bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifocal pupillographic visual field testing in glaucoma
Authors: Maddess Ted , Bedford Suzanne M , Goh Xin‐Lin , James Andrew C
Published: July 2009

Abstract

Purpose:  This preliminary study investigated a means of concurrently assessing the visual field defects of both eyes by recording pupillary responses to multifocal stimuli.

Methods:  Twenty normal subjects and 26 primary open angle glaucoma patients, age and sex matched, were examined by slit‐lamp, Humphrey Field Analyser II achromatic 24‐2 perimetry and fundus photography. The patients had moderate to severe fields in at least one eye. Two stereoscopically arranged displays presented an array of 24 stimulus regions per eye extending from fixation to 30 degrees eccentricity. Pupil responses were recorded by video cameras under infrared illumination. Four stimulus conditions were tested: each stimulus region containing either a single or a 2 × 2 array of patches, presented either steadily for 133 ms or flickered at 15 Hz for 266 ms. Mean presentation rate was 1/s/region. The 4‐min duration stimuli were presented in 8 segments of 30 s. Segments did not need to be repeated unless more than 15% of a segment record was lost as a result of blinks or fixation losses.

Results:  The 48 stimuli produced 96 direct and consensual responses per subject. The single patch, non‐flickered stimulus condition produced the best diagnostic performance, an area under the curve of 84%. The contraction amplitudes for that stimulus gave a median z‐score of 3.2.

Conclusions:  The method produced diagnostic accuracy approaching that of automated perimetry, but unlike perimetry provides standard errors for every point in each field as well as information on response delay and efferent defects. Only one pupil needs to function to measure both visual fields.
Possible neuroprotective effect of brimonidine in a mouse model of ischaemic optic neuropathy
Authors: Goldenberg‐Cohen Nitza , Dadon‐Bar‐El Shimrit , Hasanreisoglu Murat , Avraham‐Lubin Bat Chen R , Dratviman‐Storobinsky Olga , Cohen Yoram , Weinberger Dov
Published: July 2009

Abstract

Purpose: To investigate the neuroprotective effect of brimonidine following induction of ischaemic optic neuropathy in rodents (rAION).

Methods: Mice were treated with an intraperitoneal injection of brimonidine 48, 24 or 0 h before rAION induction or eye drops for 5 days after rAION induction. Retinal ganglion cell (RGC) loss and expression of genes involved in the angiogenesis (vascular endothelial growth factor [VEGF], pigment epithelium‐derived factor [PEDF], The epidermal growth factor homology domains‐2 [Tie‐2]), ischaemia (haem oxygense‐1 [HO‐1], hypoxia‐inducible factor 1α[HIF‐1α], endothelial nitric oxide synthase [eNOS]) and oxidative stress (superoxide dismutase‐1 [SOD‐1], glutathione peroxidase‐1 [GPX‐1]) response to ischaemic damage were compared with sham or rAION‐untreated mice.

Results: No RGC loss was detected in the brimonidine‐treated mice. Effect of post‐rAION eye drops: day 1 – no decrease in retinal mRNA levels of angiogenesis‐related genes, increase in ischaemia‐ and oxidative stress‐related genes except HIF‐1α; day 3 – baseline or higher levels of oxidative and ischaemia‐related genes except HIF‐1α, increase in VEGF, decrease in PEDF; day 21 – no change in angiogenesis‐related genes. Effect of pre‐rAION injection: baseline levels of angiogenesis‐related genes with all injection schedules; increase in ischaemia‐related genes with 48‐h and 0‐h pretreatment; decrease in HO‐1 and eNOS with 24‐h pretreatment; increase in oxidative‐related genes except GPX‐1. In optic nerve tissue, HO‐1, HIF‐1α and SOD‐1 decreased on day 1 after topical administration and were still below baseline on day 3.

Conclusions: The increase in HO‐1 associated with rAION is mitigated with brimonidine treatment, especially when administered intraperitoneally. Topical brimonidine apparently reduces VEGF, Tie‐2, HIF‐1α and GPX‐1 expression on day 21. These results agree with published data and may have therapeutic implications for patients diagnosed with AION in the acute phase.
The iCare rebound tonometer: comparisons with Goldmann tonometry, and influence of central corneal thickness
Authors: Poostchi Ali , Mitchell Robert , Nicholas Simon , Purdie Gordon , Wells Anthony
Published: July 2009

Abstract

Purpose:  To assess agreement between the iCare rebound tonometer and Goldmann tonometry and to assess the influence of central corneal thickness and the value of scleral rebound tonometer readings.

Methods:  Prospective single‐centre cross‐sectional study comparing iCare rebound tonometer (RT) intraocular pressure (IOP) readings taken from corneal and scleral locations to Goldmann applanation tonometer (GAT) readings in 100 subjects attending ophthalmology clinics.

Results:  There was a significant difference between RT and GAT, with RT tending to overestimate IOP. The mean difference between RT and GAT measurements was 3.36 mmHg. The mean difference between the log of RT and the log of GAT measurements was 0.2356, a ratio of 1.27 (P < 0.0001). A formula derived from a linear regression analysis suggested that a 10% increase in CCT increased the RT IOP reading by 9.9%. Scleral RT readings showed no relationship to GAT readings.

Conclusions:  The rebound tonometer cannot replace the Goldmann tonometer in the office setting given the wide limits of agreement between the two devices. Corneal rebound tonometer readings are influenced by CCT whereas scleral rebound tonometer readings are of no value.
Eye injuries in rural Victoria, Australia
Authors: Raymond Simon , Favilla Ian , Nguyen Anh , Jenkins Mark , Mason Greg
Published: July 2009

Abstract

Background:  Eye injury causes significant morbidity and is a leading cause of blindness worldwide. This study investigates the incidence, spectrum and patterns of eye injury presenting to a rural hospital in Victoria, Australia.

Methods:  A retrospective review of the medical records of all patients presenting with eye injury to the emergency department of Mildura Base Hospital, Victoria, Australia in year 2004 was conducted. As the emergency department of Mildura Base Hospital also acts as the outpatient department for this hospital, the series included all patients treated for eye injury at Mildura Base Hospital in year 2004, including admissions.

Results:  There were 435 patients present to Mildura Base Hospital emergency department for eye injury in 2004, which represented approximately 1% of the population of Mildura. The majority of eye injuries were superficial. Fifty‐six (13%) patients required specialist attention. Most patients were male (83%) and were middle‐aged. The most common locations where eye injuries took place were residential homes (47%) and workplaces (32%). The most common causes of eye injuries were trade tools and machinery (47%), followed by chemicals (12%) and branches/sticks/twigs (11%). Of particular concern for Mildura is that approximately one‐quarter of the patients treated at Mildura Base Hospital for eye injury in 2004 had been treated at Mildura Base Hospital for a separate episode of eye injury in the past.

Conclusion:  Eye injuries represent a significant socioeconomic burden. This research contributes to the knowledge required for the design and implementation of effective preventative strategy.
Temperature effect on the sulfur isotope fractionation during sulfate reduction by two strains of the hyperthermophilic Archaeoglobus fulgidus
Authors: Mitchell Kristen , Heyer Anne , Canfield Donald E. , Hoek Joost , Habicht Kirsten S.
Published: July 2009

Sulfur isotope fractionation during dissimilatory sulfate reduction by two strains of the thermophilic archaeon Archaeoglobus fulgidus (strains VC‐16 and Z) was explored over the entire temperature range of growth. The optimal cell‐specific sulfate reduction rate (14 fmol cell−1 h−1) was found at 82–84°C but growth was measured as low as 54°C. The fractionation ranged between 0.52‰ and 27‰, with largest fractionations were found at intermediate temperatures and the smallest fractionations at the lowest and highest temperatures. There was an inverse relationship between the cell‐specific sulfate reduction rate and fractionation, and the cell‐specific rate was a good indicator of the expected fractionations regardless of whether temperature or substrate concentrations controlled the rate. Comparison of the fractionation trend found in this study with similar measurements for seven other sulfate‐reducers showed that sulfate‐reducing organisms respond to temperature in three different ways and this correlated with their maximum fractionation value, but not with the cell‐specific sulfate reduction rate. A sulfur isotope model was used to reproduce the observed variation of fractionation with temperature. This approach predicted the rate of internal sulfur transformations as having the major influence on the observed fractionations in the intermediate temperature range, whereas the exchange of sulfate across the cell membrane controls fractionation at low and high temperatures.
Do preoperative factors predict subsequent diagnosis of Crohn’s disease after ileal pouch‐anal anastomosis for ulcerative or indeterminate colitis?
Authors: Melton G. B. , Kiran R. P. , Fazio V. W. , He J. , Shen B. , Goldblum J. R. , Achkar J.‐P. , Lavery Ian C. , Remzi Feza H.
Published: July 2009

Aim  The aim of this study was to determine preoperative clinical factors associated with subsequent diagnosis revision to Crohn’s disease (CD) following total proctocolectomy with ileal pouch‐anal anastomosis (IPAA) for ulcerative colitis (UC) or indeterminate colitis (IC) patients.

Method  Presumed UC and IC patients undergoing IPAA from a large single‐institution prospective database with change of diagnosis to CD were identified and compared with patients without diagnosis change.

Results  A total of 2814 patients (47% male, median age 37 years) with presumed UC (85%) or IC (15%) underwent primary IPAA. At a median follow up of 9.6 years, 184 (7%) had the diagnosis revised to CD from histopathological examination of the colectomy specimen immediately in 97 (53%) or at a median interval of 36 months in 87 (47%). CD and UC/IC patients had had a similar operative technique, length of stay and 30‐day morbidity. The postoperative CD diagnosis was associated with a preoperative diagnosis of IC (P < 0.0001) and perianal fistula (P = 0.002). Patients with a delayed diagnosis of CD were associated with a 3‐stage procedure (P < 0.0001, OR = 2.8) (95% CI = 1.8–4.4), colonic stricture (P = 0.04, OR = 2.9 [95% CI = 1.1–7.4]), perianal fistula (P = 0.02, OR = 2.9 [95% CI = 1.2–7.2]), oral ulceration (P = 0.009, OR = 3.8 [95% CI = 1.2–9.6]) and younger age (P < 0.0001, OR = 0.048 [95% CI = 0.011–0.19]).

Conclusion  A few patients having IPAA for presumed UC/IC were subsequently diagnosed to have CD which was associated with perianal fistula and the diagnosis of postoperative preoperative IC. The delayed diagnosis of CD was associated with a three‐stage procedure, colorectal stricture, anal fissure, mouth ulceration and younger age.
Preoperative chemoradiation vs radiation alone for stage II and III resectable rectal cancer: a meta‐analysis
Authors: Latkauskas T. , Paskauskas S. , Dambrauskas Z. , Gudaityte J. , Saladzinskas S. , Tamelis A. , Pavalkis D.
Published: July 2009

Aim  The aim of this systematic literature review and meta‐analysis was to compare preoperative radiotherapy (RT) with preoperative chemoradiotherapy (ChRT) in patients with stage II and III resectable rectal cancer.

Method  A comprehensive PubMed, Cohrane and Ovid electronic database search was performed. Articles published during the period 1960–2007 were included. The analysis included only randomized controlled trials, where patients with stage II and III resectable rectal cancer were randomized to one of at least two schedules of preoperative therapy including RT or ChRT followed by surgery. Secondary estimates for the experimental ChRT group were calculated and compared with the estimates pooled from trials which included short‐course radiotherapy (SRT).

Results  We identified 1017 articles including 242 clinical trials, 65 of which were randomized studies. Five trials from these randomized studies compared preoperative RT with conventional ChRT and only one included a group having SRT. The complete response rate was significantly better after preoperative chemoradiation compared with preoperative RT alone but the rate of toxicity was higher. Theoretically higher curative resection rates with less morbidity were found after ChRT compared with preoperative SRT.

Conclusion  Preoperative ChRT for patients with stage II and III resectable rectal cancer gives better complete response rates compared with RT alone but it also results in higher toxicity.
IMITATING ACCRUAL TAXATION ON A REALIZATION BASIS
Authors: Sahm Marco
Published: July 2009

Abstract While taxation of capital gains upon accrual poses problems of liquidity and valuation, taxation upon realization evokes the so‐called lock‐in effect that possibly induces distortions of the investors' liquidation and investment decision. The tax schemes, proposed in the literature in order to remedy simultaneously the shortcomings of both taxation methods, are mostly based on the idea of imitating accrual taxation on a realization basis. The paper surveys these proposals of so‐called formulaic taxation and develops a uniform formal way of describing the suggested schemes that allows them to be easily compared and evaluated from a theoretic point of view.
Single‐Index Additive Vector Autoregressive Time Series Models
Authors: LI YEHUA , GENTON MARC G.
Published: July 2009

Abstract.  We study a new class of nonlinear autoregressive models for vector time series, where the current vector depends on single‐indexes defined on the past lags and the effects of different lags have an additive form. A sufficient condition is provided for stationarity of such models. We also study estimation of the proposed model using P‐splines, hypothesis testing, asymptotics, selection of the order of the autoregression and of the smoothing parameters and nonlinear forecasting. We perform simulation experiments to evaluate our model in various settings. We illustrate our methodology on a climate data set and show that our model provides more accurate yearly forecasts of the El Niño phenomenon, the unusual warming of water in the Pacific Ocean.
Optimization of preservatives in a topical formulation using experimental design
Authors: Rahali Y. , Pensé‐Lhéritier A.‐M. , Mielcarek C. , Bensouda Y.
Published: July 2009

Synopsis

Optimizing the preservative regime for a preparation requires the antimicrobial effectiveness of several preservative combinations to be determined. In this study, three preservatives were tested: benzoic acid, sorbic acid and benzylic alcohol. Their preservative effects were evaluated using the antimicrobial preservative efficacy test (challenge‐test) of the European Pharmacopeia (EP). A D‐optimal mixture design was used to provide a maximum of information from a limited number of experiments. The results of this study were analysed with the help of the Design Expert® software and enabled us to formulate emulsions satisfying both requirements A and B of the EP.
Increased Parasellar Activity on Gallium SPECT is Not Specific for Active Cluster Headache
Authors: Sianard-Gainko J , Milet J , Ghuysen V , Schoenen J
Published: July 2009

We have performed Gallium SPECT head scans in 30 successive cluster headache (CH) patients and in 7 migraineurs without aura. Parasellar hyperactivity was judged as present in 81% of chronic CH patients, 54% of episodic CH patients in an active period, 56% of episodic CH patients in remission and 71% of migraineurs. No significant correlations were found between the SPECT images and the duration of the disease, of cluster periods or of remissions. Increased parasellar activity on Gallium SPECT is thus not specific for CH, nor for the active period of episodic CH. The method lacks reliability for investigation of putative cavernous sinus inflammation.
Link between confusional migraine, hemiplegic migraine and episodic ataxia type 2: Hypothesis, family genealogy, gene typing and classification
Authors: Cleves C , Parikh S , Rothner AD , Tepper SJ
Published: July 2009

An association between hemiplegic migraine (HM) and episodic ataxia type 2 (EA2) has been described; both disorders are linked to mutations in the CACNA1A gene. Although confusion occurs in 21% of patients with HM, we found only one case in the literature of confusional episodes associated with ataxia without hemiplegia. These findings raise the possibility of confusional episodes being part of both the HM and EA2 phenotype. However, a patient with episodic ataxia, confusional spells and CACNA1A gene mutations has not been identified. We describe four individuals, spanning three generations of a family, with episodic ataxia without hemiplegia and confusion, in association with a CACNA1A mutation. We follow with a description of the relationship between the CACNA1A mutations and the three syndromes, suggesting a potential need for a new classification in which the conditions can be subsumed.
Factors impacting the demand for repair services of household products: the disappearing repair trades and the throwaway society
Authors: McCollough John
Published: July 2009

The repair trades for common household appliances and products were once a viable trade in America, employing hundreds of thousands of skilled blue‐collar workers. However, over the past few decades, these trades have been dying out. The reason is that many household products are simply disposed of rather than repaired and reused, a result of the throwaway society. The disposal of household products, especially those considered ‘e‐waste’, can have negative consequences for the environment. Through time series analysis, this paper explores those factors that contribute to the decline in demand for repair services and, hence, the shrinking demand for employment within the repair trades. The purpose of this paper is to give the reader a greater understanding of those economic forces that contribute to a throwaway society.
Enhanced dopaminergic differentiation of human neural stem cells by synergistic effect of Bcl‐xL and reduced oxygen tension
Authors: Krabbe Christina , Courtois Elise , Jensen Pia , Jørgensen Jesper R. , Zimmer Jens , Martínez‐Serrano Alberto , Meyer Morten
Published: July 2009

Neural stem cells constitute a promising source of cells for transplantation in Parkinson’s disease, but a protocol for controlled dopaminergic differentiation is not yet available. Here we investigated the effect of the anti‐apoptotic protein Bcl‐xL and oxygen tension on dopaminergic differentiation and survival of a human ventral mesencephalic stem cell line (hVM1). hVM1 cells and a Bcl‐xL over‐expressing subline (hVMbcl‐xL) were differentiated by sequential treatment with fibroblast growth factor‐8, forskolin, sonic hedgehog, and glial cell line‐derived neurotrophic factor. After 10 days at 20% oxygen, hVMbcl‐xL cultures contained proportionally more tyrosine hydroxylase(TH)‐positive cells than hVM1 control cultures. This difference was significantly potentiated from 11 ± 0.8% to 17.2 ± 0.2% of total cells when the oxygen tension was lowered to 3%. Immunocytochemistry and Q‐PCR‐analysis revealed expression of several dopaminergic markers besides of TH just as dopamine was detected in the culture medium by HPLC analysis. Although Bcl‐xL‐over‐expression reduced cell death in the cultures, it did not alter the relative content of GABAergic, neurons, while the content of astroglial cells was reduced in hVMbcl‐xL cell cultures compared with control. We conclude that Bcl‐xL and lowered oxygen tension act in concert to enhance dopaminergic differentiation and survival of human neural stem cells.
Adenosine A2A receptors enable the synaptic effects of cannabinoid CB1 receptors in the rodent striatum
Authors: Tebano Maria Teresa , Martire Alberto , Chiodi Valentina , Pepponi Rita , Ferrante Antonella , Domenici Maria Rosaria , Frank Claudio , Chen Jiang‐Fan , Ledent Catherine , Popoli Patrizia
Published: July 2009

Adenosine A2A, cannabinoid CB1 and metabotropic glutamate 5 (mGlu5) receptors are all highly expressed in the striatum. The aim of the present work was to investigate whether, and by which mechanisms, the above receptors interact in the regulation of striatal synaptic transmission. By extracellular field potentials (FPs) recordings in corticostriatal slices, we demonstrated that the ability of the selective type 1 cannabinoid receptor (CB1R) agonist WIN55,212‐2 to depress synaptic transmission was prevented by the pharmacological blockade or the genetic inactivation of A2ARs. Such a permissive effect of A2ARs towards CB1Rs does not seem to occur pre‐synaptically as the ability of WIN55,212‐2 to increase the R2/R1 ratio under a protocol of paired‐pulse stimulation was not modified by ZM241385. Furthermore, the effects of WIN55,212‐2 were reduced in slices from mice lacking post‐synaptic striatal A2ARs. The selective mGlu5R agonist (RS)‐2‐chloro‐5‐hydroxyphenylglycine (CHPG) potentiated the synaptic effects of WIN55,212‐2, and such a potentiation was abolished by A2AR blockade. Unlike the synaptic effects, the ability of WIN55,212‐2 to prevent NMDA‐induced toxicity was not influenced by ZM241385. Altogether, these results show that the state of activation of A2ARs regulates the synaptic effects of CB1Rs and that A2ARs may control CB1 effects also indirectly, namely through mGlu5Rs.
Intra‐ versus extracellular effects of microglia‐derived cysteine proteases in a conditioned medium transfer model
Authors: Wendt Wiebke , Schulten Roxane , Stichel Christine C. , Lübbert Hermann
Published: July 2009

Activated microglia release inflammatory mediators that display either beneficial or harmful effects on neuronal survival and signaling. In the present study we demonstrate that exposure to lipopolysaccharide leads to an increase in the lysosomal cysteine proteases, cathepsin B, K, S, and X, in culture supernatants of the microglia cell line BV‐2. In addition, we observed an up‐regulation of cathepsins in the cytoplasmic fraction in response to stimulation with lipopolysaccharide. Conditioned medium from these cells was toxic to the neuroblastoma cell line Neuro2a. Experiments with membrane‐permeable and membrane‐impermeable cysteine protease inhibitors suggested that blocking extracellular cathepsins had no effect on microglia‐mediated neuron death in this medium transfer model. However, intracellular cathepsins seem to trigger the release of neurotoxic factors. In lipopolysaccharide‐stimulated BV‐2 cells, inhibition of intracellular cathepsins significantly diminished microglial activation characterized by reduced expression of different proinflammatory cytokines, thereby reducing the neurotoxic effects of the medium. This hitherto unknown intracellular effect of cysteine proteases in activated microglia might connect chronic neuroinflammation with neurodegeneration.
Docosahexaenoic acid attenuates microglial activation and delays early retinal degeneration
Authors: Ebert Stefanie , Weigelt Karin , Walczak Yana , Drobnik Wolfgang , Mauerer Richard , Hume David A. , Weber Bernhard H. F. , Langmann Thomas
Published: July 2009

Microgliosis is a common phenomenon in neurodegenerative disorders including retinal dystrophies. We performed a detailed characterization of activated microglia in the retinoschisin (Rs1h)‐deficient (Rs1h−/Y) mouse model of inherited retinal degeneration. To visualize and isolate microglia, we crossed Rs1h−/Y animals with transgenic MacGreen mice, which express green fluorescent protein under the control of the macrophage‐specific csf1r promoter. Activated microglia were detected in retinal sections and whole‐mounts of early postnatal MacGreen/Rs1h−/Y mice before the onset of overt neuronal cell death. These activated microglia contained prominent lipid droplets and analysis of the retinal lipid composition showed decreased docosahexaenoic acid (DHA) levels in Rs1h−/Y retinas. To establish a link between microglia activation, reduced DHA levels, and neurodegeneration, a dietary intervention study was performed. Female Rs1h−/− mice and their Rs1h−/Y litter were either subjected to a diet enriched with DHA, or a control chow lacking DHA. Supplementation with DHA enhanced photoreceptor survival and converted activated microglia to a quiescent phenotype. Furthermore, DHA, but not docosapentaenoic acid or adrenic acid reduced pro‐inflammatory gene expression, migration, and lipid accumulation of cultured BV‐2 microglia. We conclude that retinal DHA levels control the activity of microglia and thereby may affect the progression and extent of retinal degeneration.
Inhibition of calpain attenuates encephalitogenicity of MBP‐specific T cells
Authors: Guyton Mary K. , Brahmachari Saurav , Das Arabinda , Samantaray Supriti , Inoue Jun , Azuma Mitsuyoshi , Ray Swapan K. , Banik Naren L.
Published: July 2009

Multiple sclerosis (MS) is a T‐cell mediated autoimmune disease of the CNS, possessing both immune and neurodegenerative events that lead to disability. Adoptive transfer (AT) of myelin basic protein (MBP)‐specific T cells into naïve female SJL/J mice results in a relapsing–remitting (RR) form of experimental autoimmune encephalomyelitis (EAE). Blocking the mechanisms by which MBP‐specific T cells are activated before AT may help characterize the immune arm of MS and offer novel targets for therapy. One such target is calpain, which is involved in activation of T cells, migration of immune cells into the CNS, degradation of axonal and myelin proteins, and neuronal apoptosis. Thus, the hypothesis that inhibiting calpain in MBP‐specific T cells would diminish their encephalitogenicity in RR‐EAE mice was tested. Incubating MBP‐specific T cells with the calpain inhibitor SJA6017 before AT markedly suppressed the ability of these T cells to induce clinical symptoms of RR‐EAE. These reductions correlated with decreases in demyelination, inflammation, axonal damage, and loss of oligodendrocytes and neurons. Also, calpain : calpastatin ratio, production of truncated Bid, and Bax : Bcl‐2 ratio, and activities of calpain and caspases, and internucleosomal DNA fragmentation were attenuated. Thus, these data suggest calpain as a promising target for treating EAE and MS.
Determinants of regional and local diversity within the astroglial lineage of the normal central nervous system
Authors: Hewett James A.
Published: July 2009

Astrocytes are a major component of the resident non‐neuronal glial cell population of the CNS. They are ubiquitously distributed throughout the brain and spinal cord, where they were initially thought to function in both structural and homeostatic capacities, providing the framework and environment in which neurons performed their parenchymal duties. However, this stroma‐like view of astrocytes is no longer satisfactory. Mounting evidence particularly within the last decade indicates that astrocytes do not simply support neuronal activity but directly contribute to it. Congruent with this evolving view of astrocyte function in information processing is the emergent notion that these glial cells are not a homogeneous population of cells. Thus, astrocytes in various anatomically distinct regions of the normal CNS possess unique phenotypic characteristics that may directly influence the particular neuronal activities that define these regions. Remarkably, regional populations of astrocytes appear to exhibit local heterogeneity as well. Many phenotypic traits of the astrocyte lineage are responsive to local environmental cues (i.e., are adaptable), suggesting that plasticity contributes to this diversity. However, compelling evidence suggests that astrocytes arise from multiple distinct progenitor pools in the developing CNS, raising the intriguing possibility that some astrocyte heterogeneity may result from intrinsic differences between these progenitors. The purpose of this review is to explore the evidence for and mechanistic determinants of regional and local astrocyte diversity.
Lipidomic profiling in mouse brain reveals differences between ages and genders, with smaller changes associated with α‐synuclein genotype
Authors: Rappley Irit , Myers David S. , Milne Stephen B. , Ivanova Pavlina T. , LaVoie Matthew J. , Brown H. Alex , Selkoe Dennis J.
Published: July 2009

Advances in lipidomics technology have facilitated the precise detection, identification and profiling of lipid species within tissues. Mass spectrometry allows for identification of lipids as a function of the total number of carbons and double bonds in their acyl chains. Such detailed descriptions of lipid composition can provide a basis for further investigation of cell signaling and metabolic pathways, both physiological and pathological. Here, we applied phospholipid profiling to mouse models relevant to Parkinson’s disease, using mice that were transgenic for human α‐synuclein (αSyn) or deleted of endogenous αSyn. Proposed functions of αSyn include phospholipid binding, regulation of membrane composition, and regulation of vesicular pools. We investigated whether αSyn gene dosage interacts with differences in phospholipid composition across brain regions or with age‐related changes in brain phospholipid composition. The most dramatic phospholipid changes were observed in αSyn wild‐type animals as a function of age and gender. αSyn genotype‐specific changes were also observed in aged, but not young, mice. Our results provide a detailed and systematic characterization of brain phospholipid composition in mice and identify age‐related changes relevant both to Parkinson’s disease and to normal aging.
Do IFRS Reconciliations Convey Information? The Effect of Debt Contracting
Authors: CHRISTENSEN HANS B. , LEE EDWARD , WALKER MARTIN
Published: July 2009

We examine whether earnings reconciliation from U.K. generally accepted accounting principles (GAAP) to International Financial Reporting Standards (IFRS) convey information. As a result of debt contracting, mandatory accounting changes are expected to affect the likelihood of violating existing covenants based on rolling GAAP, leading to a redistribution of wealth between shareholders and lenders. Consistent with this prediction, we find significant market reactions to IFRS reconciliation announcements. These market reactions are more pronounced among firms that face a greater likelihood and costs of covenant violation and early announcements. While the association between later announcements and weaker market reactions is consistent with contractual implications of technical changes to earnings, which investors quickly learn to predict, it is inconsistent with IFRS forcing all firms in the sample to reveal firm‐specific information through accruals. Thus, by showing that mandatory IFRS also affects debt contracting, we expand on existing IFRS research that focuses on how accounting quality and cost of capital are impacted.
Using Financial Accounting Data to Examine the Effect of Foreign Operations Located in Tax Havens and Other Countries on U.S. Multinational Firms' Tax Rates
Authors: DYRENG SCOTT D. , LINDSEY BRADLEY P.
Published: July 2009

This paper investigates the effect tax havens and other foreign jurisdictions have on the income tax rates of multinational firms based in the United States. We develop a new regression methodology using financial accounting data to estimate the average worldwide, federal, and foreign tax rates on worldwide, federal, and foreign pretax book income for a large sample of U.S. firms with and without tax haven operations. We find that on average U.S. firms that disclosed material operations in at least one tax haven country have a worldwide tax burden on worldwide income that is approximately 1.5 percentage points lower than firms without operations in at least one tax haven country. Our results also show that U.S. firms face a 4.4% current federal tax rate on foreign income whether or not they have tax haven operations. Finally, we find that U.S. firms with operations in some tax haven countries have higher federal tax rates on foreign income than other firms. This result suggests that in some cases, tax haven operations may increase U.S. tax collections at the expense of foreign country tax collections.
Earnings Management? Erroneous Inferences Based on Earnings Frequency Distributions
Authors: DURTSCHI CINDY , EASTON PETER
Published: July 2009

A vast literature following Hayn [1995] and Burgstahler and Dichev [1997] attributed the so‐called “discontinuities” in earnings distributions around zero to earnings management. Despite recent evidence that these discontinuities are likely caused by other factors, researchers and teachers continue to point to the shapes of these distributions as evidence of earnings management. We provide three sets of further evidence that these discontinuities are likely caused by factors other than earnings management: (1) we provide, as an example, a detailed analysis of the severe effects of sample selection in a recent study; this study erroneously concludes that the shape of an earnings distribution is evidence of earnings management, (2) we provide a simple explanation for the shape of the earnings distribution that is most often cited as evidence of earnings management; the relation between earnings and prices differs with the magnitude and the sign of earnings, and (3) we provide further examples that support the main point of our paper; evidence beyond the mere shape of a distribution must be brought to bear before researchers can draw conclusions regarding the presence/absence of earnings management.
Demonstration as a Means to Translate Conservation Science into Practice
Authors: HALL JOHN A. , FLEISHMAN ERICA
Published: July 2009

Abstract:  To be relevant to societal interests and needs, conservation science must explicitly lend itself to solving real‐world problems. Failure to evaluate under field conditions how a new technology or method performs or the cost of its implementation can prevent its acceptance by end users. Demonstration, defined here as the translation of scientific understanding into metrics of performance and cost of implementation under real‐world conditions, is a logical step in the challenging progression from fundamental research to application. Demonstration reduces scientific uncertainty and validates the hypothesis that a management approach is both effective and financially sustainable. Much like adaptive management, demonstration enables researchers and resource managers to avoid trial‐and‐error approaches and instead conduct unbiased assessment of management interventions. The participation of end users and regulators in the development and execution of demonstration projects ensures that performance measures are credible and increases the probability that successful innovations will be adopted. Four actions might better connect science to the needs of resource managers via demonstration. First, we recommend that demonstration be conducted as a formal process that documents successes and failures. Second, demonstration should be budgeted as an integral component of government agencies' science programs and executed as a partnership between researchers and managers. Third, public and private funders should increase the opportunities and incentives for academics to engage in demonstration. Fourth, social influences on adoption of new technologies and methods should be further explored. When end users can evaluate explicitly whether a new approach is likely to achieve management objectives, save money, and reduce risk under uncertainty, the professional community successfully has bridged a chasm between research and application.
Informing Packaging Design Decisions at Toyota Motor Sales Using Life Cycle Assessment and Costing
Authors: Early Claire , Kidman Tim , Menvielle Michelle , Geyer Roland , McMullan Ryan
Published: July 2009

Throughout their life cycle stages—material production, package manufacture, distribution, end‐of‐life management—packaging systems consume natural resources and energy, generate waste, and emit pollutants. Each of these stages also carries a financial cost. Motivated by a desire to decrease environmental burdens while reducing financial costs associated with the packaging of accessory and service parts, Toyota Motor Sales (TMS) partnered with the Donald Bren School of Environmental Science & Management to build a life cycle assessment and costing tool to support packaging design decisions. The resulting Environmental Packaging Impact Calculator (EPIC) provides comprehensive life cycle assessment (LCA) and life cycle costing (LCC). It allows packaging designers to identify environmentally and economically preferable packaging systems in daily decision‐making. EPIC's parameterized process flow model allows users to assess many different packaging systems using a single model. Its input/output interface is designed for users without preexisting knowledge of LCA theory or practice and calculates results based on relatively few input data. The main motivation behind this environmental design tool is to provide relevant information to those individuals who are in the best position to reduce life cycle impacts and costs from TMS's packaging and distribution systems.
Prediction of number of apheresis procedures necessary in healthy donors to attain minimally required peripheral blood CD34+ cells
Authors: Namba Noriko , Matsuo Keitaro , Kubonishi Shiro , Kikuchi Tomoko , Maeda Yoshinobu , Niiya Masami , Shinagawa Katsuji , Koide Norio , Ikeda Kazuma , Tanimoto Mitsune
Published: July 2009

BACKGROUND: Allogeneic peripheral blood stem cell (PBSC) transplantation is widely performed as a curative therapy for hematopoietic malignancies. Donors for PBSC harvest (PBSCH) are usually healthy subjects and undergo granulocyte–colony‐stimulating factor treatment and apheresis procedures. A considerable proportion of donors experience poor mobilization, necessitating additional harvesting or marrow collection or remobilization. Although some characteristics have been reported to correlate with poor mobilization, they may not be taken into account in selecting PBSC donors. To protect healthy donors, it is preferable to predict the number of apheresis procedures needed for PBSCH before the procedure is initiated.

STUDY DESIGN AND METHODS: A retrospective cohort study of 83 subjects was conducted, using statistical models to predict the probability of obtaining a sufficient number of CD34+ cells (≥2.0 × 106/kg) in the first to the third apheresis procedures and the probability of failure to obtain sufficient cells within three apheresis sessions. This study explored potential candidate factors in an ordinal probit regression analysis.

RESULTS: Significant factors predicting successful PBSCH were donor age, donor sex, and body weight difference between donor and recipient. The predictive model showed good agreement with the observed number of apheresis sessions. Simulation tables are presented with this model.

CONCLUSION: The statistical model developed to predict the number of apheresis procedures for PBSCH may be useful for planning PBSCH in clinical practice.
Cell viability during platelet storage in correlation to cellular metabolism after different pathogen reduction technologies
Authors: Picker Susanne M. , Schneider Volker , Oustianskaia Larissa , Gathof Birgit S.
Published: July 2009

BACKGROUND: The objective of this study was to evaluate if pathogen reduction technologies (PRTs) affect platelet (PLT) viability by alteration of PLT metabolism during storage.

STUDY DESIGN AND METHODS: Twenty‐seven split triple‐dose apheresis PLTs were PRT treated using ultraviolet light with either riboflavin‐UVB (M) or psoralen‐UVA (I) or remained untreated (C). Samples were taken on Days 0, 1, 5, 7, and 8 and analyzed for annexin V release (enzyme‐linked immunosorbent assay), mitochondrial enzymatic activity (MTS assay), transmembrane mitochondrial potential (Δψ; JC‐1 assay), and metabolism based on pH, pO2, glucose, lactate, and ATP content.

RESULTS: During storage, Δψ and MTS reduction activity decreased, while annexin V release and acidity increased in all units, more pronounced, however, after PRT treatment, which led to higher lactate accumulation due to acceleration in glycolytic flux. No significant differences were found between C and M, whereas I was significantly different by Day 1 (pH value), Day 5 (annexin V release), and Day 7 (Δψ) of storage. Intracellular ATP content remained similar between C and M but was significantly lower in end‐stored I units. Cell viability markers of I units were highly correlated with the oxidative pathway, which appeared impaired in I but up regulated in M units.

CONCLUSION: PRT treatment using M increased both anoxidative glycolytic flux and oxidative phosphorylation. The I‐based technique was associated with an impaired mitochondria‐based respiration. During terminal storage, this resulted in significantly lower maintenance of ATP and cell viability. The impact of these findings for storage prolongation or clinical use must await further evaluation.
TRANSFUSION COMPLICATIONS: Transfusion‐transmitted Babesia microti identified through hemovigilance
Authors: Tonnetti Laura , Eder Anne F. , Dy Beth , Kennedy Jean , Pisciotto Patricia , Benjamin Richard J. , Leiby David A.
Published: July 2009

BACKGROUND: Babesia microti, the primary cause of human babesiosis in the United States, is an intraerythrocytic parasite endemic to the Northeast and upper Midwest. Published studies indicate that B. microti increasingly poses a blood safety risk. The American Red Cross Hemovigilance Program herein describes the donor and recipient characteristics of suspected transfusion‐transmitted B. microti cases reported between 2005 and 2007.

STUDY DESIGN AND METHODS: Suspected transfusion‐transmitted Babesia infections were reported by transfusion services or were discovered through recipient‐tracing investigations of prior donations from donors with a positive test for B. microti in a serologic study. Follow‐up samples from involved donors were tested by Babesia‐specific immunofluorescence assay, Western blot, and/or real‐time polymerase chain reaction analysis.

RESULTS: Eighteen definite or probable B. microti infections, including five fatalities, were identified in transfusion recipients, 16 from hospital‐reported cases and two through serologic lookback studies. Thirteen recipients were 61 to 84 years old and two were 2 years old or younger. Two recipients had sickle cell disease and four were known to be asplenic, including one with sickle cell disease. Seventeen antibody‐positive donors were implicated; 11 (65%) were residents in Babesia‐endemic areas, while four (24%) nonresident donors had a history of travel to endemic areas.

CONCLUSIONS: Transfusion‐transmitted B. microti can be a significant cause of transfusion‐related morbidity and mortality, especially in infant, elderly, and asplenic blood recipients. These data demonstrate the need for interventions, in both endemic and nonendemic areas of the United States, to reduce patient risk.
Impact of fresh‐frozen plasma from male‐only donors versus mixed‐sex donors on postoperative respiratory function in surgical patients: a prospective case‐controlled study
Authors: Nakazawa Harumasa , Ohnishi Hiroaki , Okazaki Hitoshi , Hashimoto Shiho , Hotta Hajime , Watanabe Takashi , Ohkawa Ryunosuke , Yatomi Yutaka , Nakajima Kazunori , Iwao Yasuhide , Takamoto Shigeru , Shimizu Masaru , Iijima Takehiko
Published: July 2009

BACKGROUND:To reduce the risk of transfusion‐related acute lung injury (TRALI), plasma products are mainly made from male donors in some countries because of the lower possibility of alloimmunization; other countries are considering this policy. The advantage of male‐only fresh‐frozen plasma (FFP) should be examined in a prospective case‐control study.

STUDY DESIGN AND METHODS:This study compared pulmonary function after the transfusion of FFP derived from either male donors only (FFP‐male) or mixed donors (FFP‐mixed) in informed surgical patients treated at a tertiary university hospital in Japan. The factors contributing to pulmonary distress (PD) after transfusion were then statistically examined.

RESULTS:Eighty‐two patients participated in this study (FFP‐male, n = 55; FFP‐mixed, n = 27). Nineteen patients developed PD (PaO2/FiO2ratio [P/F] < 300) within 6 hours after transfusion: seven had congestive pulmonary edema (transfusion‐associated circulatory overload), five had permeability pulmonary edema (possible TRALI), and seven had no apparent pulmonary edema. A multivariate logistic regression analysis revealed that the use of cardiopulmonary bypass and preoperative liver dysfunction were significantly associated with a P/F of less than 300 (odds ratios [ORs], 8.95 [p = 0.004] and 6.54 [p = 0.005], respectively), while the use of FFP‐male was significantly associated with the absence of PD (OR, 0.219; p = 0.022). All the patients with possible TRALI had received either white blood cell or granulocyte antibody‐positive FFP. The lysophosphatidylcholine level was not correlated with PD.

CONCLUSIONS:Our data suggests that the use of FFP derived from male donors may be advantageous for posttransfusion pulmonary function, although PD is also determined by background characteristics.
Catastrophe Bonds and Reinsurance: The Competitive Effect of Information‐Insensitive Triggers
Authors: Finken Silke , Laux Christian
Published: July 2009

Abstract

We identify a new benefit of index or parametric triggers. Asymmetric information between reinsurers on an insurer's risk affects competition in the reinsurance market: reinsurers are subject to adverse selection, since only high‐risk insurers may find it optimal to change reinsurers. The result is high reinsurance premiums and cross‐subsidization of high‐risk insurers by low‐risk insurers. A contract with a parametric or index trigger (such as a catastrophe bond) is insensitive to information asymmetry and therefore alters the equilibrium in the reinsurance market. Provided that basis risk is not too high, the introduction of contracts with parametric or index triggers provides low‐risk insurers with an alternative to reinsurance contracts, and therefore leads to less cross‐subsidization in the reinsurance market.
Spectral Imaging Analysis of Interfacial Reactions and Microstructures in Brazing of Alumina by a Hf‐Ag‐Cu Alloy
Authors: Loehman Ronald E. , Kotula Paul G.
Published: July 2009

A 59Ag‐40Cu·1Hf (at.%) alloy that was heated on 99.6% alumina for 30 min at 1000°3C in gettered Ar melted, spread, and adhered when cooled to room temperature. Conventional scanning electron microscopic analysis with energy dispersive X‐ray spectroscopy (SEM/EDXS) did not detect any reaction products at the interface. Automated X‐ray spectral image analysis of the interface region revealed small pockets of a phase containing Hf and O with a stoichiometry equivalent to HfO2. Samples for transmission electron microscopic (TEM) analysis were cut to include specific HfO2 particles using focused ion beam (FIB) milling. TEM images showed that the particles were 10 to 100 nm in diameter and embedded in the alumina grains at the interface with the alloy. Based on the measured stoichiometry, electron diffraction analysis in the transmission electron microscope, and a standard Gibbs energy of reaction of ΔG°= ‐203.3 kJ at 1300 K for the reaction 3Hf + 2Al2O3→ 3HfO2+ 4Al, the particles are judged to be HfO2 that formed from simple redox reaction between Hf and Al2O3.