Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics ...Program (TPP) of the National Institutes of Health (NIH) Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real‐world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene–drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams. TPP participant institutions developed diverse solutions to overcome many barriers, but the use of Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provided some consistency among the institutions. The TPP also collected some pharmacogenetic implementation outcomes (scientific, educational, financial, and informatics), which may inform healthcare systems seeking to implement their own pharmacogenetic testing programs.
The effects of temperature changes on the mechanical behaviour of heat exchanger piles need to be taken into account in geotechnical design. In this preliminary study, the behaviour of an axially ...loaded pile under thermal cycles was investigated using a physical model. After applying the axial load on the pile head, the pile was heated from 25°C to 50°C and subsequently cooled to 25°C. Four tests (corresponding to four values of axial load) were performed and two temperature cycles were undertaken in each test. The pile temperature and the pile head displacement were monitored. When low axial loads were applied, the heating induced heave and cooling induced settlement of the pile head. In this case, the displacement–temperature curve was found to be reversible and similar to the thermal expansion curve of the pile. However, in the case of higher axial loads, the heave of the pile head, obtained during heating, was lower than the thermal expansion of the pile, suggesting settlement of the pile toe. Irreversible settlement of the pile head was observed after these thermal cycles.
Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and ...progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome. As the disease is increasingly diagnosed through the combination of cholestatic serum liver tests and the presence of antimitochondrial antibodies, most presenting patients are not cirrhotic and the term cholangitis is more accurate. Disease course is frequently accompanied by symptoms that can be burdensome for patients, and management of patients with PBC must address, in a life-long manner, both disease progression and symptom burden. Licensed therapies include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed agents. Disease management focuses on initiation of UDCA for all patients and risk stratification based on baseline and on-treatment factors, including in particular the response to treatment. Those intolerant of treatment with UDCA or those with high-risk disease as evidenced by UDCA treatment failure (frequently reflected in trial and clinical practice as an alkaline phosphatase >1.67 × upper limit of normal and/or elevated bilirubin) should be considered for second-line therapy, of which OCA is the only currently licensed National Institute for Health and Care Excellence recommended agent. Follow-up of patients is life-long and must address treatment of the disease and management of associated symptoms.
Multi-walled carbon nanotubes were submitted to three activation procedures: nitric acid oxidation, ball-milling and air oxidation. The influence of these treatments on nanotubes surface chemistry ...and morphology was evaluated by XPS, Raman and infrared spectroscopy, TGA, TPD, nitrogen adsorption and TEM. The three activated materials were used to prepare Pt supported catalysts from the organometallic precursor Pt(CH
3)
2(COD). The influence of the activation treatments, together with that of a post-reduction thermal treatment, on the performances of the catalytic systems in the selective hydrogenation of cinnamaldehyde was investigated. It was shown that the best compromise between catalyst activity and selectivity requires a low amount of oxygenated groups on the support surface of the final catalyst, typically less than 700
μmol/g CO
+
CO
2 evolved during TPD experiments, together with an optimized platinum particle size ranging between 10 and 20
nm.
Decades of research and policy interventions on biodiversity have insufficiently addressed the dual issues of biodiversity degradation and social justice. New approaches are therefore needed. We ...devised a research and action agenda that calls for a collective task of revisiting biodiversity toward the goal of sustaining diverse and just futures for life on Earth. Revisiting biodiversity involves critically reflecting on past and present research, policy, and practice concerning biodiversity to inspire creative thinking about the future. The agenda was developed through a 2‐year dialogue process that involved close to 300 experts from diverse disciplines and locations. This process was informed by social science insights that show biodiversity research and action is underpinned by choices about how problems are conceptualized. Recognizing knowledge, action, and ethics as inseparable, we synthesized a set of principles that help navigate the task of revisiting biodiversity. The agenda articulates 4 thematic areas for future research. First, researchers need to revisit biodiversity narratives by challenging conceptualizations that exclude diversity and entrench the separation of humans, cultures, economies, and societies from nature. Second, researchers should focus on the relationships between the Anthropocene, biodiversity, and culture by considering humanity and biodiversity as tied together in specific contexts. Third, researchers should focus on nature and economies by better accounting for the interacting structures of economic and financial systems as core drivers of biodiversity loss. Finally, researchers should enable transformative biodiversity research and action by reconfiguring relationships between human and nonhuman communities in and through science, policy, and practice. Revisiting biodiversity necessitates a renewed focus on dialogue among biodiversity communities and beyond that critically reflects on the past to channel research and action toward fostering just and diverse futures for human and nonhuman life on Earth.
Una Agenda para la Investigación y la Acción hacia un Futuro Diverso y Justo para la Vida sobre la Tierra
Resumen
Las décadas de investigación e intervenciones políticas sobre la biodiversidad han tratado significativamente los temas de la degradación de la biodiversidad y la justicia social. Debido a esto, se requieren nuevas estrategias. Diseñamos una agenda de investigación y acción que llama a la labor colectiva de revisar la biodiversidad hacia el objetivo de sustentar un futuro diverso y justo para la vida sobre la Tierra. Cuando se revisa la biodiversidad, se requiere de una reflexión crítica sobre las investigaciones, políticas y prácticas presentes y pasadas sobre la biodiversidad para inspirar un pensamiento creativo acerca del futuro. Desarrollamos la agenda por medio de un proceso de diálogo de dos años que involucró a casi 300 expertos de diversas disciplinas y localidades. Este proceso estuvo orientado por el conocimiento de las ciencias sociales que muestra cómo la investigación y la acción para la biodiversidad están sostenidas por las opciones de cómo están conceptualizados los problemas. Reconocimos al conocimiento, la acción y la ética como inseparables y sintetizamos un conjunto de principios que ayuda a navegar la labor de revisar la biodiversidad. La agenda articula cuatro áreas temáticas para la investigación en el futuro. Primero, los investigadores necesitan revisar las narrativas de la biodiversidad mediante el cuestionamiento de las conceptualizaciones que excluyen a la diversidad y consolidan la separación entre humanos, culturas, economías y sociedades y la naturaleza. Segundo, los investigadores deberían enfocarse en las relaciones entre el antropoceno, la biodiversidad y la cultura al considerar a la humanidad y la biodiversidad como interconectadas en contextos específicos. Tercero, los investigadores deberían enfocarse en la naturaleza y las economías al tener en mejor cuenta la interacción de las estructuras de los sistemas económico y financiero como conductores nucleares de la pérdida de la biodiversidad. Finalmente, los investigadores deberían permitir la investigación y acción transformadoras de la biodiversidad al reconfigurar las relaciones entre las comunidades humanas y no humanas dentro y a través de la ciencia, la política y la práctica. La revisión de la biodiversidad necesita de un enfoque renovado sobre el diálogo entre las comunidades de la biodiversidad y más allá, que reflexione críticamente sobre el pasado para canalizar a la investigación y acción hacia el fomento del futuro justo y diverso para la vida humana y no humana sobre la Tierra.
Article Impact Statement: Placing diversity and justice at the heart of transformative change for biodiversity offers important new directions for research and action.
Abstract
In this work, we compare the CO oxidation performance of Pt single atom catalysts (SACs) prepared via two methods: (1) conventional wet chemical synthesis (strong electrostatic ...adsorption–SEA) with calcination at 350 °C in air; and (2) high temperature vapor phase synthesis (atom trapping–AT) with calcination in air at 800 °C leading to ionic Pt being trapped on the CeO
2
in a thermally stable form. As-synthesized, both SACs are inactive for low temperature (<150 °C) CO oxidation. After treatment in CO at 275 °C, both catalysts show enhanced reactivity. Despite similar Pt metal particle size, the AT catalyst is significantly more active, with onset of CO oxidation near room temperature. A combination of near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) and CO temperature-programmed reduction (CO-TPR) shows that the high reactivity at low temperatures can be related to the improved reducibility of lattice oxygen on the CeO
2
support.
Caenorhabditis elegans has been an invaluable model organism in research fields such as developmental biology and neurobiology. Neurotoxicity is one of the subfields greatly profiting from the C. ...elegans model within biomedical context, while the corresponding potential of the organism applied to environmental studies is relevant but has been largely underexplored. Within the biomedical scope, the implication of metals and organic chemicals with pesticide activity (hereinafter designated as pesticides) in the etiology of several neurodegenerative diseases has been extensively investigated using this nematode as a primary model organism. Additionally, as a well-known experimental model bearing high sensitivity to different contaminants and representing important functional levels in soil and aquatic ecosystems, C. elegans has high potential to be extensively integrated within Environmental Risk Assessment (ERA) routines. In spite of the recognition of some regulatory agencies, this actual step has yet to be made. The purpose of this review is to discuss the major advantages supporting the inclusion of C. elegans in lower tiers of ERA. Special emphasis was given to its sensitivity to metals and pesticides, which is similar to that of other model organisms commonly used in ERA (e.g. Daphnia magna and Eisenia sp.), and to the large array of endpoints that can be tested with the species, both concerning the aquatic and the soil compartments. The inclusion of C. elegans testing may hence represent a relevant advance in ERA, providing ecologically relevant insights toward improvement of the regulatory capacity for establishing appropriate environmental protection benchmarks.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The objective was to evaluate if expression of estrus by dairy cattle altered fertility in timed artificial insemination (AI; n=5,430) or timed embryo transfer (ET; n=2,003) programs that used ...estradiol and progesterone (P4) to synchronize ovulation. Ovarian ultrasonography was performed on d 0 (time of AI) and 7 to determine ovulatory follicle diameter and ovulation. Only cows with a visible corpus luteum on d 7 were used in this study. At the time of controlled internal drug release removal, all cows received a tail-head device for detection of estrus and were considered in estrus when the paint of the device was completely removed by d 0. Circulating P4 concentrations were evaluated on d 7. Pregnancies per AI (P/AI) or ET (P/ET) were determined by ultrasonography on d 32 and 60. At d-32 pregnancy diagnosis, cows with expression of estrus had increased P/AI no estrus=25.5% (222/846) vs. estrus=38.9% (1,785/4,584) and P/ET no estrus=32.7% (193/606) vs. estrus=46.2% (645/1,397). Similarly, at d-60 pregnancy diagnosis, expression of estrus increased P/AI no estrus=20.1% (179/846) vs. estrus=33.3% (1,530/4,584) and P/ET no estrus=25.1% (150/606) vs. estrus=37.5% (525/1,397). Pregnancy loss was lower in cows that expressed estrus in timed AI TAI; no estrus=20.1% (43/222) vs. estrus 14.4% (255/1,785) and timed ET TET; no estrus=22.7% (43/193) vs. estrus=18.6% (120/645) compared with cows with no estrus. Independent of expression of estrus cows ovulating either too small or too large of follicles had lower P/AI. No effect of ovulatory follicle diameter on P/ET was noted in cows that expressed estrus; although, cows that did not express estrus tended to have lower P/ET if they ovulated larger follicles. In cows that showed estrus, follicle diameter did not affect pregnancy loss, but cows that did not show estrus and ovulated larger follicles tended to have greater pregnancy loss after TAI and had greater pregnancy loss on TET. A positive effect of d-7 P4 concentrations on P/AI was observed, independent of estrus. In contrast, no effect of P4 was found on d 7 on P/ET. Thus, expression of estrus during protocols for TAI or TET is associated with an increase in fertility and reduction in pregnancy loss. During TAI programs, optimizing follicle diameter and increasing circulating P4 on d 7 after AI were also associated with increased fertility, independent of expression of estrus. However, in cows with TET, the association of fertility with either ovulatory follicle diameter or P4 on d 7 was less dramatic and seemed to be related to whether cows expressed estrus.
In this work we introduce a low-energy Hamiltonian for single-layer and bilayer black phosphorus that describes the electronic states at the vicinity of the Gamma point. The model is based on a ...recently proposed tight-binding description for electron and hole bands close to the Fermi level. We calculate expressions for the Landau-level spectrum as function of magnetic field, and in the case of bilayer black phosphorus we investigate the effect of an external bias on the electronic band gap. The results showcase the highly anisotropic character of black phosphorus, and in particular for bilayer BP, the presence of bias allows for a field-induced semiconductor-metal transition.
Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the ...specific mortality.
Retrospective multinational study including SCN diagnosed between 1990 and 2014.
2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1).
After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN.
IRB 00006477.
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