Antimicrobial Resistance in ESKAPE Pathogens De Oliveira, David M P; Forde, Brian M; Kidd, Timothy J ...
Clinical microbiology reviews,
06/2020, Letnik:
33, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Antimicrobial-resistant ESKAPE (
,
,
,
,
, and
species) pathogens represent a global threat to human health. The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the ...treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antimicrobial resistance surveillance. This looming health threat has restimulated interest in the development of new antimicrobial therapies, has demanded the need for better patient care, and has facilitated heightened governance over stewardship practices.
Significance We use transient spectroscopy to investigate the mechanism of singlet exciton fission, a quantum mechanical phenomenon in some organic molecules in which a spin-singlet excited state can ...split into two spin-triplet states. This process may be harnessed to boost solar cell efficiencies, but the underlying mechanism remains poorly understood. Central to most models is a triplet pair state, consisting of two triplets entangled into an overall spin-singlet configuration, but it has never before been optically detected. In a solution-based system, we detect a state with simultaneous singlet and triplet exciton character that dissociates to form triplet excitons in 120% yield. We consider that this intermediate constitutes a triplet pair state, and its observation allows important insight into the nature of triplet exciton coupling.
Singlet exciton fission is the spin-conserving transformation of one spin-singlet exciton into two spin-triplet excitons. This exciton multiplication mechanism offers an attractive route to solar cells that circumvent the single-junction ShockleyâQueisser limit. Most theoretical descriptions of singlet fission invoke an intermediate state of a pair of spin-triplet excitons coupled into an overall spin-singlet configuration, but such a state has never been optically observed. In solution, we show that the dynamics of fission are diffusion limited and enable the isolation of an intermediate species. In concentrated solutions of bis(triisopropylsilylethynyl)TIPSâtetracene we find rapid (<100 ps) formation of excimers and a slower (â¼10 ns) break up of the excimer to two triplet exciton-bearing free molecules. These excimers are spectroscopically distinct from singlet and triplet excitons, yet possess both singlet and triplet characteristics, enabling identification as a triplet pair state. We find that this triplet pair state is significantly stabilized relative to free triplet excitons, and that it plays a critical role in the efficient endothermic singlet fission process.
The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found ...increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34-2.09; p < 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.
Abstract
Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant ...variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death.
Methods
With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021.
Results
Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio aHR: 1.73; 95% confidence interval CI: 1.41–2.13; P < .0001) and 62% higher hazards of hospital admission (1.62; 1.48–1.78; P < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74–1.95; P = .45).
Conclusions
The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.
The SARS-CoV-2 alpha variant is associated with a 62% increased risk of hospitalization and a 73% increased risk of death, compared with the originally circulating wild-type virus in England between 16 November 2020 and 21 April 2021.
Eurasia has largely grown to its present enormous size through episodic addition of crustal blocks by recurring birth and demise of oceans such as Paleotethys and Neotethys. Excluding the Kopet Dagh ...Mountains in the northeast, crystalline basement rocks of various dimensions are exposed in all continental tectonic zones of Iran. These rocks have traditionally been viewed as continental fragments with Gondwanan affinity and summarily been assigned Precambrian or younger ages, despite the fact that evidence from isotopic dating has largely been lacking. This study presents new ion microprobe and thermal-ionization zircon U-Pb geochronological data from granitoids and orthogneisses from several locations in central Iran and the Sanandaj–Sirjan structural zones to determine crystallization ages and investigate the origin and continental affinity of these various crustal fragments. The resulting U-Pb crystallization ages for the granites and orthogneisses range from late Neoproterozoic to Early Cambrian, matching the mostly juvenile Arabian–Nubian shield and Peri-Gondwanan terranes constructed after the main phase of Pan-African orogenesis. TIMS analyses of zircons with inherited cores from western Iran suggest that the Neoproterozoic crust of Iran might not be entirely juvenile, pointing to the potential presence of inherited older Proterozoic components as is common in the eastern Arabian shield. More importantly, the new zircon U-Pb crystallization ages unequivocally demonstrate that crystalline basement underlying the Sanandaj–Sirjan zone, central Iran, and the Alborz Mountains is composed of continental fragments with Gondwanan affiliation, characterized by wide spread late Neoproterozoic subduction-related magmatism. The exposure of these late Neoproterozoic–Early Cambrian basement rocks in the Iranian regions north of the Zagros is structurally controlled and linked to both large-scale crustal extension and exhumation during Mesozoic and Tertiary time as well as Tertiary collisional tectonics associated with the closure of Neotethys.
Mortality from COVID-19 shows a strong relationship with age and pre-existing medical conditions, as does mortality from other causes. We aimed to investigate how specific factors are differentially ...associated with COVID-19 mortality as compared to mortality from causes other than COVID-19.
Working on behalf of NHS England, we carried out a cohort study within the OpenSAFELY platform. Primary care data from England were linked to national death registrations. We included all adults (aged ≥18 years) in the database on 1st February 2020 and with >1 year of continuous prior registration; the cut-off date for deaths was 9th November 2020. Associations between individual-level characteristics and COVID-19 and non-COVID deaths, classified according to the presence of a COVID-19 code as the underlying cause of death on the death certificate, were estimated by fitting age- and sex-adjusted logistic models for these two outcomes.
17,456,515 individuals were included. 17,063 died from COVID-19 and 134,316 from other causes. Most factors associated with COVID-19 death were similarly associated with non-COVID death, but the magnitudes of association differed. Older age was more strongly associated with COVID-19 death than non-COVID death (e.g. ORs 40.7 95% CI 37.7-43.8 and 29.6 28.9-30.3 respectively for ≥80 vs 50-59 years), as was male sex, deprivation, obesity, and some comorbidities. Smoking, history of cancer and chronic liver disease had stronger associations with non-COVID than COVID-19 death. All non-white ethnic groups had higher odds than white of COVID-19 death (OR for Black: 2.20 1.96-2.47, South Asian: 2.33 2.16-2.52), but lower odds than white of non-COVID death (Black: 0.88 0.83-0.94, South Asian: 0.78 0.75-0.81).
Similar associations of most individual-level factors with COVID-19 and non-COVID death suggest that COVID-19 largely multiplies existing risks faced by patients, with some notable exceptions. Identifying the unique factors contributing to the excess COVID-19 mortality risk among non-white groups is a priority to inform efforts to reduce deaths from COVID-19.
Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.
The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid ...receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids have a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well being in the social environment.
There is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital ...admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation.
With the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes. We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio aHR 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls p < 0.001 and 1.74, 1.61 to 1.88 versus influenza controls p < 0.001). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants.
In this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.
InP Kudos: The molecular mechanism of InP colloidal quantum dot (QD) syntheses was investigated by NMR spectroscopy. Unlike methods for monodisperse PbSe and CdSe, existing InP syntheses result in ...total depletion of molecular phosphorous species following nucleation, so QD growth is due exclusively to non‐molecular ripening. Amines inhibit precursor depletion by solvation (see picture), contrary to previous reports.
Singlet exciton fission-sensitized solar cells have the potential to exceed the Shockley-Queisser limit by generating additional photocurrent from high-energy photons. Pentacene is an organic ...semiconductor that undergoes efficient singlet fission--the conversion of singlet excitons into pairs of triplets. However, the pentacene triplet is non-emissive, and uncertainty regarding its energy has hindered device design. Here we present an in situ measurement of the pentacene triplet energy by fabricating a series of bilayer solar cells with infrared-absorbing nanocrystals of varying bandgaps. We show that the pentacene triplet energy is at least 0.85 eV and at most 1.00 eV in operating devices. Our devices generate photocurrent from triplets, and achieve external quantum efficiencies up to 80%, and power conversion efficiencies of 4.7%. This establishes the general use of nanocrystal size series to measure the energy of non-emissive excited states, and suggests that fission-sensitized solar cells are a favourable candidate for third-generation photovoltaics.
PDF
