The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

SAFETY AND TOLERABILITY OF MRI-GUIDED INFUSION OF AAV2-hAADC INTO THE MID-BRAIN OF NON-HUMAN PRIMATE.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal-recessive neurological disorder caused by mutations in the DDC gene that leads to an inability to synthesize catecholamines and serotonin. As a result, patients suffer compromised development, particularly in motor function. A recent gene replacement clinical trial explored putaminal delivery of recombinant adeno-associated virus serotype 2 vector encoding human AADC (AAV2-hAADC) in AADC-deficient children. Unfortunately, patients presented only modest amelioration of motor symptoms, which authors acknowledged could be due to insufficient transduction of putamen. We hypothesize that, with the development of a highly accurate MRI-guided cannula placement technology, a more effective approach might be to target the affected mid-brain neurons directly. Transduction of AADC-deficient dopaminergic neurons in the substantia nigra and ventral tegmental area with locally infused AAV2-hAADC would be expected to lead to restoration of normal dopamine levels in affected children. The objective of this study was to assess the long-term safety and tolerability of bilateral AAV2-hAADC MRI-guided pressurized infusion into the mid-brain of non-human primates. Animals received either vehicle, low or high AAV2-hAADC vector dose and were euthanized 1, 3 or 9 months after surgery. Our data indicate that effective mid-brain transduction was achieved without untoward effects

Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial.

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation

Catalyzing red list assessments of underrepresented Taxa through partner networks and student engagement

Global biodiversity decline is continuing largely unabated. The International Union for Conservation of Nature (IUCN) Red List of Threatened Species (hereafter, Red List) provides us with the gold standard for assessments, but taxonomic coverage, especially for invertebrates and fungi, remains very low. Many players contribute to the Red List knowledge base, especially IUCN Red List partners, IUCN-led assessment projects, and the Specialist Groups and Red List Authorities (RLA) of the IUCN Species Survival Commission. However, it is vital that we develop the next generation of contributors and bring in new, diverse voices to build capacity and to sustain the huge assessment effort required to fill data gaps. Here, we discuss a recently established partner network to build additional capacity for species assessments, by linking academia directly into the assessment processes run by Specialist Groups and RLAs. We aim to increase Red List “literacy” amongst potential future conservationists and help students to increase publication output, form professional networks, and develop writing and research skills. Professors can build Red List learning into their teaching and offer Red Listing opportunities to students as assignments or research projects that directly contribute to the Red List. We discuss the opportunities presented by the approach, especially for underrepresented species groups, and the challenges that remain

State of the climate in 2015

In 2015, the dominant greenhouse gases released into Earth\u2019s atmosphere\u2014carbon dioxide, methane, and nitrous oxide\u2014all continued to reach new high levels. At Mauna Loa, Hawaii, the annual CO2 concentration increased by a record 3.1 ppm, exceeding 400 ppm for the first time on record. The 2015 global CO2 average neared this threshold, at 399.4 ppm. Additionally, one of the strongest El Ni\uf1o events since at least 1950 developed in spring 2015 and continued to evolve through the year. The phenomenon was far reaching, impacting many regions across the globe and affecting most aspects of the climate system. Owing to the combination of El Ni\uf1o and a long-term upward trend, Earth observed record warmth for the second consecutive year, with the 2015 annual global surface temperature surpassing the previous record by more than 0.1\ub0C and exceeding the average for the mid- to late 19th century\u2014commonly considered representative of preindustrial conditions\u2014by more than 1\ub0C for the first time. Above Earth\u2019s surface, lower troposphere temperatures were near-record high. Across land surfaces, record to near-record warmth was reported across every inhabited continent. Twelve countries, including Russia and China, reported record high annual temperatures. In June, one of the most severe heat waves since 1980 affected Karachi, Pakistan, claiming over 1000 lives. On 27 October, Vredendal, South Africa, reached 48.4\ub0C, a new global high temperature record for this month. In the Arctic, the 2015 land surface temperature was 1.2\ub0C above the 1981\u20132010 average, tying 2007 and 2011 for the highest annual temperature and representing a 2.8\ub0C increase since the record began in 1900. Increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 25 February 2015, the lowest maximum sea ice extent in the 37-year satellite record was observed, 7% below the 1981\u20132010 average. Mean sea surface temperatures across the Arctic Ocean during August in ice-free regions, representative of Arctic Ocean summer anomalies, ranged from ~0\ub0C to 8\ub0C above average. As a consequence of sea ice retreat and warming oceans, vast walrus herds in the Pacific Arctic are hauling out on land rather than on sea ice, raising concern about the energetics of females and young animals. Increasing temperatures in the Barents Sea are linked to a community-wide shift in fish populations: boreal communities are now farther north, and long-standing Arctic species have been almost pushed out of the area. Above average sea surface temperatures are not confined to the Arctic. Sea surface temperature for 2015 was record high at the global scale; however, the North Atlantic southeast of Greenland remained colder than average and colder than 2014. Global annual ocean heat content and mean sea level also reached new record highs. The Greenland Ice Sheet, with the capacity to contribute ~7 m to sea level rise, experienced melting over more than 50% of its surface for the first time since the record melt of 2012. Other aspects of the cryosphere were remarkable. Alpine glacier retreat continued, and preliminary data indicate that 2015 is the 36th consecutive year of negative annual mass balance. Across the Northern Hemisphere, late-spring snow cover extent continued its trend of decline, with June the second lowest in the 49-year satellite record. Below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska, increasing by up to 0.66\ub0C decade\u20131 since 2000. In the Antarctic, surface pressure and temperatures were lower than the 1981\u20132010 average for most of the year, consistent with the primarily positive southern annular mode, which saw a record high index value of +4.92 in February. Antarctic sea ice extent and area had large intra-annual variability, with a shift from record high levels in May to record low levels in August. Springtime ozone depletion resulted in one of the largest and most persistent Antarctic ozone holes observed since the 1990s. Closer to the equator, 101 named tropical storms were observed in 2015, well above the 1981\u20132010 average of 82. The eastern/central Pacific had 26 named storms, the most since 1992. The western north Pacific and north and south Indian Ocean basins also saw high activity. Globally, eight tropical cyclones reached the Saffir\u2013Simpson Category 5 intensity level. Overlaying a general increase in the hydrologic cycle, the strong El Ni\uf1o enhanced precipitation variability around the world. An above-normal rainy season led to major floods in Paraguay, Bolivia, and southern Brazil. In May, the United States recorded its all-time wettest month in its 121-year national record. Denmark and Norway reported their second and third wettest year on record, respectively, but globally soil moisture was below average, terrestrial groundwater storage was the lowest in the 14-year record, and areas in \u201csevere\u201d drought rose from 8% in 2014 to 14% in 2015. Drought conditions prevailed across many Caribbean island nations, Colombia, Venezuela, and northeast Brazil for most of the year. Several South Pacific countries also experienced drought. Lack of rainfall across Ethiopia led to its worst drought in decades and affected millions of people, while prolonged drought in South Africa severely affected agricultural production. Indian summer monsoon rainfall was just 86% of average. Extremely dry conditions in Indonesia resulted in intense and widespread fires during August\u2013November that produced abundant carbonaceous aerosols, carbon monoxide, and ozone. Overall, emissions from tropical Asian biomass burning in 2015 were almost three times the 2001\u201314 average

Central America and the Caribbean

Título del documento: State of the climate in 2015. Dentro del archivo completo se encontra el apartado correspondiente a Central America and the Caribbean.This chapter provides summaries of the 2015 temperature and precipitation conditions across seven broad regions: North America, Central America and the Caribbean, South America, Africa, Europe, Asia, and Oceania. In most cases, summaries of notable weather events are also included. Local scientists provided the annual summary for their respective regions and, unless otherwise noted, the source of the data used is typically the agency affiliated with the authors. Please note that different nations, even within the same section, may use unique periods to define their normals. Section introductions will typically define the prevailing practices for that section, and exceptions will be noted within the text. In a similar way, many contributing authors use languages other than English as their primary professional language. To minimize additional loss of fidelity through reinterpretation after translation, editors have been conservative and careful to preserve the voice of the author. In some cases, this may result in abrupt transitions in style from section to section.U.S. Department of Energy/[DE-AC05-76RLO1830]//Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI