Magnetic and superconducting interactions couple electrons together to form complex states of matter. We show that, at the atomic scale, both types of interactions can coexist and compete to ...influence the ground state of a localized magnetic moment. Local spectroscopy at 4.5 kelvin shows that the spin-1 system formed by manganese-phthalocyanine (MnPc) adsorbed on Pb(111) can lie in two different magnetic ground states. These are determined by the balance between Kondo screening and superconducting pair-breaking interactions. Both ground states alternate at nanometer length scales to form a Moiré-like superstructure. The quantum phase transition connecting the two (singlet and doublet) ground states is thus tuned by small changes in the molecule-lead interaction.
Triple-negative breast cancer (TNBC) is characterised by poor outcomes and a historical lack of targeted therapies. Dysregulation of signalling through the phosphoinositide 3 (PI3)-kinase and AKT ...signalling pathway is one of the most frequent oncogenic aberrations of TNBC. Although mutations in individual genes occur relatively rarely, combined activating mutations in PIK3CA and AKT1, with inactivating mutations in phosphatase and tensin homologue, occur in ∼25%‒30% of advanced TNBC. Recent randomised trials suggest improved progression-free survival (PFS) with AKT-inhibitors in combination with first-line chemotherapy for patients with TNBC and pathway genetic aberrations. We review the evidence for PI3K pathway activation in TNBC, and clinical trial data for PI3K, AKT and mammalian target of rapamycin inhibitors in TNBC. We discuss uncertainty over defining which cancers have pathway activation and the future overlap between immunotherapy and pathway targeting.
Heinrich et al show that paramagnetic molecules on a superconducting substrate exhibit excited spin states with a lifetime of 10 ns. They ascribe this increase in lifetime by orders of magnitude to ...the depletion of electronic states around the Fermi level in the superconductor. This prohibits pathways of energy relaxation into the substrate and allows the magnetic molecule to be electrically pumped into higher spin states, making superconducting substrates prime candidates for spin manipulation. We further show that the proximity of the scanning tunnelling microscope tip modifies the magnetic anisotropy.
•Resource recovery from urban wastewater to promote shift towards a circular economy.•Pilot and full-scale studies show MBBR as suitable system for treated wastewater reuse.•Numerous methods ...developed for nutrient recovery from WWTP’s effluents.
Over the last years, an increasing concern has emerged regarding the eco-friendly management of wastewater. Apart from the role of wastewater treatment plants (WWTPs) for wastewater and sewage sludge treatment, the increasing need of the recovery of the resources contained in wastewater, such as nutrients and water, should be highlighted. This would allow for transforming a wastewater treatment plant (WWTP) into a sustainable technological system.
The objective of this review is to propose a moving bed biofilm reactor (MBBR) as a novel technology that contributes to the circularity of the wastewater treatment sector according to the principles of circular economy. In this regard, this paper aims to consider the MBBR process as the initial step for water reuse, and nutrient removal and recovery, within the circular economy model.
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•Membrane-based treatments and AOP combination was assessed for wastewater reclamation.•MBR and MBBR-MBR can regenerate wastewater with highest quality set in ...2018/0169/COD.•Pharmaceuticals in urban wastewater can be completely removed using MBBR-MBR + AOP.•The heterotrophic kinetics of biomass is affected by the presence of pharmaceuticals.
This research was performed to assess the production of reclaimed water from urban wastewater in membrane bioreactor – advanced oxidation process (MBR-AOP) and moving bed biofilm reactor – membrane bioreactor – advanced oxidation process (MBBR-MBR-AOP) combined treatments to study the effect of biofilm incorporation. Both combined treatments were operated at the same conditions (10 h of hydraulic retention time, 6500 mg/L of mixed liquor suspended solids and 25 mg/L of hydrogen peroxide dosage over 15 min). Additionally, the removal capacity of some pharmaceuticals (carbamazepine, ciprofloxacin and ibuprofen) and their impact on the kinetic behaviour of the biomass in both systems were evaluated. From the results, it was found a membrane-based bioreactor can achieve both wastewater secondary treatment and pre-treatment for advanced oxidation process, so both MBR-AOP and MBBR-MBR-AOP treatments have a great potential to produce high quality reclaimed water (biological oxygen demand <0.5 mgO2/L, suspended solids <1 mg/L, turbidity <1 NTU and no presence of E. coli), according to European Commission proposal 2018/0169/COD. The addition of carriers improved the biodegradation of the most persistent pharmaceuticals in the biological treatment (from 69.20 ± 1.54% to 75.14 ± 2.71% for carbamazepine and from 60.41 ± 2.16 to 63.14 ± 2.70% for ciprofloxacin). It had, as a consequence, the MBBR-MBR-AOP system showing a complete degradation of pharmaceuticals after 5 min AOP treatment compared to the MBR-AOP system. The loss of biomass in the MBR-AOP (from 5233.45 to 4451.92 mg/L) and the increase of the substrate degradation rate for organic matter in both treatments (from 37.27 to 41.42 and from 30.25 to 33.19 mgO2/(L·h) in MBR-AOP and MBBR-MBR-AOP, respectively) are some of the consequences of pharmaceuticals in urban wastewater.
Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert ...working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made.
The aims of this study were to explore the clinical distribution, by species, of the genus Nocardia and to assess the antimicrobial susceptibilities of the 10 most prevalent species identified in ...Spain.
Over a 10 year period (2005-14), 1119 Nocardia strains were molecularly identified and subjected to the Etest. The distribution and resistance trends over the sub-periods 2005-09 and 2010-14 were also examined.
Of the strains examined, 82.9% belonged to the following species: Nocardia cyriacigeorgica (25.3%), Nocardia nova (15.0%), Nocardia abscessus (12.7%), Nocardia farcinica (11.4%), Nocardia carnea (4.3%), Nocardia brasiliensis (3.5%), Nocardia otitidiscaviarum (3.1%), Nocardia flavorosea (2.6%), Nocardia rhamnosiphila (2.6%) and Nocardia transvalensis (2.4%). Their prevalence values were similar during 2005-09 and 2010-14, except for those of N. abscessus , N. farcinica and N. transvalensis , which fell significantly in the second sub-period ( P ≤ 0.05). The major location of isolation was the respiratory tract (∼86%). Half (13/27) of all strains from the CNS were N. farcinica . Significant differences in MIC results were recorded for some species between the two sub-periods. According to the CLSI's breakpoints, low resistance rates (≤15%) were recorded for seven species with respect to cefotaxime, imipenem and tobramycin; five species showed similar rates with respect to trimethoprim/sulfamethoxazole. Linezolid and amikacin were the most frequently active agents.
The accurate identification of the infecting species and the determination of its susceptibility to antimicrobial agents, given the large number of strains with atypical patterns, are crucial if patients with nocardiosis are to be successfully treated.
Background and purpose
B‐type natriuretic peptide (BNP) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) are well‐known surrogates of atrial fibrillation (AF) detection but studies usually ...present data on either BNP or NT‐proBNP. The aim was to determine and directly compare the validity of the two biomarkers as a tool to predict AF and guide prolonged cardiac monitoring in cryptogenic stroke patients.
Methods
Non‐lacunar acute ischaemic stroke (<72 h) patients over 55 years of age with cryptogenic stroke after standard evaluation were included in the Crypto‐AF study and blood was collected. BNP and NT‐proBNP levels were determined by automated immunoassays. AF was assessed by 28 days’ monitoring. Highest (optimizing specificity) and lowest (optimizing sensitivity) quartiles were used as biomarker cut‐offs to build predictive models adjusted by sex and age. The integrated discrimination improvement index (IDI) and DeLong test were used to compare the performance of the two biomarkers.
Results
From 320 patients evaluated, 218 were included in the analysis. AF was detected in 50 patients (22.9%). NT‐proBNP (P < 0.001) and BNP (P < 0.001) levels were higher in subjects with AF and their levels correlated (r = 0.495, P < 0.001). BNP showed an increased area under the curve (0.720 vs. 0.669; P = 0.0218) and a better predictive capacity (IDI = 3.63%, 95% confidence interval 1.36%–5.91%) compared to NT‐proBNP. BNP performed better than NT‐proBNP in a specific model (IDI = 3.7%, 95% confidence interval 0.87%–6.5%), whilst both biomarkers performed similarly in the case of a sensitive model.
Conclusions
Both BNP and NT‐proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT‐proBNP, especially in terms of specificity.
B‐type natriuretic peptide (BNP) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) are well‐known surrogates of atrial fibrillation (AF) detection but studies usually present data on either BNP or NT‐proBNP. In our study, both BNP and NT‐proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT‐proBNP, especially in terms of specificity.
Angiotensin converting enzyme (ACE) 2 is a homologue of ACE that catalyzes the conversion of Angiotensin (Ang) II into Ang1-7, which induces vasodilation, anti-fibrotic, anti-proliferative and ...anti-inflammatory effects. Given that ACE2 counterbalances the effects of Ang II, it has been proposed as a biomarker in kidney disease patients. Circulating ACE2 has been studied in human and experimental studies under physiological and pathological conditions and different techniques have been assessed to determine its enzymatic activity. In patients with cardiovascular (CV) disease circulating ACE2 has been shown to be increased. In addition, hypertensive and diabetic patients have also shown higher circulating ACE2 activities. A study in type 1 diabetes patients found a negative association between circulating ACE2 and estimated glomerular filtration rate in male and female patients. Recently, it has been demonstrated that circulating ACE2 is increased in male patients with chronic kidney disease (CKD) and that it is independently associated with other classical CV risk factors, such as advanced age and diabetes. Furthermore, circulating ACE2 has been shown to be associated with silent atherosclerosis and CV outcomes in CKD patients. In diabetic nephropathy, experimental studies have demonstrated an increase in circulating ACE2 activity both at early and late stages of the disease, as well as a direct association with increased urinary albumin excretion, suggesting that it may be increased as a renoprotective mechanism in these patients. In this paper we will review the measurement of circulating ACE2 and its role in kidney disease, as well as its potential role as a renal and CV biomarker.
The topography of craniopharyngiomas has proved fundamental in predicting the involvement of vital brain structures and the possibility of achieving a safe radical resection. Beyond the imprecise ...term "suprasellar," indiscriminately used for craniopharyngiomas, an accurate definition of craniopharyngioma topography should be assessed by preoperative MR imaging. The objective of this study was to investigate the MRI findings that help define craniopharyngioma topography.
This study retrospectively investigated a cohort of 200 surgically treated craniopharyngiomas with their corresponding preoperative midsagittal and coronal conventional T1- and T2-weighted MR images, along with detailed descriptions of the surgical findings. Radiologic variables related to the occupation of the tumor of intracranial compartments and the distortions of anatomic structures along the sella turcica-third ventricle axis were analyzed and correlated with the definitive craniopharyngioma topography observed during the surgical procedures. A predictive model for craniopharyngioma topography was generated by multivariate analysis.
Five major craniopharyngioma topographies can be defined according to the degree of hypothalamic distortion caused by the tumor: sellar-suprasellar, pseudointraventricular, secondary intraventricular, not strictly intraventricular, and strictly intraventricular. Seven key radiologic variables identified on preoperative MRI allowed a correct overall prediction of craniopharyngioma topography in 86% of cases: 1) third ventricle occupation, 2) pituitary stalk distortion, 3) relative level of the hypothalamus in relation to the tumor, 4) chiasmatic cistern occupation, 5) mammillary body angle, 6) type of chiasm distortion, and 7) tumor shape.
Systematic assessment of these 7 variables on conventional preoperative T1 and T2 MRI is a useful and reliable method to ascertain individual craniopharyngioma topography.
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