Promoting research-user collaboration: an assessment of funding schemes: Fifth NCCR North-South Report on Effectiveness

Donors increasingly require that the research they fund be of benefit for society and the environment. To this end, researchers addressing complex and uncertain problems should work together with research users. This is not always easy: researchers are expected to collaborate with non-academic partners, but are not funded for the additional work. Collaborative research projects often cannot tap the full potential of user engagement. Therefore, specific institutional and organisational conditions are necessary that foresee or even foster research–user engagement; funding schemes are one possible solution. Right from the start, the NCCR North-South programme introduced Partnership Actions for Mitigating Syndromes of Global Change (PAMS). This evaluation assesses the types of collaboration supported by PAMS, as well as the value of PAMS as a funding scheme for collaboration. It compares PAMS with similar funding schemes of other universities, research programmes, or projects, and contains recommendations

Reduced Inflammatory Threshold Indicates Skin Barrier Defect in Transglutaminase 3 Knockout Mice

Recently a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed impaired hair development, but no gross defects in the epidermal barrier, although increased fragility of isolated corneocytes was demonstrated. Here we investigated the functionality of skin barrier in vivo by percutaneous sensitization to fluorescein-isothiocyanate (FITC) in TGM3/KO (n=64) and C57BL/6 WT mice (n=36). Cutaneous inflammation was evaluated by mouse ear swelling test (MEST), histology, serum IgE levels, and by flow-cytometry from draining lymph nodes. Inflammation induced significant MEST difference (P<0.0001) was detected between KO and WT mice and was supported also by histopathology. A significant increase of CD4+ CD25+ activated T-cells (P<0.01) and elevated serum IgE levels (P<0.05) in KO mice indicated more the development of FITC sensibilization than an irritative reaction. P. acnes induced intracutaneous inflammation showed no difference (P=0.2254) between the reactivity of WT and KO immune system. As in vivo tracer, FITC penetration from skin surface followed by two-photon microscopy demonstrated a more invasive percutaneous penetration in KO mice. The clinically uninvolved skin in TGM3/KO mice showed impaired barrier function and higher susceptibility to FITC sensitization indicating that TGM3 has a significant contribution to the functionally intact cutaneous barrier.Journal of Investigative Dermatology accepted article preview online, 24 July 2013. doi:10.1038/jid.2013.307

Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease

Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5×10-4, per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD

Solving the chemical master equation using sliding windows

<p>Abstract</p> <p>Background</p> <p>The chemical master equation (CME) is a system of ordinary differential equations that describes the evolution of a network of chemical reactions as a stochastic process. Its solution yields the probability density vector of the system at each point in time. Solving the CME numerically is in many cases computationally expensive or even infeasible as the number of reachable states can be very large or infinite. We introduce the sliding window method, which computes an approximate solution of the CME by performing a sequence of local analysis steps. In each step, only a manageable subset of states is considered, representing a "window" into the state space. In subsequent steps, the window follows the direction in which the probability mass moves, until the time period of interest has elapsed. We construct the window based on a deterministic approximation of the future behavior of the system by estimating upper and lower bounds on the populations of the chemical species.</p> <p>Results</p> <p>In order to show the effectiveness of our approach, we apply it to several examples previously described in the literature. The experimental results show that the proposed method speeds up the analysis considerably, compared to a global analysis, while still providing high accuracy.</p> <p>Conclusions</p> <p>The sliding window method is a novel approach to address the performance problems of numerical algorithms for the solution of the chemical master equation. The method efficiently approximates the probability distributions at the time points of interest for a variety of chemically reacting systems, including systems for which no upper bound on the population sizes of the chemical species is known a priori.</p

Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Peer reviewe

PRONOMEN UTLÖSER KÖNSKATEGORISERING VID ANSIKTSIGENKÄNNING

Ansiktsigenkänning påverkas av könskategorisering, därkönskategorier antingen påskyndar eller fördröjer tiden det taratt känna igen ett ansikte. Kategoriseringseffekten av kön vidansiktsigenkänning, har i tidigare forskning visats aktiveras närett androgynt ansikte presenteras med ett könstypiskt förnamn.Könskategorier bedöms snabbare än ansiktens individuellakönsdrag. Därför kommer ansikten med en könskategori sominte motsvarar förnamnets könskategori att avfärdas snabbare.Frågan denna studie behandlar är huruvida pronomen också kanutlösa kategoriseringseffekten av kön, genom att jämföra tidendet tar att avfärda ett ansikte som inte motsvarar ett som söksvid olika pronomen. Deltagarna (n=40) genomförde ettansiktsigenkänningstest där de studerade ett androgynt ansiktesom beskrevs som antingen ’hen’, ’hon’ eller ’han’.Ansiktsigenkänningen mättes i form av avfärdningstiden för ettantal kvinnliga- och manliga ansikten. Resultatet visade att detfinns en signifikant skillnad i avfärdningstiden för ansiktenberoende på vilket pronomen de presenterats med, därpronomen med könsinformation som inte motsvarar ansiktetskönsdrag avfärdas snabbare. Det könsneutrala pronomenet ‘hen’visade sig varken påskynda eller fördröja avfärdnignstiden vidansiktsigenkänning. Slutsatserna som dras är att binärapronomen aktiverar- och könsneutrala pronomen inaktiverarkategoriseringseffekten av kön vid ansiktsigenkänning.Gender Fair Languag

“Leo from the Lea Street”. Leon Płoszewski – the editor of Wyspiański and Mickiewicz

The article is a reminiscence on Professor Leon Płoszewski (1890–1970) – the editor of the National Edition of Works of Adam Mickiewicz and the editor of Collected Works of Stanisław Wyspiański – written by his daughter, Maria Płoszewska-Paulsson. The author portrays her father as a man of a Benedictine diligence (in “Spartan” conditions of a one-room editorial office!) and she brings up the less-known side of Professor Płoszewski’s outstanding professional work and the so far untold events in the Płoszewski family’s life, depicting him as:the husband of the ever busy “working woman” who tried in vain to slow down his professional overzealousness; • a parodist who privately mocked the realities of the then Polish People’s Republic; • a collector of the stylistic incongruities and blatant lies printed in the Polish press of the time; • an author of occasional witty poetry, hilarious commentaries, pastiches and dedications; • a gregarious man, a brilliant conversationalist, etc. The Tatra Mountains played a very important role in Leon Ploszewski’s life. Despite closing the Polish-Czechoslovak border after WWII, the Tatras were his refuge for freedom and a regenerating retreat. Leon Płoszewski was a person enamoured of the Western culture (particularly the French one). He felt acutely the isolation of Poland behind the Iron Curtain. It was as late as 1960 when, for the first time after WWII, he was allowed to travel to Paris. In a way it was thanks to Stanisław Wyspiański whose tracks he followed. This journey was for him an enormous emotional experience