In Vivo Electroporation Enhances the Immunogenicity of an HIV-1 DNA Vaccine Candidate in Healthy Volunteers

DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Ecoturismo e “hotspots” de biodiversidade aviária no Mato Grosso, que relações espaciais?

O ecoturismo é uma pratica destinada à promover a descoberta do meio “natural” aos turistas, minimizando os impactos ecológicos das visitas e permitindo um desenvolvimento econômico local. A riqueza da biodiversidade é, normalmente, um dos argumentos utilizados para propor a implantação de um sistema de ecoturismo. Este estudo mostra que os centro de ecoturismo no Mato Grosso são extremamente diversos e inegavelmente preocupados com os seus impactos ecológicos. Os “hot spots” da biodiversidade não estão associados aos locais ecoturísticos os mais respeitosos do meio ambiente, mas aos lugares não turísticos e muito antropizados, os parques e jardins dos estabelecimentos agrícolas.L’éco tourisme est une pratique destinée à faire découvrir un milieu “naturel” à des touristes en minimisant les impacts écologiques des visites et en permettant un développement économique profitable au niveau local. La richesse de la biodiversité est souvent un des arguments utilisés pour proposer la mise en place d’un système d’écotourisme. Cette étude montre que les centres d’éco tourisme au Mato Grosso sont très divers et inégalement soucieux de leurs impacts écologiques. Les hot spot de la bio diversité ne sont pas associées au site éco touristiques les plus respectueux de l’environnement, mais à des lieux non touristiques et très anthropisés, les parcs et jardins des exploitations agricoles.Eco tourism is a two folded activity. It is supposed to allow tourists to discover and appreciate natural landscapes without leaving any ecological inprints. It is also supposed to help local developpement for local people and local culture. Biodiversity is often taken as a argument to promote eco tourism in a definite place: a high biodiversity is seen as attractive. This paper, which studies some eco tourism sites in Mato Grosso shows that biodiversity is not at its peak in all eco tourism establishment. It is, in deed, far greater in some agricultural sites, in gardens and in some urban sites

Effects of 21 months of acetylcholinesterase inhibitors on cognitive and functional decline in demented patients

Objectives: The aim of this study was to assess, in a natural setting, the development of cognitive, behavioral and functional performance of elderly dementia patients treated with acetylcholinesterase inhibitors (ChEIs) during a 21-month follow-up,. Another aim was to compare patterns of clinical changes in relation to the patients\u2019 level of cognitive impairment at the beginning of the therapy. Method: Of the 1987 elderly demented patients seen at our unit, 143 met the inclusion/exclusion criteria, were followed for at least 21 months, and were thus included in the study. At the baseline and each control point (up to 21 months), patients were scored for Mini Mental State Examination (MMSE), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and the Neuropsychiatric Inventory. Results: After 21 months\u2019 treatment with ChEIs, patients showed a significant reduction in MMSE, ADL and IADL values. The MMSE score decreased by -1.7 points/year (95%CI -2.1 ; -1.3), irrespective of initial cognitive level, and was lower that expected in non-treated patients (-3/-4 points/year). Conclusion: ChEI therapy is effective in slowing the progression of dementia, even in the long-term, irrespective of baseline cognitive level

Ecoturismo e “hotspots” de biodiversidade aviária no Mato Grosso, que relações espaciais?

Eco tourism is a two folded activity. It is supposed to allow tourists to discover and appreciate natural landscapes without leaving any ecological inprints. It is also supposed to help local developpement for local people and local culture. Biodiversity is often taken as a argument to promote eco tourism in a definite place: a high biodiversity is seen as attractive. This paper, which studies some eco tourism sites in Mato Grosso shows that biodiversity is not at its peak in all eco tourism establishment. It is, in deed, far greater in some agricultural sites, in gardens and in some urban sites

High-resolution Spectroscopic Metallicities of Milky Way Cepheid Standards and Their Impact on the Leavitt Law and the Hubble Constant

Milky Way Cepheid variables with accurate Hubble Space Telescope photometry have been established as standards for primary calibration of the cosmic distance ladder to achieve a percent-level determination of the Hubble constant ( H _0 ). These 75 Cepheid standards are the fundamental sample for investigation of possible residual systematics in the local H _0 determination due to metallicity effects on their period–luminosity relations. We obtained new high-resolution ( R ∼ 81,000), high-signal-to-noise (S/N ∼ 50–150) multiepoch spectra of 42 out of 75 Cepheid standards using the ESPaDOnS instrument at the 3.6 m Canada–France–Hawaii Telescope. Our spectroscopic metallicity measurements are in good agreement with the literature values with systematic differences up to 0.1 dex due to different metallicity scales. We homogenized and updated the spectroscopic metallicities of all 75 Milky Way Cepheid standards and derived their multiwavelength ( GVIJHK _s ) period–luminosity–metallicity and period–Wesenheit–metallicity relations using the latest Gaia parallaxes. The metallicity coefficients of these empirically calibrated relations exhibit large uncertainties due to low statistics and a narrow metallicity range (Δ[Fe/H] = 0.6 dex). These metallicity coefficients are up to 3 times better constrained if we include Cepheids in the Large Magellanic Cloud and range between −0.21 ± 0.07 and −0.43 ± 0.06 mag dex ^−1 . The updated spectroscopic metallicities of these Milky Way Cepheid standards were used in the Cepheid–supernovae distance ladder formalism to determine H _0 = 72.9 ± 1.0 km s ^−1 Mpc ^−1 , suggesting little variation (∼0.1 km s ^−1 Mpc ^−1 ) in the local H _0 measurements due to different Cepheid metallicity scales