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Somatodendritic missorting of the axonal protein TAU is a hallmark of Alzheimer’s disease and related tauopathies. Cultured rodent primary neurons and iPSC-derived neurons are used for studying mechanisms of neuronal polarity, including TAU trafficking. However, these models are expensive, time-consuming and/or require the sacrification of animals. In this study, we evaluated four differentiation procedures to generate mature neuron cultures from human SH-SY5Y neuroblastoma cells, in comparison to mouse primary neurons, and tested their TAU sorting capacity. We show that SH-SY5Y-derived neurons, differentiated with sequential RA/BDNF treatment, are suitable for investigating axonal TAU sorting. These human neurons show pronounced neuronal polarity, axodendritic outgrowth, expression of the neuronal maturation markers TAU and MAP2, and, importantly, efficient axonal sorting of endogenous and transfected human wild type TAU, similar to primary neurons. We demonstrate that axonal TAU enrichment requires the presence of the C-terminal half, as a C-terminus-lacking construct (N-term-TAUHA) is not axonally enriched in both neuronal cell models. Moreover, SH-SY5Y-derived neurons do not show formation of a classical axon initial segment (AIS), indicated by the lack of Ankyrin G (ANKG) and tripartite motif-containing protein 46 (TRIM46) at the proximal axon, which suggests that successful axonal TAU sorting is independent of classical AIS formation. Taken together, our results suggest i) that SH-SY5Y-derived neurons are a valuable human neuronal cell model for studying TAU sorting, which is readily accessible at low cost and without animal need, and that ii) the mechanisms of axonal TAU targeting require the TAU C-terminal half but are independent of ANKG or TRIM46 enrichment at the proximal axon.

Modernizing data systems to inform collaborative management is critical to adaptively managing fisheries in an era of climate change. In 2006, The Nature Conservancy of California purchased 13 federal groundfish permits in California with the objective of managing the fishing and reporting activities in a manner that protected sensitive habitats and species. At that time, collecting data for this fishery was done with paper logbooks. This made queries and visualization that could inform management decisions towards our objective impossible in a timely manner. To solve this problem, we built successive software prototypes that leveraged location-aware mobile devices, cloud-based computing, and visualization and query of geographic data over the web. The resulting software, eCatch, enabled avoidance of sensitive species and habitats and quantitative reporting on performance metrics related to those activities. What started as a technology solution to a problem of timely scientific monitoring revealed collateral benefits of collaboration with the fishing industry and markets that support sustainable activities.

Changes to climate are projected over the next 50 years for many peatland areas. As decomposition of peat-forming vegetation is likely to be intrinsically linked to these changes in climate, a clear understanding of climate-peat dynamics is required. There is concern that increased temperature and decreased precipitation could increase the rate of decomposition and put the carbon sink status of many peatlands at risk, yet few studies have examined the impact of both climatic factors together. To better understand the sensitivity of peatland decomposition to changes in both temperature and precipitation and their interaction, we conducted a short-term laboratory experiment in which plant litters and peat soil were incubated, in isolation, in a factorial design. Treatments simulated baseline and projected climate averages derived from the latest UK climate change projections (UKCP09) for Exmoor, a climatically marginal peatland in SW England. Regular carbon dioxide flux measurements were made throughout the simulation, as well as total mass loss and total dissolved organic carbon (DOC) leached. The largest effect on carbon loss in this multifactor experiment was from substrate, with Sphagnum/peat releasing significantly less C in total during the experiment than dwarf shrubs/graminoids. Climate effects were substrate specific, with the drier rainfall treatment increasing the DOC leaching from Calluna, but decreasing it from Sphagnum. Partitioning between CO2 and DOC was also affected by climate, but only for the peat and Sphagnum samples, where the future climate scenarios (warmer and drier) resulted in a greater proportion of C lost in gaseous form. These results suggest that indirect effects of climate through changes in species composition in peatlands could ultimately turn out to be more important for litter decomposition than direct effects of climate change from increased temperatures and decreased rainfall.

Voluntary collective agreements among fishermen can improve the environmental and economic performance of a fishery, particularly when local leadership, strong incentives, catch accountability, and operational support are in place. Rights-based fisheries, such as Individual Fishing Quota (IFQ) systems, incentivize fishermen to act collectively to reduce fishing impacts, enhance stock health, and improve economic outcomes. However, developing cooperatives requires durable contracts, operational capacity, funding, and the ability to track, monitor, and enforce agreed-upon catches and fishing practices. This project focuses on the U.S. West Coast groundfish trawl IFQ fishery, and how the formation of a voluntary collective agreement, in the form of a bycatch risk pool (California Groundfish Collective), achieved improved fishery performance and other ancillary benefits. Up-front investment in the risk pool by a conservation non-governmental organization (NGO) provided both capacity and quota to cover transaction costs and incentivize transition to a cooperative model that was implemented across 5 ports and more than 48,000 km2 of fishing grounds off California. The challenges encountered in developing and operating the risk pool offer insights into designing and implementing voluntary collective agreements. By using spatial fishing plans and technology for collecting and sharing catch information, risk pool members reduced bycatch of overfished species relative to the fleet at large. Risk pool members were also able to use their spatial fishing data to inform a seafood sustainability rating and propose areas for Essential Fish Habitat protection, their quota pounds to support collaborative research on overfished species, and their collective membership to advocate for policy.

Microplastic (MP) ingestion has been widely recorded in aquatic organisms, but few studies focus on cnidarians and ctenophores, which form a significant contribution to marine trophic interactions. Scyphozoans (Cyanea capillata, C. lamarckii and Aurelia aurita), hydrozoan (Cosmetira pilosella) and ctenophores (Beroe cucumis and Pleurobrachia bachei) collected opportunistically from Orkney, Shetland and the North Sea were thermally disintegrated, with a subsample of ingested plastics analysed using FTIR. A total of 1,986 MPs were counted (94% fibres), the majority (84.4%) in the four cnidarian species. Highest MP concentrations were recorded in B. cucumis (0.956 ml-1), whilst C. pilosella yielded the lowest (0.014 ml-1). The main polymers in digestate were PET and PP, with 27% discounted as non-plastics. In feeding trials, A. aurita ingested a greater quantity of PET fibres (60-80%), compared to nylon (0%) and HDPE fibres (0%). This study demonstrates cnidarians and ctenophores, a largely overlooked group, are a potential route for MPs entry into food webs.

Objective To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. Study design We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). Results Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. Conclusions This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.

We describe a modelling project to estimate the potential effects of wave & tidal stream renewables on the marine environment. • Realistic generic devices to be used by those without access to the technical details available to developers are described. • Results show largely local sea bed effects at the level of the currently proposed renewables developments in our study area. • Large scale 3D modelling is critical to quantify the direct, indirect and cumulative effects of renewable energy extraction. • This is critical to comply with planning & environmental impact assessment regulations and achieve Good Environmental Status.

Around the coastline of the UK, macro-debris has been observed in average densities of over 700 items per metre. Systematic beach-cleans were conducted at 35 sites around the Scottish Orkney Islands, in order to quantify and categorise the level of marine debris found there. Litter was collected from 100 m transects and categorised by its material, broad source (terrestrial or marine) and potential sector source. Variation between sites, and the relative contribution of pre-determined environmental variables in influencing said variation, were analysed using the "capscale" function for a canonical analysis of principle coordinates (CAP). 513 items/m were observed, (77% plastic), with "String/cord (1cm diameter)" being the most abundant and widely distributed litter type. 47% of macro-debris was attributed to the fishing sector and 10% to leisure, living and tourism-associated activities. Conversely, the unique regional hydrodynamics must be examined further, before the source of any given item can be categorically assigned.

Bolted connections used for connecting hollow structural steel (HSS) members are often made using bolts which have access to the HSS member from only one face. Hence, no nuts can be used in these connections. Such connections are often called as one-sided connection. Flow drilling and flow tapping techniques has the potential to make such one-sided bolted connections with relative ease. This paper presents outcomes of a study completed to determine the structural behavior of flow drilled connections made on HSS sections. The connections considered in this study were tested in tension and shear. A total of 150 tests of which 75 in tension and 75 in shear were completed. The effect of four different parameters namely HSS section geometry, screw hole drilling technique, tapping technique, and number of screw threads per unit length were considered. In all the connections considered in this study the diameter of the screw hole was kept unchanged at 19.05 mm (0.75 in). This study showed that the tension capacity of the one-sided connections can be increased to 95% by using flow drilled connections as it offers more number of threads for screw engagement. This study also showed that the flow drilling does not have significant influence on the shear behavior of the connections. Potential failure modes were identified. Analytical equations were developed to aid in the design of these connections.

Acknowledgements This work received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) and their support is gratefully acknowledged. MASTS is funded by the Scottish Funding Council (Grant reference HR09011) and contributing institutions.

Uncertainty regarding changes in dissolved organic carbon (DOC) quantity and quality has created interest in managing peatlands for their ecosystem services such as drinking water provision. The evidence base for such interventions is, however, sometimes contradictory. We performed a laboratory climate manipulation using a factorial design on two dominant peatland vegetation types (Calluna vulgaris and Sphagnum Spp.) and a peat soil collected from a drinking water catchment in Exmoor National Park, UK. Temperature and rainfall were set to represent baseline and future conditions under the UKCP09 2080s high emissions scenario for July and August. DOC leachate then underwent standard water treatment of coagulation/flocculation before chlorination. C. vulgaris leached more DOC than Sphagnum Spp. (7.17 versus 3.00 mg g(-1)) with higher specific ultraviolet (SUVA) values and a greater sensitivity to climate, leaching more DOC under simulated future conditions. The peat soil leached less DOC (0.37 mg g(-1)) than the vegetation and was less sensitive to climate. Differences in coagulation removal efficiency between the DOC sources appears to be driven by relative solubilisation of protein-like DOC, observed through the fluorescence peak C/T. Post-coagulation only differences between vegetation types were detected for the regulated disinfection by-products (DBPs), suggesting climate change influence at this scale can be removed via coagulation. Our results suggest current biodiversity restoration programmes to encourage Sphagnum Spp. will result in lower DOC concentrations and SUVA values, particularly with warmer and drier summers.

The Irish Sea represents a valuable resource to numerous industries, communities, and other stakeholders particularly in the areas of shellfisheries and aquaculture, energy development and ecosystem services. Climate change poses a substantial threat to marine environments in the region, with impacts exacerbated by struggles for ever limited space and resources, a pronounced need for conservation of important and vulnerable marine ecosystems, and lack of unified management. A concerted effort is required to: i) determine the impacts of climate change and potential risks to marine industry; ii) advise marine industries of future opportunities and areas of collaboration; and iii) develop coordinated marine management across the region to ensure the resource is exploited in an economically and environmentally sustainable manner. We propose that an Irish Sea Marine Research Forum be created that promotes a multi-disciplinary holistic research approach linking industry and research to identify and mitigate the socioeconomic and environmental impacts of climate change. Additionally, we propose that an integrated jurisdiction for the Irish Sea be formed to serve as a regulatory body on fisheries and marine policy for the entire region. Management and policy directives should consider both potential for economic development as well as protection of key environmental features and ecosystem services. Such concentrated efforts on the Irish Sea could then be used as a management model for other regional seas and resources.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the non-invasive diagnosis of pulmonary hypertension. This manuscript describes in detail the results and recommendations of the working group which were last updated in October 2011.

Purpose The purpose of this study was to evaluate the success of dental implants placed immediately into extraction sites in the presence of chronic periapical pathology. Materials and Methods The charts of 655 patients who had implants immediately placed into fresh extraction sites were reviewed for the presence or absence of periapical radiolucencies. A total of 922 implants were included. Of the 922 implants, 285 were immediately placed into sockets that had chronic periapical infections. The remaining 637 implants, without signs of periapical pathology, were used as the control group. Success of the implants was defined as successful osseointegration, successful restoration, and absence of evidence of bone loss or peri-implantitis. Other variables such as age, gender, smoking, diabetes, bisphosphonate use, lucencies of adjacent teeth, and implant stability at the time of placement were also evaluated. Results Of the 922 implants, 285 were placed into sockets with periapical radiolucencies. The success rate of implants placed in the study group was 97.5%, whereas the success rate of the control group was 98.7%. The difference was not found to be statistically significant. The mean follow-up was 19.75 months, with a maximum of 93 months and a minimum of 3 months. A statistically higher failure rate was found for implants placed adjacent to retained teeth with periapical pathology. Conclusions The placement of implants in sockets affected by chronic periapical pathology can be considered a safe and viable treatment option. There is a risk of implant failure when placing implants adjacent to teeth with periapical radiolucencies.

Many countries now recognise the need for mitigation of climate change induced by human activities and have incorporated renewable energy resources within their energy policy. There are extensive resources of renewable energy within the marine environment and increasing interest in extracting energy from locations with either large tidal range, rapid flow with and without wave interaction, or large wave resources. However, the ecological implications of altering the hydrodynamics of the marine environment are poorly understood. Ecological data for areas targeted for marine renewable developments are often limited, not least because of the considerable challenges to sampling in high energy environments. In order to predict the scale and nature of ecological implications there is a need for greater understanding of the distribution and extent of the renewable energy resource and in turn, of how marine renewable energy installations (MREIs) may alter energy in the environment. Regional ecological implications of a MREI need to be considered against the greater and global ecological threat of climate change. Finally, it is recommended that the identification of species and biotopes susceptible to the removal of hydrokinetic energy could be a suitable strategy for understanding how a MREI may alter flow conditions.

Background Between August 1 and October 30, 1998 (outbreak period), an increased incidence of central venous catheter (CVC)-associated gram-negative bacterial bloodstream infection (GN-BSI) was detected in hematopoietic stem cell transplantation (HSCT) candidates and recipients in an outpatient HSCT unit. The objectives of the present study were to determine strategies for controlling the outbreak and identify risk factors for GN-BSI. Methods Two case-control studies, an assessment of infection control practices, microbiologic studies, and water quality analysis were conducted. A case was defined as any outpatient with a CVC and a primary GN-BSI during the outbreak period. Results All of the 31 case patients identified had needleless intravenous (IV) access devices. Independent risk factors for CVC-associated GN-BSI were self-administered IV infusion (odds ratio [OR] = 6.2; P = .02), lower frequency of needleless device changes (OR = 15.2; P = .03), and more frequent baths (OR = 1.4; P = .05). Interventions included increased frequency of needleless device change, recommending showers rather than baths, and use of CVC protection during showering/bathing. After these interventions, the CVC-associated GN-BSI rate declined to below the preoutbreak period rate (2.1/1000 vs 0.3/1000 CVC-days; P Conclusions This study demonstrated an increased risk of CVC-associated GN-BSIs related to self-IV infusion, bathing habits, and frequency of needleless device change. Infection control practices associated with the use of needleless devices may expose susceptible patients to increased risk for BSI.

Epidemics of meningococcal meningitis in Africa have plagued the continent for over a century. These epidemics have a strong association with the environment and efforts are being made to develop models to predict both their location and their incidence. This review describes the predictive models based on climate/environmental information currently available, describes work in progress, and presents evidence that the distribution of the epidemics is changing in a pattern that is compatible with changes in the environment. Discussion of priorities for research in the context of the new conjugate vaccines in Africa is also provided.

We present an overview of the history of forecasting software over the past 25 years, concentrating especially on the interaction between computing and software. Initially we create a framework by describing important developments of computing technology in terms of hardware and software environments. We then concentrate on two different application areas of forecasting software: (1) research oriented forecasting software often used to analyze a small number of series (for example, in market research); and (2) forecasting modules in planning environments which are often partially automated due to the large number of time series involved. Finally we make some suggestions as to where forecasting software has room for improvement.

A sensor for determining the concentration of a target ion in a liquid sample having a particulate silica doped with: an ionophore capable of binding the target ion; and an indicator capable of producing a detectable signal in response to binding by the ionophore of the target ion. The detectable signal is related to the target ion concentration in the liquid sample.

Purpose To develop an algorithm for optimal beam arrangement selection in intensity-modulated radiotherapy (IMRT) of mixed photon and electron beams. To apply this algorithm to study the utility of modulated electron beams in the context of IMRT planning. Methods and materials The optimization algorithm selects, for a user-specified number of beams, the optimal IMRT arrangement (beam orientations, and photon/electron modality for each orientation) using a novel fast heuristic intensity modulation procedure. The algorithm was employed to select optimal beam arrangements for breast (two, four, and six axial beams) and head-and-neck (three, four, five, and seven nonaxial beams) cases. Results For the two cases, increasing the number of selected beams: (1) increased the number of electron beams for the breast case, but not more than one electron beam was selected for the head-and-neck case; (2) decreased critical structure doses for both cases; and (3) decreased target homogeneity for the breast case, but improved it for the head-and-neck case. Conclusions In the two cases analyzed using the selection algorithm, the primary role of modulated electrons differs based on treatment site—normal tissue dose reduction in breast and target homogeneity improvement in head and neck. Although this preliminary study with two cases appears to suggest that the role of intensity-modulated electrons differs based on treatment site, further investigation of large numbers of cases and varied treatment sites are required to establish a definitive conclusion.

Use of trade names is for identification only, and does not imply endorsement by the Public Health Service or the US Department of Health and Human Services.Children in Malawi receive bacille Calmette-GuéArin (BCG) vaccination within the first 3 days of life. Thus, we hypothesized that Malawian children infected with the human immunodeficiency type 1 virus (HIV-1) might be particularly vulnerable to dissemination of the BCG Mycobacterium bovis strain with which they were vaccinated. Following informed consent by parents, we studied children admitted to a Malawi general hospital during the 1998 wet and dry seasons. Blood from cohorts of acutely ill children was cultured for bacteria, including mycobacteria, and fungi, and tested for anti-HIV-1 antibodies. It was shown that non-typhi Salmonella and Escherichia coli were the predominant bloodstream pathogens during the wet and dry seasons, and that bloodstream dissemination of the BCG M. bovis strain is uncommon in HIV-1-infected children who receive the BCG vaccine.

Objectives: Published data suggest that Streptococcus pneumoniae, non-typhi Salmonella species, and Mycobacterium tuberculosis are the predominant causes of bloodstream infection (BSI) in hospitalized populations in sub-Saharan Africa. This study was conducted during the wet season to ascertain the etiology and prevalence of BSI among febrile inpatients in a hospital where the dry season BSI profile in a similar study population had already been documented.Methods: In the period from March to May 1998, consecutive febrile (≥37.5° C) adult (≥ 14 y) patients presenting to a Malawi hospital were enrolled after providing informed consent. Following clinical evaluation, blood was drawn for culture (bacteria, mycobacteria, and fungi), human immunodeficiency virus (HIV) testing, and malaria smears.Results: Of 238 enrolled patients, 173 (73%) were HIV-positive and 67 (28%) had BSI. The predominant wet season BSI pathogens were non-typhi Salmonella species (41%), M. tuberculosis (19%), and Cryptococcus neoformans (9%) (cf. the predominant dry season pathogen was S. pneumoniae). Mycobacteremia was more likely in HIV-positive than in HIV-negative patients (13173 vs. 065; P < 0.05). A logistic regression model yielded clinical predictors of BSI that included chronic fever, oral candidiasis, or acute diarrhea.Conclusion: Pathogens causing BSI in febrile inpatients in a Malawi teaching hospital vary by season. Season- and country-specific studies, such as this one, provide data that may facilitate empirical therapy of febrile illnesses whose etiologies vary by season.

We and others have previously reported that the hormone insulin alters brain noradrenergic function at the synaptic and molecular levels. In the present study, we examined the in vivo effect of insulin (administered chronically via osmotic minipumps at a dose of 5 mU/day into the third cerebral ventricle) on the acoustic startle response. Rats receiving chronic intraventricular insulin had a significantly reduced startle response relative to vehicle-treated controls (i.e., 47 ± 21% of baseline control startle response). Because our previous findings suggest that on an acute basis, insulin may enhance endogenous noradrenergic activity by inhibiting norepinephrine reuptake, we speculate here that the chronic effect of insulin is similar to that of the noradrenergic reuptake blocker, desipramine, which has been reported to decrease baseline startle performance.

A method is described for the specific detection of urocanase activity on polyacrylamide gels. It is dependent upon the reduction of nitro blue tetrazolium by the product of the urocanase reaction using phenazine methosulphate as a coupling agent. The method has been characterized using crude cell extracts of Pseudomonas testosteroni and Pseudomonas putida. After growth of the organisms in histidine-succinate medium each extract shows only one band of urocanase activity. The enzymes from the two species have significantly different electrophoretic mobilities.