Investigating the Morphological and Genetic Divergence of Arctic Char \u3ci\u3e(Salvelinus alpinus)\u3c/i\u3e Populations in Lakes of Arctic Alaska

Polymorphism facilitates coexistence of divergent morphs (e.g., phenotypes) of the same species by minimizing intraspecific competition, especially when resources are limiting. Arctic char (Salvelinus sp.) are a Holarctic fish often forming morphologically, and sometimes genetically, divergent morphs. In this study, we assessed the morphological and genetic diversity and divergence of 263 individuals from seven populations of arctic char with varying length-frequency distributions across two distinct groups of lakes in northern Alaska. Despite close geographic proximity, each lake group occurs on landscapes with different glacial ages and surface water connectivity, and thus was likely colonized by fishes at different times. Across lakes, a continuum of physical (e.g., lake area, maximum depth) and biological characteristics (e.g., primary productivity, fish density) exists, likely contributing to characteristics of present-day char populations. Although some lakes exhibit bimodal size distributions, using model-based clustering of morphometric traits corrected for allometry, we did not detect morphological differences within and across char populations. Genomic analyses using 15,934 SNPs obtained from genotyping by sequencing demonstrated differences among lake groups related to historical biogeography, but within lake groups and within individual lakes, genetic differentiation was not related to total body length. We used PERMANOVA to identify environmental and biological factors related to observed char size structure. Significant predictors included water transparency (i.e., a primary productivity proxy), char density (fish·ha-1), and lake group. Larger char occurred in lakes with greater primary production and lower char densities, suggesting less intraspecific competition and resource limitation. Thus, char populations in more productive and connected lakes may prove more stable to environmental changes, relative to food-limited and closed lakes, if lake productivity increases concomitantly. Our findings provide some of the first descriptions of genomic characteristics of char populations in arctic Alaska, and offer important consideration for the persistence of these populations for subsistence and conservation

COEXISTING PROSTATE CANCER FOUND AT THE TIME OF HOLMIUM LASER ENUCLEATION OF THE PROSTATE FOR BENIGN PROSTATIC HYPERPLASIA: PREDICTING ITS PRESENCE AND GRADE IN ANALYZED TISSUE

Objective: To determine the incidence of prostate cancer identified on holmium laser enucleation of the prostate (HoLEP) specimens and evaluate variables associated with prostate cancer identification. Patients and Methods: All patients undergoing HoLEP between 1998 and 2013 were identified. Patients with a known history of prostate cancer were excluded. Multivariable logistic regression assessed variables associated with identification of prostate cancer on HoLEP specimens and Gleason 7 or higher prostate cancer among the malignant cases. The Gleason grade was used as a proxy for disease severity. Each of the models was adjusted for age, preoperative prostate-specific antigen (PSA), and HoLEP specimen weight. Results: The cohort comprised 1272 patients, of whom 103 (8.1%) had prostate cancer identified. Prostate cancer cases had higher pre-HoLEP PSA (p=0.06) but lower HoLEP specimen weight (p=0.01). On multivariate logistic regression, age and preoperative PSA were associated with increased odds of prostate cancer being present (p<0.01 each), while increasing HoLEP specimen weight was associated with decreased odds of prostate cancer (p<0.001). Men older than 80 had 20% predicted probability of being diagnosed with prostate cancer. Seventy-eight percent of prostate cancer cases were Gleason 6 or less. The pre-HoLEP PSA was associated with increased adjusted odds of intermediate- or high-grade prostate cancer. Conclusion: Prostate cancer identified by HoLEP is not uncommon, but is generally a low-risk disease. Older patients with smaller prostate glands have the highest odds of prostate cancer identification

Shock wave lithotripsy targeting of the kidney and pancreas does not increase the severity of metabolic syndrome in a porcine model

PURPOSE: We determined whether shock wave lithotripsy of the kidney of pigs with metabolic syndrome would worsen glucose tolerance or increase the risk of diabetes mellitus. MATERIALS AND METHODS: Nine-month-old female Ossabaw miniature pigs were fed a hypercaloric atherogenic diet to induce metabolic syndrome. At age 15 months the pigs were treated with 2,000 or 4,000 shock waves (24 kV at 120 shock waves per minute) using an unmodified HM3 lithotripter (Dornier MedTech, Kennesaw, Georgia). Shock waves were targeted to the left kidney upper pole calyx to model treatment that would also expose the pancreatic tail to shock waves. The intravenous glucose tolerance test was done in conscious fasting pigs before lithotripsy, and 1 and 2 months after lithotripsy with blood samples taken for glucose and insulin measurement. RESULTS: Pigs fed the hypercaloric atherogenic diet were obese, dyslipidemic, insulin resistant and glucose intolerant, consistent with metabolic syndrome. Assessments of insulin resistance, glucose tolerance and pancreatic β cell function from fasting plasma glucose and insulin levels, and the glucose and insulin response profile to the intravenous glucose tolerance test were similar before and after lithotripsy. CONCLUSIONS: The metabolic syndrome status of pigs treated with shock wave lithotripsy was unchanged 2 months after kidney treatment with 2,000 high amplitude shock waves or overtreatment with 4,000 high amplitude shock waves. These findings do not support a single shock wave lithotripsy treatment of the kidney as a risk factor for the onset of diabetes mellitus

Distribution of Hyperpolarized Xenon in the Brain Following Sensory Stimulation: Preliminary MRI Findings

In hyperpolarized xenon magnetic resonance imaging (HP 129Xe MRI), the inhaled spin-1/2 isotope of xenon gas is used to generate the MR signal. Because hyperpolarized xenon is an MR signal source with properties very different from those generated from water-protons, HP 129Xe MRI may yield structural and functional information not detectable by conventional proton-based MRI methods. Here we demonstrate the differential distribution of HP 129Xe in the cerebral cortex of the rat following a pain stimulus evoked in the animal's forepaw. Areas of higher HP 129Xe signal corresponded to those areas previously demonstrated by conventional functional MRI (fMRI) methods as being activated by a forepaw pain stimulus. The percent increase in HP 129Xe signal over baseline was 13–28%, and was detectable with a single set of pre and post stimulus images. Recent innovations in the production of highly polarized 129Xe should make feasible the emergence of HP 129Xe MRI as a viable adjunct method to conventional MRI for the study of brain function and disease

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Robotic approach to Giant multiloculated cystadenoma of the prostate: Initial experience

Giant multiloculated cystadenoma of the prostate (GMPC) is a rare, massive and benign tumor. Recurrence rates after resection are low but have been recorded. An open approach is most common, with few laparoscopic and no robotic cases reported. We report on a case of a 65-year-old man with a new presentation of a 400 cc cystic prostatic mass thought to be GMPC. This patient underwent what is, to our knowledge, the first reported case of RARP in the treatment of GMPC. A robotic approach to massive GMPC was safe and efficacious in our initial experience

A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations

Background: For children with cancer, the clinical integration of precision medicine to enable predictive biomarkerebased therapeutic stratification is urgently needed. Methods: We have developed a hybrid-capture next-generation sequencing (NGS) panel, specifically designed to detect genetic alterations in paediatric solid tumours, which gives reliable results from as little as 50 ng of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. In this study, we offered an NGS panel, with clinical reporting via a molecular tumour board for children with solid tumours. Furthermore, for a cohort of 12 patients, we used a circulating tumour DNA (ctDNA)especific panel to sequence ctDNA from matched plasma samples and compared plasma and tumour findings. Results: A total of 255 samples were submitted from 223 patients for the NGS panel. Using FFPE tissue, 82% of all submitted samples passed quality control for clinical reporting. At least one genetic alteration was detected in 70% of sequenced samples. The overall detection rate of clinically actionable alterations, defined by modified OncoKB criteria, for all sequenced samples was 51%. A total of 8 patients were sequenced at different stages of treatment. In 6 of these, there were differences in the genetic alterations detected between time points. Sequencing of matched ctDNA in a cohort of extracranial paediatric solid tumours also identified a high detection rate of somatic alterations in plasma. Conclusion: We demonstrate that tailored clinical molecular profiling of both tumour DNA and plasma-derived ctDNA is feasible for children with solid tumours. Furthermore, we show that a targeted NGS panelebased approach can identify actionable genetic alterations in a high proportion of patients.This work was supported by Christopher’s Smile, the National Institute of Health Research (NIHR) Royal Marsden Biomedical Research Centre (BRC), Children With Cancer UK (CWC UK) Cancer Research UK (CRUK), Abbie’s Fund, the Rosetree Trust and the KiCa Fund, managed by the King Baudouin Foundation. Roche provided support for Panel development. T.S.J. is funded by The Brain Tumour Charity, CWC UK, GOSH Children’s Charity (GOSH CC), CRUK, the Olivia Hodson Cancer Fund and the NIHR GOSH BRC. J.A. and D.H. are funded by the GOSH CC and NIHR GOSH BRC. L.V.M. is funded by the Oak Foundation. The authors thank all participants and the CCLG Tissue Bank for access to samples and contributing CCLG Centres, including members of the ECMC Paediatric network. The CCLG Tissue Bank is funded by Cancer Research UK and CCL