10,787 research outputs found
Modelling frontotemporal dementia using patient-derived induced pluripotent stem cells
Frontotemporal dementia (FTD) describes a group of clinically heterogeneous conditions that frequently affect people under the age of 65 (1). There are multiple genetic causes of FTD, including coding or splice-site mutations in MAPT, GRN mutations that lead to haploinsufficiency of progranulin protein, and a hexanucleotide GGGGCC repeat expansion in C9ORF72. Pathologically, FTD is characterised by abnormal protein accumulations in neurons and glia. These aggregates can be composed of the microtubule-associated protein tau (observed in FTD with MAPT mutations), the DNA/RNA-binding protein TDP-43 (seen in FTD with mutations in GRN or C9ORF72 repeat expansions) or dipeptide proteins generated by repeat associated non-ATG translation of the C9ORF72 repeat expansion. There are currently no disease-modifying therapies for FTD and the availability of in vitro models that recapitulate pathologies in a disease-relevant cell type would accelerate the development of novel therapeutics. It is now possible to generate patient-specific stem cells through the reprogramming of somatic cells from a patient with a genotype/phenotype of interest into induced pluripotent stem cells (iPSCs). iPSCs can subsequently be differentiated into a plethora of cell types including neurons, astrocytes and microglia. Using this approach has allowed researchers to generate in vitro models of genetic FTD in human cell types that are largely inaccessible during life. In this review we explore the recent progress in the use of iPSCs to model FTD, and consider the merits, limitations and future prospects of this approach
Limb Size Discrepancy in a 29 yo Male
Please view the clinical abstract in the attached PDF fil
A massive, distant proto-cluster at z=2.47 caught in a phase of rapid formation?
Numerical simulations of cosmological structure formation show that the
Universe's most massive clusters, and the galaxies living in those clusters,
assemble rapidly at early times (2.5 < z < 4). While more than twenty
proto-clusters have been observed at z > 2 based on associations of 5-40
galaxies around rare sources, the observational evidence for rapid cluster
formation is weak. Here we report observations of an asymmetric, filamentary
structure at z = 2.47 containing seven starbursting, submillimeter-luminous
galaxies and five additional AGN within a comoving volume of 15000 Mpc.
As the expected lifetime of both the luminous AGN and starburst phase of a
galaxy is ~100 Myr, we conclude that these sources were likely triggered in
rapid succession by environmental factors, or, alternatively, the duration of
these cosmologically rare phenomena is much longer than prior direct
measurements suggest. The stellar mass already built up in the structure is
and we estimate that the cluster mass will exceed that
of the Coma supercluster at . The filamentary structure is in line
with hierarchical growth simulations which predict that the peak of cluster
activity occurs rapidly at z > 2.Comment: 7 pages, 3 figures, 2 tables, accepted in ApJL (small revisions from
previous version
Electrical characterization of the soft breakdown failure mode in MgO layers
The soft breakdown (SBD) failure mode in 20 nm thick MgO dielectric layers grown on Si substrates was investigated. We show that during a constant voltage stress, charge trapping and progressive breakdown coexist, and that the degradation dynamics is captured by a power-law time dependence. We also show that the SBD current-voltage (I-V) characteristics follow the power-law model I = aVb typical of this conduction mechanism but in a wider voltage window than the one reported in the past for SiO2. The relationship between the magnitude of the current and the normalized differential conductance was analyzed
Dynamics of silver elution from functionalised antimicrobial nanofiltration membranes
In an effort to mitigate biofouling on thin film composite membranes such as nanofiltration and reverse osmosis, a myriad of different surface modification strategies has been published. The use of silver nanoparticles (Ag-NPs) has emerged as being particularly promising. Nevertheless, the stability of these surface modifications is still poorly understood, particularly under permeate flux conditions. Leaching or elution of Ag-NPs from the membrane surface can not only affect the antimicrobial characteristics of the membrane, but could also potentially present an environmental liability when applied in industrial-scale systems. This study sought to investigate the dynamics of silver elution and the bactericidal effect of an Ag-NP functionalised NF270 membrane. Inductively coupled plasma-atomic emission spectroscopy was used to show that the bulk of leached silver occurred at the start of experimental runs, and was found to be independent of salt or permeate conditions used. Cumulative amounts of leached silver did, however, stabilise following the initial release, and were shown to have maintained the biocidal characteristics of the modified membrane, as observed by a higher fraction of structurally damaged Pseudomonas fluorescens cells. These results highlight the need to comprehensively assess the time-dependent nature of bactericidal membranes
Percutaneous Nephrolithotomy in the Superobese: A Comparison of Outcomes Based on Body Mass Index
Introduction: Percutaneous nephrolithotomy (PCNL) is considered the gold standard for treatment of large renal calculi. Although several investigators have examined the feasibility and outcomes associated with PCNL in obese patients, these studies have been limited by small sample size, lack of a comparator group, or few patients at body mass index (BMI) extremes. We thus compared outcomes of superobese (BMI >50) patients undergoing PCNL vs both an “overweight” and “ideal” cohort.
Methods: We used a prospectively maintained database to identify ideal (BMI 18.5–25), overweight (BMI 25.1–49.9), and superobese (BMI ≥50) patients who underwent PCNL. Our primary objective was to compare surgical outcomes between groups measured by the percent of patients who required secondary PCNL. We then compared complication rates, need for transfusion, and length of stay (LOS) using chi-square testing and ANOVA where appropriate.
Results: A total of 1152 patients were identified of which 254 were classified as ideal, 840 as overweight, and 58 as superobese. The overweight cohort had a higher mean age and greater proportion of males, whereas staghorn stones were more common in the superobese group. Comorbid conditions were more commonly observed in the superobese cohort. Otherwise, the groups were similar. Surgical outcomes were comparable with 47.2%, 42.0%, and 38.0% of ideal, overweight, and superobese patients requiring secondary PCNL (p = 0.25) with no difference in complication rates, need for transfusion, or LOS.
Conclusion: PCNL can be effectively and safely performed in superobese patients with no difference in surgical outcomes or complications when compared to ideal or overweight patient cohorts
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