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Additive manufacturing (AM) is fundamentally different from traditional formative or subtractive manufacturing in that it is the closest to the ‘bottom up’ manufacturing where a ...structure can be built into its designed shape using a ‘layer-by-layer’ approach rather than casting or forming by technologies such as forging or machining. AM is versatile, flexible, highly customizable and, as such, can suite most sectors of industrial production. Materials to make these parts/objects can be of a widely varying type. These include metallic, ceramic and polymeric materials along with combinations in the form of composites, hybrid, or functionally graded materials (FGMs). The challenge remains, however, to transfer this ‘making’ shapes and structures into obtaining objects that are functional. A great deal of work is needed in AM in addressing the challenges related to its two key enabling technologies namely ‘materials’ and ‘metrology’ to achieve this functionality in a predictive and reproductive ways. The good news is that there is a significant interest in industry for taking up AM as one of the main production engineering route. Additive Manufacturing, in our opinion, is definitely at the cross-road from where this new, much-hyped but somewhat unproven manufacturing process must move towards a technology that can demonstrate the ability to produce real, innovative, complex and robust products.
OBJECTIVE: To determine the independent effects of obesity and hypertension on cognitive functioning. METHODS: Using a prospective design, male (n=551) and female (n=872) participants of the ...Framingham Heart Study were classified by presence or absence of obesity and hypertension based on data collected over an 18-y surveillance period. All subjects were free from dementia, stroke, and clinically diagnosed cardiovascular disease up to the time of cognitive testing. Statistical models were adjusted for age, education, occupation, cigarette smoking, alcohol consumption, total cholesterol, and a diagnosis of type II diabetes. Body mass index status (nonobese or obese) and blood pressure status (normotensive or hypertensive) were then related to cognitive performance (learning, memory, executive functioning, and abstract reasoning) on tests administered 4-6 y later. RESULTS: Adverse effects of obesity and hypertension on cognitive performance were observed for men only. Obese and hypertensive men performed more poorly than men classified as either obese or hypertensive, and the best performance was observed in nonobese, normotensive men. CONCLUSIONS: The adverse effects of obesity and hypertension in men are independent and cumulative with respect to cognitive deficit.
Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment ...elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death.
Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals < or = 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits.
This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.
Memory loss is one of the first symptoms of typical Alzheimer's disease (AD), for which there are no effective therapies available. The precuneus (PC) has been recently emphasized as a key area for ...the memory impairment observed in early AD, likely due to disconnection mechanisms within large-scale networks such as the default mode network (DMN). Using a multimodal approach we investigated in a two-week, randomized, sham-controlled, double-blinded trial the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the PC on cognition, as measured by the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite in 14 patients with early AD (7 females). TMS combined with electroencephalography (TMS-EEG) was used to detect changes in brain connectivity. We found that rTMS of the PC induced a selective improvement in episodic memory, but not in other cognitive domains. Analysis of TMS-EEG signal revealed an increase of neural activity in patients' PC, an enhancement of brain oscillations in the beta band and a modification of functional connections between the PC and medial frontal areas within the DMN.
Our findings show that high-frequency rTMS of the PC is a promising, non-invasive treatment for memory dysfunction in patients at early stages of AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD.
•The precuneus is a key area for memory impairment in Alzheimer’s disease (AD).•We investigated the effects of precuneus-rTMS on memory in patients with early AD.•Precuneus-rTMS induced a selective improvement in episodic memory.•Precuneus-rTMS enhance precuneus activity and connectivity with frontal areas.•Precuneus-rTMS is a promising treatment for memory dysfunction in early AD patients.
Summary
Ichthyosis vulgaris is caused by loss‐of‐function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar ...hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker‐skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin‐deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.
What’s already known about this topic?
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Ichthyosis vulgaris is a common disorder characterized clinically by xerosis, excess scaling, hyperkeratosis, keratosis pilaris, and palmar and plantar hyperlinearity, as well as a strong association with atopic disorders.
What does this study add?
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This review updates the reader on the broader perspective of ichthyosis vulgaris based on recent findings and suggests that clinicians, when appropriate, should warn individuals with ichthyosis vulgaris against environmental exposures, for example nickel, irritants, cats in the household and smoking, as these may cause secondary disease.
In this work, an extrusion-based 3D printing technique was employed for processing of biobased blends of Poly(Lactic Acid) (PLA) with low-cost kraft lignin. In Fused Filament Fabrication (FFF) 3D ...printing process, objects are built in a layer-by-layer fashion by melting, extruding and selectively depositing thermoplastic fibers on a platform. These fibers are used as building blocks for more complex structures with defined microarchitecture, in an automated, cost-effective process, with minimum material waste. A sustainable material consisting of lignin biopolymer blended with poly(lactic acid) was examined for its physical properties and for its melt processability during the FFF process. Samples with different PLA/lignin weight ratios were prepared and their mechanical (tensile testing), thermal (Differential Scanning Calorimetry analysis) and morphological (optical and scanning electron microscopy, SEM) properties were studied. The composition with optimum properties was selected for the production of 3D-printing filament. Three process parameters, which contribute to shear rate and stress imposed on the melt, were examined: extrusion temperature, printing speed and fiber’s width varied and their effect on extrudates’ morphology was evaluated. The mechanical properties of 3D printed specimens were assessed with tensile testing and SEM fractography.
Carbon fiber reinforced polymer manufacturing is emerging, with multiple studies to focus on the design of interfacial reinforcement to ensure the maximum of composite properties, but also ...respectively to be able to align with zero defect manufacturing. The controversy on the engineering approach is a data-driven task that can be efficiently tackled by involving Artificial Intelligence in order to establish unbiased structure-property relations. In the present study, nanoindentation mapping data were processed with Machine Learning classification models to identify the interfacial reinforcement. The data preparation included normalization and sorting out of highly similar data with k-means clustering, since nanoindentation on epoxy matrix does not enhance insight on the mechanism of reinforcement. The trained models included neural networks, classification trees, and support vector machines. Realization of models' performance was evaluated on the test dataset as screening to obtain best fitted models for each algorithm. Transfer learning potential was demonstrated by extrapolating the prediction of best trained models to a validation dataset at different indentation depth with support vector machines outperforming the other models. Overall accuracy was 67% on the test dataset, F1 Score was 65% in the prediction of reinforcement mechanism classes and 72% in case of pristine specimen, while accuracy on validation dataset was 72.7%. Prediction metrics were comparable to other case studies of real-world classification problems. Computational time-cost for tuning and training was sustainable and equal to 2.3 min.
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•Artificial Intelligence (AI) identified the interface reinforcement in CFRPs.•Support Vector Machines performed well in both testing and validation of the model.•Functionalization on CFs was predicted with F1-score equal to 65% and accuracy 67%.•Model was validated at different nanoindentation depth with accuracy 72.7%.•Feedback from AI could enhance materials design, decision-making, and quality control.
Coral reefs face an uncertain future punctuated by recurring climate-induced disturbances. Understanding how reefs can recover from and reassemble after mass bleaching events is therefore important ...to predict their responses and persistence in a rapidly changing ocean. On naturally extreme reefs characterized by strong daily temperature variability, coral heat tolerance can vary significantly over small spatial gradients but it remains poorly understood how this impacts bleaching resilience and recovery dynamics, despite their importance as resilience hotspots and potential refugia. In the macrotidal Kimberley region in NW Australia, the 2016 global mass bleaching event had a strong habitat-specific impact on intertidal and subtidal coral communities at our study site: corals in the thermally variable intertidal bleached less severely and recovered within six months, while 68% of corals in the moderately variable subtidal died. We therefore conducted benthic surveys 3.5 years after the bleaching event to determine potential changes in benthic cover and coral community composition. In the subtidal, we documented substantial increases in algal cover and live coral cover had not fully recovered to pre-bleaching levels. Furthermore, the subtidal coral community shifted from being dominated by branching
Acropora
corals with a competitive life history strategy to opportunistic, weedy
Pocillopora
corals which likely has implications for the functioning and stress resilience of this novel coral community. In contrast, no shifts in algal and live coral cover or coral community composition occurred in the intertidal. These findings demonstrate that differences in coral heat tolerance across small spatial scales can have large consequences for bleaching resilience and that spatial patchiness in recovery trajectories and community reassembly after bleaching might be a common feature on thermally variable reefs. Our findings further confirm that reefs adapted to high daily temperature variability play a key role as resilience hotspots under current climate conditions, but their ability to do so may be limited under intensifying ocean warming.
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