bluuebunny/crossref_metadata_2025 huggingface dataset:
Cracking the Code of Genocide: The Moral Psychology of Rescuers, Bystanders, and Nazis during the Holocaust
Authors: Monroe Kristen Renwick
Published: September 2008

What turns neighbors into genocidalists? Why do some stand by, while others risk their lives to help? A narrative analysis of interviews with rescuers, bystanders, and Nazi supporters during World War II focuses attention on self‐image, worldview, and cognitive categorization as critical influences. Rescuers, bystanders, and Nazis demonstrated dramatically different self concepts, yet identity constrained choice for all groups. A critical aspect of identity is relational: the sense of self in relation to others. Worldview, canonical expectations, and idealized cognitive models are critical determinants, with the ethical importance of values emanating not from particular values but from the integration of these values into the speaker's sense of self. Finally, cognitive categorization carries strong ethical overtones. The dehumanization that spurs perpetrators and the sense of moral salience that drives rescuers work through the cognitive classification of “the other.”
Ronald Reagan's Presidency: The Impact of an Alcoholic Parent
Authors: Gilbert Robert E.
Published: September 2008

Ronald Reagan enjoyed a successful political career. Nevertheless, his political life was affected dramatically by the fact that he was the son of an alcoholic parent. Alcoholic parents leave deep marks on their children's lives, even after those children become adults. As president of the United States, Reagan clearly demonstrated these marks. He was aloof and distant, was often a disengaged leader, showed inordinate loyalty to associates even when such loyalty became problematic, was prone to live in a world of make‐believe, married compulsive women, and craved approval and applause. Each of these behavioral characteristics was part of the psychological legacy left to this president by his long‐dead alcoholic father. Some of them damaged his presidency greatly; others, however, may well have assisted it.
Global Climate Change and the Fragmentation of International Law
Authors: VAN ASSELT HARRO , SINDICO FRANCESCO , MEHLING MICHAEL A.
Published: September 2008

Born into the wider body of international law, the climate regime needs to be understood in light of preexisting regimes. By drawing on the current debate about fragmentation in international law, this article highlights challenges for international lawyers and policymakers in navigating the relationship between the climate regime and the biodiversity regime, and the relationship between the climate regime and the multilateral trading system. This article concludes that a narrow focus on conflicts misrepresents the multifaceted nature of climate change and precludes an adequate jurisprudential understanding of the relationship between the climate regime and other regimes. An improved understanding, particularly with respect to interactions with the biodiversity regime, requires a broadening of the debate that takes account of the institutional aspects of these relationships that may allow enhanced political cooperation and coordination. Further, international law, and in particular the emerging concept of systemic integration, has the potential to make a positive contribution to the climate‐trade interplay.
Maternal brain response to own baby‐cry is affected by cesarean section delivery
Authors: Swain James E. , Tasgin Esra , Mayes Linda C. , Feldman Ruth , Todd Constable R. , Leckman James F.
Published: September 2008

A range of early circumstances surrounding the birth of a child affects peripartum hormones, parental behavior and infant wellbeing. One of these factors, which may lead to postpartum depression, is the mode of delivery: vaginal delivery (VD) or cesarean section delivery (CSD). To test the hypothesis that CSD mothers would be less responsive to own baby‐cry stimuli than VD mothers in the immediate postpartum period, we conducted functional magnetic resonance imaging, 2–4 weeks after delivery, of the brains of six mothers who delivered vaginally and six who had an elective CSD. VD mothers’ brains were significantly more responsive than CSD mothers’ brains to their own baby‐cry in the superior and middle temporal gyri, superior frontal gyrus, medial fusiform gyrus, superior parietal lobe, as well as regions of the caudate, thalamus, hypothalamus, amygdala and pons. Also, within preferentially active regions of VD brains, there were correlations across all 12 mothers with out‐of‐magnet variables. These include correlations between own baby‐cry responses in the left and right lenticular nuclei and parental preoccupations (r = .64,p < .05 and .67,p < .05 respectively), as well as in the superior frontal cortex and Beck depression inventory (r = .78,p < .01). First this suggests that VD mothers are more sensitive to own baby‐cry than CSD mothers in the early postpartum in sensory processing, empathy, arousal, motivation, reward and habit‐regulation circuits. Second, independent of mode of delivery, parental worries and mood are related to specific brain activations in response to own baby‐cry.
Buying behavior, social support and credit card indebtedness of college students
Authors: Wang Jeff , Xiao Jing J.
Published: September 2008

This research examines three factors that are associated with college students' credit card indebtedness. Using survey data, we find that college students' buying patterns and social networks affect their credit card indebtedness. Specifically, students with a tendency towards compulsive buying are more likely and those with greater social support are less likely to hold credit card debts. Depth interview data further illustrate the contexts and causes of overusing credit cards as well as solutions for their debt problem. This research sheds light on reasons why college students fall into credit card debt and suggests strategies for helping them use credit cards wisely.
Antinociceptive effect of a ruthenium complex in mice
Authors: Cristiano M. P. , Cardoso D. C. , Da Silva Paula M. M. , Costa‐Campos L.
Published: September 2008

1 The ruthenium complexes are important tools in inorganic chemistry. Different biological properties are found in the presence of distinct coordinate ligands, which offer a variety of potential clinical and pharmacological uses.

2 The aim of this work was to evaluate the antinociceptive and behavioural effects of the ruthenium complex,trans‐[RuCl2(i‐dinic)4]Cl, in mice.

3 The potential analgesic activity was tested using the formalin and hot plate tests and the behavioural effect was evaluated using the rotarod and spontaneous locomotor tests. The complex was administered at concentrations of 1.3, 4.5 and 18.0 μmol kg−1i.p. Morphine (6.0 mg kg−1, i.p.) and diclofenac sodium (20.0 mg kg−1, i.p.) were used as reference drugs.

4 The compound had no sedative activity on motor ataxia in the behavioural and analgesic tests. No significant effect was observed in the first phase of the formalin test, however, an effect was observed in the second phase.

5 The complex studied was probably more powerful than the reference drugs as an antinociceptive agent, as this mechanism also involved the nitric oxide (NO) pathway. From this perspective, further experimental studies will be useful to understand the effect of these compounds on NO and the relationship between prostaglandin and NO biosynthesis.
A MULTI‐ANALYTICAL APPROACH FOR THE CHARACTERIZATION OF COMMODITIES IN A CERAMIC JAR FROM ANTINOE (EGYPT)*
Authors: RIBECHINI E. , COLOMBINI M. P. , GIACHI G. , MODUGNO F. , PALLECCHI P.
Published: September 2008

This paper describes a multi‐analytical chemical study performed on the original, almost totally conserved, content of a small ceramic jar from the Antinoe archaeological site (fifth to seventh centuries ad, Roman Egypt) and now belonging to the archaeological collection of the Istituto Papirologico ‘Girolamo Vitelli’ (Florence, Italy). Scanning electron microscopy with an energy‐dispersive X‐ray spectrometer (SEM–EDX), Fourier transformed infrared spectroscopy (FTIR) and X‐ray diffraction (XRD) were all used to characterize the inorganic components of the archaeological material. The organic substances were analysed using FTIR, direct exposure mass spectrometry (DE–MS) and gas chromatography – mass spectrometry (GC–MS). The inorganic component essentially consisted of halite (NaCl). Among the NaCl crystals, lamellar elements were identified. They were chemically characterized by carbonato‐apatite and showed a concentric morphology typical of the scales of small fish. The most prevalent organic constituents of the sample were monocarboxylic acids, α,ω‐dicarboxylic acids, and cholesterol and its oxidation products. The organic material composition was consistent with the occurrence of lipids of animal origin. In addition, diterpenes related to pine pitch were also identified. The overall results suggest that the material recovered in the small ceramic jar found in Antinoe is a residue of fish‐based pickles such as garum, muria, allex and liquamen, which were commonly used in Roman times.
A HYPOTHESIS FOR PLASTID EVOLUTION IN CHROMALVEOLATES1
Authors: Sanchez‐Puerta M. Virginia , Delwiche Charles F.
Published: September 2008

Four eukaryotic lineages, namely, haptophytes, alveolates, cryptophytes, and heterokonts, contain in most cases photosynthetic and nonphotosynthetic members—the photosynthetic ones with secondary plastids with chlcas the main photosynthetic pigment. These four photosynthetic lineages were grouped together on the basis of their pigmentation and called chromalveolates, which is usually understood to imply loss of plastids in the nonphotosynthetic members. Despite the ecological and economic importance of this group of organisms, the phylogenetic relationships among these algae are only partially understood, and the so‐called chromalveolate hypothesis is very controversial. This review evaluates the evidence for and against this grouping and summarizes the present understanding of chromalveolate evolution. We also describe a testable hypothesis that is intended to accommodate current knowledge based on plastid and nuclear genomic data, discuss the implications of this model, and comment on areas that require further examination.
MODELING THE RELEASE OF DISSOLVED ORGANIC MATTER BY PHYTOPLANKTON1
Authors: Flynn Kevin J. , Clark Darren R. , Xue Yao
Published: September 2008

Three models describing dissolved organic matter (DOM) flux and phytoplankton death, each of different levels of complexity, were constructed and tested against experimental data for a cyanobacterium, a chlorophyte, two diatoms, two dinoflagellates, and two prymnesiophytes. The simplest model described only bulk carbon (C) and nitrogen (N) forms of DOM (DOMC and DOMN) and employed a fixed relationship between phytoplankton nutrient status and DOM release and death rate. The most complex model described fractions of DOM as low molecular weight dissolved organic carbon (DOC; saccharides, low molecular weight carbohydrates [DOCs]), low molecular weight nitrogenous material (comprising C and N as DOC associated with low molecular weight compounds containing amino acids and/or nucleic acids [DOCa] and N associated with DOCa [DONa], which included dissolved free amino acids [DFAA]), and more complex materials (DOC associated with high molecular weight compounds typically requiring extracellular degradation prior to uptake or use by microbes [DOCx] and N associated with DOCx [DONx]). It also employed descriptions of DOM flux and cell death related to nutrient status and growth rates. In all instances, material lysed from dead cells contributed to the DOM pool. All three models captured the gross dynamics of the primary data (dissolved inorganic C [DIC], dissolved inorganic N [DIN], particulate organic carbon [POC], particulate organic N [PON], DOC, dissolved organic N [DON]), but there was little or no improvement of the fit with increasing model complexity. However, the simplest models tended to employ excessively high growth rates to compensate for high fixed death rates. While the proportion of newly fixed C being liberated as DOMC (DOCs plus DOCa) increased as nutrient status declined, the actual rate of release typically did not do so and often declined. The most complex model gave predictions for changes in released saccharides and DFAA in keeping with expectations. The major obstacle to future progress is the lack of suitable, mass balanced data sets for further model testing.
INTERCOLONIAL VARIABILITY IN MACROMOLECULAR COMPOSITION IN P‐STARVED AND P‐REPLETE SCENEDESMUS POPULATIONS REVEALED BY INFRARED MICROSPECTROSCOPY1
Authors: Heraud Philip , Stojkovic Slobodanka , Beardall John , McNaughton Don , Wood Bayden R.
Published: September 2008

Macromolecular variability in microalgal populations subject to different nutrient environments was investigated, using the chlorophyte alga Scenedesmus quadricauda (Turpin) Bréb. as a model organism. The large size of the four‐cell coenobia in the strain used in this study (∼35 μm diameter) conveniently allowed high quality spectra to be obtained from individual coenobia using a laboratory‐based Fourier transform infrared (FTIR) microscope with a conventional globar source of IR. By drawing sizable subpopulations of coenobia from two Scenedesmus cultures grown under either nutrient‐replete or P‐starved conditions, the population variability in macromolecular composition, and the effects of nutrient change upon this, could be estimated. On average, P‐starved coenobia had higher carbohydrate and lower protein absorbance compared with P‐replete coenobia. These parameters varied between coenobia with histograms of the ratio of absorbance of the largest protein and carbohydrate bands being Gaussian distributed. Distributions for the P‐replete and P‐starved subpopulations were nonoverlapping, with the difference in mean ratios for the two populations being statistically significant. Greater variance was observed in the P‐starved subpopulation. In addition, multivariate models were developed using the spectral data, which could accurately predict the nutrient status of an independent individual coenobium, based on its FTIR spectrum. Partial least squares discriminant analysis (PLS‐DA) was a better prediction method compared with soft independent modeling by class analogy (SIMCA).
SALT‐INDUCED ALTERATIONS IN LIPID COMPOSITION OF DIATOM NITZSCHIA LAEVIS (BACILLARIOPHYCEAE) UNDER HETEROTROPHIC CULTURE CONDITION1
Authors: Chen Guan‐Qun , Jiang Yue , Chen Feng
Published: September 2008

The diatom Nitzschia laevis Hust. is a potential producer of eicosapentaenoic acid (EPA). To elucidate its cellular response to salt stress, the effects of salinity on EPA production, lipid composition, and fatty acid distribution in the lipid pool were investigated. The highest contents of total fatty acids, EPA, and polar lipids were all obtained at NaCl of 20 g · L−1, under which 71.3% of total EPA existed in polar lipid fractions. In N. laevis, high salt concentration might induce the decrease in neutral lipids (NLs), whereas the production of polar lipids, including phospholipids (PLs) and glycolipids (GLs), was enhanced. The degree of fatty acid unsaturation of both neutral and polar lipid fractions increased sharply when NaCl concentration increased from 10 to 20 g · L−1 but decreased at NaCl concentration of 30 g · L−1. The amount of total free sterols was increased with the increase in salt concentration. All these changes in lipid and fatty acids suggested a decrease in membrane permeability and fluidity under high salt concentration, which could help the alga acclimate to the salinity stress.
MICROSATELLITE GENOTYPING OF SINGLE CELLS OF THE DINOFLAGELLATE SPECIES LINGULODINIUM POLYEDRUM (DINOPHYCEAE): A NOVEL APPROACH FOR MARINE MICROBIAL POPULATION GENETIC STUDIES1
Authors: Frommlet Jörg C. , Iglesias‐Rodríguez M. Débora
Published: September 2008

In recent years, two new approaches have been introduced in genetic studies of phytoplankton species. One is the application of highly polymorphic microsatellite markers, which allow detailed population genetic studies; the other is the development of methods that enable the direct genetic characterization of single cells as an alternative to clonal cultures. The aim of this study was to combine these two approaches in a method that would allow microsatellite genotyping of single phytoplankton cells, providing a novel tool for high‐resolution population genetic studies. The dinoflagellate species Lingulodinium polyedrum (F. Stein) J. D. Dodge was selected as a model organism to develop this novel approach. The method we describe here is based on several key developments: (i) a simple and efficient DNA extraction method for single cells, (ii) the characterization of microsatellite markers for L. polyedrum, (iii) a protocol for the species identification of single cells through the analysis of partial rRNA gene sequences, and (iv) a two‐step multiplex PCR protocol for the simultaneous amplification of microsatellite markers and partial rRNA gene sequences from single cells. Our protocol allowed the amplification of up to six microsatellite loci together with either the complete ITS1‐5.8S‐ITS2 region or a partial 18S region of the ribosomal gene of L. polyedrum from single motile cells and resting cysts. This article describes and evaluates the developed approach and discusses its significance for population genetic studies of L. polyedrum and other phytoplankton species.
CORRESPONDENCE BETWEEN COLD TOLERANCE AND TEMPERATE BIOGEOGRAPHY IN A WESTERN ATLANTIC SYMBIODINIUM (DINOPHYTA) LINEAGE1
Authors: Thornhill Daniel J. , Kemp Dustin W. , Bruns Brigitte U. , Fitt William K. , Schmidt Gregory W.
Published: September 2008

Many corals form obligate symbioses with photosynthetic dinoflagellates of the genus Symbiodinium Freudenthal (1962). These symbionts vary genotypically, with their geographical distribution and abundance dependent upon host specificity and tolerance to temperature and light variation. Despite the importance of these mutualistic relationships, the physiology and ecology of Symbiodinium spp. remain poorly characterized. Here, we report that rDNA internal transcribed spacer region 2 (ITS2) defined Symbiodinium type B2 associates with the cnidarian hosts Astrangia poculata and Oculina arbuscula from northerly habitats of the western Atlantic. Using pulse‐amplitude‐modulated (PAM) fluorometry, we compared maximum photochemical efficiency of PSII of type B2 to that of common tropical Symbiodinium lineages (types A3, B1, and C2) under cold‐stress conditions. Symbiont cultures were gradually cooled from 26°C to 10°C to simulate seasonal temperature declines. Cold stress decreased the maximum photochemical efficiency of PSII and likely the photosynthetic potential for all Symbiodinium clades tested. Cultures were then maintained at 10°C for a 2‐week period and gradually returned to initial conditions. Subsequent to low temperature stress, only type B2 displayed rapid and full recovery of PSII photochemical efficiency, whereas other symbiont phylotypes remained nonfunctional. These findings indicate that the distribution and abundance of Symbiodinium spp., and by extension their cnidarian hosts, in temperate climates correspond significantly with the photosynthetic cold tolerance of these symbiotic algae.
Carbon Nanofiber Production
Authors: Khanna Vikas , Bakshi Bhavik R. , Lee L. James
Published: September 2008

Holistic understanding of nanotechnology using systems analysis tools is essential for evaluating claims about the potential benefits of this emerging technology. This article presents one of the first assessments of the life cycle energy requirements and environmental impact of carbon nanofibers (CNFs) synthesis. Life cycle inventory data are compiled with data reported in the open literature. The results of the study indicate relatively higher life cycle energy requirements and higher environmental impact of CNFs as compared to traditional materials, like primary aluminum, steel, and polypropylene, on an equal mass basis. Life cycle energy requirements for CNFs from a range of feedstock materials are found to be 13 to 50 times that of primary aluminum on an equal mass basis. Similar trends are observed from the results of process life cycle assessment (LCA), as conveyed by different midpoint and endpoint damage indicators. Savings in life cycle energy consumption and, hence, reductions in environmental burden are envisaged if higher process yields of these fibers can be achieved in continuous operations. Since the comparison of CNFs is performed on an equal mass basis with traditional materials, these results cannot be generalized for CNF‐based nanoproducts. Quantity of use of these engineered nanomaterials and resulting benefits will decide their energy and environmental impact. Nevertheless, the life cycle inventory and the results of the study can be used for evaluating the environmental performance of specific CNF‐based nanoproducts.
Precaution in Practice
Authors: Helland Aasgeir , Kastenholz Hans , Siegrist Michael
Published: September 2008

Voluntary initiatives by industry have been frequently proposed as one of the most promising ways to reduce potential negative impacts on human health and the environment from nanomaterials. In this study, we examined the industrial perceptions, internal procedures, and performance of the nanomaterial industry. We conducted a written survey of 40 companies in Switzerland and Germany. Most companies replied that nanoparticulate materials (NPMs) should be subject to some kind of regulation, but industry did not convey a clear opinion as to who should be responsible for managing the potential environmental health impacts or how to regulate NPMs throughout their life cycle. If NPM risks were to be identified, most of the companies surveyed do not have standardized procedures for changing production technology, substituting inputs, redesigning processes, or reformulating final products to reduce or eliminate risks of NPMs. However, a majority of the survey respondents found their existing routines regarding these procedures to be sufficient.
Europe‐Wide Survey of Teaching in Geriatric Medicine
Authors: Michel Jean‐Pierre , Huber Philippe , Cruz‐Jentoft Alfonso J. ,   a representative of each surveyed country
Published: September 2008

By 2050, the European population of 720 million will include 187 million (one quarter) octogenarians. Although living longer is a true privilege, care for the graying population suffering from chronic and disabling diseases will raise enormous challenges to healthcare systems and geriatric education. Are European countries ready to cope with these challenges? An extensive 2006 survey of geriatric education in thirty‐one of 33 European countries testifies that geriatrics is a recognized medical specialty in 16 countries and a subspecialty in nine of them. Six European countries have an established chair of geriatric medicine in each of their medical schools. Undergraduate teaching activities are organized in 25 of the surveyed countries and postgraduate teaching in 22 countries under the leadership of geriatricians (n=16) or general internists (n=6). A comparison with data collected in the 1990s shows important progresses: the number of established chairs increased by 45%, the undergraduate and postgraduate teaching activities increased respectively by 23% and 19%. However, these changes are very heterogeneously organized from country to country and within each country. In most European countries, there remains a huge need for reinforcing and harmonizing geriatric teaching activities to prepare the next generation of medical doctors to address the projected increase in chronic and disabled older patients. Several different innovative strategies are proposed.
Effectiveness of a Falls‐and‐Fracture Nurse Coordinator to Reduce Falls: A Randomized, Controlled Trial of At‐Risk Older Adults
Authors: Elley C. Raina , Robertson M. Clare , Garrett Sue , Kerse Ngaire M. , McKinlay Eileen , Lawton Beverley , Moriarty Helen , Moyes Simon A. , Campbell A. John
Published: September 2008

OBJECTIVES: To assess the effectiveness of a community‐based falls‐and‐fracture nurse coordinator and multifactorial intervention in reducing falls in older people.

DESIGN: Randomized, controlled trial.

SETTING: Screening for previous falls in family practice followed by community‐based intervention.

PARTICIPANTS: Three hundred twelve community‐living people aged 75 and older who had fallen in the previous year.

INTERVENTION: Home‐based nurse assessment of falls‐and‐fracture risk factors and home hazards, referral to appropriate community interventions, and strength and balance exercise program. Control group received usual care and social visits.

MEASUREMENTS: Primary outcome was rate of falls over 12 months. Secondary outcomes were muscle strength and balance, falls efficacy, activities of daily living, self‐reported physical activity level, and quality of life (Medical Outcomes Study 36‐item Short Form Questionnaire).

RESULTS: Of the 3,434 older adults screened for falls, 312 (9%) from 19 family practices were enrolled and randomized. The average age was 81±5, and 69% (215/312) were women. The incidence rate ratio for falls for the intervention group compared with the control group was 0.96 (95% confidence interval=0.70–1.34). There were no significant differences in secondary outcomes between the two groups.

CONCLUSION: This nurse‐led intervention was not effective in reducing falls in older people who had fallen previously. Implementation and adherence to the fall‐prevention measures was dependent on referral to other health professionals working in their usual clinical practice. This may have limited the effectiveness of the interventions.
At the Tipping Point: Predicting Severe Mobility Difficulty in Vulnerable Older Women
Authors: Rivera Josette A. , Fried Linda P. , Weiss Carlos O. , Simonsick Eleanor M.
Published: September 2008

OBJECTIVES: To identify clinical measures that aid detection of impending severe mobility difficulty in older women.

DESIGN: Cross‐sectional and longitudinal cohort study.

SETTING: Urban community in Baltimore, Maryland.

PARTICIPANTS: One thousand two community‐dwelling, moderate to severely disabled women aged 65 and older in the Women's Health and Aging Study I.

MEASUREMENTS: Self‐report and performance measures representing six domains necessary for mobility: central and peripheral nervous systems, muscles, bones and joints, perception, and energy. Severe mobility difficulty was defined as usual gait of 0.5 m/s or less, any reported difficulty walking across a small room, or dependence on a walking aid during a 4‐m walking test.

RESULTS: Four hundred sixty‐seven out of 984 (47%) had severe mobility difficulty at baseline, and 104/474 (22%) developed it within 12 months. Baseline mobility difficulty was correlated with poor vision, knee pain, feelings of helplessness, inability to stand with feet side by side for 10 seconds, difficulty keeping balance while dressing or walking, inability to rise from a chair five times, and cognitive impairment. Of these, knee pain (odds ratio (OR)=1.74, 95% confidence interval (CI)=1.05–2.89), helplessness (OR=1.87, 95% CI=1.10–3.24), poor vision (OR=2.03, 95% CI=1.06–3.89), inability to rise from a chair five times (OR=2.50, 95% CI=1.15–5.41), and cognitive impairment (OR=4.75, 95% CI=1.67–13.48) predicted incident severe mobility difficulty within 12 months, independent of age.

CONCLUSION: Five simple measures may aid identification of disabled older women at high risk of severe mobility difficulty. Further studies should determine generalizability to men and higher‐functioning individuals.
Prescription Drug Benefits and Use of Guideline Recommended Medications by Elderly Medicare Beneficiaries with Diabetes Mellitus
Authors: Tjia Jennifer , Briesacher Becky A.
Published: September 2008

OBJECTIVES: To determine whether prescription drug benefits are associated with the use of guideline recommended medications by older persons with type 2 diabetes mellitus (DM).

DESIGN: Cross‐sectional study.

PARTICIPANTS: A national sample of Medicare beneficiaries with DM aged 65 and older and an indication for angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin II–receptor blocker (ARB) use or high risk of coronary heart disease (hypertension or current smoking) who participated in the 2003 Medicare Current Beneficiary Survey.

MEASUREMENTS: Prescription drug coverage was measured according to self‐report and verified according to insurance claims. Outcome variables were use of an ACEI or an ARB (ACEI/ARB) or a statin or use of an ACEI/ARB and a statin. Survey‐weighted multinomial logistic regression was used to identify the independent effect of drug coverage on one of two categories of recommended medication use (ACEI/ARB or statin or ACEI/ARB and statin) compared with the reference category of none after controlling for sociodemographic characteristics and health status.

RESULTS: The final study sample was 1,181 (weighted N=4.0 million). Overall, 23% had no drug coverage, 16% Medicaid coverage, 43% employer coverage, 9% Medigap coverage, and 9% Department of Veterans Affairs (VA) or state‐sponsored low‐income coverage. Overall, 33% received a statin and an ACEI/ARB, 44% only an ACEI/ARB or a statin, and 23% neither. After adjustment, VA and state‐sponsored drug benefits were most strongly associated with combined ACEI/ARB and statin use (relative risk ratio (RRR)=4.83, 95% confidence interval (CI)=2.24–10.4)), followed by employer‐sponsored coverage (RRR=2.60, 95% CI=1.67–4.03)).

CONCLUSIONS: Prescription drug benefits from VA and state‐sponsored drug programs are strongly associated with use of recommended medications by older adults with DM.
What Explains Racial Differences in the Use of Advance Directives and Attitudes Toward Hospice Care?
Authors: Johnson Kimberly S. , Kuchibhatla Maragatha , Tulsky James A.
Published: September 2008

Cultural beliefs and values are thought to account for differences between African Americans and whites in the use of advance directives and beliefs about hospice care, but few data clarify which beliefs and values explain these differences. Two hundred five adults aged 65 and older who received primary care in the Duke University Health System were surveyed. The survey included five scales: Hospice Beliefs and Attitudes, Preferences for Care, Spirituality, Healthcare System Distrust, and Beliefs About Dying and Advance Care Planning. African Americans were less likely than white subjects to have completed an advance directive (35.5% vs 67.4%, P<.001) and had less favorable beliefs about hospice care (Hospice Beliefs and Attitudes Scale score, P<.001). African Americans were more likely to express discomfort discussing death, want aggressive care at the end of life, have spiritual beliefs that conflict with the goals of palliative care, and distrust the healthcare system. In multivariate analyses, none of these factors alone completely explained racial differences in possession of an advance directive or beliefs about hospice care, but when all of these factors were combined, race was no longer a significant predictor of either of the two outcomes. These findings suggest that ethnicity is a marker of common cultural beliefs and values that, in combination, influence decision‐making at the end of life. This study has implications for the design of healthcare delivery models and programs that provide culturally sensitive end‐of‐life care to a growing population of ethnically diverse older adults.
Views of Older Persons with Multiple Morbidities on Competing Outcomes and Clinical Decision‐Making
Authors: Fried Terri R. , McGraw Sarah , Agostini Joseph V. , Tinetti Mary E.
Published: September 2008

OBJECTIVES: To examine the ways in which older persons with multiple conditions think about potentially competing outcomes in order to gain insight into how processes to elicit values regarding these outcomes can be grounded in the patient's perspective.

DESIGN: Qualitative study consisting of purposefully sampled focus groups.

SETTING: Community.

PARTICIPANTS: Persons aged 65 and older taking five or more medications.

MEASUREMENTS: Participants were asked their perceptions about whether their illnesses or treatment interacted with each other, goals of their treatment, and decisions to change or stop treatment.

RESULTS: Although participants were largely unaware that treatment of one condition could worsen another, many had experience with adverse medication effects as a competing outcome. Participants initially discussed their conditions in terms of disease‐specific outcomes, such as achieving a target blood pressure or lipid level. In the context of decision‐making, participants shifted their discussion from disease‐specific to global, cross‐disease health outcomes, such as survival, preservation of physical function, and relief of symptoms. Despite having some misconceptions regarding the likelihood of these outcomes, they weighed the outcomes against one another to consider what was most important to them. Their preference was for the treatment that would achieve the most desired outcome.

CONCLUSION: Because of their experience with adverse medication effects, older persons with multiple morbidities can understand the concept of competing outcomes. The task of prioritizing global, cross‐disease outcomes can help to clarify what is most important to seniors who are faced with complex healthcare decisions.
Elevated C‐Reactive Protein Is Related to Cognitive Decline in Older Adults with Cardiovascular Disease
Authors: Hoth Karin F. , Haley Andreana P. , Gunstad John , Paul Robert H. , Poppas Athena , Jefferson Angela L. , Tate David F. , Ono Makoto , Jerskey Beth A. , Cohen Ronald A.
Published: September 2008

OBJECTIVES: To prospectively relate C‐reactive protein (CRP), a systemic marker of inflammation, to cognitive change over a 1‐year follow‐up period.

DESIGN: Prospective 1‐year follow‐up.

SETTING: Outpatient university medical setting.

PARTICIPANTS: Seventy‐eight adults (aged 56–84; 39% female) with cardiovascular disease.

MEASUREMENTS: CRP levels were measured using a high‐sensitivity assay, and participants completed a neuropsychological battery at study entry. Neuropsychological assessment was repeated 1 year later.

RESULTS: The association between CRP and change in cognition over the 1‐year follow‐up was examined using hierarchical linear regression modeling for five cognitive domains (global cognition, language, memory, visuospatial abilities, and attention‐executive‐psychomotor). High CRP levels were associated with subtle declines in attention‐executive‐psychomotor performance (CRP β=−0.22, P=.04) after adjusting for the effects of age and cognitive performance at study entry. CRP was not significantly associated with change in language, memory, or visuospatial performance.

CONCLUSION: These data provide preliminary evidence that inflammation, potentially contributing to atherosclerotic processes, may underlie the association between high CRP and changes in attention‐executive‐psychomotor performance.
Generic Antiepileptic Drugs: Current Controversies and Future Directions
Authors: Privitera Michael D.
Published: September 2008

The Food and Drug Administration requires rigorous testing of generic formulations of antiepileptic drugs to assure bioequivalence to the brand product and asserts that all approved formulations are interchangeable. Physician surveys, case reports, and “switchback” rates from large-scale generic conversions imply that all generic formulations may not be equal to the brand drug for all patient groups. This review presents the current state of the data on bioequivalence and therapeutic equivalence and proposes a series of studies to better clarify the risks of generic formulation substitution in susceptible populations. Until such studies are completed, when switching to generic formulations, health-care providers and people with epilepsy would do well to proceed cautiously and understand the potential risks and benefits of substitution. Extra caution may be needed for patients at highest risk of seizure complications, such as the pregnant patient, patients with recurrent status epilepticus, or patients who have been seizure-free for long periods of time and are driving.
Outcomes Remain Ambivalent for Deep Brain Stimulation and Epilepsy
Authors: Ben-Menachem Elinor
Published: September 2008

Deep Brain Stimulation in Patients with Refractory Temporal Lobe Epilepsy. Boon P, Vonck K, De Herdt V, Van Dycke A, Goethals M, Goossens L, Van Zandijcke M, De Smedt T, Dewaele I, Achten R, Wadman W, Dewaele F, Caemaert J, Van Roost D. Epilepsia 2007;48(8):1551–1560. PURPOSE: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy. METHODS: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. RESULTS: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12–52 months), one of 10 stimulated patients are seizure-free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of ≥50%; two of 10 patients had a seizure-frequency reduction of 30–49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred. CONCLUSIONS: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.
Thalamus: The “Inner Chamber” Reveals Its Secrets
Authors: Blume Warren T.
Published: September 2008

A Subcortical Network of Dysfunction in TLE Measured by Magnetic Resonance Spectroscopy. Hetherington HP, Kuzniecky RI, Vives K, Devinsky O, Pacia S, Luciano D, Vasquez B, Haut S, Spencer DD, Pan JW. Neurology 2007;69(24):2256–2265. OBJECTIVE: The goal of this work was to evaluate the relationship between neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe epilepsy (TLE) patients using 1H magnetic resonance spectroscopic imaging. METHODS: 1H spectroscopic images from the hippocampus and thalamus of controls and patients with TLE were acquired at 4 T. The spectroscopic imaging data were reconstructed using an automated voxel-shifting method based on anatomic landmarks providing four, six, and three loci for the hippocampus, thalamus, and putamen, respectively. For correlation analysis, the hippocampal and striatal loci were averaged to provide single estimates of the entire structure, whereas the thalamus was divided into two regions, an anterior and posterior measure, using the average of three loci each. RESULTS: The ratio of N-acetyl aspartate to creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the ipsilateral hippocampus was significantly correlated with the ipsilateral and contralateral anterior and posterior thalami, putamen, and contralateral hippocampus. In control subjects, the hippocampi were only correlated with each other. CONCLUSIONS: The data demonstrate that there is significant neuronal injury/loss in both the ipsilateral and contralateral thalami in temporal lobe epilepsy patients, with greater impairment in the anterior portions of the ipsilateral thalamus. The degree of injury/loss in the ipsilateral and contralateral thalamus and putamen is directly correlated with that of the ipsilateral hippocampus. This is consistent with the hypothesis that the impairment and damage associated with recurrent seizures as measured by N-acetyl aspartate originating in the hippocampus results in injury and impairment in other subcortical structures.
Animal Models of Infantile Spasms: Is the Holy Grail Finally in Sight?
Authors: Stafstrom Carl E.
Published: September 2008

A New Animal Model of Infantile Spasms with Unprovoked Persistent Seizures. Lee CL, Frost JD Jr, Swann JW, Hrachovy RA. Epilepsia 2008;49(2):298–307. PURPOSE: Infantile spasms is one of the most severe epileptic syndromes of infancy and early childhood. Progress toward understanding the pathophysiology of this disorder and the development of effective therapies has been hindered by the lack of a relevant animal model. We report here the creation of such a model. METHODS: The sodium channel blocker, tetrodotoxin (TTX), was chronically infused into the developing neocortex or hippocampus of infant rats by way of an osmotic minipump starting on postnatal day 10–12. RESULTS: After a minimum of 10 days of infusion, approximately one-third of these rats began to display very brief (1–2 s) spasms, which consisted of symmetric or asymmetric flexion or extension of the trunk and sometimes involvement of one or both forelimbs. The typical ictal EEG pattern associated with the behavioral spasms consisted of an initial generalized, high amplitude, slow wave followed by an electrodecrement with superimposed fast activity. The interictal EEG revealed multifocal spikes and sharp waves, and in most animals that had spasms a hypsarrhythmic pattern was seen, at least intermittently, during NREM sleep. Like in humans, the spasms in the rat often occurred in clusters especially during sleep–wake transitions. Comparison of the ictal and interictal EEGs recorded in this model and those from humans with infantile spasms revealed that the patterns and the frequency components of both the ictal events and hypsarrhythmia were very similar. DISCUSSION: The TTX model of infantile spasms should be of value in furthering an understanding of the pathophysiology of this seizure disorder.
Rational Polypharmacy: When Two Old Drugs Are Better than One
Authors: Mathews Gregory C.
Published: September 2008

Bumetanide Enhances Phenobarbital Efficacy in a Neonatal Seizure Model. Dzhala VI, Brumback AC, Staley KJ. Ann Neurol 2008;63(2):222–235. OBJECTIVES: High levels of expression of the Na+-K+-2Cl- (NKCC1) cotransporter in immature neurons cause the accumulation of intracellular chloride and, therefore, a depolarized Cl- equilibrium potential (ECl). This results in the outward flux of Cl- through GABAA channels, the opposite direction compared with mature neurons, in which GABAA receptor activation is inhibitory because Cl- flows into the cell. This outward flow of Cl- in neonatal neurons is excitatory and contributes to a greater seizure propensity and poor electroencephalographic response to GABAergic anticonvulsants such as phenobarbital and benzodiazepines. Blocking the NKCC1 transporter with bumetanide prevents outward Cl- flux and causes a more negative GABA equilibrium potential (EGABA) in immature neurons. We therefore tested whether bumetanide enhances the anticonvulsant action of phenobarbital in the neonatal brain. METHODS: Recurrent seizures were induced in the intact hippocampal preparation in vitro by continuous 5-hour exposure to low-Mg2+ solution. The anticonvulsant efficacy of phenobarbital, bumetanide, and the combination of these drugs was studied. RESULTS: Phenobarbital failed to abolish or depress recurrent seizures in 70% of hippocampi. In contrast, phenobarbital in combination with bumetanide abolished seizures in 70% of hippocampi and significantly reduced the frequency, duration, and power of seizures in the remaining 30%. INTERPRETATION: Thus, alteration of Cl- transport by bumetanide enables the anticonvulsant action of phenobarbital in immature brain. This is a mechanistic demonstration of rational anticonvulsant polypharmacy. The combination of these agents may comprise an effective therapy for early-life seizures.
VEGF as a Target for Neuroprotection
Authors: Vezzani Annamaria
Published: September 2008

Vascular Endothelial Growth Factor Is Up-Regulated after Status Epilepticus and Protects against Seizure-Induced Neuronal Loss in Hippocampus. Nicoletti JN, Shah SK, McCloskey DP, Goodman JH, Elkady A, Atassi H, Hylton D, Rudge JS, Scharfman HE, Croll SD. Neuroscience 2008;151(1):232–241. Vascular endothelial growth factor (VEGF) is a protein factor which has been found to play a significant role in both normal and pathological states. Its role as an angiogenic factor is well-established. More recently, VEGF has been shown to protect neurons from cell death both in vivo and in vitro. While VEGF's potential as a protective factor has been demonstrated in hypoxia–ischemia, in vitro excitotoxicity, and motor neuron degeneration, its role in seizure-induced cell loss has received little attention. A potential role in seizures is suggested by Newton et al.'s [Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, Duman RS (2003) Gene profile of electroconvulsive seizures: Induction of neurotrophic and angiogenic factors. J Neurosci 23:10841–10851] finding that VEGF mRNA increases in areas of the brain that are susceptible to cell loss after electroconvulsive-shock induced seizures. Because a linear relationship does not always exist between expression of mRNA and protein, we investigated whether VEGF protein expression increased after pilocarpine-induced status epilepticus. In addition, we administered exogenous VEGF in one experiment and blocked endogenous VEGF in another to determine whether VEGF exerts a neuroprotective effect against status epilepticus-induced cell loss in one vulnerable brain region, the rat hippocampus. Our data revealed that VEGF is dramatically up-regulated in neurons and glia in hippocampus, thalamus, amygdala, and neocortex 24 h after status epilepticus. VEGF induced significant preservation of hippocampal neurons, suggesting that VEGF may play a neuroprotective role following status epilepticus.
GABA Regulates Stem Cell Proliferation before Nervous System Formation
Authors: Wang Doris D. , Kriegstein Arnold R. , Ben-Ari Yehezkel
Published: September 2008

Histone H2AX-Dependent GABAA Receptor Regulation of Stem Cell Proliferation. Andäng M, Hjerling-Leffler J, Moliner A, Lundgren TK, Castelo-Branco G, Nanou E, Pozas E, Bryja V, Halliez S, Nishimaru H, Wilbertz J, Arenas E, Koltzenburg M, Charnay P, El Manira A, Ibañez CF, Ernfors P. Nature 2008;451(7177):460–464. Stem cell self-renewal implies proliferation under continued maintenance of multipotency. Small changes in numbers of stem cells may lead to large differences in differentiated cell numbers, resulting in significant physiological consequences. Proliferation is typically regulated in the G1 phase, which is associated with differentiation and cell cycle arrest. However, embryonic stem (ES) cells may lack a G1 checkpoint. Regulaton of proliferation in the “DNA damage” S/G2 cell cycle checkpoint pathway is known for its role in the maintenance of chromatin structural integrity. Here we show that autocrine/paracrine γ-aminobutyric acid (GABA) signalling by means of GABAA receptors negatively controls ES cell and peripheral neural crest stem (NCS) cell proliferation, preimplantation embryonic growth and proliferation in the boundary-cap stem cell niche, resulting in an attenuation of neuronal progenies from this stem cell niche. Activation of GABAA receptors leads to hyperpolarization, increased cell volume and accumulation of stem cells in S phase, thereby causing a rapid decrease in cell proliferation. GABAA receptors signal through S-phase checkpoint kinases of the phosphatidylinositol-3-OH kinase-related kinase family and the histone variant H2AX. This signalling pathway critically regulates proliferation independently of differentiation, apoptosis and overt damage to DNA. These results indicate the presence of a fundamentally different mechanism of proliferation control in these stem cells, in comparison with most somatic cells, involving proteins in the DNA damage checkpoint pathway.