Constraining volatile abundance in chondritic components

Accepted versio

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

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

Pain Assessment in INTensive care (PAINT): an observational study of physician-documented pain assessment in 45 intensive care units in the United Kingdom

Pain is a common and distressing symptom experienced by intensive care patients. Assessing pain in this environment is challenging, and published guidelines have been inconsistently implemented. The Pain Assessment in INTensive care (PAINT) study aimed to evaluate the frequency and type of physician pain assessments with respect to published guidelines. This observational service evaluation considered all pain and analgesia‐related entries in patients’ records over a 24‐h period, in 45 adult intensive care units (ICUs) in London and the South‐East of England. Data were collected from 750 patients, reflecting the practice of 362 physicians. Nearly two‐thirds of patients (n = 475, 64.5%, 95%CI 60.9–67.8%) received no physician‐documented pain assessment during the 24‐h study period. Just under one‐third (n = 215, 28.6%, 95%CI 25.5–32.0%) received no nursing‐documented pain assessment, and over one‐fifth (n = 159, 21.2%, 95%CI 19.2–23.4)% received neither a doctor nor a nursing pain assessment. Two of the 45 ICUs used validated behavioural pain assessment tools. The likelihood of receiving a physician pain assessment was affected by the following factors: the number of nursing assessments performed; whether the patient was admitted as a surgical patient; the presence of tracheal tube or tracheostomy; and the length of stay in ICU. Physician‐documented pain assessments in the majority of participating ICUs were infrequent and did not utilise recommended behavioural pain assessment tools. Further research to identify factors influencing physician pain assessment behaviour in ICU, such as human factors or cultural attitudes, is urgently needed

Computing Power and Sample Size for Case-Control Association Studies with Copy Number Polymorphism: Application of Mixture-Based Likelihood Ratio Test

Recent studies suggest that copy number polymorphisms (CNPs) may play an important role in disease susceptibility and onset. Currently, the detection of CNPs mainly depends on microarray technology. For case-control studies, conventionally, subjects are assigned to a specific CNP category based on the continuous quantitative measure produced by microarray experiments, and cases and controls are then compared using a chi-square test of independence. The purpose of this work is to specify the likelihood ratio test statistic (LRTS) for case-control sampling design based on the underlying continuous quantitative measurement, and to assess its power and relative efficiency (as compared to the chi-square test of independence on CNP counts). The sample size and power formulas of both methods are given. For the latter, the CNPs are classified using the Bayesian classification rule. The LRTS is more powerful than this chi-square test for the alternatives considered, especially alternatives in which the at-risk CNP categories have low frequencies. An example of the application of the LRTS is given for a comparison of CNP distributions in individuals of Caucasian or Taiwanese ethnicity, where the LRTS appears to be more powerful than the chi-square test, possibly due to misclassification of the most common CNP category into a less common category

The effect of price increases on predicted alcohol purchasing decisions and choice to substitute

Introduction: Few studies have undertaken to explore whether people who consume particular alcoholic beverages have a greater tendency to substitute with cheaper alcohol in response to price increases. The aim of this study was to investigate the effect of price increases on alcohol purchasing decisions, specifically the influence on brand and cross-beverage substitution across demographic, drinking level and socio-economic factors. Method: Data on participants’ alcohol purchasing habits and consumption were collected via an online survey, including their reactions to three price increases to alcoholic beverages types previously purchased. Data were analysed using logistic regression, with substitution behaviour the dependent variable, controlling for demographic and socio-economic factors. Results: Responses to different price increases varied by drinking level, which was consistently and significantly associated with likelihood of substitution behaviour across beverage types. For a 50% increase in price, regardless of whether participants purchased beer, wine, bottled spirits or premixed spirits, drinking at levels which put participants at high risk of short-term harms was associated with a higher likelihood of substitution with cheaper brands or beverage types (OR: 1.729; OR: 1.787; OR: 1.729 and OR: 1.729, respectively). Conclusions: No consistent trends in responses occurred according to respondent characteristics, suggesting that increasing price may be an effective tool to influence purchasing behaviour across the population. Results also suggested that those who drink at levels which put them at high risk of short-term harms may be more likely to circumvent price increases by switching to a cheaper product

Primique: automatic design of specific PCR primers for each sequence in a family

<p>Abstract</p> <p>Background</p> <p>In many contexts, researchers need specific primers for all sequences in a family such that each primer set amplifies only its target sequence and none of the others, e.g. to detect which transcription factor out of a family of very similar proteins that is present in a sample, or to design diagnostic assays for the identification of pathogen strains.</p> <p>Results</p> <p>This paper presents primique, a new graphical, user-friendly, fast, web-based tool which solves the problem: It designs specific primers for each sequence in an uploaded set. Further, a secondary set of sequences <it>not </it>to be amplified by any primer pair may be uploaded. Primers with high sequence similarity to non-target sequences are selected against. Lastly, the suggested primers may be checked against the National Center for Biotechnology Information databases for possible mis-priming.</p> <p>Conclusion</p> <p>Results are presented in interactive tables, and various primer properties are listed and displayed graphically. Any close match alignments can be displayed. Given 30 sequences, the running time of primique is about 20 seconds.</p> <p>primique can be reached via this web address: <url>http://cgi-www.daimi.au.dk/cgi-chili/primique/front.py</url></p

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

An off-board quantum point contact as a sensitive detector of cantilever motion

Recent advances in the fabrication of microelectromechanical systems (MEMS) and their evolution into nanoelectromechanical systems (NEMS) have allowed researchers to measure extremely small forces, masses, and displacements. In particular, researchers have developed position transducers with resolution approaching the uncertainty limit set by quantum mechanics. The achievement of such resolution has implications not only for the detection of quantum behavior in mechanical systems, but also for a variety of other precision experiments including the bounding of deviations from Newtonian gravity at short distances and the measurement of single spins. Here we demonstrate the use of a quantum point contact (QPC) as a sensitive displacement detector capable of sensing the low-temperature thermal motion of a nearby micromechanical cantilever. Advantages of this approach include versatility due to its off-board design, compatibility with nanoscale oscillators, and, with further development, the potential to achieve quantum limited displacement detection.Comment: 5 pages, 5 figure