New grass phylogeny resolves deep evolutionary relationships and discovers C4 origins.

• Grasses rank among the world's most ecologically and economically important plants. Repeated evolution of the C(4) syndrome has made photosynthesis highly efficient in many grasses, inspiring intensive efforts to engineer the pathway into C(3) crops. However, comparative biology has been of limited use to this endeavor because of uncertainty in the number and phylogenetic placement of C(4) origins. • We built the most comprehensive and robust molecular phylogeny for grasses to date, expanding sampling efforts of a previous working group from 62 to 531 taxa, emphasizing the C(4)-rich PACMAD (Panicoideae, Arundinoideae, Chloridoideae, Micrairoideae, Aristidoideae and Danthonioideae) clade. Our final matrix comprises c. 5700 bp and is > 93% complete. • For the first time, we present strong support for relationships among all the major grass lineages. Several new C(4) lineages are identified, and previously inferred origins confirmed. C(3)/C(4) evolutionary transitions have been highly asymmetrical, with 22-24 inferred origins of the C(4) pathway and only one potential reversal. • Our backbone tree clarifies major outstanding systematic questions and highlights C(3) and C(4) sister taxa for comparative studies. Two lineages have emerged as hotbeds of C(4) evolution. Future work in these lineages will be instrumental in understanding the evolution of this complex trait.

Methods for Determining Frequency- and Region-Dependent Relationships Between Estimated LFPs and BOLD Responses in Humans

The relationship between electrophysiological and functional magnetic resonance imaging (fMRI) signals remains poorly understood. To date, studies have required invasive methods and have been limited to single functional regions and thus cannot account for possible variations across brain regions. Here we present a method that uses fMRI data and singe-trial electroencephalography (EEG) analyses to assess the spatial and spectral dependencies between the blood-oxygenation-level-dependent (BOLD) responses and the noninvasively estimated local field potentials (eLFPs) over a wide range of frequencies (0-256 Hz) throughout the entire brain volume. This method was applied in a study where human subjects completed separate fMRI and EEG sessions while performing a passive visual task. Intracranial LFPs were estimated from the scalp-recorded data using the ELECTRA source model. We compared statistical images from BOLD signals with statistical images of each frequency of the eLFPs. In agreement with previous studies in animals, we found a significant correspondence between LFP and BOLD statistical images in the gamma band (44-78 Hz) within primary visual cortices. In addition, significant correspondence was observed at low frequencies (<14 Hz) and also at very high frequencies (>100 Hz). Effects within extrastriate visual areas showed a different correspondence that not only included those frequency ranges observed in primary cortices but also additional frequencies. Results therefore suggest that the relationship between electrophysiological and hemodynamic signals thus might vary both as a function of frequency and anatomical region.

Phylogenetic relationships and divergence times among dormice (Rodentia, Gliridae) based on three nuclear genes

We examined phylogenetic relationships among six species representing three subfamilies, Glirinae, Graphiurinae and Leithiinae with sequences from three nuclear protein-coding genes (apolipoprotein B, APOB; interphotoreceptor retinoid-binding protein, IRBP; recombination-activating gene 1, RAG1). Phylogenetic trees reconstructed from maximum-parsimony (MP), maximum-likelihood (ML) and Bayesian-inference (BI) analyses showed the monophyly of Glirinae (Glis and Glirulus) and Leithiinae (Dryomys, Eliomys and Muscardinus) with strong support, although the branch length maintaining this relationship was very short, implying rapid diversification among the three subfamilies. Divergence time estimates were calculated from ML (local clock model) and Bayesian-dating method using a calibration point of 25 Myr (million years) ago for the divergence between Glis and Glirulus, and 55 Myr ago for the split between lineages of Gliridae and Sciuridae on the basis of fossil records. The results showed that each lineage of Graphiuros, Glis, Glirulus and Muscardinus dates from the Late Oligocene to the Early Miocene period, which is mostly in agreement with fossil records. Taking into account that warm climate harbouring a glirid-favoured forest dominated from Europe to Asia during this period, it is considered that this warm environment triggered the prosperity of the glirid species through the rapid diversification. Glirulus japonicas is suggested to be a relict of this ancient diversification during the warm period.

Sequential therapist interventions and the therapeutic alliance: a pilot study

(from the journal abstract) Scientific interest for the concept of alliance has been maintained and stimulated by repeated findings that a strong alliance is associated with facilitative treatment process and favourable treatment outcome. However, because the alliance is not in itself a therapeutic technique, these findings were unsuccessful in bringing about significant improvements in clinical practice. An essential issue in modern psychotherapeutic research concerns the relation between common factors which are known to explain great variance in empirical results and the specific therapeutic techniques which are the primary basis of clinical training and practice. This pilot study explored sequences in therapist interventions over four sessions of brief psychodynamic investigation. It aims at determining if patterns of interventions can be found during brief psychodynamic investigation and if these patterns can be associated with differences in the therapeutic alliance. Therapist interventions where coded using the Psychodynamic Intervention Rating Scale (PIRS) which enables the classification of each therapist utterance into one of 9 categories of interpretive interventions (defence interpretation, transference interpretation), supportive interventions (question, clarification, association, reflection, supportive strategy) or interventions about the therapeutic frame (work-enhancing statement, contractual arrangement). Data analysis was done using lag sequential analysis, a statistical procedure which identifies contingent relationships in time among a large number of behaviours. The sample includes N = 20 therapist-patient dyads assigned to three groups with: (1) a high and stable alliance profile, (2) a low and stable alliance profile and (3) an improving alliance profile. Results suggest that therapists most often have one single intention when interacting with patients. Large sequences of questions, associations and clarifications were found, which indicate that if a therapist asks a question, clarifies or associates, there is a significant probability that he will continue doing so. A single theme sequence involving frame interventions was also observed. These sequences were found in all three alliance groups. One exception was found for mixed sequences of interpretations and supportive interventions. The simultaneous use of these two interventions was associated with a high or an improving alliance over the course of treatment, but not with a low and stable alliance where only single theme sequences of interpretations were found. In other words, in this last group, therapists were either supportive or interpretative, whereas with high or improving alliance, interpretations were always given along with supportive interventions. This finding provides evidence that examining therapist interpretation individually can only yield incomplete findings. How interpretations were given is important for alliance building. It also suggests that therapists should carefully dose their interpretations and be supportive when necessary in order to build a strong therapeutic alliance. And from a research point of view, to study technical interventions, we must look into dynamic variables such as dosage, the supportive quality of an intervention, and timing. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

Five years of sleep apnea treatment with a mandibular advancement device. Side effects and technical complications

Objective: To determine the variation in prevalence of temporomandibular disorders (TMD), other side effects, and technical complications during 5 years of sleep apnea treatment with a mandibular advancement device. Materials and Methods: Forty patients diagnosed with obstructive sleep apnea received an adjustable appliance at 70% of the maximum protrusion. The protrusion was then progressively increased. TMD (diagnosed according to the Research Diagnostic Criteria for TMD), overjet, overbite, occlusal contacts, subjective side effects, and technical complications were recorded before and a mean of 14, 21, and 58 months after treatment and analyzed by the Wilcoxon test (P Less-than .05). Results: Fifteen patients still used the oral appliance at the 5-year follow-up, and no significant variation in TMD prevalence was observed. Subjective side effects were common, and a significant reduction was found in overjet, overbite, and in the number of occlusal contacts. Furthermore, the patients made a mean of 2.5 unscheduled dental visits per year and a mean of 0.8 appliance repairs/relines per year by a dental technician. The most frequent unscheduled visits were needed during the first year and were a result of acrylic breakage on the lateral telescopic attachment, poor retention, and other adjustments to improve comfort. Conclusions: Five-year oral appliance treatment does not affect TMD prevalence but is associated with permanent occlusal changes in most sleep apnea patients during the first 2 years. Patients seek several unscheduled visits, mainly because of technical complications.

Time-Temperature Strength-Reaction Product Relationships in Lime-Bentonite-Water Mixtures, HR-111, 1965

The interrelation of curing time, curing temperature, strength, and reactions in lime-bentonite-water mixtures was examined. Samples were molded at constant density and moisture content and then cured for periods of from 1 to 56 days at constant temperatures that ranged from 5C to 60C. After the appropriate curing time the samples were tested for unconfined compressive strength. The broken samples were then analyzed by x-ray diffractometer and spectrophotometer to determine the identity of the reaction products present after each curing period. It was found that the strength gain of lime-clay mixtures cured at different temperatures is due to different phases of the complex reaction, lime & clay to CSH(gel) to CSH(II) to CSH(I) to tobermorite. The farther the reaction proceeds, the higher the strength. There was also evidence of lattice substitutions in the structure of the calcium silicate hydrates at curing temperatures of 50C and higher. No consistent relationship between time, temperature, strength, and the S/A ration of reaction products existed, but in order to achieve high strengths the apparent C/S ration had to be less than two. The curing temperature had an effect on the strength developed by a given amount of reacted silica in the cured lime-clay mixture, but at a given curing temperature the cured sample that had the largest amount of reacted silica gave the highest strength. Evidence was found to indicate that during the clay reaction some calcium is indeed adsorbed onto the clay structure rather than entering into a pozzolanic reaction. Finally, it was determined that it is possible to determine the amount of silica and alumina in lime-clay reaction products by spectrophotometric analysis with sufficient accuracy for comparison purposes. The spectrophotometric analysis techniques used during the investigation were simple and were not time consuming.

Forestry Practices Manual Technical Guide, June 24, 2005

Technical Guide to Forestry Practices Manual.

Systematic and biogeographic relationships of the Japanese white-toothed shrew (Crocidura dsinezumi)

To assess the zoogeographic and phylogenetic relationships of C. dsinezumi, its systematic position has been investigated through electrophoretic comparisons. These comparisons comprise typical Indomalayan and Palaearctic species, including C. russula, the supposed sister taxon of the Japanese white-toothed shrew. The range of measured genetic distances that separate dsinezumi from the other shrews (Nei's D = 0.232-0.406) is typical for interspecific comparisons among Crocidura taxa. Our results reinforce morphologic considerations that suggest C. dsinezumi be treated as a valid species. Phylogenetic relationships deduced from a cladistic treatment of allozyme data refute the possibility that the western Palaearctic C. russula is the sister taxon of C. dsinezumi. Zoogeographic interpretation of the genetic results indicates that the Southeast Asian representatives constitute a clade distinct from one that includes the Palaearctic species. However, C. dsinezumi is difficult to assign to either clade due to many intermediate or plesiomorphic electrophoretic characters. Unlike the major karyologic and biochemical separation that divides Afrotropical and Palaearctic species, the subdivision between Palaearctic and Indomalayan Crocidura is not correlated with any trend in karyotypic evolution. It also is shown that the Eurasiatic species of Crocidura possessing 2n = 40 chromosomes (including C. dsinezumi) do not represent a particular clade, but probably share a plesiomorphic character. Further analysis of other Indian or Asiatic species is needed to test whether the Palaearctic versus Indomalayan separation is due to real zoogeographic barriers or whether it is the result of limited samples.

Prediction of cross-recognition of peptide-HLA A2 by Melan-A-specific cytotoxic T lymphocytes using three-dimensional quantitative structure-activity relationships.

The cross-recognition of peptides by cytotoxic T lymphocytes is a key element in immunology and in particular in peptide based immunotherapy. Here we develop three-dimensional (3D) quantitative structure-activity relationships (QSARs) to predict cross-recognition by Melan-A-specific cytotoxic T lymphocytes of peptides bound to HLA A*0201 (hereafter referred to as HLA A2). First, we predict the structure of a set of self- and pathogen-derived peptides bound to HLA A2 using a previously developed ab initio structure prediction approach [Fagerberg et al., J. Mol. Biol., 521-46 (2006)]. Second, shape and electrostatic energy calculations are performed on a 3D grid to produce similarity matrices which are combined with a genetic neural network method [So et al., J. Med. Chem., 4347-59 (1997)] to generate 3D-QSAR models. The models are extensively validated using several different approaches. During the model generation, the leave-one-out cross-validated correlation coefficient (q (2)) is used as the fitness criterion and all obtained models are evaluated based on their q (2) values. Moreover, the best model obtained for a partitioned data set is evaluated by its correlation coefficient (r = 0.92 for the external test set). The physical relevance of all models is tested using a functional dependence analysis and the robustness of the models obtained for the entire data set is confirmed using y-randomization. Finally, the validated models are tested for their utility in the setting of rational peptide design: their ability to discriminate between peptides that only contain side chain substitutions in a single secondary anchor position is evaluated. In addition, the predicted cross-recognition of the mono-substituted peptides is confirmed experimentally in chromium-release assays. These results underline the utility of 3D-QSARs in peptide mimetic design and suggest that the properties of the unbound epitope are sufficient to capture most of the information to determine the cross-recognition.

Decision curve analysis revisited: overall net benefit, relationships to ROC curve analysis, and application to case-control studies.

ABSTRACT: BACKGROUND: Decision curve analysis has been introduced as a method to evaluate prediction models in terms of their clinical consequences if used for a binary classification of subjects into a group who should and into a group who should not be treated. The key concept for this type of evaluation is the "net benefit", a concept borrowed from utility theory. METHODS: We recall the foundations of decision curve analysis and discuss some new aspects. First, we stress the formal distinction between the net benefit for the treated and for the untreated and define the concept of the "overall net benefit". Next, we revisit the important distinction between the concept of accuracy, as typically assessed using the Youden index and a receiver operating characteristic (ROC) analysis, and the concept of utility of a prediction model, as assessed using decision curve analysis. Finally, we provide an explicit implementation of decision curve analysis to be applied in the context of case-control studies. RESULTS: We show that the overall net benefit, which combines the net benefit for the treated and the untreated, is a natural alternative to the benefit achieved by a model, being invariant with respect to the coding of the outcome, and conveying a more comprehensive picture of the situation. Further, within the framework of decision curve analysis, we illustrate the important difference between the accuracy and the utility of a model, demonstrating how poor an accurate model may be in terms of its net benefit. Eventually, we expose that the application of decision curve analysis to case-control studies, where an accurate estimate of the true prevalence of a disease cannot be obtained from the data, is achieved with a few modifications to the original calculation procedure. CONCLUSIONS: We present several interrelated extensions to decision curve analysis that will both facilitate its interpretation and broaden its potential area of application.

Results from a prospective, randomized, controlled study evaluating the acceptability and effects of routine pre-IVF counselling.

BACKGROUND: The aim of this study was to evaluate a model of routine pre-IVF counselling focusing on the narrative capacities of couples. The acceptability of counselling, the effects on emotional factors and the participants' assessments were considered. METHODS: The study included 141 consecutive childless couples preparing for their first IVF. Randomization was carried out through sealed envelopes attributing participants to counselled and non-counselled groups and was accepted by 100 couples. Another 12 couples refused randomization because they wanted counselling and 29 because they did not. Questionnaires including the State-Trait Anxiety Inventory, the Beck Depression Inventory and assessments of help were mailed to couples before IVF and counselling, and after the IVF outcome. RESULTS: Counselling was accepted by 79% (112/141) of couples. There was no significant effect of counselling on anxiety and depression scores which were within normal ranges at both times. Counselling provided help for 86% (75/87) of initially non-demanding subjects and 96% (25/26) of those initially requesting a session. Help was noted in areas of psychological assistance, technical explanations and discussing relationships. CONCLUSIONS: This model of routine counselling centred on the narrative provides an acceptable form of psychological assistance for pre-IVF couples.