Metastatic Liposarcoma: A Cause of Symptomatic Acute Pericarditis

We describe a patient presenting with a myxoid liposarcoma of the lower thigh in whom an episode of acute pericarditis indicated the recurrence of widespread metastatic disease

Small-Cell Lung Cancer: 8 Years Experience of a Single Multidisciplinary Team

Aims. We have audited the changes in treatment practice for small-cell lung cancer (SCLC) presented to a single multidisciplinary team (MDT) at Doncaster and Bassetlaw Hospitals between January 1998 and December 2005. Materials and Methods. The MDT database was used to identify all patients with SCLC. Anonymised demographic, treatment, and outcome details were extracted from the database supplemented by patient records. Results. 235 patients were identified. 112 (48%) had limited disease at presentation. Chemotherapy was the initial treatment for 195 patients, 77% of whom had a documented radiological response with a complete response in 24%. Chemotherapy regimes evolved during the study period with the increasing use of platinum-based chemotherapy. Anthracycline-based chemotherapy was most used before 2004 and was given to 57% of all patients. 42% received consolidation thoracic radiotherapy and 24% prophylactic cranial irradiation. The median and 2-year survival were 8 months and 18%, respectively, for patients with limited disease and 5 months and 5%, respectively, for extensive disease. Conclusion. We have documented changes in treatment practice and service delivery of SCLC over the 8 years during which the MDT has been operating. However, there has not achieve any significant improvement in outcome for the population of patients with SCLC

Long-Term Stability of n-Alkane-in-Water Pickering Nanoemulsions: Effect of Aqueous Solubility of Droplet Phase on Ostwald Ripening

High-pressure microfluidization is used to prepare a series of oil-in-water Pickering nanoemulsions using sterically-stabilized diblock copolymer nanoparticles as the Pickering emulsifier. The droplet phase comprised either n-octane, n-decane, n-dodecane, or n-tetradecane. This series of oils enabled the effect of aqueous solubility on Ostwald ripening to be studied, which is the primary instability mechanism for such nanoemulsions. Analytical centrifugation (LUMiSizer instrument) was used to evaluate the long-term stability of these Pickering nanoemulsions over time scales of weeks/months. This technique enables convenient quantification of the fraction of growing oil droplets and confirmed that using n-octane (aqueous solubility = 0.66 mg dm–3 at 20 °C) leads to instability even over relatively short time periods. However, using n-tetradecane (aqueous solubility = 0.386 μg dm–3 at 20 °C) leads to significantly improved long-term stability with respect to Ostwald ripening, with all droplets remaining below 1 μm diameter after 6 weeks storage at 20 °C. In the case of n-dodecane, the long-term stability of these new copolymer-stabilized Pickering nanoemulsions is significantly better than the silica-stabilized Pickering nanoemulsions reported in the literature by Persson et al. (Colloids Surf., A,2014,459, 48–57). This is attributed to a much greater interfacial yield stress for the former system, as recently described in the literature (see P. J. Betramo et al. Proc. Natl. Acad. Sci. U.S.A.,2017,114, 10373–10378)

Prognostic value and functional consequences of cell cycle inhibitor p27Kip1 loss in medulloblastoma

BACKGROUND: The cyclin-dependent kinase inhibitor p27(Kip1) functions during normal cerebellar development and has demonstrated tumor suppressor functions in mouse models of medulloblastoma. Because P27 loss is associated with increased proliferation, we assessed whether P27 absence in surgical medulloblastoma specimens correlated with response to therapy in pediatric patients enrolled in two large studies. Additionally, we examined the functional consequence of p27(Kip1) loss in the SmoA1 medulloblastoma model to distinguish whether p27(Kip1) reduces tumor initiation or slows tumor progression. FINDINGS: Analysis of 87 well-characterized patient samples identified a threshold of P27 staining at which significant P27 loss correlated with poor patient outcome. The same criteria, applied to a second test set of tissues from 141 patients showed no difference in survival between patients with minimal P27 staining and others, suggesting that P27 levels alone are not a sufficient prognostic indicator for identifying standard-risk patients that may fail standard therapy. These findings were in contrast to prior experiments completed using a mouse medulloblastoma model. Analysis of cerebellar tumor incidence in compound mutant mice carrying the activated Smoothened (SmoA1) allele that were heterozygous or nullizygous for p27(Kip1) revealed that p27(Kip1) loss did not alter the frequency of tumor initiation. Tumors haploinsufficient or nullizygous for p27(Kip1) were, however, more invasive and displayed a higher proliferative index, suggesting p27(Kip1) loss may contribute to SmoA1 medulloblastoma progression. CONCLUSIONS: These studies revealed P27 loss affects medulloblastoma progression rather than initiation and that this putative biomarker should not be used for stratifying children with medulloblastoma to risk-based therapeutic regimens

Underdiagnosis of mild cognitive impairment: A consequence of ignoring practice effects

INTRODUCTION: Longitudinal testing is necessary to accurately measure cognitive change. However, repeated testing is susceptible to practice effects, which may obscure true cognitive decline and delay detection of mild cognitive impairment (MCI). METHODS: We retested 995 late-middle-aged men in a ∼6-year follow-up of the Vietnam Era Twin Study of Aging. In addition, 170 age-matched replacements were tested for the first time at study wave 2. Group differences were used to calculate practice effects after controlling for attrition effects. MCI diagnoses were generated from practice-adjusted scores. RESULTS: There were significant practice effects on most cognitive domains. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%. Importantly, practice effects were present although there were declines in uncorrected scores. DISCUSSION: Accounting for practice effects is critical to early detection of MCI. Declines, when lower than expected, can still indicate practice effects. Replacement participants are needed for accurately assessing disease progression.Published versio

Synthesis, Characterization, and Pickering Emulsifier Performance of Anisotropic Cross-Linked Block Copolymer Worms: Effect of Aspect Ratio on Emulsion Stability in the Presence of Surfactant

Reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization is used to prepare epoxy-functional PGMA–P(HPMA-stat-GlyMA) diblock copolymer worms, where GMA, HPMA, and GlyMA denote glycerol monomethacrylate, 2-hydroxypropyl methacrylate, and glycidyl methacrylate, respectively. The epoxy groups on the GlyMA residues were ring-opened using 3-aminopropyltriethoxysilane (APTES) in order to cross-link the worm cores via a series of hydrolysis–condensation reactions. Importantly, the worm aspect ratio can be adjusted depending on the precise conditions selected for covalent stabilization. Relatively long cross-linked worms are obtained by reaction with APTES at 20 °C, whereas much shorter worms with essentially the same copolymer composition are formed by cooling the linear worms from 20 to 4 °C prior to APTES addition. Small-angle X-ray scattering (SAXS) studies confirmed that the mean aspect ratio for the long worms is approximately eight times greater than that for the short worms. Aqueous electrophoresis studies indicated that both types of cross-linked worms acquired weak cationic surface charge at low pH as a result of protonation of APTES-derived secondary amine groups within the nanoparticle cores. These cross-linked worms were evaluated as emulsifiers for the stabilization of n-dodecane-in-water emulsions via high-shear homogenization at 20 °C and pH 8. Increasing the copolymer concentration led to a reduction in mean droplet diameter, indicating that APTES cross-linking was sufficient to allow the nanoparticles to adsorb intact at the oil/water interface and hence produce genuine Pickering emulsions, rather than undergo in situ dissociation to form surface-active diblock copolymer chains. In surfactant challenge studies, the relatively long worms required a thirty-fold higher concentration of a nonionic surfactant (Tween 80) to be displaced from the n-dodecane–water interface compared to the short worms. This suggests that the former nanoparticles are much more strongly adsorbed than the latter, indicating that significantly greater Pickering emulsion stability can be achieved by using highly anisotropic worms. In contrast, colloidosomes prepared by reacting the hydroxyl-functional adsorbed worms with an oil-soluble polymeric diisocyanate remained intact when exposed to high concentrations of Tween 80

4D In-Situ Microscopy of Aerosol Filtration in a Wall Flow Filter

The transient nature of the internal pore structure of particulate wall flow filters, caused by the continuous deposition of particulate matter, makes studying their flow and filtration characteristics challenging. In this article we present a new methodology and first experimental demonstration of time resolved in-situ synchrotron micro X-ray computed tomography (micro-CT) to study aerosol filtration. We directly imaged in 4D (3D plus time) pore scale deposits of TiO2 nanoparticles (nominal mean primary diameter of 25 nm) with a pixel resolution of 1.6 μm. We obtained 3D tomograms at a rate of ∼1 per minute. The combined spatial and temporal resolution allows us to observe pore blocking and filling phenomena as they occur in the filter’s pore space. We quantified the reduction in filter porosity over time, from an initial porosity of 0.60 to a final porosity of 0.56 after 20 min. Furthermore, the penetration depth of particulate deposits and filtration rate was quantified. This novel image-based method offers valuable and statistically relevant insights into how the pore structure and function evolves during particulate filtration. Our data set will allow validation of simulations of automotive wall flow filters. Evolutions of this experimental design have potential for the study of a wide range of dry aerosol filters and could be directly applied to catalysed automotive wall flow filters

In Situ Small-Angle X-ray Scattering Studies During Reversible Addition–Fragmentation Chain Transfer Aqueous Emulsion Polymerization

Polymerization-induced self-assembly (PISA) is a powerful platform technology for the rational and efficient synthesis of a wide range of block copolymer nano-objects (e.g., spheres, worms or vesicles) in various media. In situ small-angle X-ray scattering (SAXS) studies of reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization have previously provided detailed structural information during self-assembly (see M. J. Derry et al., Chem. Sci. 2016, 7, 5078–5090). However, conducting the analogous in situ SAXS studies during RAFT aqueous emulsion polymerizations poses a formidable technical challenge because the inherently heterogeneous nature of such PISA formulations requires efficient stirring to generate sufficiently small monomer droplets. In the present study, the RAFT aqueous emulsion polymerization of 2-methoxyethyl methacrylate (MOEMA) has been explored for the first time. Chain extension of a relatively short non-ionic poly(glycerol monomethacrylate) (PGMA) precursor block leads to the formation of sterically-stabilized PGMA-PMOEMA spheres, worms or vesicles, depending on the precise reaction conditions. Construction of a suitable phase diagram enables each of these three morphologies to be reproducibly targeted at copolymer concentrations ranging from 10 to 30% w/w solids. High MOEMA conversions are achieved within 2 h at 70 °C, which makes this new PISA formulation well-suited for in situ SAXS studies using a new reaction cell. This bespoke cell enables efficient stirring and hence allows in situ monitoring during RAFT emulsion polymerization for the first time. For example, the onset of micellization and subsequent evolution in particle size can be studied when preparing PGMA29-PMOEMA30 spheres at 10% w/w solids. When targeting PGMA29-PMOEMA70 vesicles under the same conditions, both the micellar nucleation event and the subsequent evolution in the diblock copolymer morphology from spheres to worms to vesicles are observed. These new insights significantly enhance our understanding of the PISA mechanism during RAFT aqueous emulsion polymerization

Mediators of the Effect of Childhood Socioeconomic Status on Late Midlife Cognitive Abilities : A Four Decade Longitudinal Study

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