Assessing the cumulative environmental effects of marine renewable energy developments: establishing common ground

Assessing and managing the cumulative impacts of human activities on the environment remains a major challenge to sustainable development. This challenge is highlighted by the worldwide expansion of marine renewable energy developments (MREDs) in areas already subject to multiple activities and climate change. Cumulative effects assessments in theory provide decision makers with adequate information about how the environment will respond to the incremental effects of licensed activities and are a legal requirement in many nations. In practise, however, such assessments are beset by uncertainties resulting in substantial delays during the licensing process that reduce MRED investor confidence and limit progress towards meeting climate change targets. In light of these targets and ambitions to manage the marine environment sustainably, reducing the uncertainty surrounding MRED effects and cumulative effects assessment are timely and vital. This review investigates the origins and evolution of cumulative effects assessment to identify why the multitude of approaches and pertinent research have emerged, and discusses key considerations and challenges relevant to assessing the cumulative effects of MREDs and other activities on ecosystems. The review recommends a shift away from the current reliance on disparate environmental impact assessments and limited strategic environmental assessments, and a move towards establishing a common system of coordinated data and research relative to ecologically meaningful areas, focussed on the needs of decision makers tasked with protecting and conserving marine ecosystems and services

Interleukin-2 druggability is modulated by global conformational transitions controlled by a helical capping switch.

Interleukin-2 (IL-2) is a small α-helical cytokine that regulates immune cell homeostasis through its recruitment to a high-affinity heterotrimeric receptor complex (IL-2Rα/IL-2Rβ/γc). IL-2 has been shown to have therapeutic efficacy for immune diseases by preferentially expanding distinct T cell compartments, and several regulatory T cell (Treg)-biasing anti-IL-2 antibodies have been developed for combination therapies. The conformational plasticity of IL-2 plays an important role in its biological actions by modulating the strength of receptor and drug interactions. Through an NMR analysis of milliseconds-timescale dynamics of free mouse IL-2 (mIL-2), we identify a global transition to a sparse conformation which is regulated by an α-helical capping "switch" at the loop between the A and B helices (AB loop). Binding to either an anti-mouse IL-2 monoclonal antibody (mAb) or a small molecule inhibitor near the loop induces a measurable response at the core of the structure, while locking the switch to a single conformation through a designed point mutation leads to a global quenching of core dynamics accompanied by a pronounced effect in mAb binding. By elucidating key details of the long-range allosteric communication between the receptor binding surfaces and the core of the IL-2 structure, our results offer a direct blueprint for designing precision therapeutics targeting a continuum of conformational states

Solitary Mandibular Lesion as the Presenting Sign of Multiple Myeloma: A Rare Case Report

Multiple myeloma (MM) is a rare hematological malignancy caused by monoclonal proliferation of plasma cells in the marrow of various bones. It is more common in men in the sixth and seventh decade of life. Patients usually present with bone pain, fatigue, recurrent infections, renal failure and nervous system dysfunction. Rarely, oral lesions may be the initial sign of multiple myeloma presenting with pain, jaw swelling, tooth mobility, multiple punched out radiolucencies and parasthesia. A case of multiple myeloma occurring in a 71 year old male patient who presented with a solitary lesion in the mandible is presented here. This paper highlights the importance of knowing oral manifestations of multiple myeloma and interdisciplinary approach required for early diagnosis

Florid Cemento-Osseous Dysplasia - A dilemma to intervene or not?!

Florid cemento - osseous dysplasia (FCOD) is a benign, non-neoplastic lesion characterized by multiple sclerosing masses within the jaw bones. We present an uncommon case of FCOD in a 37-year-old Indian woman incidentally discovered on a radiograph. She presented with bilaterally symmetrical lesions of variable radiodensities in the posterior mandible. In this asymptomatic case, the diagnosis of FCOD was made radiologically as biopsy is contraindicated. No treatment was imparted as the lesions were asymptomatic and the patient continues to be reviewed annually. The rationale of the present work is to describe this uncommon entity with only eleven reported cases noted in the literature amongst Indians. The case is unusual in its combination of the disease itself (FCOD) and the race (Indian). The confirmative role of radiography without histopathological evaluation and the need for no intervention is emphasized.   &nbsp

Sampling a Littoral Fish Assemblage: Comparison of Small-Mesh Fyke Netting and Boat Electrofishing

We compared small-mesh (4-mm) fyke netting and boat electrofishing for sampling a littoral fish assemblage in Muskegon Lake, Michigan. We hypothesized that fyke netting selects for small-bodied fishes and electrofishing selects for large-bodied fishes. Three sites were sampled during May (2004 and 2005), July (2005 only), and September (2004 and 2005). We found that the species composition of captured fish differed considerably between fyke netting and electrofishing based on nonmetric multidimensional scaling (NMDS). Species strongly associated with fyke netting (based on NMDS and relative abundance) included the brook silverside Labidesthes sicculus, banded killifish Fundulus diaphanus, round goby Neogobius melanostomus, mimic shiner Notropis volucellus, and bluntnose minnow Pimephales notatus, whereas species associated with electrofishing included the Chinook salmon Oncorhynchus tshawytscha, catostomids (Moxostoma spp. and Catostomus spp.), freshwater drum Aplodinotus grunniens, walleye Sander vitreus, gizzard shad Dorosoma cepedianum, and common carp Cyprinus carpio. The total length of fish captured by electrofishing was 12.8 cm (95% confidence interval ¼ 5.5– 17.2 cm) greater than that of fish captured by fyke netting. Size selectivity of the gears contributed to differences in species composition of the fish captured, supporting our initial hypothesis. Thus, small-mesh fyke nets and boat electrofishers provided complementary information on a littoral fish assemblage. Our results support use of multiple gear types in monitoring and research surveys of fish assemblages. Copyright by the American Fisheries Society 2007, Originally published in the North American Journal of Fisheries Management 27: 825-831, 2007

Ocular Gene Transfer with Self-Complementary AAV Vectors

PURPOSE. Self-complementary AAV (scAAV) vectors have been developed to circumvent rate-limiting second-strand synthesis in single-stranded AAV vector genomes and to facilitate robust transgene expression at a minimal dose. In this study, the authors investigated the effects of intraocular injections of type 2 scAAV.GFP in mice. METHODS. Dose-response experiments were performed to compare conventional single-strand AAV type 2 (ssAAV2) vectors with scAAV2 vectors encoding an identical expression cassette. RESULTS. Subretinal injection of 5 X 108viral particles (vp) of scAAV.CMV-GFP resulted in green fluorescent protein (GFP) expression in almost all retinal pigment epithelial (RPE) cells within the area of the small detachment caused by the injection by 3 days and strong, diffuse expression by 7 days. Expression was strong in all retinal cell layers by days 14 and 28. In contrast, 3 days after subretinal injection of 5 X 108vp of ssAAV.CMV-GFP, GFP expression was detectable in few RPE cells. Moreover, the ssAAV vector required 14 days for the attainment of expression levels comparable to those observed using scAAV at day 3. Expression in photoreceptors was not detectable until day 28. Dose-response experiments confirmed that onset of GFP expression was more rapid and robust after subretinal injection of scAAV.CMV-GFP than of ssAAV.CMV-GFP, resulting in pronounced expression in photoreceptors and other retinal neurons. Similar results were obtained for intravitreous injections. CONCLUSIONS. These data suggest that scAAV vectors may be advantageous for ocular gene therapy, particularly in retinal diseases that require rapid and robust transgene expression in photoreceptor cells

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

Over the past decade, nine gene therapy clinical trials for Parkinson's disease (PD) have been initiated and completed. Starting with considerable optimism at the initiation of each trial, none of the programs has yet borne sufficiently robust clinical efficacy or found a clear path toward regulatory approval. Despite the immediately disappointing nature of the efficacy outcomes in these trials, the clinical data garnered from the individual studies nonetheless represent tangible and significant progress for the gene therapy field. Collectively, the clinical trials demonstrate that we have overcome the major safety hurdles previously suppressing central nervous system (CNS) gene therapy, for none produced any evidence of untoward risk or harm after administration of various vector-delivery systems. More importantly, these studies also demonstrated controlled, highly persistent generation of biologically active proteins targeted to structures deep in the human brain. Therefore, a renewed, focused emphasis must be placed on advancing clinical efficacy by improving clinical trial design, patient selection and outcome measures, developing more predictive animal models to support clinical testing, carefully performing retrospective analyses, and most importantly moving forward—beyond our past limits

The Category of Node-and-Choice Forms, with Subcategories for Choice-Sequence Forms and Choice-Set Forms

The literature specifies extensive-form games in many styles, and eventually I hope to formally translate games across those styles. Toward that end, this paper defines $\mathbf{NCF}$, the category of node-and-choice forms. The category's objects are extensive forms in essentially any style, and the category's isomorphisms are made to accord with the literature's small handful of ad hoc style equivalences. Further, this paper develops two full subcategories: $\mathbf{CsqF}$ for forms whose nodes are choice-sequences, and $\mathbf{CsetF}$ for forms whose nodes are choice-sets. I show that $\mathbf{NCF}$ is "isomorphically enclosed" in $\mathbf{CsqF}$ in the sense that each $\mathbf{NCF}$ form is isomorphic to a $\mathbf{CsqF}$ form. Similarly, I show that $\mathbf{CsqF_{\tilde a}}$ is isomorphically enclosed in $\mathbf{CsetF}$ in the sense that each $\mathbf{CsqF}$ form with no-absentmindedness is isomorphic to a $\mathbf{CsetF}$ form. The converses are found to be almost immediate, and the resulting equivalences unify and simplify two ad hoc style equivalences in Kline and Luckraz 2016 and Streufert 2019. Aside from the larger agenda, this paper already makes three practical contributions. Style equivalences are made easier to derive by [1] a natural concept of isomorphic invariance and [2] the composability of isomorphic enclosures. In addition, [3] some new consequences of equivalence are systematically deduced.Comment: 43 pages, 9 figure

Psychotherapy Process and Relationship in the Context of a Brief, Attachment-Based, Mother-Infant Intervention

©American Psychological Association, 2015. This paper is not the copy of record and may not exactly replicate the authoritative document published in the APA journal. The final article is available, upon publication, at: https://doi.org/10.1037/a0037335The present study investigated links between the observer-rated process of psychotherapy and 2 key psychotherapy relationship constructs (i.e., working alliance and attachment to the therapist) in the context of a brief, attachment-based, home-visiting, mother–infant intervention that aimed to promote later secure infant attachment. Additionally, links between observer ratings of intervener and mother contributions to process were examined. Participants included 85 economically stressed mothers of first-born, 5.5-month-old, temperamentally irritable infants. Therapists included 2 doctoral-level and 4 master’s-level home visitors. Observer-rated therapist psychotherapy process variables (i.e., warmth, exploration, and negative attitude) were not linked to maternal ratings of working alliance. Therapist warmth, however, was positively associated with maternal ratings of security of attachment to the therapist, and therapist negative attitude was positively related to maternal ratings of preoccupied-merger attachment to the therapist. As expected, both therapist warmth and exploration were positively associated with both maternal participation and exploration. Therapist negative attitude was inversely related to maternal exploration, but not to maternal participation. Results support the idea that attention to the psychotherapy process and relationship may be important in the context of a brief home-visiting parenting intervention with a nonclinical sample. (APA PsycInfo Database Record (c) 2016 APA, all rights reserved)https://doi.org/10.1037/a003733