed an inconstant relationship between intracranial atherosclerosis and senile dementia. These early studies did not utilize statistical methods, however, and the investigators did not appear to consider the possibility that intracranial atherosclerosis might have a probabilistic, rather than an absolute, effect on AD risk. Recent studies by three independent groups have found a significant statistical association between postmortem measures of circle of Willis atherosclerosis and AD. The present study was undertaken to further address the validity of this association in a large autopsy series, including cases diagnosed neuropathologically with vascular dementia (VaD) and non-AD dementias. Postmortem gross anatomical grading of circle of Willis atherosclerosis was performed in 397 subjects classified by neuropathological diagnosis, including 92 non-demented elderly controls, 215 with AD, 30 with VaD and 60 with non-AD dementias. Circle of Willis atherosclerosis was more severe in subjects with AD and VaD than in control subjects, while it was equivalent between control subjects and subjects with non-AD dementias. Increasing atherosclerotic grade increased the odds ratios (OR) for the diagnoses of both AD and VaD and also increased the ORs for both increased neuritic plaque density and higher Braak neurofibrillary tangle stage. The significance of these associations was retained after consideration of the effects of age, gender and the apolipoprotein E-ε4 allele. The results suggest that the statistical association between intracranial atherosclerosis and AD is not an artifact of diagnostic misclassification or of unequal distribution of the apolipoprotein E-ε4 allele.

Characterization of Firefighter Exposures During Fire Overhaul

Previous studies have characterized firefighter exposures during fire suppression. However, minimal information is available regarding firefighter exposures during overhaul, when firefighters look for hidden fire inside attics, ceilings, and walls, often without respiratory protection. A comprehensive air monitoring study was conducted to characterize City of Phoenix firefighter exposures during the overhaul phase of 25 structure fires. Personal samples were collected for aldehydes; benzene; toluene; ethyl benzene; xylene; hydrochloric acid; polynuclear aromatic hydrocarbons (PNA); respirable dust; and hydrogen cyanide (HCN). Gas analyzers were employed to continuously monitor carbon monoxide (CO), HCN, nitrogen dioxide (NO2), and sulfur dioxide (SO2). Area samples were collected for asbestos, metals (Cd, Cr, Pb), and total dust. During overhaul the following exceeded published ceiling values: acrolein (American Conference of Governmental Industrial Hygienists [ACGIH] 0.1 ppm) at 1 fire; CO (National Institute for Occupational Safety and Health [NIOSH] 200 ppm) at 5 fires; formaldehyde (NIOSH 0.1 ppm) at 22 fires; and glutaraldehyde (ACGIH 0.05 ppm) at 5 fires. In addition, the following exceeded published short-term exposure limit values: benzene (NIOSH 1 ppm) at two fires, NO2 (NIOSH 1 ppm) at two fires, and SO2 (ACGIH 5 ppm) at five fires. On an additive effects basis, PNA concentrations exceeded the NIOSH recommended exposure limits (0.1 mg/M3) for coal tar pitch volatiles at two fires. Maximum concentrations of other sampled substances were below their respective permissible exposure limits. Initial 10-min average CO concentrations did not predict concentrations of other products of combustion. The results indicate that firefighters should use respiratory protection during overhaul. In addition, these findings suggest that CO should not be used as an indicator gas for other contaminants found in this atmosphere.

Just Modeling Through: a Rough Guide to Modeling

Skill in modeling is one of the keys to success in OR/MS practice. This has been recognized for many years, but we often give it only lip service. Models are used in many ways in OR/MS practice. A few simple principles of modeling may be useful. The six principles discussed here cover simplicity versus complexity; model development as a gradual, almost piecemeal process; dividing larger models into smaller components; using analogies; proper uses of data; and finally the way in which the modeling process can seem chaotic. Others may wish to comment on these principles and add their own.

An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity

OBJECT Despite improvements in the medical and surgical management of patients with glioblastoma, tumor recurrence remains inevitable. For recurrent glioblastoma, however, the clinical value of a second resection remains uncertain. Specifically, what proportion of contrast-enhancing recurrent glioblastoma tissue must be removed to improve overall survival and what is the neurological cost of incremental resection beyond this threshold? METHODS The authors identified 170 consecutive patients with recurrent supratentorial glioblastomas treated at the Barrow Neurological Institute from 2001 to 2011. All patients previously had a de novo glioblastoma and following their initial resection received standard temozolomide and fractionated radiotherapy. RESULTS The mean clinical follow-up was 22.6 months and no patient was lost to follow-up. At the time of recurrence, the median preoperative tumor volume was 26.1 cm(3). Following re-resection, median postoperative tumor volume was 3.1 cm(3), equating to an 87.4% extent of resection (EOR). The median overall survival was 19.0 months, with a median progression-free survival following re-resection of 5.2 months. Using Cox proportional hazards analysis, the variables of age, Karnofsky Performance Scale (KPS) score, and EOR were predictive of survival following repeat resection (p = 0.0001). Interestingly, a significant survival advantage was noted with as little as 80% EOR. Recursive partitioning analysis validated these findings and provided additional risk stratification at the highest levels of EOR. Overall, at 7 days after surgery, a deterioration in the NIH stroke scale score by 1 point or more was observed in 39.1% of patients with EOR ≥ 80% as compared with 16.7% for those with EOR < 80% (p = 0.0049). This disparity in neurological morbidity, however, did not endure beyond 30 days postoperatively (p = 0.1279). CONCLUSIONS For recurrent glioblastomas, an improvement in overall survival can be attained beyond an 80% EOR. This survival benefit must be balanced against the risk of neurological morbidity, which does increase with more aggressive cytoreduction, but only in the early postoperative period. Interestingly, this putative EOR threshold closely approximates that reported for newly diagnosed glioblastomas, suggesting that for a subset of patients, the survival benefit of microsurgical resection does not diminish despite biological progression.

Auricular acupuncture, education, and smoking cessation: a randomized, sham-controlled trial.

OBJECTIVES This study examined the effect of acupuncture alone and in combination with education on smoking cessation and cigarette consumption. METHODS We prospectively studied 141 adults in a quasi-factorial design using acupuncture, sham acupuncture, and education. RESULTS All groups showed significant reductions in smoking and posttreatment cigarette consumption, with the combined acupuncture-education group showing the greatest effect from treatment. The trend continued in follow-up; however, significant differences were not maintained. Greater pack-year history (i.e. the number of years smoking multiplied by baseline number of cigarettes smoked per year, divided by 20 cigarettes per pack) negatively correlated with treatment effect. Trend analysis suggested 20 pack-years as the cutoff point for this correlation. CONCLUSIONS Acupuncture and education, alone and in combination, significantly reduce smoking; however, combined they show a significantly greater effect, as seen in subjects with a greater pack-year history.

Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer’s disease

The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein biomarkers in neuropathologically confirmed Alzheimer’s disease (AD), non-demented (ND) elderly controls and non-AD dementias (NADD) was assessed. Candidate markers were selected on the basis of initial two-dimensional gel electrophoresis studies or by literature review. Markers selected by the former method included apolipoprotein A-1 (ApoA1), haemopexin (HPX), transthyretin (TTR) and pigment epithelium-derived factor (PEDF), while markers identified from the literature included Aβ1-40, Aβ1-42, total tau, phosphorylated tau, α-1 acid glycoprotein (A1GP), haptoglobin, zinc α-2 glycoprotein (Z2GP) and apolipoprotein E (ApoE). Ventricular CSF concentrations of the markers were measured by enzyme-linked immunosorbent assay (ELISA). The concentrations of Aβ1-42, ApoA1, A1GP, ApoE, HPX and Z2GP differed significantly among AD, ND and NADD subjects. Logistic regression analysis for the diagnostic discrimination of AD from ND found that Aβ1-42, ApoA1 and HPX each had significant and independent associations with diagnosis. The CSF concentrations of these three markers distinguished AD from ND subjects with 84% sensitivity and 72% specificity, with 78% of subjects correctly classified. By comparison, using Aβ1-42 alone gave 79% sensitivity and 61% specificity, with 68% of subjects correctly classified. For the diagnostic discrimination of AD from NADD, only the concentration of Aβ1-42 was significantly related to diagnosis, with a sensitivity of 58%, specificity of 86% and 86% correctly classified. The results indicate that for the discrimination of AD from ND control subjects, measurement of a set of markers including Aβ1-42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of Aβ1-42 alone. For the discrimination of AD from NADD subjects, measurement of Aβ1-42 alone was superior.

An empirical investigation of the potential confounding variables in student evaluation of teaching

Abstract Prior research in psychology and education has extensively investigated the propriety of using student evaluation of teaching (SET) for administrative control purposes. This literature is in general agreement that SET are susceptible to variables which affect the SET but do not relate to effective instruction. A recent American Accounting Association (AAA) -sponsored monograph by Williams, Tiller, Herring and Scheiner (1988) suggested that accounting education research explore the extent to which reported validity results in these literatures carry over to accounting. The objective of the present study is to investigate three major questions: (a) Do SET differ across upper-level undergraduate accounting courses?, (b) What potential confounding variables are most highly associated with SET?, and (c) Can a model which includes these variables be constructed so that administrators might use it to control for these variables? Our results indicate that significant associations exist between SET, course identity, and grading policy.

Interaction of cardiovascular disease and neurodegeneration : transcranial Doppler ultrasonography and Alzheimer's disease

Abstract Objective: Recent post-mortem studies have reported that the severity of atheromatous deposits in the circle of Willis is significantly greater, relative to non-demented (ND) elderly persons, in subjects with neuropathologically diagnosed Alzheimers disease (AD). Additionally, the severity of intracranial atherosclerosis correlates significantly with the densities of neuritic plaques and neurofibrillary tangles. In this study, we examine the arteries of the circle of Willis by transcranial Doppler (TCD) ultrasonography. Methods: TCD was used to measure, in 25 AD patients and 30 ND elderly subjects, mean flow velocities and pulsatility indices in 16 different segments of the circle of Willis. The data were compared with and without adjustment for age, gender and systolic blood pressure. Results: The AD patients had systematically higher pulsatility indices (p<0.005) than the ND group. Incremental increases of pulsatility indices in these segments had odds ratios ranging from 1.8 to 48 for the presence of AD when adjusted for age, gender and systolic blood pressure. The left internal carotid artery siphon and the left posterior cerebral artery were the two vessels that were strongly associated with AD diagnosis. Mean flow velocities were generally lower in patients with AD but the differences did not reach the significance level. Discussion: The pulsatility indices of the arteries of AD patients were generally greater than those of similarly-aged ND subjects. This difference is most likely due to increased arterial wall rigidity imposed by atherosclerotic changes. Atherosclerotic disease of intracranial arteries may be a risk factor for AD.

Chi-square tests for comparing vectors of proportions for several cluster samples

Test statistics are developed for comparing vectors of proportions obtained from several independent two–stage cluster samples. It is assumed that clusters are selected with probability proportional to size for each sample. Walds general method of constructing quadratic forms is used to obtain a large sample chi–square test. More easily evaluted chi–square tests are derived from the Dirichlet–multinnomial model. Corresponding goodness–of–fit test for the Dirichlet–multinomial model are also derived.

The impact of extent of resection on malignant transformation of pure oligodendrogliomas: Clinical article

OBJECT Recent evidence suggests that a greater extent of resection (EOR) extends malignant progression-free survival among patients with low-grade gliomas (LGGs). These studies, however, rely on the combined analysis of oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas-3 histological subtypes with distinct genetic and molecular compositions. To assess the value of EOR in a homogeneous LGG patient population and delineate its impact on LGG transformation, the authors examined its effect on newly diagnosed supratentorial oligodendrogliomas. METHODS The authors identified 93 newly diagnosed adult patients with WHO Grade II oligodendrogliomas treated with microsurgical resection at Barrow Neurological Institute. Clinical, laboratory, and radiographic data were collected retrospectively, including 1p/19q codeletion status and volumetric analysis based on T2-weighted MRI. RESULTS The median preoperative and postoperative tumor volumes and EOR were 29.0 cm(3) (range 1.3-222.7 cm(3)), 5.2 cm(3) (range 0-156.1 cm(3)), and 85% (range 6%-100%), respectively. Median follow-up was 75.4 months, and there were 14 deaths (15%). Progression and malignant progression were identified in 31 (33%) and 20 (22%) cases, respectively. A greater EOR was associated with longer overall survival (p = 0.005) and progression-free survival (p = 0.004); however, a greater EOR did not prolong the interval to malignant progression, even when controlling for 1p/19q codeletion. CONCLUSIONS A greater EOR is associated with an improved survival profile for patients with WHO Grade II oligodendrogliomas. However, for this particular LGG patient population, the interval to tumor transformation is not influenced by cytoreduction. These data raise the possibility that the capacity for microsurgical resection to modulate malignant progression is mediated through biological mechanisms specific to nonoligodendroglioma LGG histologies.