Spatial quantitation of drugs in tissues using liquid extraction surface analysis mass spectrometry imaging

Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported

Back to thiazide-diuretics for hypertension: reflections after a decade of irrational prescribing

BACKGROUND: Whether newer antihypertensive drugs, such as calcium channel blockers, angiotensin converting enzyme inhibitors and α blockers are more effective than thiazides and β blockers in preventing coronary disease, has been debated for years. DISCUSSION: Recently several trials addressing this issue have been finalised, and they provide a convincing answer: the newer drugs are no better than the older ones. In the largest trial to date (ALLHAT), thiazide-type diuretic was found to offer advantages over newer drugs. The medical community should now be capable of reaching consensus, and recommend thiazides as the first line therapy for the treatment of hypertension. Prescribing physicians, cardiologists, drug companies and health authorities are all partly responsible for the years of irrational prescribing that we have witnessed. SUMMARY: All stakeholders should now contribute in order to achieve what is clearly in the public's interest: implementing the use of thiazides in clinical practice

Implementing structured functional assessments in general practice for persons with long-term sick leave: a cluster randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The increasing attention on functional assessments in medical and vocational rehabilitation requires a focus change for the general practitioners (GP) into paying attention to patient resources, possibilities and coping instead of symptoms, problems and limitations. The GPs report difficulties in performing the requested explicit functional assessments. The purpose of this study was to implement a structured method in general practice for assessing functional ability in persons with long-term sick leave. The study aim was to evaluate intervention effects on important GP parameters; knowledge, attitudes, self-efficacy towards functional assessments and knowledge about patient work factors.</p> <p>Methods</p> <p>Fifty-seven GPs were randomly assigned to an intervention or a control group. The intervention group GPs attended an introductory one-day work-shop and implemented structured functional assessments during an eight months intervention period. GP knowledge, GP attitudes, and GP self-efficacy towards functional assessments, as well as GP knowledge of patient work factors, were collected before, after and six months after the intervention period started. Evaluation score-sheets were filled in by both the intervention GPs and their patients immediately after the consultation to evaluate the GPs' knowledge of patient work factors.</p> <p>Results</p> <p>The intervention GPs reported increased knowledge (B: 0.56, 95% CI (0.19, 0.91)) and self-efficacy (B: 0.90, 95% CI (0.53, 1.26)) towards functional assessments, and increased knowledge about their patients' workplace (B: 0.75, 95% CI (0.35, 1.15)) and perceived stressors (B: 0.55, 95% CI (0.23, 0.88)) with lasting effects at the second follow-up. No intervention effect was seen in relation to GP attitudes. Both before and after the intervention, the GPs were most informed about physical stressors, and less about mental and work organisational stressors (Guttman's reproducibility coefficient: 0.95 and 1.00). After the consultation, both the intervention GPs and their patients reported that the GPs' knowledge about patient work factors had increased (GP B: 0.60 (95% CI: 0.42, 0.78); patient B: 0.50 (95% CI: 0.34, 0.66)).</p> <p>Conclusion</p> <p>Introducing and implementing structured functional assessments in general practice made the GPs capable to assess functional ability of their patients in a structured manner. Intervention effects of increased GP knowledge and GP self-efficacy sustained at the second follow-up.</p

Paving the way for research findings: writers' rhetorical choices in education and applied linguistics

Notwithstanding the existence of previous investigations into how research results are presented in different academic disciplines, fewer studies have looked into how authors pave the way for their results, the interdisciplinary differences in ‘result pavements’, and the interconnections between their communicative functions and linguistic choices. Using the techniques of genre analysis, I have analyzed two corpora of research reports in applied linguistics and education in order to identify the possible ways in which experienced writers schematically pave the way for their findings. Using evidence based on authentic research articles, this study demonstrates how writers set the stage for their research results by (i) demonstrating their control of the structure and flow of result-related information, (ii) connecting past research with a current finding while furnishing pertinent background elements that lead the readership progressively to specific findings, (iii) regenerating readers’ interest in their initial research purposes, and (iv) deploying locatives to embed results in a ‘space-saving strategy’ aimed at presenting an abridged Results section. I have also analyzed interdisciplinary differences in the frequencies of these rhetorical steps and the range of intricate linguistic mechanisms employed by authors as communicative resources in each step to establish a smooth rhetorical transition that sets the stage for their research results

"Being in a Knowledge Space": information behaviour of cult media fan communities

This article describes the first two parts of a three-stage study investigating the information behaviour of fans and fan communities, focusing on fans of cult media. A literature analysis shows that information practices are an inherent and major part of fan activities, and that fans are practitioners of new forms of information consumption and production, showing sophisticated activities of information organisation and dissemination. A subsequent Delphi study, taking the novel form of a 'serious leisure' Delphi, in which the participants are not experts in the usual sense, identifies three aspects of fan information behaviour of particular interest beyond the fan context: information gatekeeping; classifying and tagging; and entrepreneurship and economic activity

Plasticity of Adult Human Pancreatic Duct Cells by Neurogenin3-Mediated Reprogramming

AIMS/HYPOTHESIS: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it. METHODS: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming. RESULTS: Ngn3 stimulates duct cells to express a focused set of genes that are characteristic for islet endocrine cells and/or neural tissues. This neuro-endocrine shift however, is incomplete with less than 10% of full duct-to-endocrine reprogramming achieved. Transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1. CONCLUSIONS/INTERPRETATION: The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes

Reproductive Ecology and Severe Pollen Limitation in the Polychromic Tundra Plant, Parrya nudicaulis (Brassicaceae)

Pollen limitation is predicted to be particularly severe in tundra habitats. Numerous reproductive patterns associated with alpine and arctic species, particularly mechanisms associated with reproductive assurance, are suggested to be driven by high levels of pollen limitation. We studied the reproductive ecology of Parrya nudicaulis, a species with relatively large sexual reproductive investment and a wide range of floral pigmentation, in tundra habitats in interior montane Alaska to estimate the degree of pollen limitation. The plants are self-compatible and strongly protandrous, setting almost no seed in the absence of pollinators. Supplemental hand pollinations within pollinator exclusion cages indicated no cage effect on seed production. Floral visitation rates were low in both years of study and particularly infrequent in 2010. A diversity of insects visited P. nudicaulis, though syrphid and muscid flies composed the majority of all visits. Pollen-ovule ratios and levels of heterozygosity are consistent with a mixed mating system. Pollen limitation was severe; hand pollinations increased seed production per plant five-fold. Seed-to-ovule ratios remained low following hand pollinations, indicating resource limitation is likely to also be responsible for curtailing seed set. We suggest that pollen limitation in P. nudicaulis may be the result of selection favoring an overproduction of ovules as a bet-hedging strategy in this environmental context of highly variable pollen receipt

The influence of organizational culture and climate on entrepreneurial intentions among research scientists

Over the past decades, universities have increasingly become involved in entrepreneurial activities. Despite efforts to embrace their ‘third mission’, universities still demonstrate great heterogeneity in terms of their involvement in academic entrepreneurship. This papers adopts an institutional perspective to understand how organizational characteristics affect research scientists’ entrepreneurial intentions. Specifically, we study the impact of university culture and climate on entrepreneurial intentions, including intentions to spin off a company, to engage in patenting or licensing and to interact with industry through contract research or consulting. Using a sample of 437 research scientists from Swedish and German universities, our results reveal that the extent to which universities articulate entrepreneurship as a fundamental element of their mission fosters research scientists’ intentions to engage in spin-off creation and intellectual property rights, but not industry-science interaction. Furthermore, the presence of university role models positively affects research scientists’ propensity to engage in entrepreneurial activities, both directly and indirectly through entrepreneurial self-efficacy. Finally, research scientists working at universities which explicitly reward people for ‘third mission’ related output show higher levels of spin-off and patenting or licensing intentions. This study has implications for both academics and practitioners, including university managers and policy makers