bluuebunny/crossref_metadata_2025 huggingface dataset:
Extrinsic Cues Suppress the Encoding of Intrinsic Cues
Authors: Sheth Bhavin R. , Shimojo Shinsuke
Published: April 2004

Remembering where objects are in space is fundamental to adaptive behavior. Little is known about how intact humans combine information from intrinsic (egocentric) and extrinsic (exocentric, allocentric, or landmark-based) coordinate systems to locate objects. Using a simple location estimation paradigm, this study finds that we mostly remember position in extrinsic coordinates. Intrinsic-coordinate-based mapping of space is less precise in the presence of landmarks or extrinsic cues than in their absence. Thus, not only do extrinsic frames of reference dominate internal representations of space, they suppress intrinsic-based representations as well. We speculate that this dominance-suppression hierarchy undercuts intersystem conflicts and underlies a single, undissociated spatial map in intact humans.
Bifurcation into Functional Niches in Adaptation
Authors: White Justin S. , Adami Christoph
Published: April 2004

One of the central questions in evolutionary biology concerns the dynamics of adaptation and diversification. This issue can be addressed experimentally if replicate populations adapting to identical environments can be investigated in detail. We have studied 501 such replicas using digital organisms adapting to at least two fundamentally different functional niches (survival strategies) present in the same environment: one in which fast replication is the way to live, and another where exploitation of the environment's complexity leads to complex organisms with longer life spans and smaller replication rates. While these two modes of survival are closely analogous to those expected to emerge in so-called r and K selection scenarios respectively, the bifurcation of evolutionary histories according to these functional niches occurs in identical environments, under identical selective pressures. We find that the branching occurs early, and leads to drastic phenotypic differences (in fitness, sequence length, and gestation time) that are permanent and irreversible. This study confirms an earlier experimental effort using microorganisms, in that diversification can be understood at least in part in terms of bifurcations on saddle points leading to peak shifts, as in the picture drawn by Sewall Wright.
Avida: A Software Platform for Research in Computational Evolutionary Biology
Authors: Ofria Charles , Wilke Claus O.
Published: April 2004

Avida is a software platform for experiments with self-replicating and evolving computer programs. It provides detailed control over experimental settings and protocols, a large array of measurement tools, and sophisticated methods to analyze and post-process experimental data. We explain the general principles on which Avida is built, as well as its main components and their interactions. We also explain how experiments are set up, carried out, and analyzed.
Pursuit deterrent signalling by the bonaire whiptail lizard Cnemidophorus murinus
Authors: Baird Troy , Cooper William , Caldwell Janalee , Pérez-Mellado Valentín , Vitt Laurie
Published: April 2004

Pursuit-deterrent signalling may account for several behaviors, often subtle, that have no current satisfactory explanation. We conducted field observations and experiments to determine whether arm-waving by Bonaire whiptail lizards, Cnemidophorus murinus, is consistent with pursuit deterrent signalling. The hypotheses that lizards wave their arms to remove feet from hot substrates and that arm-waving is solely a social signal were falsified. Lizards preferentially waved the arm closer to an investigator simulating a predator, typically while looking directly at the predator. This strongly suggests signalling and contradicts the hypothesis that arm-waving is merely a flight intention movement. Most individuals retreat, providing a margin of safety, and then wave. As expected for a pursuit-deterrent signal, arm-waving is related to risk. During direct approaches lizards waved when the predator drew within 3-6 m if approached slowly, but fled without signalling if approached rapidly. Lizards approached tangentially signalled frequently when the minimum bypass distance was 2-4 m, but rarely when it was 10 m. They arm-waved when predators approached, but rarely while they retreated. Arm-waving was rare where lizards were habituated to human presence, but frequent elsewhere. Collectively, the data strongly suggest that arm-waving has a pursuit-deterrent function.
Long-term persistence of song performance rules in nightingales (Luscinia megarhynchos): a longitudinal field study on repertoire size and composition
Authors: Hultsch Henrike , Kipper Silke , Mundry Roger , Todt Dietmar
Published: April 2004

Common nightingales (Luscinia megarhynchos) are among those bird species that possess an extremely large repertoire and perform it in a versatile singing style. Thereby, repertoire size, composition, and performance differs considerably among individuals. In this longitudinal field study, we investigated the long-term stability of these differences in the song characteristics of free-ranging nightingales. We determined the repertoire characteristics for nine adult male individuals in two successive years (three of these individuals were investigated over the course of three years) and compared these to similar measurements obtained from comparisons of song samples of different birds. Comparisons revealed remarkable differences among males, but we did not find systematic differences in the song performance of birds in successive years. Instead, song characteristics were remarkably stable within successive years. The long-term persistence of individual song characteristics suggests that they are not related to dynamically changing individual attributes, but may reflect long-term storage of information during song acquisition as juveniles. In addition, we found that the repertoire performance of adult nightingales allows fine-tuned vocal interactions among several neighbouring males.
The Effects of Global Economic Restructuring on Urban Women's Work and Income-Generating Strategies in Dhaka, Bangladesh
Authors: Ward Kathryn , Rahman Fahmida , Saiful Islam A.K.M. , Akhter Rifat , Kamal Nashid
Published: April 2004

This research examines women's work and shifts among factory, domestic service, sex work, and urban micro credit sectors in Bangladesh using a continuum of formal-informal-household labor. We explore women's income generating strategies and possible alternatives during global restructuring and changes in trade agreements. The end of Multi-Fibre Agreement in 2004 threatens women's garment employment and Bangladesh's dependence on garments to produce 76 percent of its export earnings.
Globalization and Regulation: The New Economy, Gender and Labor Regimes
Authors: Ng Cecilia
Published: April 2004

The paper examines, from a Southeast Asian perspective, the issues of globalization, regulation and gender and labor regimes in relation to the recent papers by Sylvia Walby (2001, 2002). The comments are linked to the conceptual debates and empirical evidence from the UK experience, which I argue, is too narrow a focus if one wants to discuss a process as broad as globalization. The paper then looks at the processes of the modernization of the gender regime and its connections to changing capital/labor relations by re-visiting the nation state, the impact of European Union regionalism and the relative power of the gender regime.
The prothrombin 3′end formation signal reveals a unique architecture that is sensitive to thrombophilic gain-of-function mutations
Authors: Danckwardt Sven , Gehring Niels H. , Neu-Yilik Gabriele , Hundsdoerfer Patrick , Pforsich Margit , Frede Ute , Hentze Matthias W. , Kulozik Andreas E.
Published: April 2004

The functional analysis of the common prothrombin 20210 G>A(F2 20210*A) mutation has recently revealed gain of function of 3′end processing as a novel genetic mechanism predisposing to human disease. We now show that the physiologic G at the cleavage site at position 20210 is the functionally least efficient nucleotide to support 3′end processing but has evolved to be physiologically optimal. Furthermore, the F2 3′end processing signal is characterized by a weak downstream cleavage stimulating factor (CstF) binding site with a low uridine density, and the functional efficiency of F2 3′end processing can be enhanced by the introduction of additional uridine residues. The recently identified thrombosis-related mutation (F2 20221*T) within the CstF binding site up-regulates F2 3′end processing and prothrombin biosynthesis in vivo. F2 20221*T thus represents the first example of a likely pathologically relevant mutation of the putative CstF binding site in the 3′flanking sequence of a human gene. Finally, we show that the low-efficiency F2 cleavage and CstF binding sites are balanced by a stimulatory upstream uridine-rich element in the 3′UTR. The architecture of the F2 3′end processing signal is thus characterized by a delicate balance of positive and negative signals. This balance appears to be highly susceptible to being disturbed by clinically relevant gain-of-function mutations. (Blood. 2004;104:428-435)
LDL oxidized by hypochlorous acid causes irreversible platelet aggregation when combined with low levels of ADP, thrombin, epinephrine, or macrophage-derived chemokine (CCL22)
Authors: Coleman Leon G. , Polanowska-Grabowska Renata K. , Marcinkiewicz Marek , Gear Adrian R. L.
Published: April 2004

The in vitro oxidation of low-density lipoprotein (LDL) by hypochlorous acid produces a modified form (HOCl-LDL) capable of stimulating platelet function. We now report that HOCl-LDL is highly effective at inducing platelet function, causing stable aggregation and α-granule secretion. Such stimulation depended on the presence of low levels of primary agonists such as adenosine diphosphate (ADP) and thrombin, or others like epinephrine (EPI) and macrophage-derived chemokine (MDC, CCL22). Agonist levels, which by themselves induced little or reversible aggregation, caused strong stable aggregation when combined with low levels of HOCl-LDL. Platelet activation by HOCl-LDL and ADP (1 μM) caused P-selectin (CD62P) exposure, without serotonin or adenosine triphosphate (ATP) secretion. Intracellular calcium levels rose slowly (from 100 to 200 nM) in response to HOCl-LDL alone and rapidly when combined with ADP to about 300 nM. p38 mitogen-activated protein kinase (MAPK) became phosphorylated in response to HOCl-LDL alone. This phosphorylation was not blocked by the protein kinase C (PKC) inhibitor bisindolylmaleimide, which reduced the extent of aggregation and calcium increase. However, the p38 MAPK inhibitor SB203580 blocked platelet aggregation and phosphorylation of p38 MAPK. These findings suggest that HOCl-LDL exposed during atherosclerotic plaque rupture, coupled with low levels of primary agonists, can rapidly induce extensive and stable thrombus formation. (Blood. 2004;104:380-389)
Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment
Authors: Huang Yiming , Rezzoug Francine , Chilton Paula M. , Grimes H. Leighton , Cramer Daniel E. , Ildstad Suzanne T.
Published: April 2004

The events that regulate engraftment and long-term repopulating ability of hematopoietic stem cells (HSCs) after transplantation are not well defined. We report for the first time that major histocompatibility complex (MHC) class I K plays a critical role in HSC engraftment via interaction with recipient natural killer (NK) cells. Durable engraftment of purified HSCs requires MHC class I K matching between HSC donor and recipient. In the absence of MHC class I K matching, HSCs exhibit impaired long-term engraftment (P = .01). Dependence on MHC class I K matching is eliminated in B6 beige mice that lack NK cell function, as well as in wild-type mice depleted of NK cells, implicating a possible regulatory role of NK cells for HSC engraftment. The coadministration of CD8+/T-cell receptor–negative (TCR-) graft facilitating cells (FCs) matched at MHC class I K to the HSC donor overcomes the requirement for MHC class I K matching between HSCs and recipient. These data demonstrate that FCs inhibit NK cell effects on the HSCs. Notably, FCs do not suppress the cytotoxic activity of activated NK cells. Enhanced green fluorescent protein–positive (EGFP+) FCs persist for one month following allogeneic transplantation, making cold target inhibition an unlikely mechanism. Therefore, MHC class I may play a critical role in the initiating events that dictate HSC engraftment and/or NK-mediated rejection following allogeneic transplantation.
Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia
Authors: Rombouts Elwin J. C. , Pavic Biljana , Löwenberg Bob , Ploemacher Rob E.
Published: April 2004

Recently it was shown that, analogous to normal hematopoietic cells, the level of CXC chemokine receptor 4 (CXCR-4) expression on acute myeloid leukemia (AML) cells correlates with stromal cell derived factor-1 alpha (SDF-1)-induced chemotaxis. As we speculated that an anomalous organ distribution of AML cells could affect cell survival and thus result in an altered fraction surviving chemotherapy, we examined a possible correlation between patient prognosis and CXCR-4 expression in AML patients. We found that patients with a high CXCR-4 expression in the CD34+ subset had a significantly reduced survival and a higher probability of relapse, resulting in a median relapse-free survival (RFS) of only 8.3 months. CXCR-4 expression was significantly higher in fetal liver tyrosine kinase-3 (Flt3)/internal tandem duplication (ITD) AML than in Flt3/wild-type (wt) AML. Covariate analysis indicated that the prognostic significance of Flt3/ITDs with respect to RFS was no more apparent when analyzed in conjunction with the expression of CXCR-4 in the CD34+ subset, suggesting that the poor prognosis of Flt3/ITD AML might be subordinate to the increased CXCR-4 expression. Using a granulocyte colony-stimulating factor receptor (G-CSF-R)-expressing 32D cell line, we observed that SDF-1/CXCR-4 interaction is required for the survival of myeloid differentiating cells, and it also induces a block in G-CSF-induced myeloid differentiation. These data suggest that the SDF-1/CXCR-4 axis may influence therapy responsiveness and defines unfavorable prognosis in AML. (Blood. 2004;104:550-557)
Experimental analysis of the performances of variable refrigerant flow systems
Authors: Xia J , Winandy E , Georges B , Lebrun J
Published: April 2004

This paper presents a testing methodology applicable to variable refrigerant flow (VRF) equipment. A test bench is presented: it consists of a set of six calorimeters, each one fully instrumented and controlled in such a way to compensate almost all combinations of sensible, latent, heating and cooling loads. This test bench is used for a three-pipe VRF system with ve indoor units and one outdoor unit. Examples of testing results are presented in the paper, in order to illustrate the methodology and also validate a simulation model. The (heating or cooling) emission of each indoor unit is identi® ed thanks to a very accurate `air’ balance inside each calorimeter. Refrigerant side (pressure and temperature) measurements are used in order to identify the refrigerant flow rate and the characteristics of the compressors (isentropic effectiveness) and of the terminal units (heat transfer coef® cients) in different regimes. Examples of global performance evaluation are also presented in the paper.
Design and simulation of a fuzzy controller for naturally ventilated buildings
Authors: Marjanovic Ljiljana , Eftekhari Mahroo
Published: April 2004

In this paper the design and validation process of a supervisory control for a single-sided naturally ventilated test room is described. The controller is based on fuzzy logic reasoning and sets of linguistic rules in the form of IF-THEN rules are used. The inputs to the controller are the outside wind speed, outside and inside temperatures. The output is the position of the opening. The basis of any fuzzy rule system is the inference engine responsible for the input's fuzzi® cation, fuzzy processing of the rule base and defuzzi® cation of the output. The choice of the inference engine, starting with the selection of input and output variables and their membership functions. Three rule bases of different complexity were developed and are presented and analysed here. Validation through simulation offers possibility of testing the controller under extreme conditions regardless of physical limitations of an experimental test cell. Simulations were performed for different typical levels of input parameters and also for extreme ctitious conditions. Simulations were carefully designed to allow simultaneous comparison of different controllers' performances. Simulation results have shown that all three controllers are capable of responding to the changes in outside conditions by adjusting the opening positions. They satisfy security requirements due to strong wind and successfully, in a stable manner respond to sudden changes in wind velocity and outdoor temperature. A controller with more membership functions and therefore a larger number of IF-THEN rules was more responsive to the changes in outside conditions.
Use of linear predictive control for a solar electric generating system
Authors: Stuetzle T , Blair N , Beckman W A , Mitchell J W
Published: April 2004

In a solar electric generating system (SEGS), it is important to maintain a specied set point for the collector outlet temperature. Currently, a skilled plant operator adjusts the volume flow rate of the heat transfer fluid circulating through the collectors to achieve this goal. In this paper, a linear model predictive controller that approximates the behaviour of the operator and that can be used to control the plant is described. The development of the plant model and controller are presented. The performance of the controller is evaluated and the influence of the control on the gross output of the plant is examined. The use of the linear model predictive controller to control building energy systems that have signi® cant capacitance and fluid time delays is discussed.
Is there anything there when there is not there? Null expletives and second language data
Authors: Oshita Hiroyuki
Published: April 2004

This article explores the issue of the psychological reality of null expletives, i.e., the silent counterparts of the so-called dummy subjects such as English it and there. Following Jackendoff’s (1997; 2002) notion of `defective’ lexical item, I define null expletives as extremely `defective’ words with syntactic properties but no semantic or phonological content. By comparing native speakers of pro-drop languages and those of topic-drop languages in terms of their grammatical judgement of and productive use of English, I argue that null expletives are very likely psychologically real to speakers of pro-drop languages but not to those of topic-drop languages. This conclusion is based on observations made in previous second language (L2) studies and the analysis of data obtained from a large corpus of nonnative English. The question of the unaccusative-unergative distinction in L2 grammar and the linguistic characterization of so-called free subject-verb inversion in pro-drop languages are also discussed in relation to the issue of the psychological reality of null expletives.
Effect of cannabinoid ingestion (in the form of bhang) on the immune system of high school and university students
Authors: EL–Gohary Mona , Eid Manal A
Published: April 2004

The discovery of cannabinoid receptors in the immune system and a family of endogenous ligands of these receptors provides a basis for understanding the cellular and molecular mechanisms of cannabis–induced immunotoxicity. The present study was conducted on 90 nonsmoker males of high school and university students living in Tanta city of matched age and socioeconomic lifetyle. They were divided into a control group (30 males) and a bhang user group (60 males), which used bhang by eating its sweet juice after boiling with a little water and drying in an oven, ‘fola’. The bhang group was divided equally into two subgroups: subgroup 1 used bhang for 6–24 months (average 199–1.2) and subgroup 2 used bhang for 24 / 36 months (average 319–1.7). The immunotoxic effects of using bhang appeared in the form of a significant decrease in serum immunoglobulins (IgG and IgM), and C3 and C4 complement protein concentrations (P<0.05). In addition, our results demonstrated a significant decrease in the absolute number of functionally different subsets of peripheral blood mononuclear lymphocytes, T and B lymphocytes and natural killer (NK) cells in bhang users as compared to controls (P<0.05). Moreover, the fatty acid amide hydrolase (FAAH) showed significant decrease in bhang users as compared to controls and in subgroup 2 as compared to subgroup 1 (P<0.05), indicating that the decrease in FAAH protein level is closely related to the duration of bhang use. Positive correlations were found between FAAH level and the absolute number of mononuclear cells (T, B lymphocytes and NK cells) among bhang user subgroups. The present study is the first study to report on the effect of bhang on complement proteins and immunoglobulins in humans. Our study revealed that bhang–induced immunotoxicity could be attributed to decrease in FAAH protein.
Risk assessment of lung cancer related to environmental PAH pollution sources
Authors: Vyskocil Adolf , Viau Claude , Camus Michel
Published: April 2004

We assessed the lung cancer risk in six localities with aluminium smelting activities and five with other polycyclic aromatic hydrocarbon (PAH) pollution sources, using two quantitative risk assessment (QRA) approaches for PAH mixtures and compared their risk predictions against actual cancer incidence. In the first approach, carcinogen exposure was estimated from animal-derived BaP toxic equivalents (BaPeq) of individual PAHs. The upper bound lifetime risk estimates ranged between 0.012-4.7×10-5 and 0.019-0.94×10-5 in the aluminium and other localities, respectively. The second approach assumed that the potency of PAH mixtures was linked to their BaP content and lifetime lung cancer unit risk gradients were estimated from epidemiological studies based on BaP exposure measurements. Lifetime risks ranged between 0.02-89×10-5 and 0.06-6.8×10-5 in the aluminium and other localities, respectively. Predicted risks were generally higher in smelter towns, and higher when based on epidemiological studies than on BaPeq. In smelting communities, there was a linear relationship (R2≈0.8) between female lung cancer rates and PAH exposure estimates. To conclude, animal/BaPeq-based QRAs predicted lower risks than occupational/BaP-based QRAs. Epidemiological validation of the QRA could be performed for elevated past exposure to PAHs, but not for currently lower concentrations.
Delayed toxicity following acute ingestion of valpromide
Authors: Payen C , Frantz P , Martin O , Parant F , Moulsma M , Pulce C , Descotes J
Published: April 2004

As valpromide is a prodrug of valproic acid (valproate), the clinical presentation of overdoses with either valpromide or valproate sodium is generally considered similar. Whereas plasma peak levels and signs of central nervous system depression occur within a few hours after the acute ingestion of regular-release forms of valproate sodium, delayed toxicity and time to peak levels following valpromide ingestion can be seen as shown by the three reported cases. They were initially considered as mild because patients presented with no or only moderate symptoms and serum valproate levels were below or at therapeutic levels on admission more than 3 hours post-ingestion in two of the three patients. Serum valproate levels were not monitored until marked deterioration more than 10 hours after ingestion. At the time of deterioration, serum valproate was at toxic level in the three reported cases. Therefore, large intake of valpromide should be closely monitored because no or moderate symptoms together with low plasma levels in the first few hours after ingestion do not exclude a subsequent severe intoxication. Despite the usual favourable outcome and the poor correlation between plasma levels and toxic symptoms, patients should not be discharged until plasma levels are documented to remain at low levels for at least 10 hours after the ingestion of valpromide and the patient asymptomatic.
SaGA S, the Short and Graphic A bility Score: an alternative scoring method for the motor components of the Multiple Sclerosis Functional C omposite
Authors: Vaney C , Vaney S , Wade D T
Published: April 2004

The timed performances of the 10-m timed walk (TMTW) and the nine-ho le peg test (NHPT) of 881 consecutive patients with multiple sclerosis (MS) undergoing a rehabilitation stay, were expressed as a logarithmic function of time in two subscores to form a composite score called the Short and G raphic A bility Score (SaGA S). The subscores (sS) were constructed in such a way that any interval of 0.5 unit corresponds to a change of 25% in the tests. The SaGA S was computed as the mean of four subscores: SaGAS=(2×2-TMTWsS+NHPTsS right hand+NHPTsS left hand). With the aid of a nomogram, the timed values of the tests are easily transformed into the corresponding subscores, which are then displayed graphically to facilitate follow-up over time. The correlation coefficients between the SaGA S and the two motor components of the MS Functional C omposite (MSFC) (r =0.987), the Expanded Disability Status Scale (EDSS)(r = -0.83), the Nottingham EADL Index (r =0.80) and the Rivermead Mobility Index (RMI) (r =0.90) were all statistically significant (P B-0.001), supporting the validity of the measure. SaGA S had a similar sensitivity to the RMI, but was significantly more sensitive than the EDSS in detecting changes occurring during the rehabilitation stay (14.9% versus 5.0%; P B-0.001) and over a one-year follow-up (35.3% versus 19.7%; P B-0.001). C ompared with the motor components of the MSFC, with which it shares several features, SaGA S has several advantages: it does not depend on the stratification of the study population; it does not skew the results of the NHPT towards improvement at the lower end; and it offers an independent assessment of both hands. SaGA S is a simple, intuitive, nonphysician-based measure, which could provide consistent scoring in future clinical trials.
Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis
Authors: Petkau A John , White Richard A , Ebers George C , Reder Anthony T , Sibley William A , Lublin Fred D , Paty Donald W ,   IFNB Multiple Sclerosis Study Group
Published: April 2004

We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NA B) assays (C PE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal appro ach, where the influence of NA Bs in individual patients is assessed by comparing responses during NAB- positive and NA B-negative periods. There are apparent influences on exacerbation rate related to dose of IFNB, titer level, and duration of positivity. With the MxA assay, exacerbation rates after switching to NA B-positive status are estimated to be 28% higher [95% confidence interval (CI): (-15%, 92%)] and -2% higher [95% CI: (-21%, 21%)] on the low- and high-dose IFNB arms, respectively. When compared with all NA B-negative periods, exacerbation rates during NA B-positive periods are estimated to be 29% higher [95% C I: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NA B-positive patients again become NA B-negative, no evidence of increased exacerbation rates could then be demonstrated. More detailed exploratory analyses indicate that the effects are most evident in the approximately 20% of patients developing high titers. In these patients, the influence of NABs may be self-limited, as titers often diminish or NA Bs become undetectable with time.
Multiple sclerosis attacks are associated with picornavirus infections
Authors: Kriesel John D , White Andrea , Hayden Frederick G , Spruance S L , Petajan Jack
Published: April 2004

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, which often follows a relapsing-remitting (RR) course with discrete attacks. MS attacks have been associated with upper respiratory infections (URIs), but the specific viruses responsible have not been identified. We studied a cohort of 16 RRMS patients experiencing URI and followed them for clinically identifiable attacks. The viral causes of 21 separate URIs were investigated using culture and polymerase chain reactio n (PCR) of nasal swab specimens, and by serology. Sibley’s ‘at-risk’ period for MS attacks, beginning two weeks before and continuing for five weeks after a URI, was used for the analysis. Seven of the nine (78%) URIs due to picornaviruses were associated with an MS attack during the at-risk period. By contrast, only two of 12 (17%) picornavirus-negative URIs were associated with an MS attack (P =0.01). The possible role of picornaviruses in the patho genesis of MS deserves further study.
What affects your MS? Responses to an anonymous, Internet-based epidemiological survey
Authors: Simmons Rex D , Ponsonby Anne-Louise , van der Mei Ingrid AF , Sheridan Peter
Published: April 2004

Evolving information techno logy has raised the possibility of new methods of data collection in multiple sclerosis (MS) research. A n anonymous, self-report, Internet-based survey was developed, which asked people with MS their opinion on how various extrinsic factors affected their condition. From September 2001 to July 2002, a total of 2529 people completed the questionnaire. The demographic and clinical profiles of the anonymous respondents indicated that most were likely to have MS. C ommon factors reported as beneficial were cannabis, cold baths, meditation and dietar y factors. C ommon adverse factors reported were high stress, exposure to high temperatures and viral infections. There was an increasing report of high temperatures as being adverse with increasing respondent age (test for trend, P B-0.001). The adverse report of high temperatures correlated significantly with the report of strong sunlight apparently making MS worse (r =0.35, P B-0.0001). In A ustralia, high temperatur es were more likely to be reported as adverse in warmer, lower latitude regions. The association between strong sunlight as adverse and age or region did not persist after adjustment for high temperatures. Thus, this apparent adverse factor appeared to relate to solar heat, not solar light. People with MS may risk vitamin D deficiency because of sun avoidance due to heat-related fatigue or intolerance. This is of clinical significance not only for bone health but because vitamin D may have beneficial immunomodulatory properties. The present study provides new information from people with MS on factors that may influence symptoms or clinical course. This information will now be used in the design of formal epidemiological cohort studies.
Caregivers of people with multiple sclerosis: experiences of support
Authors: McKeown L P , Porter-Armstrong A P , Baxter G D
Published: April 2004

The aim of this pheno menological study was to gain an understanding of the experiences of a group of caregivers of people with multiple sclerosis (MS). Sixteen caregivers from Northern Ireland and the Republic of Ireland participated in focus group interviews. The theme of support, either sought or received, emerged as a major aspect of the experiences described. C aregivers’ feelings about, and experiences of, support appeared to change over time. Four common phases that caregivers experienced in relation to support were identified as: ‘rejecting’, ‘resisting’, ‘seeking’ and ‘accepting’ support. This paper will present and discuss these four phases. The study findings highlight the complexity of issues surrounding a caregiver’s decision to seek and accept support. It is hoped that the phases identified within this study are useful in depicting how caregivers of people with MS may progress through stages in their desire for, and acceptance of, support. Findings from this study are useful to healthcare professionals who work with people with MS and their caregivers by increasing awareness that a caregiver’s attitude toward and acceptance of support changes over time.
Risk of bone loss in men with multiple sclerosis
Authors: Weinstock-Guttman Bianca , Gallagher Eileen , Baier Monika , Green Lydia , Feichter Joan , Patrick Kara , Miller Colleen , Wrest Kathleen , Ramanathan Murali
Published: April 2004

Context: O steoporosis and the increased fracture risk associated with osteoporosis become apparent in men appro ximately 10 years later than women. However, in recent studies, appro ximately 20% of healthy men in the age range 55-64 years were found to be osteopenic. Emerging data suggest a significantly increased prevalence of osteoporosis in men and women with multiple sclerosis (MS) compared to age-matched controls, but no specific clinical testing recommendations are available for men. Objective: To determine the proportion of male MS patients with osteoporosis and to identify the factors associated with the reduction in bone mass. Design: C onsecutive male MS patients seen at our MS clinic were screened with dual-X-ray absorptiometry (DEXA) scan for determining the bone mineral density (BMD). A ll patients had neurological Expanded Disability Status Scale (EDSS) evaluation. The results were compared to healthy age-matched male reference population using the Z score and to a cohort of women MS patients and women controls. C alcium, total testosterone, sex-hormone binding globulin (SHBG), 25-hydro xy-vitamin-D, and parathyroid hormone (PTH) were evaluated in male patients with decreased BMD. Relevant data on body mass index (BMI), medicatio n, alcohol consumption, smoking, and sexual dysfunction were recorded. Setting: Academic MS C entre. Patients and other participants: Forty consecutive male MS patients, age mean 51.2±8.7 years, and mean EDSS of 5.8±1.9 were evaluated with DEXA scan. O f these, 17.5% patients were relapsing - remitting (RR) MS, 57.5% were secondary progressive (SP) MS and 25% were primary progressive (PP) MS. Main outcome measure: Proportion of male MS patients with reduced BMD at the lumbar spine and femoral neck. Results: Thirty-two (80%) of our patients had a reduced bone mass of either lumbar spine or the femoral neck; of these 17 patients (42.5%) had osteopenia and 15 patients (37.5%) had osteoporosis. Twenty-o ne per cent (eight out of 38 patients) had vertebral, rib or extremities fractures. Multivariate linear regression analysis indicated that the EDSS (P B-0.0001) and BMI (P =0.0004) were the important factors associated with low BMD at the femoral neck and the EDSS was the important factor (P =0.0017) associated with low BMD at the lumbar spine. The same factors emerged as significantly associated with the corresponding Z scores, which are corrected for age and sex. No clear association between intravenous steroid therapy and BMD was evident in the multivariate analysis. Low levels of 25-hydroxy-vitamin-D were seen in 37.5% of patients. Conclusions: The proportion of male MS patients with reduced bone mass is high and disproportionate to their age and ambulation, consistent with an association between the MS disease process and patho logical bone loss. Increased awareness and bone density screening of male and female MS patients over 40 years of age is warranted.
Ethnic differences in peripheral arterial disease in the NHLBI Genetic Epidemiology Network of Arteriopathy (GENOA) study
Authors: Kullo Iftikhar J , Bailey Kent R , Kardia Sharon LR , Mosley Thomas H , Boerwinkle Eric , Turner Stephen T
Published: April 2004

Few studies have investigated whether ethnic groups differ in the prevalence of peripheral arterial disease (PAD). We compared the distribution of the ankle-brachial index (ABI), a measure of PAD, between African Americans and non-Hispanic white individuals. Subjects (n = 931) belonged to the Genetic Epidemiology Network of Arteriopathy (GENOA) study, a community-based study of hypertensive sibships, and included 453 African Americans from Jackson, Mississipi (mean age 72 6 years, 69% women) and 478 non-Hispanic white individuals from Rochester, Minnesota (mean age 58 7 years, 64% women). ABI was determined at two sites in each lower extremity and the lowest of four indices was used in the analyses. PAD was defined as an ABI of 0.95. Information about conventional risk factors was derived from interviews and from blood samples drawn at the study visit. The prevalence of diabetes and hypertension was significantly higher in African Americans than in non-Hispanic white individuals. After adjusting for age, African American subjects had a lower mean ABI (women 0.97 vs 1.04, p < 0.001; men 0.96 vs 1.12, p < 0.001) and a greater prevalence of PAD (women 34% vs 22%, p = 0.010; men 33% vs 11%, p < 0.001) than their non-Hispanic white counterparts. In multiple regression analyses, African American ethnicity was a predictor of a lower ABI and the presence of PAD in each sex after adjusting for age and other conventional risk factors. In conclusion, the lower ABI and greater prevalence of PAD in African Americans than in non-Hispanic white individuals is not explained by differences in conventional risk factors. Identifying additional ‘novel’ risk factors that account for the ethnic differences in PAD is an important next step towards understanding why such differences exist and developing more effective strategies to reduce the burden of PAD.
Marketing the ‘rain forest’: Raw Vanilla fragrance and the ongoing transformation of the jungle
Authors: Slater Candace
Published: April 2004

This article focuses on perceived differences between rain forests and jungles as reflected in marketers’ attempts to convince consumers to purchase particular ‘rainforest’ products. The author contrasts an ad for Raw Vanilla men’s cologne (‘It’s like meeting in the rainforest!’) with ads for a number of environmentally friendly products exemplified by Rainforest Crunch. To the extent that Raw Vanilla conjures up a twenty-first century jungle in rainforest garb, the cologne provides a useful jumping-off point for larger questions about present-day representations of rainforest areas.
cultural geographies in practice
Authors: Revill George
Published: April 2004

We can best understand music by being in the middle of it... the starting point must be how we (and that includes you and me) actually use, internalize, or otherwise care about music, whether by going to concerts or discos, relaxing to it in the sitting-room, or whistling it at work. It avoids prescriptive judgements inherited from another age, about what we (and that means you) ought to listen to and how. It assumes that to study music is to study your own participation in it - to study yourself...
Impact of T and N Stage and Treatment on Survival and Relapse in Adjuvant Rectal Cancer
Authors: Gunderson Leonard L. , Sargent Daniel J. , Tepper Joel E. , Wolmark Norman , O'Connell Michael J. , Begovic Mirsada , Allmer Cristine , Colangelo Linda , Smalley Steven R. , Haller Daniel G. , Martenson James A. , Mayer Robert J. , Rich Tyvin A. , Ajani Jaffer A. , MacDonald John S. , Willett Christopher G. , Goldberg Richard M.
Published: April 2004

Purpose

To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies.

Patients and Methods

Data were pooled from 3,791 eligible patients enrolled onto North Central Cancer Treatment Group (NCCTG) 79-47-51, NCCTG 86-47-51, US Gastrointestinal Intergroup 0114, National Surgical Adjuvant Breast and Bowel Project (NSABP) R01, and NSABP R02. Surgery alone (S) was the treatment arm in 179 patients. The remaining patients received adjuvant treatment as follows: irradiation (RT) alone (n = 281), RT + fluorouracil (FU) ± semustine bolus chemotherapy (CT; n = 779), RT + protracted venous infusion CT (n = 325), RT + FU ± leucovorin or levamisole bolus CT (n = 1,695), or CT alone (n = 532). Five-year follow-up was available in 94% of surviving patients, and 8-year follow-up, in 62%.

Results

Overall (OS) and disease-free survival were dependent on TN stage, NT stage, and treatment method. Even among N2 patients, T substage influenced 5-year OS (T1-2, 67%; T3, 44%; T4, 37%; P < .001). Three risk groups of patients were defined: (1) intermediate (T1-2/N1, T3/N0), (2) moderately high (T1-2/N2, T3/N1, T4/N0), and (3) high (T3/N2, T4/N1, T4/N2). For intermediate-risk patients, those receiving S plus CT had 5-year OS rates of 85% (T1-2/N1) and 84% (T3/N0), which was similar to results with S plus RT plus CT (T1-2/N1, 78% to 83%; T3/N0, 74% to 80%). For moderately high-risk lesions, 5-year OS ranged from 43% to 70% with S plus CT, and 44% to 80% with S plus RT plus CT. For high-risk lesions, 5-year OS ranged from 25% to 45% with S plus CT, and 29% to 57% with S plus RT plus CT.

Conclusion

Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement.
Forkhead L2 Is Expressed in the Ovary and Represses the Promoter Activity of the Steroidogenic Acute Regulatory Gene
Authors: Pisarska Margareta D. , Bae Jeehyeon , Klein Cynthia , Hsueh Aaron J. W.
Published: April 2004

Premature ovarian failure in a subgroup of women with blepharophimosis-ptosis-epicanthus inversus type 1 syndrome has been associated with nonsense mutations in the gene encoding a Forkhead transcription factor, Forkhead L2 (FOXL2). However, the exact function of FOXL2 in the ovary is unclear. We investigated the expression of FOXL2 in the mouse ovary during follicular development and maturation by RT-PCR and in situ hybridization. The FOXL2 mRNA is expressed in ovaries throughout development and adulthood and is localized to the undifferentiated granulosa cells in small and medium follicles as well as cumulus cells of preovulatory follicles. FOXL2 belongs to a group of transcription factors capable of interacting with specific DNA sequences in diverse gene promoters. With the presence of multiple putative forkhead DNA consensus sites, the promoter of the human steroidogenic acute regulatory (StAR) gene was used to test for regulation by FOXL2. Cotransfection studies revealed that wild-type FOXL2 represses the activity of the StAR promoter, and the first 95 bp upstream of the transcriptional start site of the StAR gene is sufficient for FOXL2 repression. EMSAs confirmed that FOXL2 interacts directly with this region. Analyses using FOXL2 mutants also demonstrated the importance of the entire alanine/proline-rich carboxyl terminus of FOXL2 for transcriptional repression. Furthermore, these mutations produce a protein with a dominant-negative effect that disables the transcriptional repressor activity of wild-type FOXL2. Dominant-negative mutations of FOXL2 could increase expression of StAR and other follicle differentiation genes in small and medium follicles to accelerate follicle development, resulting in increased initial recruitment of dormant follicles and thus the premature ovarian failure phenotype.
Neuropeptide Y Is Required for Hyperphagic Feeding in Response to Neuroglucopenia
Authors: Sindelar Dana K. , Ste. Marie Linda , Miura Grant I. , Palmiter Richard D. , McMinn Julie E. , Morton Gregory J. , Schwartz Michael W.
Published: April 2004

To investigate the role played by the orexigenic peptide, neuropeptide Y (NPY), in adaptive responses to insulin-induced hypoglycemia, we measured hypothalamic, feeding, and hormonal responses to this stimulus in both wild-type (Npy+/+) and NPY-deficient (Npy−/−) mice. After administration of insulin at a dose (60 mU ip) sufficient to cause moderate hypoglycemia (plasma glucose levels, 40 ± 3 and 37 ± 2 mg/dl for Npy+/+ and Npy−/− mice, respectively; P = not significant), 4-h food intake was increased 2.5-fold in Npy+/+ mice relative to saline-injected controls. By comparison, the increase of intake in Npy−/− mice was far smaller (45%) and did not achieve statistical significance (P = 0.08). Hyperphagic feeding in response to insulin-induced hypoglycemia was therefore markedly attenuated in mice lacking NPY, and a similar feeding deficit was detected in these animals after neuroglucopenia induced by 2-deoxyglucose (500 mg/kg ip). A role for NPY in glucoprivic feeding is further supported by our finding that Npy mRNA content (measured by real-time PCR) increased 2.4-fold in the hypothalamus of Npy+/+ mice by 7 h after insulin injection. Unlike the feeding deficits observed in mice lacking NPY, the effect of hypoglycemia to increase plasma glucagon and corticosterone levels was fully intact in these animals, as were both the nadir glucose value and time to recovery of euglycemia after insulin injection (P = not significant). We conclude that NPY signaling is required for hyperphagic feeding, but not neuroendocrine responses to moderate hypoglycemia.
Absorption of taurocholic acid by the ileum of normal and transgenic ΔF508 cystic fibrosis mice
Authors: Hardcastle J , Harwood M D , Taylor C J
Published: April 2004

Changes in intestinal transport in cystic fibrosis (CF) include both defective Cl− secretion and alterations in absorption. This study focused on the effects of CF on the active re-absorption of bile acids in the ileum of normal and transgenic CF mice. Taurocholic acid absorption was monitored as changes in short-circuit current (SCC) in intact and stripped ileal sheets from normal (Swiss) and transgenic CF (Cftrtm2Cam) mice with the ΔF508 mutation. Taurocholic acid uptake was measured directly in everted ileal sacs and in brush-border membrane vesicles (BBMVs) using radiolabelled bile acid. Taurocholic acid caused a biphasic increase in SCC in both intact and stripped ileal sheets from Swiss mice. The initial phase of the response was associated with active bile acid absorption as it was inhibited by a low mucosal Na+ concentration, but unaffected by Cl−-free conditions, serosal furosemide or mucosal diphenylamine-2-carboxylic acid (DPC). The first phase was concentration-dependent and was reduced in the presence of other actively transported bile acids. Intact ileal sheets from wild-type Cftrtm2Cam mice also exhibited a biphasic SCC response to taurocholic acid, but in CF tissues the initial phase was reduced and the second phase was absent. Taurocholic acid was actively taken up by everted ileal sacs from Swiss mice. This process was inhibited by a low mucosal Na+ concentration or the presence of other actively transported bile acids. A similar taurocholic acid uptake was observed in ileal sacs from wild-type mice, but in those from CF mice transport of the bile acid was significantly reduced. However, taurocholic acid uptake was similar in BBMVs from wildtype and CF ilea. Active absorption of taurocholic acid occurs in mouse ileum and this process is reduced in transgenic mouse models of CF with the ΔF508 mutation. However, this difference cannot be detected in an isolated preparation of brush-border membranes.