Comparison of effectiveness between a conventional catheter and a manual commercial catheter: randomized trial of simulation of intraosseous access in a biological model

Introduction: In the emergency services an action of paramount importance in critically ill patients is to obtain an early vascular access. When vascular access is not established, an intraosseous route should be obtained; otherwise, the mortality of these critically ill patients is almost 100%. In Colombia, the intraosseous access is not used because of the high costs of the devices and the lack of training of the healthcare staff to conduct the procedure.Objective: To determine the efficacy of a low-cost device to establish intraosseous access.Materials and methods: Quantitative approach, experimental design in a simulated environment with chicken tarsus and metatarsus. An analysis was conducted using frequency tables and central tendency measurements. Likewise, further analyses were done using Fisher's exact test, Chi2, and Mann-Whitney test.Results: A total of 99% of the procedures were successful with both catheters. The average time for intraosseous access was 6.6 seconds with Insyte 14 catheter and 4.7 seconds with Din 1515x Illinois Desch device (P=0.001). There were no significant differences in the number of attempts to secure a successful intraosseous access using any of the 2 devices (P=0.56).Conclusion: There was no significant difference between the Ci 14 and the Si 14 catheter to establish a successful intraosseous access in the chicken tarsus and metatarsus in a simulated environment. © 2019 Sociedad Colombiana de Anestesiología y Reanimación (S.C.A.R.E.)

The wideband backend at the MDSCC in Robledo. A new facility for radio astronomy at Q- and K- bands

The antennas of NASA's Madrid Deep Space Communications Complex (MDSCC) in Robledo de Chavela are available as single-dish radio astronomical facilities during a significant percentage of their operational time. Current instrumentation includes two antennas of 70 and 34 m in diameter, equipped with dual-polarization receivers in K (18 - 26 GHz) and Q (38 - 50 GHz) bands, respectively. We have developed and built a new wideband backend for the Robledo antennas, with the objectives (1) to optimize the available time and enhance the efficiency of radio astronomy in MDSCC; and (2) to tackle new scientific cases impossible to that were investigated with the old, narrow-band autocorrelator. The backend consists of an IF processor, a FFT spectrometer (FFTS), and the software that interfaces and manages the events among the observing program, antenna control, the IF processor, the FFTS operation, and data recording. The whole system was end-to-end assembled in August 2011, at the start of commissioning activities, and the results are reported in this paper. Frequency tunings and line intensities are stable over hours, even when using different synthesizers and IF channels; no aliasing effects have been measured, and the rejection of the image sideband was characterized. The first setup provides 1.5 GHz of instantaneous bandwidth in a single polarization, using 8192 channels and a frequency resolution of 212 kHz; upgrades under way include a second FFTS card, and two high-resolution cores providing 100 MHz and 500 MHz of bandwidth, and 16384 channels. These upgrades will permit simultaneous observations of the two polarizations with instantaneous bandwidths from 100 MHz to 3 GHz, and spectral resolutions from 7 to 212 kHz.Comment: 9 pages, 8 figures. Accepted to Astronomy and Astrophysic

Mendelian Randomization Analysis of the Relationship Between Native American Ancestry and Gallbladder Cancer Risk

Background A strong association between the proportion of Native American ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest Native American people in Chile. We set out to investigate the causal association between Native American Mapuche ancestry and GBC risk, and the possible mediating effects of gallstone disease and body mass index (BMI) on this association. Methods Markers of Mapuche ancestry were selected based on the informativeness for assignment measure and then used as instrumental variables in two-sample mendelian randomization (MR) analyses and complementary sensitivity analyses. Result We found evidence of a causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% for every 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.6×10-5). Mapuche ancestry was also causally linked to gallstone disease (IVW risk increase of 3.6% per 1% increase in Mapuche proportion, 95% CI 3.1% to 4.0%, p = 1.0×10-59), suggesting a mediating effect of gallstones in the relationship between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative causal effect on BMI (IVW estimate -0.006 kg/m2 per 1% increase in Mapuche proportion, 95% CI -0.009 to -0.003, p = 4.4×10-5). Conclusions The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between Mapuche ancestry and GBC risk previously noted in observational studies appears to be causal, primary and secondary prevention strategies that take into account the individual proportion of Mapuche ancestry could be particularly efficient

RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer.

BACKGROUND: BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging agents or to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed in clinical trials. Numerous mechanisms of PARPi resistance have been described, whose clinical relevance in gBRCA-mutated breast cancer is unknown. This highlights the need to identify functional biomarkers to better predict PARPi sensitivity. PATIENTS AND METHODS: We investigated the in vivo mechanisms of PARPi resistance in gBRCA1 patient-derived tumor xenografts (PDXs) exhibiting differential response to PARPi. Analysis included exome sequencing and immunostaining of DNA damage response proteins to functionally evaluate HRR. Findings were validated in a retrospective sample set from gBRCA1/2-cancer patients treated with PARPi. RESULTS: RAD51 nuclear foci, a surrogate marker of HRR functionality, were the only common feature in PDX and patient samples with primary or acquired PARPi resistance. Consistently, low RAD51 was associated with objective response to PARPi. Evaluation of the RAD51 biomarker in untreated tumors was feasible due to endogenous DNA damage. In PARPi-resistant gBRCA1 PDXs, genetic analysis found no in-frame secondary mutations, but BRCA1 hypomorphic proteins in 60% of the models, TP53BP1-loss in 20% and RAD51-amplification in one sample, none mutually exclusive. Conversely, one of three PARPi-resistant gBRCA2 tumors displayed BRCA2 restoration by exome sequencing. In PDXs, PARPi resistance could be reverted upon combination of a PARPi with an ataxia-telangiectasia mutated (ATM) inhibitor. CONCLUSION: Detection of RAD51 foci in gBRCA tumors correlates with PARPi resistance regardless of the underlying mechanism restoring HRR function. This is a promising biomarker to be used in the clinic to better select patients for PARPi therapy. Our study also supports the clinical development of PARPi combinations such as those with ATM inhibitors

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Monitoring Drug Use in Mexico: Surveys, surveillance systems and other sources. Bulletin on Narcotics.

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El contexto del uso y abuso del alcohol en jóvenes. En: Alcohol y políticas públicas. Colegio Nacional, México, p.p.61-81. ISBN: 978-607-724-017-4

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