Differential Protein Expression in Small Intestinal Neuroendocrine Tumors and Liver Metastases

OBJECTIVE: Small intestinal neuroendocrine tumors (SI-NETs) are often detected after they have become metastatic. Using a novel protein array, we identified pathways important in SI-NET metastasis development in surgically resected patients. METHODS: Paired primary tumors and liver metastases from 25 patients undergoing surgical resection for metastatic SI-NETs were harvested. Extracted proteins were separated by sodium dodecyl sulfate gel and multiplex immunoblots were performed with 136 antibodies. Significant Analysis of Microarray was used to select for differentially expressed proteins. A tissue microarray was constructed from 27 archived specimens and stained by immunohistochemistry. RESULTS: Comparing primary SI-NETs with matched normal small-bowel mucosa, 9 proteins were upregulated and cyclin E was downregulated. The SI-NET liver metastases demonstrated upregulation of P-ERK and p27 but downregulation of CDK2 and CDC25B. When comparing primary SI-NET with their paired liver metastases, cyclin E demonstrated a significant upregulation in the liver metastasis. Tissue microarray demonstrated higher p38 expression and lower Cdc 25b expression in SI-NETs versus liver metastases and confirmed higher expression of p27 in liver metastases versus normal liver. CONCLUSIONS: Few studies have compared protein expression in paired primary and metastatic SI-NETs. Our findings reveal changes in a limited number of proteins, suggesting that these may be targets for therapy

Clinically Significant Gains in Skillful Grasp Coordination by an Individual With Tetraplegia Using an Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation

© 2019 American Congress of Rehabilitation Medicine Objective: To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic. Design: Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478. Setting: Tertiary care outpatient rehabilitation center. Participant: A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury Interventions: After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control dynamic, coordinated forearm, wrist, and hand movements. Main Outcome Measures: Performance on standardized tests of arm motor ability (Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP], Action Research Arm Test [ARAT], Grasp and Release Test [GRT], Box and Block Test), grip myometry, and functional activity measures (Capabilities of Upper Extremity Test [CUE-T], Quadriplegia Index of Function-Short Form [QIF-SF], Spinal Cord Independence Measure–Self-Report [SCIM-SR]) with and without the BCI-FES. Results: With BCI-FES, scores improved from baseline on the following: Grip force (2.9 kg); ARAT cup, cylinders, ball, bar, and blocks; GRT can, fork, peg, weight, and tape; GRASSP strength and prehension (unscrewing lids, pouring from a bottle, transferring pegs); and CUE-T wrist and hand skills. QIF-SF and SCIM-SR eating, grooming, and toileting activities were expected to improve with home use of BCI-FES. Pincer grips and mobility were unaffected. BCI-FES grip skills enabled the participant to play an adapted “Battleship” game and manipulate household objects. Conclusions: Using BCI-FES, the participant performed skillful and coordinated grasps and made clinically significant gains in tests of upper limb function. Practice generalized from training objects to household items and leisure activities. Motor ability improved for palmar, lateral, and tip-to-tip grips. The expects eventual home use to confer greater independence for activities of daily living, consistent with observed neurologic level gains from C5-6 to C7-T1. This marks a critical translational step toward clinical viability for BCI neuroprosthetics

Personal preferences for Personalised Trials among patients with chronic diseases: an empirical Bayesian analysis of a conjoint survey.

OBJECTIVE: To describe individual patient preferences for Personalised Trials and to identify factors and conditions associated with patient preferences. DESIGN: Each participant was presented with 18 conjoint questions via an online survey. Each question provided two choices of Personalised Trials that were defined by up to eight attributes, including treatment types, clinician involvement, study logistics and trial burden on a patient. SETTING: Online survey of adults with at least two common chronic conditions in the USA. PARTICIPANTS: A nationally representative sample of 501 individuals were recruited from the Chronic Illness Panel by Harris Poll Online. Participants were recruited from several sources, including emails, social media and telephone recruitment of the target population. MAIN OUTCOME MEASURES: The choice of Personalised Trial design that the participant preferred with each conjoint question. RESULTS: There was large variability in participants\u27 preferences for the design of Personalised Trials. On average, they preferred certain attributes, such as a short time commitment and no cost. Notably, a population-level analysis correctly predicted 62% of the conjoint responses. An empirical Bayesian analysis of the conjoint data, which supported the estimation of individual-level preferences, improved the accuracy to 86%. Based on estimates of individual-level preferences, patients with chronic pain preferred a long study duration (p≤0.001). Asthma patients were less averse to participation burden in terms of data-collection frequency than patients with other conditions (p=0.002). Patients with hypertension were more cost-sensitive (p\u3c0.001). CONCLUSION: These analyses provide a framework for elucidating individual-level preferences when implementing novel patient-centred interventions. The data showed that patient preference in Personalised Trials is highly variable, suggesting that individual differences must be accounted for when marketing Personalised Trials. These results have implications for advancing precise interventions in Personalised Trials by indicating when rigorous scientific principles, such as frequent monitoring, is feasible in a substantial subset of patients

Ductile Metallic Glasses in Supercooled Martensitic Alloys

We report ductile bulk metallic glasses based on martensitic alloys. The slowly cooled specimens contain a mixture of parent 'austenite' and martensite phase. The slightly faster cooled bulk metallic glasses with 2-5 nm sized 'austenite'-like crystalline cluster reveal high strength and large ductility (16%). Shear bands propagate in a slither mode in this spatially inhomogeneous glassy structure and undergo considerable 'thickening' from 5-25 nm. A 'stress induced displacive transformation' is proposed to be responsible for both plasticity and work-hardening-like behavior of these 'M-Glasses'

Spatial variability of soil salinity in Bohai Sea coastal wetlands, China: Partition into four management zones

Soil salinization constitutes an environmental hazard worldwide. The Bohai Sea coastal wetland area is experiencing dramatic soil salinization, which is affecting its economic development. This study focused on the spatial variation and distribution characteristics of soil salinity in this area using geostatistical analysis combined with the kriging interpolation method, based on a large-scale field investigation and layered soil sampling (0-30, 30-60 and 60-100cm). The results revealed that soil salinity in these layers demonstrated strong variability, obvious spatial structure characteristics and strong spatial autocorrelation. Soil salinity displayed a significant zonal distribution, gradually decreasing with increasing distance from the coastline. Apart from the northern part of the study area, which appeared to be not affected by soil salinization, there were varying degrees of soil salinization in nearly 70% of the total area. With increasing soil depth, the areas of non-salinized and mild salinized soil gradually decreased, while those of moderate salinized and strong salinized soils increased. The area of saline soil first decreased and then increased. The study area could be divided into four management zones according to soil salinities in the top 1-m soil body, and utilization measures, adapted to local conditions, were proposed for each zone. The results of our study present an important theoretical basis for the improvement of saline soils, for wetland re-vegetation and for the sustainable utilization of soil resources in the Bohai Sea coastal wetland.Soil salinization constitutes an environmental hazard worldwide. The Bohai Sea coastal wetland area is experiencing dramatic soil salinization, which is affecting its economic development. This study focused on the spatial variation and distribution characteristics of soil salinity in this area using geostatistical analysis combined with the kriging interpolation method, based on a large-scale field investigation and layered soil sampling (0-30, 30-60 and 60-100cm). The results revealed that soil salinity in these layers demonstrated strong variability, obvious spatial structure characteristics and strong spatial autocorrelation. Soil salinity displayed a significant zonal distribution, gradually decreasing with increasing distance from the coastline. Apart from the northern part of the study area, which appeared to be not affected by soil salinization, there were varying degrees of soil salinization in nearly 70% of the total area. With increasing soil depth, the areas of non-salinized and mild salinized soil gradually decreased, while those of moderate salinized and strong salinized soils increased. The area of saline soil first decreased and then increased. The study area could be divided into four management zones according to soil salinities in the top 1-m soil body, and utilization measures, adapted to local conditions, were proposed for each zone. The results of our study present an important theoretical basis for the improvement of saline soils, for wetland re-vegetation and for the sustainable utilization of soil resources in the Bohai Sea coastal wetland

The redmapper galaxy cluster catalog from DES Science Verification data

We describe updates to the redMaPPer algorithm, a photometric red-sequence cluster finder specifically designed for large photometric surveys. The updated algorithm is applied to 150 {{deg}}2 of Science Verification (SV) data from the Dark Energy Survey (DES), and to the Sloan Digital Sky Survey (SDSS) DR8 photometric data set. The DES SV catalog is locally volume limited and contains 786 clusters with richness lambda \gt 20 (roughly equivalent to {M}{{500c}}≳ {10}14 {h}70-1 {M}o ) and 0.2\lt z\lt 0.9. The DR8 catalog consists of 26,311 clusters with 0.08\lt z\lt 0.6, with a sharply increasing richness threshold as a function of redshift for z≳ 0.35. The photometric redshift performance of both catalogs is shown to be excellent, with photometric redshift uncertainties controlled at the {sigma }z/(1+z)~ 0.01 level for z≲ 0.7, rising to ~0.02 at z~ 0.9 in DES SV. We make use of Chandra and XMM X-ray and South Pole Telescope Sunyaev--Zeldovich data to show that the centering performance and mass--richness scatter are consistent with expectations based on prior runs of redMaPPer on SDSS data. We also show how the redMaPPer photo-z and richness estimates are relatively insensitive to imperfect star/galaxy separation and small-scale star masks

Train model acceleration and deceleration

In order to accelerate a heavy train model with great dimensions to a speed higher than 300 km h(-1) in a moving train model testing system, compressed air is utilized to drive the train model indirectly. The gas from an air gun pushes the piston in an accelerating tube forward. The piston is connected to the trailer through a rope, and the trailer pulls the train model to the desired speed. After the testing section, the train model enters the deceleration section. The speed of the train model gradually decreases because of the braking force of the magnetic braking device on the bottom of the train model and the steel plates fixed on the floor of this device. The dissipation of kinetic energy of the trailer is also based on a similar principle. The feasibility of these methods has been examined in a 180 m-long moving train model testing system. The speed of the trailer alone reaches up to 490 km h(-1). Consequently, a 34.8 kg model accelerates up to 350 km h(-1); the smooth and safe stopping of the model is also possible

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]