The contribution of global aviation to anthropogenic climate forcing for 2000 to 2018.

Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO2), nitrogen oxides (NOx), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960-2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr-1, and in terms of climate change impacts, with CO2 emissions increasing by a factor of 6.8 to 1034 Tg CO2 yr-1. Over the period 2013-2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000-2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO2 and NOx emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m-2 (5-95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m-2), CO2 (34.3 mW m-2), and NOx (17.5 mW m-2). Non-CO2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m-2. Uncertainty distributions (5%, 95%) show that non-CO2 forcing terms contribute about 8 times more than CO2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone. CO2 and NOx aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions.

Loss to follow-up among youth accessing outpatient HIV care and treatment services in Kisumu, Kenya.

Youth are particularly vulnerable to acquiring HIV, yet reaching them with HIV prevention interventions and engaging and retaining those infected in care and treatment remains a challenge. We sought to determine the incidence rate of loss to follow-up (LTFU) and explore socio-demographic and clinical characteristics associated with LTFU among HIV-positive youth aged 15-21 years accessing outpatient care and treatment clinics in Kisumu, Kenya. Between July 2007 and September 2010, youth were enrolled into two different HIV care and treatment clinics, one youth specific and the other family oriented. An individual was defined as LTFU when absent from the HIV treatment clinic for ≥ 4 months regardless of their antiretroviral treatment status. The incidence rate of LTFU was calculated and Cox regression analysis used to identify factors associated with LTFU. A total of 924 youth (79% female) were enrolled, with a median age of 20 years (IQR 18-21). Over half, (529 (57%)), were documented as LTFU, of whom 139 (26%) were LTFU immediately after enrolment. The overall incidence rate of LTFU was 52.9 per 100 person-years (p-y). Factors associated with LTFU were pregnancy during the study period (crude HR 0.68, 95% CI 0.53-0.89); CD4 cell count >350 (adjusted hazard ratios (AHR) 0.59, 95% CI 0.39-0.90); not being on antiretroviral therapy (AHR 4.0, 95% CI 2.70-5.88); and non-disclosure of HIV infection status (AHR 1.43, 95% CI 1.10-1.89). The clinic of enrolment, age, marital status, employment status, WHO clinical disease stage and education level were not associated with LTFU. Interventions to identify and enrol youth into care earlier, support disclosure, and initiate ART earlier may improve retention of youth and need further investigation. Further research is also needed to explore the reasons for LTFU from care among HIV-infected youth and the true outcomes of these patients.

Batrachochytrium dendrobatidis in amphibians of Cameroon, including first records for caecilians.

Amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has been hypothesised to be an indigenous parasite of African amphibians. In Cameroon, however, previous surveys in one region (in the northwest) failed to detect this pathogen, despite the earliest African Bd having been recorded from a frog in eastern Cameroon, plus one recent record in the far southeast. To reconcile these contrasting results, we present survey data from 12 localities across 6 regions of Cameroon from anurans (n = 1052) and caecilians (n = 85) of ca. 108 species. Bd was detected in 124 amphibian hosts at 7 localities, including Mt. Oku, Mt. Cameroon, Mt. Manengouba and lowland localities in the centre and west of the country. None of the hosts were observed dead or dying. Infected amphibian hosts were not detected in other localities in the south and eastern rainforest belt. Infection occurred in both anurans and caecilians, making this the first reported case of infection in the latter order (Gymnophiona) of amphibians. There was no significant difference between prevalence and infection intensity in frogs and caecilians. We highlight the importance of taking into account the inhibition of diagnostic qPCR in studies on Bd, based on all Bd-positive hosts being undetected when screened without bovine serum albumin in the qPCR mix. The status of Bd as an indigenous, cosmopolitan amphibian parasite in Africa, including Cameroon, is supported by this work. Isolating and sequencing strains of Bd from Cameroon should now be a priority. Longitudinal host population monitoring will be required to determine the effects, if any, of the infection on amphibians in Cameroon.

The impact of routine cryptococcal antigen screening on survival among HIV-infected individuals with advanced immunosuppression in Kenya.

OBJECTIVES: To test the hypothesis that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV-infected individuals with low CD4 cell counts. METHODS: Newly enrolled patients at Family AIDS Care and Education Services (FACES) in Kenya with CD4 ≤ 100 cells/µl were tested for serum cryptococcal antigen (sCrAg). Individuals with sCrAg titre ≥ 1:2 were treated with high-dose fluconazole. Cox proportional hazard models of Kaplan-Meier curves were used to compare survival among individuals with CD4 ≤ 100 cells/µl in the intervention and historical control groups. RESULTS: The median age was 34 years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/µl [IQR: 18,71]. Follow-up time was 1224 person-years. In the intervention group, 66% (514/782) were tested for sCrAg; of whom, 11% (59/514) were sCrAg positive. Mortality was 25% (196/782) in the intervention group and 25% (191/771) in the control group. There was no significant difference between the intervention and control group in overall survival [hazard ratio (HR): 1.1 (95%CI:0.9,1.3)] or three-month survival [HR: 1.0 (95%CI:0.8,1.3)]. Within the intervention group, sCrAg-positive individuals had significantly lower survival rates than sCrAg-negative individuals [HR:1.8 (95%CI: 1.0, 3.0)]. CONCLUSIONS: A screening and treatment intervention to identify sCrAg-positive individuals and treat them with high-dose fluconazole did not significantly improve overall survival among HIV-infected individuals with CD4 counts ≤ 100 cells/µl compared to a historical control, perhaps due to intervention uptake rates or poor efficacy of high-dose oral fluconazole.

Transport impacts on atmosphere and climate: Aviation.

Aviation alters the composition of the atmosphere globally and can thus drive climate change and ozone depletion. The last major international assessment of these impacts was made by the Intergovernmental Panel on Climate Change (IPCC) in 1999. Here, a comprehensive updated assessment of aviation is provided. Scientific advances since the 1999 assessment have reduced key uncertainties, sharpening the quantitative evaluation, yet the basic conclusions remain the same. The climate impact of aviation is driven by long-term impacts from CO2 emissions and shorter-term impacts from non-CO2 emissions and effects, which include the emissions of water vapour, particles and nitrogen oxides (NO x ). The present-day radiative forcing from aviation (2005) is estimated to be 55 mW m-2 (excluding cirrus cloud enhancement), which represents some 3.5% (range 1.3-10%, 90% likelihood range) of current anthropogenic forcing, or 78 mW m-2 including cirrus cloud enhancement, representing 4.9% of current forcing (range 2-14%, 90% likelihood range). According to two SRES-compatible scenarios, future forcings may increase by factors of 3-4 over 2000 levels, in 2050. The effects of aviation emissions of CO2 on global mean surface temperature last for many hundreds of years (in common with other sources), whilst its non-CO2 effects on temperature last for decades. Much progress has been made in the last ten years on characterizing emissions, although major uncertainties remain over the nature of particles. Emissions of NO x result in production of ozone, a climate warming gas, and the reduction of ambient methane (a cooling effect) although the overall balance is warming, based upon current understanding. These NO x emissions from current subsonic aviation do not appear to deplete stratospheric ozone. Despite the progress made on modelling aviation's impacts on tropospheric chemistry, there remains a significant spread in model results. The knowledge of aviation's impacts on cloudiness has also improved: a limited number of studies have demonstrated an increase in cirrus cloud attributable to aviation although the magnitude varies: however, these trend analyses may be impacted by satellite artefacts. The effect of aviation particles on clouds (with and without contrails) may give rise to either a positive forcing or a negative forcing: the modelling and the underlying processes are highly uncertain, although the overall effect of contrails and enhanced cloudiness is considered to be a positive forcing and could be substantial, compared with other effects. The debate over quantification of aviation impacts has also progressed towards studying potential mitigation and the technological and atmospheric tradeoffs. Current studies are still relatively immature and more work is required to determine optimal technological development paths, which is an aspect that atmospheric science has much to contribute. In terms of alternative fuels, liquid hydrogen represents a possibility and may reduce some of aviation's impacts on climate if the fuel is produced in a carbon-neutral way: such fuel is unlikely to be utilized until a 'hydrogen economy' develops. The introduction of biofuels as a means of reducing CO2 impacts represents a future possibility. However, even over and above land-use concerns and greenhouse gas budget issues, aviation fuels require strict adherence to safety standards and thus require extra processing compared with biofuels destined for other sectors, where the uptake of such fuel may be more beneficial in the first instance.

The U.S. Thrombosis and Hemostasis Centers pilot sites program.

Venous thromboembolism (VTE) is a common disorder associated with significant morbidity and mortality. Despite important advances in understanding the etiology of VTE, delivery of care to patients with thrombosis and thrombophilia is frequently incomplete and highly variable. A comprehensive model of health care has been used successfully to treat and prevent complications for people with hemophilia and other chronic disorders. The effectiveness of an integrated healthcare model for patients with all coagulation disorders has yet to be evaluated. The Division of Hereditary Blood Disorders of the Centers for Disease Control and Prevention (CDC) is collaborating with eight Thrombosis and Hemostasis Centers (pilot sites) to provide health-related services and conduct research directed toward the reduction or prevention of complications of thrombosis and thrombophilia. The initial objectives of the collaboration are to (1) determine the efficacy of integrated multidisciplinary care and prevention services for people with hemostatic disorders, (2) assess unmet needs for service delivery and identify outreach strategies to improve access to care, (3) develop effective messages aimed at disease management and prevention, and (4) foster the development of training programs to enhance provider skills for the delivery of patient care. To address these objectives, the investigators and CDC have developed and implemented a web-based patient registry to follow prospectively service allocation and patient outcomes. Funding for the program began in October 2001. All eight funded centers are affiliated with U.S. medical schools. Principal investigators at the centers are hematologists (five adult, two pediatric) or cardiologists. Faculty in obstetrics-gynecology, surgery, and multiple other specialties are integral to the model of care at the centers. Other critical components at the centers are clinical laboratory services, training programs, research networks, and education and outreach programs. From August 2003 to March 2006, over 2,600 patients were enrolled in the registry, accounting for a total of more than 5,000 visits to the centers. Immediate goals of the data collection at the centers are to characterize patients receiving care at centers and document the state of health services provided. Long-term goals are to evaluate prospectively clinical outcomes for patients receiving multidisciplinary care and prevention services at centers. The network of data collection across centers will facilitate future collaborative clinical and epidemiologic investigations and enhance collective expertise in hemostasis and coagulation disorders.

Formation of C7F15COOH (PFOA) and other perfluorocarboxylic acids during the atmospheric oxidation of 8:2 fluorotelomer alcohol.

Calculations using a three-dimensional global atmospheric chemistry model (IMPACT) indicate that n-C8F17CH2CH2OH (widely used in industrial and consumer products) degrades in the atmosphere to give perfluorooctanoic acid (PFOA) and other perfluorocarboxylic acids (PFCAs). PFOA is persistent, bioaccumulative, and potentially toxic. Molar yields of PFOA depend on location and season, are in the range of 1-10%, and are of the correct order of magnitude to explain the observed levels in Arctic fauna. Fluorotelomer alcohols such as n-C8F17CH2CH2OH appear to be a significant global source of persistent bioaccumulative perfluorocarboxylic acid pollution. This is the first modeling study of the atmospheric chemistry of a fluorotelomer alcohol.

Successful treatment of high titer inhibitors in mild hemophilia A with avoidance of factor VIII and immunosuppressive therapy.

We describe two patients with mild hemophilia A (MHA) who developed high titer inhibitor (HTI) following intensive recombinant factor VIII (rFVIII) concentrate replacement for surgery and trauma. Intranasal desmopressin was instituted shortly following immunosuppressive therapy (IST) and activated prothrombin complex concentrate (APCC) in one case, and following APCC alone in the second case. Avoidance of factor VIII (FVIII) coupled with intranasal desmopressin prophylaxis three times a week resulted in undetectable inhibitor levels. Both patients have had no further bleeding episodes and have been maintained on desmopressin prophylaxis prior to activity for the past 2 to 3 years. Recombinant factor VIIa (rFVIIa) was used successfully prior to a second surgery in one patient without complication.

Classification of Proteus vulgaris biogroup 3 with recognition of Proteus hauseri sp. nov., nom. rev. and unnamed Proteus genomospecies 4, 5 and 6.

Strains traditionally identified as Proteus vulgaris formed three biogroups. Biogroup 1, characterized by negative reactions for indole production, salicin fermentation and aesculin hydrolysis, is now known as Proteus penneri. Biogroup 2, characterized by positive reactions for indole, salicin and aesculin, was shown by DNA hybridization (hydroxyapatite method) to be a genetic species separate from biogroup 1 and from biogroup 3 which is positive for indole production and negative for salicin and aesculin. In this study, 52 strains were examined, of which 36 strains were Proteus vulgaris biogroup 3, which included the current type strain of the species P. vulgaris (ATCC 29905T), and compared to seven strains of Proteus vulgaris biogroup 2 and nine type strains of other species in the genera Proteus, Providencia and Morganella. By DNA hybridization, these 36 strains were separated into four distinct groups, designated as Proteus genomospecies 3, 4, 5 and 6. DNAs within each separate Proteus genomospecies were 74-99% related to each other in 60 degrees C hybridization reactions with < or = 4.5% divergence between related sequences. Proteus genomospecies 3 contained the former P. vulgaris type strain and one other strain and was negative in reactions for salicin fermentation, aesculin hydrolysis and deoxyribonuclease, unlike the reactions associated with strains considered as typical P. vulgaris which are positive in reactions for salicin, aesculin and DNase. Genomospecies 3 can be distinguished from Proteus genomospecies 4, 5 and 6 because it is negative for Jordan's tartrate. Proteus genomospecies 4, containing five strains, was differentiated from Proteus penneri, genomospecies 3 and 6 and most, but not all, strains of genomospecies 5, by its ability to ferment L-rhamnose. Proteus genomospecies 5 and 6, containing 18 and 11 strains, respectively, could not be separated from each other by traditional biochemical tests, by carbon source utilization tests or SDS-PAGE of whole-cell proteins. In an earlier publication, a request was made to the Judicial Commission that the former type strain of P. vulgaris (ATCC 13315) be replaced by P. vulgaris biogroup 2 strain ATCC 29905T, a strain considered more biochemically typical of P. vulgaris strains. This would have the effect of assigning the name P. vulgaris to P. vulgaris biogroup 2. Since this request has been acceded to, the name Proteus hauseri is herein proposed for Proteus vulgaris genomospecies 3. Its type strain is ATCC 700826T. Proteus genomospecies 4, 5 and 6 will remain unnamed until better phenotypic differentiation can be accomplished. All Proteus genomospecies were similar in their antimicrobial susceptibility patterns. Nineteen strains were isolated from urine, four from faeces, two from wounds, nine from other human sources and two from animals.

Presentation of low anorectal malformations beyond the neonatal period.

OBJECTIVE: Anorectal malformations are usually diagnosed at birth, but some patients have presented to this institution beyond the early newborn period without recognition of their anorectal malformations. To quantify the extent of this problem, we undertook a review of all patients presenting to this hospital with anorectal malformations. METHODS: We reviewed all new cases of anorectal malformations treated at British Columbia's Children's Hospital during the past 11 years. We looked specifically at the time of diagnosis, patient age, sex and mode of presentation, the type of anorectal malformations, and any associated anomalies. RESULTS: One hundred twenty new cases of anorectal malformations were seen here, of whom, 15 patients (9 girls and 6 boys) presented beyond the early newborn period. Of these, 1 male infant was diagnosed at 2 weeks of age and another girl at 14 years of age. The remaining 13 presented between 3 and 11 months of age because of increasing constipation, usually associated with the introduction of solid foods. All had low anorectal malformations. Nine patients had at least 1 other feature of the VACTERL complex. CONCLUSIONS: Most anorectal malformations are identified at birth, but a significant number of the milder lesions may not be recognized until later. Therefore, this condition must be considered in older infants and children presenting with constipation, particularly if they also have cardiac or genitourinary anomalies. constipation, imperforate anus, VACTERL.

Management of haemophilia in patients with high-titre inhibitors: focus on the evolution of activated prothrombin complex concentrate AUTOPLEX T.

Numerous therapeutic strategies have been applied to the management of patients with inhibitors to factors VIII or IX. Different treatment approaches are analysed including prothrombin complex concentrates (PCCs), activated prothrombin complex concentrates (aPCCs), porcine factor VIII concentrate, inhibitor neutralization, immune tolerance therapy, immunosuppressive regimens and recombinant factor VIIa. Clinical data are reported in the analysis of several treatments. PCCs and aPCCs have gained widespread acceptance as the standard first-line approach for patients with inhibitors. The aPCC AUTOPLEX T has achieved a high response rate with a low level of thrombotic events. Four case studies are presented in which AUTOPLEX T has been used successfully. Administration of platelet concentrate or, in elective surgery, waiting for inhibitor levels to decline are useful adjuncts to some treatments. The optimal treatment depends on the patient's inhibitor status--low responder (minimal or no increase in inhibitor levels upon administration of replacement clotting factor) or high responder (replacement clotting factor generates inhibitor production). A suggested algorithm for treating high-responder inhibitor patients is presented.

The use of a retinoid receptor antagonist in a new model to study vitamin A-dependent developmental events.

Multiple fetal anomalies occur in vitamin A deficient animals as well as in retinoic acid receptor gene 'knockout' mice, indicating that retinoic acid (an active metabolite of vitamin A) performs some essential functions in normal development. Additional approaches are needed to probe directly the stages and sites in the embryo where a presence of endogenous retinoic acid is indispensable. We have employed a new strategy for this purpose which involved an intervention in retinoic acid receptor (RAR)-dependent functions at specific developmental stages by means of a highly effective RAR antagonist, AGN 193109. We report that in an in vitro cell differentiation bioassay, AGN 193109 completely reversed the inhibitory action of a potent RAR agonist, AGN 190121. In pregnant mice, a single oral 1 mg/kg dose of the antagonist given on 8 day post coitum (dpc) produced a severe craniofacial anomaly (median cleft face or frontonasal dysplasia) and eye malformations in virtually all exposed fetuses. On the other hand, treatment on 11 dpc, a time in development when RARs are strategically expressed in the limb bud primordium, no limb anomalies could be induced by the antagonist. Even after a high dose of 100 mg/kg, limb development progressed normally in spite of the fact that measurable concentrations of the antagonist were present. Because retinoids are long known to influence skin morphology, we next monitored the effects of the antagonist on skin development. When given late in gestation, on 14 dpc, we found that the antagonist delayed differentiation and maturation of the fetal skin and hair follicles. We conclude that this model provides a convenient and pertinent system which enables us to seek and clarify true functions of retinoic acid and its cognate receptors in embryogenesis and in adult animals.

Developmental toxicity of purified fumonisin B1 in pregnant Syrian hamsters.

The purpose of this study was to characterize the developmental toxicity of fumonisin B1 (FB1), a mycotoxin produced by Fusarium moniliforme, on fetal Syrian hamsters. Fusarium moniliforme has been associated with a variety of diseases in animals and esophageal cancer in humans. Purified FB1 causes leukoencephalomalacia in horses and is hepatocarcinogenic in rats. Fumonisin B1 has been associated with fetal toxicity in rats and mice and has been suggested to be involved in reproductive failure in pregnant sows. Results from a preliminary developmental toxicity study using an aqueous extract of F. moniliforme corn-culture material in hamsters suggested that FB1 was a developmental toxicant. These results were verified using purified FB1. Six groups of ten time-mated female Syrian hamsters were dosed with 0.0-18 mg kg(-1) day(-1) of FB1 by gavage on days 8-12 of gestation and euthanized on day 15. Live fetuses were weighed and examined for gross external and internal abnormalities and skeletal anomalies. Purified fumonisin B1 was shown to cause dose-dependent fetal death and delayed fetal development without causing fetal abnormalities.

Disseminated intravascular coagulation in patients with multiple organ failure of non-septic origin.

Disseminated intravascular coagulation (DIC) and associated multi-organ failure are serious and often terminal events of a variety of non-septic conditions. For the most part, these conditions are a result of tissue factor (thromboplastin) release from damaged tissues creating situations that favor thrombin formation. Thrombin's role in this process is critical and serves to induce the coagulopathy, as well as many of the other aspects of inflammation that contribute to the associated morbidity and mortality. Clinical disorders giving rise to DIC fall into categories of trauma, obstetrical complications, malignancies and a variety of inflammatory conditions. Diagnostic patterns for these disorders are well established with an expected decrease in platelets and fibrinogen, as well as antithrombin III, in addition to elevated levels of thrombin-antithrombin III complex, prothrombin fragment 1 + 2, and D-dimer; all of which serve to identify the hypercoagulable state. Management of these coagulopathies requires attention to the bleeding diathesis and the ongoing thrombotic complication. Supportive therapy usually is required to provide hemostasis. However, control of the coagulopathy is of equal importance and requires not only early intervention, but also administration of sufficient antithrombotic agents to reduce thrombin's ability to consume coagulation factors, as well as to stimulate inflammatory processes. Heparin has been employed effectively in many of these situations, but suffers from its potential to induce hemorrhage. Antithrombin III concentrate, however, is devoid of this risk and provides a unique alternative that has had a limited, but effective record of benefits. Further proof of its efficacy in multi-organ failure disorders is awaited.