Understanding how species' thermal limits have evolved across the tree of life is central to predicting species' responses to climate change. Here, using experimentally-derived estimates of thermal ...tolerance limits for over 2000 terrestrial and aquatic species, we show that most of the variation in thermal tolerance can be attributed to a combination of adaptation to current climatic extremes, and the existence of evolutionary 'attractors' that reflect either boundaries or optima in thermal tolerance limits. Our results also reveal deep-time climate legacies in ectotherms, whereby orders that originated in cold paleoclimates have presently lower cold tolerance limits than those with warm thermal ancestry. Conversely, heat tolerance appears unrelated to climate ancestry. Cold tolerance has evolved more quickly than heat tolerance in endotherms and ectotherms. If the past tempo of evolution for upper thermal limits continues, adaptive responses in thermal limits will have limited potential to rescue the large majority of species given the unprecedented rate of contemporary climate change.
How climate affects species distributions is a longstanding question receiving renewed interest owing to the need to predict the impacts of global warming on biodiversity. Is climate change forcing ...species to live near their critical thermal limits? Are these limits likely to change through natural selection? These and other important questions can be addressed with models relating geographical distributions of species with climate data, but inferences made with these models are highly contingent on non-climatic factors such as biotic interactions. Improved understanding of climate change effects on species will require extensive analysis of thermal physiological traits, but such data are both scarce and scattered. To overcome current limitations, we created the GlobTherm database. The database contains experimentally derived species' thermal tolerance data currently comprising over 2,000 species of terrestrial, freshwater, intertidal and marine multicellular algae, plants, fungi, and animals. The GlobTherm database will be maintained and curated by iDiv with the aim to keep expanding it, and enable further investigations on the effects of climate on the distribution of life on Earth.
The Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, ...we report results on the final efficacy and interim safety analyses of the phase 3 trial.
This double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990).
Study enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7–70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up IQR 36–58). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 0·1% of 18 363 Ad5-nCoV recipients and 10 0·1% of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 2·4% of 18 363 Ad5-nCoV recipients and 411 2·2% of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p<0·0001), of which headache was the most common (699 44% of Ad5-nCoV recipients and 481 30·6% of placebo recipients; p<0·0001). 971 (61·3%) of 1584 Ad5-nCoV recipients and 314 (20·0%) of 1573 placebo recipients reported an injection-site adverse event (p<0·0001), of which pain at the injection site was the most frequent; reported by 939 (59%) Ad5-nCoV recipients and 303 (19%) placebo recipients.
One dose of Ad5-nCoV is efficacious and safe in healthy adults aged 18 years and older.
CanSino Biologics and the Beijing Institute of Biotechnology.
Background. Mismatch between circulating influenza B viruses (Yamagata and Victoria lineages) and vaccine strains occurs frequently. Methods. In a randomized controlled trial, immunogenicity and ...safety of an inactivated quadrivalent influenza vaccine candidate (QIV) versus trivalent inactivated influenza vaccine (TIV)-Victoria(Vic) and TIV-Yamagata(Yam) in children 3-17 years of age was evaluated. In an open-label study arm, QIV only was assessed in children 6-35 months of age. Results. A total of 3094 children (932 QIV, 929 TIV-Vic, 932 TIV-Yam, and 301 QIV only) were vaccinated. QIV was noninferior to the TIVs for shared strains (A/H3N2 and A/H1N1) based on hemagglutination-inhibition (HI) antibodies 28 days after last vaccination, and superior for the unique B strains Victoria and Yamagata (geometric mean titer ratios 2.61, 3.78; seroconversion rate differences 33.96%, 44.63%). Among children in the randomized trial, adverse event rates were similar except for injection site pain (dose 1: 65.4% QIV, 54.6% TIV-Vic, 55.7% TIV-Yam). Conclusion. QIV elicited superior HI responses to the added B strains compared to TIV controls, potentially improving its effectiveness against influenza B. HI responses were similar between QIV and TIV controls for the shared strains. QIV had an acceptable safety profile relative to TIVs. Clinical Trials Registration. NCT01198756.
The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, ...pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na(+) regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na(+) homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na(+) homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes.
Abstract
Background
Injection drug use (IDU) following treatment for hepatitis C virus (HCV) infection may lead to reinfection, particularly if access to harm reduction services is suboptimal. This ...study assessed HCV reinfection risk following direct-acting antiviral therapy within Australian prisons that had opioid agonist therapy (OAT) programs but did not have needle and syringe programs (NSPs).
Methods
The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study enrolled people incarcerated in 4 prisons between 2014 and 2019. Participants treated for HCV were followed every 3–6 months to identify reinfection (confirmed by sequencing). Reinfection incidence and associated factors were evaluated.
Results
Among 388 participants receiving treatment, 161 had available posttreatment follow-up and were included in analysis (92% male; median age, 33 years; 67% IDU in prison; median follow-up 9 months). Among those with recent (in the past month) IDU (n = 71), 90% had receptive needle/syringe sharing. During 145 person-years (PY) of follow-up, 18 cases of reinfection were identified. Reinfection incidence was 12.5/100 PY (95% confidence interval CI: 7.9–19.8) overall, increasing to 28.7/100 PY (95% CI: 16.3–50.6) among those with recent IDU and needle/syringe sharing. In adjusted analysis, recent IDU with needle/syringe sharing was associated with increased reinfection risk (adjusted hazard ratio aHR, 4.74 95% CI: 1.33–16.80; P = .016) and longer HCV testing interval with decreased risk (ie, chance of detection; aHR, 0.41 per each month increase 95% CI: .26–.64; P < .001).
Conclusions
A high rate of HCV reinfection was observed within prison. Posttreatment surveillance and retreatment are essential to limit the impact of reinfection. High-coverage OAT and NSPs should be considered within prisons.
Clinical Trials Registration
NCT02064049
A high reinfection incidence (13/100 person-years PY) was observed among people treated for hepatitis C virus in prison. Risk was highest in those with injection drug use and receptive needle/syringe sharing (29/100 PY). Increased access to harm reduction in prisons is needed.
People in prison are at high risk of HCV given high injecting drug use prevalence. This study evaluated HCV incidence and associated injecting drug use characteristics in prison. The SToP‐C study ...enrolled people incarcerated in four Australian prisons. Participants were tested for HCV at enrolment and then every 3–6 months (October‐2014 to November‐2019). Participants eligible for this analysis included those at‐risk of HCV primary infection (anti‐HCV negative) or re‐infection (anti‐HCV positive, HCV RNA negative) with follow‐up assessment. A total of 1643 eligible participants were included in analyses (82% male; median age 33 years; 30% injected drugs in prison; 1818 person‐years of follow‐up). Overall HCV incidence was 6.11/100 person‐years (95%CI: 5.07–7.35), with higher rate of re‐infection (9.34/100 person‐years; 95%CI: 7.15–12.19) than primary infection (4.60/100 person‐years; 95%CI: 3.56–5.96). In total population (n = 1643), HCV risk was significantly higher among participants injecting drugs in prison vs. no injecting; adjusted hazard ratio (aHR): 10.55, 95%CI: 5.88–18.92), and those who were released and re‐incarcerated during follow‐up (vs. remained incarcerated; aHR: 1.60, 95%CI: 1.03–2.49). Among participants who injected recently (during past month, n = 321), HCV risk was reduced among those receiving high‐dosage opioid agonist therapy (OAT), i.e. methadone ≥60 mg/day or buprenorphine ≥16 mg/day, (vs. no OAT, aHR: 0.11, 95%CI: 0.02–0.80) and increased among those sharing needles/syringes without consistent use of disinfectant to clean injecting equipment (vs. no sharing, HR: 4.60, 95%CI: 1.35–15.66). This study demonstrated high HCV transmission risk in prison, particularly among people injecting drugs. High‐dosage OAT was protective, but improved OAT coverage and needle/syringe programmes to reduce sharing injecting equipment are required.
Purpose
The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood ...medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods.
Methods
The RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995–2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages.
Results
The fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine.
Conclusion
The RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.
Understanding how temperature determines the distribution of life is necessary to assess species' sensitivities to contemporary climate change. Here, we test the importance of temperature in limiting ...the geographic ranges of ectotherms by comparing the temperatures and areas that species occupy to the temperatures and areas species could potentially occupy on the basis of their physiological thermal tolerances. We find that marine species across all latitudes and terrestrial species from the tropics occupy temperatures that closely match their thermal tolerances. However, terrestrial species from temperate and polar latitudes are absent from warm, thermally tolerable areas that they could potentially occupy beyond their equatorward range limits, indicating that extreme temperature is often not the factor limiting their distributions at lower latitudes. This matches predictions from the hypothesis that adaptation to cold environments that facilitates survival in temperate and polar regions is associated with a performance trade-off that reduces species' abilities to contend in the tropics, possibly due to biotic exclusion. Our findings predict more direct responses to climate warming of marine ranges and cool range edges of terrestrial species.
Surveillance for blood-fed female mosquitoes was performed between August 2015 and February 2016 at sites along the periphery of the Aripo Savannas Environmentally Reserve (ASSR) located in ...northeastern Trinidad, West Indies. We collected engorged female mosquitoes representing 13 species. DNA extractions from dissected abdomens were subjected to PCR amplification with three primer pairs targeting the mitochondrial cytochrome oxidase I and cytochrome b gene sequences. High-quality sequence information and host identification were obtained for 42 specimens representing eight mosquito species with at least one primer combination. A broad range of vertebrates including humans were identified, but the majority were nonhuman mammals, both domestic and wild. Domestic dogs were the most common host and may represent potential sentinel species for monitoring local enzootic arbovirus activity in Trinidad. Culex declarator Dyer and Knab and Culex nigripalpus Theobald were the most common blood-fed mosquito species comprising 79.1% of the total number identified. These species obtained blood meals from birds, nonhuman mammals, and human hosts, and therefore pose significant risks as potential bridge vectors for epizootic arbovirus transmission in the ASSR area as well as other sylvan areas in Trinidad. These data represent the first such results for Trinidad.
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