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

Coupling of marine and continental oxygen isotope records during the Eocene-Oligocene transition

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148587/1/Sheldon_et_al_2016_GSA_Bulletin-EOT_marine-terrestrial_comparison.pd

Using hospital discharge data for determining neonatal morbidity and mortality: a validation study

<p>Abstract</p> <p>Background</p> <p>Despite widespread use of neonatal hospital discharge data, there are few published reports on the accuracy of population health data with neonatal diagnostic or procedure codes. The aim of this study was to assess the accuracy of using routinely collected hospital discharge data in identifying neonatal morbidity during the birth admission compared with data from a statewide audit of selected neonatal intensive care (NICU) admissions.</p> <p>Methods</p> <p>Validation study of population-based linked hospital discharge/birth data against neonatal intensive care audit data from New South Wales, Australia for 2,432 babies admitted to NICUs, 1994–1996. Sensitivity, specificity and positive predictive values (PPV) with exact binomial confidence intervals were calculated for 12 diagnoses and 6 procedures.</p> <p>Results</p> <p>Sensitivities ranged from 37.0% for drainage of an air leak to 97.7% for very low birthweight, specificities all exceeded 85% and PPVs ranged from 70.9% to 100%. In-hospital mortality, low birthweight (≤1500 g), retinopathy of prematurity, respiratory distress syndrome, meconium aspiration, pneumonia, pulmonary hypertension, selected major anomalies, any mechanical ventilation (including CPAP), major surgery and surgery for patent ductus arteriosus or necrotizing enterocolitis were accurately identified with PPVs over 92%. Transient tachypnea of the newborn and drainage of an air leak had the lowest PPVs, 70.9% and 83.6% respectively.</p> <p>Conclusion</p> <p>Although under-ascertained, routinely collected hospital discharge data had high PPVs for most validated items and would be suitable for risk factor analyses of neonatal morbidity. Procedures tended to be more accurately recorded than diagnoses.</p

Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium

AbstractFibroblasts are a diverse cell type and display clear topographic differentiation and positional memory. In a screen for fibroblast specific markers we have characterized four monoclonal antibodies to endosialin (TEM1/CD248). Previous studies have reported that endosialin is a tumour endothelium marker and is localized intracellularly. We demonstrate conclusively that endosialin is a cell surface glycoprotein and is predominantly expressed by fibroblasts and a subset of pericytes associated with tumour vessels but not by tumour endothelium. These novel antibodies will facilitate the isolation and classification of fibroblast and pericyte lineages as well as the further functional analysis of endosialin

The counselling self-estimate inventory (COSE): Does it work in Chinese counsellors?

Counselling self-efficacy is an important construct for research and evaluation in counsellors' competencies and training effectiveness. Larson et al. developed the Counselling Self-Estimate Inventory (COSE) for counsellors in America and examined its factor structure using exploratory factor analysis. They recommended a five-factor model (microskills, counselling process, difficult client behaviour, cultural competence, and awareness of values) and the use of the COSE for future research. However, little research has investigated the validity of the COSE in the context of counselling Chinese students in schools. In the present study, the factor structure of responses to the Chinese version of the Counselling Self-Estimate Inventory in a sample of 578 Hong Kong secondary school guidance teachers was examined using the EQS approach to confirmatory factor analysis. The results showed that while a five-factor model was fairly able to fit the data, the deletion of items related to the awareness of values factor yielded a better fitting model. The discussion of potential uses and limitations of the C-COSE in the context of preparing and supervising school guidance personnel in student counselling is relevant to counselling psychologists and researchers in Hong Kong and other parts of the world.postprin

Bioassay studies support the potential for latrogenic transmission of variant Creutzfeldt Jakob disease through dental procedures

Background: Evidence is required to quantify the potential risks of transmission of variant Creutzfeldt Jakob (vCJD) through dental procedures. Studies, using animal models relevant to vCJD, were performed to address two questions. Firstly, whether oral tissues could become infectious following dietary exposure to BSE? Secondly, would a vCJD-contaminated dental instrument be able to transmit disease to another patient? Methods: BSE-301V was used as a clinically relevant model for vCJD. VM-mice were challenged by injection of infected brain homogenate into the small intestine (Q1) or by five minute contact between a deliberately-contaminated dental file and the gingival margin (Q2). Ten tissues were collected from groups of challenged mice at three or four weekly intervals, respectively. Each tissue was pooled, homogenised and bioassayed in indicator mice. Findings: Challenge via the small intestine gave a transmission rate of 100% (mean incubation 157±17 days). Infectivity was found in both dental pulp and the gingival margin within 3 weeks of challenge and was observed in all tissues tested within the oral cavity before the appearance of clinical symptoms. Following exposure to deliberately contaminated dental files, 97% of mice developed clinical disease (mean incubation 234±33 days). Interpretation: Infectivity was higher than expected, in a wider range of oral tissues, than was allowed for in previous risk assessments. Disease was transmitted following transient exposure of the gingiva to a contaminated dental file. These observations provide evidence that dental procedures could be a route of cross-infection for vCJD and support the enforcement of single-use for certain dental instruments

Habitual Physical Activity in Mitochondrial Disease

Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype.Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. = −0.49; 95% CI −0.33, −0.63, P<0.01). There were no systematic differences in physical activity between different genotypes mitochondrial disease.These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation