An ammonia-oxidizing, carbon-fixing archaeon, Candidatus "Nitrosopumilus maritimus," recently was isolated from a salt-water aquarium, definitively confirming that chemoautotrophy exists among the ...marine archaea. However, in other incubation studies, pelagic archaea also were capable of using organic carbon. It has remained unknown what fraction of the total marine archaeal community is autotrophic in situ. If archaea live primarily as autotrophs in the natural environment, a large ammonia-oxidizing population would play a significant role in marine nitrification. Here we use the natural distribution of radiocarbon in archaeal membrane lipids to quantify the bulk carbon metabolism of archaea at two depths in the subtropical North Pacific gyre. Our compound-specific radiocarbon data show that the archaea in surface waters incorporate modern carbon into their membrane lipids, and archaea at 670 m incorporate carbon that is slightly more isotopically enriched than inorganic carbon at the same depth. An isotopic mass balance model shows that the dominant metabolism at depth indeed is autotrophy (83%), whereas heterotrophic consumption of modern organic carbon accounts for the remainder of archaeal biomass. These results reflect the in situ production of the total community that produces tetraether lipids and are not subject to biases associated with incubation and/or culture experiments. The data suggest either that the marine archaeal community includes both autotrophs and heterotrophs or is a single population with a uniformly mixotrophic metabolism. The metabolic and phylogenetic diversity of the marine archaea warrants further exploration; these organisms may play a major role in the marine cycles of nitrogen and carbon.
Aims: Research into the relationship between pathogens, faecal indicator microbes and environmental factors in beach sand has been limited, yet vital to the understanding of the microbial ...relationship between sand and the water column and to the improvement of criteria for better human health protection at beaches. The objectives of this study were to evaluate the presence and distribution of pathogens in various zones of beach sand (subtidal, intertidal and supratidal) and to assess their relationship with environmental parameters and indicator microbes at a non-point source subtropical marine beach. Methods and Results: In this exploratory study in subtropical Miami (Florida, USA), beach sand samples were collected and analysed over the course of 6 days for several pathogens, microbial source tracking markers and indicator microbes. An inverse correlation between moisture content and most indicator microbes was found. Significant associations were identified between some indicator microbes and pathogens (such as nematode larvae and yeasts in the genus Candida), which are from classes of microbes that are rarely evaluated in the context of recreational beach use. Conclusions: Results indicate that indicator microbes may predict the presence of some of the pathogens, in particular helminthes, yeasts and the bacterial pathogen Staphylococcus aureus including methicillin-resistant forms. Indicator microbes may thus be useful for monitoring beach sand and water quality at non-point source beaches. Significance and Impact of the Study: The presence of both indicator microbes and pathogens in beach sand provides one possible explanation for human health effects reported at non-point sources beaches.
Herein we report an advancement in the application of visible light photoredox catalysts in the oxidation of electron-rich arenes resulting in the selective deprotection of para-methoxybenzyl (PMB) ...ethers. This method is highlighted by excellent functional group tolerance, protecting group orthogonality, mild reaction conditions and avoidance of stoichiometric redox byproducts.
Abstract Anomalous aortic origin of a coronary artery (AAOCA) from the inappropriate sinus of Valsalva is increasingly recognized by cardiac imaging. Although most AAOCA subtypes are benign, autopsy ...studies report an associated risk of sudden death with interarterial anomalous left coronary artery (ALCA) and anomalous right coronary artery (ARCA). Despite efforts to identify high-risk ALCA and ARCA patients who may benefit from surgical repair, debate remains regarding their classification, prevalence, risk stratification, and management. We comprehensively reviewed 77 studies reporting the prevalence of AAOCA among >1 million patients, and 20 studies examining outcomes of interarterial ALCA/ARCA patients. Observational data suggests that interarterial ALCA is rare (weighted prevalence = 0.03%; 95% confidence interval CI: 0.01% to 0.04%) compared with interarterial ARCA (weighted prevalence = 0.23%; 95% CI: 0.17% to 0.31%). Recognizing the challenges in managing these patients, we review cardiac tests used to examine AAOCA and knowledge gaps in management.
Respiratory syncytial virus (RSV) infection in lung transplant (LTx) patients is associated with an increased incidence of bronchiolitis obliterans syndrome (BOS). ALN-RSV01 is a small interfering ...RNA targeting RSV replication that was shown in an earlier Phase 2a trial to be safe and to reduce the incidence of BOS when compared with placebo.
We performed a Phase 2b randomized, double-blind, placebo-controlled trial in RSV-infected LTx patients to examine the impact of ALN-RSV01 on the incidence of new or progressive BOS. Subjects were randomized (1:1) to receive aerosolized ALN-RSV01 or placebo daily for 5 days.
Of 3,985 symptomatic patients screened, 218 were RSV-positive locally, of whom 87 were randomized to receive ALN-RSV01 or placebo (modified intention-to-treat mITT cohort). RSV infection was confirmed by central laboratory in 77 patients (ALN-RSV01, n = 44; placebo, n = 33), which comprised the primary analysis cohort (central mITT mITTc). ALN-RSV01 was found to be safe and well-tolerated. At Day 180, in ALN-RSV01-treated patients, compared with placebo, in the mITTc cohort there was a trend toward a decrease in new or progressive BOS (13.6% vs 30.3%, p = 0.058), which was significant in the per-protocol cohort (p = 0.025). Treatment effect was enhanced when ALN-RSV01 was started <5 days from symptom onset, and was observed even without ribavirin treatment. There was no significant impact on viral parameters or symptom scores.
These results confirm findings of the earlier Phase 2a trial and provide further support that ALN-RSV01 reduces the risk of BOS after RSV in LTx recipients.
Pediatric multidrug-resistant tuberculosis (MDR-TB) is complicated by difficult diagnosis, complex treatment, and high mortality. In South Africa, these challenges are amplified by human ...immunodeficiency virus (HIV) co-infection; however, evidence on treatment outcomes among co-infected children is limited.
Using conventional and new pediatric definitions, to describe treatment outcomes and identify risk factors for unfavorable outcome and mortality in children aged <15 years with MDR-TB or extensively drug-resistant TB (XDR-TB) in KwaZulu-Natal, South Africa.
Retrospective cohort study in a regional TB referral hospital.
From January 2009 to June 2010, 84 children (median age 8 years, IQR 4-12) with MDR-TB (n = 78) or XDR-TB (n = 6) initiated treatment. Sixty-four (77%) were HIV-positive and 62 (97%) received antiretroviral therapy. Sixty-six (79%) achieved favorable treatment outcomes. Overall mortality was 11% (n = 9) at 18 months after initiation of treatment. Malnutrition (aOR 27.4, 95%CI 2.7-278.7) and severe radiographic findings (aOR 4.68, 95%CI 1.01-21.9) were associated with unfavorable outcome. New pediatric outcome definitions increased the proportion classified as cured.
It is possible to successfully treat pediatric MDR-TB-HIV even in resource-poor settings. Malnutrition is a marker for severe TB-HIV disease, and is a potential target for future interventions in these patients.
Heart Failure (HF) is the most common cause of death in Friedreich's ataxia (FRDA), an inherited mitochondrial disease. Myocardial fibrosis and myocardial hypertrophy are well-documented autopsy ...features among FRDA patients with HF.
To leverage the unique tissue characterization features of cardiac magnetic resonance (CMR) for characterizing myocardial remodeling in patients with genetically confirmed FRDA without HF and preserved left ventricular ejection fraction (LVEF > 55%).
Twenty-seven FRDA's patients (age 27.6 ± 9.7 years, 15 women) and 10 healthy controls (32.6±7.3 years, 5 women) underwent a CMR for assessment of LV function, myocardial T1, late gadolinium enhancement (LGE), extracellular volume fraction (ECV), and intracellular water-lifetime (τic), a marker of cardiomyocyte size.
As compared to controls, FRDA patients had a preserved LVEF (LVEF: 70.5±7.4% vs. 63.9±9.0%, P<0.058), larger LV mass index (LVMASSi: 61±21.7 vs. 45±4.2g/m2, P<0.02), and decreased LV end-diastolic volume index (LVEDVi 53.1±12.0 vs. 75.7±16.1ml/m2, P<0.001), compared with controls. Additionally, ECV and cardiomyocyte size (τic,) were larger in FRDA patients (ECV: 0.36 ±0.05 vs. 0.25±0.02, P<0.001; τic: 0.15±0.08 vs. 0.06±0.03 s, P = 0.02). ECV and τic were positively associated with LV mass-to-volume ratio (ECV: r = 0.57, P = 0.003; τic: r = 0.39; P = 0.05). LVMASSi and cardiomyocyte mass-index (1-ECV)·LVMASSi declined with age at the CMR exam, independent of the age at initial diagnosis.
LV hypertrophy and concentric LV remodeling in FRDA are associated at the tissue level with an expansion of the ECV and an increase in cardiomyocyte size. The adverse tissue remodeling assessed by ECV and τic is associated with more severe cardiomyopathy classification, suggesting a role for these markers in tracking disease progression.
Dual-phase microstructures arising out of eutectic reactions offer several advantages: ease of casting, composite properties and tunable characteristic length scale of the phases. Eutectic high ...entropy alloys (EHEA) with a multi-component solution phase and a hard intermetallic phase are candidate materials to identify alternate high-temperature materials. Alloying elements can be chosen to improve the resistance to lamellar microstructure degradation and coarsening. In this work, we present the CALPHAD guided design of a hypo-eutectic high entropy alloy CoCrFeNiTa0.395 with primary dendritic FCC phase and fine eutectic (FCC solution + Laves phase) microstructure possessing good high-temperature mechanical properties. The primary FCC phase fraction is 0.42 ± 0.02. The interlamellar spacing of the eutectic is 0.69 ± 0.12 μm. The alloy exhibited a balanced yield strength of 1303 ± 18 MPa, a fracture strength of 2237 ± 23 MPa and a fracture strain of 0.3 under room temperature compression testing. The mechanism for change in the lamellar morphology during deformation at temperatures beyond 0.8 TE is explained schematically. Strain field distribution obtained by FEM simulation correlates well with the observed microstructure gradients in the deformed samples. The formation of nano-scale precipitates in the low strain rate deformation is attributed to thermal effects. High-temperature precipitation of two types of precipitates (L12 ordered and Ni3Ta type) in the FCC-solution phase extended the useable temperature range of this alloy.
Eutectic high entropy alloy with seven components is designed based on the integrated computational materials engineering (ICME) framework. The framework includes thermodynamic prediction using ...calculation of phase diagrams (CALPHAD), microstructure simulation using phase-field method, and experimental validation. The designed alloy shows the eutectic structure consisting of FCC and laves phase in the composition range from 8.25 to 10 at. pct Ta. The simulation and experimental results are co-related and a framework is proposed that can be used for high entropy alloy design subjected to various manufacturing processes.
Chronic recurrent multifocal osteomyelitis (CRMO) is a little known inflammatory bone disease occurring primarily in children and adolescents. Delays in referral and diagnosis may lead to prolonged ...courses of antibiotics with in-patient care, unnecessary radiation exposure from multiple plain radiographs or bone scans and repeated surgery including bone biopsies. Children (aged < 18 years) diagnosed with CRMO between January 2005 and December 2012, reviewed at Bristol Royal Hospital for Children were included and all available data collected. Information regarding CRMO was sent to all orthopaedic surgeons in the region in 2009. The aim of the study was to examine the features of the cohort, to examine the length of time to diagnosis and to explore the criteria used for diagnosis with and without biopsy.
Over an 8 year period, 41 patients were diagnosed with CRMO. Symptom onset occurred at a median of 9 years of age and time to diagnosis had a median of 15 months (range 0-92). Correlation coefficient analysis for time to diagnosis by year showed statistical significance with a decreasing trend. From the cohort data, diagnostic criteria were developed; applied retrospectively, 34 (83 %) children may have been diagnosed using the criteria, without a biopsy.
The data suggest that increasing knowledge of this condition may shorten time to diagnosis. Use of the Bristol diagnostic criteria by an experienced clinician may obviate the need for biopsy in some patients.
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