bluuebunny/crossref_metadata_2025 huggingface dataset:
Heritabilities and quantitative trait loci for blood gases and blood pH in swine
Authors: Reiner G. , Fischer R. , Köhler F. , Berge T. , Hepp S. , Willems H.
Published: December 2008

Maintaining pH and blood gases in a narrow range is essential to sustain normal biochemical reactions. Decreased oxygenation, poor tissue perfusion, disturbance to CO2 expiration, and shortage of HCO3− can lead to metabolic acidosis. This is a common situation in swine, and originates from a broad range of medical conditions. pH and blood gases appear to be under genetic control, and populations with physiological traits closer to the pathological thresholds may be more susceptible to developing pathological conditions. However, little is known about the genetic basis of such traits. We have therefore estimated phenotypic and genetic variability and identified quantitative trait loci (QTL) for pH and blood gases in blood samples from 139 F2 pigs from the Meishan/Pietrain family. Samples were taken before and after challenge with Sarcocystis miescheriana, a protozoan parasite of muscle. Twenty‐seven QTL influencing pH and blood gases were identified on nine chromosomes. Five of the QTL were significant on a genome‐wide level; 22 QTL were significant on a chromosome‐wide level. QTL for pH‐associated traits have been mapped to SSC3, 18 and X. QTL associated with CO2 have been detected on SSC6, 7, 8 and 9, and QTL associated with O2 on SSC2 and SSC8. QTL showed specific health/disease patterns that were related to the physiological state of the pigs from day 0, to acute disease (day 14), convalescence (day 28) and chronic disease (day 42). The results demonstrate that pH and blood gases are influenced by multiple chromosomal areas, each with relatively small effects.
Pain on injection with microemulsion propofol
Authors: Sim Ji‐Yeon , Lee Soo‐Han , Park Do‐Yang , Jung Jin‐Ah , Ki Kyoung‐Ho , Lee Dong‐Ho , Noh Gyu‐Jeong
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Aqueous free propofol in lipid emulsion elicits pain.

• No data on the incidence and severity of injection pain for Aquafol™ (Daewon Pharmaceutical Co., Ltd, Seoul, Korea), a lipid‐free microemulsion propofol, are available.

• Two hypotheses involving plasma bradykinin generation have been proposed to explain propofol‐induced pain; one implicates aqueous free propofol, the other implicates the lipid solvent.

WHAT THIS STUDY ADDS

• Microemulsion propofol produces more frequent and severe pain on injection, an effect that may be attributable to the high concentration of aqueous free propofol.

• There was no evidence that plasma bradykinin generation caused propofol‐induced pain.

• In addition, agents known to prevent propofol‐induced pain did not decrease aqueous free propofol concentrations.

AIMS

To evaluate the incidence and severity of injection pain caused by microemulsion propofol and lipid emulsion propofol in relation to plasma bradykinin generation and aqueous free propofol concentrations.

METHODS

Injection pain was evaluated in 147 patients. Aqueous free propofol concentrations in each formulation, and in formulation mixtures containing agents that reduce propofol‐induced pain, were measured by high‐performance liquid chromatography. Plasma bradykinin concentrations in both formulations and in their components mixed with blood sampled from six volunteers were measured by radioimmunoassays. Injection pain caused by 8% polyethylene glycol 660 hydroxystearate (PEG660 HS) was evaluated in another 10 volunteers.

RESULTS

The incidence of injection pain [visual analogue scale (VAS) >30 mm] caused by microemulsion and lipid emulsion propofol was 69.7 and 42.3% (P < 0.001), respectively. The median VAS scores for microemulsion and lipid emulsion propofol were 59 and 24 mm, respectively (95% confidence interval for the difference 12.5, 40.0). The aqueous free propofol concentration of microemulsion propofol was seven times higher than that of lipid emulsion propofol. Agents that reduce injection pain did not affect aqueous free propofol concentrations. Microemulsion propofol and 8% PEG660 HS enhanced plasma bradykinin generation, whereas lipid emulsion propofol and lipid solvent did not. PEG660 HS did not cause injection pain.

CONCLUSIONS

Higher aqueous free propofol concentrations of microemulsion propofol produce more frequent and severe pain. The plasma kallikrein–kinin system may not be involved, and the agents that reduce injection pain may not act by decreasing aqueous free propofol concentrations.
A hybrid fast algorithm for first arrivals tomography
Authors: Mendes Manuela
Published: December 2008

A hybrid algorithm, combining Monte‐Carlo optimization with simultaneous iterative reconstructive technique (SIRT) tomography, is used to invert first arrival traveltimes from seismic data for building a velocity model. Stochastic algorithms may localize a point around the global minimum of the misfit function but are not suitable for identifying the precise solution. On the other hand, a tomographic model reconstruction, based on a local linearization, will only be successful if an initial model already close to the best solution is available. To overcome these problems, in the method proposed here, a first model obtained using a classical Monte Carlo‐based optimization is used as a good initial guess for starting the local search with the SIRT tomographic reconstruction. In the forward problem, the first‐break times are calculated by solving the eikonal equation through a velocity model with a fast finite‐difference method instead of the traditional slow ray‐tracing technique. In addition, for the SIRT tomography the seismic energy from sources to receivers is propagated by applying a fast Fresnel volume approach which when combined with turning rays can handle models with both positive and negative velocity gradients. The performance of this two‐step optimization scheme has been tested on synthetic and field data for building a geologically plausible velocity model.This is an efficient and fast search mechanism, which permits insertion of geophysical, geological and geodynamic a priori constraints into the grid model and ray path is completed avoided. Extension of the technique to 3D data and also to the solution of ‘static correction’ problems is easily feasible.
Variable shifts in spring and autumn migration phenology in North American songbirds associated with climate change
Authors: VAN BUSKIRK JOSH , MULVIHILL ROBERT S. , LEBERMAN ROBERT C.
Published: December 2008

Monitoring studies find that the timing of spring bird migration has advanced in recent decades, especially in Europe. Results for autumn migration have been mixed. Using data from Powdermill Nature Reserve, a banding station in western Pennsylvania, USA, we report an analysis of migratory timing in 78 songbird species from 1961 to 2006. Spring migration became significantly earlier over the 46‐year period, and autumn migration showed no overall change. There was much variation among species in phenological change, especially in autumn. Change in timing was unrelated to summer range (local vs. northern breeders) or the number of broods per year, but autumn migration became earlier in neotropical migrants and later in short‐distance migrants. The migratory period for many species lengthened because late phases of migration remained unchanged or grew later as early phases became earlier. There was a negative correlation between spring and autumn in long‐term change, and this caused dramatic adjustments in the amount of time between migrations: the intermigratory periods of 10 species increased or decreased by > 15 days. Year‐to‐year changes in timing were correlated with local temperature (detrended) and, in autumn, with a regional climate index (detrended North Atlantic Oscillation). These results illustrate a complex and dynamic annual cycle in songbirds, with responses to climate change differing among species and migration seasons.
Climate change at the landscape scale: predicting fine‐grained spatial heterogeneity in warming and potential refugia for vegetation
Authors: ASHCROFT MICHAEL B. , CHISHOLM LAURIE A. , FRENCH KRISTINE O.
Published: December 2008

Current predictions of how species will respond to climate change are based on coarse‐grained climate surfaces or idealized scenarios of uniform warming. These predictions may erroneously estimate the risk of extinction because they neglect to consider spatially heterogenous warming at the landscape scale or identify refugia where species can persist despite unfavourable regional climate. To address this issue, we investigated the heterogeneity in warming that has occurred in a 10 km × 10 km area from 1972 to 2007. We developed estimates by combining long‐term daily observations from a limited number of weather stations with a more spatially comprehensive dataset (40 sites) obtained during 2005–2006. We found that the spatial distribution of warming was greater inland, at lower elevations, away from streams, and at sites exposed to the northwest (NW). These differences corresponded with changes in weather patterns, such as an increasing frequency of hot, dry NW winds. As plant species were biased in the topographic and geographic locations they occupied, these differences meant that some species experienced more warming than others, and are at greater risk from climate change. This species bias could not be detected at coarser scales. The uneven seasonal nature of warming (e.g. more warming in winter, minimums increased more than maximums) means that climate change predictions will vary according to which predictors are selected in species distribution models. Models based on a limited set of predictors will produce erroneous predictions when the correct limiting factor is not selected, and this is difficult to avoid when temperature predictors are correlated because they are produced using elevation‐sensitive interpolations. The results reinforce the importance of downscaling coarse‐grained (∼50 km) temperature surfaces, and suggest that the accuracy of this process could be improved by considering regional weather patterns (wind speed, direction, humidity) and topographic exposure to key wind directions.
Climatic changes and 13‐year trends in stream macroinvertebrate assemblages in New South Wales, Australia
Authors: CHESSMAN BRUCE C.
Published: December 2008

Over the period from 1994 to 2007, air and water temperatures in the Australian state of New South Wales (NSW) increased while rainfall and river flows declined. Data on the occurrence of stream macroinvertebrate families in bioassessment samples collected in NSW during this period were examined to see whether a biological response to these climatic and hydrological trends could be discerned. Multiple logistic regression was used to test for long‐term trends in the probability of detection of individual macroinvertebrate families within the samples, taking account of the latitude, longitude, altitude, hydraulic habitat, time of year and subsampling method associated with each sample. Of the 124 families and family groups tested, 33 had statistically significant increasing trends, 37 had significantly declining trends and 54 had no significant trend; however, many of the last group were seldom collected and their trend estimates had wide confidence limits. Significant relationships were found between the thermophily and rheophily of the families and the estimated strength and direction of their long‐term trends, with families that favour colder waters and faster‐flowing habitats more likely to have declined. Although many families showed trends of increasing detection within samples, such trends do not necessarily equate to increasing prevalence in the environment because the extent of wetted habitat has probably declined, especially flowing habitat. In addition, because of likely intrafamilial trait diversity, increasing or apparently increasing families may include species in decline. Many freshwater macroinvertebrate species in NSW may be threatened by anthropogenic climate change, exacerbated by water withdrawals. The thermal tolerances, rheophily and other pertinent traits of individual species need to be determined to identify those most at risk.
Effects of landscape and history on diversification of a montane, stream‐breeding amphibian
Authors: Koscinski Daria , Yates Adam G. , Handford Paul , Lougheed Stephen C.
Published: December 2008

Aim  The aim of this study was to understand the roles of landscape features in shaping patterns of contemporary and historical genetic diversification among populations of the Andean tree frog (Hypsiboas andinus) across spatial scales.

Location  Andes mountains, north‐western Argentina, South America.

Methods  Mitochondrial DNA control region sequences were utilized to assess genetic differentiation among populations and calculate population pair‐wise genetic distances. Three models of movement, namely traditional straight‐line distance and two effective distances based on habitat classification, were examined to determine which of these explained the most variation in pair‐wise population genetic differentiation. The two habitat classifications were based on digital vegetation and hydrology layers that were generated from a 90‐m resolution digital elevation model (DEM) and known relationships between elevation and habitat. Mantel tests were conducted to test for correlations between geographic and genetic distance matrices and to estimate the percentage variation explained by each type of geographic distance. To investigate the location of possible barriers to gene flow, we used Monmonier’s maximum difference algorithm as implemented in barrier 2.2.

Results  At both geographic scales, effective distances explained more variation in genetic differentiation than did straight‐line distance. The least‐cost distances based on the simple classification performed better than the more detailed habitat classification. We controlled for the effects of historical range fragmentation determined from previous nested clade analyses, and therefore evaluated the effect of different distances on the genetic variation attributable to more recent factors. Effective distances identified populations that were highly divergent as a result of isolation in unsuitable habitats. The proposed locations of barriers to gene flow identified using Monmonier’s maximum difference algorithm corresponded well with earlier analyses and supported findings from our partial Mantel tests.

Main conclusions  Our results indicate that landscape features have been important in both historical and contemporary genetic structuring of populations of H. andinus at both large and small spatial scales. A landscape genetic perspective offers novel insights not provided by traditional phylogeographic studies: (1) effective distances can better explain patterns of differentiation in populations, especially in heterogeneous landscapes where barriers to dispersal may be common; and (2) least‐cost path analysis can help to identify corridors of movement between populations that are biologically more realistic.
Stress and coping in older people with Alzheimer’s disease
Authors: de Souza‐Talarico Juliana Nery , Chaves Eliane Corrêa , Nitrini Ricardo , Caramelli Paulo
Published: December 2008

Aim. To investigate stress intensity and coping style in older people with mild Alzheimer’s disease.

Background. The potential risk assessment of a stress event and the devising of coping strategies are dependent on cognitive function. Although older individuals with Alzheimer’s disease present significant cognitive impairment, little is known about how these individuals experience stress events and select coping strategies in stress situations.

Design. Survey.

Method. A convenient sample of 30 cognitively healthy older people and 30 individuals with mild Alzheimer’s disease were given an assessment battery of stress indicators (Symptom Stress List, Cornell Scale for Depression in Dementia, State‐Trait Anxiety Inventory), coping style (Jalowiec Coping Scale) and cognitive performance (mini‐mental state exam) were applied in both groups. Statistical analysis of the data employed the Mann–Whitney test to compare medians of stress indicators and coping style, Fischer’s exact test to compare proportions when expected frequencies were lower than five, and Spearman’s correlation coefficient to verify correlation between coping style and cognitive performance.

Results. Both groups suffered from the same stress intensity (p = 0·254). Regarding coping styles, although differences were not statistically significant (p = 0·124), emotion‐oriented coping was predominant in the patients with Alzheimer’s disease. However, those individuals displaying better cognitive performance in the Alzheimer’s disease group had selected coping strategies focused on problem solving (p = 0·0074).

Conclusions. Despite a tendency for older people with Alzheimer’s disease to select escape strategies and emotional control, rather than attempting to resolve or lesser the consequences arising from a problem, coping ultimately depends on cognitive performance of the individual.

Relevance to clinical practice. The findings of this study provide information and data to assist planning of appropriate support care for individuals with Alzheimer’s disease who experience stress situations, based on their cognitive performance.
Malnutrition in a home‐living older population: prevalence, incidence and risk factors. A prospective study
Authors: Johansson Yvonne , Bachrach‐Lindström Margareta , Carstensen John , Ek Anna‐Christina
Published: December 2008

Aims and objectives.  To prospectively investigate and describe the prevalence and incidence of malnutrition among home‐living older people, related to demographic and medical factors, self‐perceived health and health‐related quality of life. Another aim was to find predictors for developing risk of malnutrition.

Background.  Risk factors for malnutrition have previously been identified as diseases, several medications, low functional status, symptoms of depression and inadequate nutrient intake. Most studies are cross‐sectionally performed at hospitals or in nursing care settings.

Design.  A prospective study with a sample of 579 home‐living older people, randomly selected from a local national register. Examinations were performed at baseline and yearly follow‐ups two to four times.

Method.  Questionnaires validated and tested for reliability, to detect risk of malnutrition (Mini Nutritional Assessment), symptoms of depression (Geriatric Depression Scale‐20), cognitive function (Mini Mental State Examination), health‐related quality of life (Nottingham Health Profile), well‐being (Philadelphia Geriatric Center Multilevel Assessment Instrument) self‐perceived health, demographic factors, anthropometry and biochemical examinations. Predictors were searched for through multiple logistic regression analysis with the MNA as dependent factor.

Results.  The prevalence of risk for malnutrition was 14·5%, according to the MNA. Two risk factors for malnutrition were lower handgrip strength and lower self‐perceived health. The incidence of risk for malnutrition at follow‐ups was between 7·6% and 16·2%. Predictors for developing malnutrition were higher age, lower self‐perceived health and more symptoms of depression. Men with symptoms of depression had a higher risk of developing malnutrition.

Conclusion.  Lower self‐perceived health had the highest power to predict risk for malnutrition, with increased number of depression symptoms and higher age as second and third predictors.

Relevance to clinical practice.  A regular and combined assessment using the Mini Nutrition Assessment, Geriatric Depression Scale‐20 and self‐perceived health as a base for identifying people in need, is one way to prevent the development of malnutrition.
Verbal, visual, and spatio‐sequential short‐term memory: assessment of the storage capacities of children and teenagers with Down's syndrome
Authors: Frenkel S. , Bourdin B.
Published: December 2008

Background  It is recognized that individuals with Down's syndrome have a specific deficit in verbal short‐term memory. On the other hand, non‐verbal short‐term memory seems to be preserved or even be a strong point for these persons. Nevertheless, the extent and specificity of the deficit must be determined. To do so, we carried out a research programme that allowed us to simultaneously assess various short‐term memory systems in a developmental perspective, and to compare our participants' performance to that obtained by typically developing individuals of the same mental age.

Method  Three span tasks are used (auditory word span/visual patterns test/Corsi blocks task) with 54 children and teenagers with Down's syndrome and 54 typically developing children as control group. Participants were matched according to their cognitive level.

Results  For the auditory word span task, participants with Down's syndrome obtained performances significantly lower than those of the typically developing participants. On the other hand, compared with typically developing children, children and teenagers with Down's syndrome have a spatio‐sequential span significantly higher for the lowest developmental ages. No significant differences were found for visual span.

Conclusions  Individuals with Down's syndrome exhibited a distinctive pattern of memory performance, in addition to their developmental specificities.
The documentation of health problems in relation to prescribed medication in people with profound intellectual and multiple disabilities
Authors: Van Der Heide D. C. , Van Der Putten A. A. J. , Van Den Berg P. B. , Taxis K. , Vlaskamp C.
Published: December 2008

Background  Persons with profound intellectual and multiple disabilities (PIMD) suffer from a wide range of health problems and use a wide range of different drugs. This study investigated for frequently used medication whether there was a health problem documented in the medical notes for the drug prescribed.

Method  Persons with PIMD with an estimated intelligence quotient of 25 and profound or severe motor disorders were studied. Data on health problems were taken from medical notes and prescribing data were obtained from pharmacies. Data covering 1 year were analysed. For four therapeutic areas (anticonvulsants, laxatives, drugs for peptic ulcer and gastro‐oesophageal reflux disease and psycholeptics), we determined whether we could find an indication for prescribed medication.

Results  Some 254 persons with PIMD (46% male, 54% female; median age 49 years, range 6–82) from eight residential facilities participated. Some 226 participants (89%) were prescribed medication over the course of 1 year. An indication for the prescribed medication was documented for 92% (n = 130) (95% confidence interval 88–96%) of 141 participants on anticonvulsants, for 68% (n = 112) (61–75%) of 165 participants on laxatives, for 44% (n = 58) (36–52%) of 132 participants on drugs for peptic ulcer and gastro‐oesophageal reflux disease, and for 89% (n = 102) (83–95%) of 115 participants on psycholeptic drugs.

Conclusions  The best level of documentation was found for anticonvulsants the worst for drugs for peptic ulcer and gastro‐oesophageal reflux disease. Lack of documenting an indication may be due to off‐label use, inadvertent continuation of no longer indicated medication, inadequate documentation and underdiagnosis. Adequate documentation practices are essential because of the communication problems that are characteristic for persons with PIMD.
FIERY1 regulates light‐mediated repression of cell elongation and flowering time via its 3′(2′),5′‐bisphosphate nucleotidase activity
Authors: Kim Byung‐Hoon , Von Arnim Albrecht G.
Published: December 2008

Light is one of the most important environmental factors that regulate plant development. Here we report that a mutation in the Arabidopsis FIERY1 gene (FRY1) caused a shortened hypocotyl and shorter petioles, most dramatically under low‐intensity red light and less pronounced under far‐red and blue‐light conditions. Furthermore, the fry1 mutant flowered late, probably due to a reduced level of FLOWERING LOCUS T (FT) transcript. However, although the transcript level of FRY1 was light‐regulated, the chlorophyll level and the expression of typical light‐regulated genes were not affected in the fry1 mutant. FRY1 is known as a regulator of abiotic stress responses, and its protein product has dual enzymatic activity comprising inositol polyphosphate‐1‐phosphatase and 3′(2′),5′‐bisphosphate nucleotidase activity. Genetic complementation data obtained using cDNA of the FRY1 paralog AHL (Arabidopsis HAL2‐like) and the similar phenotype of an xrn2/xrn3 double mutant suggest that FRY1 attenuates light responses via its 3′(2′),5′‐bisphosphate nucleotidase activity rather than its inositol polyphosphate‐1‐phosphatase activity. We discuss the relationship between the FRY1‐associated nucleotidase activity, a step in the pathway for sulfur metabolism and utilization, and the Arabidopsis light response.
Gibberellin controls the nodulation signaling pathway in Lotus japonicus
Authors: Maekawa Takaki , Maekawa‐Yoshikawa Makoto , Takeda Naoya , Imaizumi‐Anraku Haruko , Murooka Yoshikatsu , Hayashi Makoto
Published: December 2008

Root nodule formation is regulated by several plant hormones, but the details of the regulation of the nodulation signaling pathway are largely unknown. In this study, the role of gibberellin (GA) in the control of root nodule symbiosis was investigated at the physiological and genetic levels in Lotus japonicus. Exogenous application of biologically active GA, GA3, inhibited the formation of infection threads and nodules, which was counteracted by the application of a biosynthesis inhibitor of GA, Uniconazole P. Nod factor‐induced root hair deformation was severely blocked in the presence of GA, which was phenocopied by nsp2 mutants. The number of spontaneous nodules triggered by the gain‐of‐function mutation of calcium/calmodulin‐dependent kinase (CCaMK) or the lotus histidine kinase 1 (LHK1) was decreased upon the addition of GA; moreover, the overexpression of the gain‐of‐function mutation of L. japonicus, SLEEPY1, a positive regulator of GA signaling, resulted in a reduced nodule number, without other aspects of root development being affected. These results indicate that higher GA signaling levels specifically inhibit the nodulation signaling pathway. Nod factor‐dependent induction of NSP2 and NIN was inhibited by exogenous GA. Furthermore, the cytokinin‐dependent induction of NIN was suppressed by GA. From these results, we conclude that GA inhibits the nodulation signaling pathway downstream of cytokinin, possibly at NSP2, which is required for Nod factor‐dependent NIN expression. These results clarify the roles of GA in the nodulation signaling pathway, and in relation to the cytokinin signaling pathway for nodulation in L. japonicus.
NRAMP genes function in Arabidopsis thaliana resistance to Erwinia chrysanthemi infection
Authors: Segond Diego , Dellagi Alia , Lanquar Viviane , Rigault Martine , Patrit Oriane , Thomine Sébastien , Expert Dominique
Published: December 2008

AtNRAMP3 and AtNRAMP4 are two Arabidopsis metal transporters sharing about 50% sequence identity with mouse NRAMP1. The NRAMP1/Slc11A1 metal ion transporter plays a crucial role in the innate immunity of animal macrophages targeted by intracellular bacterial pathogens. AtNRAMP3 and AtNRAMP4 localize to the vacuolar membrane. We found that AtNRAMP3 is upregulated in leaves challenged with the bacterial pathogens Pseudomonas syringae and Erwinia chrysanthemi, whereas AtNRAMP4 expression is not modified. Using single and double nramp3 and nramp4 mutants, as well as lines ectopically expressing either of these genes, we show that AtNRAMP3 and, to a lesser extent, AtNRAMP4 are involved in Arabidopsis thaliana resistance against the bacterial pathogen E. chrysanthemi. The susceptibility of the double nramp3 nramp4 mutant is associated with the reduced accumulation of reactive oxygen species and ferritin (AtFER1), an iron storage protein known to participate in A. thaliana defense. Interestingly, roots from infected plants accumulated transcripts of AtNRAMP3 as well as the iron‐deficiency markers IRT1 and FRO2. This finding suggests the existence of a shoot‐to‐root signal reminiscent of an iron‐deficiency signal activated by pathogen infection. Our data indicate that the functions of NRAMP proteins in innate immunity have been conserved between animals and plants.
Resetting and regulation of FLOWERING LOCUS C expression during Arabidopsis reproductive development
Authors: Choi Jean , Hyun Youbong , Kang Min‐Jeong , In Yun Hye , Yun Jae‐Young , Lister Clare , Dean Caroline , Amasino Richard M. , Noh Bosl , Noh Yoo‐Sun , Choi Yeonhee
Published: December 2008

The epigenetic regulation of the floral repressor FLOWERING LOCUS C (FLC) is one of the critical factors that determine flowering time in Arabidopsis thaliana. Although many FLC regulators, and their effects on FLC chromatin, have been extensively studied, the epigenetic resetting of FLC has not yet been thoroughly characterized. Here, we investigate the FLC expression during gametogenesis and embryogenesis using FLC::GUS transgenic plants and RNA analysis. Regardless of the epigenetic state in adult plants, FLC expression disappeared in gametophytes. Subsequently, FLC expression was reactivated after fertilization in embryos, but not in the endosperm. Both parental alleles contributed equally to the expression of FLC in embryos. Surprisingly, the reactivation of FLC in early embryos was independent of FRIGIDA (FRI) and SUPPRESSOR OF FRIGIDA 4 (SUF4) activities. Instead, FRI, SUF4 and autonomous‐pathway genes determined the level of FLC expression only in late embryogenesis. Many FLC regulators exhibited expression patterns similar to that of FLC, indicating potential roles in FLC reprogramming. An FVE mutation caused ectopic expression of FLC in the endosperm. A mutation in PHOTOPERIOD‐INDEPENDENT EARLY FLOWERING 1 caused defects in FLC reactivation in early embryogenesis, and maintenance of full FLC expression in late embryogenesis. We also show that the polycomb group complex components, Fertilization‐Independent endosperm and MEDEA, which mediate epigenetic regulation in seeds, are not relevant for FLC reprogramming. Based on our results, we propose that FLC reprogramming is composed of three phases: (i) repression in gametogenesis, (ii) reactivation in early embryogenesis and (iii) maintenance in late embryogenesis.
The impact of primary health care on malaria morbidity – defining access by disease burden
Authors: O’Meara W. P. , Noor A. , Gatakaa H. , Tsofa B. , McKenzie F. E. , Marsh K.
Published: December 2008

Objectives  Primary care facilities are increasingly becoming the focal point for distribution of malaria intervention strategies, but physical access to these facilities may limit the extent to which communities can be reached. To investigate the impact of travel time to primary care on the incidence of hospitalized malaria episodes in a rural district in Kenya.

Methods  The incidence of hospitalized malaria in a population under continuous demographic surveillance was recorded over 3 years. The time to travel to the nearest primary health care facility was calculated for every child between birth and 5 years of age and trends in incidence of hospitalized malaria as a function of travel time were evaluated.

Results  The incidence of hospitalized malaria more than doubled as travel time to the nearest primary care facility increased from 10 min to 2 h. Good access to primary health facilities may reduce the burden of disease by as much as 66%.

Conclusions  Our results highlight both the potential of the primary health care system in reaching those most at risk and reducing the disease burden. Insufficient access is an important risk factor, one that may be inequitably distributed to the poorest households.
Total serum IgE levels are associated with ambient ozone concentration in asthmatic adults
Authors: Rage E. , Jacquemin B. , Nadif R. , Oryszczyn M.‐P. , Siroux V. , Aguilera I. , Kauffmann F. , Künzli N. ,   on behalf of the Epidemiological Study on the Genetics Environment of Asthma (EGEA)
Published: December 2008

Background:  Effects of air pollution exposure on IgE‐mediated response in asthmatics are poorly investigated. The aim was to examine the relationship between air pollution concentrations and total IgE levels in adult asthmatics.

Methods:  The present study relates to the 369 asthmatic adults from the French Epidemiological study on Genetics and Environment of Asthma (EGEA), with availability of data on both total serum IgE measurements and air pollution concentrations. Geo‐statistical models were performed on 4 × 4 km grids to assess individual outdoor air pollution exposure. Annual outdoor concentrations of ozone (O3), nitrogen dioxide (NO2), sulphur dioxide (SO2), and particulate matter smaller than 10 μm size (PM10), and concentrations of summer ozone were assigned to subject’s home address.

Results:  The geometric mean of total IgE was 161 IU/ml and the average of O3 exposure was 44.9 ± 9.5 μg/m3. Ozone concentrations were positively related to total IgE levels and an increase of 10 μg/m3 of O3 resulted in an increase of 20.4% (95% CI = 3.0–40.7) in total IgE levels. Adjustment for age, gender, smoking habits and previous life in the countryside did not change the results, and an increase of 19.1% (2.4–38.6) in total IgE was observed with O3. Negative associations observed between NO2 and total IgE levels disappeared after including O3 in the models. Neither SO2 nor PM10 were correlated with total IgE levels.

Conclusions:  Results suggest that O3 or related ambient pollutants may up‐regulate total IgE levels among asthmatic adults.
Clinical relevance of sensitization to lupine in peanut‐sensitized adults
Authors: Peeters K. A. B. M. , Koppelman S. J. , Penninks A. H. , Lebens A. , Bruijnzeel‐Koomen C. A. F. M. , Hefle S. L. , Taylor S. L. , Van Hoffen E. , Knulst A. C.
Published: December 2008

Background:  The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut‐allergic patients. The frequency and the degree of cross‐reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanut‐sensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double‐blind placebo‐controlled food challenges (DBPCFC).

Methods:  Thirty‐nine unselected peanut‐sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy.

Results:  Eighty‐two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found.

Conclusion:  In peanut‐sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only fivefold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness.
Expression of osteopontin in chronic rhinosinusitis with and without nasal polyps
Authors: Lu X. , Zhang X. H. , Wang H. , Long X. B. , You X. J. , Gao Q. X. , Cui Y. H. , Liu Z.
Published: December 2008

Background:  Osteopontin (OPN) is a multifunctional 34‐kDa extracellular matrix protein that can influence the inflammatory process. However, the presence of OPN in human sinonasal mucosa and its roles in the inflammatory process of chronic rhinosinusitis (CRS) are not clear. This study investigated the expression of OPN in human sinonasal mucosa, its cytokine‐driven expression regulation, and its effect on cytokine production in sinonasal mucosa.

Methods:  Surgical samples were investigated by means of quantitative reverse transcriptase polymerase chain reaction for evaluation of OPN messenger RNA (mRNA) expression, and the presence and location of OPN protein expression were analyzed using immunohistochemistry. Furthermore, nasal explant culture was used to investigate the mutual regulatory interactions between interferon (IFN)‐γ, interleukin (IL)‐4, IL‐5, IL‐13, IL‐1β, and tumor necrosis factor (TNF)‐α and OPN in sinonasal mucosa.

Results:  Osteopontin expression was significantly upregulated in CRS tissues compared with control tissues. There was a further significant increase of OPN expression in patients with nasal polyps (NPs) and asthma. Immunohistochemistry revealed positive staining of OPN in epithelial cells, submucosal glands, infiltrating cells, and extracellular matrix. Osteopontin mRNA was induced by IFN‐γ, IL‐1β, and TNF‐α, but inhibited by IL‐4 and IL‐13. On the contrary, OPN induced IFN‐γ, IL‐4, IL‐5, IL‐13, IL‐1β, and TNF‐α production in sinonasal mucosa.

Conclusions:  The expression of OPN is upregulated in CRS. The mutual regulatory interactions between OPN and inflammatory cytokines suggest that OPN may play an important role in the pathogenesis of CRS.
Impact of peanut allergy on quality of life, stress and anxiety in the family
Authors: King R. M. , Knibb R. C. , Hourihane J. O’B.
Published: December 2008

Background:  Peanut allergy (PA) is known to impact on quality of life (QoL) of the sufferer, but little research has focused on all family members. We therefore sought to establish the impact of PA on QoL and reported anxiety of children with clinically confirmed PA, their parents and older siblings.

Methods:  Forty‐six families, who had a child with PA, completed QoL (PedsQLTM or WHOQOL‐BREF), anxiety (SCAS or STAI) and perceived stress (PSS) scales. PA children completed a PA specific QoL questionnaire (Pediatr Allergy Immunol 2003;14:378). Parents and sibling also completed QoL proxy questionnaires for the PA child (PedsQLTM, Pediatr Allergy Immunol 2003;14:378).

Results:  Mothers rated their own psychological (P < 0.01) and physical (P < 0.05) QoL significantly worse than fathers rated theirs, and had higher scores than fathers for anxiety (P < 0.05) and stress (P < 0.001). Children with PA had significantly poorer physical health‐related QoL (P < 0.05), QoL within school (P < 0.01) and general QoL (P < 0.05) than their siblings did, and greater separation anxiety (P < 0.05). The majority of differences were between girls with PA and female siblings. Mothers felt that there was a greater impact on QoL for their PA child, compared with that reported by siblings, fathers or the PA children themselves (P < 0.01).

Conclusions:  Mothers report that they have significantly poorer QoL and suffer more anxiety and stress than fathers do; this inter‐parental difference may be an important feature of family stress caused by PA. Siblings have a similar view of how QoL affects the PA child as the PA child does, while mothers may possibly overestimate this impact.
Ten‐year progress report of the International Cell Exchange
Authors: Loon J. , Takemura S. , Terasaki P. I.
Published: December 2008

For the past 10 years, the International Cell Exchange has been a useful tool for testing rare and unusual HLA antigens and monitoring the progress in detection of recognized specificities. Of special interest are the antigens proposed in the 8th Workshop — 8w57, 8w58, 8w59, and 8w66. Marked improvement could be seen in the detection of 8w59 (29%) and 8w66 (31%). Possible new variants of the A9 and A10 complexes were tested in several exchanges. As shown by the increasing yearly average percentages of detection, laboratories are improving in their ability to type Aw23, Aw24, A25, A26, A29; Bw39, Bw41, Bw54, Bw55, Bw57, Bw58, Bw60 and Bw62. Over 90% of the laboratories are now able to detect Aw24; B5, B17, and B40, and A29 has attained the status of being well defined.
Third order linkage disequilibrium*
Authors: Thomson Glenys , Baur Max P.
Published: December 2008

For third order linkage disequilibrium there is a constraint on the maximum value the disequilibrium can take, given pairwise disequilibria values and allele frequencies. As distinct from second order disequilibrium (considered in the context of a two locus model) there is also in some cases a constraint on the minimum value. The appropriate procedures to determine these maximum and minimum values are given, as well as numerical values utilizing HLA data.
Factors responsible for successful HLA‐DR typing of mononuclear cells from cord blood
Authors: Radvany Ruta M. , Patel Kantilal M. , Duria Rosalinda F. , Lee Ae Za , Remendado Ines O. , Andersen Rhonda L. , Hsieh Yin S.
Published: December 2008

Of 115 cord blood samples tested, both HLA‐DR antigens were identified in 79% of fresh samples, 66% of older samples and 55% of freshly frozen samples. Because of weak reactions, one or two questionable antigens were present in 21% of fresh samples as compared to 34% of older samples and 45% of freshly frozen samples. Older samples showed lower cell viability, more extra reactions, and a high frequency of weak reactions. Comparison of cord blood DR antigens with parental DR antigens revealed that antigens were missed or inappropriately assigned in 5 known cases. This was more frequent with older blood samples. The critical factors in successful DR typing of cord blood samples were 1) dilution of cord blood samples with medium, 2) processing of the samples as soon as possible, and 3) overnight incubation to remove adherent cells.

We are grateful to Drs. Rose Payne, Angenie‐ta Biegel, Helen Bashir, Rene Duquesnoy, Helene Mervart, John Hansen, Paul Reekers, Ieke Schroeder and Paul Terasaki and NIH Serum Bank for their gifts of typing sera; the faculty of the Department of Obstetrics and Gynecology at Northwestern University and the Maternity Ward patients who permitted us to collect and use post‐pregnancy sera as tissue typing reagents.

We also wish to thank Mrs. Donna Wilson for expert assistance in preparing this manuscript.
HLA antigen associations with extra‐articular rheumatoid arthritis
Authors: Ollier W. , Venables P. J. W. , Mumford P. A. , Maini R. N. , Awad J. , Jaraquemada D. , D'Amaro J. , Festenstein H.
Published: December 2008

Seventy‐seven patients with rheumatoid arthritis were investigated to examine the frequency of HLA antigens and their relationship to clinical and serological manifestations of extra‐articular disease. The phenotype frequencies of DR4, DRw53, Bw62 and Cw3 were significantly increased, compared to normal controls, and there were negative associations with DR2 and DR7. The HLA antigen in strongest association with rheumatoid arthritis was DR4 (73.6%) and the relationship with DRw53 appeared to be secondary. The frequency of DR4 rose to 92% in seropositive patients with extra‐articular disease manifestations whose serum contained immune complexes. A high frequency of DR4 was also seen in male patients (86%), reaching 100% in the small group of seropositive male patients with immune complexes. It is suggested that extra‐articular disease represents a manifestation of severe classical rheumatoid arthritis and is not an ‘overlap’syndrome. We propose that the HLA haplotype Cw3‐Bw62‐Dw4‐DR4‐DRw53 makes a greater genetic contribution to disease susceptibility in both extra‐articular and male rheumatoid arthritis patients than in other subsets of RA.
HLA antigens in Japanese patients with narcolepsy
Authors: Juji Takeo , Satake Masahiro , Honda Yutaka , Doi Yuko
Published: December 2008

A surprisingly high association between an HLA‐DR locus antigen and narcolepsy was revealed in the Japanese. All 40 Japanese patients with narcolepsy (22 males and 18 females) were confirmed to be DR2 positive. However, the DR2 of the patients was found to associate negatively with Bw52, whereas Bw52‐DR2 is the commonest haplotype in normal Japanese population. These data suggested that a “disease” allele predisposing to narcolepsy was inherited with relatively rare haplotypes with DR2 in the Japanese.
HLA alleles in the population of Cartagena (Colombia)
Authors: Caraballo Luis R. , Marrugo G. Javier , Erlich C. Henry , Mildred Pastorizo L.
Published: December 2008

Abstract: It is known from historical records that the population of Cartagena (Colombia) is a mixture of caucasoids (Spaniards) and negroids (Africans) that is named mulattos. The present study was carried out to determine the distribution of HLA antigens in this population. A sample of 370 individuals was HLA serologically typed; 91 of them were typed for Complement alleles and 47 were DNA typed using PCR amplification and oligonucleotide probes for the HLA‐DQAI locus. The analysis of the allele and haplotype frequencies obtained, together with the genetic distances calculated with other populations, showed that most of the HLA genes of mulattos are from negroids and Caucasoids. The Asian and Amerindian contribution is small, consistent with the historical and socio‐anthropological documentation. For example, A23, Aw34, Aw36 and Bw45, as well as DQA1*0101, DQA1*0301 and BfF have frequencies similar to that observed in negroids. In contrast, many significant differences were observed when comparing the antigen and allele frequencies of mulattos with that of Asians and Amerindians. Our results add evidence to the notion that the arrival of Spaniards in America 500 years ago established several racial mixtures. The HLA characterization of one of these, mulattos, will allow a better application of the HLA technology in the fields of basic research, organ transplantation and forensic medicine among this population.
HLA‐DQA1 and MLC among HLA (generic)‐identical unrelated individuals
Authors: Yunis Iván , Salazar Marcela , Alosco Sharon M. , Gomex Natalia , Yunis Edmond J.
Published: December 2008

Abstract: We modified a previously published PCR‐RFLP for DQA1 typing (1) and examined the predictive value of HEA‐DQA1 in mixed lymphocyte cultures (MLC) among matched (HLA generic types) pairs of unrelated individuals. There were 61/102 (60%) pairs with positive MLC, one‐third of which could be predicted by DQA1* typing alone. DQA1 matching and MLC reactions were classified into 3 groups: 1) DQA1 mismatches showing positive MLC: 19/102 (19%); 2) DQA1 matches showing negative MLC: 41/102 (40%); 3) DQA1 identical showing positive MLC: 42/102 (41%). Five different HLA haplotypes that result from non‐random association of HLA generic types (high delta haplotypes) were overrepresented in the individuals tested. One of these haplotypes carrying HLA‐B7, DR2 was found associated with three different DQA1 alleles (*0201, *0103, *0102). The remaining four high delta haplotypes were associated with one DQA1 allele in all independent examples tested: HLA‐A1, B8, DR3 with DQA1*0501; HLA‐A26, B38, DR4 with DQA 1*0301; HLA‐A2, Bw62, DR4 with DQA1*0301 and HLA‐AI, Bw57, DR7 with DQA1*0201. Forty per cent of the negative MLC were explained in part by the excessive number of individuals carrying two of these four haplotypes, which probably carry determinants in linkage disequilibrium with HLA. Nineteen per cent of HLA‐identical (generic types) unrelated pairs show positive MLC reactions and all of them are DQA1* mismatched, suggesting that DQA1* allele typing should be used to screen samples prior to performing MLC.