Fish, Polychlorinated Biphenyls (PCBs) and Natural Resource Injury

The Natural Resource Damage Assessment (NRDA) program is authorized by the Comprehensive Environmental Response Compensation and Liability Act (CERCLA) and the Oil Pollution Act (OPA) to pursue compensation for injury to, or destruction and loss of, natural resources. Fish are an important natural resource present in almost all aquatic ecosystems. Polychlorinated biphenyls (PCBs) are a hazardous substance and have been shown to cause harm to fish (and fish-eating animals). A series of investigations were conducted to determine if injury had occurred to creek chub (Semotilus atromaculatus) and in one study, the fish community that creek chubs were a part of, at several PCB-contaminated study locations. We examined: hepatic condition and oxidative stress enzymes; a comprehensive look at reproductive condition; age and growth; and several metrics of fish community structure and function. Although the determination of hepatic oxidative stress is a response to PCBs, this in and of itself is not considered injury. However, it is a good biomarker of potential injury especially in the presence of other injuries, like reproductive failure. Consistent with the PCB toxicity literature, we consider hepatomegaly and lipidosis injuries that result from PCB exposure. Given that other common factors can also cause lipidosis, this is not an effective injury assessment tool. The age and growth analysis shows significantly reduced survivorship in females at the PCB sites; this is clearly an injury. Aspects of creek chub reproduction have also been adversely impacted: reduced vitellogenin (Vtg), altered sex steroid ratios, reduced fecundity, delayed/ impaired spawning of ova, and reduced / impaired testes maturation. Although not an injury per se, the reduced and seasonally altered pattern of the male secondary sex characteristic nuptial tubercles provides another line of evidence that neuroendocrine disruption is occurring at the PCB-contaminated stream sites. An assessment of the fish community at these PCB-contaminated streams also indicated that growth and survival were issues for the entire fish community. From Frye\u27s standard of evidence [Frye v. United States, 293 F.1013 (D.C. Cir. 1923)], much of this work would have been extremely useful to trustees in court. What we found would be generally acceptable in our professional sphere. But scientists and lawyers look at facts differently: same language, same word, different meaning. The science of reproduction impacts is very complicated, and some aspects (i.e. neuroendocrine disruption) while clearly injury, are too complicated to prevail in the courtroom. The impacts to reproduction, including reduced vitellogenin (Vtg), reduced fecundity and delayed/ impaired spawning of ova have significant ecosystem consequences. Growth effects that follow a non-monotonic non-standard dose response curve would do poorly in court. While reduced survivorship should easily be translated to the injury known as death , nothing in court is certain. Because it is extremely difficult to put a value on natural resources, it is very important to do whatever can be done early on to avoid litigation. A complete win on injury determinations (albeit unlikely), could still result in little or no restoration relief

Modulation of Synaptic Responses in the Entorhinal Cortex Evoked by Repetitive Stimulation of the Parasubiculum

The entorhinal cortex provides the hippocampus with the majority of its sensory input. The entorhinal cortex also receives the largest output projection of the parasubiculum, a structure that receives output projections from the hippocampus. The parasubicular projection to the entorhinal cortex could play a critical role in determining how the entorhinal cortex responds to incoming sensory inputs. Therefore, alterations in how the entorhinal cortex responds to and processes sensory input, influenced by its projection from the parasubiculum, could be important for mnemonic processing the hippocampus. Neural activity in brain regions throughout the hippocampal formation, including the parasubiculum and entorhinal cortex, is heavily modulated by the neurotransmitter acetylcholine and the associated theta- and gamma-frequency oscillatory EEG rhythms. However, it is not known how cholinergic activity and synaptic inputs at these frequencies affect communication between the parasubiculum and entorhinal cortex, and how this could influence the processing of sensory inputs within the entorhinal cortex. The first experiments in this thesis utilized field potential recordings of excitatory postsynaptic potentials (fEPSPs), and found that activation of cholinergic receptors, despite reducing the amplitude of responses to single pulses of stimulation, facilitated entorhinal cortex responses during trains of stimulation of the parasubiculum at both theta- and gamma- frequencies. This effect was found to be reliant upon M1 muscarinic receptors and was associated with cholinergic reductions in the cationic conductance Ih. In a second series of experiments, intracellular recordings of EPSPs in stellate cells in layer II of the medial entorhinal cortex replicated the findings obtained in field potential recordings, and indicated that the facilitation of train-evoked responses at theta- and gamma-frequencies by cholinergic agonism is due in part to reductions in Ih that lead to increased input resistance and widening of EPSPs. In a third series of experiments, when a second stimulating electrode was placed in layer I of the medial entorhinal cortex to activate sensory input pathways, it was found that trains of stimulation in the iii parasubiculum at theta-frequency modulated the strength of subsequent entorhinal cortex responses to incoming layer I sensory inputs. Stimulation of the parasubiculum was found to either suppress or facilitate responses to layer I inputs depending on the interval between parasubicular and layer I stimulation, suggesting that the parasubiculum can influence the ongoing processing of sensory inputs by the entorhinal cortex. When prolonged, repetitive, delivery of theta-frequency parasubicular stimulation trains was paired with single pulses of stimulation of layer I at short intervals after each train, it was found that co-activation of these inputs pathways resulted in a selective and lasting depression of entorhinal cortex responses to layer I stimulation. These results indicate that activation of the parasubiculum can have a lasting impact on how the entorhinal cortex responds to sensory inputs. Overall these results have strong implications for how information is processed in the hippocampal formation, and suggest that parasubicular inputs to the entorhinal cortex can influence the nature of the sensory and associational information that the entorhinal cortex provides to the hippocampus

Supersymmetric AdS_5 Solutions of Type IIB Supergravity

We analyse the most general bosonic supersymmetric solutions of type IIB supergravity whose metrics are warped products of five-dimensional anti-de Sitter space AdS_5 with a five-dimensional Riemannian manifold M_5. All fluxes are allowed to be non-vanishing consistent with SO(4,2) symmetry. We show that the necessary and sufficient conditions can be phrased in terms of a local identity structure on M_5. For a special class, with constant dilaton and vanishing axion, we reduce the problem to solving a second order non-linear ODE. We find an exact solution of the ODE which reproduces a solution first found by Pilch and Warner. A numerical analysis of the ODE reveals an additional class of local solutions.Comment: 33 page

Vascularised bone transfer: history, blood supply and contemporary problems

Background Since the description of the free fibula flap by Taylor in 1975, many flaps composed of bone have been described. This review documents the history of vascularised bone transfer and reflects on the current understanding of blood supply in an effort to define all clinically described osseous flaps. Methods A structured review of MEDLINE and Google Scholar was performed to identify all clinically described bone flaps in humans. Data regarding patterns of vascularity were collected where available from the anatomical literature. Results Vascularised bone transfer has evolved stepwise in concert with advances in reconstructive surgery techniques. This began with local flaps of the craniofacial skeleton in the late 19th century, followed by regional flaps such as the fibula flap for tibial reconstruction in the early 20th century. Prelaminated and pedicled myo-osseous flaps predominated until the advent of microsurgery and free tissue transfer in the 1960s and 1970s. Fifty-two different bone flaps were identified from 27 different bones. These flaps can be broadly classified into three types to reflect the pedicle: nutrient vessel (NV), penetrating periosteal vessel (PPV) and non-penetrating periosteal vessel (NPPV). NPPVs can be further classified according to the anatomical structure that serves as a conduit for the pedicle which may be direct-periosteal, musculoperiosteal or fascioperiosteal. Discussion The blood supply to bone is well described and is important to the reconstructive surgeon in the design of reliable vascularised bone suitable for transfer into defects requiring osseous replacement. Further study in this field could be directed at the implications of the pattern of bone flap vascularity on reconstructive outcomes, the changes in bone vascularity after osteotomy and the existence of “true” and “choke” anastomoses in cortical bone

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Common Data Elements to Facilitate Sharing and Re-use of Participant-Level Data: Assessment of Psychiatric Comorbidity Across Brain Disorders

The Ontario Brain Institute\u27s “Brain-CODE” is a large-scale informatics platform designed to support the collection, storage and integration of diverse types of data across several brain disorders as a means to understand underlying causes of brain dysfunction and developing novel approaches to treatment. By providing access to aggregated datasets on participants with and without different brain disorders, Brain-CODE will facilitate analyses both within and across diseases and cover multiple brain disorders and a wide array of data, including clinical, neuroimaging, and molecular. To help achieve these goals, consensus methodology was used to identify a set of core demographic and clinical variables that should be routinely collected across all participating programs. Establishment of Common Data Elements within Brain-CODE is critical to enable a high degree of consistency in data collection across studies and thus optimize the ability of investigators to analyze pooled participant-level data within and across brain disorders. Results are also presented using selected common data elements pooled across three studies to better understand psychiatric comorbidity in neurological disease (Alzheimer\u27s disease/amnesic mild cognitive impairment, amyotrophic lateral sclerosis, cerebrovascular disease, frontotemporal dementia, and Parkinson\u27s disease)

Trapping \u3ci\u3ePhyllophaga \u3c/i\u3espp. (Coleoptera: Scarabaeidae: Melolonthinae) in the United States and Canada using sex attractants.

The sex pheromone of the scarab beetle, Phyllophaga anxia, is a blend of the methyl esters of two amino acids, L-valine and L-isoleucine. A field trapping study was conducted, deploying different blends of the two compounds at 59 locations in the United States and Canada. More than 57,000 males of 61 Phyllophaga species (Coleoptera: Scarabaeidae: Melolonthinae) were captured and identified. Three major findings included: (1) widespread use of the two compounds [of the 147 Phyllophaga (sensu stricto) species found in the United States and Canada, males of nearly 40% were captured]; (2) in most species intraspecific male response to the pheromone blends was stable between years and over geography; and (3) an unusual pheromone polymorphism was described from P. anxia. Populations at some locations were captured with L-valine methyl ester alone, whereas populations at other locations were captured with L-isoleucine methyl ester alone. At additional locations, the L-valine methyl ester-responding populations and the L-isoleucine methyl ester-responding populations were both present, producing a bimodal capture curve. In southeastern Massachusetts and in Rhode Island, in the United States, P. anxia males were captured with blends of L-valine methyl ester and L-isoleucine methyl ester

The Child Welfare Inequalities Project: final report

The Child Welfare Inequalities Project (CWIP), 2014-19, aimed to establish child welfare inequalities as a core concept in policy making, practice and research in the UK and internationally. Key research tasks were to identify the scale of inequalities in social welfare intervention rates as they affect children in different places, of different ages and identities, and their families, and to begin to understand how different factors in family lives and service responses interact to produce inequalities. A longer term intention was that remedies could subsequently be developed by policy makers and service providers and their impact tested. CWIP was the main project in a programme of research conducted over the period 2013-2019. It was designed to provide the foundations for the development of an inequalities perspective on child welfare, not the last word. By developing and testing a set of concepts, theory and methods and by securing a range of evidence, we hoped to set the baseline for subsequent reflection, research and action, in the UK and internationally (Bywaters, 2015). A social welfare system reflects the society in which it operates: its assumptions, priorities and attitudes to children, parents and family life. It also reflects the role of the state: how policy is made, the values that underpin policy, the power it exercises over its citizens, how it manages and polices that power and what it counts as success. All of these themes are explicit or implicit in our work. In summary, this project reports on a system which treats its citizens – parents and children – remarkably unequally but which focuses more attention on policy aspirations and implementation processes than on either the causes of family difficulties or the consequences of state responses

Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement

IMPORTANCE: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more common monogenic autoinflammatory diseases, with an estimate of more than 35 000 cases worldwide, but currently, there are no guidelines for diagnostic evaluation or management. OBJECTIVE: To review the available evidence and develop multidisciplinary consensus statements for the evaluation and management of DADA2. EVIDENCE REVIEW: The DADA2 Consensus Committee developed research questions based on data collected from the International Meetings on DADA2 organized by the DADA2 Foundation in 2016, 2018, and 2020. A comprehensive literature review was performed for articles published prior to 2022. Thirty-two consensus statements were generated using a modified Delphi process, and evidence was graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence. FINDINGS: The DADA2 Consensus Committee, comprising 3 patient representatives and 35 international experts from 18 countries, developed consensus statements for (1) diagnostic testing, (2) screening, (3) clinical and laboratory evaluation, and (4) management of DADA2 based on disease phenotype. Additional consensus statements related to the evaluation and treatment of individuals with DADA2 who are presymptomatic and carriers were generated. Areas with insufficient evidence were identified, and questions for future research were outlined. CONCLUSIONS AND RELEVANCE: DADA2 is a potentially fatal disease that requires early diagnosis and treatment. By summarizing key evidence and expert opinions, these consensus statements provide a framework to facilitate diagnostic evaluation and management of DADA2

Brown marmorated stink bug, Halyomorpha halys (Stål), genome: putative underpinnings of polyphagy, insecticide resistance potential and biology of a top worldwide pest

Background Halyomorpha halys (Stål), the brown marmorated stink bug, is a highly invasive insect species due in part to its exceptionally high levels of polyphagy. This species is also a nuisance due to overwintering in human-made structures. It has caused significant agricultural losses in recent years along the Atlantic seaboard of North America and in continental Europe. Genomic resources will assist with determining the molecular basis for this species’ feeding and habitat traits, defining potential targets for pest management strategies. Results Analysis of the 1.15-Gb draft genome assembly has identified a wide variety of genetic elements underpinning the biological characteristics of this formidable pest species, encompassing the roles of sensory functions, digestion, immunity, detoxification and development, all of which likely support H. halys’ capacity for invasiveness. Many of the genes identified herein have potential for biomolecular pesticide applications. Conclusions Availability of the H. halys genome sequence will be useful for the development of environmentally friendly biomolecular pesticides to be applied in concert with more traditional, synthetic chemical-based controls