GASCan 2 payload integration

This project, conducted in cooperation with the NASA Advanced Space Design Program, is part of an ongoing effort to place an experiment package into space. The goal of this project is to build and test flight-ready hardware that can be launched from the Space Shuttle. Get Away Special Canister 2 (GASCan 2) consists of three separate experiments. The Ionospheric Properties and Propagation Experiment (IPPE) determines effects of the ionosphere on radio wave propagation. The Microgravity Ignition experiment (MGI) tests the effects of combustion in a microgravity environment. The Rotational Fluid Flow experiment (RFF) examines fluid behavior under varying levels of gravity. This year the following tasks were completed: design of the IPPE antenna, X- and J-cell battery boxes, J-cell battery box enclosure, and structural bumpers; construction of the MGI canisters, MGI mounting brackets, IPPE antenna, and battery boxes; and the selection of the RFF's operating fluid and the analysis of the fluid behavior under microgravity test conditions

Transcranial static magnetic stimulation reduces seizures in a mouse model of Dravet syndrome

Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick evolution toward an increase in the frequency of the seizures, accompanied by a delay in motor and cognitive development, and does not respond well to antiepileptic medication. Most patients carry a mutation in the gene SCN1A encoding the α subunit of the voltage-gated sodium channel Nav1.1, resulting in hyperexcitability of neural circuits and seizure onset. In this work, we applied transcranial static magnetic stimulation (tSMS), a non-invasive, safe, easy-to-use and affordable neuromodulatory tool that reduces neural excitability in a mouse model of Dravet syndrome. We demonstrate that tSMS dramatically reduced the number of crises. Furthermore, crises recorded in the presence of the tSMS were shorter and less intense than in the sham condition. Since tSMS has demonstrated its efficacy at reducing cortical excitability in humans without showing unwanted side effects, in an attempt to anticipate a possible use of tSMS for Dravet Syndrome patients, we performed a numerical simulation in which the magnetic field generated by the magnet was modeled to estimate the magnetic field intensity reached in the cerebral cortex, which could help to design stimulation strategies in these patients. Our results provide a proof of concept for nonpharmacological treatment of Dravet syndrome, which opens the door to the design of new protocols for treatmentXunta de Galicia | Ref. ED431C 2022/05 (CR)Instituto de Salud Carlos III | Ref. PI16/00425Agencia Estatal de Investigación | Ref. PID2019-108250RJ-100Agencia Estatal de Investigación | Ref. RYC2019–026380-

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

Competencies of the nurses in the limitation of therapeutic effort in the intensive care unit: An integrative review

Objective: Nurses inevitably encounter patients who require care aimed at limiting therapeutic effort (LTE), even though many of them are not prepared to provide support to individuals with terminal illnesses and their families. One of the contexts in which the LTE is considered is the intensive care unit (ICU). This review is to describe the competencies for the execution of a nursing professional role in the LTE in the ICU. Method: An integrative review of the literature published between the years 2010 and 2023. The search was carried out in five databases: Medline, Wiley Online Library, SciELO, ScienceDirect, and Web of Science. The Critical Appraisal Skills Programme in Spanish was used as the template for study evaluation. The methodology of the Oxford Center for Evidence-Based Medicine (CEBM) was used to assess the level of evidence and the degree of recommendation. Result: A total of 25 articles in a wide range of studies were included. The findings suggest that the competencies for LTE in the ICU are direct patient care, family-centered care, and the role of the nurse within the team. However, more high-quality studies are needed to confirm these conclusions. Three categories were identified: (a) competencies as defender agent between the patient, his family, and the interdisciplinary team; (b) competencies for decision-making in limiting the therapeutic effort; and (c) competencies for nursing therapeutic interventions at the end of life. Conclusion: The competencies of the nursing professionals who work in the adult ICU in the LTE are essential to the patient's quality of life, dignity of their death, and comprehensive family support for coping with grief

Serous cystic neoplasm of the pancreas: A multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)

OBJECTIVES: 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. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58\u2005years (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\u2005mm (2-200)), 9% had resection beyond 1\u2005year of follow-up (3\u2005years (1-20), size at diagnosis: 25\u2005mm (4-140)) and 39% had no surgery (3.6\u2005years (1-23), 25.5\u2005mm (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\u2005year (n=1271), size increased in 37% (growth rate: 4\u2005mm/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). CONCLUSIONS: 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

Robust signatures of solar neutrino oscillation solutions

With the goal of identifying signatures that select specific neutrino oscillation parameters, we test the robustness of global oscillation solutions that fit all the available solar and reactor experimental data. We use three global analysis strategies previously applied by different authors and also determine the sensitivity of the oscillation solutions to the critical nuclear fusion cross section, S_{17}(0), for the production of 8B. The favored solutions are LMA, LOW, and VAC in order of g.o.f. The neutral current to charged current ratio for SNO is predicted to be 3.5 +- 0.6 (1 sigma), which is separated from the no-oscillation value of 1.0 by much more than the expected experimental error. The predicted range of the day-night difference in charged current rates is (8.2 +- 5.2)% and is strongly correlated with the day-night effect for neutrino-electron scattering. A measurement by SNO of either a NC to CC ratio > 3.3 or a day-night difference > 10%, would favor a small region of the currently allowed LMA neutrino parameter space. The global oscillation solutions predict a 7Be neutrino-electron scattering rate in BOREXINO and KamLAND in the range 0.66 +- 0.04 of the BP00 standard solar model rate, a prediction which can be used to test both the solar model and the neutrino oscillation theory. Only the LOW solution predicts a large day-night effect(< 42%) in BOREXINO and KamLAND. For the KamLAND reactor experiment, the LMA solution predicts 0.44 of the standard model rate; we evaluate 1 sigma and 3 sigma uncertainties and the first and second moments of the energy spectrum.Comment: Included predictions for KamLAND reactor experiment and updated to include 1496 days of Super-Kamiokande observation

Population policies and education: exploring the contradictions of neo-liberal globalisation

The world is increasingly characterised by profound income, health and social inequalities (Appadurai, 2000). In recent decades development initiatives aimed at reducing these inequalities have been situated in a context of increasing globalisation with a dominant neo-liberal economic orthodoxy. This paper argues that neo-liberal globalisation contains inherent contradictions regarding choice and uniformity. This is illustrated in this paper through an exploration of the impact of neo-liberal globalisation on population policies and programmes. The dominant neo-liberal economic ideology that has influenced development over the last few decades has often led to alternative global visions being overlooked. Many current population and development debates are characterised by polarised arguments with strongly opposing aims and views. This raises the challenge of finding alternatives situated in more middle ground that both identify and promote the socially positive elements of neo-liberalism and state intervention, but also to limit their worst excesses within the population field and more broadly. This paper concludes with a discussion outling the positive nature of middle ground and other possible alternatives

Biomimetic Magnetic Nanocarriers Drive Choline Kinase Alpha Inhibitor inside Cancer Cells for Combined Chemo-Hyperthermia Therapy

Choline kinase a1 (ChoKa1) has become an excellent antitumor target. Among all the inhibitors synthetized, the new compound Ff35 shows an excellent capacity to inhibit ChoKa1 activity. However, soluble Ff35 is also capable of inhibiting choline uptake, making the inhibitor not selective for ChoKa1. In this study, we designed a new protocol with the aim of disentangling whether the Ff35 biological action is due to the inhibition of the enzyme and/or to the choline uptake. Moreover, we offer an alternative to avoid the inhibition of choline uptake caused by Ff35, since the coupling of Ff35 to novel biomimetic magnetic nanoparticles (BMNPs) allows it to enter the cell through endocytosis without interacting with the choline transporter. This opens the possibility of a clinical use of Ff35. Our results indicate that Ff35-BMNPs nanoassemblies increase the selectivity of Ff35 and have an antiproliferative effect. Also, we demonstrate the effectiveness of the tandem Ff35-BMNPs and hyperthermia.This research was funded by the Ministerio de Economía y Competitividad (CGL2013-46612 and CGL2016-76723 projects), Ramón y Cajal programme (RYC-2014-16901) and the Fondo Europeo de Desarrollo Regional (FEDER). Also, this research was aided by the Andalusian regional government (CTS-236)

Ecomorph or Endangered Coral? DNA and Microstructure Reveal Hawaiian Species Complexes: Montipora dilatata/flabellata/turgescens & M. patula/verrilli

M. dilatata, M. flabellata, and M. patula and 80 other scleractinian corals were petitioned to be listed under the US Endangered Species Act (ESA), which would have major conservation implications. One of the difficulties with this evaluation is that reproductive boundaries between morphologically defined coral species are often permeable, and morphology can be wildly variable. We examined genetic and morphological variation in Hawaiian Montipora with a suite of molecular markers (mitochondrial: COI, CR, Cyt-B, 16S, ATP6; nuclear: ATPsβ, ITS) and microscopic skeletal measurements. Mitochondrial markers and the ITS region revealed four distinct clades: I) M. patula/M. verrilli, II) M. cf. incrassata, III) M. capitata, IV) M. dilatata/M. flabellata/M. cf. turgescens. These clades are likely to occur outside of Hawai'i according to mitochondrial control region haplotypes from previous studies. The ATPsβ intron data showed a pattern often interpreted as resulting from hybridization and introgression; however, incomplete lineage sorting may be more likely since the multicopy nuclear ITS region was consistent with the mitochondrial data. Furthermore, principal components analysis (PCA) of skeletal microstructure was concordant with the mitochondrial clades, while nominal taxa overlapped. The size and shape of verrucae or papillae contributed most to identifying groups, while colony-level morphology was highly variable. It is not yet clear if these species complexes represent population-level variation or incipient speciation (CA<1MYA), two alternatives that have very different conservation implications. This study highlights the difficulty in understanding the scale of genetic and morphological variation that corresponds to species as opposed to population-level variation, information that is essential for conservation and for understanding coral biodiversity