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1.
Cancer ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33951180

RESUMO

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.

2.
J Mass Spectrom ; 56(6): e4726, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33955098

RESUMO

Cannabis extracts and products were analyzed by gas chromatography-mass spectrometry (GC-MS) with Cold EI for their full content including terpenes, sesquiterpenes, sesquiterpinols, fatty acids, delta 9-tetrahydrocannabinol (THC), cannabidiol (CBD), other cannabinoids, hydrocarbons, sterols, diglycerides, triglycerides, and impurities. GC-MS with Cold EI is based on interfacing GC and MS with supersonic molecular beams (SMB) along with electron ionization of vibrationally cold sample compounds in the SMB in a fly-through ion source (hence the name Cold EI). GC-MS with Cold EI improves all the performance aspects of GC-MS, enables the analysis of Cannabinoids with OH groups without derivatization, while providing enhanced molecular ions for improved identification, and enables internal quantitation without calibration. We found over 50 cannabinoid compounds including a new one with a Cold EI mass spectrum very similar to delta 9-THC as well as relatively large cannabinoids with molecular weight above m/z = 400. Because the analysis was universal in full scan and not targeted, we found impurities such as bromo CBD and fluticasone propionate and could monitor the formation of oxidized CBD during decarboxylation. In addition, GC-MS with Cold EI enabled nontargeted full analysis of terpenes, sesquiterpenes, and sesquiterpinols in cannabis extracts with good internal quantitation. GC-MS with Cold EI further served with very good sensitivity for the concentration determination of delta 9-THC in CBD-related products. Finally, cannabis drugs such as EP-1 used in Israel for treatment of epilepsy and for children with autism spectrum disorder (ASD) were analyzed for their full cannabinoids content for learning on the entourage effect and for drug activity optimization.

3.
Biochemistry ; 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33961402

RESUMO

Copper-zinc superoxide dismutase (SOD1) is a major antioxidant metalloenzyme that protects cells from oxidative damage by superoxide anions (O2-). Structural, biophysical, and other characteristics have in the past been compiled for mammalian SOD1s and for the highly homologous fungal and bovine SOD1s. Here, we characterize the biophysical properties of a plant SOD1 from tomato chloroplasts and present several of its crystal structures. The most unusual of these structures is a structure at low pH in which tSOD1 harbors zinc in the copper-binding site but contains no metal in the zinc-binding site. The side chain of D83, normally a zinc ligand, adopts an alternate rotameric conformation to form an unusual bidentate hydrogen bond with the side chain of D124, precluding metal binding in the zinc-binding site. This alternate conformation of D83 appears to be responsible for the previously observed pH-dependent loss of zinc from the zinc-binding site of SOD1. Titrations of cobalt into apo tSOD1 at a similar pH support the lack of an intact zinc-binding site. Further characterization of tSOD1 reveals that it is a weaker dimer relative to human SOD1 and that it can be activated in vivo through a copper chaperone for the SOD1-independent mechanism.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33946754

RESUMO

The block periodization training paradigm has been shown to produce enhanced gains in strength and power. The purpose of this study is to assess resistance training induced alterations in lean body mass and cross-sectional area using a block periodization training model among individuals (n = 15) of three differing strength levels (high, moderate and low) based on one repetition maximum back squat relative to body weight. A 3 × 5 mixed-design ANOVA was used to examine within-and between-subject changes in cross-sectional area (CSA), lean body mass (LBM), lean body mass adjusted (LBMadjusted) and total body water (TBW) over an 11-week resistance training program. LBMadjusted is total body water subtracted from lean body mass. The ANOVA revealed no statistically significant between-group differences in any independent variable (p > 0.05). Within-group effects showed statistically significant increases in cross-sectional area (p < 0.001), lean body mass (p < 0.001), lean body mass adjusted (p ˂ 0.001) and total body water (p < 0.001) from baseline to post intervention: CSA: 32.7 cm2 ± 8.6; 36.3 cm2 ± 7.2, LBM: 68.0 kg ± 9.5; 70.6 kg ± 9.4, LBMadjusted: 20.4 kg ± 3.1; 21.0 kg ± 3.3 and TBW: 49.8 kg ± 6.9; 51.7 kg ± 6.9. In conclusion, the results of this study suggest subjects experienced an increase in both lean body mass and total body water, regardless of strength level, over the course of the 11-week block periodized program. Gains in lean body mass and cross-sectional area may be due to edema at the early onset of training.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33941871

RESUMO

The use of HLA-mismatched (un)related donors is historically associated with a higher incidence of transplant-related complications and mortality. However, the use of such donors may overcome the limited availability of HLA-matched donors for patients with ß-thalassemia major (TM) and sickle cell disease (SCD). We investigated hematopoietic stem cell transplantation (HSCT) outcomes of pediatric TM and SCD patients treated with a mismatched donor using a treosulfan-based conditioning in combination with ATG and post-transplant cyclophosphamide (PT-CY) and compared these results to the clinical outcome of patients treated by matched donor HSCT without PT-CY. Thirty-eight children (n = 24 HLA-identical or 10/10-matched donors; n = 14 HLA-mismatched donors), who received a non-depleted bone marrow graft were included. Event-free survival (EFS) and GvHD were not higher in the mismatched PT-Cy group as compared to the matched group. Moreover, despite delayed neutrophil engraftment (day +22 vs. +26, p = 0.002) and immune recovery in the mismatched PT-Cy group, this did not result in more infectious complications. Therefore, we conclude that in the absence of an HLA-identical or a matched unrelated donor, HSCT with a mismatched unrelated or haploidentical donor in combination with ATG plus PT-CY can be considered a safe and effective treatment option for pediatric hemoglobinopathy patients.

6.
Antiviral Res ; 191: 105079, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33933515

RESUMO

This study aimed to assess the antiviral susceptibility of influenza A(H5N8) viruses isolated in Russia in 2014-2018. Genetic analysis of 57 Russian isolates with full genome sequences did not find any markers of reduced susceptibility to baloxavir. Only one strain bore an amino acid substitution associated with adamantane resistance (M2-S31N). The neuraminidase of 1 strain had an NA-N293/294S (N8/N2 numbering) substitution associated with reduced inhibition by oseltamivir and normal inhibition by zanamivir, which was confirmed phenotypically. There were no other strains with reduced inhibition by oseltamivir and zanamivir in the phenotypic analysis. In order to estimate the worldwide prevalence of influenza A(H5N8) viruses bearing genetic markers of antiviral resistance, genome sequences deposited in the GISAID database were analyzed (database access: October 2020). The M2 protein of A(H5N8) viruses from the 2.3.4.4c clade had an M2-S31N substitution associated with reduced susceptibility to adamantanes. On the contrary, the majority (94%) of viruses from the 2.3.4.4b clade had the M2-S31 genotype. Fewer than 1% of analyzed viruses had amino acid substitutions associated with reduced susceptibility to baloxavir (PA-E199G, PA-E199E/G) or reduced or highly reduced inhibition by neuraminidase inhibitors (NA-R150/152K, NA-I221/222M, NA-I221/222I/M, NA-I221/222V, NA-I115/117V, NA-G145/147R, NA-R291/292R/K). An NA-N293/294S substitution was not present in sequences from the GISAID database. To the best of our knowledge, influenza A(H5N8) viruses with reduced inhibition by oseltamivir bearing an NA-N293/294S substitution have not been previously reported in epidemiological surveillance studies.

7.
BMJ Case Rep ; 14(4)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883113

RESUMO

A 35-year-old Hispanic man presented with fever, chills, dysuria, diarrhoea, scleral icterus, tachycardia and tachypnea. He was found to be COVID-19 positive, CT of the pelvis revealed prostatic abscess, and urine culture grew Klebsiella pneumoniae Additionally, he was found to have diabetes and cirrhosis. During treatment, the patient developed vision loss, and was diagnosed with endogenous Klebsiella endophthalmitis. The patient was treated with intravenous antibiotics, pars plana vitrectomy, intravitreal antibiotics and cystoscopy/suprapubic catheter placement. On follow-up, the patient has had the suprapubic catheter removed, and successfully passed a voiding trial, but suffers permanent vision loss in both eyes.


Assuntos
Diabetes Mellitus , Endoftalmite , Infecções por Klebsiella , Prostatite , Adulto , Antibacterianos/uso terapêutico , Cegueira , Diabetes Mellitus/virologia , Endoftalmite/complicações , Endoftalmite/diagnóstico , Endoftalmite/terapia , Humanos , Infecções por Klebsiella/complicações , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Masculino , Prostatite/complicações , Prostatite/microbiologia , Vitrectomia
8.
PLoS One ; 16(4): e0251019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33914831

RESUMO

Outbreaks of influenza, which is a contagious respiratory disease, occur throughout the world annually, affecting millions of people with many fatal cases. The D222G/N mutations in the hemagglutinin (HA) gene of A(H1N1)pdm09 are associated with severe and fatal human influenza cases. These mutations lead to increased virus replication in the lower respiratory tract (LRT) and may result in life-threatening pneumonia. Targeted NGS analysis revealed the presence of mutations in major and minor variants in 57% of fatal cases, with the proportion of viral variants with mutations varying from 1% to 98% in each individual sample in the epidemic season 2018-2019 in Russia. Co-occurrence of the mutations D222G and D222N was detected in a substantial number of the studied fatal cases (41%). The D222G/N mutations were detected at a low frequency (less than 1%) in the rest of the studied samples from fatal and nonfatal cases of influenza. The presence of HA D222Y/V/A mutations was detected in a few fatal cases. The high rate of occurrence of HA D222G/N mutations in A(H1N1)pdm09 viruses, their increased ability to replicate in the LRT and their association with fatal outcomes points to the importance of monitoring the mutations in circulating A(H1N1)pdm09 viruses for the evaluation of their epidemiological significance and for the consideration of disease prevention and treatment options.

9.
Proc Natl Acad Sci U S A ; 118(18)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33906949

RESUMO

Microbial community responses to environmental change are largely associated with ecological processes; however, the potential for microbes to rapidly evolve and adapt remains relatively unexplored in natural environments. To assess how ecological and evolutionary processes simultaneously alter the genetic diversity of a microbiome, we conducted two concurrent experiments in the leaf litter layer of soil over 18 mo across a climate gradient in Southern California. In the first experiment, we reciprocally transplanted microbial communities from five sites to test whether ecological shifts in ecotypes of the abundant bacterium, Curtobacterium, corresponded to past adaptive differentiation. In the transplanted communities, ecotypes converged toward that of the native communities growing on a common litter substrate. Moreover, these shifts were correlated with community-weighted mean trait values of the Curtobacterium ecotypes, indicating that some of the trait variation among ecotypes could be explained by local adaptation to climate conditions. In the second experiment, we transplanted an isogenic Curtobacterium strain and tracked genomic mutations associated with the sites across the same climate gradient. Using a combination of genomic and metagenomic approaches, we identified a variety of nonrandom, parallel mutations associated with transplantation, including mutations in genes related to nutrient acquisition, stress response, and exopolysaccharide production. Together, the field experiments demonstrate how both demographic shifts of previously adapted ecotypes and contemporary evolution can alter the diversity of a soil microbiome on the same timescale.

10.
Ann Surg Oncol ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830357

RESUMO

BACKGROUND: Many hospitals postponed elective surgical care during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. Some centers continued elective surgery, including esophageal cancer surgery, with the use of preoperative screening methods; however, there is no evidence supporting the safety of this strategy as postoperative outcomes after esophageal cancer surgery during the COVID-19 pandemic have not yet been investigated. METHODS: This multicenter study in four European tertiary esophageal cancer referral centers included consecutive adult patients undergoing elective esophageal cancer surgery from a prospectively maintained database in a COVID-19 pandemic cohort (1 March 2020-31 May 2020) and a control cohort (1 October 2019-29 February 2020). The primary outcome was the rate of respiratory failure requiring mechanical ventilation. RESULTS: The COVID-19 cohort consisted of 139 patients, versus 168 patients in the control cohort. There was no difference in the rate of respiratory failure requiring mechanical ventilation (13.7% vs. 8.3%, p = 0.127) and number of pulmonary complications (32.4% vs. 29.9%, p = 0.646) between the COVID-19 cohort and the control cohort. Overall, postoperative morbidity and mortality rates were comparable between both cohorts. History taking and reverse transcription polymerase chain reaction (RT-PCR) were used as preoperative screening methods to detect a possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in all centers. No patients were diagnosed with COVID-19 pre- or postoperatively. CONCLUSION: Esophageal cancer surgery during the first wave of the COVID-19 pandemic was not associated with an increase in pulmonary complications as no patients were diagnosed with COVID-19. Esophageal cancer surgery can be performed safely with the use of adequate preoperative SARS-CoV-2 screening methods.

11.
J Neurol ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871711

RESUMO

BACKGROUND: Electroencephalography (EEG) significantly contributes to the neuroprognostication after resuscitation from cardiac arrest. Recent studies suggest that the prognostic value of EEG is highest for continuous recording within the first days after cardiac arrest. Early continuous EEG, however, is not available in all hospitals. In this observational study, we sought to evaluate the predictive value of a 'late' EEG recording 5-14 days after cardiac arrest without sedatives. METHODS: We retrospectively analyzed EEG data in consecutive adult patients treated at the medical intensive care units (ICU) of the Charité-Universitätsmedizin Berlin. Outcome was assessed as cerebral performance category (CPC) at discharge from ICU, with an unfavorable outcome being defined as CPC 4 and 5. RESULTS: In 187 patients, a 'late' EEG recording was performed. Of these patients, 127 were without continuous administration of sedative agents for at least 24 h before the EEG recording. In this patient group, a continuously suppressed background activity < 10 µV predicted an unfavorable outcome with a sensitivity of 31% (95% confidence interval (CI) 20-45) and a specificity of 99% (95% CI 91-100). In patients with suppressed background activity and generalized periodic discharges, sensitivity was 15% (95% CI 7-27) and specificity was 100% (95% CI 94-100). GPDs on unsuppressed background activity were associated with a sensitivity of 42% (95% CI 29-46) and a specificity of 92% (95% CI 82-97). CONCLUSIONS: A 'late' EEG performed 5 to 14 days after resuscitation from cardiac arrest can aide in prognosticating functional outcome. A suppressed EEG background activity in this time period indicates poor outcome.

12.
Am J Epidemiol ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33831172

RESUMO

We evaluate whether randomly sampling and testing a set number of individuals for coronavirus disease 2019 (COVID-19) while adjusting for misclassification error captures the true prevalence. We also quantify the impact of misclassification error bias on publicly reported case data in Maryland. Using a stratified random sampling approach, 50,000 individuals were selected from a simulated Maryland population to estimate the prevalence of COVID-19. We examined the situation when the true prevalence is low (0.07%-2%), medium (2%-5%) and high (6%-10%). Bayesian models informed by published validity estimates were used to account for misclassification error when estimating COVID-19 prevalence. Adjustment for misclassification error captured the true prevalence 100% of the time, irrespective of the true prevalence level. When adjustment for misclassification error was not done, the results highly varied depending on the population's underlying true prevalence and the type of diagnostic test used. Generally, the prevalence estimates without adjustment for misclassification error worsened as the true prevalence level increased. Adjustment for misclassification error for publicly reported Maryland data led to a minimal but not significant increase in the estimated average daily cases. Random sampling and testing of COVID-19 are needed with adjustment for misclassification error to improve COVID-19 prevalence estimates.

13.
Preprint | medRxiv | ID: ppmedrxiv-21254656

RESUMO

BackgroundIndividuals with chronic inflammatory diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the effectiveness of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management. MethodsWe conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+ binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination. ResultsCompared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization. ConclusionsCID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.

14.
J Nat Prod ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33899471

RESUMO

While marine natural products have been investigated for anticancer drug discovery, they are barely screened against rare cancers. Thus, in our effort to discover potential drug leads against the rare cancer pseudomyxoma peritonei (PMP), which currently lacks effective drug treatments, we screened extracts of marine actinomycete bacteria against the PMP cell line ABX023-1. This effort led to the isolation of nine rearranged angucyclines from Streptomyces sp. CNZ-748, including five new analogues, namely, grincamycins P-T (1-5). The chemical structures of these compounds were unambiguously established based on spectroscopic and chemical analyses. Particularly, grincamycin R (3) possesses an S-containing α-l-methylthio-aculose residue, which was discovered in nature for the first time. All of the isolated compounds were evaluated against four PMP cell lines and some exhibited low micromolar inhibitory activities. To identify a candidate biosynthetic gene cluster (BGC) encoding the grincamycins, we sequenced the genome of the producing strain, Streptomyces sp. CNZ-748, and compared the BGCs detected with those linked to the production of angucyclines with different aglycon structures.

15.
Perioper Care Oper Room Manag ; : 100168, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33898769

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) airway response teams concentrate equipment and expertise while minimizing the number of providers exposed to aerosol generating procedures. These airway teams were implemented in various hospitals around the world to respond to the acute increase of critical ill patients requiring ventilatory support. We created a financial model to estimate the costs for staffing and maintaining a dedicated COVID-19 airway response team based on the experience at an urban academic hospital in the Northeastern United States between March and June of 2020. METHODS: The institutional review board at Brigham and Women's Hospital approved this protocol and the requirement for informed consent was waived. The average reimbursement for 125 COVID-19 airway consultations was measured. Our team estimated the costs of consumable items for each airway based on previously published recommendations for equipment and personal protective equipment. A sensitivity analyses was performed for variable numbers of monthly airway consults and different staffing patterns based on a literature review of available COVID-19 airway team structures. RESULTS: Based on the average reimbursements and estimates of the consumable costs, each airway procedure represented a net loss of $34 to the institution. The overall estimated cost of staffing a dedicated airway team was between $109,472 and $204,575 per month. CONCLUSIONS: Development and implementation of a dedicated COVID-19 airway response teams represents a significant institutional expense. Institutions should establish necessary cost sharing, consider volume and team structure, and identify reimbursement opportunities that mitigate the necessary expense associated with airway response programs.

16.
Polymers (Basel) ; 13(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802821

RESUMO

The development of advanced composite biomaterials combining the versatility and biodegradability of polymers and the unique characteristics of metal oxide nanoparticles unveils new horizons in emerging biomedical applications, including tissue regeneration, drug delivery and gene therapy, theranostics and medical imaging. Nanocrystalline cerium(IV) oxide, or nanoceria, stands out from a crowd of other metal oxides as being a truly unique material, showing great potential in biomedicine due to its low systemic toxicity and numerous beneficial effects on living systems. The combination of nanoceria with new generations of biomedical polymers, such as PolyHEMA (poly(2-hydroxyethyl methacrylate)-based hydrogels, electrospun nanofibrous polycaprolactone or natural-based chitosan or cellulose, helps to expand the prospective area of applications by facilitating their bioavailability and averting potential negative effects. This review describes recent advances in biomedical polymeric material practices, highlights up-to-the-minute cerium oxide nanoparticle applications, as well as polymer-nanoceria composites, and aims to address the question: how can nanoceria enhance the biomedical potential of modern polymeric materials?

17.
Antibiotics (Basel) ; 10(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807345

RESUMO

Antimicrobial resistance (AMR) is a global public health threat associated with increased mortality, morbidity and costs. Inappropriate antimicrobial prescribing, particularly of broad-spectrums antimicrobials (BSAs), is considered a major factor behind growing AMR. The aim of this study was to explore physician perception and views about BSAs and factors that impact upon their BSAs prescribing decisions. Qualitative semistructured telephone interviews over an eleven-week period were conducted with physicians in a single tertiary care hospital in Riyadh, Saudi Arabia. Purposeful and snowball sampling techniques were adopted as sampling strategy. All interviews were audio recorded, transcribed verbatim, uploaded to NVivo® software and analysed following thematic analysis approach. Four major themes emerged: views on BSAs, factors influencing BSA prescribing and antimicrobial stewardship: practices and barriers and recommendations to improve appropriate BSA prescribing. Recommendations for the future include improving clinical knowledge, feedback on prescribing, multidisciplinary team decision-making and local guideline implementation. Identification of views and determinants of BSA prescribing can guide the design of a multifaceted intervention to support physicians and policymakers to improve antimicrobial prescribing practices.

18.
Nat Commun ; 12(1): 1349, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649339

RESUMO

The Arctic has the highest warming rates on Earth. Glaciated fjord ecosystems, which are hotspots of carbon cycling and burial, are extremely sensitive to this warming. Glaciers are important for the transport of iron from land to sea and supply this essential nutrient to phytoplankton in high-latitude marine ecosystems. However, up to 95% of the glacially-sourced iron settles to sediments close to the glacial source. Our data show that while 0.6-12% of the total glacially-sourced iron is potentially bioavailable, biogeochemical cycling in Arctic fjord sediments converts the glacially-derived iron into more labile phases, generating up to a 9-fold increase in the amount of potentially bioavailable iron. Arctic fjord sediments are thus an important source of potentially bioavailable iron. However, our data suggests that as glaciers retreat onto land the flux of iron to the sediment-water interface may be reduced. Glacial retreat therefore likely impacts iron cycling in coastal marine ecosystems.

20.
J Chem Phys ; 154(10): 104117, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33722034

RESUMO

Computational schemes for comprehensive studies of molecular electron-attached states and the calculation of electron affinities (EAs) are formulated and implemented employing the intermediate state representation (ISR) formalism and the algebraic-diagrammatic construction approximation for the electron propagator (EA-ADC). These EA-ADC(n)/ISR(m) schemes allow for a consistent treatment of not only electron affinities and pole strengths up to third-order of perturbation theory (n = 3) but also one-electron properties of electron-attached states up to second order (m = 2). The EA-ADC/ISR equations were implemented in the Q-Chem program for Sz-adapted intermediate states, allowing also open-shell systems to be studied using unrestricted Hartree-Fock references. For benchmarking of the EA-(U)ADC/ISR schemes, EAs and dipole moments of various electron-attached states of small closed- and open-shell molecules were computed and compared to full configuration interaction data. As an illustrative example, EA-ADC(3)/ISR(2) has been applied to the thymine-thymine (6-4) DNA photolesion.

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