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Large Variability (large + variability)
Selected AbstractsBreast cancer survivors in the United StatesCANCER, Issue 9 20092005-201, Geographic Variability, Time Trends Abstract BACKGROUND: Breast cancer continues to place a significant burden on the healthcare system. Regional prevalence measures are instrumental in the development of cancer control policies. Very few population-based cancer registries are able to provided local, long-term incidence and follow-up information that permits the direct calculation of prevalence. Model-based prevalence estimates are an alternative when this information is lacking or incomplete. The current work represents a comprehensive collection of female breast cancer prevalence from 2005 to 2015 in the United States and the District of Columbia (DC). METHODS: Breast cancer prevalence estimates were derived from state-specific cancer mortality and survival data using a statistical package called the Mortality-Incidence Analysis Model or MIAMOD. Cancer survival models were derived from the Surveillance, Epidemiology, and End Results Program data and were adjusted to represent state-specific survival. Comparisons with reported incidence for 39 states and DC had validated estimates. RESULTS: By the year 2010, 2.9 million breast cancer survivors are predicted in the US, equaling 1.85% of the female population. Large variability in prevalent percentages was reported between states, ranging from 1.4% to 2.4% in 2010. Geographic variability was reduced when calculating age-standardized prevalence proportions or cancer survivors by disease duration, including 0 to 2 years and 2 to 5 years. The residual variability in age-adjusted prevalence was explained primarily by the state-specific, age-adjusted breast cancer incidence rates. State-specific breast cancer survivors are expected to increase from 16% to 51% in the decennium from 2005 to 2015 and by 31% at the national level. CONCLUSIONS: To the authors' knowledge, the current study is the first to provide systematic estimations of breast cancer prevalence in all US states through 2015. The estimated levels and time trends were consistent with the available population-based data on breast cancer incidence, prevalence, and population aging. Cancer 2009. © 2009 American Cancer Society. [source] Temporal and spatial variations in periglacial soil movements on alpine crest slopesEARTH SURFACE PROCESSES AND LANDFORMS, Issue 1 2005Norikazu Matsuoka Abstract This paper describes up to ten years of continuous monitoring of frost heave, creep and associated parameters on high mountain crest slopes in the Japanese and Swiss Alps, aiming to evaluate spatial and interannual variations in the rates and controls of soil movement. Shallow frost creep re,ecting diurnal frost heave activity dominates the crest slopes that lack a vegetation mat and have a thin debris mantle with good drainage. Seasonal frost heave activity can induce slightly deeper movement where ,ne soil exists below the depth reached by diurnal freeze,thaw penetration, although the shallow bedrock impedes movements below 20 cm depth. As a result, downslope velocity pro,les display strong concavity with surface velocities of 2,50 cm a,1. The frost creep rates vary spatially, depending on the soil texture, slope gradient, frequency of temperature cycling across 0 °C and moisture availability during freeze,thaw periods. Soil movements recur in every freeze,thaw period, although with some interannual variations affected by the length of seasonal snow cover and the occurrence of precipitation during freeze,thaw periods. The Swiss Alps encounter more signi,cant interannual variations than the Japanese Alps, re,ecting the large variability of the annual snow regime. Copyright © 2005 John Wiley & Sons, Ltd. [source] Interdemic variation of cannibalism in a wolf spider (Pardosa monticola) inhabiting different habitat typesECOLOGICAL ENTOMOLOGY, Issue 2 2006Jeroen Vanden Borre Abstract., 1.,Cannibalism was investigated in the wolf spider Pardosa monticola (Clerck) using spiders collected from four populations with varying densities, inhabiting two different coastal dune habitat types. Sampled individuals were paired randomly and tested immediately for their cannibalism propensity. 2.,The occurrence of cannibalism was found to be influenced by the size (cephalothorax width) of both the smaller and the larger spider of a pair. Larger size differences enhanced cannibalism. 3.,Cannibalism rates were not significantly different in spiders from high-density compared with low-density populations. Cannibalism rates showed, however, large variability between habitat types, with higher rates in spiders from dune grasslands than from dune slacks. This is suggested to result from differences in prey availability throughout the growing season between both habitat types. 4.,Different size classes of spiders did not use different microhabitats, indicating that microhabitat segregation as a cannibalism-avoidance behaviour is absent in this species. [source] Full scale experiments for evaluating theoretical fire wall modelsFIRE AND MATERIALS, Issue 6 2004P. Clancy Abstract The aim of the research described in this paper was to provide experimental results for the evaluation of theoretical models for predicting the behaviour and time-to-failure of loadbearing and non-loadbearing wood framed walls in fire. References for thermal and mechanical properties of wood and gypsum board are given to provide comprehensive input for the evaluation of theoretical wall models. The scope of the research involved full-scale uninsulated cavity walls with well-controlled clearly known conditions including initial ambient vertical load capacity for benchmarking the reduction in capacity and stiffness, rotational stiffness of supports, eccentricity of vertical load, elastic moduli of wood and gypsum board in compression, stiffness of slip between gypsum board and studs and end stud effects. The experiments were repeated and they demonstrated that the controls led to high consistency in the results despite the inherent large variability of the mechanical properties of wood. The results include temperature distributions, initial vertical load capacity, load-deflection plots and times-to-failure. The results show that the temperatures in the studs are approximately uniform until all the moisture is vaporized. Thermal properties of wood will not vary significantly for consistent density, moisture content and species of wood. The main structural actions that should be modelled for different loading regimes are deduced. Copyright © 2004 John Wiley & Sons, Ltd. [source] Copepod life cycle adaptations and success in response to phytoplankton spring bloom phenologyGLOBAL CHANGE BIOLOGY, Issue 6 2009HANNO SEEBENS Abstract In a seasonal environment, the timing of reproduction is usually scheduled to maximize the survival of offspring. Within deep water bodies, the phytoplankton spring bloom provides a short time window of high food quantity and quality for herbivores. The onset of algal bloom development, however, varies strongly from year to year due to interannual variability in meteorological conditions. Furthermore, the onset is predicted to change with global warming. Here, we use a long-term dataset to study (a) how a cyclopoid copepod, Cyclops vicinus, is dealing with the large variability in phytoplankton bloom phenology, and (b) if bloom phenology has an influence on offspring numbers. C. vicinus performed a two-phase dormancy, that is, the actual diapause of fourth copepodid stages at the lake bottom is followed by a delay in maturation, that is, a quiescence, within the fifth copepodid stage until the start of the spring bloom. This strategy seems to guarantee a high temporal match of the food requirements for successful offspring development, especially through the highly vulnerable naupliar stages, with the phytoplankton spring bloom. However, despite this match with food availability in all study years, offspring numbers, that is, offspring survival rates were higher in years with an early start of the phytoplankton bloom. In addition, the phenology of copepod development suggested that also within study years, early offspring seems to have lower mortality rates than late produced offspring. We suggest that this is due to a longer predator-free time period and/or reduced time stress for development. Hence, within the present climate variability, the copepod benefited from warmer spring temperatures resulting in an earlier phytoplankton spring bloom. Time will show if the copepod's strategy is flexible enough to cope with future warming. [source] Pharmacokinetics of factor VIII and factor IXHAEMOPHILIA, Issue 2003M. Morfini Summary., A survey of principal pharmacokinetic (PK) studies on factor VIII (FVIII) and factor IX (FIX) plasma- and rDNA-derived concentrates, analysed by means of the PKRD program, has been performed. Notwithstanding the accurate definition of the study design, released in 1991 by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (SSC-ISTH), a large variability of PK parameters has been pointed out. In the majority of the PK studies, the size of the population is small. In this situation, a careful individualization of haemophilia therapy is strongly recommended. The tailored prediction of loading and maintenance dosages and the need for strict control of trough FVIII/IX levels are mandatory not only to decrease the risk of bleeds but also to spare financial resources. Recently, the old problem of FVIII assay standardization has again become a concern among physicians, especially after the introduction of B-domain deleted rFVIII concentrate. The discrepancies between the widely used one-stage clotting assay and the chromogenic substrate assay seem to be solved by the introduction of a product-specific laboratory standard. [source] Novel tools for extraction and validation of disease-related mutations applied to fabry disease,HUMAN MUTATION, Issue 9 2010Remko Kuipers Abstract Genetic disorders are often caused by nonsynonymous nucleotide changes in one or more genes associated with the disease. Specific amino acid changes, however, can lead to large variability of phenotypic expression. For many genetic disorders this results in an increasing amount of publications describing phenotype-associated mutations in disorder-related genes. Keeping up with this stream of publications is essential for molecular diagnostics and translational research purposes but often impossible due to time constraints: there are simply too many articles to read. To help solve this problem, we have created Mutator, an automated method to extract mutations from full-text articles. Extracted mutations are crossreferenced to sequence data and a scoring method is applied to distinguish false-positives. To analyze stored and new mutation data for their (potential) effect we have developed Validator, a Web-based tool specifically designed for DNA diagnostics. Fabry disease, a monogenetic gene disorder of the GLA gene, was used as a test case. A structure-based sequence alignment of the alpha-amylase superfamily was used to validate results. We have compared our data with existing Fabry mutation data sets obtained from the HGMD and Swiss-Prot databases. Compared to these data sets, Mutator extracted 30% additional mutations from the literature. Hum Mutat 31:1026,1032, 2010. © 2010 Wiley-Liss, Inc. [source] Differential toxicity on monocytes and monocyte-derived dendritic Cells: a new tool to differentiate allergens from irritants?INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2007Laetitia Furio Phenotypic activation of monocyte-derived dendritic cells has been proposed as an in vitro alternative assay to discriminate potential sensitizers from irritants, but the sensitivity of the assay remains controversial. In this study, we first determined the dynamic range of expression of activation/maturation markers on human monocyte-derived dendritic cells cultured in the presence or absence of transforming growth factor ß (TGF,)? On day three of culture, most monocytes had already differentiated into dendritic cells that expressed low levels of costimulatory molecules especially in the presence TGF,-treatment of 3-day-old TGF,-treated monocyte-derived dendritic cells with several chemicals at sub-toxic concentrations induced significant phenotypic changes for all the strong and mild sensitizers tested, whereas the irritant sodium lauryl sulfate had no effect. However, a very large variability was observed among the experiments. Most interestingly, we could show here for the first time that at concentrations sub-toxic for monocyte-derived dendritic cells all the allergens tested induced monocyte apoptosis within 2 days of culture. In contrast, sodium lauryl sulfate displayed similar toxicity on monocytes and monocyte-derived dendritic cells and these results were confirmed with other irritants such as benzoic acid or methylsalicylate. Although testing of far more chemicals is required, these results indicate that differential toxicity of chemicals to monocytes and monocyte-derived dendritic cells could be a rapid, simple and valuable tool to differentiate sensitizers from irritants. [source] Architectural properties of the first dorsal interosseous muscleJOURNAL OF ANATOMY, Issue 4 2010Benjamin W. Infantolino Abstract Muscle architecture is considered to reflect the function of muscle in vivo, and is important for example to clinicians in designing tendon-transfer and tendon-lengthening surgeries. The purpose of this study was to quantify the architectural properties of the FDI muscle. It is hypothesized that there will be consistency, that is low variability, in the architectural parameters used to describe the first dorsal interosseous muscle because of its clear functional role in index finger motion. The important architectural parameters identified were those required to characterize a muscle adequately by modeling. Specifically the mass, cross-sectional area, and length of the tendon and muscle were measured in cadavers along with the muscle fiber optimum length and pennation angle, and the moment arm of the first dorsal interosseous at the metacarpophalangeal joint. These parameters provide a characterization of the architecture of the first dorsal interosseous, and were used to indicate the inherent variability between samples. The results demonstrated a large amount of variability for all architectural parameters measured; leading to a rejection of the hypothesis. Ratios designed to describe the functioning of the muscles in vivo, for example the ratio of tendon to fiber optimum lengths, also demonstrated a large variability. The results suggest that function cannot be deduced from form for the first dorsal interosseous, and that subject-specific architectural parameters may be necessary for the formulation of accurate musculoskeletal models or making clinical decisions. [source] Recovery from bark harvesting of 12 medicinal tree species in Benin, West AfricaJOURNAL OF APPLIED ECOLOGY, Issue 3 2009Claire Delvaux Summary 1The growing interest in medicinal plants from both international industry and local markets requires management of tree bark harvesting from natural forests in order to prevent inappropriate exploitation of target species. This study was designed to determine the bark re-growth response of a selected number of medicinal tree species as a basis for the development of an optimal bark harvesting method. 2In 2004, bark was harvested from 925 trees belonging to 12 species in 38 sites in a dry forest in Benin, West Africa. Two years later, the response of trees to bark harvesting was examined with respect to re-growth (edge or sheet), development of vegetative growth around the wound, and the sensitivity of the wound to insect attack. 3Two species, Khaya senegalensis and Lannea kerstingii, showed complete wound recovery by edge growth. At the other extreme, Afzelia africana, Burkea africana and Maranthes polyandra had very poor edge growth. M. polyandra showed good sheet growth, whereas the other 11 species had none or poor sheet growth after total bark harvesting. In contrast, partial bark removal allowed better sheet growth in all 12 species studied. 4Insect sensitivity was species-specific. Insect attacks were negatively correlated with non-recovered wound area, but there was a marked species effect for the same rate of regeneration. L. kerstingii and K. senegalensis had very good and similar re-growth, but L. kerstingii was very susceptible to insect attack, whereas K. senegalensis appeared to be very resistant. Only a few individuals developed vegetative growth, and each tree usually developed only one or two agony shoots, but there was no significant difference between species. 5Synthesis and applications. This is the first study to provide data on the ability of trees to close wounds after bark harvesting in West Africa. We report large variability in the response of different species to our bark harvesting technique, and identify just two out of the 12 study species as suitable for sustainable bark harvesting. Based on our results, we developed a decisional step method to help forest managers select the best techniques for managing medicinal tree species as an alternative to bark harvesting, for example, coppice management, harvesting leaves instead of bark, stand establishment, and collaboration with timber companies. [source] Water Framework Directive: ecological classification of Danish lakesJOURNAL OF APPLIED ECOLOGY, Issue 4 2005MARTIN SØNDERGAARD Summary 1The European Water Framework Directive (WFD) requires that all European waterbodies are assigned to one of five ecological classes, based primarily on biological indicators, and that minimum good ecological quality is obtained by 2015. However, the directive provides only general guidance regarding indicator definitions and determination of boundaries between classes. 2We used chemical and biological data from 709 Danish lakes to investigate whether and how lake types respond differently to eutrophication. In the absence of well-defined reference conditions, lakes were grouped according to alkalinity and water depth, and the responses to eutrophication were ordered along a total phosphorus (TP) gradient to test the applicability of pre-defined boundaries. 3As a preliminary classification we suggest a TP-based classification into high, good, moderate, bad and poor ecological quality using 0,25, 25,50, 50,100, 100,200 and > 200 µg P L,1 boundaries for shallow lakes, and 0,12·5, 12·5,25, 25,50, 50,100 and > 100 µg P L,1 boundaries for deep lakes. Within each TP category, median values are used to define preliminary boundaries for the biological indicators. 4Most indicators responded strongly to increasing TP, but there were only minor differences between low and high alkalinity lakes and modest variations between deep and shallow lakes. The variability of indicators within a given TP range was, however, high, and for most indicators there was a considerable overlap between adjacent TP categories. Cyanophyte biomass, submerged macrophyte coverage, fish numbers and chlorophyll a were among the ,best' indicators, but their ability to separate different TP classes varied with TP. 5When using multiple indicators the risk that one or more indicators will indicate different ecological classes is high because of a high variability of all indicators within a specific TP class, and the ,one out , all out' principle in relation to indicators does not seem feasible. Alternatively a certain compliance level or a ,mean value' of the indicators can be used to define ecological classes. A precise ecological quality ratio (EQR) using values between 0 and 1 can be calculated based on the extent to which the total number of indicators meets the boundary conditions, as demonstrated from three Danish lakes. 6Synthesis and applications. The analysis of Danish lakes has identified a number of useful indicators for lake quality and has suggested a method for calculating an ecological quality ratio. However, it also demonstrates that the implementation of the Water Framework Directive faces several challenges: gradual rather than stepwise changes for all indicators, large variability of indicators within lake classes, and problems using the one out , all out principle for lake classification. [source] Impact of shade on the spatial distribution of Sahlbergella singularis in traditional cocoa agroforestsAGRICULTURAL AND FOREST ENTOMOLOGY, Issue 1 2010Régis Babin 1Shade management is commonly considered to be an effective pest management strategy for cocoa mirids, yet shade management recommendations are not based on extensive knowledge of the mirid ecology in traditional cocoa agroforests. 2The main objectives of the present study were an assessment of the impact of shade on the spatial distribution of mirid populations and thus the evaluation of shade management strategies. 3Mirid densities were measured and shade was characterized for three plots located in three different agroecological zones in the Centre region of Cameroon. Mirid densities generally followed a negative binomial law. Geostatistical procedures were used to characterize spatial distribution of mirid density. Light conditions were assessed using hemispherical photography. 4Populations of Sahlbergella singularis were highly aggregated in the plots. Semivariance analysis and kriging visualized the spatial dependence of mirid densities. Clearly distinguishable mirid pockets of 20,30 adjacent infested cocoa trees were identified in two of the three plots. 5The high diversity of shade tree species and the large variability in density and size of shade trees resulted in a considerable heterogeneity of plot light conditions. Percentage transmitted light varied in the range 9.4,80.1% in the most heterogeneous plot. 6For two of the three plots, mirid pockets were aggregated in those areas where light transmission was highest. In the third plot, relatively high mirid densities and the presence of an alternative host resulted in a more homogeneous distribution. The importance of these findings for improved mirid control is discussed. [source] Effects of alternative instrumentation strategies in adolescent idiopathic scoliosis: A biomechanical analysisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2009Martin Robitaille Abstract The recent advent of modern instrumentation systems has improved the correction of scoliosis, but complicated the surgical decision-making process, especially with the introduction of diverse spinal fixation devices, new preoperative corrective maneuvers, and the reevaluation of many rules concerning the selection of fusion levels and other guidelines for surgical correction. Our objective was to assess the biomechanical effects of different instrumentation strategies for the same scoliotic cases. Several instrumentation strategies suggested by a group of 32 experienced senior surgeons for five cases were individually simulated using a validated computer model implemented in a spine surgery simulator. The resulting geometric indices varied among the five cases (e.g., range of main thoracic Cobb angles: 5,17°, 16,29°, 25,44°, 15,34°, 16,32°; kyphosis: 22,33°, 20,54°, 33,55°, 24,49°, 29,46°; and lordosis: 10,52°, 24,38°, 26,54°, 8,28°, 34,53°). The average correction was better with pedicle screws (71%) than with hooks (51%) and hybrid constructs (67%). For the first time, to our knowledge, the effect of different instrumentation strategies was compared on the same patients, which is possible only with a surgery simulator. A large variability of instrumentation strategies existed among experienced surgeons and produced rather different results. This study questions the criteria for optimal configuration and standards to design the best surgical construct. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:104,113, 2009 [source] Effect of Implant Angulation upon Retention of Overdenture AttachmentsJOURNAL OF PROSTHODONTICS, Issue 1 2005MSEd, MSciDent, Michael P. Gulizio DMD Introduction: Overdentures supported and retained by endosteal implants depend upon mechanical components to provide retention. Ball attachments are frequently described because of simplicity and low cost, but retentive capacity of these components may be altered by a lack of implant parallelism. Purpose: The aim of this in vitro study was to investigate the retention of gold and titanium overdenture attachments when placed on ball abutments positioned off-axis. Methods and Materials: Four ball abutments were hand-tightened onto ITI dental implants and placed in an aluminum fixture that allowed positioning of the implants at 0°, 10°, 20°, and 30° from a vertical reference axis. Gold and titanium matrices were then coupled to the ball abutments at various angles and then subjected to pull tests at a rate of 2 mm/second; the peak loads of release (maximum dislodging forces) were recorded and subjected to statistical analyses. A balanced and randomized factorial experimental design testing procedure was implemented. Results: Statistically significant differences in retention of gold matrices were noted when ball abutments were positioned at 20° and 30°, but not at 0° and 10°. Statistically significant differences were noted among the titanium matrices employed for the testing procedure, as well as for the 4 ball abutments tested. Angle was not a factor affecting retention for titanium matrices. Conclusions: (1) The gold matrices employed for the testing procedures exhibited consistent values in retention compared to titanium matrices, which exhibited large variability in retention. (2) Angle had an effect upon the retention of gold matrices, but not for titanium matrices. [source] CLIMATE CHHANGE SENSITIVITY ASSESSMENT ON UPPER MISSISSIPPI RIVER BASIN STREAMFLOWS USING SWAT,JOURNAL OF THE AMERICAN WATER RESOURCES ASSOCIATION, Issue 4 2006Manoj Jha ABSTRACT: The Soil and Water Assessment Tool (SWAT) model was used to assess the effects of potential future climate change on the hydrology of the Upper Mississippi River Basin (UMRB). Calibration and validation of SWAT were performed using monthly stream flows for 1968,1987 and 1988,1997, respectively. The R2 and Nash-Sutcliffe simulation efficiency values computed for the monthly comparisons were 0.74 and 0.69 for the calibration period and 0.82 and 0.81 for the validation period. The effects of nine 30-year (1968 to 1997) sensitivity runs and six climate change scenarios were then analyzed, relative to a scenario baseline. A doubling of atmospheric CO2 to 660 ppmv (while holding other climate variables constant) resulted in a 36 percent increase in average annual streamflow while average annual flow changes of ,49, ,26, 28, and 58 percent were predicted for precipitation change scenarios of ,20, ,10, 10, and 20 percent, respectively. Mean annual streamflow changes of 51,10, 2, ,6, 38, and 27 percent were predicted by SWAT in response to climate change projections generated from the CISRO-RegCM2, CCC, CCSR, CISRO-Mk2, GFDL, and HadCMS general circulation model scenarios. High seasonal variability was also predicted within individual climate change scenarios and large variability was indicated between scenarios within specific months. Overall, the climate change scenarios reveal a large degree of uncertainty in current climate change forecasts for the region. The results also indicate that the simulated UMRB hydrology is very sensitive to current forecasted future climate changes. [source] Motor evoked potentials from the pelvic floorNEUROUROLOGY AND URODYNAMICS, Issue 7 2003Søren Brostrøm Proper function of the lower urinary tract depends on the integrity of the central and peripheral nervous pathways on multiple levels, and the complexity of this system leaves it susceptible to even minor lesions. While dysfunction of the lower urinary tract is prevalent amongst patients with nervous system disease, e.g., multiple sclerosis (MS), most women with lower urinary tract dysfunction (LUTD) have no overt neurological cause. Refined neuro-diagnostic approaches are needed to reveal neurogenicity in these patients. A potential method is transcranial magnetic stimulation (TMS), which is used routinely to test the motor innervation of limb muscles, but also can be applied to test pelvic floor efferents. To resolve the lack of methodological clarity and the need for normative values for the use of pelvic floor motor evoked potentials (MEPs), 30 healthy women and 16 women with MS were studied. Methods The healthy women underwent MEP studies with various stimulus and recording modalities, and, to test reproducibility, 18 of them were retested at a separate session. The women with MS underwent MEP testing as well as urodynamic studies. Results From the methodological studies of healthy women, the use of invasive concentric needle electrodes was found to be superior to surface electrodes. When applying magnetic stimuli over the sacral region, various methodological problems were encountered. In the healthy women, a large variability of responses was noted, the long-term reproducibility of pelvic floor MEP latencies was poor, and in some cases responses could not be obtained. In the study of women with MS, prolonged central conduction times were found, along with many cases of unevokable responses, and a poor correlation of MEPs to urodynamic findings. The problems of obtaining selective recordings from the inaccessible pelvic floor musculature are discussed, and possible sources of variability in MEPs from the pelvic floor are considered. By relating the findings in the present studies to those of others using different modalities, some reflections are presented on the nature of the neural pathways to the pelvic floor activated by magnetic stimulation. As unevokable responses from the pelvic floor were an occasional finding among the healthy women, it is argued that a pelvic floor non-response in a patient with suspected corticospinal lesion should be interpreted with care, and should not carry the same clinical significance as an absent limb response. Conclusions The inherent limitations of pelvic floor MEPs are discussed, and it is concluded that while there seems to be only limited clinical value of pelvic floor MEP testing, there might be some interesting scientific perspectives in studies that aim to control and explain the variability of responses. Neurourol. Urodynam. 22:620,637, 2003. © 2003 Wiley-Liss, Inc. [source] Pharmacokinetics of valerenic acid after single and multiple doses of valerian in older womenPHYTOTHERAPY RESEARCH, Issue 10 2010Gail D. Anderson Abstract Insomnia is a commonly reported clinical problem with as many as 50% of older adults reporting difficulty in falling and/or remaining asleep. Valerian (Valeriana officinalis) is a commonly used herb that has been advocated for promoting sleep. Valerenic acid is used as a marker for quantitative analysis of valerian products with evidence of pharmacological activity relevant to the hypnotic effects of valerian. The objective of this study was to determine the pharmacokinetics of valerenic acid in a group of elderly women after receiving a single nightly valerian dose and after 2 weeks of valerian dosing. There was not a statistically significant difference in the average peak concentration (Cmax), time to maximum concentration (Tmax) area under the time curve (AUC), elimination half-life (T1/2) and oral clearance after a single dose compared with multiple dosing. There was considerable inter- and intra-subject variability in the pharmacokinetic parameters. Cmax and AUC deceased and T1/2 increased with increased body weight. The variability between the capsules was extremely low: 2.2%, 1.4% and 1.4%, for hydroxyvalerenic acid, acetoxyvalerenic acid and valerenic acid, respectively. In conclusion, large variability in the pharmacokinetics of valerenic acid may contribute to the inconsistencies in the effect of valerian as a sleep aid. Copyright © 2010 John Wiley & Sons, Ltd. [source] Use of chlorophyll fluorescence to evaluate the cold acclimation and freezing tolerance of winter and spring oatsPLANT BREEDING, Issue 5 2001F. Rizza Abstract The efficiency of the excitation capture by open Photosystem II (PSII) reaction centres was measured by the Fv/Fm ratios in a collection of winter and spring oats in order to assess the effects of hardening and freezing on the functionality of PSII and also the suitability of a chlorophyll fluorescence-based method to screen oat cultivars for frost tolerance. A significant reversible decrease in Fv/Fm was found in all genotypes during acclimation to low, non-freezing temperatures. Fv/Fm analysis appears to be an attractive test for the evaluation of frost tolerance in oats, being rapid, non-invasive and capable of monitoring a trait related to a crucial stage in the acquisition of frost tolerance. It is more sensitive and precise than other standard methods and highly correlated with field-evaluated frost damage. The measurements made during recovery 1 or 2 days after stress when the visual symptoms are not yet expressed, were especially advantageous because of the large variability in genotype response. The r-values (close to 0.8) were reduced due to the non-standard behaviour of the winter cultivar ,Aintree'. The cold acclimation response of this genotype has been analysed in detail and the limits of artificial freezing tests are discussed. [source] ,18O of water vapour, evapotranspiration and the sites of leaf water evaporation in a soybean canopyPLANT CELL & ENVIRONMENT, Issue 9 2008LISA R. WELP ABSTRACT Stable isotopes in water have the potential to diagnose changes in the earth's hydrological budget in response to climate change and land use change. However, there have been few measurements in the vapour phase. Here, we present high-frequency measurements of oxygen isotopic compositions of water vapour (,v) and evapotranspiration (,ET) above a soybean canopy using the tunable diode laser (TDL) technique for the entire 2006 growing season in Minnesota, USA. We observed a large variability in surface ,v from the daily to the seasonal timescales, largely explained by Rayleigh processes, but also influenced by vertical atmospheric mixing, local evapotranspiration (ET) and dew formation. We used ,ET measurements to calculate the isotopic composition at the sites of evaporative enrichment in leaves (,L,e) and compared that with the commonly used steady-state prediction (,L,s). There was generally a good agreement averaged over the season, but larger differences on individual days. We also found that vertical variability in relative humidity and temperature associated with canopy structure must be addressed in canopy-scale leaf water models. Finally, we explored this data set for direct evidence of the Péclet effect. [source] Attitudes towards diabetes and its care: Evaluation before, immediately post-course and ,1 year after a practical, international inter-disciplinary course for diabetes teams.PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 2 2001Peter Rossing MD Abstract The objective of the study was to evaluate differences in attitudes to diabetes and its management among diabetes health care professionals, and to evaluate whether these attitudes could be persistently modified by participation in courses in practical diabetology. The courses emphasize self-care, inter-disciplinary teamwork and applicability of acquired knowledge. Pre- and immediate post-course evaluation as well as a ,1 year post-course follow-up of attitudes to 12 general but central statements concerning diabetes and its management was performed for 144 participants (80 physicians, 52 nurses and 12 other team members) from 28 countries. Both pre- and post-course attitudes to the statements varied considerably even among experienced diabetes professionals. In general, a shift in attitudes in the intended direction was observed at the immediate post-course test. These changes were to a large extent maintained more than one year post-course although a large variability persisted. We conclude that international and inter-disciplinary education of health professionals is feasible and successful despite major linguistic and cultural barriers. Copyright © 2001 John Wiley & Sons, Ltd. [source] Long-term variation in fruiting and the food habits of wild Japanese nacaques on Kinkazan Island, northern JapanAMERICAN JOURNAL OF PRIMATOLOGY, Issue 11 2006Yamato Tsuji Abstract We studied the relationship between the food habits of Japanese macaques (Macaca fuscata) and the availability of nuts (Fagus crenata, Zelkova serrata, Carpinus spp., and Torreya nucifera) on Kinkazan Island, northern Japan, from 1997 to 2005 to examine the long-term variations in both food habits and availability. The food habits of the monkeys showed clear seasonal changes: the staple foods were woody leaves and flowers in spring (May and June), woody leaves and seeds or fruits other than nuts in summer (July and August), nuts and seeds or fruits other than nuts in fall (September,November), and herbaceous plants in winter (December,April). The availability of nuts, combinations of masting species, and energy production varied among years. Food habits varied among years, but the magnitude of variability of food habits differed among seasons, with large variability during summer and winter, and small variability in spring. Food availability was poor in summer and winter, but in several years the monkeys were able to consume nuts during those seasons. We emphasize the importance of conducting long-term studies on both food availability and the food habits of animals in the temperate zone. Am. J. Primatol. 68:1068,1080, 2006. © 2006 Wiley-Liss, Inc. [source] Postnatal development of synaptic transmission in local networks of L5A pyramidal neurons in rat somatosensory cortexTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007Andreas Frick The probability of synaptic transmitter release determines the spread of excitation and the possible range of computations at unitary connections. To investigate whether synaptic properties between neocortical pyramidal neurons change during the assembly period of cortical circuits, whole-cell voltage recordings were made simultaneously from two layer 5A (L5A) pyramidal neurons within the cortical columns of rat barrel cortex. We found that synaptic transmission between L5A pyramidal neurons is very reliable between 2 and 3 weeks of postnatal development with a mean unitary EPSP amplitude of ,1.2 mV, but becomes less efficient and fails more frequently in the more mature cortex of ,4 weeks of age with a mean unitary EPSP amplitude of 0.65 mV. Coefficient of variation and failure rate increase as the unitary EPSP amplitude decreases during development. The paired-pulse ratio (PPR) of synaptic efficacy at 10 Hz changes from 0.7 to 1.04. Despite the overall increase in PPR, short-term plasticity displays a large variability at 4 weeks, ranging from strong depression to strong facilitation (PPR, range 0.6,2.1), suggesting the potential for use-dependent modifications at this intracortical synapse. In conclusion, the transmitter release probability at the L5A,L5A connection is developmentally regulated in such a way that in juvenile animals excitation by single action potentials is efficiently transmitted, whereas in the more mature cortex synapses might be endowed with a diversity of filtering characteristics. [source] Evolution of the stable water isotopic composition of the rain sampled along Sahelian squall lines,THE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue S1 2010Camille Risi Abstract In the Tropics, the stable isotopic composition (HDO, HO) of precipitation is strongly modulated by convective activity. To better understand how convective processes impact the precipitation isotopic composition, we analyze the isotopic composition of rain collected during the passage of four squall lines over the Sahel (Niamey, Niger) in August 2006 during the African Monsoon Multidisciplinary Analysis (AMMA) campaign. The high-frequency sampling (5,10 min) of the precipitation allows us to investigate the evolution of the precipitation isotopic composition in different phases of the squall lines. Despite a large variability among the different squall lines, some robust isotopic features appear: the W shape of the ,18O evolution and the deuterium excess decrease in the first part of the stratiform zone. To understand more quantitatively how convective processes impact the precipitation isotopic composition, a simple stationary two-dimensional transport model including a representation of cloud microphysics and isotopic fractionation is developed and forced by three-dimensional winds retrieved from the Massachusetts Institute of Technology (MIT) radar on 11 August 2006. The model reproduces the robust observed features and a large sensitivity to the squall-line dynamics. This model suggests that the main controlling factors of the isotopic evolution are (1) squall-line dynamics, especially the downward advection of air at the rear of the squall lines, affecting the vapour composition and, by isotopic equilibration, the subsequent precipitation composition and (2) rain re-evaporation. This suggests that water isotopes have the potential to better constrain squall-line dynamics and rain re-evaporation, and to evaluate the representation of convective processes in numerical models. Copyright © 2009 Royal Meteorological Society [source] The use of sugammadex in a patient with myasthenia gravisANAESTHESIA, Issue 3 2010C. Unterbuchner Summary Myasthenia gravis, affecting neuromuscular transmission, leads to a large variability in sensitivity to depolarising and non-depolarising neuromuscular blocking drugs. We report the successful use of the modified ,-cyclodextrin sugammadex in a myasthenic patient to reverse a rocuronium-induced deep level of neuromuscular block. After spontaneous neuromuscular recovery of T2 (second twitch of the train-of-four series), we administered 2 mg.kg,1 of sugammadex intravenously, reversing neuromuscular blockade to a train-of-four ratio (T4/T1) > 90% within 210 s. Sugammadex, in combination with objective neuromuscular monitoring, can be used to reverse rocuronium-induced neuromuscular blockade in patients with myasthenia gravis, thereby avoiding the need for reversal with acetylcholinesterase inhibitors. [source] Pond-to-pond variability in post-larval shrimp, Litopenaeus vannamei, survival and growth in inland low-salinity waters of west AlabamaAQUACULTURE RESEARCH, Issue 16 2009Luke A Roy Abstract Despite the recent success of Alabama shrimp farmers in culturing the Pacific white shrimp, Litopenaeus vannamei, in inland low-salinity waters there is large variability in growth and survival among ponds. Farmers suspect that high mortality occurs during the first weeks of culture following stocking of postlarvae (PL). In order to determine the effect of pond ionic composition on PL growth and survival, three trials were carried out at a shrimp farm. Trials 1 and 2 evaluated PL growth and survival over 21- and 28-day periods, respectively, using static water from different production ponds. Trial 3 evaluated growth and survival over 7, 14, 21 and 28 days using water from one production pond. Results suggest that initial mortality (8,10%) is attributed to the acclimation process and occurs immediately following stocking. Pond-to-pond variations in ionic profiles could be a contributing factor but are not likely the major reason for variable ,survival'. Mortalities after stocking appear to occur quickly as there were no differences in survival from 7 to 28 days post stock. Variable survival is likely due to a combination of reasons including environmental factors, but is largely due to poor handling of PL and stocking errors that produce perceived reductions in survival. [source] Variability and Impact on Design of Bioequivalence StudiesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2010Achiel Van Peer Revisions of the regulatory guidance are based upon many questions over the past years and sometimes continuing scientific discussions on the use of the most suitable statistical analysis methods and study designs, particularly for drugs and drug products with high within-subject variability. Although high within-subject variability is usually associated with a coefficient of variation of 30% or more, new approaches are available in the literature to allow a gradual increase and a levelling off of the bioequivalence limits to some maximum wider values (e.g. 75,133%), dependent on the increase in the within-subject variability. The two-way, cross-over single dose study measuring parent drug is still the design of first choice. A partial replicate design with repeating the reference product and scaling the bioequivalence for the reference variability are proposed for drugs with high within-subject variability. In case of high variability, more regulatory authorities may accept a two-stage or group-sequential bioequivalence design using appropriately adjusted statistical analysis. This review also considers the mechanisms why drugs and drug products may exhibit large variability. The physiological complexity of the gastrointestinal tract and the interaction with the physicochemical properties of drug substances may contribute to the variation in plasma drug concentration-time profiles of drugs and drug products and to variability between and within subjects. A review of submitted bioequivalence studies at the Food and Drug Administration's Office of Generic Drugs over the period 2003,2005 indicated that extensive pre-systemic metabolism of the drug substance was the most important explanation for consistently high variability drugs, rather than a formulation factor. These scientific efforts are expected to further lead to revisions of earlier regulatory guidance in other regions as is the current situation in Europe. [source] An analysis of variability in the manufacturing of dexosomes: Implications for development of an autologous therapy,BIOTECHNOLOGY & BIOENGINEERING, Issue 2 2005Sanjay Patel Abstract Dexosomes are nanometer-size vesicles released by dendritic-cells, possessing much of the cellular machinery required to stimulate an immune response (i.e. MHC Class I and II). The ability of patient-derived dexosomes loaded with tumor antigens to elicit anti-tumor activity is currently being evaluated in clinical trials. Unlike conventional biologics, where variability between lots of product arises mostly from the manufacturing process, an autologous product has inherent variability in the starting material due to heterogeneity in the human population. In an effort to assess the variability arising from the dexosome manufacturing process versus the human starting material, 144 dexosome preparations from normal donors (111) and cancer patients (33) from two Phase I clinical trials were analyzed. A large variability in the quantity of dexosomes (measured as the number of MHC Class II molecules) produced between individual lots was observed (,>,50-fold). An analysis of intra-lot variability shows that the manufacturing process introduces relatively little of this variability. To identify the source(s) of variability arising from the human starting material, distributions of the key parameters involved in dexosome production were established, and a model created. Computer simulations using this model were performed, and compared to the actual data observed. The main conclusion from these simulations is that the number of cells collected per individual and the productivity of these cells of are the principal sources of variability in the production of Class II. The approach described here can be extended to other autologous therapies in general to evaluate control of manufacturing processes. Moreover, this analysis of process variability is directly applicable to production at a commercial scale, since the large scale manufacture of autologous products entails an exact process replication rather than scale-up in volume, as is the case with traditional drugs or biologics. © 2005 Wiley Periodicals, Inc. [source] Application of near-infrared (NIR) spectroscopy for screening of raw materials used in the cell culture medium for the production of a recombinant therapeutic proteinBIOTECHNOLOGY PROGRESS, Issue 2 2010Alime Ozlem Kirdar Abstract Control of raw materials based on an understanding of their impact on product attributes has been identified as a key aspect of developing a control strategy in the Quality by Design (QbD) paradigm. This article presents a case study involving use of a combined approach of Near-infrared (NIR) spectroscopy and Multivariate Data Analysis (MVDA) for screening of lots of basal medium powders based on their impact on process performance and product attributes. These lots had identical composition as per the supplier and were manufactured at different scales using an identical process. The NIR/MVDA analysis, combined with further investigation at the supplier site, concluded that grouping of medium components during the milling and blending process varied with the scale of production and media type. As a result, uniformity of blending, impurity levels, chemical compatibility, and/or heat sensitivity during the milling process for batches of large-scale media powder were deemed to be the source of variation as detected by NIR spectra. This variability in the raw materials was enough to cause unacceptably large variability in the performance of the cell culture step and impact the attributes of the resulting product. A combined NIR/MVDA approach made it possible to finger print the raw materials and distinguish between good and poor performing media lots. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] Normal head-hair length is correlated with its diameterCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2004J. Nissimov Summary Shed head-hair fibres of young (16,20-year-old), nonalopecic women (n = 25), exhibiting both exogen clubs and anagen tips (EA) were studied. Such fibres are shown, for the first time, to comprise , 44% of shed hair and to form a uni-modal, positively skewed distribution with a mean length of 16.7 ± 4.9 cm, which is also correlated with the length of the haircut. As individual fibres exit the skin in early anagen VI, their major-axis diameters increase rapidly to maxima at about 25% of their total potential length and subsequently decrease to their exogen clubs, at a rate of 1.31% per cm (n = 28). EA diameters are further correlated with their lengths. Maximal and proximal diameters increase by 1.40% per cm and 1.02% per cm increments in fibre lengths, respectively (P < 0.0001 each; n = 14), these changes being also different from each other (P < 0.001). Besides identifying and characterizing a new class of normal hair (EA) which will probably feature prominently in future hair research, this study reveals several other important aspects of hair growth: (i) the classically described concept of hair miniaturization in androgenetic alopecia (AGA) is excessively broad and should therefore be revised; (ii) female AGA need not necessarily require a mechanism for rapid miniaturization as recently proposed; and (iii) the putative large variability of normal hair diameters is significantly overestimated, which further opens the field of hair diameter evaluation as a biological indicator of disease and physiological function. [source] Heterogeneity Of The Properties Of INa in Epicardial And Endocardial Cells Of Rat VentricleCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2002Bonny N Honen SUMMARY 1. Ventricular INa heterogeneity was investigated in adult rat hearts. Differences in transient outward potassium current (Ito) were used to confirm isolation of subepicardial and subendocardial cells. Mean peak Ito was 6.0 ± 0.7 and 1.6 ± 0.45 pA/pF in epicardial and endocardial cells, respectively (P < < 0.01). 2. Maximum sodium conductance was smaller in subendocardial cells compared with subepicardial cells (2.39 ± 0.11 vs 2.78 ± 0.12 nS/pF, respectively; n = 17 for both; 0.01 < P < 0.05) and 50% activation occurred at a slightly more negative potential (,47.6 ± 0.8 vs,44.9 ± 0.9 mV, respectively; n = 10 for both; 0.01 < P < 0.05). 3. The potential for 50% inactivation was not significantly different in subepicardial compared with subendocardial cells (72.2 ± 1.0 vs 72.8 ± 2.2 mV, respectively; n = 17 for both; NS). 4. Persistent sodium current density appeared smaller in subendocardial (n = 19) compared with subepicardial (n = 11) cells (at a test potential of ,25 mV current, density was 0.118 ± 0.041 vs 0.144 ± 0.085 pA/pF, respectively), although this was not statistically significant due to large variability between cells. 5. Mathematical modelling of the cardiac action potential indicated that the combined effects of differences in current density and voltage dependence of sodium currents are unlikely to contribute to ventricular action potential heterogeneity between epicardial and endocardial cells. [source] | ||||||||||||||||||||||||||||