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The high-temperature superconducting cuprate La 2−x Sr x CuO₄ (LSCO) shows several phases ranging from antiferromagnetic insulator to metal with increasing hole doping. To understand how the nature of the hole state evolves with doping, we have carried out high-resolution Compton scattering measurements at room temperature together with first-principles electronic structure computations on a series of LSCO single crystals in which the hole doping level varies from the underdoped (UD) to the overdoped (OD) regime. Holes in the UD system are found to primarily populate the O 2p x /p y orbitals. In contrast, the character of holes in the OD system is very different in that these holes mostly enter Cu d orbitals. High-resolution Compton scattering provides a bulk-sensitive method for imaging the orbital character of dopants in complex materials.

Visceral pain and intestinal dysbiosis are associated with Irritable Bowel Syndrome (IBS), a common functional gastrointestinal disorder without available efficient therapies. In this study, a decrease of Faecalibacterium prausnitzii presence has been observed in an IBS-like rodent model induced by a neonatal maternal separation (NMS) stress. Moreover, it was investigated whether F. prausnitzii may have an impact on colonic sensitivity. The A2-165 reference strain, but not its supernatant, significantly decreased colonic hypersensitivity induced by either NMS in mice or partial restraint stress in rats. This effect was associated with a reinforcement of intestinal epithelial barrier. Thus, F. prausnitzii exhibits anti-nociceptive properties, indicating its potential to treat abdominal pain in IBS patients.

While the notion of evenness is generally undisputed, its opposite, unevenness, is vague. Conventionally, evenness is understood to decrease, and thus unevenness to increase, as the effective number of types of positive frequency tends towards one while the number of types is held constant. Complete unevenness can thus be approached but never realized for more than one type. In order to arrive at explicit states of minimum evenness for any number of types, equalness is introduced as a complementary concept of evenness. Realization of the new concept turns out to require a change in orientation from unevenness to unequalness. Decreasing evenness in the sense of increasing unequalness entails an increase in inequality among type frequencies. Unequalness can effectively be envisioned as the diversity in the distribution of step‐heights in a frequency distribution ranked in decreasing order (frequency profile). Application of appropriate measures of diversity reveals that maximum unequalness (minimum equalness) is assumed for linearly decreasing frequency profiles (stepladders). A consistent diversity‐based measure of equalness is obtained by normalizing the step‐height diversity with respect to the number of types, with the result that this measure equals one for complete equalness/evenness (uniformity) and zero for complete unequalness (as in stepladders). It turns out that the new equalness measure is highly sensitive to characteristics of frequency profiles that are commonly associated with the evenness notion but are poorly reflected by the conventional evenness measures as a consequence of the realization of their minimum for monomorphism.

Background Declining resources due to climate change may endanger the persistence of populations by reducing fecundity and thus population fitness via effects on gamete production. The optimal mode of generative reproduction allocates the limited resources to ovule and pollen production in proportions that maximize the number of fertilized ovules in the population. In order to locate this optimum and derive reproduction modes that compensate for declined resources to maintain reproductive success, a model of gamete production, pollen dispersal, and ovule fertilization is developed. Specification of opportunities for compensation is given priority over specification of physiological or evolutionary mechanisms of adaptation. Thus model parameters summarize gametic production resources, resource investment per gamete, resource allocation as proportion of resources invested in ovules, and pollen density as size of the pollen dispersal range and proportion of pollen retained within the range. Retained pollen disperses randomly, and an ovule is fertilized if at least one pollen settles on its surface. The outcome is the expected number of fertilized ovules. Results Maximization of fertilization success is found to require the investment of more gametic production resources in ovules than in pollen, irrespective of the parameter values. Resource decline can be compensated by adjusting the resource allocation if the maximum expected number of fertilized ovules after the decline is not less than the expected number the population experienced before the decline. Compensation is also possible under some conditions by increasing the pollen density, either by raising a low pollen retention or by shrinking the dispersal range. Conclusion Fertilization success in populations affected by resource decline may be maintainable by adjustment of the sexual allocation of gametic production resources or by increasing pollen density. The results have implications for insect pollination, sexual allocation bias, management measures, and metapopulation fragmentation.

(1) Background: Is variation among the communities of a metacommunity higher than within the communities? Community ecologists and population geneticists often characterize the structure of metacommunities by partitioning variation (diversity) into the two following components using measures such as FST or GST and α- and β-diversity. The within-communities component is usually some average of (type, species, genetic) diversities within the communities, and the among-communities component is the additive or multiplicative complement of the overall diversity. Such an among-communities component lacks independent conceptual specification, a matter of long-standing dispute. Only if the two components are independently and commensurably specified can the central question of comparability be answered meaningfully. (2) Methods: A novel approach to overcoming this conceptual weakness identifies two principles of the partitioning of variation among communities (concentration and division) then relates these principles to the common notions of variation (diversity) within and among communities, distinguishes primary indicators to quantify the partitioning principles, transforms the indicators into conceptually independent measures (indices) of variation within and among communities, and by this attains their commensurability and thus comparability. The application of the methods to quantifying the effects of evolutionary mechanisms is outlined. (3) Results: Common approaches are corrected and extended. (a) Analyses of metacommunity/metapopulation structures that rely on apportionment or related indices and take its complement to be differentiation yield incomparable measures of variation within and among communities. (b) The common practice of partitioning the total diversity into additive or multiplicative components produces the inconsistent ranking of the two components. (c) Community concentration and division can result from elementary processes of adaptive differentiation and migration (gene flow) among communities, where the (commensurable) amounts of community concentration and division reflect the relative participation of these processes in metacommunity structuring and translate directly into the measures of diversity within and among communities. (d) The modelling of the contributions of the two partitioning principles to the metacommunity structure is restricted by the marginal distributions of types and community affiliation. (e) The model demonstrates the degree to which adaptational processes at the metacommunity level are mixtures of adaptational events within and among communities.

Biological variation is commonly measured at two basic levels: variation within individual communities, and the distribution of variation over communities or within a metacommunity. We develop a classification for the measurement of biological variation on both levels: Within communities into the categories of dispersion and diversity, and within metacommunities into the categories of compositional differentiation and partitioning of variation. There are essentially two approaches to characterizing the distribution of trait variation over communities in that individuals with the same trait state or type tend to occur in the same community (describes differentiation tendencies), and individuals with different types tend to occur in different communities (describes apportionment tendencies). Both approaches can be viewed from the dual perspectives of trait variation distributed over communities (CT perspective) and community membership distributed over trait states (TC perspective). This classification covers most of the relevant descriptors (qualified measures) of biological variation, as is demonstrated with the help of major families of descriptors. Moreover, the classification is shown to open ways to develop new descriptors that meet current needs. Yet the classification also reveals the misclassification of some prominent and widely applied descriptors: Dispersion is often misclassified as diversity, particularly in cases where dispersion descriptor allow for the computation of effective numbers; the descriptor GST of population genetics is commonly misclassified as compositional differentiation and confused with partitioning-oriented differentiation, whereas it actually measures partitioning-oriented apportionment; descriptors of β-diversity are ambiguous about the differentiation effects they are supposed to represent and therefore require conceptual reconsideration.

Purpose This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms’ tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients. Methods Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab–chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A–C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination. Results Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely. Conclusions Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab–chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.

This study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liège, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4 ± 10.4 % vs. 90.3 ± 6.6 %, p  = 0.0013; antibiotics documented 87.9 ± 9.0 % vs. 95.6 ± 5.1 %, p  < 0.0001; and duration or review date documented 31.9 ± 15.4 % vs. 67.7 ± 15.2 %, p  < 0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators.

While evenness is understood to be maximal if all types (species, genotypes, alleles, etc.) are represented equally (via abundance, biomass, area, etc.), its opposite, maximal unevenness, either remains conceptually in the dark or is conceived as the type distribution that minimizes the applied evenness index. The latter approach, however, frequently leads to conceptual inconsistency due to the fact that the minimizing distribution is not specifiable or is monomorphic. The state of monomorphism, however, is indeterminate in terms of its evenness/unevenness characteristics. Indeed, the semantic indeterminacy also shows up in the observation that monomorphism represents a state of pronounced discontinuity for the established evenness indices. This serious conceptual inconsistency is latent in the widely held idea that evenness is an independent component of diversity. As a consequence, the established evenness indices largely appear as indicators of relative polymorphism rather than as indicators of evenness. In order to arrive at consistent measures of evenness/unevenness, it seems indispensable to determine which states are of maximal unevenness and then to assess the position of a given type distribution between states of maximal evenness and maximal unevenness. Since semantically, unevenness implies inequality among type representations, its maximum is reached if all type representations are equally different. For given number of types, this situation is realized if type representations, when ranked in descending order, show equal differences between adjacent types. We term such distributions “stepladders” as opposed to “plateaus” for uniform distributions. Two approaches to new evenness measures are proposed that reflect different perspectives on the positioning of type distributions between the closest stepladders and the closest plateaus. Their two extremes indicate states of complete evenness and complete unevenness, and the midpoint is postulated to represent the turning point between prevailing evenness and prevailing unevenness. The measures are graphically illustrated by evenness surfaces plotted above frequency simplices for three types, and by transects through evenness surfaces for more types. The approach can be generalized to include variable differences between types (as required in analyses of functional evenness) by simply replacing types with pairs of different types. Pairs, as the new types, can be represented by their abundances, for example, and these can be modified in various ways by the differences between the two types that form the pair. Pair representations thus consist of both the difference between the paired types and their frequency. Omission of pair frequencies leads to conceptual ambiguity. Given this specification of pair representations, their evenness/unevenness can be evaluated using the same indices developed for simple types. Pair evenness then turns out to quantify dispersion evenness.

In ruminants, cis and trans C18:1 isomers are intermediates of fatty acid transformations in the rumen and their relative amounts shape the nutritional quality of ruminant products. However, their exact synthetic pathways are unclear and their proportions change with the forage:concentrate ratio in ruminant diets. This study traced the metabolism of vaccenic acid, the main trans C18:1 isomer found in the rumen, through the incubation of labeled vaccenic acid with mixed ruminal microbes adapted to different diets. [1- 13 C] trans -11 C18:1 was added to in vitro cultures with ruminal fluids of sheep fed either a forage or a concentrate diet. 13 C enrichment in fatty acids was analyzed by gas-chromatography-mass spectrometry after 0, 5 and 24 h of incubation. 13 C enrichment was found in stearic acid and in all cis and trans C18:1 isomers. Amounts of 13 C found in fatty acids showed that 95% of vaccenic acid was saturated to stearic acid after 5 h of incubation with the concentrate diet, against 78% with the forage diet. We conclude that most vaccenic acid is saturated to stearic acid, but some is isomerized to all cis and trans C18:1 isomers, with probably more isomerization in sheep fed a forage diet.