Search

Background: The number of abdominal procedures performed via a robotic-assisted approach is increasing as potential advantages of the modality are recognised. We report the first in human case series of major colorectal resection performed using a new system, Versius®, and assess the feasibility of its use. Methods: The initial cases performed using Versius® at a single centre in the UK were included in the study. Anonymised data were prospectively collected including patient demographics, operative details and postoperative outcomes. Results: Twenty-three operations were performed, including left (n = 14) and right (n = 9)-sided colonic resections. Rectal mobilisation was performed in 13. Fifty-seven percent of the patients were male, with a malignant indication for surgery in 70% of cases. Overall mean age was 59.1 ± 15.3 (range 23–89) years. Overall mean body mass index was 28.9 ± 5.2 with a mean of 31.3 ± 4.5 for left-sided resections. The median console operating time was 166 min (range 75–320 min). All malignant cases had negative resection margins and the mean lymph node yield was 18 (SD 9.4). Only one operation (4%) was converted from robotic to open approach. Postoperative length of stay was a median of 5 days (range 3–34 days) and there were no readmissions within 30 days. Conclusions: These results compare favourably with the literature on existing robotic systems and also conventional laparoscopic surgery; hence, we believe that this series indicates the Versius® system is feasible for use in major colorectal resection. These early results from a robot-naïve centre show exciting promise for an expanding robotic market and highlight the need for further evaluation. [ABSTRACT FROM AUTHOR]

In VISION Cohort A, tepotinib showed robust and durable clinical activity in pts with MET ex14 skipping NSCLC. Here, we present biomarker analyses on serial LBx samples. LBx samples at baseline (BL), Week 6, 12, and end of treatment (EOT) were analyzed (73 genes). Investigator (INV)-assessed clinical outcome was evaluated per BL biomarker profiles and molecular response (MR; >75% depletion from BL in MET ex14 variant allele frequency [VAF] ctDNA confirmed in 2 consecutive samples) or molecular progression (MP; VAF increase >0 from BL). Per INV, acquired resistance was investigated in EOT samples. Of 99 LBx pts, median age was 72 yrs (range 49–88), 53% were male, 44% never smokers, and 85% had adenocarcinoma. INV ORR was 53% (95% CI: 42, 63); ORR in first line (1L; n=44) was 59% (43, 74) and 47% (33, 61) in ≥2L (n=55). 94 pts had BL biomarker profiles, similar in 1L to ≥2L except for EGFR amp (1/43 [2%] vs 8/51 [16%]). Location/type of MET ex14 alteration did not affect outcomes. 1 pt with concomitant MET M1250T had a 17.3-month PFS. A trend toward improved efficacy was seen with concomitant MET amp (6/8 responses). Tepotinib response occurred in pts with wt or mutant TP53 , but there was a trend for longer mDOR and mPFS with wt TP53. Concomitant oncogenic mutations were rare: 3 pts with KRAS, NRAS alterations (no responses) and 5 with PI3K/AKT alterations (3 responses). 65 pts had 2 consecutive on-treatment samples (30 1L, 35 ≥2L): 46 (71%) had confirmed MR, 5 (8%) had confirmed MP, and 14 (22%) had no change in VAF/lacked confirmation. MR was associated with clinical response and MP with no response/short PFS (Table). 52 pts with progression had EOT LBx samples. Emerging MET resistance mutations (Y1230H/C & D1228H/N) occurred in 7 pts (13%): all responders and 5 had PFS >10 months. Non-MET-driven resistance mechanisms will be presented. LBx biomarker analysis from the largest on-treatment data set for a MET inhibitor in MET ex14 skipping NSCLC showed that ctDNA depletion in MET ex14 VAF is associated with improved clinical response in pts treated with tepotinib. Serial LBx could help monitor responses, understand resistance and guide dose-adjustment strategies to improve outcomes and quality of life. [ABSTRACT FROM AUTHOR]

MET amp, an oncogenic driver occurring in 1–5% of NSCLC cases, confers a poor prognosis and lacks approved targeted therapies. Tepotinib, a highly selective MET inhibitor, provided durable response in advanced NSCLC with MET exon 14 (MET ex14) skipping in VISION Cohort A. VISION Cohort B evaluated tepotinib in patients with advanced NSCLC and MET amp, as detected by a convenient and minimally invasive liquid biopsy (LBx) assay. Patients with advanced NSCLC, ECOG PS 0–1, 0–2 prior therapy lines, EGFR / ALK wild-type status, no MET ex14 skipping, and MET amp by LBx (MET gene copy number ≥2.5) received oral tepotinib 500 mg QD (450 mg active moiety). Primary endpoint was objective response rate (ORR) (RECIST v1.1) by independent review committee (IRC). Duration of response (DOR), progression-free survival (PFS), and safety were secondary endpoints. The data cut-off was July 1, 2020. Of 24 enrolled patients, the median age was 63.4 years (range 38–73), 21 patients were male (88%), 21 had ECOG PS 1, and 21 were smokers. Seven patients (29%) received tepotinib in first line (1L), 10 (42%) in second line (2L), and seven patients in third line (3L). As of November 2020, treatment was ongoing for >1 year in five patients (1L, n=2; 2L, n=2; 3L, n=1). The ORR was 42% (10/24 patients) overall, 71% (5/7) in 1L, 30% (3/10) in 2L and 29% (2/7) in 3L (Table). The median DOR was not estimable (NE). Five patients (20.8%) discontinued due to adverse events (AEs) considered unrelated to tepotinib. 16 patients reported treatment-related AEs (67%; Grade 3/4 in seven patients [29%]), including peripheral edema (nine patients [38%]; Grade 3/4 in two [8%]), generalized edema (four patients [17%]; Grade 3/4 in two [8%]), and constipation (four patients [17%]; none with Grade 3/4). In the first study of a MET inhibitor in advanced NSCLC with MET amp prospectively detected by LBx, tepotinib had high and clinically meaningful activity, especially in 1L, and was generally well tolerated. Tepotinib warrants further evaluation in advanced NSCLC with MET amp. [ABSTRACT FROM AUTHOR]

Silvicultural practices lead to changes in forest composition and structure and may impact species diversity from the overall regional species pool to stand-level species occurrence. We explored to what extent fine-scale occupancy patterns in differently managed forest stands are driven by environment and ecological traits in three regions in Germany using a multi-species hierarchical model. We tested for the possible impact of environmental variables and ecological traits on occupancy dynamics in a joint modelling exercise while taking possible variation in coefficient estimates over years and plots into account. Bird species richness differed across regions and years, and trends in species richness across years were different in the three regions. On the species level, forest management affected occupancy of species in all regions, but only 3-5% of the total assemblage-level variation in occurrence probability was explained by either forest type and successional stage and < 1% by forest edge. On the assemblage level, bird occurrence decreased with body mass in all regions. Species with smaller breeding ranges had lower occurrence probabilities in one region, while later spring arrival decreased occurrence probabilities in the two other regions. Spatial variation in the effect size of trait covariates such as species phylogeny and breeding strata showed that variation in patch occupancy due to fine-scale differences in forest management is, to some extent, predictable from ecological traits. Our results show that environmental factors and ecological traits jointly predict variation in bird occupancy patterns and their response to forest management. Observations at the fine scale of forest stands, at which conservation efforts can be arranged along with forest management practices in heterogeneous environments, have been shown to provide meaningful insights despite the difficulties involved in monitoring mobile organisms such as birds at the plot level. [ABSTRACT FROM AUTHOR]

Abstract: We have developed a new optimisation based shape from shading algorithm which is able to make use of sophisticated camera and reflectance models and does not require a good initialising surface. Surface shape consistent with ground truth is obtained when the technique is applied to both synthetic rendered surfaces and real images captured by the Mars Express orbiter and HRSC instrument. The obtained surfaces provide improved fine surface detail over that found using stereo techniques and demonstrate the applicability of the technique to real images. [Copyright &y& Elsevier]

Historical catch records of Atlantic salmon Salmo salar from three rivers discharging to the Baltic Sea in an area free from tides and from strong effects of the moon on illumination were analysed to investigate whether timing of S. salar river entry was associated with lunar cycles directly. Although a significant effect of lunar phase on river entry was detected, with more fish entering rivers around the full moon than other phases, the effect of the lunar cycle was very small compared with other sources of variation. Hence, the biological role of lunar cycle as a determinant of the timing of S. salar runs in the investigated populations was negligible, suggesting that lunar cycle per se does not play a role in the timing of S. salar river entry. [ABSTRACT FROM AUTHOR]

The analysis of mark–recapture data is undergoing a period of development and expansion. Here we contribute to that by presenting a model which includes both births and immigration, as well as the usual deaths. Data come from a long-term study of the willow tit ( Parus montanus), where we can assume that all births are recorded, and hence immigrants can also be identified as birds captured as adults for the first time. We model the rates of immigration, birth rate per parent, and death rates of juveniles and adults. Using a hierarchical model allows us to incorporate annual variation in these parameters. The model is fitted to the data using Markov chain Monte Carlo, as a Bayesian analysis. In addition to the model fitting, we also check several aspects of the model fit, in particular whether survival varies with age or immigrant status, and whether capture probability is affected by previous capture history. The latter check is important, as independence of capture histories is a key assumption that simplifies the model considerably. Here we find that the capture probability depends strongly on whether the individual was captured in the previous year. [ABSTRACT FROM AUTHOR]

The study of evolutionary quantitative genetics has been advanced by the use of methods developed in animal and plant breeding. These methods have proved to be very useful, but they have some shortcomings when used in the study of wild populations and evolutionary questions. Problems arise from the small size of data sets typical of evolutionary studies, and the additional complexity of the questions asked by evolutionary biologists. Here, we advocate the use of Bayesian methods to overcome these and related problems. Bayesian methods naturally allow errors in parameter estimates to propagate through a model and can also be written as a graphical model, giving them an inherent flexibility. As packages for fitting Bayesian animal models are developed, we expect the application of Bayesian methods to evolutionary quantitative genetics to grow, particularly as genomic information becomes more and more associated with environmental data. [ABSTRACT FROM AUTHOR]

We present a Bayesian hierarchical model for the joint spatial dynamics of a host-parasite system. The model was fitted to long-term data on regional plague dynamics and metapopulation dynamics of the black-tailed prairie dog, a declining keystone species of North American prairies. The rate of plague transmission between colonies increases with increasing precipitation, while the rate of infection from unknown sources decreases in response to hot weather. The mean annual dispersal distance of plague is about 10 km, and topographic relief reduces the transmission rate. Larger colonies are more likely to become infected, but colony area does not affect the infectiousness of colonies. The results suggest that prairie dog movements do not drive the spread of plague through the landscape. Instead, prairie dogs are useful sentinels of plague epizootics. Simulations suggest that this model can be used for predicting long-term colony and plague dynamics as well as for identifying which colonies are most likely to become infected in a specific year. [ABSTRACT FROM AUTHOR]

Comparative studies of quantitative genetic and neutral marker differentiation have provided means for assessing the relative roles of natural selection and random genetic drift in explaining among-population divergence. This information can be useful for our fundamental understanding of population differentiation, as well as for identifying management units in conservation biology. Here, we provide comprehensive review and meta-analysis of the empirical studies that have compared quantitative genetic ( QST) and neutral marker ( FST) differentiation among natural populations. Our analyses confirm the conclusion from previous reviews – based on ca. 100% more data – that the QST values are on average higher than FST values [mean difference 0.12 (SD 0.27)] suggesting a predominant role for natural selection as a cause of differentiation in quantitative traits. However, although the influence of trait (life history, morphological and behavioural) and marker type (e.g. microsatellites and allozymes) on the variance of the difference between QST and FST is small, there is much heterogeneity in the data attributable to variation between specific studies and traits. The latter is understandable as there is no reason to expect that natural selection would be acting in similar fashion on all populations and traits (except for fitness itself). We also found evidence to suggest that QST and FST values across studies are positively correlated, but the significance of this finding remains unclear. We discuss these results in the context of utility of the QST– FST comparisons as a tool for inferring natural selection, as well as associated methodological and interpretational problems involved with individual and meta-analytic studies. [ABSTRACT FROM AUTHOR]

The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic–pituitary–adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.Molecular Psychiatry (2007) 12, 544–555. doi:10.1038/sj.mp.4001978; published online 13 March 2007 [ABSTRACT FROM AUTHOR]

Comparison of population differentiation in neutral marker genes and in genes coding quantitative traits by means of FST and QST indexes has become commonplace practice. While the properties and estimation of FST have been the subject of much interest, little is known about the precision and possible bias in QST estimates. Using both simulated and real data, we investigated the precision and bias in QST estimates and various methods of estimating the precision. We found that precision of QST estimates for typical data sets (i.e., with <20 populations) was poor. Of the methods for estimating the precision, a simulation method, a parametric bootstrap, and the Bayesian approach returned the most precise estimates of the confidence intervals. [ABSTRACT FROM AUTHOR]

Several ecologists have recently suggested that ecology has several laws. This conclusion contrasts with the views of some philosophers of science, who have suggested that biology cannot have laws. I argue that the debate has been confused because two very different types of law can be recognised: correlative and causal laws. Once we recognise that there is a difference, the argument against causal laws becomes stronger, and instead I suggest that ecologists should recognise that they can and do produce generalisations that are used to build models– nomological machines– that describe the ecological systems they are studying. [ABSTRACT FROM AUTHOR]

1. Several species richness estimators (two non-parametric, four based on rarefaction curves and two from fitting of abundance distributions) were compared by examining their performance in estimating the species richness for two moth data sets from the United Kingdom. Comparisons were also made using data simulated from the fitted abundance distributions.2. The different species richness estimators gave different estimates. The non-parametric estimates and the rarefaction estimates were similar, but were smaller than the parametric estimates. When the simulated data were used, the only methods to give estimates near the true value was the parametric method using the distribution from which the data were simulated.3. At present it is impossible to decide whether any of the estimation methods will give a realistic estimate, as not enough is known about the true numbers of species in communities. Until this is rectified, the most that can be hoped for is to obtain upper and lower bounds on species richness.Journal of Animal Ecology(2005)74, 375 –386doi: 10.1111/j.1365-2656.2005.00940.x [ABSTRACT FROM AUTHOR]

Abstract The relative roles of natural selection and direct environmental induction, as well as of natural selection and genetic drift, in creating clinal latitudinal variation in quantitative traits have seldom been assessed in vertebrates. To address these issues, we compared molecular and quantitative genetic differentiation between six common frog (Rana temporaria ) populations along an approximately 1600 km long latitudinal gradient across Scandinavia. The degree of population differentiation (Q ST ≈ 0.81) in three heritable quantitative traits (age and size at metamorphosis, growth rate) exceeded that in eight (neutral) microsatellite loci (F ST = 0.24). Isolation by distance was clear for both neutral markers and quantitative traits, but considerably stronger for one of the three quantitative traits than for neutral markers. Q ST estimates obtained using animals subjected to different rearing conditions (temperature and food treatments) revealed some environmental dependency in patterns of population divergence in quantitative traits, but in general, these effects were weak in comparison to overall patterns. Pairwise comparisons of F ST and Q ST estimates across populations and treatments revealed that the degree of quantitative trait differentiation was not generally predictable from knowledge of that in molecular markers. In fact, both positive and negative correlations were observed depending on conditions where the quantitative genetic variability had been measured. All in all, the results suggest a very high degree of genetic subdivision both in neutral marker genes and genes coding quantitative traits across a relatively recently (< 9000 years) colonized environmental gradient. In particular, they give evidence for natural selection being the primary agent behind the observed latitudinal differentiation in quantitative traits. [ABSTRACT FROM AUTHOR]

We examined the effect of the apolipoprotein E (apo E) epsilon4 allele on the relationship between self-reported stress and mood in caregivers of patients with Alzheimer's disease. Eighty-six female subjects between the ages of 28 and 82 years who were community-dwelling AD patient caregivers participated in the study. A cross-sectional analysis of stress and mood was performed using the Revised Memory and Behavior Problem Checklist and the Geriatric Depression Scale. All subjects were evaluated for normal cognitive function (Mini-Mental Status Examination) and apo E genotype. The results indicated that increased levels of stress were associated with increased levels of depressive symptoms in nondemented caregivers with the epsilon4 allele. This relationship was not observed in caregivers without the epsilon4 allele. These results suggest that carriers of the epsilon4 allele may respond differently to psychological stress than do individuals without the epsilon4 allele. [ABSTRACT FROM AUTHOR]

The effect of the use of different doses of the fungicide fenpropimorph on populations of barley powdery mildew Blumeria (Erysiphe) graminis f. sp. hordei was investigated in a laboratory selection experiment. A sample from the Danish aerial population of powdery mildew was split into populations, and these were kept separately for 31 generations on susceptible barley seedlings treated with fungicide at two concentrations, as well as on a control. Samples from these populations were tested for their resistance to fenpropimorph and their virulence spectra. There was a large amount of environmental variation in the ED50 values used to measure fungicide resistance. In both treated populations, the average level of fungicide resistance increased, this increase being faster and greater in the population treated with the high dose. The diversity of pathotypes of the treated populations decreased, with the decline being more rapid in the population treated with the high dose, where one pathotype dominated the population after 31 generations. This pathotype was apparently not the fittest in the population treated with the low dose. This implies that knowledge of ED50 is not sufficient to predict pathotype evolution under different fungicide treatments. The dominant pathotype in the high-dose treatment may not have been clonal, as there was evidence of two levels of fungicide resistance. The large environmental variation observed in estimated ED50 values for resistance towards fenpropimorph may help to explain why this resistance has evolved at a slower rate than resistance towards other fungicides. [ABSTRACT FROM AUTHOR]

Presents an overview of the work of Mary Whilton Calkins in the area of association and memory. Research setting; Paired associates method; Recency effects; Modality efforts; Negative recency effects; Primacy effects; Unlearning effects; Initial reaction to Calkins's work.

The author reflects on the microarray studies of genetic differences between populations in the U.S. He said that microarray studies of genetic differences involves strengths and weaknesses such as producing large amount of data and the difficulties of interpreting these data. He added that studies on genetic differences require hard work in laboratory and detailed investigation of translating the data into variation between people.

We studied the within-night temporal call variation of Leptodactylus mystacinus using automated bioacoustic survey and pattern recognition techniques. Based on ca 50,000 detected calls we report on large-scale variation of dominant frequency, call duration, peak power, call interval, call period, and call rate. The "absolute" calling effort (as absolute seconds per hour spent on calling calculated as the sum of all detected calls during one hour) was between 165 and 716 s/ hour (535 ± 191) with a peak at around 23:00 h, followed by a decrease until the end of the calling period. This might be due to vocal fatigue. In comparison with literature, the overall call production was higher than expected, but calling effort is comparable to estimates from the literature for other leptodactylid frogs. We hypothesize that species-specific mating tactics might be employed to achieve high calling effort during sustained calling. Further intra- and interspecific studies should aim at studying contest behaviour in mating frogs to test this hypothesis. [ABSTRACT FROM AUTHOR]

The article reviews recent research in heredity. F. Hoti and M. J. Sillanpää proposed taking measurements of gene expression using a microarray assay and combining it into a single regression with the traditional QTL analysis, to identify the expressed genes and marker loci that can explain the variation in the phenotype. A statistical technique is used to assign probabilities to whether a locus or gene affects the quantitive trait.

This article discusses a pilot study that aimed to test the reliability of a proposed scoring system for quantifying the image quality of transvaginal ultrasound (TVUS) images. The scoring system, which could be used in the development of artificial intelligence tools for diagnosing endometriosis, assigned a score of 1-3 to each image based on its quality. The study involved six raters who assessed 150 images, and the results showed poor to moderate levels of interobserver and intraobserver reliability. The authors suggest that further refinement of the scoring system may be necessary to improve reliability. [Extracted from the article]

Characterization of developmental trajectories across the lifespan is integral to understanding the prodromal course of many neuropsychiatric illnesses and the significant risk factors for disease onset or unfavorable outcomes. However, the standard experimental designs used in psychiatric research are not ideal for this purpose. The authors review the limitations of the most commonly employed designs in studies that make developmental or lifespan inferences in psychiatry: cross-sectional, single-cohort longitudinal, and unstructured multicohort longitudinal designs. Cross-sectional studies completely confound within- and between-subject sources of variation and hence rely on the presence of parallel trajectories and negligible sampling and age cohort differences for making valid developmental inferences. Delineating trajectories of within-individual change over substantial periods of time requires data covering long age spans that often cannot be covered using single-cohort longitudinal designs. Unstructured multicohort longitudinal designs are a commonly used alternative that can cover a longer age span in a shorter interval than necessary for a single-cohort design. However, the impact of cohort and sampling effects is often minimized or ignored in unstructured multicohort longitudinal designs. The authors propose that structured multicohort longitudinal designs are a particularly viable and underutilized class of designs in psychiatry that represents a significant improvement over cross-sectional designs and unstructured multicohort longitudinal designs for making developmental inferences while being more practical to implement than single-cohort longitudinal designs. As an example of this approach, the authors analyze changes in entorhinal cortex thickness in Alzheimer's disease in relation to APOE-ε4 genotype. [ABSTRACT FROM AUTHOR]

When phenotypic change occurs over time in wildlife populations, it can be difficult to determine to what degree it is because of genetic effects or phenotypic plasticity. Here, we assess phenotypic changes over time in horn length and volume of thinhorn sheep ( Ovis dalli) rams from Yukon Territory, Canada. We considered 42 years of horn growth from over 50 000 growth measurements in over 8000 individuals. We found that weather explained a large proportion of the annual fluctuation in horn growth, being particularly sensitive to spring weather. Only 2.5% of variance in horn length growth could be explained by an individual effect, and thus any genetic changes over the time period could only have had a small effect on phenotypes. Our findings allow insight into the capacity for horn morphology to react to selection pressures and demonstrate the overall importance of climate in determining growth. [ABSTRACT FROM AUTHOR]

Abstract: We used generalized additive mixed models to analyze data on striped marlin (Tetrapturus audax) catches in Baja California sport fisheries (1987–1989) to investigate the relative importance of lunar phase, sea surface temperature (SST), El Niño/Southern Oscillation (ENSO) index, and vessel effects on catch per unit effort (CPUE). The results indicate that the moon phase has no or little (<1% of variance explained) influence on CPUE. In contrast, both SST (10%) and ENSO (6%) influenced CPUE positively. While most of the variation in CPUE remains unexplained (53%), the vessel identity explained small (ca. 1.5%) but significant amount of variance in CPUE. Hence, sport fishermen wishing to maximise their striped marlin catches would best plan their trips on the basis of weather conditions and boat/crew identities, rather than on the basis of lunar phase. [Copyright &y& Elsevier]

Asexuals often occupy broad geographical and ecological ranges. Two models have been proposed to explain the ubiquity of asexuals: the General-Purpose Genotype (GPG) and the Frozen Niche Variation (FNV) model. According to these models, asexuals differ in their ecological niche width and may occupy narrow specialist niches or ubiquitous niches. A thousand water frogs from 37 different populations located in France in different habitats were studied, and two (hemi)clonal hybrid types were identified genetically, Rana esculenta and R. grafi. Altogether, 13 hemiclones were identified both in R. grafi and R. esculenta. Three of these were geographically and ecologically widely distributed, and usually very common in populations. In contrast, the remaining 10 hemiclones had small geographical ranges and were restricted to special habitat types, suggesting ecological niche specialization. The results suggest that in hybridogenetic water frogs GPG and FNV hemiclones coexist. [ABSTRACT FROM AUTHOR]

Four of the eight hypotheses proposed in the literature for explaining the relationship between abundance and range size (the sampling artifact, phylogenetic non-independence, range position and resource breadth hypotheses) were tested by using atlas data for carabid beetles (Coleoptera, Carabidae) from Belgium, Denmark and the Netherlands. A positive relationship between abundance and partial range size was found in all three countries, and the variation in abundance was lower for widespread species. Analysis of the data did not support three of the proposed hypotheses, but did support the resource breadth hypothesis (species having broader environmental tolerances and being able to use a wider range or resources will have higher local densities and be more widely distributed than more specialised species). Examination of species' characteristics revealed that widespread species are generally large bodied, generalists (species with wide niche breadths occurring in a variety of habitat types) and are little influenced by human-altered landscapes, while species with restricted distributions are smaller bodied, specialists (species with small niche breadths occurring in only one or two habitat types), and favour natural habitat. Landscape alteration may be an important factor influencing carabid abundance and range size in these three countries with a long history of human-induced environmental changes. [ABSTRACT FROM AUTHOR]

The influence of environmental stress on the expression of genetic and maternal effects on the viability traits has seldom been assessed in wild vertebrates. We have estimated genetic and maternal effects on the viability (viz probability of survival, probability of being deformed, and body size and shape) of common frog, Rana temporaria, tadpoles under stressful (low pH) and nonstressful (neutral pH) environmental conditions. A Bayesian analysis using generalized linear mixed models was applied to data from a factorial laboratory experiment. The expression of additive genetic variance was independent of pH treatments, and all traits were significantly heritable (survival: h[SUP2] &ap; 0.08; deformities: h[SUP2] &ap; 0.26; body size: h[SUP2] &ap; 0.12; body shape: h[SUP2] &ap; 0.14). Likewise, nonadditive genetic contributions to variation in all traits were significant, independent of pH treatments and typically of magnitude similar to the additive genetic effects. Maternal effects were large for all traits, especially for viability itself, and their expression was partly dependent on the environment. In the case of body size, the maternal effects were mediated largely through egg size. In general, the results give little evidence for the conjecture that environmental stress created by low pH would impact strongly on the genetic architecture of fitness-related traits in frogs, and hamper adaptation to stress caused by acidification. The low heritabilities and high dominance contributions conform to the pattern typical for traits subject to relatively strong directional selection. [ABSTRACT FROM AUTHOR]

Experiential small group workshops on taking a sexual history were introduced at Imperial College School of Medicine (ICSM). With the introduction of a new curriculum and an increase in the number of students, together with a growing awareness of economic constraints in medical education, a large group session on the same topic was developed. In both sessions students identify barriers to taking a sexual history, contexts in which a sexual history is appropriate and skills necessary for an effective sexual history interview. This paper describes and contrasts the content, methodology and student evaluations of both types of sessions. The results showed that in the short term students perceived benefits from both methods of teaching. Further work is required to determine the long-term effects of such training. [ABSTRACT FROM AUTHOR]

Women appear to become more impaired than men after drinking equivalent amounts of alcohol, achieving higher blood alcohol concentrations even when doses are adjusted for body weight. This finding may be attributable in part to gender differences in total body water content. Men and women appear to eliminate approximately the same total amount of alcohol per unit body weight per hour. However, women seem to eliminate significantly more alcohol per unit of lean body mass per hour than men. Some studies report that women are more susceptible than men to alcohol-related impairment of cognitive performance, especially in tasks involving delayed memory or divided attention functions. Psychomotor performance impairment, however, does not appear to be affected by gender. This article provides an overview of alcohol metabolism (pharmacokinetics) and reviews recent studies on gender differences in alcohol absorption, distribution, elimination, and impairment. Speculation that gender differences in alcohol pharmacokinetics or alcohol-induced performance impairment may be caused by the menstrual cycle and variations in female sex hormones are discussed. It is concluded that the menstrual cycle is unlikely to influence alcohol pharmacokinetics. [ABSTRACT FROM AUTHOR]

Advances in phenology and pole- and up-ward shifts in geographic ranges are well-documented signs that species are responding to climate change. A deeper understanding of such responses across ecologically different species groups will help to assess future consequences for entire ecosystems. A less well-studied pattern linked with climate change is increases in abundances of warm-adapted species compared with cold-adapted species. To compare how recent climate change has affected the abundances of species across different taxonomic groups, we analyzed long-term local population trends and related them to the species temperature niche, as inferred from geographic distributions. We used population data sets collected in different regions of Central Europe, primarily Germany, for bats, birds, butterflies, ground beetles, springtails and dry grassland plants. We found that temperature niche was positively associated with long-term population trends in some of the taxonomic groups (birds, butterflies, ground beetles) but was less important in others (bats, springtails, and grassland plants). This variation in the importance of temperature niche suggested that some populations have been affected more than others by climate change, which may be explained by differences in species attributes, such as generation time and microhabitat preference. Our findings indicate that relating temperature niches of species to population trends is a useful method to quantify the impact of climate change on local population abundances. We show that this widely applicable approach is particularly suited for comparative cross-system analyses to identify which types of organisms, in which habitats, are responding the most to climate change. [ABSTRACT FROM AUTHOR]

Introduction Previous analyses suggest that over the first 3 years of the national Quality and Outcomes Framework (QOF) quality of care has improved and inequalities in diabetes care between practices have significantly reduced. In this study, we have reviewed the literature and undertook an exploratory analysis of the first 5-year QOF data with practices ranked by deprivation tertiles to assess the impact of QOF on the quality of diabetes care and health care inequalities. Objectives To use data from QOF to assess whether the quality of diabetes care has continued to improve between its introduction in 2004/2005 and 2008/2009, whether the gap between practices in the most deprived and the least deprived tertiles has closed, and whether the national patterns are also seen in a city with significant geographical inequalities. Design Exploratory analysis of the QOF data from 2004/2005 to 2008/2009. Participants All general practices in England and practices in the city of Sheffield. Main Outcome Measure Trends in the process and outcome measures of diabetes care and in the gap between the most deprived and the least deprived tertiles. Results In England the mean proportions of patients with HbA1c, blood pressure (BP) and cholesterol reviewed and the mean proportions of those achieving outcome targets for HbA1c (7.5%), BP (145/85) and cholesterol (5 mmol/l) were noted to be higher than the QOF upper thresholds of 90% and 60% for the process and outcome indicators, respectively, and these increased over time with most practices levelling off by 2008/2009. A comparison of these increasing trends between practices in the most deprived and least deprived areas revealed that the gap that was significantly wide in 2004/2005 had narrowed over the years and appeared to have disappeared by 2008/2009. For Sheffield, a city with significant geographical inequalities, although the mean proportions achieving the outcome targets were generally above the QOF upper threshold of 60%, these tended to fluctuate between practices in the most deprived and least deprived areas—without consistent narrowing of the gap for all indicators. Conclusion Overall there was narrowing of the inequality gap and improvements in the quality of diabetes care for Sheffield and England as a whole with most of the improvements levelling off by the year 2008/2009. However, for some of the indicators there were differences between Sheffield and England as a whole. [ABSTRACT FROM AUTHOR]

Introduction Previous analyses suggest that over the first 3 years of the national Quality and Outcomes Framework (QOF) quality of care has improved and inequalities in diabetes care between practices have significantly reduced. In this study, we have reviewed the literature and undertook an exploratory analysis of the first 5-year QOF data with practices ranked by deprivation tertiles to assess the impact of QOF on the quality of diabetes care and health care inequalities. Objectives To use data from QOF to assess whether the quality of diabetes care has continued to improve between its introduction in 2004/2005 and 2008/2009, whether the gap between practices in the most deprived and the least deprived tertiles has closed, and whether the national patterns are also seen in a city with significant geographical inequalities. Design Exploratory analysis of the QOF data from 2004/2005 to 2008/2009. Participants All general practices in England and practices in the city of Sheffield. Main Outcome Measure Trends in the process and outcome measures of diabetes care and in the gap between the most deprived and the least deprived tertiles. Results In England the mean proportions of patients with HbA1c, blood pressure (BP) and cholesterol reviewed and the mean proportions of those achieving outcome targets for HbA1c (7.5%), BP (145/85) and cholesterol (5 mmol/l) were noted to be higher than the QOF upper thresholds of 90% and 60% for the process and outcome indicators, respectively, and these increased over time with most practices levelling off by 2008/2009. A comparison of these increasing trends between practices in the most deprived and least deprived areas revealed that the gap that was significantly wide in 2004/2005 had narrowed over the years and appeared to have disappeared by 2008/2009. For Sheffield, a city with significant geographical inequalities, although the mean proportions achieving the outcome targets were generally above the QOF upper threshold of 60%, these tended to fluctuate between practices in the most deprived and least deprived areas—without consistent narrowing of the gap for all indicators. Conclusion Overall there was narrowing of the inequality gap and improvements in the quality of diabetes care for Sheffield and England as a whole with most of the improvements levelling off by the year 2008/2009. However, for some of the indicators there were differences between Sheffield and England as a whole. [ABSTRACT FROM PUBLISHER]

Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commonality of biological function among rare risk alleles, we compared functional knowledge of genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In this study we show that biological processes associated with synapse function and neurotransmission are significantly enriched, with replication, in ASD subjects versus controls. Analysis of phenotypes observed for mouse models of copy-variant genes established significant and replicated enrichment of observable phenotypes consistent with ASD behaviors. Most functional terms retained significance after excluding previously reported ASD loci. These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology and suggest a sizable pool of additional potential ASD risk loci. [ABSTRACT FROM AUTHOR]

To address the growing need for ethnically unbiased cognitive screening, we examined whether the Mini Mental State Exam (MMSE), the abbreviated Fuld Object Memory Evaluation (FOME), or a combination of the two provided optimal detection of dementia in an ethnically diverse group of older adults with no cognitive impairment (normal); cognitive impairment not dementia (CIND); and dementia. Participants included 509 Caucasians, 124 African Americans, and 68 Latinos (>70 years old) from the Aging, Demographics, and Memory Study who completed the MMSE and FOME. Empirically derived decision trees were computed using signal detection software for receiver operator characteristics (ROC). Among the three ethnic groups, ROC analyses revealed that lower scores on both the MMSE and FOME provided better detection of CIND or dementia. Sensitivity and specificity of the MMSE was augmented by the addition of the FOME among Caucasian and African American older adults. The MMSE alone was the best screen in Latino older adults to distinguish any cognitive impairment from normal. When comparing CIND versus dementia, however, the FOME alone was best for detecting dementia among Latinos. The abbreviated FOME is recommended to increase clinical validity and thus minimize ethnic biases when administering the MMSE to Caucasian and African American older adults. The MMSE alone is preferred for older Latinos unless comparing CIND and dementia, in which case the FOME alone would then be recommended. Findings suggest that ethnicity is important in the selection of an appropriate cognitive screen and cut-score to use with older adults. [ABSTRACT FROM AUTHOR]

Objectives: Magnetic Resonance Spectroscopy (MRS) may provide a precise and reliable assessment of the extent and severity of neural tissue loss caused by various diseases. In particular, the N-Acetyl Aspartate (NAA) and Creatine (Cr) ratio has been found to be an indicator of the degree of neuronal loss in Alzheimer's disease (AD). Memantine is thought to benefit the AD brain by stabilizing the NMDA receptors on neurons in turn reducing excitotoxicity. Despite its effectiveness in treating moderate to severe AD, memantine has not had similar success in the treatment of mildly demented AD patients. The objective of this study was to test whether memantine would slow or prevent the loss of neurons in mild to moderate AD patients. Methods: A double-blind placebo-controlled study was designed to measure the effect of a year-long course of memantine in patients with a probable AD diagnosis with mild to moderate dementia. The primary outcome measure was stipulated to be change in MRS NAA/Cr ratio in inferior parietal cortex in memantine relative to the placebo treatment condition. The secondary outcome measures were changes in cognitive and function scale scores. Results: This pilot study failed to demonstrate a benefit of memantine on the primary outcome measure, the inferior parietal NAA/Cr ratio, or the secondary outcome measures. Conclusions: More studies are needed to determine the effect of memantine on regions of the brain significantly affected by AD pathology. [ABSTRACT FROM AUTHOR]

Objectives: Magnetic Resonance Spectroscopy (MRS) may provide a precise and reliable assessment of the extent and severity of neural tissue loss caused by various diseases. In particular, the N-Acetyl Aspartate (NAA) and Creatine (Cr) ratio has been found to be an indicator of the degree of neuronal loss in Alzheimer's disease (AD). Memantine is thought to benefit the AD brain by stabilizing the NMDA receptors on neurons in turn reducing excitotoxicity. Despite its effectiveness in treating moderate to severe AD, memantine has not had similar success in the treatment of mildly demented AD patients. The objective of this study was to test whether memantine would slow or prevent the loss of neurons in mild to moderate AD patients. Methods: A double-blind placebo-controlled study was designed to measure the effect of a year-long course of memantine in patients with a probable AD diagnosis with mild to moderate dementia. The primary outcome measure was stipulated to be change in MRS NAA/Cr ratio in inferior parietal cortex in memantine relative to the placebo treatment condition. The secondary outcome measures were changes in cognitive and function scale scores. Results: This pilot study failed to demonstrate a benefit of memantine on the primary outcome measure, the inferior parietal NAA/Cr ratio, or the secondary outcome measures. Conclusions: More studies are needed to determine the effect of memantine on regions of the brain significantly affected by AD pathology. [ABSTRACT FROM AUTHOR]

Objectives: Magnetic Resonance Spectroscopy (MRS) may provide a precise and reliable assessment of the extent and severity of neural tissue loss caused by various diseases. In particular, the N-Acetyl Aspartate (NAA) and Creatine (Cr) ratio has been found to be an indicator of the degree of neuronal loss in Alzheimer's disease (AD). Memantine is thought to benefit the AD brain by stabilizing the NMDA receptors on neurons in turn reducing excitotoxicity. Despite its effectiveness in treating moderate to severe AD, memantine has not had similar success in the treatment of mildly demented AD patients. The objective of this study was to test whether memantine would slow or prevent the loss of neurons in mild to moderate AD patients.Methods: A double-blind placebo-controlled study was designed to measure the effect of a year-long course of memantine in patients with a probable AD diagnosis with mild to moderate dementia. The primary outcome measure was stipulated to be change in MRS NAA/Cr ratio in inferior parietal cortex in memantine relative to the placebo treatment condition. The secondary outcome measures were changes in cognitive and function scale scores.Results: This pilot study failed to demonstrate a benefit of memantine on the primary outcome measure, the inferior parietal NAA/Cr ratio, or the secondary outcome measures.Conclusions: More studies are needed to determine the effect of memantine on regions of the brain significantly affected by AD pathology. [ABSTRACT FROM AUTHOR]

In this article, we review current research regarding diagnosis of cognitive impairment in nondemented adults and discuss why medications and cognitive training together may be more beneficial than either alone. We also review potential cognitive enhancers and future research challenges. There are major reasons for such research: (a) Large numbers of older adults without dementia but with cognitive problems are not treatable with current cognitive training techniques; (b) some medications offer a rationale (i.e., cognitive enhancement) and some evidence that they might be a useful adjunct; and (c) there are unanswered questions about which population to target, which medications to use, how to administer them, and issues regarding tolerance and use of appropriate (active) placebo controls. As the number of cognitively impaired older adults grows, it is likely that there will be pressure to treat more broadly with both medications and cognitive training. [ABSTRACT FROM AUTHOR]

The current study used Department of Veteran's Affairs (VA) clinical records, State of California pesticide application records, spatial maps of distribution of Parkinson's disease patients, and pesticide applications to determine if there was evidence for "blow-in" of pesticides as a factor in explaining the prevalence of Central Valley Parkinson's disease. The results did not support the hypothesis of increasing prevalence of Parkinsonism attributable to wind drift. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the role of the acute-phase protein serum amyloid A (A-SAA) in regulating cell adhesion molecule expression, leukocyte recruitment, and angiogenesis in rheumatoid arthritis (RA). METHODS: Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and matrix metalloproteinase 1 (MMP-1) expression was examined in RA fibroblast-like synoviocytes (FLS) and human microvascular endothelial cells (HMVECs) using flow cytometry and enzyme-linked immunosorbent assay techniques. Peripheral blood mononuclear cell (PBMC) adhesion to FLS/HMVECs was determined by flow cytometry. Angiogenesis was examined using a Boyden chemotaxis chamber and Matrigel tubule formation. NF-kappaB/IkappaBalpha mediation of the effects of A-SAA was investigated using a specific NF-kappaB inhibitor and Western blotting. RESULTS: A-SAA significantly enhanced the time- and dose-dependent expression of ICAM-1 and VCAM-1 as effectively as interleukin-1beta/tumor necrosis factor alpha. A-SAA promoted the adhesion of PBMCs to FLS and HMVECs. In addition, A-SAA at 10 mug/ml and 50 mug/ml significantly increased endothelial cell tube formation by 69% and 207%, respectively. At 50 mug/ml and 100 mug/ml, A-SAA increased HMVEC migration by 188 +/- 54% and 296 +/- 71%, respectively (mean +/- SEM). A-SAA-induced expression of VCAM-1, ICAM-1, and MMP-1 was down-regulated by NF-kappaB inhibition. Furthermore, A-SAA induced IkappaBalpha degradation and NF-kappaB translocation, suggesting that its proinflammatory effects are mediated in part by NF-kappaB signaling. CONCLUSION: Our findings demonstrate the ability of A-SAA to induce adhesion molecule expression, angiogenesis, and matrix degradation, mechanisms that are mediated by NF-kappaB. Targeting A-SAA and its signaling pathways may represent a new therapeutic approach in the treatment of RA. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess whether pharmacy database information from US Department of Veterans Affairs (VA) medical centers could be used to screen for areas of higher Parkinson's disease prevalence in patients exposed to pesticides. The authors used pharmacy data sets and compared the use of antiparkinsonian medications at 2 VA medical centers in California: one in Palo Alto, near the ocean, and one in Fresno, downwind from extensively farmed parts of the Central Valley. They found that patients at Fresno had higher odds ratios (1.5-1.8) for the use of Parkinson's disease medications than patients at Palo Alto. These data are consistent with the observations of prior epidemiologic studies and suggest that VA pharmacy databases can prioritize locations for further epidemiologic research. However, a thorough exploration of alternative explanations is needed to reach definitive conclusions regarding the findings suggested by this method. [ABSTRACT FROM AUTHOR]