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Tape storage is still a cost effective way to keep large amounts of data over a long period of time and it is expected that this will continue in the future. The GridKa tape environment is a complex system of many hardware components and software layers. Configuring this system for optimal performance for all use cases is a non-trivial task and requires a lot of experience. We present the current status of the GridKa tape environment, report on recent upgrades and improvements and plans to further develop and enhance the system, especially with regard to the future requirements of the HEP experiments and their large data centers. The short-term planning mainly includes the transition from TSM to HPSS as the backend and the effects on the connection of dCache and xrootd. Recent changes of the vendor situation of certain tape technologies require a precise analysis of the impact and eventual adaptation of the mid-term planning, in particular with respect to scalability challenge that comes with HL-LHC on the horizon.

Floods are the most important natural hazard in the EU and US, causing 700 deaths and at least €25 billion in insured economic losses in Europe since 1998, and causing nearly $10 billion annual average flood losses in the US. Flood control is commonly viewed as a matter of building dykes, dams, and other structures, but effective flood management within the perspective of Integrated Water Resource Management (IWRM) must address multiple components of the flood risk management cycle (Figure 1). We systematically reviewed governance structures, guidance documents, and mapping products in both the EU and US, drawing particular examples from California and Spain, to determine how the US and the EU approach the flood risk management within different IWRM initiatives, which strategies and agencies are involved in the different phases –characterization (flood hazard and risk assessment and mapping), mitigation (prevention and protection), emergency (preparation and response), and (short and long term) recovery-, and how these agencies relate to each other. The regions have strong similarities in economy and environmental values, but have evolved very different approaches to cope with floods. The US and EU have similar organizational structures, but very different legislative frameworks. In the US overarching policy and large scale infrastructure funding have traditionally resided at the federal level with state and local agencies exercising strong land use control. EU member states have arguably advanced ahead of the US in some significant ways since adoption of the EU Floods Directive in 2007, a more top-down approach. Among the Directive’s many components, one important requirement is submission of flood risk management plans (by the end of 2015), which, for first time, take into account all phases of flood management. This umbrella strategy to cope with floods is creating a more consistent and integrated flood risk management approach in Europe. In 2008, the State of California, with over 2500 km of levees, enacted a comprehensive package of flood management legislation and state bond financing that far exceeds federal and other state’s actions. This program known as FloodSafe California provided funding for projects within Integrated Regional Water Management Plans, an attempt to implement IWRM at regional scale. Although the efforts of FloodSafe California represent as a major change in direction in US flood risk management, the actions still do not fully implement the integrated flood risk approach promoted by the EU.

Abstract Background Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. Methods HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. Results 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Conclusions Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

Surveys often estimate vaccination intentions using dichotomous ("Yes"/"No") or trichotomous ("Yes," "Unsure," "No") response options presented in different orders. Do survey results depend on these variations? This controlled experiment randomized participants to dichotomous or trichotomous measures of vaccine intentions (with "Yes" and "No" options presented in different orders). Intentions were measured separately for COVID-19, its booster, and influenza vaccines. Among a sample of U.S. adults (N = 4,764), estimates of vaccine intention varied as much as 37.5 ± 17.4 percentage points as a function of the dichotomous or trichotomous response set. Among participants who had not received the COVID-19 vaccine, the "Unsure" option was more likely to reduce the share of "No" (versus "Yes") responses, whereas among participants who had received the COVID-19 vaccine, the "Unsure" option was more likely to reduce the share of "Yes" (versus "No") responses. The "Unsure" category may increase doubt and decrease reliance on past vaccination behavior when forming intentions. The order of "Yes" and "No" responses had no significant effect. Future research is needed to further evaluate why the effects of including the "Unsure" option vary in direction and magnitude., (© 2024. The Author(s).)

The United States health care system is facing an unprecedented nursing shortage, increasing complexity of care, and fewer experienced nurse mentors. These factors contribute to a cycle of burnout, turnover, decreased quality and safety, and a worsening financial bottom line. Improving these contributing factors depends on our ability to mitigate the structural causes of burnout and turnover. The clinical nurse specialist role is essential to improving the work environment, advancing evidence-based nursing practice, reducing turnover, and stabilizing the bottom line., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Financial incentives are a controversial strategy for increasing vaccination. In this systematic review, we evaluated: 1) the effects of incentives on COVID-19 vaccinations; 2) whether effects differed based on study outcome, study design, incentive type and timing, or sample sociodemographic characteristics; and 3) the cost of incentives per additional vaccine administered. We searched PubMed, EMBASE, Scopus, and Econlit up to March 2022 for terms related to COVID, vaccines, and financial incentives, and identified 38 peer-reviewed, quantitative studies. Independent raters extracted study data and evaluated study quality. Studies examined the impact of financial incentives on COVID-19 vaccine uptake (k = 18), related psychological outcomes (e.g., vaccine intentions, k = 19), or both types of outcomes. For studies of vaccine uptake, none found that financial incentives had a negative effect on uptake, and most rigorous studies found that incentives had a positive effect on uptake. By contrast, studies of vaccine intentions were inconclusive. While three studies concluded that incentives may negatively impact vaccine intentions for some individuals, they had methodological limitations. Study outcomes (uptake versus intentions) and study design (experimental versus observational frameworks) appeared to influence results more than incentive type or timing. Additionally, income and political affiliation may moderate responses to incentives. Most studies evaluating cost per additional vaccine administered found that they ranged from $49-75. Overall, fears about financial incentives decreasing COVID-19 vaccine uptake are not supported by the evidence. Financial incentives likely increase COVID-19 vaccine uptake. While these increases appear to be small, they may be meaningful across populations. Registration: PROSPERO, CRD42022316086 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316086)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: This research seeks to understand how the transition to a new generation of younger, more diverse farmers affects disease prevention efforts on UK farms., Methods: We apply multivariate regression analysis to analyse survey responses from 112 Welsh cattle farm operators., Results: Our results indicate that young farm operators (less than 40 years of age) receive less frequent visits from veterinarians. Further, farm operators who identify as female are less likely to screen and vaccinate against a range of diseases. Finally, both young farmers and female farm operators are less likely to achieve disease-free certification for various economically meaningful livestock diseases., Conclusion: One possible explanation for these outcomes is that female farm operators and young farmers may feel excluded from long-standing social networks in the farm animal health sector., (© 2022 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

This paper assesses the economic value of genetically engineered (GE) Anopheles gambiae mosquitoes as a malaria control strategy. We use an epidemiological-economic model of malaria transmission to evaluate this technology for a range of village-level transmission settings. In each setting, we evaluate public health outcomes following introduction of GE mosquitoes relative to a "status quo" baseline scenario. We also assess results both in contrast to-and in combination with-a Mass Drug Administration (MDA) strategy. We find that-in low transmission settings-the present value (PV) public health benefits of GE mosquito release are substantial, both relative to status quo dynamics and MDA. In contrast, in high transmission settings, the release of GE mosquitoes may increase steady-state infection rates. Our results indicate that there are substantial policy complementarities when GE mosquito release is combined with local MDA-the combined control strategy can lead to local eradication., (© 2021 Wiley-VCH GmbH.)

This research evaluates the effects of the twelve statewide vaccine lottery schemes that were announced as of June 7, 2021 on state vaccination rates. We construct a dataset that matches information on the timing and location of these lotteries with daily, county-level data from the U.S. Centers for Disease Control (CDC) on the cumulative number of people who have received at least one dose of an emergency-authorized Covid-19 vaccine. We find that 10 of the 12 statewide lotteries studied (i.e., all but Arkansas and California) generated a positive, statistically significant, and economically meaningful impact on vaccine uptake after thirty days. On average, the cost per marginal vaccination across these programs was approximately $55., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier B.V. All rights reserved.)

This article investigates how the shift from food-away-from-home and towards food-at-home at the onset of the COVID-19 pandemic affected the U.S. egg industry. We find that the pandemic increased retail and farm-gate prices for table eggs by approximately 141% and 182%, respectively. In contrast, prices for breaking stock eggs-which are primarily used in foodservice and restaurants-fell by 67%. On April 3, 2020, the FDA responded by issuing temporary exemptions from certain food safety standards for breaking stock egg producers seeking to sell into the retail table egg market. We find that this regulatory change rapidly pushed retail, farm-gate, and breaking stock prices towards their long-run pre-pandemic equilibrium dynamics. The pandemic reduced premiums for credence attributes, including cage-free, vegetarian-fed, and organic eggs, by as much as 34%. These premiums did not fully recover following the return to more "normal" price dynamics, possibly signaling that willingness-to-pay for animal welfare and environmental sustainability have fallen as consumers seek to meet basic needs during the pandemic. Finally, in spite of widespread claims of price gouging, we do not find that the pandemic (or the subsequent FDA regulatory changes) had a meaningful impact on the marketing margin for table eggs sold at grocery stores., (© 2021 Elsevier Ltd. All rights reserved.)

Economic insights are powerful for understanding the challenge of managing a highly infectious disease, such as COVID-19, through behavioral precautions including social distancing. One problem is a form of moral hazard, which arises when some individuals face less personal risk of harm or bear greater personal costs of taking precautions. Without legal intervention, some individuals will see socially risky behaviors as personally less costly than socially beneficial behaviors, a balance that makes those beneficial behaviors unsustainable. For insights, we review health insurance moral hazard, agricultural infectious disease policy, and deterrence theory, but find that classic enforcement strategies of punishing noncompliant people are stymied. One mechanism is for policymakers to indemnify individuals for losses associated with taking those socially desirable behaviors to reduce the spread. We develop a coherent approach for doing so, based on conditional cash payments and precommitments by citizens, which may also be reinforced by social norms., (© The Author(s) 2020. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Recent concerns regarding the clinical utilization of clustered regularly interspaced short palindromic repeats (CRISPR) involve uncertainties about the potential detrimental effects that many arise due to unintended genetic changes, as in off-target mutagenesis, during CRISPR genome surgery. This review gives an overview of off-targeting detection methods and CRISPR's place in the clinical setting, specifically in the field of ophthalmology., Results: As CRISPR utilization in the laboratory setting has increased, knowledge regarding CRISPR mechanisms including its off-target effects has also increased. Although a perfect method for achieving 100% specificity is yet to be determined, the past few years have seen many developments in off-targeting detection and in increasing efficacy of CRISPR tools., Conclusion: The CRISPR system has high potential to be an invaluable therapeutic tool as it has the ability to modify and repair pathogenic retinal lesions. Although it is not yet a perfect system, with further efforts to improve its specificity and efficacy along with careful screening of off-target mutations, CRISPR-mediated genome surgery potential can become maximized and applied to patients.

Mutations that activate the protease calpain-5 ( CAPN5) cause a nonsyndromic adult-onset autoinflammatory eye disease characterized by uveitis, altered synaptic signaling, retinal degeneration, neovascularization, and intraocular fibrosis. We describe a pediatric patient with severe inflammatory vitreoretinopathy accompanied by hearing loss and developmental delay associated with a novel, de novo CAPN5 missense mutation (c.865C>T, p.Arg289Trp) that shows greater hyperactivation of the calpain protease, indicating a genotype-phenotype correlation that links mutation severity to proteolytic activity and the possibility of earlier onset syndromic disease with auditory and neurological abnormalities., (© 2018 Velez et al.; Published by Cold Spring Harbor Laboratory Press.)

Purpose of Review: Clustered regularly interspaced short palindromic repeats (CRISPR) is a genome engineering system with great potential for clinical applications due to its versatility and programmability. This review highlights the development and use of CRISPR-mediated ophthalmic genome surgery in recent years., Recent Findings: Diverse CRISPR techniques are in development to target a wide array of ophthalmic conditions, including inherited and acquired conditions. Preclinical disease modeling and recent successes in gene editing suggest potential efficacy of CRISPR as a therapeutic for inherited conditions. In particular, the treatment of Leber congenital amaurosis with CRISPR-mediated genome surgery is expected to reach clinical trials in the near future., Summary: Treatment options for inherited retinal dystrophies are currently limited. CRISPR-mediated genome surgery methods may be able to address this unmet need in the future.

Background: Foveal hypoplasia (FH) in the absence of albinism, aniridia, microphthalmia, or achromatopsia is exceedingly rare, and the molecular basis for the disorder remains unknown. FH is characterized by the absence of both the retinal foveal pit and avascular zone, but with preserved retinal architecture. SLC38A8 encodes a sodium-coupled neutral amino acid transporter with a preference for glutamate as a substrate. SLC38A8 has been linked to FH. Here, we describe a novel mutation to SLC38A8 which causes FH, and report the novel use of OCT-angiography to improve the precision of FH diagnosis. More so, we used computational modeling to explore possible functional effects of known SLC38A8 mutations., Methods: Fundus autofluorescence, SD-OCT, and OCT-angiography were used to make the clinical diagnosis. Whole-exome sequencing led to the identification of a novel disease-causing variant in SLC38A8 . Computational modeling approaches were used to visualize known SLC38A8 mutations, as well as to predict mutation effects on transporter structure and function., Results: We identified a novel point mutation in SLC38A8 that causes FH. A conclusive diagnosis was made using OCT-angiography, which more clearly revealed retinal vasculature penetrating into the foveal region. Structural modeling of the channel showed the mutation was near previously published mutations, clustered on an extracellular loop. Our modeling also predicted that the mutation destabilizes the protein by altering the electrostatic potential within the channel pore., Conclusion: Our results demonstrate a novel use for OCT-angiography in confirming FH, and also uncover genotype-phenotype correlations of FH-linked SLC38A8 mutations.

Purpose: We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular compartments., Methods: CAPN5 gene variants were classified using the exome variant server, and RNA-sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions., Results: Most CAPN5 genetic variation occurs outside its protease core; and searches of cancer and epilepsy/autism genetic databases found no variants similar to hyperactivating retinal disease alleles. The mouse retina expressed one transcript for CAPN5 plus those of nine other calpains, similar to the human retina. In Y79 retinoblastoma cells, the level of CAPN5 transcript was very low. Immunohistochemistry detected CAPN5 expression in the inner and outer nuclear layers and at synapses in the outer plexiform layer. Western analysis of fractionated retinal extracts confirmed CAPN5 synapse localization. Western blots of fractionated brain neuronal extracts revealed distinct subcellular patterns and the potential presence of autoproteolytic CAPN5 domains., Conclusions: CAPN5 is moderately expressed in the retina and, despite higher expression in other tissues, hyperactive disease mutants of CAPN5 only manifest as eye disease. At the cellular level, CAPN5 is expressed in several different functional compartments. CAPN5 localization at the photoreceptor synapse and with mitochondria explains the neural circuitry phenotype in human CAPN5 disease alleles.

Spinocerebellar ataxia type 7 (SCA7) is a late-onset neurodegenerative disease characterized by ataxia and vision loss with no effective treatments in the clinic. The most striking feature is the degeneration of Purkinje neurons of the cerebellum caused by the presence of polyglutamine-expanded ataxin-7. Ataxin-7 is part of a transcriptional complex, and, in the setting of mutant ataxin-7, there is misregulation of target genes. Here, we designed RNAi sequences to reduce the expression of both wildtype and mutant ataxin-7 to test if reducing ataxin-7 in Purkinje cells is both tolerated and beneficial in an animal model of SCA7. We observed sustained reduction of both wildtype and mutant ataxin-7 as well as a significant improvement of ataxia phenotypes. Furthermore, we observed a reduction in cerebellar molecular layer thinning and nuclear inclusions, a hallmark of SCA7. In addition, we observed recovery of cerebellar transcripts whose expression is disrupted in the presence of mutant ataxin-7. These data demonstrate that reduction of both wildtype and mutant ataxin-7 by RNAi is well tolerated, and contrary to what may be expected from reducing a component of the Spt-Taf9-Gcn5 acetyltransferase complex, is efficacious in the SCA7 mouse.

To ensure science better informs the decision-making process, researchers and policy/program managers need to understand and respect each other's way of working, culture and operational timelines. However, there is little practical guidance on how this should be done and even less documented experience with specific mechanisms that better link these two groups. The published literature on information transfer has largely emphasized the dissemination of standard packages of information to ill-defined constituencies whose needs for scientific information are not well understood. Environment Canada's National Water Research Institute, on behalf of the Canadian Council of Ministers of the Environment, led a series of "Linking Water Science to Policy Workshops" as one such mechanism by which recent science could be delivered to practitioners, and practitioners could identify their research needs to scientists and research managers. There is a pressing need to explore and share experiences using creative mechanisms for sustained dialogue and networking between scientists and policy and program managers. The lessons learned from the workshop series and the need for science to continually inform the decision-making process has particular relevance for Canada's Ecosystem Initiatives given their integrated, place-based focus on long-term restoration and protection, and the challenge of continually changing ecosystems.

There is a general consensus that caring is an important personal attribute of helping professionals. One way for educational institutions to develop a caring attitude in students is to provide an academic climate for caring. A total of 45 doctoral students in a clinical psychology program were asked to list specific faculty-student and student-student interactions which they believed reflected a caring attitude towards others. Components of this student-perceived climate for caring include mutual respect and support, personal interest, and informal socialization.