Oxygen is essential for animal life, and while geochemical proxies have been instrumental in determining the broad evolutionary history of oxygen on Earth, much of our insight into Phanerozoic oxygen ...comes from biogeochemical modelling. The GEOCARBSULF model utilizes carbon and sulphur isotope records to produce the most detailed history of Phanerozoic atmospheric O
currently available. However, its predictions for the Paleozoic disagree with geochemical proxies, and with non-isotope modelling. Here we show that GEOCARBSULF oversimplifies the geochemistry of sulphur isotope fractionation, returning unrealistic values for the O
sourced from pyrite burial when oxygen is low. We rebuild the model from first principles, utilizing an improved numerical scheme, the latest carbon isotope data, and we replace the sulphur cycle equations in line with forwards modelling approaches. Our new model, GEOCARBSULFOR, produces a revised, highly-detailed prediction for Phanerozoic O
that is consistent with available proxy data, and independently supports a Paleozoic Oxygenation Event, which likely contributed to the observed radiation of complex, diverse fauna at this time.
Summary Sensitivity and specificity of the modified Duke criteria for native valve endocarditis are both suboptimal, at approximately 80%. Diagnostic accuracy for intracardiac prosthetic ...material-related infection is even lower. Non-invasive imaging modalities could potentially improve diagnosis of infective endocarditis; however, their diagnostic value is unclear. We did a systematic literature review to critically appraise the evidence for the diagnostic performance of these imaging modalities, according to PRISMA and GRADE criteria. We searched PubMed, Embase, and Cochrane databases. 31 studies were included that presented original data on the performance of electrocardiogram (ECG)-gated multidetector CT angiography (MDCTA), ECG-gated MRI,18 F-fluorodeoxyglucose (18 F-FDG) PET/CT, and leucocyte scintigraphy in diagnosis of native valve endocarditis, intracardiac prosthetic material-related infection, and extracardiac foci in adults. We consistently found positive albeit weak evidence for the diagnostic benefit of18 F-FDG PET/CT and MDCTA. We conclude that additional imaging techniques should be considered if infective endocarditis is suspected. We propose an evidence-based diagnostic work-up for infective endocarditis including these non-invasive techniques.
Carbon cycling in the coastal zone affects global carbon budgets and is critical for understanding the urgent issues of hypoxia, acidification, and tidal wetland loss. However, there are no regional ...carbon budgets spanning the three main ecosystems in coastal waters: tidal wetlands, estuaries, and shelf waters. Here we construct such a budget for eastern North America using historical data, empirical models, remote sensing algorithms, and process‐based models. Considering the net fluxes of total carbon at the domain boundaries, 59 ± 12% (± 2 standard errors) of the carbon entering is from rivers and 41 ± 12% is from the atmosphere, while 80 ± 9% of the carbon leaving is exported to the open ocean and 20 ± 9% is buried. Net lateral carbon transfers between the three main ecosystem types are comparable to fluxes at the domain boundaries. Each ecosystem type contributes substantially to exchange with the atmosphere, with CO2 uptake split evenly between tidal wetlands and shelf waters, and estuarine CO2 outgassing offsetting half of the uptake. Similarly, burial is about equal in tidal wetlands and shelf waters, while estuaries play a smaller but still substantial role. The importance of tidal wetlands and estuaries in the overall budget is remarkable given that they, respectively, make up only 2.4 and 8.9% of the study domain area. This study shows that coastal carbon budgets should explicitly include tidal wetlands, estuaries, shelf waters, and the linkages between them; ignoring any of them may produce a biased picture of coastal carbon cycling.
Plain Language Summary
A carbon budget for a particular site or region describes the inputs and outputs of carbon to that site or region as well as the processes that change carbon from one form to another. A carbon budget is needed to fully understand many important issues facing coastal waters. We constructed the carbon budget for coastal waters of eastern North America. We found that about 60% of the carbon entering the domain is from rivers and about 40% is from the atmosphere, while about 80% of the carbon leaving the domain goes to the open ocean and about 20% is buried. Transfers of carbon from wetlands to estuaries and from estuaries to the ocean were as important as transfers of carbon at the domain boundaries. Tidal wetlands and estuaries were found to be important to the carbon budget despite making up only 2.4 and 8.9% of the study domain area, respectively. This study shows that coastal carbon budgets should explicitly consider tidal wetlands, estuaries, shelf waters, and the linkages between them; ignoring any of them may produce a biased picture of coastal carbon cycling.
Key Points
Tidal wetlands, estuaries, and shelf waters each contribute substantially to the carbon budget of eastern North American coastal waters
Study region net ecosystem production, atmospheric uptake, and burial are 20.2 ± 4.4, 5.1 ± 2.4, and 2.5 ± 0.7 Tg C yr−1, respectively
Net lateral carbon fluxes between tidal wetlands, estuaries, and shelf waters are large terms in the carbon budget of eastern North American coastal waters
The atom‐efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious‐metal‐based catalysts, with few ...exceptions. Presented here is the first cobalt‐catalyzed hydrogenation of esters to the corresponding alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates.
Getting involved: The atom‐efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious‐metal‐based catalysts. Presented here is the first cobalt‐catalyzed hydrogenation of esters to alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates.
The clinical management of meningioma is guided by tumor grade and biological behavior. Currently, the assessment of tumor grade follows surgical resection and histopathologic review. Reliable ...techniques for pre-operative determination of tumor grade may enhance clinical decision-making.
A total of 175 meningioma patients (103 low-grade and 72 high-grade) with pre-operative contrast-enhanced T1-MRI were included. Fifteen radiomic (quantitative) and 10 semantic (qualitative) features were applied to quantify the imaging phenotype. Area under the curve (AUC) and odd ratios (OR) were computed with multiple-hypothesis correction. Random-forest classifiers were developed and validated on an independent dataset (n = 44).
Twelve radiographic features (eight radiomic and four semantic) were significantly associated with meningioma grade. High-grade tumors exhibited necrosis/hemorrhage (ORsem = 6.6, AUCrad = 0.62-0.68), intratumoral heterogeneity (ORsem = 7.9, AUCrad = 0.65), non-spherical shape (AUCrad = 0.61), and larger volumes (AUCrad = 0.69) compared to low-grade tumors. Radiomic and sematic classifiers could significantly predict meningioma grade (AUCsem = 0.76 and AUCrad = 0.78). Furthermore, combining them increased the classification power (AUCradio = 0.86). Clinical variables alone did not effectively predict tumor grade (AUCclin = 0.65) or show complementary value with imaging data (AUCcomb = 0.84).
We found a strong association between imaging features of meningioma and histopathologic grade, with ready application to clinical management. Combining qualitative and quantitative radiographic features significantly improved classification power.
Mesoporous ceramics and semiconductors enable low-cost solar power, solar fuel, (photo)catalyst and electrical energy storage technologies. State-of-the-art, printable high-surface-area electrodes ...are fabricated from thermally sintered pre-formed nanocrystals. Mesoporosity provides the desired highly accessible surfaces but many applications also demand long-range electronic connectivity and structural coherence. A mesoporous single-crystal (MSC) semiconductor can meet both criteria. Here we demonstrate a general synthetic method of growing semiconductor MSCs of anatase TiO2 based on seeded nucleation and growth inside a mesoporous template immersed in a dilute reaction solution. We show that both isolated MSCs and ensembles incorporated into films have substantially higher conductivities and electron mobilities than does nanocrystalline TiO2. Conventional nanocrystals, unlike MSCs, require in-film thermal sintering to reinforce electronic contact between particles, thus increasing fabrication cost, limiting the use of flexible substrates and precluding, for instance, multijunction solar cell processing. Using MSC films processed entirely below 150 °C, we have fabricated all-solid-state, low-temperature sensitized solar cells that have 7.3 per cent efficiency, the highest efficiency yet reported. These high-surface-area anatase single crystals will find application in many different technologies, and this generic synthetic strategy extends the possibility of mesoporous single-crystal growth to a range of functional ceramics and semiconductors.
In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from ...the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for non-surgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics.
•Surgical excision with negative margins is an important goal whenever feasible.•Radiotherapy is indicated for inoperable cSCC or patients not suitable for surgical intervention.•Multidisciplinary board decisions are necessary in the management of patients with advanced disease.•Anti-PD-1 antibody therapy is first-line systemic treatment for locally advanced or mcSCC.•Follow-up evaluations depend on underlying risk characteristics.
Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR ...scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good‐quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi‐adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.
Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC ...etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (<4%). Further risk stratification into low-risk or high-risk common primary cSCC is recommended based on proposed high-risk factors. Advanced cSCC is classified as locally advanced (lacSCC), and metastatic (mcSCC) including locoregional metastatic or distant metastatic cSCC. Current systems used for staging include the American Joint Committee on Cancer (AJCC) 8th edition, the Union for International Cancer Control (UICC) 8th edition, and Brigham and Women’s Hospital (BWH) system. Physical examination for all cSCCs should include total body skin examination and clinical palpation of lymph nodes, especially of the draining basins. Radiologic imaging such as ultrasound of the regional lymph nodes, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography–computed tomography (PET-CT) scans are recommended for staging of high-risk cSCC. Sentinel lymph node biopsy is currently not recommended. Nicotinamide, oral retinoids, and topical 5-FU have been used for the chemoprevention of subsequent cSCCs in high-risk patients but are not routinely recommended. Education about sun protection measures including reducing sun exposure, use of protective clothing, regular use of sunscreens and avoidance of artificial tanning, is recommended.
•Clinical diagnosis of cSCC is confirmed by histology.•Ιnvasive cSCC is classified as high-risk or low risk for recurrence or metastasis.•Risk classification is based on tumour- and patient-related risk characteristics.•Staging systems of cSCC are based on TNM classification and require refinement.