Beyond mandates: for open science to become a norm, it must be recognised and rewarded

Calls to align incentives in academia to promote open research practices are not new. However, in recent years research funders are increasingly implementing policies and schemes designed to promote open science practices amongst researchers. In this post, Maria Cruz and Hans de Jonge outline details of the Dutch Research Council’s (NWO) new Open Science Fund, which they suggest is the natural next step towards a culture of open science in Dutch research

Campuses, Cities and Innovation:

The locations of technology campuses determine where innovation takes place. In a knowledge-based economy, the future of cities increasingly depends on the presence of universities, their industry partners, talent and (start-up) businesses. The relationship between (technology) campuses and cities was a central theme in Flavia Curvelo Magdaniel’s doctoral research, which was defended and published in September 2016. During her PhD study, she collected data of thirty-nine technology campuses, which we – as her promotor and co-promotor – considered worth a spin-off publication. This publication “Campuses, cities and innovation” contains descriptions of 39 international cases that accommodate tech-based research activities. These case descriptions (in part B) are introduced with background information about concepts and methods (in part A) and reflected upon in conclusions and recommendations (in part C). Based on our experience - after more than twenty years of campus research at TU Delft – we identified a demand for case study references to support decision making at both universities and municipalities. TU Delft’s campus research team aims at generating management information on all campus levels: from the changing academic workplace and new concepts for university buildings to the sustainable campus and the knowledge city. This book is part of a book series that combines insights from theory with references from practice, to contribute to smarter campus management. With a large number of facts, figures and maps this book “Campuses, cities and innovation” is relevant for board members and (campus) management staff at universities as well as policymakers at municipalities and regional authorities. Additionally, decision-makers of industry partners, (start-up) businesses and (other) members of the campus community could be interested in comparing their campuses with worldwide examples. “Innovation is what happens when preparation meets opportunity” was one of the propositions that Flavia Curvelo Magdaniel defended in September 2016. With this book, we wanted to take the opportunity to support the preparation process and hope to stimulate innovation

Topotecan lacks third space sequestration

The objective of this study was to determine the influence of pleural and ascitic fluid on the pharmacokinetics of the antitumor camptothecin derivative topotecan. Four patients with histological proof of malignant solid tumor received topotecan (0.45 or 1.5 mg/m2) p.o. on several occasions in both the presence and absence of third space volumes. Serial plasma and pleural or ascitic fluid samples were collected during each dosing and analyzed by high-performance liquid chromatography for both the intact lactone form of topotecan and its ring-opened carboxylate form. The apparent topotecan clearance demonstrated substantial interpatient variability but remained unchanged within the same patient in the presence [110 +/- 55.6 liters/ h/m2 (mean +/- SD of eight courses)] or absence of pleural and ascitic fluid [118 +/- 31.1 liters/h/m2 (mean +/- SD of seven courses)]. Similarly, terminal half-lives and area under the concentration-time curve ratios of lactone:total drug in plasma were similar between courses within each patient. Topotecan penetration into pleural and ascitic fluid demonstrated a mean lag time of 1.61 h (range, 1.37-1.86 h), and ratios with plasma concentration increased with time after dosing in all patients. The mean ratio of third space topotecan total drug area under the concentration-time curve to that in plasma was 0.55 (range, 0.26-0.87). These data indicate that topotecan can be safely administered to patients with pleural effusions or ascites and that there is substantial penetration of topotecan into these third spaces, which may prove beneficial for local antitumor effects

Inter- and intrapatient variability in oral topotecan pharmacokinetics: implications for body-surface area dosage regimens

Anticancer drugs still are dosed based on the body-surface area (BSA) of the individual patient, although the BSA is not the main predictor of the clearance for the majority of drugs. The relevance of BSA-based dosing has not been evaluated for topotecan yet. A retrospective pharmacological analysis was performed of kinetic data from four clinical Phase I studies in which topotecan was administered p.o. as a single agent combined with data from a combination study of topotecan and cisplatin. A strong correlation (r = 0.91) was found between the area under the plasma concentration time curve of the lactone and carboxylate forms of topotecan by plotting 326 data sets obtained from 112 patients receiving oral topotecan at dose levels ranging from 0.15-2.70 mg/m2. The intrapatient variability, studied in 47 patients sampled for 3 or more days, for the apparent lactone clearance, ranged from 7.4-69% (mean, 24 +/- 13%; median, 20%). The interpatient variabilities in the lactone clearance, calculated with the data of all studied patients, expressed in liter/h/m2 and in liter/h were 38% and 42%, respectively. In view of the relatively high inter- and intrapatient variabilities in topotecan clearance, in contrast to a variability of only 12% in the BSA of the studied patients, no advantage of BSA-based dosing was found over fixed dose regimens

One-year follow-up of a randomised controlled trial on added splinting to eccentric exercises in chronic midportion Achilles tendinopathy

OBJECTIVE: The study examined whether the addition of a night splint to eccentric exercises is beneficial for functional outcome in chronic mid-portion Achilles tendinopathy. DESIGN: One-year follow-up of a randomised controlled single blinded clinical trial. SETTING: Sports medicine department in a general hospital. PATIENTS: 58 patients (70 tendons) were included. INTERVENTIONS: All patients completed a 12-week heavy load eccentric training programme. One group received a night splint in addition to eccentric exercises. Main outcome measurements: Outcome scores were: Victorian Institute of Sport Assessment - Achilles (VISA-A) score, subjective patient satisfaction and neovascularisation score measured with Power Doppler Ultrasonography. RESULTS: For both groups the VISA-A score increased significantly (from 50 to 76 (P < 0.01) in the eccentric group and from 49 to 78 (P < 0.01) in the night splint group). No significant differences in VISA-A score were found between the groups from baseline to one year (P = 0.32). Presence of neovessels at baseline did not predict change in VISA-A score after one year in the whole group (P = 0.71). CONCLUSION: Eccentric exercises with or without a night splint improved functional outcome at one-year follow-up. At follow-up there

The Neurospora mitochondrial genome:the region coding for the polycistronic cytochrome oxidase subunit I transcript is preceded by a transfer RNA gene

AbstractWe have sequenced a 682 bp fragment of Neurospora crassa mitochondrial DNA to complete the sequence between the gene for cytochrome b and the unassigned reading frame, URF U. The sequence contains a gene for a cysteine tRNA. The 5' end of the 6 kb polycistronic transcript of cytochrome c oxidase subunit 1 is immediately downstream from this tRNA. This shows that also in fungal mitochondria tRNAs can be used as processing signals, whereas palindromic sequences containing double Pst I sites, also present in this region, are not used for processing

Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients

Introduction The aim of this study was to investigate whether in-hospital mortality was associated with the administered fraction of oxygen in inspired air (FiO(2)) and achieved arterial partial pressure of oxygen (PaO(2)). Methods This was a retrospective, observational study on data from the first 24 h after admission from 36,307 consecutive patients admitted to 50 Dutch intensive care units (ICUs) and treated with mechanical ventilation. Oxygenation data from all admission days were analysed in a subset of 3,322 patients in 5 ICUs. Results Mean PaO(2) and FiO(2) in the first 24 h after ICU admission were 13.2 kPa (standard deviation (SD) 6.5) and 50% (SD 20%) respectively. Mean PaO(2) and FiO(2) from all admission days were 12.4 kPa (SD 5.5) and 53% (SD 18). Focusing on oxygenation in the first 24 h of admission, in-hospital mortality was shown to be linearly related to FiO(2) value and had a U-shaped relationship with PaO(2) (both lower and higher PaO(2) values were associated with a higher mortality), independent of each other and of Simplified Acute Physiology Score (SAPS) II, age, admission type, reduced Glasgow Coma Scale (GCS) score, and individual ICU. Focusing on the entire ICU stay, in-hospital mortality was independently associated with mean FiO(2) during ICU stay and with the lower two quintiles of mean PaO(2) value during ICU stay. Conclusions Actually achieved PaO(2) values in ICU patients in The Netherlands are higher than generally recommended in the literature. High FiO(2), and both low PaO(2) and high PaO(2) in the first 24 h after admission are independently associated with in-hospital mortality in ICU patients. Future research should study whether this association is causal or merely a reflection of differences in severity of illness insufficiently corrected for in the multivariate analysis

Ultrasonographic tissue characterisation of human Achilles tendons: quantification of tendon structure through a novel non-invasive approach

OBJECTIVE: To asses if three-dimensional imaging of the Achilles tendon by Ultrasonographic Tissue Characterisation (UTC) can differentiate between symptomatic and asymptomatic tendons. DESIGN: Case-control study. SETTING: Sports medical department of The Hague medical centre. PATIENTS: Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included. The "matched" control group consisted of 26 asymptomatic tendons. INTERVENTIONS: Symptomatic and asymptomatic tendons were scanned using the UTC-procedure. One researcher performed the ultrasonographic data-collection. These blinded data were randomised and outcome measures were determined by two independent observers. Main outcome measurements: The raw ultrasonographic images were analysed with a custom-designed algorithm that quantifies the three-dimensional stability of echopatterns, qua intensity and distribution over contiguous transverse images. This three-dimensional stability was related to tendon structure in previous studies. UTC categorizes four different echo-types that represent: I) highly stable; II) medium stable; III) highly variable and IV) constantly low intensity and variable distribution. The percentages of echo-types were calculated and the maximum tendon-thickness was measured. Finally, the inter-observer reliability of UTC was determined. RESULTS: Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons (51.5% versus 76.6%, p<0.001), thus less three-dimensional stability of the echopattern. The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group (p<0.001). The Intra-class Correlation Coefficient (ICC) for the inter-observer reliability of determining the echo-types I+II was 0.95. The ICC for tendon thickness was 0.84. CONCLUSION: UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons. As such UTC might be useful to monitor treatment protocols

Spontaneous rescue from cystic fibrosis in a mouse model

BACKGROUND: From the original Cftr(TgH(neoim)Hgu )mutant mouse model with a divergent genetic background (129P2, C57BL/6, MF1) we have generated two inbred Cftr(TgH(neoim)Hgu )mutant strains named CF/1-Cftr(TgH(neoim)Hgu )and CF/3-Cftr(TgH(neoim)Hgu), which are fertile and show normal growth and lifespan. Initial genome wide scan analysis with microsatellite markers indicated that the two inbred strains differed on the genetic level. In order to further investigate whether these genetic differences have an impact on the disease phenotype of cystic fibrosis we characterised the phenotype of the two inbred strains. RESULTS: Reduced amounts, compared to wild type control animals, of correctly spliced Cftr mRNA were detected in the nasal epithelia, lungs and the intestine of both inbred Cftr(TgH(neoim)Hgu )strains, with higher residual amount observed for CF/1-Cftr(TgH(neoim)Hgu )than CF/3-Cftr(TgH(neoim)Hgu )for every investigated tissue. Accordingly the amounts of wild type Cftr protein in the intestine were 9% for CF/1-Cftr(TgH(neoim)Hgu )and 4% for CF/3-Cftr(TgH(neoim)Hgu). Unlike the apparent strain and/or tissue specific regulation of Cftr mRNA splicing, short circuit current measurements in the respiratory and intestinal epithelium revealed that both strains have ameliorated the basic defect of cystic fibrosis with a presentation of a normal electrophysiology in both tissues. CONCLUSION: Unlike the outbred Cftr(TgH(neoim)Hgu )insertional mouse model, which displayed the electrophysiological defect in the gastrointestinal and respiratory tracts characteristic of cystic fibrosis, both inbred Cftr(TgH(neoim)Hgu )strains have ameliorated the electrophysiological defect. On the basis of these findings both CF/1-Cftr(TgH(neoim)Hgu )and CF/3-Cftr(TgH(neoim)Hgu )offer an excellent model whereby determination of the minimal levels of protein required for the restoration of the basic defect of cystic fibrosis can be studied, along with the modulating factors which may affect this outcome