Morphine for elective endotracheal intubation in neonates: a randomized trial [ISRCTN43546373]

BACKGROUND: Elective endotracheal intubations are still commonly performed without premedication in many institutions. The hypothesis tested in this study was that morphine given prior to elective intubations in neonates would decrease fluctuations in vital signs, shorten the duration of intubation and reduce the number of attempts. METHODS: From December 1999 to September 2000, infants of all gestations admitted to a level III neonatal intensive care unit and requiring an elective endotracheal intubation were randomly assigned to receive morphine 0.2 mg/kg IV or placebo 5 minutes before intubation. Duration of severe hypoxemia (HR< 90/min and Sp0(2)<85%), duration of procedure, duration of hypoxemia (Sp0(2)<85%), number of attempts and change in mean blood pressure were compared between groups. RESULTS: 34 infants (median 989 g and 28 weeks gestation) were included. The duration of severe hypoxemia was similar between groups. Duration of procedure, duration of hypoxemia, number of attempts and increases in mean blood pressure were also similar between groups. 94% of infants experienced bradycardia during the procedure. CONCLUSION: We failed to demonstrate the effectiveness of morphine in reducing the physiological instability or time needed to perform elective intubations. Alternatives, perhaps with more rapid onset of action, should be considered

MALT-45: a 7 mm survey of the southern Galaxy - I. Techniques and spectral line data

We present the first results from the MALT-45 (Millimetre Astronomer's Legacy Team-45 GHz) Galactic Plane survey. We have observed 5 square degrees (l = 330°–335°, b = ±0 ∘ . 5) for spectral lines in the 7 mm band (42–44 and 48–49 GHz), including CS (1–0), class I CH3OH masers in the 7(0,7)–6(1,6) A+ transition and SiO (1–0) v = 0, 1, 2, 3. MALT-45 is the first unbiased, large-scale, sensitive spectral line survey in this frequency range. In this paper, we present data from the survey as well as a few intriguing results; rigorous analyses of these science cases are reserved for future publications. Across the survey region, we detected 77 class I CH3OH masers, of which 58 are new detections, along with many sites of thermal and maser SiO emission and thermal CS. We found that 35 class I CH3OH masers were associated with the published locations of class II CH3OH, H2O and OH masers but 42 have no known masers within 60 arcsec. We compared the MALT-45 CS with NH3 (1,1) to reveal regions of CS depletion and high opacity, as well as evolved star-forming regions with a high ratio of CS to NH3. All SiO masers are new detections, and appear to be associated with evolved stars from the Spitzer Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE). Generally, within SiO regions of multiple vibrational modes, the intensity decreases as v = 1, 2, 3, but there are a few exceptions where v = 2 is stronger than v = 1

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

Recent updates on the Maser Monitoring Organisation

The Maser Monitoring Organisation (M2O) is a research community of telescope operators, astronomy researchers and maser theoreticians pursuing a joint goal of reaching a deeper understanding of maser emission and exploring its variety of uses as tracers of astrophysical events. These proceedings detail the origin, motivations and current status of the M2O, as was introduced at the 2021 EVN symposium

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Assessing and Displaying Landslide Hazards, Badlands National Park, South Dakota

The goal of this study is to assess and communicate hazards associated with landslides in the Badlands National Park using geological mapping and innovative GIS data gathering and display techniques. The current geological map of the Badlands National Park (1:62,500 scale) was published in 1976. While an excellent map, it gives little information useful for hazard assessment other than distribution of slide deposits. The goal here is to create a detailed map of slide distribution together with information on slide mechanisms, timing, and bedrock geologic factors that contribute to hazards. These data are displayed in GIS formats that are interactive, can be quickly updated, and useful for analysis. Landslide zones in the Badlands are especially hazardous to park infrastructure; the main road through the park crosses three of the largest slide zones. At these crossings, road stabilization has been ongoing and expensive. Creep rates of 50 to 125 mm/week were recorded by geotechnical investigators at Cedar Pass prior to stabilization efforts in 2000. In addition to creep, there is significant danger of catastrophic slumping and rock toppling in these zones. Geologic conditions that contribute to slide formation include loosely consolidated strata, precipitation events, the presence of swelling clays, vertical jointing, and a structural dip towards the river valley. In addition to assessing hazards, we are attempting to use GIS techniques in innovative ways. In this first phase of the project, using data gathered in three field seasons, we created a digital base map of the project area in ESRI’s ArcGIS Software. Point, line and polygon vector data were gathered with the use of both sub-meter Trimble GeoXT and Garmin GPS units. Together with field notes, drawings and hyperlinked digital images at specific landslide locations, data was checked into the project Geodatabase and specific feature classes were created/updated and overlaid on high-resolution imagery. Analysis was then performed on the layers to create distinct spatial and temporal boundaries based on geologic beds and historic activity. This state of the art geospatial digital map allows the map user greater access to spatial/geologic information and interpretation of the field area than a traditional geologic map

Learning GIS Through Faculty-Guided Research Projects

Student participation in faculty-guided research builds geoscience content knowledge and develops professional skills. Faculty benefit from student\u27s familiarity with rapidly changing digital technology, including photography, data sharing, social media, and GIS. Here students report on field studies in the Badlands National Park, SD and the Tungurahua volcano, Ecuador. At Badlands National Park students spent two seasons assisting landslide and landscape development studies. Students provided field support by taking field notes, gathering GPS data, taking photos and creating an ArcGIS basemap. Students learned basic GPS operation by creating points, lines and polygons with handheld Garmin GPS units. Specific examples of polygon mapping include mapping the base of a sod table using the track feature on the Garmin handheld unit. At basecamp, students processed geospatial field data, created ESRI shapefiles using the DNR GPS application, and overlaid vectors features on the basemap. At Tungurahua in Baños, Ecuador, students mapped lahar hazards, provided field support by taking field notes, collected location data, took digital photos and created a basemap of the project area. Students also helped prepare for the expedition by performing a literature review and utilizing EndNote to share resources. Students learned the unpredictability of fieldwork; in Ecuador, the Tungurahua was erupting and students were not able to get too close. To map lahar hazards, students used heads-up digitizing. They placed additional lines and points on the map using data collected by the volcano observation center, which was collected by the volcanologists from the Instituto Geofísico, Escuela Politocnica Nacional, in Quito Ecuador. Both projects required a basemap, digital data collection, and a data management plan. Students also learned to work collaboratively with students and faculty outside NSU through creation of work groups in the new ArcGIS.com application and exchanging documents and data through file sharing applications. In summary, through these guided research projects, students expanded their GIS knowledge, learned techniques for field studies, and implemented best practices for managing data. Collaboration with faculty and students from outside NSU was an added benefit