The Pharmaceutical Sciences in 2020: Report of a Conference Organized by the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation (FIP)

The Board of Pharmaceutical Sciences (BPS) of the International Pharmaceutical Federation (FIP) has developed a view on the future of pharmaceutical sciences in 2020. This followed an international conference with invited participants from various fields (academicians, scientists, regulators, industrialists, venture capitalists) who shared their views on the forces that might determine how the pharmaceutical sciences will look in 2020. The commentary here provides a summary of major research activities that will drive drug discovery and development, enabling technologies for pharmaceutical sciences, paradigm shifts in drug discovery, development and regulations, and changes in education to meet the demands of academia, industry and regulatory institutions for pharmaceutical sciences in 2020

Diet and bone mineral density study in postmenopausal women from the TwinsUK registry shows a negative association with a traditional English dietary pattern and a positive association with wine

Background: The effect of diet on bone mineral density (BMD) remains controversial, mainly because of difficulties in isolating dietary factors from the confounding influences of age, lifestyle, and genetic factors. Objective: The aim of this study was to use a novel method to examine the relation between BMD and diet. Design: A co-twin control study design with linear regression modeling was used to test for associations between BMD and habitual intakes of calcium, vitamin D, protein, and alcohol plus 5 previously identified dietary patterns in postmenopausal women from the TwinsUK registry. This approach exploited the unique matching of twins to provide an estimate of an association that was not confounded by age, genetic background, or shared lifestyle. Results: In >2000 postmenopausal women (BMD data on 1019, 1218, and 1232 twin pairs at the hip neck, hip, and spine, respectively), we observed a positive association between alcohol intake (from wine but not from beer or spirits) and spine BMD (P = 0.01) and a negative association with a traditional 20th-century English diet at the hip neck (P = 0.01). Both associations remained borderline significant after adjustment for mean twin-pair intakes (P = 0.04 and P = 0.055, respectively). Other dietary patterns and intakes of calcium, vitamin D, and protein were unrelated to BMD. Conclusion: Our results showed that diet has an independent but subtle effect on BMD; wine intake was positively associated with spine BMD, whereas a traditional (20th-century) English diet had a negative association with hip BMD

Proposal of serovars 17 and 18 of Actinobacillus pleuropneumoniae based on serological and genotypic analysis

The aim of this study was to investigate isolates of Actinobacillus pleuropneumoniae previously designated serologically either as NT or as ‘K2:07’, which did not produce serovar-specific amplicons in PCR assays. We used whole genome sequencing to identify the capsule (CPS) loci of six previously designated biovar 1 non-typable (NT) and two biovar 1 ‘K2:O7’ isolates of A. pleuropneumoniae from Denmark, as well as a recent biovar 2 NT isolate from Canada. All of the NT isolates have the same six-gene type I CPS locus, sharing common cpsABC genes with serovars 2, 3, 6, 7, 8, 9, 11 and 13. The two ‘K2:O7’ isolates contain a unique three-gene type II CPS locus, having a cpsA gene similar to that of serovars 1, 4, 12, 14 and 15. The previously NT isolates share the same O-antigen genes, found between erpA and rpsU, as serovars 3, 6, 8, and 15. Whereas the ‘K2:O7’ isolates, have the same O-antigen genes as serovar 7, which likely contributed to their previous mis-identification. All of the NT and ‘K2:O7’ isolates have only the genes required for production of ApxII (apxIICA structural genes, and apxIBD export genes). Rabbit polyclonal antisera raised against representative isolates with these new CPS loci demonstrated distinct reactivity compared to the 16 known serovars. The serological and genomic results indicate that the isolates constitute new serovars 17 (previously NT) and 18 (previously ‘K2:O7’). Primers designed for amplification of specific serovar 17 and 18 sequences for molecular diagnostics will facilitate epidemiological tracking of these two new serovars of A. pleuropneumoniae

The Grizzly, October 3, 1995

Akin to Become Director of Athletics, Davidson to Focus Solely on Chair of ESS • Cracking the Case of the Bomberger Window • Law School Forum a Success • 1995 Pledging Rules and Guidelines • Trash Revisited • A Rainbow is Better • Closed-Mindedness is the Real Problem • The Government is Trying to Starve You! • Berman Museum Receives Grant • Economics Department Rated High in Study • Chemistry Department Receives Research Grant • Where Have All the Glasses Gone? • Silken Rhythm: Ursinus Students Harmonize • Family Day 1995 • Soccer Wins a Pair • Win Streak Stopped At Four • Struggle Continues • Swarthmore Edges Ursinushttps://digitalcommons.ursinus.edu/grizzlynews/1364/thumbnail.jp

The Effect of Ethanol on the Release of Opioids from Oral Prolonged-Release Preparations

Recent experience has prompted the US FDA to consider whether ethanol ingestion may modify the release characteristics of prolonged-release formulations, where dose dumping may be an issue for patient safety

Identification of candidate MYB transcription factors that influence CslF6 expression in barley grain

(1,3;1,4)-β-Glucan is a non-cellulosic polysaccharide required for correct barley grain fill and plant development, with industrial relevance in the brewing and the functional food sector. Barley grains contain higher levels of (1,3;1,4)-β-glucan compared to other small grain cereals and this influences their end use, having undesirable effects on brewing and distilling and beneficial effects linked to human health. HvCslF6 is the main gene contributing to (1,3;1,4)-β-glucan biosynthesis in the grain. Here, the transcriptional regulation of HvCslF6 was investigated using an in-silico analysis of transcription factor binding sites (TFBS) in its putative promoter, and functional characterization in a barley protoplast transient expression system. Based on TFBS predictions, TF classes AP2/ERF, MYB, and basic helix-loop-helix (bHLH) were over-represented within a 1,000 bp proximal HvCslF6 promoter region. Dual luciferase assays based on multiple HvCslF6 deletion constructs revealed the promoter fragment driving HvCslF6 expression. Highest HvCslF6 promoter activity was narrowed down to a 51 bp region located −331 bp to −382 bp upstream of the start codon. We combined this with TFBS predictions to identify two MYB TFs: HvMYB61 and HvMYB46/83 as putative activators of HvCslF6 expression. Gene network analyses assigned HvMYB61 to the same co-expression module as HvCslF6 and other primary cellulose synthases (HvCesA1, HvCesA2, and HvCesA6), whereas HvMYB46/83 was assigned to a different module. Based on RNA-seq expression during grain development, HvMYB61 was cloned and tested in the protoplast system. The transient over-expression of HvMYB61 in barley protoplasts suggested a positive regulatory effect on HvCslF6 expression

Pretreatment CT texture features for prognostication in patient with Stage III Non-Small Cell Lung Cancer

Purpose: To determine whether CT texture features can yield prognostic information in addition to conventional prognostic factors in stage III non-small cell lung cancer (NSCLC).Methods: We conducted a retrospective review of 91 patients with stage III NSCLC treated with definitive chemoradiation. All patients received a four-dimensional (4D) CT simulation, where we utilized the average image (average-CT) and an expiratory image (T50-CT), and a diagnostic contrast enhanced CT image (CE-CT). A penalized cox regression model was used for covariate selection and model development. Models incorporating texture features from the 3 image types and clinical factors were compared to models incorporating clinical factors alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Stratification into low-risk and high-risk groups was based on a patient’s predicted outcome being greater or less than the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients. The concordance correlation coefficient (CCC) was used to assess texture feature reproducibility and classification accuracy was used to assess reproducibility of texture features within the context of our models.         Results: Models incorporating both texture and clinical features demonstrated a significant improvement in stratification compared to models using clinical features alone in cross-validated Kaplan-Meier curves in terms of OS (p = 0.046), LRC (p = 0.01), and FFDM (p = 0.005). The average CCC was 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility uncertainties within our model yielded 80.4 (SD = 3.7), 78.3 (SD = 4.0), and 78.8 (SD = 3.9) percent classification accuracy for OS, LRC, and FFDM, respectively.    Conclusion: Pretreatment tumor texture may provide prognostic information in additional to routinely obtained clinical features. Reproducibility of CE-CT appears inferior to average-CT and T50-CT; however model classification accuracy rates of ~80% were still achieved.----------------------Cite this article as: Fried DV, Tucker SL, Zhou S, Liao ZX, Ibbott GS, Court LE.   Pretreatment CT texture features for prognostication in patient with Stage III Non-Small Cell Lung Cancer. Int J Cancer Ther Oncol 2014; 2(2):020223. DOI: 10.14319/ijcto.0202.2