Adult survival and reproduction in an Argentine bottlenose dolphin population: The science needed for its conservation

Several small populations of bottlenose dolphins (Tursiops truncatus) are known to inhabit the Atlantic coast of Argentina, however, apparently with little exchange between them. The study population in Bahia San Antonio (San Matías Gulf, province of Río Negro) appears to be one of the southernmost populations (42°S/65°W). Adult survival and calving rates are critical for the survival of this population. Boat-based photo-identification surveys between 2008 and 2011 were used for a mark-recapture analysis of the survival of 35 distinctly marked adults. Survey trips in September 2008 (n=9), August 2009 (n=10), September 2010 (n=6) and in September 2011 (n=6) were used as secondary periods for a Pollock’s Robust Design analysis within MARK. The population was assumed to be closed within the secondary periods, and model selection indicated random migrations (rather than Markovian or No migration) outside the secondary periods. Adult survival was very high. Calving interval was calculated for 14 reproductive females with 28 calves since 2006 with the average being 3.5 ± 1.03 years. Assuming a population size of approximately 100 individuals, the minimum annual birth rate is 4.7% per year. Of the 28 calves, 3 are presumed to have died within the first 2-3 years of life, whereas 14 are known to have survived that period. Although bottlenose dolphins occur further south along the Argentine coast, the study population appears to be the most southerly stable population after the neighboring Valdez population was recently reported to be vanishing. Interactions with fishing and contamination appear to be the most likely impacts on adult survival and reproduction. So far, our results indicate a relatively small population with apparently healthy birth and survival rates

Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling

Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells

Expanded access to investigational drugs in psychiatry:A systematic review

Some psychiatric patients have exhausted all approved treatment options. Numerous investigational drugs are currently being developed and tested in clinical trials. However, not all patients can participate in clinical trials. Expanded access programs may provide an opportunity for patients who cannot participate in clinical trials to use investigational drugs as a therapeutic option outside of clinical trials. It is unknown to what extent expanded access occurs in psychiatry. We conducted a systematic literature search on PubMed, Embase, and PscyInfo, with additional information from ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and FDA/EMA approvals, in order to find all expanded access programs ever conducted, globally, in the field of psychiatry. This resulted in a total of fourteen expanded access programs ever conducted in psychiatry. Given the prevalence of psychiatric disorders, the activity in clinical research in psychiatry, the regulatory framework enabling expanded access, and the impact of psychiatric disorders on patients, their families, and society, we had expected a higher utilization of expanded access. We propose that the psychiatric community, with pharmaceutical industry, should consider establishing and optimizing expanded access programs.</p

Optimization of quantitative polymerase chain reactions for detection and quantification of eight periodontal bacterial pathogens

BACKGROUND: The aim of this study was to optimize quantitative (real-time) polymerase chain reaction (qPCR) assays for 8 major periodontal pathogens, i.e. Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Parvimonas micros, Porphyromonas gingivalis, Prevotella intermedia, Tanerella forsythia and Treponema denticola, and of the caries pathogen Streptococcus mutans. RESULTS: Eighteen different primer pairs were analyzed in silico regarding specificity (using BLAST analysis) and the presence of secondary structures at primer binding sites (using mFOLD). The most specific and efficiently binding primer pairs, according to these analyses, were selected for qPCR-analysis to determine amplification efficiency, limit of quantification and intra-run reproducibility. For the selected primer pairs, one for each species, the specificity was confirmed by assessing amplification of DNA extracts from isolates of closely related species. For these primer pairs, the intercycler portability was evaluated on 3 different thermal cyclers (the Applied Biosystems 7300, the Bio-Rad iQ5 and the Roche Light Cycler 480). For all assays on the different cyclers, a good correlation of the standard series was obtained (i.e. r2 >= 0.98), but quantification limits varied among cyclers. The overall best quantification limit was obtained by using a 2 mul sample in a final volume of 10 mul on the Light Cycler 480. CONCLUSIONS: In conclusion, the proposed assays allow to quantify the bacterial loads of S. mutans, 6 periodontal pathogenic species and the genus Fusobacterium.This can be of use in assessing periodontal risk, determination of the optimal periodontal therapy and evaluation of this treatment

Long-term fertilizer field trials: comparison of three mathematical response models

Accession to the European Union caused a drop of nearly 60 per cent from 1994 to 1995 in prices of wheat, barley and oats in Finland. The economic use of fertilizer therefore decreased accordingly. To calculate the effect of the price changes on the economic optima, the physical production function must be known. Three physical production functions, the quadratic, the linear response and plateau (LRP) and the exponential function were estimated for this purpose. The models differed little in respect of the R2adj value (0.82-0.90) but the calculated optimum varied, depending on the production function. Data on a long-term field trial (21 years) were analysed. The field trial was established in 1973 to demonstrate the effect of mineral fertilizer in crop production. The crops grown in the trial were barley, wheat and oats. Different varieties were included in the models

Comparison of procedures for RNA-extraction from peripheral blood mononuclear cells

RNA quality and quantity are important factors for ensuring the accuracy of gene expression analysis and other RNA-based downstream applications. Thus far, only a limited number of methodological studies have compared sample storage and RNA extraction procedures for human cells. We compared three commercially available RNA extraction kits, i.e., (NucliSENS) easyMAG, RNeasy (Mini Kit) and RiboPure (RNA Purification Kit–blood). In addition, additional conditions, such as storage medium and storage temperature of human peripheral blood mononuclear cells were evaluated, i.e., 4 °C for RNAlater or -80 °C for QIAzol and for the respective cognate lysis buffers; easyMAG, RNeasy or RiboPure. RNA was extracted from aliquots that had been stored for one day (Run 1) or 83 days (Run 2). After DNase treatment, quantity and quality of RNA were assessed by means of a NanoDrop spectrophotometer, 2100 Bioanalyzer and RT-qPCR for the ACTB reference gene. We observed that high-quality RNA can be obtained using RNeasy and RiboPure, regardless of the storage medium, whereas samples stored in RNAlater resulted in the least amount of RNA extracted. In addition, RiboPure combined with storage of samples in its cognate lysis buffer yielded twice as much RNA as all other procedures. These results were supported by RT-qPCR and by the reproducibility observed for two independent extraction runs

eLabEL: Technology-supported living labs in primary care

Telecare technologies and eHealth applications can support patients and care professionals. However, these technologies are currently not being implemented in primary care. The eLabEL project aims to contribute to a solution for this problem by establishing Living Labs in which patients, healthcare professionals, entrepreneurs and researchers collaborate during the selection, integration, implementation and evaluation of such technologies in primary care. So far, seven primary care centers across the Netherlands have been included. Needs and requirements of healthcare professionals and patients regarding telecare technologies and eHealth applications were studied using semi-structured interviews and focus group interviews respectively. Healthcare professionals and patients were positive towards the use of technologies that can improve accessibility of care for the entire patient population and also expressed a need for technologies that can support self-management in patients with chronic conditions. Requirements voiced by care professionals were the need for clear organization of the user-interface, availability of workflow directives for eHealth usage, minimal steps to perform a task, and integration with their current information system. Patients indicated that care technology should be easy to use and easy to learn, should provide real-time feedback based on self-measured data, and should improve communication between patients and healthcare professionals. Entrepreneurs from the eLabEL consortium will integrate their eHealth and telecare services to meet the requirements of the end-users. The large scale implementation of these technologies will be monitored and the impact on experiences of patients, professionals and organization of care will be studied during a two-year follow-up study. Stakeholders of the eLabEL consortium will join forces to advance the large scale implementation of telecare technologies and eHealth applications in primary care