Multimodality local ablative therapy of 23 lung metastases with surgical resection and percutaneous cryoablation in a patient with Li-Fraumeni Syndrome: A case report

Patients with Li-Fraumeni syndrome (LFS) are prone to develop a variety of malignancies due to insufficient activity of the encoded tumor suppressor protein P53, including adrenocortical carcinoma, breast cancer, lung cancer, pancreatic cancer, and sarcoma. In the setting of LFS, local treatment options for lung metastases are limited to surgery and thermal ablation since radiotherapy and some systemic therapies predispose patients to additional future malignancies. We present the case of a 45-year-old woman with LFS with leiomyosarcoma metastases to both lungs who underwent bilateral wedge resections to treat a total of eight lung metastases followed by six percutaneous cryoablation sessions to treat 15 additional lung metastases over a period of 24 months. Our case demonstrates the option of multimodal local ablative therapies for lung metastases in patients with LFS, including percutaneous cryoablation

The Proteomics Identifications database: 2010 update

The Proteomics Identifications database (PRIDE, http://www.ebi.ac.uk/pride) at the European Bioinformatics Institute has become one of the main repositories of mass spectrometry-derived proteomics data. For the last 2 years, PRIDE data holdings have grown substantially, comprising 60 different species, more than 2.5 million protein identifications, 11.5 million peptides and over 50 million spectra by September 2009. We here describe several new and improved features in PRIDE, including the revised submission process, which now includes direct submission of fragment ion annotations. Correspondingly, it is now possible to visualize spectrum fragmentation annotations on tandem mass spectra, a key feature for compliance with journal data submission requirements. We also describe recent developments in the PRIDE BioMart interface, which now allows integrative queries that can join PRIDE data to a growing number of biological resources such as Reactome, Ensembl, InterPro and UniProt. This ability to perform extremely powerful across-domain queries will certainly be a cornerstone of future bioinformatics analyses. Finally, we highlight the importance of data sharing in the proteomics field, and the corresponding integration of PRIDE with other databases in the ProteomExchange consortium.European Union (ProDaC grant LSHG-CT-2006-036814)Burroughs Wellcome Fund (Grant WT085949MA

The Next Generation Virgo Cluster Survey. IX. Estimating the Efficiency of Galaxy Formation on the Lowest-Mass Scales

The Next Generation Virgo Cluster Survey has recently determined the luminosity function of galaxies in the core of the Virgo cluster down to unprecedented magnitude and surface brightness limits. Comparing simulations of cluster formation to the derived central stellar mass function, we attempt to estimate the stellar-to-halo-mass ratio (SHMR) for dwarf galaxies, as it would have been before they fell into the cluster. This approach ignores several details and complications, e.g., the contribution of ongoing star formation to the present-day stellar mass of cluster members, and the effects of adiabatic contraction and/or violent feedback on the subhalo and cluster potentials. The final results are startlingly simple, however; we find that the trends in the SHMR determined previously for bright galaxies appear to extend down in a scale-invariant way to the faintest objects detected in the survey. These results extend measurements of the formation efficiency of field galaxies by two decades in halo mass, or five decades in stellar mass, down to some of the least massive dwarf galaxies known, with stellar masses of $\sim 10^5 M_\odot$.Comment: 18 pages, 12 figures; published in ApJ July 1st 201

The draft genome and transcriptome of Cannabis sativa

Background: Cannabis sativa has been cultivated throughout human history as a source of fiber, oil and food, and for its medicinal and intoxicating properties. Selective breeding has produced cannabis plants for specific uses, including high-potency marijuana strains and hemp cultivars for fiber and seed production. The molecular biology underlying cannabinoid biosynthesis and other traits of interest is largely unexplored. Results: We sequenced genomic DNA and RNA from the marijuana strain Purple Kush using shortread approaches. We report a draft haploid genome sequence of 534 Mb and a transcriptome of 30,000 genes. Comparison of the transcriptome of Purple Kush with that of the hemp cultivar 'Finola' revealed that many genes encoding proteins involved in cannabinoid and precursor pathways are more highly expressed in Purple Kush than in 'Finola'. The exclusive occurrence of \u3949-tetrahydrocannabinolic acid synthase in the Purple Kush transcriptome, and its replacement by cannabidiolic acid synthase in 'Finola', may explain why the psychoactive cannabinoid \u3949-tetrahydrocannabinol (THC) is produced in marijuana but not in hemp. Resequencing the hemp cultivars 'Finola' and 'USO-31' showed little difference in gene copy numbers of cannabinoid pathway enzymes. However, single nucleotide variant analysis uncovered a relatively high level of variation among four cannabis types, and supported a separation of marijuana and hemp. Conclusions: The availability of the Cannabis sativa genome enables the study of a multifunctional plant that occupies a unique role in human culture. Its availability will aid the development of therapeutic marijuana strains with tailored cannabinoid profiles and provide a basis for the breeding of hemp with improved agronomic characteristics.Peer reviewed: YesNRC publication: Ye

Vermont Legislators\u27 Opinions Regarding the Opioid Epidemic

Introduction • The VT General Assembly includes 180 legislators: 150 representatives and 30 senators • State legislators have substantial power to create opioid-related policies • During the 2017-18 VT legislative session 22 opioid related bills were introduced and 9 were passed • No data currently exist on how VT legislators gather information and formulate public health decisions regarding opioid policies Purpose • Examine VT legislators’ understanding of the opioid epidemic • Identify what drives legislators to draft legislation, including beliefs, priorities, and voting decisions • Inform health and human services professionals to best respond to legislators’ knowledge gaps and continuing education needshttps://scholarworks.uvm.edu/comphp_gallery/1270/thumbnail.jp

ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats

Cardiomyopathies are a heterogeneous group of myocardial disorders of mostly unknown etiology, and they occur commonly in cats. In some cats, they are well-tolerated and are associated with normal life expectancy, but in other cats they can result in congestive heart failure, arterial thromboembolism or sudden death. Cardiomyopathy classification in cats can be challenging, and in this consensus statement we outline a classification system based on cardiac structure and function (phenotype). We also introduce a staging system for cardiomyopathy that includes subdivision of cats with subclinical cardiomyopathy into those at low risk of life-threatening complications and those at higher risk. Based on the available literature, we offer recommendations for the approach to diagnosis and staging of cardiomyopathies, as well as for management at each stage

Embedding experiential learning in HE sport coaching courses: An action research study

Despite recommendations imploring coach educators to utilise experiential learning, analyses of how this has been implemented are sparse. This study analyses the integration of experiential learning within a UK Higher Education Institution (HEI) context. Student coaches were provided with coaching opportunities with local school-children. Data were collected over three years through student interviews, coach educator reflections and discussions with a critical friend. Experiential learning presented two key challenges; 1) dealing with difficult emotions and competence awareness by students and the coach educator; 2) ensuring children received appropriate coaching practice. The integration of mediated pedagogical strategies helped overcome these problems

The InfraRed Imaging Spectrograph (IRIS) for TMT: latest science cases and simulations

The Thirty Meter Telescope (TMT) first light instrument IRIS (Infrared Imaging Spectrograph) will complete its preliminary design phase in 2016. The IRIS instrument design includes a near-infrared (0.85 - 2.4 micron) integral field spectrograph (IFS) and imager that are able to conduct simultaneous diffraction-limited observations behind the advanced adaptive optics system NFIRAOS. The IRIS science cases have continued to be developed and new science studies have been investigated to aid in technical performance and design requirements. In this development phase, the IRIS science team has paid particular attention to the selection of filters, gratings, sensitivities of the entire system, and science cases that will benefit from the parallel mode of the IFS and imaging camera. We present new science cases for IRIS using the latest end-to-end data simulator on the following topics: Solar System bodies, the Galactic center, active galactic nuclei (AGN), and distant gravitationally-lensed galaxies. We then briefly discuss the necessity of an advanced data management system and data reduction pipeline.Comment: 15 pages, 7 figures, SPIE (2016) 9909-0

A Next-generation Marker Genotyping Platform (AmpSeq) in Heterozygous Crops: A Case Study for Marker-assisted Selection in Grapevine

Marker-assisted selection (MAS) is often employed in crop breeding programs to accelerate and enhance cultivar development, via selection during the juvenile phase and parental selection prior to crossing. Next-generation sequencing and its derivative technologies have been used for genome-wide molecular marker discovery. To bridge the gap between marker development and MAS implementation, this study developed a novel practical strategy with a semi-automated pipeline that incorporates traitassociated single nucleotide polymorphism marker discovery, low-cost genotyping through amplicon sequencing (AmpSeq) and decision making. The results document the development of a MAS package derived from genotyping-by-sequencing using three traits (flower sex, disease resistance and acylated anthocyanins) in grapevine breeding. The vast majority of sequence reads ( ⩾99%) were from the targeted regions. Across 380 individuals and up to 31 amplicons sequenced in each lane of MiSeq data, most amplicons (83 to 87%) had o10% missing data, and read depth had a median of 220–244 × . Several strengths of the AmpSeq platform that make this approach of broad interest in diverse crop species include accuracy, flexibility, speed, high-throughput, lowcost and easily automated analysis

Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule.

Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications compared to single agents, albeit with increased toxicity. Leveraging the observation that PD-1 and CTLA-4 are co-expressed by tumor-infiltrating lymphocytes, an investigational PD-1 x CTLA-4 bispecific DART molecule, MGD019, is engineered to maximize checkpoint blockade in the tumor microenvironment via enhanced CTLA-4 blockade in a PD-1-binding-dependent manner