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The need for new antimicrobial agents is greater than ever because of the emergence of multidrug resistance in common pathogens, the rapid emergence of new infections, and the potential for use of multidrug-resistant agents in bioweapons. Paradoxically, some pharmaceutical companies have indicated that they are curtailing anti-infective research programs. We evaluated the United States Food and Drug Administration (FDA) databases of approved drugs and the research and development programs of the world's largest pharmaceutical and biotechnology companies to document trends in the development of new antimicrobial agents. FDA approval of new antibacterial agents decreased by 56% over the past 20 years (1998-2002 vs. 1983-1987). Projecting future development, new antibacterial agents constitute 6 of 506 drugs disclosed in the developmental programs of the largest pharmaceutical and biotechnology companies. Despite the critical need for new antimicrobial agents, the development of these agents is declining. Solutions encouraging and facilitating the development of new antimicrobial agents are needed.

During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: \"proven,\" \"probable,\" and \"possible.\" The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.

The evolution of C4 photosynthesis in plants has allowed the maintenance of high CO2 assimilation rates despite lower stomatal conductances. This underpins the greater water-use efficiency in C4 species and their tendency to occupy drier, more seasonal environments than their C3 relatives. The basis of interspecific variation in maximum stomatal conductance to water (g max), as defined by stomatal density and size, was investigated in a common-environment screening experiment. Stomatal traits were measured in 28 species from seven grass lineages, and comparative methods were used to test for predicted effects of C3 and C4 photosynthesis, annual precipitation and habitat wetness on g max. Novel results were as follows: significant phylogenetic patterns exist in g max and its determinants, stomatal size and stomatal density; C4 species consistently have lower g max than their C3 relatives, associated with a shift towards smaller stomata at a given density. A direct relationship between g max and precipitation was not supported. However, we confirmed associations between C4 photosynthesis and lower precipitation, and showed steeper stomatal size–density relationships and higher g max in wetter habitats. The observed relationships between stomatal patterning, photosynthetic pathway and habitat provide a clear example of the interplay between anatomical traits, physiological innovation and ecological adaptation in plants.

Plastic deformation in metallic materials is generally governed by highly localized and intrinsically heterogeneous deformation processes, including crystallographic slip banding, deformation twinning, phase transformation and grain-boundary sliding. These mechanisms operate at the sub-grain scale where they are competing, interacting, and are sometimes incompatible for short-range transmission due to deformation confinement within individual grains. The heterogeneous nature of irreversible deformation at the microstructure scale also applies at the mesoscale, . the scale of the crystalline aggregate. Capturing experimentally the discrete and heterogeneous deformation processes at the microstructure scale is essential to understand elementary deformation processes involved for specific loading conditions, quantifying their intensity to finally achieve a better dialogue with numerical models of crystal plasticity for the prediction of mechanical behavior and the lifetime of parts. High-resolution digital image correlation (HR-DIC), implemented on scanning electron microscopy images, has emerged as a key technique to quantify these phenomena by providing full-field measurements of in-plane displacement and strain at sub-micron spatial resolution over statistically representative fields of view. This review outlines the experimental foundations, data-processing strategies, and correlative analysis frameworks that underpin the use of HR-DIC for studying strain localization in metals.

Background Equine gut microbiology studies to date have primarily focused on horses and ponies, which represent only one of the eight extant equine species. This is despite asses and mules comprising almost half of the world’s domesticated equines, and donkeys being superior to horses/ponies in their ability to degrade dietary fiber. Limited attention has also been given to commensal anaerobic fungi and archaea even though anaerobic fungi are potent fiber degrading organisms, the activity of which is enhanced by methanogenic archaea. Therefore, the objective of this study was to broaden the current knowledge of bacterial, anaerobic fungal and archaeal diversity of the equine fecal microbiota to multiple species of equines. Core taxa shared by all the equine fecal samples ( n  = 70) were determined and an overview given of the microbiota across different equine types (horse, donkey, horse × donkey and zebra). Results Equine type was associated with differences in both fecal microbial concentrations and community composition. Donkey was generally most distinct from the other equine types, with horse and zebra not differing. Despite this, a common bacterial core of eight OTUs (out of 2070) and 16 genus level groupings (out of 231) was found in all the fecal samples. This bacterial core represented a much larger proportion of the equine fecal microbiota than previously reported, primarily due to the detection of predominant core taxa belonging to the phyla Kiritimatiellaeota (formerly Verrucomicrobia subdivision 5) and Spirochaetes . The majority of the core bacterial taxa lack cultured representation. Archaea and anaerobic fungi were present in all animals, however, no core taxon was detected for either despite several taxa being prevalent and predominant. Conclusions Whilst differences were observed between equine types, a core fecal microbiota existed across all the equines. This core was composed primarily of a few predominant bacterial taxa, the majority of which are novel and lack cultured representation. The lack of microbial cultures representing the predominant taxa needs to be addressed, as their availability is essential to gain fundamental knowledge of the microbial functions that underpin the equine hindgut ecosystem.

Cavity magnon polaritons are mixed quasiparticles that arise from the strong coupling between cavity photons and quantized magnons. Combining high-speed photons with long-coherence-time magnons, such polaritons promise to be a potential candidate for quantum information processing. For harnessing coherent information contained in spatially distributed polariton states, it is highly desirable to manipulate cavity magnon polaritons in a two-dimensional system. Here, we demonstrate that tunable cavity magnon polariton transport can be achieved by strongly coupling magnons to microwave photons in a cross-cavity. An analog to the dynamic Hall effect has been demonstrated in a planar cavity spintronic device, where the propagation of cavity-magnon-polaritons is deflected transversally due to hybrid magnon-photon dynamics. Implementing this device as a Michelson-type interferometer using the coherent nature of the dynamic Hall and longitudinal signals, we have developed a proof-of-principle logic device to control the amplitude of cavity-magnon-polaritons by encoding the input microwave phase. Exploring photon-polariton interactions advances not only the understanding of polariton dynamics but also the modern technologies. Here the authors take advantage of strong coupled magnons and microwave photons in a cross-cavity to achieve tunable cavity magnon polariton transport which can be potentially applied as logic devices.

Background Compared to horses and ponies, donkeys have increased degradation of dietary fiber. The longer total mean retention time of feed in the donkey gut has been proposed to be the basis of this, because of the increased time available for feed to be acted upon by enzymes and the gut microbiota. However, differences in terms of microbial concentrations and/or community composition in the hindgut may also underpin the increased degradation of fiber in donkeys. Therefore, a study was conducted to assess if differences existed between the fecal microbiota of pony, donkey and hybrids derived from them (i.e. pony × donkey) when fed the same forage diet. Results Fecal community composition of prokaryotes and anaerobic fungi significantly differed between equine types. The relative abundance of two bacterial genera was significantly higher in donkey compared to both pony and pony x donkey: Lachnoclostridium 10 and ‘probable genus 10’ from the Lachnospiraceae family. The relative abundance of Piromyces was significantly lower in donkey compared to pony × donkey, with pony not significantly differing from either of the other equine types. In contrast, the uncultivated genus SK3 was only found in donkey (4 of the 8 animals). The number of anaerobic fungal OTUs was also significantly higher in donkey than in the other two equine types, with no significant differences found between pony and pony × donkey. Equine types did not significantly differ with respect to prokaryotic alpha diversity, fecal dry matter content or fecal concentrations of bacteria, archaea and anaerobic fungi. Conclusions Donkey fecal microbiota differed from that of both pony and pony × donkey. These differences related to a higher relative abundance and diversity of taxa with known, or speculated, roles in plant material degradation. These findings are consistent with the previously reported increased fiber degradation in donkeys compared to ponies, and suggest that the hindgut microbiota plays a role. This offers novel opportunities for pony and pony × donkey to extract more energy from dietary fiber via microbial mediated strategies. This could potentially decrease the need for energy dense feeds which are a risk factor for gut-mediated disease.

We conducted a prospective, multicenter observational study of adults (n = 1447) and children (n = 144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P < .001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P < .001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials.

An understanding of the perceived importance of a variety of factors affecting the ease of handling of sheep and the interactions between these factors is valuable in improving profitability and welfare of the livestock. Many factors may contribute to animal behaviour during handling, and traditionally these factors have been assessed in isolation under experimental conditions. A human social component to this phenomenon also exists. The aim of this study was to gain a deeper understanding of the importance of a variety of factors affecting ease of handling, and the interactions between these from the perspective of the livestock transporter. Qualitative interviews were used to investigate the factors affecting sheep behaviour during handling. Interview transcripts underwent thematic analysis. Livestock transporters discussed the effects of attitudes and behaviours towards sheep, helpers, facilities, distractions, environment, dogs and a variety of sheep factors including breed, preparation, experience and sex on sheep behaviour during handling. Transporters demonstrated care and empathy and stated that patience and experience were key factors determining how a person might deal with difficult sheep. Livestock transporters strongly believed facilities (ramps and yards) had the greatest impact, followed by sheep experience (naivety of the sheep to handling and transport) and breed. Transporters also discussed the effects of distractions, time of day, weather, dogs, other people, sheep preparation, body condition and sheep sex on ease of handling. The concept of individual sheep temperament was indirectly expressed.

The incidence of disseminated candidiasis has increased dramatically over the past several decades. Fortunately, in recent years, a variety of new antifungal agents have become available to treat these infections. On the basis of efficacy, safety, and cost considerations, fluconazole is the agent of choice for the empirical treatment of disseminated candidiasis in nonneutropenic, hemodynamically stable patients, unless a patient is suspected to be infected with an azole-resistant species (i.e., Candida glabrata or Candida krusei). For hemodynamically unstable or neutropenic patients, agents with broader species coverage, such as polyenes, echinocandins, or, possibly, voriconazole, are preferred for empirical treatment of candidemia. Modification of the initial, empirical regimen depends on the response to therapy and the subsequent identification of the species of the offending pathogen. Echinocandins or high-dose polyenes are preferred for the treatment of infections with C. glabrata or C. krusei. Central venous catheters should be removed from all patients who have disseminated candidiasis, if feasible, and antifungal therapy should be administered to all patients who have candidemia or proven candidiasis.