Effects of watershed land use on nitrogen concentrations and δ15 Nitrogen in groundwater

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Biogeochemistry 77 (2006): 199-215, doi:10.1007/s10533-005-1036-2.Eutrophication is a major agent of change affecting freshwater, estuarine, and marine systems. It is largely driven by transportation of nitrogen from natural and anthropogenic sources. Research is needed to quantify this nitrogen delivery and to link the delivery to specific land-derived sources. In this study we measured nitrogen concentrations and δ15N values in seepage water entering three freshwater ponds and six estuaries on Cape Cod, Massachusetts and assessed how they varied with different types of land use. Nitrate concentrations and δ15N values in groundwater reflected land use in developed and pristine watersheds. In particular, watersheds with larger populations delivered larger nitrate loads with higher δ15N values to receiving waters. The enriched δ15N values confirmed nitrogen loading model results identifying wastewater contributions from septic tanks as the major N source. Furthermore, it was apparent that N coastal sources had a relatively larger impact on the N loads and isotopic signatures than did inland N sources further upstream in the watersheds. This finding suggests that management priorities could focus on coastal sources as a first course of action. This would require management constraints on a much smaller population.This work was supported by funds from the Woods Hole Oceanographic Institution Sea Grant Program, from the Cooperative Institute for Coastal and Estuarine Environmental Technology, from Massachusetts Department of Environmental Protection to Applied Science Associates, Narragansett, RI, as well as from Palmer/McLeod and NOAA National Estuarine Research Reserve Fellowships to Kevin Kroeger. This work is the result of research sponsored by NOAA National Sea Grant College Program Office, Department of Commerce, under Grant No. NA86RG0075, Woods Hole Oceanographic Institution Sea Grant Project No. R/M-40

The SPTPoL extended cluster survey

We describe the observations and resultant galaxy cluster catalog from the 2770 deg2 SPTpol Extended Cluster Survey (SPT-ECS). Clusters are identified via the Sunyaev-Zel'dovich (SZ) effect and confirmed with a combination of archival and targeted follow-up data, making particular use of data from the Dark Energy Survey (DES). With incomplete follow-up we have confirmed as clusters 244 of 266 candidates at a detection significance ξ ≥ 5 and an additional 204 systems at 4 4 threshold, and 10% of their measured SZ flux. We associate SZ-selected clusters, from both SPT-ECS and the SPT-SZ survey, with clusters from the DES redMaPPer sample, and we find an offset distribution between the SZ center and central galaxy in general agreement with previous work, though with a larger fraction of clusters with significant offsets. Adopting a fixed Planck-like cosmology, we measure the optical richness-SZ mass (l - M) relation and find it to be 28% shallower than that from a weak-lensing analysis of the DES data-a difference significant at the 4σ level-with the relations intersecting at λ = 60. The SPT-ECS cluster sample will be particularly useful for studying the evolution of massive clusters and, in combination with DES lensing observations and the SPT-SZ cluster sample, will be an important component of future cosmological analyses

Warts and all: Fingolimod and unusual HPV-associated lesions

Background: Fingolimod is used to reduce relapse rates in relapsing-remitting multiple sclerosis (MS). It is a sphingosine 1-phosphate (S1P) analogue having antagonistic effects on S1P receptors. Its immunosuppressive effect is due to reduced circulating lymphocyte numbers, and it may also be associated with impaired intrinsic cancer surveillance. Fingolimod side effects include increased rates and severity of viral infections particularly varicella zoster. Methods: We present five cases of chronic and treatment refractory warts associated with fingolimod therapy. Results: Each of the five cases presenting with chronic warts while receiving fingolimod therapy had prolonged periods of lymphopenia and improvements were seen following dose reduction or cessation of fingolimod. Conclusion: Cutaneous warts are associated with human papilloma virus (HPV) infection, suggesting an increased risk of other HPV-driven conditions such as cervical cancer following fingolimod administration. HPV viruses are responsible for approximately 90% of cervical cancers as well as a significant portion of anogenital cancers and have a high prevalence in sexually active adults. Given the reduced immune response to viral infections and potential impaired cancer surveillance in those receiving fingolimod, HPV vaccination and frequent assessment for the development of HPV-associated malignancies are recommended

Use of whole-exome sequencing for diagnosis of Limb-Girdle muscular dystrophy

Importance To our knowledge, the efficacy of transferring next-generation sequencing from a research setting to neuromuscular clinics has never been evaluated. Objective To translate whole-exome sequencing (WES) to clinical practice for the genetic diagnosis of a large cohort of patients with limb-girdle muscular dystrophy (LGMD) for whom protein-based analyses and targeted Sanger sequencing failed to identify the genetic cause of their disorder. Design, Setting, and Participants We performed WES on 60 families with LGMDs (100 exomes). Data analysis was performed between January 6 and December 19, 2014, using the xBrowse bioinformatics interface (Broad Institute). Patients with LGMD were ascertained retrospectively through the Institute for Neuroscience and Muscle Research Biospecimen Bank between 2006 and 2014. Enrolled patients had been extensively investigated via protein studies and candidate gene sequencing and remained undiagnosed. Patients presented with more than 2 years of muscle weakness and with dystrophic or myopathic changes present in muscle biopsy specimens. Main Outcomes and Measures The diagnostic rate of LGMD in Australia and the relative frequencies of the different LGMD subtypes. Our central goals were to improve the genetic diagnosis of LGMD, investigate whether the WES platform provides adequate coverage of known LGMD-related genes, and identify new LGMD-related genes. Results With WES, we identified likely pathogenic mutations in known myopathy genes for 27 of 60 families. Twelve families had mutations in known LGMD-related genes. However, 15 families had variants in disease-related genes not typically associated with LGMD, highlighting the clinical overlap between LGMD and other myopathies. Common causes of phenotypic overlap were due to mutations in congenital muscular dystrophy–related genes (4 families) and collagen myopathy–related genes (4 families). Less common myopathies included metabolic myopathy (2 families), congenital myasthenic syndrome (DOK7), congenital myopathy (ACTA1), tubular aggregate myopathy (STIM1), myofibrillar myopathy (FLNC), and mutation of CHD7, usually associated with the CHARGE syndrome. Inclusion of family members increased the diagnostic efficacy of WES, with a diagnostic rate of 60% for “trios” (an affected proband with both parents) vs 40% for single probands. A follow-up screening of patients whose conditions were undiagnosed on a targeted neuromuscular disease–related gene panel did not improve our diagnostic yield. Conclusions and Relevance With WES, we achieved a diagnostic success rate of 45.0% in our difficult-to-diagnose cohort of patients with LGMD. We expand the clinical phenotypes associated with known myopathy genes, and we stress the importance of accurate clinical examination and histopathological results for interpretation of WES, with many diagnoses requiring follow-up review and ancillary investigations of biopsy specimens or serum samples