What is the nature and extent of evidence on methodologies for monitoring and evaluating marine spatial management measures in UK and similar coastal waters? A systematic map protocol

Background Anthropogenic degradation of marine ecosystems is widely accepted as a major social-ecological problem. The growing urgency to better manage marine ecosystems has led to the increasing application of ‘spatial management measures’ including marine protected areas, sectoral (e.g. fishery) closures, and marine spatial planning. However, the designation of varied spatial management regimes is just the first step; achievement of objectives relies upon effective implementation, monitoring, evaluation and adaptation. Despite spatial management being a core component of the marine management portfolio, to our knowledge, there is no systematic overview of the evidence on methodologies available, and employed, to monitor and evaluate their effectiveness across social, economic and ecological outcomes. Methods This systematic map will examine existing evidence describing methodologies for monitoring the effects, and evaluating the effectiveness, of marine spatial management across ecological, social and economic outcomes. Our aim is to provide a resource for decision-makers, primarily in the UK but also internationally, that supports effective marine management, and to describe the current evidence base. Identification and evaluation of relevant studies will therefore be restricted to coastal countries identified by our Stakeholder Group as being relevant to the UK, and searches will be restricted to the period 2009 to 2019 to align with the current UK policy context. Searches for relevant grey and academic literature, published in English, will be conducted in four bibliographic search engines, Google Scholar, 38 organisational websites and one specialist data repository. Eligibility screening will be conducted first at title and abstract level, and then at full text. Coding and meta-data extraction from eligible studies will include: bibliographic information, general information about the spatial management measure studied, and methodological information on the monitoring and evaluation undertaken. Consistency checking amongst reviewers will be undertaken during screening, coding and data extraction phases. The outcome of the systematic map will be a database that displays the meta-data of identified relevant studies. Findings will be presented in a descriptive report detailing the evaluation approaches and analytical methodologies employed, and data collection methods applied and/or data required by relevant studies to inform evaluations on the effectiveness of marine spatial management measures

The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake

We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms

An unbiased survey of 500 nearby stars for debris disks: A JCMT legacy program

We present the scientific motivation and observing plan for an upcoming detection survey for debris disks using the James Clerk Maxwell Telescope. The SCUBA‐2 Unbiased Nearby Stars (SUNS) survey will observe 500 nearby main‐sequence and subgiant stars (100 of each of the A, F, G, K, and M spectral classes) to the 850 μm extragalactic confusion limit to search for evidence of submillimeter excess, an indication of circumstellar material. The survey distance boundaries are 8.6, 16.5, 22, 25, and 45 pc for M, K, G, F, and A stars, respectively, and all targets lie between the declinations of −40° to 80°. In this survey, no star will be rejected based on its inherent properties: binarity, presence of planetary companions, spectral type, or age. The survey will commence in late 2007 and will be executed over 390 hr, reaching 90% completion within 2 years. This will be the first unbiased survey for debris disks since the Infrared Astronomical Satellite. We expect to detect ~125 debris disks, including ~50 cold disks not detectable in current shorter wavelength surveys. To fully exploit the order of magnitude increase in debris disks detected in the submillimeter, a substantial amount of complementary data will be required, especially at shorter wavelengths, to constrain the temperatures and masses of discovered disks. High‐resolution studies will likely be required to resolve many of the disks. Therefore, these systems will be the focus of future observational studies using a variety of observatories, including Herschel, ALMA, and JWST, to characterize their physical properties. For nondetected systems, this survey will set constraints (upper limits) on the amount of circumstellar dust, of typically 200 times the Kuiper Belt mass, but as low as 10 times the Kuiper Belt mass for the nearest stars in the sample (≈2 pc)

The nature and extent of evidence on methodologies for monitoring and evaluating marine spatial management measures in the UK and similar coastal waters : a systematic map

Background: Anthropogenic degradation of marine ecosystems is widely accepted as a major social-ecological problem. The growing urgency to manage marine ecosystems more effectively has led to increasing application of spatial management measures (marine protected areas [MPAs], sectoral [e.g. fishery] closures and marine spatial planning [marine plans]). Understanding the methodologies used to evaluate the effectiveness of these measures against social, economic, and ecological outcomes is key for designing effective monitoring and evaluation programmes. Methods: We used a pre-defined and tested search string focusing on intervention and outcome terms to search for relevant studies across four bibliographic databases, Google Scholar, 39 organisational websites, and one specialist data repository. Searches were conducted in English and restricted to the period 2009 to 2019 to align with current UK marine policy contexts. Relevant studies were restricted to UK-relevant coastal countries, as identified by key stakeholders. Search results were screened for relevance against pre-defined eligibility criteria first at title and abstract level, and then at full text. Articles assessed as not relevant at full text were recorded with reasons for exclusion. Two systematic map databases of meta-data and coded data from relevant primary and secondary studies, respectively, were produced. Review findings: Over 19,500 search results were identified, resulting in 391 relevant primary articles, 33 secondary articles and 49 tertiary reviews. Relevant primary articles evaluated spatial management measures across a total of 22 social, economic and ecological outcomes; only 2.8% considered all three disciplines, with most focused exclusively on ecological (67.8%) or social (13.3%) evaluations. Secondary articles predominately focused on ecological evaluations (75.8%). The majority of the primary and secondary evidence base aimed to evaluate the effectiveness of MPAs (85.7% and 90.9% respectively), followed by fisheries closures (12.5%; 3.0%) with only 1.8% of primary, and 6.1% of secondary, articles focused on marine plans or on MPAs and fisheries closures combined. Most evaluations reported within primary articles were conducted for a single site (60.4%) or multiple individual sites (32.5%), with few evaluating networks of sites (6.9%). Secondary articles mostly evaluated multiple individual sites (93.9%). Most (70.3%) primary articles conducted principal evaluations, i.e. basic description of effects; 29.4% explored causation; and 0.3% undertook benefit evaluations. Secondary articles predominately explored causation (66.7%) with the remainder conducting principal evaluations. Australia (27.4%), the USA (18.4%) and the UK (11.3%) were most frequently studied by primary articles, with secondary articles reporting mostly global (66.7%) or European (18.2%) syntheses. Conclusions: The systematic map reveals substantial bodies of evidence relating to methods of evaluating MPAs against ecological outcomes. However, key knowledge gaps include evaluation across social and economic outcomes and of overall merit and/or worth (benefit evaluation), as well as of: marine plans; networks of sites; real-time, temporary or seasonal closures; spatial management within offshore waters, and lagoon or estuary environments. Although the evidence base has grown over the past two decades, information to develop comprehensive evaluation frameworks remains insufficient. Greater understanding on how to evaluate the effectiveness of spatial management measures is required to support improved management of global ocean resources and spaces

Self-assembled hydrogel fibers for sensing the multi-compartment intracellular milieu

Targeted delivery of drugs and sensors into cells is an attractive technology with both medical and scientific applications. Existing delivery vehicles are generally limited by the complexity of their design, dependence on active transport, and inability to function within cellular compartments. Here, we developed self-assembled nanofibrous hydrogel fibers using a biologically inert, low-molecular-weight amphiphile. Self-assembled nanofibrous hydrogels offer unique physical/mechanical properties and can easily be loaded with a diverse range of payloads. Unlike commercially available E. coli membrane particles covalently bound to the pH reporting dye pHrodo, pHrodo encapsulated in self-assembled hydrogel-fibers internalizes into macrophages at both physiologic (37°C) and sub-physiologic (4°C) temperatures through an energy-independent, passive process. Unlike dye alone or pHrodo complexed to E. coli, pHrodo-SAFs report pH in both the cytoplasm and phagosomes, as well the nucleus. This new class of materials should be useful for next-generation sensing of the intracellular milieu

Rapid characterisation of vegetation structure to predict refugia and climate change impacts across a global biodiversity hotspot

Identification of refugia is an increasingly important adaptation strategy in conservation planning under rapid anthropogenic climate change. Granite outcrops (GOs) provide extraordinary diversity, including a wide range of taxa, vegetation types and habitats in the Southwest Australian Floristic Region (SWAFR). However, poor characterization of GOs limits the capacity of conservation planning for refugia under climate change. A novel means for the rapid identification of potential refugia is presented, based on the assessment of local-scale environment and vegetation structure in a wider region. This approach was tested on GOs across the SWAFR. Airborne discrete return Light Detection And Ranging (LiDAR) data and Red Green and Blue (RGB) imagery were acquired. Vertical vegetation profiles were used to derive 54 structural classes. Structural vegetation types were described in three areas for supervised classification of a further 13 GOs across the region.Habitat descriptions based on 494 vegetation plots on and around these GOs were used to quantify relationships between environmental variables, ground cover and canopy height. The vegetation surrounding GOs is strongly related to structural vegetation types (Kappa = 0.8) and to its spatial context. Water gaining sites around GOs are characterized by taller and denser vegetation in all areas. The strong relationship between rainfall, soil-depth, and vegetation structure (R2 of 0.8–0.9) allowed comparisons of vegetation structure between current and future climate. Significant shifts in vegetation structural types were predicted and mapped for future climates. Water gaining areas below granite outcrops were identified as important putative refugia. A reduction in rainfall may be offset by the occurrence of deeper soil elsewhere on the outcrop. However, climate change interactions with fire and water table declines may render our conclusions conservative. The LiDAR-based mapping approach presented enables the integration of site-based biotic assessment with structural vegetation types for the rapid delineation and prioritization of key refugia

"A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies"

<p>Abstract</p> <p>Background</p> <p>The study of breast cancer metastasis depends on the use of established breast cancer cell lines that do not accurately represent the heterogeneity and complexity of human breast tumors. A tumor model was developed using primary breast tumor-initiating cells isolated from patient core biopsies that would more accurately reflect human breast cancer metastasis.</p> <p>Methods</p> <p>Tumorspheres were isolated under serum-free culture conditions from core biopsies collected from five patients with clinical diagnosis of invasive ductal carcinoma (IDC). Isolated tumorspheres were transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity <it>in vivo</it>. Tumors and metastatic lesions were analyzed by hematoxylin and eosin (H+E) staining and immunohistochemistry (IHC).</p> <p>Results</p> <p>Tumorspheres were successfully isolated from all patient core biopsies, independent of the estrogen receptor α (ERα)/progesterone receptor (PR)/Her2/neu status or tumor grade. Each tumorsphere was estimated to contain 50-100 cells. Transplantation of 50 tumorspheres (1-5 × 10³cells) in combination with Matrigel into the mammary fat pad of NUDE mice resulted in small, palpable tumors that were sustained up to 12 months post-injection. Tumors were serially transplanted three times by re-isolation of tumorspheres from the tumors and injection into the mammary fat pad of NUDE mice. At 3 months post-injection, micrometastases to the lung, liver, kidneys, brain and femur were detected by measuring content of human chromosome 17. Visible macrometastases were detected in the lung, liver and kidneys by 6 months post-injection. Primary tumors variably expressed cytokeratins, Her2/neu, cytoplasmic E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. In lung and liver metastases, variable redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples.</p> <p>Conclusions</p> <p>Tumorspheres isolated under defined culture conditions from patient core biopsies were tumorigenic when transplanted into the mammary fat pad of NUDE mice, and metastasized to multiple mouse organs. Micrometastases in mouse organs demonstrated a dormancy period prior to outgrowth of macrometastases. The development of macrometastases with organ-specific phenotypic distinctions provides a superior model for the investigation of organ-specific effects on metastatic cancer cell survival and growth.</p

Imaging in breast cancer: Diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are non-invasive diagnostic techniques that employ near-infrared (NIR) light to quantitatively characterize the optical properties of centimeter-thick, multiple-scattering tissues. Although NIR was first applied to breast diaphanography more than 70 years ago, quantitative optical methods employing time- or frequency-domain 'photon migration' technologies have only recently been used for breast imaging. Because their performance is not limited by mammographic density, optical methods can provide new insight regarding tissue functional changes associated with the appearance, progression, and treatment of breast cancer, particularly for younger women and high-risk subjects who may not benefit from conventional imaging methods. This paper reviews the principles of diffuse optics and describes the development of broadband DOS for quantitatively measuring the optical and physiological properties of thick tissues. Clinical results are shown highlighting the sensitivity of diffuse optics to malignant breast tumors in 12 pre-menopausal subjects ranging in age from 30 to 39 years and a patient undergoing neoadjuvant chemotherapy for locally advanced breast cancer. Significant contrast was observed between normal and tumor regions of tissue for deoxy-hemoglobin (p = 0.005), oxy-hemoglobin (p = 0.002), water (p = 0.014), and lipids (p = 0.0003). Tissue hemoglobin saturation was not found to be a reliable parameter for distinguishing between tumor and normal tissues. Optical data were converted into a tissue optical index that decreased 50% within 1 week in response to neoadjuvant chemotherapy. These results suggest a potential role for diffuse optics as a bedside monitoring tool that could aid the development of new strategies for individualized patient care

Identification of Methylated Genes Associated with Aggressive Bladder Cancer

Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively). We then validated the association between methylation of these candidate loci with tumor grade in a third population (n = 245) through bisulfite pyrosequencing of candidate loci. Array based analyses identified 5 loci for further confirmation with bisulfite pyrosequencing. We identified and confirmed that increased promoter methylation of HOXB2 is significantly and independently associated with invasive bladder cancer and methylation of HOXB2, KRT13 and FRZB together significantly predict high-grade non-invasive disease. Methylation of these genes may be useful as clinical markers of the disease and may point to genes and pathways worthy of additional examination as novel targets for therapeutic treatment

The Kinetics of Early T and B Cell Immune Recovery after Bone Marrow Transplantation in RAG-2-Deficient SCID Patients

The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT) is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2)-deficient severe combined immunodeficiency (SCID) patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR) and the B cell receptor (BCR) repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa-deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT