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Viruses are the most numerically abundant biological entities on Earth. As ubiquitous replicators of molecular information and agents of community change, viruses have potent effects on the life on Earth, and may play a critical role in human spaceflight, for life-detection missions to other planetary bodies and planetary protection. However, major knowledge gaps constrain our understanding of the Earth's virosphere: (1) the role viruses play in biogeochemical cycles, (2) the origin(s) of viruses and (3) the involvement of viruses in the evolution, distribution and persistence of life. As viruses are the only replicators that span all known types of nucleic acids, an expanded experimental and theoretical toolbox built for Earth's viruses will be pivotal for detecting and understanding life on Earth and beyond. Only by filling in these knowledge and technical gaps we will obtain an inclusive assessment of how to distinguish and detect life on other planetary surfaces. Meanwhile, space exploration requires life-support systems for the needs of humans, plants and their microbial inhabitants. Viral effects on microbes and plants are essential for Earth's biosphere and human health, but virus–host interactions in spaceflight are poorly understood. Viral relationships with their hosts respond to environmental changes in complex ways which are difficult to predict by extrapolating from Earth-based proxies. These relationships should be studied in space to fully understand how spaceflight will modulate viral impacts on human health and life-support systems, including microbiomes. In this review, we address key questions that must be examined to incorporate viruses into Earth system models, life-support systems and life detection. Tackling these questions will benefit our efforts to develop planetary protection protocols and further our understanding of viruses in astrobiology.
Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.
Throughout most of the Anglo-French Wars of 1793-1815, the burden of defending France’s interests against Britain fell primarily upon its navy. Having suffered several major defeats and the loss of New France and other colonies, France and its navy re-emerged to contest Britain’s dominance at sea during the American Revolutionary War in1778-1783. Although the French navy had scored several strategic victories for their American allies, the defeat at the Battle of the Saints in 1782 left France with little to show for its efforts except a massive debt. As a navy required extensive logistical systems to mobilize both its resources and manpower, this endeavour presented ever increasingly strenuous challenge to the French monarchy. Faced with needs to modernize both its fiscal, social, and political structures, the French monarchy failed to navigate the tumultuous process of reform. While the resulting French Revolution removed some of the impediments to reform, it also presented its own difficulties as revolutionary principles often clashed with the needs of military service. Although Napoleon Bonaparte brought relatively stability to France and invested massive amount of resources to regenerate the French navy, his insatiable desire for aggrandizing the French Empire and the nearly constant state of war made it difficult to achieve his naval aspirations.
Every five years a survey of this sort is attempted with the goal of reflecting the “democratic weathervane” of Latin American politics. Since Russell Fitzgibbon launched the experiment in 1945, regular attempts have been made to tap the minds of expert panelists in a reputational evaluation of which countries are the most and least democratic. Many Latin American nations claim that political democracy is their goal (my understanding of democracy in theory and practice is alluded to in the notes below), although they choose to reach it via contrasting routes. Blatant dictatorships often use the plebiscite as a means of demonstrating that they enjoy popular approval and acclaim, and single-party “democracies” regularly give the appearance of popular support via controlled elections. Latin Americans may feel that North Americans have an excess baggage of ego and ethnocentricity in pretending to evaluate democracy to the south according to our criteria; that is probably a just reaction. But the Latin Americans do boast constitutional structures and theoretic pronouncements patterned after ours. They have also accepted considerable North American assistance and financial largesse in the alleged quest for the democratic “good life.” And Latin American scholars frequently evaluate the status of political democracy in the so-called Anglo-American parliamentary states. Evaluating democracy is thus a two-way street, and the enterprise may yield mutual rewards and pitfalls.
As practiced contemporaneously in most of Latin America, political democracy is more accurately elite governance, with many of the thornier authoritarian trappings cloaked behind an often transparent facade of “popular suffrage” and “parliamentary government.” Democracy, as a normative basis for the “good life,” is difficult to describe and conceptualize, especially when one assumes that the democratic prototype is to be discovered somewhere within that caldron of slippery political variables known as the Anglo-American model. I do not assume in this report that the nations of Latin America should be trying to move in the direction of the Anglo-American model (assuming we can describe, more or less generically, the constituent parts of that model). Nevertheless, I would be remiss in not stating the general outlines of what I understand political democracy to mean as related to the quinquennial survey of scholarly images to be reported herein.
Ice internal temperature and basal geothermal heat flux (GHF) are analyzed along a study line in northwestern Greenland. The temperatures were obtained from a previously reported inversion of airborne microwave brightness-temperature spectra. The temperatures vary slowly through the upper ice sheet and more rapidly near the base increasing from ~259 K near Camp Century to values near the melting point near NorthGRIP. The flow-law rate factor is computed from temperature data and analytic expressions. The rate factor increases from ~1 × 10−8 to 8 × 10−8 kPa−3 a−1 along the line. A laminar flow model combined with the depth-dependent rate factor is used to estimate horizontal velocity. The modeled surface velocities are about a factor of 10 less than interferometric synthetic aperture radar (InSAR) surface velocities. The laminar velocities are fitted to the InSAR velocities through a factor of 8 enhancement of the rate factor for the lower 25% of the column. GHF values retrieved from the brightness temperature spectra increase from ~55 to 84 mW m−2 from Camp Century to NorthGRIP. A strain heating correction improves agreement with other geophysical datasets near Camp Century and NEEM but differ by ~15 mW m−2 in the central portion of the profile.
OBJECTIVES/GOALS: To facilitate the development of innovative injection products by providing translational researchers with a regulatory and manufacturing road map for producing small batch sterile products for Phase 1 research use. To leverage recent AMC investments in facility improvements and pharmacy training in the areas of sterile product production, testing, and environmental controls, that can be used to support production of phase 1 clinical trial supplies METHODS/STUDY POPULATION: Searching and organizing relevant data and information from web portals and databases in the following: areas: FDA, EMA, USP regulations, regulatory science, pharmaceutical formulation and analytics, supply vendors, analytical testing laboratories, and product testing laboratories. Present the information using a user friendly format including flow charts and development timelines, taking the perspective of the translational investigator. RESULTS/ANTICIPATED RESULTS:
Choosing AMC resources vs outside consultants and vendors, leveraging local resources where possible
Qualifying and monitoring suppliers, testing laboratories, in-house departments, and Contract Drug Manufacturing Organizations (CDMO)
Bringing together the deliverables for the IND CMC section
Where and how to leverage available products and science to simplify safe and reliable production
DISCUSSION/SIGNIFICANCE OF IMPACT: Use and utility of injectable drug products, both small molecule and biologics, is growing rapidly, and is projected to continue to escalate well into the next decade. This is due not only to advances in medicine, but also to improvements in AMC-based sterile product production, and a better understanding of small batch manufacturing methods. All three trends align in academic medical centers (AMC) and can be utilized by translational researchers, if they can understand the potential and regulatory requirements.
At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case–control and one nested case–cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
The administration of naloxone therapy is restricted by scope of practice to Advanced Life Support (ALS) in many Emergency Medical Services (EMS) systems throughout the United States. In Delaware’s two-tiered EMS system, Basic Life Support (BLS) often arrives on-scene prior to ALS, but BLS providers were not previously authorized to administer naloxone. Through a BLS naloxone pilot study, the researchers sought to evaluate BLS naloxone administration and timing compared to ALS.
After undergoing specialized training, BLS providers would be able to appropriately administer naloxone to opioid overdose patients in a more timely manner than ALS providers.
This was a retrospective, observational study using data collected from February 2014 through May 2015 throughout a state BLS naloxone pilot program. A total of 14 out of 72 state BLS agencies participated in the study. Pilot BLS agencies attended a training session on the indications and administration of naloxone, and then were authorized to carry and administer naloxone. Researchers then compared vital signs and the time of BLS arrival to administration of naloxone by BLS and ALS. Data were analyzed using paired and independent sample t-tests, as well as chi-square, as appropriate.
A total of 131 incidents of naloxone administration were reviewed. Of those, 62 patients received naloxone by BLS (pilot group) and 69 patients received naloxone by ALS (control group). After naloxone administration, BLS patients showed improvements in heart rate (HR; P < .01), respiratory rate (RR; P < .01), and pulse oximetry (spO2; P < .01); ALS patients also showed improvement in RR (P < .01), and in spO2 (P = .005). There was no significant improvement in HR for ALS providers (P = .189).
There was a significant difference in arrival time of BLS to the time of naloxone administration between the two groups, with shorter times in the BLS group compared to the ALS group (1.9 minutes versus 9.8 minutes; P < .01); BLS administration was 7.8 minutes faster when compared to ALS administration (95% CI, 6.2-9.3 minutes).
Patients improved similarly and received naloxone therapy sooner when treated by BLS agencies carrying naloxone than those who awaited ALS arrival. All EMS systems should consider allowing BLS to carry and administer naloxone for an effective and potentially faster naloxone administration when treating respiratory compromise related to opiate overdose.
Altica's location in the Patlachique Range, 10 km away from the Otumba obsidian source, suggests its potential role in the distribution of Otumba obsidian. Altica may have been an important Formative middleman and processing site for obsidian exchange within the Basin of Mexico. To the south, Coapexco's position along a natural, restricted inlet to the Basin of Mexico may have enabled it to function as a node for pooling and distributing material into the Basin. This paper combines geochemical sourcing and technological data drawn from several Early and Middle Formative obsidian assemblages to reconstruct the movement of obsidian in this period to identify obsidian sources and consumption sites. In doing so, the paper assesses the role that intermediary sites like Altica and Coapexco could have played in the processing and distribution of obsidian into more distant consumption sites.
Inadequate protein quality may be a risk factor for poor growth. To examine the effect of a macronutrient–micronutrient supplement KOKO Plus (KP), provided to infants from 6 to 18 months of age, on linear growth, a single-blind cluster-randomised study was implemented in Ghana. A total of thirty-eight communities were randomly allocated to receive KP (fourteen communities, n 322), a micronutrient powder (MN, thirteen communities, n 329) and nutrition education (NE, eleven communities, n 319). A comparison group was followed cross-sectionally (n 303). Supplement delivery and morbidity were measured weekly and anthropometry monthly. NE education was provided monthly. Baseline, midline and endline measurements at 6, 12 and 18 months included venous blood draws, diet, anthropometry, morbidity, food security and socio-economics. Length-for-age Z-score (LAZ) was the primary outcome. Analyses were intent-to-treat using mixed-effects regressions adjusted for clustering, sex, age and baseline. No differences existed in mean LAZ scores at endline (−1·219 (sd 0·06) KP, −1·211 (sd 0·03) MN, −1·266 (sd 0·03) NE). Acute infection prevalence was lower in the KP than NE group (P = 0·043). Mean serum Hb was higher in KP infants free from acute infection (114·02 (sd 1·87) g/l) than MN (107·8 (sd 2·5) g/l; P = 0·047) and NE (108·8 (sd 0·99) g/l; P = 0·051). Compliance was 84·9 % (KP) and 87·2 % (MN) but delivery 60 %. Adjusting for delivery and compliance, LAZ score at endline was significantly higher in the KP v. MN group (+0·2 LAZ; P = 0·026). A macro- and micronutrient-fortified supplement KP reduced acute infection, improved Hb and demonstrated a dose–response effect on LAZ adjusting consumption for delivery.
Powerful synergies between phosphonate, zinc oxide, and acrylamido-tert-butyl-sulfonate (ATBS) copolymer chemical additives render superior performance in a high-temperature retarder system for oil well grade Portland cement. The phosphonate retarder and ATBS-based retarders establish a two-tiered strength development where amorphous C-S-H converts to crystalline dicalcium silicate hydrate (C2SH) in the first (low compressive strength) tier prior to the reaction of Portlandite with quartz. The three additive retarder system can be tuned with nanosilica to eliminate the two-tiered strength development effect leading to a smooth transition from the cement in the slurry form directly to its highest compressive strength.
Background: Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord impairment. In a public healthcare system, wait times to see spine specialists and eventually access surgical treatment for CSM can be substantial. The goals of this study were to determine consultation wait times (CWT) and surgical wait times (SWT), and identify predictors of wait time length. Methods: Consecutive patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) prospective and observational CSM study from March 2015 to July 2017 were included. A data-splitting technique was used to develop and internally validate multivariable models of potential predictors. Results: A CSORN query returned 264 CSM patients for CWT. The median was 46 days. There were 31% mild, 35% moderate, and 33% severe CSM. There was a statistically significant difference in median CWT between moderate and severe groups; 207 patients underwent surgical treatment. Median SWT was 42 days. There was a statistically significant difference in SWT between mild/moderate and severe groups. Short symptom duration, less pain, lower BMI, and lower physical component score of SF-12 were predictive of shorter CWT. Only baseline pain and medication duration were predictive of SWT. Both CWT and SWT were shorter compared to a concurrent cohort of lumbar stenosis patients (p <0.001). Conclusions: Patients with shorter duration (either symptoms or medication) and less neck pain waited less to see a spine specialist in Canada and to undergo surgical treatment. This study highlights some of the obstacles to overcome in expedited care for this patient population.
The table that begins overleaf provides a quick-reference, country-by-country listing for Christianity and its major traditions for all the countries that appear in this volume. These statistics are found in the World Christian Database (see Methodology and Sources) and all figures relate to 1970 and 2015. Small numbers are left unrounded to distinguish known small populations from zero but do not represent precise estimates.
The columns are as follows:
• Country (name of country in English)
• Region in which country is located
• Total population of country (United Nations estimate, 1970, 2015) and total numbers and percentage of population in each tradition
• Percentage mean annual growth rate, 1970–2015.
The last page of the table presents regional totals.