Calcium sulfate minerals such as gypsum play important roles in natural and industrial processes, but their precipitation mechanisms remain largely unexplored. We used time-resolved sample quenching ...and high-resolution microscopy to demonstrate that gypsum forms via a three-stage process: (i) homogeneous precipitation of nanocrystalline hemihydrate bassanite below its predicted solubility, (ii) self-assembly of bassanite into elongated aggregates co-oriented along their c axis, and (iii) transformation into dihydrate gypsum. These findings indicate that a stable nanocrystalline precursor phase can form below its bulk solubility and that in the CaSO₄ system, the self-assembly of nanoparticles plays a crucial role. Understanding why bassanite forms prior to gypsum can lead to more efficient anti-scaling strategies for water desalination and may help to explain the persistence of CaS0 4 phases in regions of low water activity on Mars.
Summary
Objective
To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE).
Methods
...This multicenter, retrospective, 1‐year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included.
Results
The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic–clonic seizures GTCS only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure‐free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add‐on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent.
Significance
In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real‐world evidence with perampanel across different seizure types in IGE.
Ecogenomics of the SAR11 clade Haro‐Moreno, Jose M.; Rodriguez‐Valera, Francisco; Rosselli, Riccardo ...
Environmental microbiology,
20/May , Letnik:
22, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Summary
Members of the SAR11 clade, despite their high abundance, are often poorly represented by metagenome‐assembled genomes. This fact has hampered our knowledge about their ecology and genetic ...diversity. Here we examined 175 SAR11 genomes, including 47 new single‐amplified genomes. The presence of the first genomes associated with subclade IV suggests that, in the same way as subclade V, they might be outside the proposed Pelagibacterales order. An expanded phylogenomic classification together with patterns of metagenomic recruitment at a global scale have allowed us to define new ecogenomic units of classification (genomospecies), appearing at different, and sometimes restricted, metagenomic data sets. We detected greater microdiversity across the water column at a single location than in samples collected from similar depth across the global ocean, suggesting little influence of biogeography. In addition, pangenome analysis revealed that the flexible genome was essential to shape genomospecies distribution. In one genomospecies preferentially found within the Mediterranean, a set of genes involved in phosphonate utilization was detected. While another, with a more cosmopolitan distribution, was unique in having an aerobic purine degradation pathway. Together, these results provide a glimpse of the enormous genomic diversity within this clade at a finer resolution than the currently defined clades.
Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are ...active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m
2
plus cyclophosphamide 600 mg/m
2
for 4 cycles) followed either by D (docetaxel 100 mg/m
2
× 4 cycles; EC–D) or DCb (docetaxel 75 mg/m
2
plus carboplatin AUC 6 × 4 cycles; EC–DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC–D, 48 EC–DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC–D and 14 patients (30 %) with EC–DCb (
P
value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56–83) in the EC–D arm and 77 % (95 % CI 65–87) in the EC–DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC–D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.
Poor nutritional status leads to multiple adverse outcomes, but few studies have assessed its role as a risk factor for incident frailty and death in community-dwelling older adults. Hence, the aim ...of this paper is to assess the role of nutritional status using the Global Leadership Initiative on Malnutrition (GLIM) criteria in the risk of frailty and mortality in Spanish community-dwelling older adults.
We used data from two waves (waves 2 (2011–2013) and 3 (2015–2017)) from the Toledo Study of Healthy Ageing, which is an observational, prospective cohort (average follow-up = 3.18 years) of 1660 older (≥65 years) adults living in the community. Nutritional status categories were defined according to the GLIM criteria, which uses a two-step approach. First, screening for malnutrition risk. Once positive, individuals were classified as malnourished according to some phenotypic (body mass index, grip strength and unintentional weight loss) and etiologic (disease burden/inflammation and reduced food intake or assimilation) criteria. Frailty was assessed using both the Frailty Index (FI) and Frailty Trait Scale (FTS). Mortality data was obtained through the National Death Index.
From the 1660 older adults, 248 participants (14.04%) were classified as ‘at malnutrition risk’ (AMR) and 209 (12.59%) as malnourished (MN). AMR and MN subjects were older and with worse functional status (frailer). Adjusted cross-sectional analysis showed an association between nutritional status and frailty by both FI and FTS. Adjusted longitudinal analyses showed that AMR was associated with higher risk of frailty, using both the FTS (OR: 1.262; 95% CI: 1.078–1.815) and the FI (OR: 1.116; 95% CI: 1.098–1.686), while being malnourished was associated with higher mortality risk (OR: 1.748; 95% CI: 1.073–2.849), but not with incident frailty at follow-up period.
Nutritional status, assessed through GLIM, predicts in a dose-dependent manner the risk of frailty and death. Being at malnutrition risk predicts the risk of becoming frail at follow-up period, whereas being malnourished predicts mortality. These findings highlight the importance of assessing the nutritional status of community-dwelling older adults to identify the ones at risk of developing frailty or death and inform targeted nutrition-focused interventions.
To assess the role of frailty in predicting death and incident disability in older adults with type 2 diabetes mellitus.
Prospective cohort study.
Community dwelling.
A total of 1825 individuals ...≥65 years old recruited between June 2006 and September 2009 were followed for a median of 5.5 years for mortality and 4.98 years for incident functional disability in activities of daily living. Self-reported diabetes, comorbidities (Charlson index), cardio- and cerebrovascular diseases, drug treatments, Frailty Trait Score (FTS) and Frailty Index (FI), activities of daily living, heart rate, and blood pressure among others were collected at baseline.
Survival analysis (Kaplan-Meier), adjusted Cox proportional-hazards models, and binary logistic regression were used to assess the relationship between frailty, comorbidity, and vascular diseases and time to death and incident disability.
A total of 363 people had diabetes. Among them, 83 deaths and 84 cases of incident disability occurred during follow-up. People with diabetes died more frequently than those without diabetes hazard ratio = 1.36, 95% confidence interval (CI) 1.06-1.75; P = .002, showing a poorer functional status at baseline. Survival analysis showed a relationship between frailty quartiles and the risk of death. In the adjusted Cox-models, only age and frailty indices, but not comorbidity or cardio/cerebrovascular diseases, were associated with the risk of death and incident disability after adjusting for measures of frailty. The hazard ratio for death was 1.51 (95% CI 1.28-1.77) and 1.83 (95% CI 1.49-2·26) for each 10 points increase in the FTS and FI; odds ratio for incident disability was 1·64 (95% CI 1.22-2.20) and 1·35 (95% CI 1.09-1.67) when using FI and FTS, respectively.
Frailty is an important risk factor for death and disability in older adults with diabetes, supporting the recent recommendations that frailty status should be routinely assessed in these patients.
Smart City Research Meijer, Albert J.; Gil-Garcia, J. Ramon; Bolívar, Manuel Pedro Rodríguez
Social science computer review,
12/2016, Letnik:
34, Številka:
6
Journal Article
Recenzirano
There are three issues that are crucial to advancing our academic understanding of smart cities: (1) contextual conditions, (2) governance models, and (3) the assessment of public value. A brief ...review of recent literature and the analysis of the included papers provide support for the assumption that cities cannot simply copy good practices but must develop approaches that fit their own situation (contingency) and concord with their own organization in terms of broader strategies, human resource policies, information policies, and so on (configuration). A variety of insights into the mechanisms and building blocks of smart city practices are presented, and issues for further research are identified.
The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs.
This was a ...multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated.
A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months 95% confidence interval (CI) 4.8-14.1. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively.
Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201).
NCT01280201.
The stress shielding and the poor osseointegration in titanium implants are still problems to be resolved. In this context, this work proposes a balanced solution. Titanium samples were fabricated, ...with a porosity of 100–200μm of pore size employing space-holder technique (50vol% NH4HCO3, 800MPa at 1250°C during 2h under high vacuum conditions), obtaining a good equilibrium between stiffness and mechanical resistance. The porous titanium substrates were coated with hydroxyapatite, obtained by sol-gel technique: immersion, dried at 80°C and heat treatment at 450°C during 5h under vacuum conditions. Phases, surface morphology and interfacial microstructure of the transverse section were analyzed by Micro-Computed Tomography, SEM and confocal laser, as well as the infiltration capability of the coating into the metallic substrate pores. The FTIR and XRD showed the crystallinity of the phases and the chemical composition homogeneity of the coating. The size and interconnected pores obtained allow the infiltration of hydroxyapatite (HA), possible bone ingrowth and osseointegration. The scratch resistance of the coating corroborated a good adherence to the porous metallic substrate. The coated titanium samples have a biomechanical and biofunctional equilibrium, as well as a potential use in biomedical applications (partial substitution of bone tissue).
•Porous Ti substrates were coated with hydroxyapatite by the sol-gel technique.•A HA porous thin films onto the porous titanium substrates was obtained.•The HA - porous Ti showed good mechanical interlocking and chemical bonding.•The HA coatings can prevent the corrosion of Ti substrate and make it bioactive.•The proposed HA coating on porous Ti allows a biofunctional and mechanical balance.
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