4,268 research outputs found

    Revisiting the Thermodynamic Stability of Indomethacin Polymorphs with Low-Frequency Vibrational Spectroscopy and Quantum Mechanical Simulations

    Get PDF
    The two major polymorphs of the active pharmaceutical ingredient indomethacin were studied using a combination of experimental low-frequency vibrational spectroscopies, theoretical solid-state density functional theory and ab initio molecular dynamics calculations. The results enable a complete spectral assignment of the low-frequency IR and Raman spectra, and yield new insight into the energetic and dynamical factors present within the solids to be understood. Ultimately, these results are used to rationalize the thermodynamic properties of the two crystals, which result in a contradiction to the long-held belief that the γ-form is the more stable polymorph at ambient conditions due to its predominant abundance. Overall, the study highlights the combined role that molecular conformation, bulk packing arrangement, and intermolecular forces have on the ultimate properties of pharmaceutical crystals, and the need for detailed analyses into all of these effects in order to predict the properties of materials

    Gene expression patterns during adaptation of a helminth parasite to different environmental niches

    Get PDF
    Using a genomic microarray, gene expression at three different developmental stages of the schistosome parasite were analyzed, resulting in the identification of 1154 developmentally enriched transcripts

    Benefiting from trial spacing without the cost of prolonged training: frequency, not duration, of trials with absent stimuli enhances perceived contingency

    Get PDF
    The statistical relation between two events influences the perception of how one event relates to the presence or absence of another. Interestingly, the simultaneous absence of both events, just like their mutual occurrence, is relevant for describing their contingency. In three experiments, we explored the relevance of coabsent events by varying the duration and frequency of trials without stimuli. We used a rapid trial streaming procedure and found that the perceived association between events is enhanced with increasing frequency of coabsent events, unlike the duration of coabsent events, which had little effect. These findings suggest ways in which the benefits of trial spacing, during which both events are absent, could be obtained without increasing total training time. Centrally, this can be done by frequent repeating of shortened coabsent events, each marked by a trial contextual cue. We discuss four potential accounts of how coabsent experience might be processed contributing to this effect: (a) contingency sensitivity, (b) testing effect, (c) reduced associative interference by the context, and (d) reduced encoding interference. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

    Physician Practice Patterns and Variation in the Delivery of Preventive Services

    Get PDF
    BACKGROUND: Strategies to improve preventive services delivery (PSD) have yielded modest effects. A multidimensional approach that examines distinctive configurations of physician attributes, practice processes, and contextual factors may be informative in understanding delivery of this important form of care. OBJECTIVE: We identified naturally occurring configurations of physician practice characteristics (PPCs) and assessed their association with PSD, including variation within configurations. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred thirty-eight family physicians in 84 community practices and 4,046 outpatient visits. MEASUREMENTS: Physician knowledge, attitudes, use of tools and staff, and practice patterns were assessed by ethnographic and survey methods. PSD was assessed using direct observation of the visit and medical record review. Cluster analysis identified unique configurations of PPCs. A priori hypotheses of the configurations likely to perform the best on PSD were tested using a multilevel random effects model. RESULTS: Six distinct PPC configurations were identified. Although PSD significantly differed across configurations, mean differences between configurations with the lowest and highest PSD were small (i.e., 3.4, 7.7, and 10.8 points for health behavior counseling, screening, and immunizations, respectively, on a 100-point scale). Hypotheses were not confirmed. Considerable variation of PSD rates within configurations was observed. CONCLUSIONS: Similar rates of PSD can be attained through diverse physician practice configurations. Significant within-configuration variation may reflect dynamic interactions between PPCs as well as between these characteristics and the contexts in which physicians function. Striving for a single ideal configuration may be less valuable for improving PSD than understanding and leveraging existing characteristics within primary care practices

    What could assistance robots learn from assistance dogs?

    Get PDF
    These studies are part of our broader project that aims at revealing relevant aspects of human-dog interactions, which could help to develop and test robot social behaviour. We suggest that the cooperation between assistance dogs and their disabled owners could serve as a model to design successful assistance robot–human interactions. In Study 1, we analysed the behaviour of 32 assistance dog–owner dyads performing a fetch and carry task. In addition to important typical behaviours (attracting attention, eye-contact, comprehending pointing gestures), we found differences depending on how experienced the dyad was and whether the owner used a wheel chair or not. In Study 2 we investigated the reactions of a subsample of dogs to unforeseen difficulties during a retrieving task. We revealed different types of communicative and displacement behaviours, and importantly, dogs showed a strong commitment to execute the insoluble task or at least their behaviours lent a “busy” appearance to them, which can attenuate the owners’ disappointment. We suggest that assistant robots should communicate their inability to solve a problem using simple behaviours (non-verbal vocalisation, orientation alternation), and/or could show displacement behaviours rather than simply not performing the task. In sum, we propose that assistant dogs’ communicative behaviours and problem solving strategies could inspire the development of the relevant functions and social behaviours of assistance robots

    The cytochrome p450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease

    Get PDF
    Fatty liver disease is an emerging public health problem without effective therapies, and chronic hepatic inflammation is a key pathologic mediator in its progression. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory effects. Although promoting the effects of EETs elicits anti-inflammatory and protective effects in the cardiovascular system, the contribution of CYP-derived EETs to the regulation of fatty liver disease-associated inflammation and injury is unknown. Using the atherogenic diet model of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH), our studies demonstrated that induction of fatty liver disease significantly and preferentially suppresses hepatic CYP epoxygenase expression and activity, and both hepatic and circulating levels of EETs in mice. Furthermore, mice with targeted disruption of Ephx2 (the gene encoding soluble epoxide hydrolase) exhibited restored hepatic and circulating EET levels and a significantly attenuated induction of hepatic inflammation and injury. Collectively, these data suggest that suppression of hepatic CYP-mediated EET biosynthesis is an important pathological consequence of fatty liver disease-associated inflammation, and that the CYP epoxygenase pathway is a central regulator of the hepatic inflammatory response in NAFLD/NASH. Future studies investigating the utility of therapeutic strategies that promote the effects of CYP-derived EETs in NAFLD/NASH are warranted

    Randomised controlled trial of mammographic screening in women from age 40: results of screening in the first 10 years

    Get PDF
    Debate continues over the effectiveness of screening by mammography in women below age 50. We report here on results of screening in the first 10 years of a randomised trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 compared to first invitation to the 3-yearly UK national programme at age 50–52. The trial is taking place in 23 NHS breast screening centres. Between 1991 and 1997, 160 921 women were randomised in the ratio 1 : 2 to intervention and control arms. Screening is by two views at first screen and single view subsequently; data on screening up to and including round five are now complete. Uptake of invitation to screening is between 68 and 70% at all but the latest screening rounds. Rates of referral for assessment are 4.6% at first screen and 3.4% at subsequent screens. Invasive cancer detection rates are 0.09% at first screen, and similar at rescreens until the sixth and later screens. There is little evidence of regular mammography in the trial control arm. The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme

    Noncoding RNA, antigenic variation, and the virulence genes of Plasmodium falciparum

    Get PDF
    Long non-coding RNAs (lncRNA) are being increasingly recognized as important regulators of gene expression. A recent paper in Genome Biology reports the identification of a lncRNA family in Plasmodium falciparum, the cause of the most deadly form of malaria, that may help to explain the mechanism of antigenic variation in virulence genes of this important pathogen
    corecore