First-in-Human Randomized, Controlled Trial of Mosaic HIV-1 Immunogens Delivered via a Modified Vaccinia Ankara Vector.

Background: Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains. Methods: This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365. Results: All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine. Conclusions: No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited. Clinical Trials Registration: NCT02218125.

Long-term decline of the Amazon carbon sink.

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades, with a substantial fraction of this sink probably located in the tropics, particularly in the Amazon. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale, and is contrary to expectations based on models.

Postoperative antibacterial prophylaxis for the prevention of infectious complications associated with tube thoracostomy in patients undergoing elective general thoracic surgery: a double-blind, placebo-controlled, randomized trial.

OBJECTIVE: To determine whether extended postoperative antibacterial prophylaxis for patients undergoing elective thoracic surgery with tube thoracostomy reduces the risk of infectious complications compared with preoperative prophylaxis only. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Brigham and Women's Hospital, an 800-bed tertiary care teaching hospital in Boston, Massachusetts. PARTICIPANTS: A total of 251 adult patients undergoing elective thoracic surgery requiring tube thoracostomy between April 2008 and April 2011. INTERVENTIONS: Patients received preoperative antibacterial prophylaxis with cefazolin sodium (or other drug if the patient was allergic to cefazolin). Postoperatively, patients were randomly assigned (at a 1:1 ratio) using a computer-generated randomization sequence to receive extended antibacterial prophylaxis (n = 125) or placebo (n = 126) for 48 hours or until all thoracostomy tubes were removed, whichever came first. MAIN OUTCOME MEASURES: The combined occurrence of surgical site infection, empyema, pneumonia, and Clostridium difficile colitis by postoperative day 28. RESULTS: A total of 245 patients were included in the modified intention-to-treat analysis (121 in the intervention group and 124 in the placebo group). Thirteen patients (10.7%) in the intervention group and 8 patients (6.5%) in the placebo group had a primary end point (risk difference, -4.3% [95% CI, -11.3% to 2.7%]; P = .26). Six patients (5.0%) in the intervention group and 5 patients (4.0%) in the placebo group developed surgical site infections (risk difference, -0.93% [95% CI, -6.1% to 4.3%]; P = .77). Seven patients (5.8%) in the intervention group and 3 patients (2.4%) in the placebo group developed pneumonia (risk difference, -3.4% [95% CI, -8.3% to 1.6%]; P = .21). One patient in the intervention group developed empyema. No patients experienced C difficile colitis. CONCLUSIONS: Extended postoperative antibacterial prophylaxis for patients undergoing elective thoracic surgery requiring tube thoracostomy did not reduce the number of infectious complications compared with preoperative prophylaxis only. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00818766.

Are functional traits good predictors of demographic rates? Evidence from five neotropical forests.

A central goal of comparative plant ecology is to understand how functional traits vary among species and to what extent this variation has adaptive value. Here we evaluate relationships between four functional traits (seed volume, specific leaf area, wood density, and adult stature) and two demographic attributes (diameter growth and tree mortality) for large trees of 240 tree species from five Neotropical forests. We evaluate how these key functional traits are related to survival and growth and whether similar relationships between traits and demography hold across different tropical forests. There was a tendency for a trade-off between growth and survival across rain forest tree species. Wood density, seed volume, and adult stature were significant predictors of growth and/or mortality. Both growth and mortality rates declined with an increase in wood density. This is consistent with greater construction costs and greater resistance to stem damage for denser wood. Growth and mortality rates also declined as seed volume increased. This is consistent with an adaptive syndrome in which species tolerant of low resource availability (in this case shade-tolerant species) have large seeds to establish successfully and low inherent growth and mortality rates. Growth increased and mortality decreased with an increase in adult stature, because taller species have a greater access to light and longer life spans. Specific leaf area was, surprisingly, only modestly informative for the performance of large trees and had ambiguous relationships with growth and survival. Single traits accounted for 9-55% of the interspecific variation in growth and mortality rates at individual sites. Significant correlations with demographic rates tended to be similar across forests and for phylogenetically independent contrasts as well as for cross-species analyses that treated each species as an independent observation. In combination, the morphological traits explained 41% of the variation in growth rate and 54% of the variation in mortality rate, with wood density being the best predictor of growth and mortality. Relationships between functional traits and demographic rates were statistically similar across a wide range of Neotropical forests. The consistency of these results strongly suggests that tropical rain forest species face similar trade-offs in different sites and converge on similar sets of solutions.