A historical survey of the office of Kansas county superintendent of schools

Call number: LD2668 .R4 1964 F98

Driving under the influence of an intoxicant in Ireland.

The number of specimens analysed by the MBRS has been increasing for both alcohol and drugs. Blood and urine specimens are analysed for the concentration of alcohol using Headspace Gas Chromatography. Specimens testing positive were forwarded to the State Laboratory for confirmatory analysis by either GC/MS or LC/MS. In 2000, 93 per cent of blood specimens, 91 per cent of urine specimens and 82 per cent of breath specimens were over the limit. In the same year, 57 per cent of blood specimens, 66 per cent of urine specimens and 33 per cent of breath specimens were over twice the limit. Of the 78 specimens tested for the presence of a drug or drugs, 37 were blood specimens and 41 urine specimens. Of these, 34 blood specimens and 37 urine specimens were found to be positive, while seven specimens were negative for the drug or drug classes tested (three blood and four urine specimens). There were 23 specimens found positive for one drug class and 48 for more than one drug.The number of requests for the presence of drugs in RTA blood and urine specimens is increasing annually and the high percentage of positives found in the specimens tested indicates the need for such analyses. The results showed excellent agreement for drug detection in the blood specimens analysed by the different methods, except for the cannabinoids. The number of specimens in this study is small and care must be exercised in interpreting the results

SAM: A Tool for Measurement of Moderate to Vigorous Physical Activity (MVPA) in School Physical Education

Int J Exerc Sci 5(2) : 127-135, 2012. Observational methods have been a primary methodology used by physical educators for assessing teacher and student behaviors in school physical education (PE) classes for over 30 years. Observational instruments traditionally used in PE are economical, but are time intensive and complicated. Recently national PE recommendations have been promoted to encourage practitioners to achieve ≥ 50% of PE class in moderate to vigorous physical activity (MVPA). The purpose of this preliminary study was to develop, validate, and test the reliability of the Simple Activity Measurement (SAM) instrument for assessing MVPA during school PE classes. Students (N=36, representing grades 3-10) from a convenient sample of schools in San Antonio, TX were randomly selected to wear SUUNTOTM heart rate (HR) monitors during PE classes as an MVPA intensity measure, and the SAM instrument was used to observe 6 classes (N=281 students) for MVPA each minute using the SAM 0-10 scale. The SAM instrument was found to be a significant predictor for HR (r=0.555, r2=0.308, p\u3c0.05) using linear regression, and the intra class correlation coefficient to test reliability was found to be R=0.803, p\u3c0.05. Students averaged 88.5 % of class time spent in MVPA at the elementary level and only 36.5 % of class time spent in MVPA at the high school level. The results of this preliminary study indicate that the SAM has promise to provide school PE evaluators with an effective economical observation tool to document minutes of student MVPA in PE classes, and to promote accountability with national MVPA recommendations

Mitochondrial dysfunction and immune activation are detectable in early Alzheimer's disease blood.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tAlzheimer's disease (AD), like other dementias, is characterized by progressive neuronal loss and neuroinflammation in the brain. The peripheral leukocyte response occurring alongside these brain changes has not been extensively studied, but might inform therapeutic approaches and provide relevant disease biomarkers. Using microarrays, we assessed blood gene expression alterations occurring in people with AD and those with mild cognitive changes at increased risk of developing AD. Of the 2,908 differentially expressed probes identified between the three groups (p < 0.01), a quarter were altered in blood from mild cognitive impairment (MCI) and AD subjects, relative to controls, suggesting a peripheral response to pathology may occur very early. There was strong evidence for mitochondrial dysfunction with decreased expression of many of the respiratory complex I-V genes and subunits of the core mitochondrial ribosome complex. This mirrors changes previously observed in AD brain. A number of genes encoding cell adhesion molecules were increased, along with other immune-related genes. These changes are consistent with leukocyte activation and their increased the transition from circulation into the brain. In addition to expression changes, we also found increased numbers of basophils in people with MCI and AD, and increased monocytes in people with an AD diagnosis. Taken together this study provides both an insight into the functional response of circulating leukocytes during neurodegeneration and also identifies potential targets such as the respiratory chain for designing and monitoring future therapeutic interventions using blood.InnoMed, European Union of the Sixth Framework programAlzheimer’s Research TrustJohn and Lucille van Geest FoundationNIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation TrustInstitute of Psychiatry Kings College Londo

The dynamics of mutation rate, aging and extrinsic risk in melanoma development

The gradual accumulation of intrinsic mutations linked to cell division, and the mutational imprints caused by extrinsic or environmental factors on the genome, afford the opportunity to examine the relationship between intrinsic and extrinsic risk in cancer subtypes with varying lifetime incidences. The incidence of the distinct molecular subtypes of cutaneous melanoma varies depending on anatomical site, intensity and pattern of ultraviolet (UV) light exposure, and age. Cutaneous melanoma has been subdivided into four groups, with tumor groups defined by driver mutations in either BRAF, NRAS, or NF1; with the final group defined by the absence of mutations in these genes (triple wild-type).Here we analyze the relative contributions of intrinsic risk, measured by characteristic age-related (clock-like) mutations, and extrinsic risk, measured by canonical UV light-induced signatures, to tumor development in melanoma subtypes. We show that the contributions of intrinsic and extrinsic mutations differ in magnitude and chronology during the molecular evolution of the distinct disease subtypes. We observe a gradual decline in intrinsic cell division rates as patients’ age. Our analysis of UV light-driven mutations reveals that gradual UV damage drives non-BRAF melanomas, and punctuated UV damage is linked to BRAF melanomagenesis. These data suggest that mutations accumulate at different rates in the disease subtypes, independently of germline melanoma susceptibility, from cells of origin with distinct proliferation rates. Based on our results we propose that models examining the relative roles of extrinsic and intrinsic risk in cancer consider subtype-specific lifetime risks, germline susceptibility and somatic mutational processes. <br/

Harnessing Dithiolene Complexes for Carbon Dioxide Activation

Molybdenum and tungsten are found in the active site of a number of metalloenzymes. Bound to these atoms are sulphide-containing ligands, more commonly referred to in the literature as dithiolene ligands. The combination of metal and ligand allows for catalysis close to the thermodynamic limit of carbon dioxide reduction to formate to take place. Thus, these active sites are attractive targets for chemists, as their potential for industrial application is limitless. This thesis focuses on the synthesis of mimics of the active site of the formate dehydrogenase enzyme (FDH). By providing functional models of the active site, we wish to identify the necessity of proton relays in close proximity to the central metal ion for catalysis; their presence is seen in the native enzyme, but is missing from the catalytically-competent models in the literature. A route to a novel molybdenum-oxo bis-dithiolene complex was successfully created, streamlined and improved by previous researchers within the group. This novel route was then used to generate more ligands and subsequent complexes in an effort to showcase the versatility of the synthesis. The terminal functionality of the FDH active site is not limited to just oxo ligands, but to other elements in Group 18 such as sulphur and selenium. Attempts at synthesising the sulphido analogue of the target complex were made, but unfortunately this was unsuccessful. A ‘third generation’ pro-ligand was also synthesised with the goal of creating novel, bridged molybdenum-oxo dithiolene complexes. Unfortunately, attempts to synthesise this new kind of dithiolene complex were unsuccessful. The synthesis of the tungsten analogues of these compounds was explored but merely added to the reputation of the difficulty in working with tungsten compounds; fortunately, the tungsten analogue of the target complex was synthesised for a time, and key data points were recorded. Computational methods were employed to better understand the physical properties of the synthesised complexes, with a focus on the accurate prediction of the infrared stretching band of the Mo O bond. This process of identifying this stretch was aided by the use of five functionals, each with varying constraints. The functionals that achieved the most accurate predictions can now be reused as a standard for other researchers to conduct computational studies on molybdenumoxo dithiolene complexes with a high degree of certainty in the accuracy of their results. The importance of electrochemical methods for understanding the behaviour of redox-active metals cannot be understated. Several of the synthesised complexes were subjected to cyclic voltammetry, allowing structure-activity relationships to be derived for the MoIV/MoV and MoV/MoVI redox couples. The target complex and its non-functionalised analogue were tested for their catalytic activity with the goal of seeing the catalytic reduction of carbon dioxide into formate. Although the results for the reduction of carbon dioxide to formate and oxygen atom transfer catalysis were poor, oxidation catalysis of formate showed that the complexes were four times more effective with the proton relays than without. [This abstract contains characters which can't be rendered here, please see original abstract in .PDF

A blood gene expression marker of early Alzheimer's disease.

PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tA marker of Alzheimer's disease (AD) that can accurately diagnose disease at the earliest stage would significantly support efforts to develop treatments for early intervention. We have sought to determine the sensitivity and specificity of peripheral blood gene expression as a diagnostic marker of AD using data generated on HT-12v3 BeadChips. We first developed an AD diagnostic classifier in a training cohort of 78 AD and 78 control blood samples and then tested its performance in a validation group of 26 AD and 26 control and 118 mild cognitive impairment (MCI) subjects who were likely to have an AD-endpoint. A 48 gene classifier achieved an accuracy of 75% in the AD and control validation group. Comparisons were made with a classifier developed using structural MRI measures, where both measures were available in the same individuals. In AD and control subjects, the gene expression classifier achieved an accuracy of 70% compared to 85% using MRI. Bootstrapping validation produced expression and MRI classifiers with mean accuracies of 76% and 82%, respectively, demonstrating better concordance between these two classifiers than achieved in a single validation population. We conclude there is potential for blood expression to be a marker for AD. The classifier also predicts a large number of people with MCI, who are likely to develop AD, are more AD-like than normal with 76% of subjects classified as AD rather than control. Many of these people do not have overt brain atrophy, which is known to emerge around the time of AD diagnosis, suggesting the expression classifier may detect AD earlier in the prodromal phase. However, we accept these results could also represent a marker of diseases sharing common etiology.InnoMed, European Union of the Sixth Framework programAlzheimer’s Research UKJohn and Lucille van Geest FoundationNIHRBiomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation TrustInstitute of Psychiatry Kings College LondonNIA/NIH RC

Laboratory investigation of a load carriage task observed in forestry

The objective of the present study was to investigate and compare the human responses to two load carriage tasks performed with three different load masses and on three different gradients. The task of carrying hydrogel in one hand was observed in a silviculture industry and crude physiological and perceptual responses were measured. This task was simulated in a laboratory setting together with a suggested intervention of backpack carriage. Eighteen conditions were established which consisted of the two modes of carriage and a combination of three load masses (9kg, 12kg and 15kg) and three gradients (5%, 10% and 15%). Twenty eight Rhodes University female students comprised the sample and the experimental procedures were conducted on a Quinton treadmill. Each participant was required to complete nine of the eighteen conditions which were each four minutes in duration. Postural changes were assessed using lateral and posterior digital images taken at the second and fourth minute and compression and shearing forces were estimated with the ErgolmagerTM Physiological responses (heart rate, ventilation and metabolic responses) were measured continuously with the Quark b² and perceptual responses ('central' and 'local' RPE) were measured every minute during the experimentation and body discomfort was rated at the completion of each condition. Overall responses revealed that hand carriage (146 bt.min⁻¹ , 25.09 mIO₂. kg-l.min⁻¹) was generally found to be more physiologically stressful than backpack carriage (130 bt.min⁻¹, 22.15 mIO₂.kg⁻¹ .min⁻¹) independent of load mass and gradient. Physiological responses were higher (113 bt.min-1 to 174 bt.min⁻¹ ) in responses to increasing gradient as opposed to increasing load mass (104 bt.min-1 to 153 bt.min⁻¹ ) for both backpack and hand carriage. Categorisation using the guidelines of Sanders and McCormick (1993) allowed for classification of conditions, with respect to physiological responses, into 'moderate', 'heavy' and 'very heavy' stress. For almost all of the physiological responses the majority of conditions which were classified as 'moderate' were backpack carriage conditions and the conditions classified as 'very heavy' were mostly hand carriage conditions. In terms of postural responses hand carriage resulted in more strain and greater compression and shearing forces on the spine. In terms of the compression forces increasing gradient had a greater affect on backpack carriage (681 N to 935 N) compared to hand carriage (570N to 793N). In contrast, increasing load mass had a larger affect on hand carriage postures and compression forces (751 N to 935N) in comparison to backpack carriage (723N to 780N). Shearing forces were found to be worse in hand carriage conditions overall. Although participants generally underrated perceived exertion in relation to cardiorespiratory responses, these perceptions revealed that backpack carriage, with a mean 'central' RPE of 12 compared to 11 for hand carriage, was somewhat preferred to hand carriage and that increasing gradient was perceived to be marginally more straining than increasing load mass

Absence of a serum melatonin rhythm under acutely extended darkness in the horse

<p>Abstract</p> <p>Background</p> <p>In contrast to studies showing gradual adaptation of melatonin (MT) rhythms to an advanced photoperiod in humans and rodents, we previously demonstrated that equine MT rhythms complete a 6-h light/dark (LD) phase advance on the first post-shift day. This suggested the possibility that melatonin secretion in the horse may be more strongly light-driven as opposed to endogenously rhythmic and light entrained. The present study investigates whether equine melatonin is endogenously rhythmic in extended darkness (DD).</p> <p>Methods</p> <p>Six healthy, young mares were maintained in a lightproof barn under an LD cycle that mimicked the ambient natural photoperiod outside. Blood samples were collected at 2-h intervals for 48 consecutive h: 24-h in LD, followed by 24-h in extended dark (DD). Serum was harvested and stored at -20°C until melatonin and cortisol were measured by commercial RIA kits.</p> <p>Results</p> <p>Two-way repeated measures ANOVA (n = 6/time point) revealed a significant circadian time (CT) x lighting condition interaction (<it>p < .0001</it>) for melatonin with levels non-rhythmic and consistently high during DD (CT 0-24). In contrast, cortisol displayed significant clock-time variation throughout LD and DD (<it>p = .0009</it>) with no CT x light treatment interaction (<it>p </it>= .4018). Cosinor analysis confirmed a significant 24-h temporal variation for melatonin in LD <it>(p = .0002) </it>that was absent in DD <it>(p = .51)</it>, while there was an apparent circadian component in cortisol, which approached significance in LD <it>(p = .076)</it>, and was highly significant in DD <it>(p = .0059).</it></p> <p>Conclusions</p> <p>The present finding of no 24 h oscillation in melatonin in DD is the first evidence indicating that melatonin is not gated by a self-sustained circadian process in the horse. Melatonin is therefore not a suitable marker of circadian phase in this species. In conjunction with recent similar findings in reindeer, it appears that biosynthesis of melatonin in the pineal glands of some ungulates is strongly driven by the environmental light cycle with little input from the circadian oscillator known to reside in the SCN of the mammalian hypothalamus.</p