bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivation and appraisal in perception of poorly specified speech
Authors: LIDESTAM BJÖRN , BESKOW JONAS
Published: March 2006

Normal‐hearing students (n= 72) performed sentence, consonant, and word identification in either A (auditory), V (visual), or AV (audiovisual) modality. The auditory signal had difficult speech‐to‐noise relations. Talker (human vs. synthetic), topic (no cue vs. cue‐words), and emotion (no cue vs. facially displayed vs. cue‐words) were varied within groups. After the first block, effects of modality, face, topic, and emotion on initial appraisal and motivation were assessed. After the entire session, effects of modality on longer‐term appraisal and motivation were assessed. The results from both assessments showed that V identification was more positively appraised than A identification. Correlations were tentatively interpreted such that evaluation of self‐rated performance possibly depends on subjective standard and is reflected on motivation (if below subjective standard, AV group), or on appraisal (if above subjective standard, A group). Suggestions for further research are presented.
Psychological adaptation after marital disruption: The effects of optimism and perceived control
Authors: THUEN FRODE , RISE JOSTEIN
Published: March 2006

The present study explored the extent to which the two personality factors – perceived control and dispositional optimism – are related to psychological adaptation after marital disruption. A sample of 658 recently divorced individuals participated in the study by filling in an anonymous questionnaire. Bivariate findings revealed that perceived control and optimism were strongly related to psychological adaptation. However, when both predictors were included in a multiple regression analysis, optimism had a much larger effect than perceived control. The findings clearly indicate that personality factors account for a substantial proportion of the variance in adaptation to marital disruption.
Types of work‐family interface: Well‐being correlates of negative and positive spillover between work and family
Authors: KINNUNEN ULLA , FELDT TARU , GEURTS SABINE , PULKKINEN LEA
Published: March 2006

The aim of the present study was to test the structure of the work‐family interface measure, which was intended to take into account both the positive and negative spillover between work and family demands in both directions. In addition, the links among the types of work‐family spillover and the subjects’ general and domain‐specific well‐being were examined. The sample (n= 202) consisted of Finnish employees, aged 42, who had a spouse/partner. Confirmatory factor analyses indicated that a four‐factor model, including negative work‐to‐family spillover, negative family‐to‐work spillover, positive work‐to‐family spillover, and positive family‐to‐work spillover, was superior compared to the other factor models examined. Path analysis showed, as hypothesized, that the negative work‐to‐family spillover was most strongly related to low well‐being at work (job exhaustion) and next strongly to low general well‐being (psychological distress), whereas the negative family‐to‐work spillover was associated with low well‐being in the domain of family (marital dissatisfaction). Positive work‐to‐family spillover was positively related both to well‐being at work and general well‐being. Inconsistent with our expectations, positive family‐to‐work spillover was not directly related to any of the well‐being indicators examined.
On the Unification of Families of Skew‐normal Distributions
Authors: ARELLANO‐VALLE REINALDO B. , AZZALINI ADELCHI
Published: March 2006

Abstract.  The distribution theory literature connected to the multivariate skew‐normal distribution has grown rapidly in recent years, and a number of extensions and alternative formulations have been put forward. Presently there are various coexisting proposals, similar but not identical, and with rather unclear connections. The aim of this paper is to unify these proposals under a new general formulation, clarifying at the same time their relationships. The final part sketches an extension of the argument to the skew‐elliptical family.
Livelihoods, fire and policy in eastern Indonesia
Authors: Tacconi Luca , Ruchiat Yayat
Published: March 2006

Indonesian legislation calls for a zero‐burning policy. This approach to fire management is largely in response to significant negative impacts on the economy and the environment, not only in Indonesia but also the neighbouring region, that result annually from peat fires in Kalimantan and Sumatra. In this context, the present paper investigates the local use and management of fire in Flores and Sumba islands in eastern Indonesia. Our appraisals show that people's livelihoods depend on fire to maintain grasslands and, therefore, that the national policy and legislation for zero‐burning is inappropriate and needs to be revised. This follows from the fact that not all fires cause damage and are unwanted. Through a series of rapid rural appraisal interviews, we found that the fires in grasslands are often lit intentionally to maintain the grasslands that local people use to sustain a variety of livelihood activities such as cattle rearing, hunting and farming. Although fires can damage or destroy remnant dry forests in eastern Indonesia, in order to be effective, future policy formulations need to account for this human livelihood dimension and the geographic variation in fuels, climate and land use.
Integrity Tests and Morality: Associations with Ego Development, Moral Reasoning, and Psychopathic Personality
Authors: Connelly Brian S. , Lilienfeld Scott O. , Schmeelk Kelly M.
Published: March 2006

Although past research has shown links between integrity tests and the Big Five personality traits, little is known about the relationship between integrity and other individual difference constructs used to predict moral behavior. The present study expands this research by examining the relationships between ego development, moral reasoning, psychopathic personality, and three commonly used integrity tests. Both overt and personality‐based integrity tests showed the strongest (negative) correlations with psychopathic personality but only modest correlations with ego development and moral reasoning. On the whole, these findings suggest that integrity tests may be more closely related to overt moral behavior than to moral reasoning.
Structure and function of the eastern grey kangaroo (Macropus giganteus) foot thump
Authors: Bender H.
Published: March 2006

Most species of the family Macropodidae (kangaroos and wallabies) make a distinctive foot thump by striking the ground with their hind feet when they detect potential danger. I used the eastern grey kangarooMacropus giganteusas a model to examine (1) the acoustic characteristics and structure of the thump, (2) the social context in which free‐ranging kangaroos thumped when approached by a human observer on foot and (3) the intended recipient of the signal. Thumps were about two‐thirds of a second in length, generally composed of two noisy pulses, and had the majority of the signal energy below 7 kHz. Only adult kangaroos, of both sexes, were observed to thump. A higher proportion of solitary kangaroos thumped than grouped kangaroos, and a higher proportion of kangaroos thumped when visibility was poor, either because of habitat type or low light levels. Given the context in which thumps were given, the foot thump appears to be a signal to a potential predator with three possible functions: to startle, signal detection or deter pursuit.
Sulfated polymannuroguluronate, a novel anti‐acquired immune deficiency syndrome drug candidate, blocks neuroinflammatory signalling by targeting the transactivator of transcription (Tat) protein
Authors: Hui Bin , Xia Wei , Li Jing , Wang Limei , Ai Jing , Geng Meiyu
Published: March 2006

Impaired inflammatory functions may be critical factors in the mechanisms of severe CNS disorders classified as the human immunodeficiency virus‐1 (HIV‐1)‐associated dementia (HAD). Evidence indicates that a viral gene product, the transactivator of transcription protein (Tat), can markedly contribute to these events. We herein report that sulfated polymannuroguluronate (SPMG), a novel anti‐acquired immunodeficiency syndrome drug candidate now in a phase II clinical trial, significantly reversed Tat‐induced release of pro‐inflammatory cytokines [tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β) and IL‐6] and dose dependently decreased the accumulation of reactive oxygen species and nitric oxide in THP‐1 cells. Furthermore, SPMG potently arrested Tat‐triggered protein kinase C (PKC)‐dependent PKC‐μ activation, and blocked the downstream extracellular‐signal regulated kinase 1/2‐ and c‐jun amino‐terminal kinase‐mediated signalling pathways. These molecular mechanisms could be attributed to the fact that SPMG preferentially bound to the basic domain (amino acids 47–57) of the Tat protein with high affinity (KD ≈ 8.69 × 10−10 m), leading to abrogation of Tat‐mediated neuroinflammation and neurotoxicity. These data demonstrate that SPMG might serve as a valuable therapeutic intervention for Tat‐induced profound pro‐inflammatory effects in the brain, and subsequent pathologic events of HAD.
The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes
Authors: Minich Tobias , Riemer Jan , Schulz Jörg B. , Wielinga Peter , Wijnholds Jan , Dringen Ralf
Published: March 2006

Astrocytes play an important role in the glutathione (GSH) metabolism of the brain. To test for an involvement of multidrug resistance protein (Mrp) 1 and 5 in the release of GSH and glutathione disulfide (GSSG) from astrocytes, we used astrocyte cultures from wild‐type, Mrp1‐deficient [Mrp1(–/–)] and Mrp5‐deficient [Mrp5(–/–)] mice. During incubation of wild‐type or Mrp5(–/–) astrocytes, GSH accumulated in the medium at a rate of about 3 nmol/(h.mg), whereas the export of GSH from Mrp1(–/–) astrocytes was only one‐third of that. In addition, Mrp1(–/–) astrocytes had a 50% higher specific GSH content than wild‐type or Mrp5(–/–) cells. The presence of 50 μmof the Mrp inhibitor MK571 inhibited the rate of GSH release from wild‐type and Mrp5(–/–) astrocytes by 60%, but stimulated at the low concentration of 1 μmGSH release by 40%. In contrast, both concentrations of MK571 did not affect GSH export from Mrp1(–/–) astrocytes. Moreover, in contrast to wild‐type and Mrp5(–/–) cells, GSSG export during H2O2stress was not observed for Mrp1(–/–) astrocytes. These data demonstrate that in astrocytes Mrp1 mediates 60% of the GSH export, that Mrp1 is exclusively responsible for GSSG export and that Mrp5 does not contribute to these transport processes.
Substance P initiates NFAT‐dependent gene expression in spinal neurons
Authors: Seybold V. S. , Coicou L. G. , Groth R. D. , Mermelstein P. G.
Published: March 2006

Persistent hyperalgesia is associated with increased expression of proteins that contribute to enhanced excitability of spinal neurons, however, little is known about how expression of these proteins is regulated. We tested the hypothesis that Substance P stimulation of neurokinin receptors on spinal neurons activates the transcription factor nuclear factor of activated T cells isoform 4 (NFATc4). The occurrence of NFATc4 in spinal cord was demonstrated with RT‐PCR and immunocytochemistry. Substance P activated NFAT‐dependent gene transcription in primary cultures of neonatal rat spinal cord transiently transfected with a luciferase DNA reporter construct. The effect of Substance P was mediated by neuronal neurokinin‐1 receptors that coupled to activation of protein kinase C, l‐type voltage‐dependent calcium channels, and calcineurin. Interestingly, Substance P had no effect on cyclic AMP response element (CRE)‐dependent gene expression. Conversely, calcitonin gene‐related peptide, which activated CRE‐dependent gene expression, did not activate NFAT signaling. These data provide evidence that peptides released from primary afferent neurons regulate discrete patterns of gene expression in spinal neurons. Because the release of Substance P and calcitonin gene‐related peptide from primary afferent neurons is increased following peripheral injury, these peptides may differentially regulate the expression of proteins that underlie persistent hyperalgesia.
Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease
Authors: Ginsberg Stephen D. , Che Shaoli , Wuu Joanne , Counts Scott E. , Mufson Elliott J.
Published: March 2006

Dysfunction of cholinergic basal forebrain (CBF) neurons of the nucleus basalis (NB) is a cardinal feature of Alzheimer's disease (AD) and correlates with cognitive decline. Survival of CBF neurons depends upon binding of nerve growth factor (NGF) with high‐affinity (trkA) and low‐affinity (p75NTR) neurotrophin receptors produced within CBF neurons. Since trkA and p75NTR protein levels are reduced within CBF neurons of people with mild cognitive impairment (MCI) and mild AD, trkA and/or p75NTR gene expression deficits may drive NB degeneration. Using single cell expression profiling methods coupled with custom‐designed cDNA arrays and validation with real‐time quantitative PCR (qPCR) and in situ hybridization, individual cholinergic NB neurons displayed a significant down regulation of trkA, trkB, and trkC expression during the progression of AD. An intermediate reduction was observed in MCI, with the greatest decrement in mild to moderate AD as compared to controls. Importantly, trk down regulation is associated with cognitive decline measured by the Global Cognitive Score (GCS) and the Mini‐Mental State Examination (MMSE). In contrast, there is a lack of regulation of p75NTR expression. Thus, trk defects may be a molecular marker for the transition from no cognitive impairment (NCI) to MCI, and from MCI to frank AD.
Cortical choline transporter function measuredin vivousing choline‐sensitive microelectrodes: clearance of endogenous and exogenous choline and effects of removal of cholinergic terminals
Authors: Parikh V. , Sarter M.
Published: March 2006

The capacity of the high‐affinity choline transporter (CHT) to import choline into presynaptic terminals is essential for acetylcholine synthesis. Ceramic‐based microelectrodes, coated at recording sites with choline oxidase to detect extracellular choline concentration changes, were attached to multibarrel glass micropipettes and implanted into the rat frontoparietal cortex. Pressure ejections of hemicholinium‐3 (HC‐3), a selective CHT blocker, dose‐dependently reduced the uptake rate of exogenous choline as well as that of choline generated in response to terminal depolarization. Following the removal of CHTs, choline signal recordings confirmed that the demonstration of potassium‐induced choline signals and HC‐3‐induced decreases in choline clearance require the presence of cholinergic terminals. The results obtained from lesioned animals also confirmed the selectivity of the effects of HC‐3 on choline clearance in intact animals. Residual cortical choline clearance correlated significantly with CHT‐immunoreactivity in lesioned and intact animals. Finally, synaptosomal choline uptake assays were conducted under conditions reflectingin vivobasal extracellular choline concentrations. Results from these assays confirmed the capacity of CHTs measuredin vivoand indicated that diffusion of substrate away from the electrode did not confound thein vivofindings. Collectively, these results indicate that increases in extracellular choline concentrations, irrespective of source, are rapidly cleared by CHTs.
Characterization of an extended receptive ligand repertoire of the human olfactory receptor OR17‐40 comprising structurally related compounds
Authors: Jacquier Valérie , Pick Horst , Vogel Horst
Published: March 2006

Molecular properties of odorant compounds essential for activation of the human olfactory receptor hOR17‐40 were investigated using a collection of 23 variants of its cognate ligand helional. Coupling receptor activation to an optically detectable intracellular Ca2+ ion flux allowed dose‐dependent screening of different odorant molecules in human embryonic kidney (HEK)293 cells. We found an extended collection of activating ligands and provide first evidence for hOR17‐40‐specific antagonists. The C‐terminal fusion of enhanced green fluorescent protein to the hOR17‐40 retained full receptor function and permitted the selection of cells with defined receptor expression levels, which was an essential step for optimizing our screening protocol. Interestingly, cells with a low EGFP fluorescence intensity exhibited efficient hOR17‐40 cell surface targeting and odorant‐evoked signal transduction; in contrast, highly fluorescent cells displayed mainly incorrectly targeted, intracellular receptors. Fluorescence‐activated cell sorting was used to separate hOR17‐40‐expressing cells on the basis of their endogenous EGFP fluorescence intensity, thereby increasing the fraction of odorant‐responsive cells to up to 80% of the total cell number.
Expression of the Otx2 homeobox gene in the developing mammalian brain: embryonic and adult expression in the pineal gland
Authors: Rath Martin F. , Muñoz Estela , Ganguly Surajit , Morin Fabrice , Shi Qiong , Klein David C. , Møller Morten
Published: March 2006

Otx2 is a vertebrate homeobox gene, which has been found to be essential for the development of rostral brain regions and appears to play a role in the development of retinal photoreceptor cells and pinealocytes. In this study, the temporal expression pattern of Otx2 was revealed in the rat brain, with special emphasis on the pineal gland throughout late embryonic and postnatal stages. Widespread high expression of Otx2 in the embryonic brain becomes progressively restricted in the adult to the pineal gland. Crx (cone–rod homeobox), a downstream target gene of Otx2, showed a pineal expression pattern similar to that of Otx2, although there was a distinct lag in time of onset. Otx2 protein was identified in pineal extracts and found to be localized in pinealocytes. Total pineal Otx2 mRNA did not show day–night variation, nor was it influenced by removal of the sympathetic input, indicating that the level of Otx2 mRNA appears to be independent of the photoneural input to the gland. Our results are consistent with the view that pineal expression of Otx2 is required for development and we hypothesize that it plays a role in the adult in controlling the expression of the cluster of genes associated with phototransduction and melatonin synthesis.
Suppressive effects of 4‐phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress
Authors: Kubota Kyoko , Niinuma Yoshifumi , Kaneko Masayuki , Okuma Yasunobu , Sugai Mami , Omura Tomohiro , Uesugi Mai , Uehara Takashi , Hosoi Toru , Nomura Yasuyuki
Published: March 2006

Endoplasmic reticulum (ER) stress is defined as an accumulation of unfolded proteins in the endoplasmic reticulum. 4‐phenylbutyrate (4‐PBA) has been demonstrated to promote the normal trafficking of the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) mutant from the ER to the plasma membrane and to restore activity. We have reported that 4‐PBA protected against cerebral ischemic injury and ER stress‐induced neuronal cell death. In this study, we revealed that 4‐PBA possesses chemical chaperone activityin vitro, which prevents the aggregation of denatured α‐lactalbumin and bovine serum albumin (BSA). Furthermore, we investigated the effects of 4‐PBA on the accumulation of Parkin‐associated endothelin receptor‐like receptor (Pael‐R) pathologically relevant to the loss of dopaminergic neurons in autosomal recessive juvenile parkinsonism (AR‐JP). Interestingly, 4‐PBA restored the normal expression of Pael‐R protein and suppressed ER stress induced by the overexpression of Pael‐R. In addition, we showed that 4‐PBA attenuated the activation of ER stress‐induced signal transduction pathways and subsequent neuronal cell death. Moreover, 4‐PBA restored the viability of yeasts that fail to induce an ER stress response under ER stress conditions. These results suggest that 4‐PBA suppresses ER stress by directly reducing the amount of misfolded protein, including Pael‐R accumulated in the ER.
Identification and characterization of two novel splice forms of GRIP1 in the rat brain
Authors: Charych Erik I. , Li Rongwen , Serwanski David R. , Li Xuejing , Miralles Celia P. , Pinal Noelia , De Blas Angel L.
Published: March 2006

We cloned two novel alternatively‐spliced mRNA isoforms of glutamate receptor interacting protein 1 (GRIP1) which we named GRIP1d and GRIP1e 4–7. GRIP1d is a 135 kDa, 7‐PDZ‐domain variant of GRIP1, containing the 12 amino acid C‐terminus originally described for the 4‐PDZ‐domain GRIP1c 4–7. GRIP1e 4–7 is a 75 kDa 4‐PDZ‐domain variant of GRIP1, containing the 12 amino acid C‐terminus originally described for the 7‐PDZ‐domain GRIP1a/b. Northern blots indicated that GRIP1d mRNA is 5.1 kb long and abundant in brain. An antibody to the C‐terminus of the 75 kDa GRIP1c 4–7 also recognized an abundant 135 kDa protein, consistent with the predicted size of GRIP1d. Similarly, an antibody to the C‐terminus of the 135 kDa GRIP1a/b also recognized a low abundance 75 kDa protein, consistent with the predicted size of GRIP1e 4–7. Immunocytochemistry of hippocampal cultures and intact brain using these antibodies showed that (i) these isoforms are present in both GABAergic and glutamatergic synapses, and (ii) the isoforms co‐localize in individual synapses. While GRIP1a/b isoforms are abundant in interneurons and highly concentrated in GABAergic presynaptic terminals, the isoforms recognized by the antibody to the C‐terminus common to GRIP1c 4–7 and GRIP1d are much less abundant in interneurons and preferentially concentrate at the postsynaptic complex.
Effect of ammonia on astrocytic glutamate uptake/release mechanisms
Authors: Rose Christopher
Published: March 2006

Hyperammonemic disorders such as acute liver failure (ALF) or urea cycle enzymopathies are associated with hyperexcitability, seizures, brain edema and increased extracellular brain glutamate. Mechanisms responsible for increased glutamate content in the extracellular space of the brain include decreased uptake by perineuronal astrocytes and/or increased release from neurons and/or astrocytes. Exposure of astrocytes to millimolar concentrations of ammonia results in cell swelling, loss of expression of the glutamate transporters excitatory amino acid transporter (EAAT‐1) and EAAT‐2 and increased release of glutamate. Three distinct mechanisms are theoretically possible to explain ammonia‐induced glutamate release from astrocytes namely: release due to swelling; reversal of glutamate transporters and due to Ca2+‐dependent vesicular release. Recent identification of vesicular docking and fusion proteins in astrocytes together with glutamate‐release (due to intracellular alkanization and mobilization of intracellular Ca2+‐stores) studies implies that vesicular release is a predominant mechanism responsible for ammonia‐induced release of glutamate from astrocytes.
Health Services Research as a Source of Legislative Analysis and Input: The Role of the California Health Benefits Review Program
Authors: Oliver Thomas R. , Singer Rachel Friedman
Published: March 2006

This article examines the role of the California Health Benefits Review Program (CHBRP) as a source of information in state health policy making. It explains why the California benefits review process relies heavily on university‐based researchers and employs a broad set of criteria for review, which set it apart from similar programs in other states. It then analyzes the politics of health insurance mandates and how independent research and analysis might alter the perceived benefits and costs of health insurance mandates and thus political outcomes. It considers how research and analysis is typically used by policy makers, and illustrates how participants inside and outside of state government have used the reports prepared by CHBRP as both guidance in policy design and as political ammunition. Although there is consensus that the review process has reduced the number of mandate bills that are passed out of the legislature, both supporters and opponents favor the new process and generally believe the reports strengthen their case in legislative debates over health insurance mandates. The role of the CHBRP is narrowly defined by statute at the present time, but the program may well face pressure to evolve from its current academic orientation into a more interactive, advisory role for legislators in the future.
Carboplatin for treatment of a Sertoli cell tumor in a mallard (Anas platyrhynchos)
Authors: Childs‐Sanford S. E. , Rassnick K. M. , Alcaraz A.
Published: March 2006

A 13‐year‐old male mallard was diagnosed with a non‐resectable Sertoli cell tumor involving the left testis. The duck was treated with four doses of single‐agent carboplatin given at 4‐ to 5‐week intervals. Heteropenia, 2 weeks after each treatment, was the acute dose‐limiting toxicity. The tumor reduced in size by 25%, and the duck's clinical condition improved for 12 months. Sertoli cell tumors are rare in birds, and this is the first report, to our knowledge, of attempted chemotherapy treatment in the veterinary literature.
Epidermal growth factor receptor expression in feline oral squamous cell carcinomas
Authors: Looper J. S. , Malarkey D. E. , Ruslander D. , Proulx D. , Thrall D. E.
Published: March 2006

Feline oral squamous cell carcinomas (SCC) have a poor prognosis despite aggressive treatment with surgery, radiation and anticancer drugs. Overexpression of the epidermal growth factor receptor (EGFR), a membrane‐bound tyrosine kinase receptor, has been found in many human epithelial neoplasms, including oral SCC. EGFR overexpression has been associated with advanced disease and a poor prognosis. The purpose of this study was to determine whether feline oral SCC express EGFR. Thirteen formalin‐fixed paraffin wax‐embedded biopsy samples from feline oral SCC were analysed for EGFR expression using immunohistochemistry. Nine of 13 tumours (69%) were positive for EGFR expression, suggesting that altered EGFR expression plays a role in feline oral SCC and provides a rationale for a potential clinical benefit using EGFR inhibitors in combination with conventional treatments.
The cognitive complaint interview (CCI)
Authors: THOMAS‐ANTÉRION Catherine , HONORÉ‐MASSON Sandrine , LAURENT Bernard
Published: March 2006

Background:  The objective is to devise a cognitive complaint interview (CCI) that can be used in the early stages of dementia. The interview consists in two questions about general memory functioning and eight questions about more particular cognitive complaints: a ‘yes’ response to one of these questions reflects what we refer to as a memory complaint. The administration of this interview takes approximately 10 min.

Methods:  One hundred and ninety‐five interviews were conducted. We studied 73 normal subjects, 73 patients (Alzheimer's disease (AD), n = 49; depression, n = 24) and 49 caregivers for AD patients.

Results:  The number of ‘yes’ responses in the CCI was not accounted by age, gender, educational level or Mini‐Mental State Examination. Only the AD subgroup presents more general complaints than the control subgroup. Only three out of the 73 controls (<4.1%) complained more than three times, which suggests that a complaint score superior to three (obviously without mood, social or sensorial explanations) should lead to additional testing. The AD patient's feelings may be similar to those of his family. Nevertheless, once the patient has a clear dementia syndrome, the patient and/or their caregiver may stop complaining and develop an anosognosia.

Conclusion:  This CCI could constitute a tool to provide an etiological explanation of the memory complaints.
Recognition and Therapeutic Management of Migraine in 2004, in France: Results of FRAMIG 3, a French Nationwide Population‐Based Survey
Authors: Lucas Christian , Géraud Gilles , Valade Dominique , Chautard Marie‐Hélène , Lantéri‐Minet Michel
Published: March 2006

Objective.—To evaluate the proportion of migraineurs who are self‐aware of their disease in France, to determine the factors (disability, quality of life, psychiatric comorbidities, and medical consultation) that may promote self‐awareness of migraine, and to assess the influence of these factors on migraine attacks.

Background.—New recommendations for migraine diagnosis and medical management were released in 2003 by the French medicoeconomic evaluation service (ANAES). In addition, the revised classification of headache disorders recently issued by the International Headache Society includes probable migraine as a form of migraine. However, strict and probable migraine now appear to be part of the same spectrum of disease.

Methods.—Subjects with migraine (strict or probable) according to the revised classification were identified by a postal questionnaire from a large representative sample of the French adult population. Migraine‐related disability was assessed using the MIDAS questionnaire, anxiety and depression by the Hospital Anxiety and Depression scale (HADS), and health‐related quality of life (HRQoL) by the 8 concepts of the Short‐Form 12 (SF‐12) questionnaire. Migraine management was assessed according to the use of recommended or nonrecommended treatments, and treatment efficacy according to the set of 4 questions designed by the ANAES.

Results.—Of the 10,532 subjects interviewed, 1,179 subjects (21.3%) were identified as migraineurs. Sixty percent of all migraine subjects were not self‐aware that they had migraine. Medical consultation, duration of migraine history, severe intensity of attacks, impact on daily living, and female gender promoted self‐awareness of migraine. On the other hand, HRQoL and anxiety and depression scores were not different between subjects self‐aware or not self‐aware of migraine. Only 20% of all migraine subjects were medically followed‐up. Quality of the first medical consultation appears determinant for continued consulting. Subjects self‐aware of migraine more frequently used recommended acute treatments of migraine, which proved more effective than nonrecommended treatments as assessed according to the ANAES set of questions.

Conclusions.—Migraine medical diagnosis and follow‐up remain low in France. Careful medical consultation is a prime factor for migraine subject self‐awareness of migraine, continued consultation, and use of recommended medications for the treatment of migraine attacks.
Factors Influencing Migraineur‐Consulting Behavior in a University Population
Authors: Skomo Monica L. , Desselle Shane P. , Berdine Hildegarde J.
Published: March 2006

Objective.—The purpose of this study was to identify factors that contribute to treatment‐seeking behavior in migraineurs in a large employer population. Specifically, the impact of psychographic variables, such as social support, attitudes toward medication, locus of control, and migraine‐associated disability, are considered concomitantly with demographic and disease severity variables.

Background.—Migraine remains an underconsulted condition. Previous explorations of demographic factors and headache characteristics have not adequately predicted migraineur physician‐consulting behavior.

Methods.—University employees and students experiencing headaches were interviewed by pharmacists to determine whether they suffer from migraine using the International Headache Society (IHS) criteria for migraine. Identified migraineurs were categorized into 3 groups: (1) never‐consulter, (2) lapsed‐consulter, and (3) current‐consulter. Each group was asked to complete an instrument that assesses perceived social support (Headache Social Support Questionnaire), medication attitudes (Beliefs about Medicines Questionnaire), locus of control (Headache‐Specific Locus of Control Scale), and migraine‐associated disability (Migraine Disability Assessment Questionnaire). Univariate (ANOVA) and multivariate (logistic regression) approaches were used to identify factors associated with migraineur‐consulting behavior.

Results.—A total of 100 subjects participated in the study. Eighty‐two participants met IHS criteria for migraine, of whom 22 were never‐consulters, 20 were lapsed‐consulters, and 40 were current‐consulters. The consulter groups differed on scores acquired from the Social Support Active Involvement subscale (P= .04) and the Healthcare Professional Locus of Control subscale (P= .010). The logistic regression procedures confirmed the contributions of social support and healthcare locus of control in predicting migraineur‐consulting behavior.

Conclusion.—Results suggest that attitudes concerning the role of healthcare professionals and the presence of a supportive social network have greater influence on migraineur‐consulting behavior than do patient demographic characteristics, beliefs about medications, and migraine frequency and severity. With an understanding of the link between psychosocial variables and consulting behavior, healthcare professionals may be able to positively impact migraineur physician consultation rates, drug therapy, and quality of life.
EFFECTS OF PARENTAL FACTORS AND MEIOSIS ON SEXUAL OFFSPRING OF GYMNODINIUM NOLLERI (DINOPHYCEAE)1
Authors: Figueroa Rosa Isabel , Rengefors Karin , Bravo Isabel
Published: March 2006

Clonal strains of the dinoflagellate Gymnodinium nolleri Ellegaard and Moestrup were intercrossed to determine if cyst‐related traits are genetically regulated and to clarify unknown aspects in the sexuality of this species. The objectives were to determine whether the parental identity influenced the physiological and morphological aspects of the cyst offspring, and to describe and compare nuclear development and cell division of encysting and non‐encysting zygotes. Variables characteristic of each parental cross (difference in growth rates among parents, cyst production (CP), and genetic distance (GD) among parents assessed via an amplified fragment length analysis analysis) were studied to seek for possible relationships of the parental crosses with some characteristics of the cyst offspring (cyst size, length of dormancy period, germination success, and germling viability (V)). A principal component analysis using these variables showed three main results: (1) the dormancy period of cysts responded to a simple pattern of inheritance, (2) the larger the GD between parents, the smaller the CP, and progeny V, and (3) the size of cysts was influenced by both CP and the parental strain identity. A stable inheritance of the short dormancy period (14.6±5.5 days), dominant over medium (31.0±8.5 days) and long periods (52.7±9.2 days), was confirmed through two subsequent generations of cysts. The regulation of the sexual processes by a multiple loci system is discussed based on the pattern of inheritance of the dormancy period and the number of sexual recombination events recorded within cultures with self‐CP capability. Fusion of the gamete nuclei happened 0–48 h after the total cytoplasmic fusion. The nucleus of the zygote was bilobed and had thick and distinct chromosomes. Similar processes of nuclear and cell division occurred in the non‐encysting or encysting planozygote, and were characterized by the loss of the chromosomal structure, an apparent increase of the DNA content, and the formation of thinner chromosomes.
MOVEMENT MODALITIES AND RESPONSES TO ENVIRONMENTAL CHANGES OF THE MUDFLAT DIATOM CYLINDROTHECA CLOSTERIUM (BACILLARIOPHYCEAE)1
Authors: Apoya‐Horton Melba D. , Yin Liang , Underwood Graham J. C. , Gretz Michael R.
Published: March 2006

Cylindrotheca closterium (Ehrenberg) Reiman et Lewin is a raphid diatom widely distributed in mudflat assemblages. Video microscopy showed various movement modalities defined as smooth and corkscrew gliding, pirouette, pivot, rock and roll, rollover, and simultaneous pirouette and gliding. Z‐axis projection analysis of images revealed a unique gliding motif with corkscrew motions, which may have important ecological implications for C. closterium movement in muds. The general response to salinity alteration was a decrease in gliding movements with a concomitant increase in other modalities listed above. Short‐term responses to salinity change include dramatic alteration in modalities in hypo‐saline conditions and cessation of motility in extreme hyper‐saline environments. Modality changes were rapid and occurred within 5 s in response to hyper‐saline conditions. Hypo‐ or hyper‐saline conditions resulted in decreased gliding speed in standard media. Five‐ and 15‐day acclimation to salinity changes resulted in a progressive reduction in gliding movement, increased non‐gliding modalities and increased cell aggregation. Aggregation in hypo‐saline conditions was accompanied by a large increase in the polymer extracted by hot bicarbonate‐ and ethylenediamine tetraaceticacid‐ fractions of extracellular polymeric substance (EPS), the polymers of which have been implicated in cell attachment/motility phenomena. The monosaccharide profiles of these fractions were altered in response to hypo‐saline conditions. In general, monosaccharide profiles showed increased diversity upon cessation of motility and aggregation of cultures. The movement responses of C. closterium in response to environmental changes, accompanied by modifications in EPS, may form part of an adaptive strategy to survive in mudflats and could be useful as bioindicators of environmental changes.
A naturally occurring Leu33Val mutation in β3‐integrin impairs the HPA‐1a epitope: the third allele of HPA‐1
Authors: Santoso Sentot , Kroll Hartmut , Andrei‐Selmer Cornelia L. , Socher Ines , Rankin Angela , Kretzschmar Evelyne , Watkins Nicholas A. , Ouwehand Willem H.
Published: March 2006

BACKGROUND:  Single‐amino‐acid substitution Leu33Pro in the β3‐integrin is responsible for the formation of the human platelet antigen (HPA)‐1. Alloimmunization against HPA‐1a (β3‐Leu33) is the most frequent cause of neonatal alloimmune thrombocytopenia and posttransfusion purpura.

STUDY DESIGN AND METHODS:  While HPA‐1 genotyping a large cohort of patients with thromboembolic disease with a thermal cycler (LightCycler), one patient was identified with a unique HPA‐1a melting curve.

RESULTS:  Sequence analysis revealed a C‐to‐G transversion at nucleotide 175 in the β3‐integrin (ITGB3) gene that alters the Leu33 codon to Val33. Further genotyping of healthy blood donors (n = 2950) identified one nonrelated Pro33Val33‐positive individual. To examine whether the presence of Val33 affected the binding pattern of HPA‐1 alloantibodies, transfectants were generated expressing recombinant β3‐Leu33 or β3‐Val33. Interestingly, differences in the reactivity of anti‐HPA‐1a were observed, with some HPA‐1a alloantibodies showing diminished reactivity with β3‐Val33 compared to β3‐Leu33 and others reacting equally with both types. Similar findings were observed with recombinant human HPA‐1a antibodies, with one of the three not binding to β3‐Val33.

CONCLUSIONS:  Our results demonstrate that the naturally occurring Leu33Val mutation in the β3‐integrin can disrupt some HPA‐1a epitopes. These findings provide evidence for a heterogeneous humoral response against HPA‐1a that may have potential clinical implications for alloimmune thrombocytopenia disorders.
Bayesian Modeling of Differential Gene Expression
Authors: Lewin Alex , Richardson Sylvia , Marshall Clare , Glazier Anne , Aitman Tim
Published: March 2006

Summary We present a Bayesian hierarchical model for detecting differentially expressing genes that includes simultaneous estimation of array effects, and show how to use the output for choosing lists of genes for further investigation. We give empirical evidence that expression‐level dependent array effects are needed, and explore different nonlinear functions as part of our model‐based approach to normalization. The model includes gene‐specific variances but imposes some necessary shrinkage through a hierarchical structure. Model criticism via posterior predictive checks is discussed. Modeling the array effects (normalization) simultaneously with differential expression gives fewer false positive results. To choose a list of genes, we propose to combine various criteria (for instance, fold change and overall expression) into a single indicator variable for each gene. The posterior distribution of these variables is used to pick the list of genes, thereby taking into account uncertainty in parameter estimates. In an application to mouse knockout data, Gene Ontology annotations over‐ and underrepresented among the genes on the chosen list are consistent with biological expectations.
A General Method for Dealing with Misclassification in Regression: The Misclassification SIMEX
Authors: Küchenhoff Helmut , Mwalili Samuel M. , Lesaffre Emmanuel
Published: March 2006

Summary We have developed a new general approach for handling misclassification in discrete covariates or responses in regression models. The simulation and extrapolation (SIMEX) method, which was originally designed for handling additive covariate measurement error, is applied to the case of misclassification. The statistical model for characterizing misclassification is given by the transition matrix Π from the true to the observed variable. We exploit the relationship between the size of misclassification and bias in estimating the parameters of interest. Assuming that Π is known or can be estimated from validation data, we simulate data with higher misclassification and extrapolate back to the case of no misclassification. We show that our method is quite general and applicable to models with misclassified response and/or misclassified discrete regressors. In the case of a binary response with misclassification, we compare our method to the approach of Neuhaus (1999, Biometrika86, 843–855), and to the matrix method of Morrissey and Spiegelman (1999, Biometrics55, 338–344) in the case of a misclassified binary regressor. We apply our method to a study on caries with a misclassified longitudinal response.
Bayesian Robust Inference for Differential Gene Expression in Microarrays with Multiple Samples
Authors: Gottardo Raphael , Raftery Adrian E. , Yee Yeung Ka , Bumgarner Roger E.
Published: March 2006

Summary We consider the problem of identifying differentially expressed genes under different conditions using gene expression microarrays. Because of the many steps involved in the experimental process, from hybridization to image analysis, cDNA microarray data often contain outliers. For example, an outlying data value could occur because of scratches or dust on the surface, imperfections in the glass, or imperfections in the array production. We develop a robust Bayesian hierarchical model for testing for differential expression. Errors are modeled explicitly using a t‐distribution, which accounts for outliers. The model includes an exchangeable prior for the variances, which allows different variances for the genes but still shrinks extreme empirical variances. Our model can be used for testing for differentially expressed genes among multiple samples, and it can distinguish between the different possible patterns of differential expression when there are three or more samples. Parameter estimation is carried out using a novel version of Markov chain Monte Carlo that is appropriate when the model puts mass on subspaces of the full parameter space. The method is illustrated using two publicly available gene expression data sets. We compare our method to six other baseline and commonly used techniques, namely the t‐test, the Bonferroni‐adjusted t‐test, significance analysis of microarrays (SAM), Efron's empirical Bayes, and EBarrays in both its lognormal–normal and gamma–gamma forms. In an experiment with HIV data, our method performed better than these alternatives, on the basis of between‐replicate agreement and disagreement.
Factors Influencing Soay Sheep Survival: A Bayesian Analysis
Authors: King R. , Brooks S. P. , Morgan B. J. T. , Coulson T.
Published: March 2006

Summary This article presents a Bayesian analysis of mark‐recapture‐recovery data on Soay sheep. A reversible jump Markov chain Monte Carlo technique is used to determine age classes of common survival, and to model the survival probabilities in those classes using logistic regression. This involves environmental and individual covariates, as well as random effects. Auxiliary variables are used to impute missing covariates measured on individual sheep. The Bayesian approach suggests different models from those previously obtained using classical statistical methods. Following model averaging, features that were not previously detected, and which are of ecological importance, are identified.
Estimating and Comparing the Distribution of Onset of Disease from Prevalence Case–Control Data
Authors: Bagiella Emilia
Published: March 2006

SummaryAge at ascertainment from prevalence case–control data identifies the age‐specific odds of disease. When age at onset is available from the cases, the conditional distribution of age at onset, given that disease occurs, is identifiable. Combining both kinds of information by introducing a multiplicative intercept allows identification of the marginal distribution of age at onset. Here, the approach is extended to the two‐sample setting through a generalization of the multiplicative intercept model. The efficiency of the approach is explored and a test statistic based on the integrated difference between distribution function estimates is proposed. An approach to regularization of the likelihood is discussed. The methods are illustrated through an application to data on colorectal polyps obtained from a case–control study of individuals undergoing colonoscopy.
Statistical Methods for Expression Quantitative Trait Loci (eQTL) Mapping
Authors: Kendziorski C. M. , Chen M. , Yuan M. , Lan H. , Attie A. D.
Published: March 2006

Summary Traditional genetic mapping has largely focused on the identification of loci affecting one, or at most a few, complex traits. Microarrays allow for measurement of thousands of gene expression abundances, themselves complex traits, and a number of recent investigations have considered these measurements as phenotypes in mapping studies. Combining traditional quantitative trait loci (QTL) mapping methods with microarray data is a powerful approach with demonstrated utility in a number of recent biological investigations. These expression quantitative trait loci (eQTL) studies are similar to traditional QTL studies, as a main goal is to identify the genomic locations to which the expression traits are linked. However, eQTL studies probe thousands of expression transcripts; and as a result, standard multi‐trait QTL mapping methods, designed to handle at most tens of traits, do not directly apply. One possible approach is to use single‐trait QTL mapping methods to analyze each transcript separately. This leads to an increased number of false discoveries, as corrections for multiple tests across transcripts are not made. Similarly, the repeated application, at each marker, of methods for identifying differentially expressed transcripts suffers from multiple tests across markers. Here, we demonstrate the deficiencies of these approaches and propose a mixture over markers (MOM) model that shares information across both markers and transcripts. The utility of all methods is evaluated using simulated data as well as data from an F2 mouse cross in a study of diabetes. Results from simulation studies indicate that the MOM model is best at controlling false discoveries, without sacrificing power. The MOM model is also the only one capable of finding two genome regions previously shown to be involved in diabetes.