Journal articles on the topic 'Credential loss'

Purpose The foreign-born skilled immigrant population is growing rapidly in Canada but finding a job that utilizes immigrants’ skills, knowledge and experience is challenging for them. The purpose of this paper is to understand the self-perceived health and social status of skilled immigrants who were working in low-skilled jobs in the service sector in Ottawa, Canada. Design/methodology/approach In this qualitative study, semi-structured interviews with 19 high-skilled immigrants working as taxi drivers and convenience store workers in the city of Ottawa, Canada were analysed using a grounded theory approach. Findings Five major themes emerged from the data: high expectations but low achievements; credential devaluation, deskilling and wasted skills; discrimination and loss of identity; lifestyle change and poor health behaviour; and poor mental and physical health status. Social implications The study demonstrates the knowledge between what skilled immigrants expect when they arrive in Canada and the reality of finding meaningful employment in a country where international credentials are less likely to be recognized. The study therefore contributes to immigration policy reform which would reduce barriers to meaningful employment among immigrants reducing the impacts on health resulting from employment in low-skilled jobs. Originality/value This study provides unique insights into the experience and perceptions of skilled immigrants working in low-skilled jobs. It also sheds light on the “healthy worker effect” hypothesis which is a highly discussed and debated issue in the occupational health literature.

Inactivation of the retinoblastoma gene (RB1) product, pRB, is common in many human cancers. Targeting downstream effectors of pRB that are central to tumorigenesis is a promising strategy to block the growth of tumors harboring loss-of-function RB1 mutations. One such effector is retinoblastoma-binding protein 2 (RBP2, also called JARID1A or KDM5A), which encodes an H3K4 demethylase. Binding of pRB to RBP2 has been linked to the ability of pRB to promote senescence and differentiation. Importantly, genetic ablation of RBP2 is sufficient to phenocopy pRB’s ability to induce these cellular changes in cell culture experiments. Moreover, germline Rbp2 deletion significantly impedes tumorigenesis in Rb1+/− mice. The value of RBP2 as a therapeutic target in cancer, however, hinges on whether loss of RBP2 could block the growth of established tumors as opposed to simply delaying their onset. Here we show that conditional, systemic ablation of RBP2 in tumor-bearing Rb1+/− mice is sufficient to slow tumor growth and significantly extend survival without causing obvious toxicity to the host. These findings show that established Rb1-null tumors require RBP2 for growth and further credential RBP2 as a therapeutic target in human cancers driven by RB1 inactivation.

In recent times, electronic portfolios (e-portfolios) are being increasingly used by students and lifelong learners as digital online multimedia résumés that showcase their skill sets and achievements. E-portfolios require secure, reliable, and privacy-preserving credential issuance and verification mechanisms to prove learning achievements. However, existing systems provide private institution-wide centralized solutions that primarily rely on trusted third parties to issue and verify credentials. Furthermore, they do not enable learners to own, control, and share their e-portfolio information across organizations, which increases the risk of forged and fraudulent credentials. Therefore, we propose a consortium blockchain-based e-portfolio management scheme that is decentralized, secure, and trustworthy. Smart contracts are leveraged to enable learners to completely own, publish, and manage their e-portfolios, and also enable potential employers to verify e-portfolio credentials and artifacts without relying on trusted third parties. Blockchain is used as an immutable distributed ledger that records all transactions and logs for tamper-proof trusted data provenance, accountability, and traceability. This system guarantees the authenticity and integrity of user credentials and e-portfolio data. Decentralized identifiers and verifiable credentials are used for user profile identification, authentication, and authorization, whereas verifiable claims are used for e-portfolio credential proof authentication and verification. We have designed and implemented a prototype of the proposed scheme using a Quorum consortium blockchain network. Based on the evaluations, our solution is feasible, secure, and privacy-preserving. It offers excellent performance.

Soil health is an emerging paradigm for which much research in row crop agriculture has been undertaken. Research involving grazing lands and soil health has not been as active, a feature partially attributed to (i) greater erosional rates in cropland, (ii) loss of soil organic matter and reduced soil structure attributed to annual tillage practices, (iii) cash flow from cropland is easier to visualize than the value-added nature of grazing lands, and (iv) there exists more competitive grant funding sources for croplands. Grazing lands do require soil quality augmentation and investment in soil health to optimize their ecosystem services potential. This manuscript, with an emphasis on beef cattle grazing in the central USA, attempts to survey the literature to (i) identify the influence of grazing on important ecosystem services provided by Mollisols and Alfisols, (ii) develop a listing of soil indicators that may be selected to quantify and credential soil quality, and (iii) develop guidelines that align soil indicators and changes in grazing management to support the restoration of ecosystem services.

Soil health is an emerging paradigm for which much research in row crop agriculture has been undertaken. Research involving grazing lands and soil health has not been as active, a feature partially attributed to (i) greater erosional rates in cropland, (ii) loss of soil organic matter and reduced soil structure attributed to annual tillage practices, (iii) cash flow from cropland is easier to visualize than the value-added nature of grazing lands, and (iv) there exists more competitive grant funding sources for croplands. Grazing lands do require soil quality augmentation and investment in soil health to optimize their ecosystem services potential. This manuscript, with an emphasis on beef cattle grazing in the central USA, attempts to survey the literature to (i) identify the influence of grazing on important ecosystem services provided by Mollisols and Alfisols, (ii) develop a listing of soil indicators that may be selected to quantify and credential soil quality, and (iii) develop guidelines that align soil indicators and changes in grazing management to support the restoration of ecosystem services.

Prostate cancer resistance to next-generation hormonal treatment with enzalutamide is a major problem and eventuates into disease lethality. Biologically active glucocorticoids that stimulate glucocorticoid receptor (GR) have an 11β-OH moiety, and resistant tumors exhibit loss of 11β-HSD2, the oxidative (11β-OH → 11-keto) enzyme that normally inactivates glucocorticoids, allowing elevated tumor glucocorticoids to drive resistance by stimulating GR. Here, we show that up-regulation of hexose-6-phosphate dehydrogenase (H6PD) protein occurs in prostate cancer tissues of men treated with enzalutamide, human-derived cell lines, and patient-derived prostate tissues treated ex vivo with enzalutamide. Genetically silencing H6PD blocks NADPH generation, which inhibits the usual reductive directionality of 11β-HSD1, to effectively replace 11β-HSD2 function in human-derived cell line models, suppress the concentration of biologically active glucocorticoids in prostate cancer, and reverse enzalutamide resistance in mouse xenograft models. Similarly, pharmacologic blockade of H6PD with rucaparib normalizes tumor glucocorticoid metabolism in human cell lines and reinstates responsiveness to enzalutamide in mouse xenograft models. Our data show that blockade of H6PD, which is essential for glucocorticoid synthesis in humans, normalizes glucocorticoid metabolism and reverses enzalutamide resistance in mouse xenograft models. We credential H6PD as a pharmacologic vulnerability for treatment of next-generation androgen receptor antagonist–resistant prostate cancer by depleting tumor glucocorticoids.

As a part of our continued venture to develop a safe and effective spermicide, we have identified a triterpene glycoside (Acaciaside-B (Ac-B))-enriched fraction (Ac-B-en) isolated from the seeds of Acacia auriculiformis and evaluated its spermicidal potential in vitro. Sperm motility was completely inhibited within 20 s at a minimum effective concentration (MEC) of 120 μg/ml. Tests for sperm viability by dual fluoroprobe staining showed the effect to be spermicidal with an EC50 of 35.20 μg/ml. A series of investigations including tests for hypo-osmotic swelling, membrane lipid peroxidation, and electron microscopy document that the spermicidal effect of the fraction involves loss of sperm plasma membrane integrity and dissolution of the acrosomal vesicle – the two most important structural components that play diverse roles in physiological functions of sperm including fertilization. The fraction at 10×MEC exerted no detrimental effects on in vitro growth of Lactobacillus acidophilus, which is considered the major constituent of vaginal microflora that maintains vaginal health. Ames tests performed with different strains of Salmonella typhimurium including TA 97a, 98, 100, and 102, which detect mutagens causing bp substitution or frameshifting at G-C or A-T bp, demonstrate no mutagenic potential of the fraction. Significant spermicidal potential with no possible mutagenic effect and adverse impacts on lactobacilli growth attests to the credential of Ac-B-en as a prospective future spermicide for the development of a safe and effective vaginal contraceptive formulation.

Abstract Epigenetic dysregulation is frequently observed in the disease pathology of pediatric cancers, including neuroblastoma, the most common extracranial solid tumor in pediatric patients. Neuroblastoma tumors co-opt developmentally linked adrenergic or mesenchymal super-enhancer landscapes that rewire their transcriptional programs. Here, we describe that the lineage commitment to a mesenchymal epigenetic state is an important mechanism of resistance to anti-GD2 therapy through loss of GD2 antigen, a ganglioside glycolipid expressed on the cell surface. Low GD2 expression was significantly correlated with the mesenchymal state in a large panel of neuroblastoma cell lines and a forced adrenergic-to-mesenchymal transition conferred downregulation of GD2 and resistance to anti-GD2 antibody. Mechanistically, low-GD2 expressing cell lines demonstrated significantly reduced expression of the ganglioside synthesis enzyme ST8SIA1 (GD3 synthase), resulting in a bottlenecking of GD2 synthesis. Genome-wide CRISPR/Cas9 screening to identify regulators of GD2 in neuroblastoma revealed that the ablation of the polycomb repressive complex 2 (PRC2) significantly upregulates GD2 expression in GD2-low cells. Pharmacologic inhibition of EZH2 resulted in epigenetic rewiring of mesenchymal neuroblastoma cells into an adrenergic-like state, re-expressed ST8SIA1, and restored surface expression of GD2 and sensitivity to anti-GD2 antibody. These data identify developmental lineage as a key determinant of sensitivity to anti-GD2 based immunotherapies and credential PRC2 inhibitors for clinical testing in combination with anti-GD2 antibody to enhance outcomes for children with neuroblastoma. Citation Format: Nathaniel W. Mabe, Min Huang, Daniel A. Schaefer, Guillermo N. Dalton, Giulia Digiovanni, Gabriela Alexe, Anna C. Geraghty, Delan Khalid, Marius M. Mader, Michal Sheffer, Miles H. Linde, Nghi Ly, Maria Caterina Rotiroti, Benjamin A. H. Smith, Marius Wernig, Carolyn R. Bertozzi, Michelle Monje, Constantine Mitsiades, Ravindra Majeti, Ansuman T. Satpathy, Kimberly Stegmaier, Robbie G. Majzner. Lineage plasticity dictates responsiveness to anti-GD2 therapy in neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr PR003.

AbstractSociologists have not attempted to explain the causes of higher levels of perceived job insecurity among racial/ethnic minorities than those of Whites in privileged occupations. This study examines two possible explanations for this finding among White, African American, and Latino professionals and managers. The first emphasizes the discrimination-induced, structural marginality experienced by minorities in the workplace (the marginalized-worker perspective), and the second emphasizes learned dispositions—i.e., fatalism and mistrust—that are brought to the workplace (the dispositional perspective). Using data from the General Social Survey (GSS) and ordered probit regression analyses for both men and women, our findings provide greater support for the marginalized-worker perspective. Results reveal African Americans and Latino men and women have a greater fear of job loss than their White counterparts, regardless of their human capital credentials (e.g., education, work experience) and job/labor market advantages (e.g., job authority, job autonomy, unionized status, favorable market sector). Along these lines, these traditional, stratification-based predictors provide greater insulation from perceived job insecurity for Whites than racial/ethnic minorities. Less support is found for the dispositional perspective: one disposition—fatalism—is associated with greater fear of job loss for African American men and women compared to Whites.

The article examines the current state of cybersecurity and identification of cyber threats in the use of credentials, the formulation of measures to minimize the risk of theft, damage or loss of confidential accounting information in the cyber environment of its use and maintenance

The Pouncing of Delicate Information like Private Data or Rumours is a serious issue in Online social media Now-a-days. One Solution for stopping the Pouncing of Delicate Data is Limiting the spreading among social media users. However, the spreading of Limiting measures also stops the spreading of Non-Delicate Data which will result in worst experience for the user. To handle this situation, in our paper, we will study the problem of how to reduce the Delicate data while storing the non-Delicate data as same without effecting it. In our study we use known Diffusion credentials of all users for Completely-Known Networks and unknown Diffusion credentials of some users for Partially-Known Networks in Prior. For this we use Bandit Framework to Combinedly design the Result with Polynomial Convolution in both situations. Finally, we can say that our solution ensures that non-Delicate Diffusion loss will be 40% less compared to four baseline Algorithm.

This article describes how an iconic mystical Sufi ritual of body wounding, zarf, was stripped of its mystical credentials and conventional efficacy amid tensions between Rifai reformists and traditionalists in a small Roma neighborhood in Skopje, Macedonia. The death of a sorcerer and a funeral event-series set the scene for acts of ‘anti-wonder’ and demystification by the Rifai reformists. Despite the history of socialist secularism and inadvertently secularizing Islamic reforms in the region, demystification signaled not the loss of enchantment per se, but a competition for legitimate forms of wonder. In addition to accounting for socio-historical context and relational forms of Islam, the real challenge is how to see a demystified ritual for its explicit intellectual capacity to stimulate speculation about itself.

The dairy industry can be considered a contributor to biodiversity loss in Australia. To address this, many forms of governance can be enlisted, including traditional legislation and regulations, persuasive techniques such as publicly funded subsidy programs or education, and participation in voluntary stewardship programs. This paper explores the benefits of collaborative governance programs, which have international applications to reduce the impact of the dairy industry on biodiversity loss. However, as the Australian sector is unique, the specific opportunities and present challenges are discussed. This paper reports three important objectives that could underpin industry-led initiatives by supporting improved biodiversity conservation on dairy farms: (1) Increase the personal and financial capacities of individual farmers to operate profitable, biodiverse farms; (2) Facilitate market rewards to incentivise pro-conservation behaviours; and (3) Improve the effectiveness of the implementation of biodiversity protection laws and regulatory objectives via collaborative governance arrangements. Existing environmental programs that have been developed by the dairy industry could be suitable for incorporation into more formal co-governance structures sympathetic to biodiversity conservation. However, to be successful in addressing sustainability issues, including biodiversity loss, strengthening the integrity mechanisms around farmers’ self-reporting of performance is required to ensure that the industry can credibly refute claims of greenwashing and defend their environmental credentials in the global marketplace.

AbstractUsers’ devices, e.g., smartphones or laptops, are typically incapable of securely storing and processing cryptographic keys.We present Tandem, a novel set of protocols for securing cryptographic keys with support from a central server. Tandem uses one-time-use key-share tokens to preserve users’ privacy with respect to a malicious central server. Additionally, Tandem enables users to block their keys if they lose their device, and it enables the server to limit how often an adversary can use an unblocked key. We prove Tandem’s security and privacy properties, apply Tandem to attributebased credentials, and implement a Tandem proof of concept to show that it causes little overhead.

Purpose: Low vision rehabilitation research is a quickly growing area, due in part to the increase in the demand for services geared at older adults with age-related vision loss. Various professions collaborate to provide such rehabilitation services; however, it is currently unclear which profession takes the leading role in advancing the frontiers of low vision rehabilitation research. A recent review article proposed that in Canada, this role is held by physicians. The present study was conducted to replicate these findings under conditions of a systematic review. Method: A search of seven databases and a hand-search of four vision rehabilitation journals identified articles on low vision rehabilitation whose first author had an affiliation at a Canadian institution. Data on professional credentials, funding source, and study content was tabulated. Results: Of the 1,870 references, data from 215 eligible articles were extracted. The top four author credentials were optometrists (with or without PhD; 56 papers, 26.0%), followed by researchers with PhDs only (48 papers, 22.3%), researchers with master’s degrees (43 papers, 20.0%), and medical doctors (with or without PhD; 39 papers, 18.1%). Vision rehabilitation journals published 38 per cent of all papers, followed by ophthalmology (27%) and optometry journals (22%). Publications in the past 11 years amounted to over 50 per cent of the output over the 64-year publication history in this field in Canada, 70 per cent of which were based in universities. Conclusion: The results reflect the mosaic structure of low vision rehabilitation research in Canada, highlighting collaborations among researchers, clinicians, funding sources and rehabilitation agencies. Given its multidisciplinary nature, low vision rehabilitation research seems to be driven by collaboration among the professions.

This article describes how as day-to-day Android users are increasing, the Internet has become the type of environment preferred by attackers to inject malicious packages. This is content with the intention of gathering critical information, spying on user details, credentials, call logs, contact details, and tracking user location. Regrettably it is very hard to detect malware even with antivirus software/packages. In addition, this type of attack is increasing day by day. In this article the authors have chosen a Supervised Learning Classification Tree-based algorithm to detect malware on the data set. Comparison amongst all the classifiers on the basis of accuracy and execution time are used to build the classifier model which has the highest executed detections.

An intruder of a company’s network may use stolen login credentials to silently collect sensitive data. Such malicious user behavior is difficult to detect as long as it does not trigger access violation or data leak alert. In this paper, we propose to use an ensemble of three unsupervised anomaly detection algorithms, namely OCSVM, RNN and Isolation Forest, to detect abnormal user behavior patterns. Besides, an User Behavior Analytics (UBA) Platform is proposed to collect logs, extract features and conduct experiments. The experiment results indicate that our algorithm outperforms each individual algorithm with recall of 96.55% and precision of 91.24% on average, while both OCSVM and RNN suffer from anomalies in the training set, and [Formula: see text] produces more false positives and false negatives in prediction.

The Politics of Public Management: The HRDC Audit of Grants and Contributions, David A. Good, The Institute of Public Administration of Canada Series in Public Management and Governance; Toronto, University of Toronto Press, 2003, pp. 240The literature in public administration in some ways suffers from not having more practitioners reflecting, writing and analyzing their experiences. Thus David Good's book analyzing the HRDC's so-called “billion dollar boondoggle” is a welcome contribution. His background as both a senior manager/executive within the Federal government and his academic credentials—a doctorate in policy and administration sets him apart—as a practitioner-academic. Good possesses the senior public manager's mind for detail and this book provides a clear account of the ebbing and flowing of events, beginning with the January 2000 release of HRDC's internal audit that implied a loss of a billion dollars, to the Auditor General's report of October that same year which, while critical of monitoring and reporting practices, concluded that only $85,000 was unaccounted for. The media and the opposition, at this point quickly lost interest.

Professors Cain and Grofman were kind enough to suggest that I review the expert witness declarations inBadham v. Eu(D.C. California, 1984) in the light of my own previous research on expert witness testimony to identify frequently used modes of argumentation.The single most important observation I can make about the nature of the expert witness testimony inBadhamis to note its high quality. The experts inBadhamare addressing real issues. The differences among these experts rest on differing normative views and on disputes about difficult empirical and methodological questions. Moreover, the genuine expertise of these social scientists cannot be in dispute. Thus, the most common techniques used in disputations among experts: (1) impeaching an expert witness' motives (e.g., accusing him of being a “hired gun” or an “ideological partisan”); (2) downgrading his academic credentials or claims to subject matter expertise; and (3) finding instances where his testimony has been repudiated by the courts, are simply inapplicable. This has not left the experts inBadhamat a loss for words—but none of the disagreements among them are in the nature of ad hominem attacks.

Objective: To present athletic trainers with recommendations for safe weight loss and weight maintenance practices for athletes and active clients and to provide athletes, clients, coaches, and parents with safe guidelines that will allow athletes and clients to achieve and maintain weight and body composition goals.Background: Unsafe weight management practices can compromise athletic performance and negatively affect health. Athletes and clients often attempt to lose weight by not eating, limiting caloric or specific nutrients from the diet, engaging in pathogenic weight control behaviors, and restricting fluids. These people often respond to pressures of the sport or activity, coaches, peers, or parents by adopting negative body images and unsafe practices to maintain an ideal body composition for the activity. We provide athletic trainers with recommendations for safe weight loss and weight maintenance in sport and exercise. Although safe weight gain is also a concern for athletic trainers and their athletes and clients, that topic is outside the scope of this position statement.Recommendations: Athletic trainers are often the source of nutrition information for athletes and clients; therefore, they must have knowledge of proper nutrition, weight management practices, and methods to change body composition. Body composition assessments should be done in the most scientifically appropriate manner possible. Reasonable and individualized weight and body composition goals should be identified by appropriately trained health care personnel (eg, athletic trainers, registered dietitians, physicians). In keeping with the American Dietetics Association (ADA) preferred nomenclature, this document uses the terms registered dietitian or dietician when referring to a food and nutrition expert who has met the academic and professional requirements specified by the ADA's Commission on Accreditation for Dietetics Education. In some cases, a registered nutritionist may have equivalent credentials and be the commonly used term. All weight management and exercise protocols used to achieve these goals should be safe and based on the most current evidence. Athletes, clients, parents, and coaches should be educated on how to determine safe weight and body composition so that athletes and clients more safely achieve competitive weights that will meet sport and activity requirements while also allowing them to meet their energy and nutritional needs for optimal health and performance.

The Accreditation Council for Graduate Medical Education imposed 80-hour work week constraints on residency programs in July 2003. Certain programs were granted an additional 10 per cent for specific educational purposes, bringing restrictions to 88 hours per week. The increased demand for residents to leave the hospital has placed teaching institutions in exhaustive situations to provide comprehensive patient care. In response to the work hour constraints among residents and emergency room staff, a unique group of registered nurses, trauma nurse specialists (TNSs), were credentialed with advanced practice skill sets. Governed by practice guidelines and overseen by a medical director, TNSs perform invasive procedures that are normally the responsibility of the surgical resident. The purpose of this study was to evaluate work hours saved for surgery residents using credentialed nurses (TNSs). Procedure logs were maintained by the TNSs over a 6-month period, and surgical house staff (postgraduate year 1–3) over a 4-month period. A total of 423 procedures were recorded, reflecting time taken for attempted/completed procedures and complications. Resident procedures numbered 98; TNS procedures numbered 325. TNSs spent an average of 42 hours per month (10.6 hours per week) completing advanced procedures with no statistical difference in time or complications compared with surgical residents. By using the TNSs, work hours for surgery residents were saved while maintaining a safe and reliable work atmosphere for patients.

Inadequacies and faults that are the reason of vulnerabilities are hazardous for the websites. The authors' chief intention is to trim down those assailon websites by restraining the attributes accountable for these assails. This article categorizes those cases/ attributes into 10 categories and arranges them inpriority according to their severity. These attributes influence which contributes to losses in terms of monetary as well as humanity. By prioritizing these attributes, web designers as well as users will check twice on these aspects before entering confidential information into the website. The opinion of different web designers and experts of different companies was captured to prioritize these attributes using an analytical hierarchical process and two way assessment methods so that the loss should be minimized. Research confirms that total severity measure aids the severities of these attribute's contribution towards vulnerabilities. The findings of the two way assessment technique show that there is only one such attribute which happens to be extremely severe in comparison to other attributes and needs imperative consideration while designing websites and also by users before entering their confidential credentials on a website to curtail the losses caused by black hat guys.

Professors Cain and Grofman were kind enough to suggest that I review the expert witness declarations in Badham v. Eu (D.C. California, 1984) in the light of my own previous research on expert witness testimony to identify frequently used modes of argumentation.The single most important observation I can make about the nature of the expert witness testimony in Badham is to note its high quality. The experts in Badham are addressing real issues. The differences among these experts rest on differing normative views and on disputes about difficult empirical and methodological questions. Moreover, the genuine expertise of these social scientists cannot be in dispute. Thus, the most common techniques used in disputations among experts: (1) impeaching an expert witness' motives (e.g., accusing him of being a “hired gun” or an “ideological partisan”); (2) downgrading his academic credentials or claims to subject matter expertise; and (3) finding instances where his testimony has been repudiated by the courts, are simply inapplicable. This has not left the experts in Badham at a loss for words—but none of the disagreements among them are in the nature of ad hominem attacks.

AbstractWe investigate data exfiltration by third-party scripts directly embedded on web pages. Specifically, we study three attacks: misuse of browsers’ internal login managers, social data exfiltration, and whole-DOM exfiltration. Although the possibility of these attacks was well known, we provide the first empirical evidence based on measurements of 300,000 distinct web pages from 50,000 sites. We extend OpenWPM’s instrumentation to detect and precisely attribute these attacks to specific third-party scripts. Our analysis reveals invasive practices such as inserting invisible login forms to trigger autofilling of the saved user credentials, and reading and exfiltrating social network data when the user logs in via Facebook login. Further, we uncovered password, credit card, and health data leaks to third parties due to wholesale collection of the DOM. We discuss the lessons learned from the responses to the initial disclosure of our findings and fixes that were deployed by the websites, browser vendors, third-party libraries and privacy protection tools.

Abstract Identification of rational therapeutic targets is an important strategy to improve the cure rate of diffuse large B-cell lymphoma (DLBCL). We previously showed that inhibition of the phosphodiesterase 4B (PDE4B) unleashes cyclic-AMP (cAMP) inhibitory effects toward the PI3K/AKT pathway and induces apoptosis. These data raised important considerations as to which upstream regulators mediate cAMP inhibition of PI3K/AKT, and how identifying this signaling route could be translated into clinical initiatives. We found that in normal and malignant B cells, cAMP potently inhibit the phosphorylation and activity of the tyrosine kinase SYK. Using genetic models of gain- and loss-of-function, we demonstrated the essential role for PDE4B in controlling these effects in DLBCL. Furthermore, we used a constitutively active SYK mutant to confirm its central role in transducing cAMP effects to PI3K/AKT. Importantly, given SYK credentials as a therapeutic target in B-cell tumors, we explored the role of PDE4B in these responses. In multiple DLBCL models, we found that genetically, hence specifically, inhibiting PDE4B expression significantly improved the efficacy of SYK inhibitors. Our data defined a hitherto unknown role for cAMP in negatively regulating SYK and indicate that combined inhibition of PDE4B and SYK should be actively pursued.

The World Wide Web (www) has become an interactive medium for millions of Internet users across the world, daily visiting occur for various purposes. However, their behavior could be monitored by various service providers or company’s website they visited for several purposes. Thus, we can see that if certain data pre-processing techniques are practiced correctly, results will be of high quality and in turn provide substantial evidence of the user and its web session. This paper provides a way of knowing user behavior on the web. It explains the use of cookies: Cookies allow you to do many things such as log on to Internet Banking, have us 'remember' your log-in preferences, when logging on, a pop-up window appears stating the service is not available and to try later. A misspelled domain name in the address line. Lotteries that charge a fee to collect your winnings, apply for products and services online, and use financial tools like our ‘find and compare’ mortgage calculators., servers, and proxy logs with some scripting to be able not only to get a user’s IP address but also get personal information like age, identity, and any other credential as long as the user puts them down while using the web.

4029 Background: The safety of laparoscopic gastrectomy for advanced gastric cancer is controversial. We conducted a multi-institutional, randomized controlled trial to compare short- and long-term outcomes of laparoscopic distal gastrectomy (LAP) with D2 lymph node dissection for advanced gastric cancer in comparison to open distal gastrectomy (OP) in Japan (UMIN000003420). We herein demonstrate short-term outcomes of this trial. Methods: Patients with potentially curable gastric cancer (T2-T4, N0-2 and M0) by distal gastrectomy were eligible for inclusion. Between November 2009 and July 2016, 507 patients were randomly assigned to either the LAP group (n = 252) or the OP group (n = 255). Only credentialed surgeons in both the procedures from 37 Japanese institutions participated in the study. The primary endpoint was 5-year relapse free survival. Secondary endpoints were 5-year overall survival, adverse events and short-term clinical outcomes. Results: According to study protocol, 47 patients among the total eligible patients were excluded because of distant metastasis or tumor extension intraoperatively. The remaining 460 patients underwent distal gastrectomy with D2 lymph node dissection and were analyzed as per protocol. Estimated blood loss was lower in LAP than in OP (30 vs. 150 ml, P < 0.001) and operative time was longer in LAP than in OP (291 vs. 205 min, P < 0.001). Post-operative analgesics use was less in LAP than in OP (38.3 vs. 53.6 %, P = 0.001), and first day of flatus was shorter in LAP than in OP (2 vs. 3 days, P < 0.001). There were no significant differences in all grade intra-operative complications (LAP 0.9% vs. OP 2.6%, P = 0.285). In addition, there were no significant differences in grade 3 and higher post-operative complications between the two groups (LAP 3.1% vs. OP 4.7%, P = 0.473). Hospital mortality was 0.4 % in each group. Conclusions: Credentialed surgeons could safely perform laparoscopic distal gastrectomy with D2 lymph node dissection for locally advanced gastric cancer. The laparoscopic approach could be accepted without increasing major surgical complications in this setting. Clinical trial information: 000003420.

With the large-scale deployment of industrial Internet of things (IIoT) devices in 5/6G environments, the number of vulnerabilities threatening IIoT security is growing dramatically, including a mass of undisclosed IIoT vulnerabilities that lack mitigation measures. Coordination vulnerability disclosure (CVD) is one of the most popular vulnerabilities sharing solutions, in which security workers (SWs) can develop undisclosed vulnerability patches together. However, CVD assumes that SWs are all honest and thus offering chances for dishonest SWs to internally leak undisclosed IIoT vulnerabilities. To combat such internal threats, we propose an undisclosed IIoT vulnerabilities sharing protection (UIV-TSP) scheme against internal leakage. In this paper, a dynamic token is an implicit access credential for an SW to acquire an undisclosed vulnerability message, which is only held by the system and constantly updated with the SW access. The latest updated token can be stealthily sneaked into the acquired information as the traceability token to prevent internal leakage. To quickly distinguish dishonest SWs, the feedforward neural network (FNN) is adopted to evaluate the trust value of SWs. Meanwhile, we design a blockchain-assisted continuous logs storage method to achieve the tamper-proofing of dynamic token and the transparency of undisclosed IIoT vulnerabilities sharing. The simulation results indicate that our proposed scheme is resilient to suppress dishonest SWs and protect the IIoT undisclosed vulnerabilities effectively.

The Canadian Earning Supplement Project (ESP) was conducted from 1994 through 1996 to test a wage subsidy program that made supplemental payments to individuals who found a new full-time job that paid less than their previous job within 26 weeks of job search. contrary to the optimistic expectations held by researchers and previous studies, the impact of ESP was disappointing. This paper attempts to uncover the reasons why ESP did not have sufficient impact by analyzing the reemployment experiences of ESP participants. I found that the insufficient impacts of ESP could be attributed to the fact that a significant proportion (65 percent) of sample members set initial reservation wages lower than their previous wages. Workers who enjoyed wage premiums in their previous jobs (whether job-specific, industry-specific, or union-specific premiums) were found to have low initial reservation wages. In contrast, workers with high education credentials, white-collar workers, and workers in knowledge-based industries appeared to be not interested in the ESP offer, because they expected no earnings loss and thus no gain in lifetime wealth from receipt of the supplement. To be discordant with the propositions made by past theroretical works on wage subsidy programs, job-search intensity was not the major link through which ESP impacts were channeled. Another important finding is that ESP manifested a significantly large impact on the optimal timing of leaving unemployment, even through its impact on the overall probabililty of leaving unemployment was minuscule.

Immigrants are often pressed to show how they will contribute to a host country, thus proving through their conditions of entry and human capital whether they will be perceived as an asset or burden, and this is juxtaposed with the host country’s institutions offering an improved quality of life, mainly through employment. Seeking employment is often a key factor to be economically assimilated, and in the case of highly educated Turkish migrants, the opportunity to reclaim their previous professional and quality of life statuses. Based on qualitative research, we have examined the experiences of highly educated Turkish people (n = 42) in the recently forced migrant population. Following events including terrorism and the coup on 15 July 2016, Türkiye experienced the highest forced migration in her history. With exiled Turkish migrants, the forced aspect of their migration prompts them to seek a host country that provides safety, and they are also driven to transfer their educational degrees and professional credentials. However, changing careers to become educated and certified in new fields takes time and resources, contributing to a fluctuating economic status and loss of well-being. Once this is regained, their economic situation is improved, but there is still the lost time from the immigration and transfer period. Thus, the process has positive and negative components, but understanding this nuanced process provides opportunities for policy reform that can shorten the time of re-education, increase employability, and support well-being.

The level of students’ involvement in examination malpractice in Junior High Schools in Ghana has become increasingly worrying, problematic and threatening to the well-being of Ghanaian educational system. However, there seems to be paucity of studies on the causes and effects of examination malpractices among Junior High School students in Ghana and Adansi South District (New Edubiase) of the Ashanti Region of Ghana in particular. This research seeks to bridge this knowledge gap by identifying and discussing the causes and effects of examination malpractices among Junior High School students in New Edubiase. Study methods include the use of questionnaire (open and close ended questions). A total of ninety (90) respondents comprising of sixty (60) students and thirty (30) teachers who took part in this study were randomly and purposively selected. The results indicate that collusion, examination leakages, smuggling of answers scripts and late submission of parcels, sending foreign materials into the examination hall, impersonation, dubbing, writing on items (sheets of papers, handkerchief, erasers, and covers of calculator), writing answers on question papers and exchanging them with others to copy, communicating orally or through gestures during examination and using fake names index numbers, buying examination questions for students and offering money to examination authorities to assist their children and mass cheating are the nature of examination malpractices among Junior High School students in New Edubiase. The study revealed that examination malpractices brings total loss of trust in the educational system, reduced enrolmentof students in school, frequent cancellation of results, discourages good students/candidates from studying hard, derives innocent students’ opportunity for admission, decrease job efficiency, bring dissatisfaction on the part of the candidates, renders the goals of education invalid, examination cheats obtain certificates which they cannot defend, examination malpractice has reduced the quality and standard of education in the country, examination malpractice adversely affects national productivity as the certificates workers possess are not backed with commensurate knowledge, skills and values, examination malpractice makes employers of labour lose confidence in the educational system and the credentials that are paraded by job seekers and lastly examination malpractice leads to high educational wastage as those who cheat to pass examinations at a lower level, achieve very poorly at a higher level.Keywords: Causes, Effects, Examination, Malpractices, Junior High School, Students, New Edubiase, Ashanti Region, Ghana.

IntroductionIt is important to ascertain the cost-effectiveness of alternative services to traditional cardiac rehabilitation while the economic credentials of the Smartphone Cardiac Rehabilitation, Assisted self-Management (SCRAM) programme among people with coronary heart disease (CHD) are unknown. This economic protocol outlines the methods for undertaking a trial-based economic evaluation of SCRAM in the real-world setting in Australia.Methods and analysisThe within-trial economic evaluation will be undertaken alongside a randomised controlled trial (RCT) designed to determine the effectiveness of SCRAM in comparison with the usual care cardiac rehabilitation (UC) alone in people with CHD. Pathway analysis will be performed to identify all the costs related to the delivery of SCRAM and UC. Both a healthcare system and a limited societal perspective will be adopted to gauge all costs associated with health resource utilisation and productivity loss. Healthcare resource use over the 6-month participation period will be extracted from administrative databases (ie, Pharmaceutical Benefits Scheme and Medical Benefits Schedule). Productivity loss will be measured by absenteeism from work (valued by human capital approach). The primary outcomes for the economic evaluation are maximal oxygen uptake (VO2max, mL/kg/min, primary RCT outcome) and quality-adjusted life years estimated from health-related quality of life as assessed by the Assessment of Quality of Life-8D instrument. The incremental cost-effectiveness ratio will be calculated using the differences in costs and benefits (ie, primary and secondary outcomes) between the two randomised groups from both perspectives with no discounting. All costs will be valued in Australian dollars for year 2020.Ethics and disseminationThe study protocol has been approved under Australia’s National Mutual Acceptance agreement by the Melbourne Health Human Research Ethics Committee (HREC/18/MH/119). It is anticipated that SCRAM is a cost-effective cardiac telerehabilitation programme for people with CHD from both a healthcare and a limited societal perspective in Australia. The evaluation will provide evidence to underpin national scale-up of the programme to a wider population. The results of the economic analysis will be submitted for publication in a peer-reviewed journal.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12618001458224).

ABSTRACT Background Training residents to become competent in common bedside procedures can be challenging. Some hospitals have attending physician–led procedure teams with oversight of all procedures to improve procedural training, but these teams require significant resources to establish and maintain. Objective We sought to improve resident procedural training by implementing a resident-run procedure team without routine attending involvement. Methods We created the role of a resident procedure coordinator (RPC). Interested residents on less time-intensive rotations voluntarily served as RPC. Medical providers in the hospital contacted the RPC through a designated pager when a bedside procedure was needed. A structured credentialing process, using direct observation and a procedure-specific checklist, was developed to determine residents' competence for completing procedures independently. Checklists were developed by the residency program and approved by institutional subspecialists. The service was implemented in June 2016 at an 850-bed academic medical center with 70 internal medicine and 32 medicine-pediatrics residents. The procedure service functioned without routine attending involvement. The impact was evaluated through resident procedure logs and surveys of residents and attending physicians. Results Compared with preimplementation procedure logs, there were substantial increases postimplementation in resident-performed procedures and the number of residents credentialed in paracenteses, thoracenteses, and lumbar punctures. Fifty-nine of 102 (58%) residents responded to the survey, with 42 (71%) reporting the initiative increased their ability to obtain procedural experience. Thirty-one of 36 (86%) attending respondents reported preferentially using the service. Conclusions The RPC model increased resident procedural training opportunities using a structured sign-off process and an operationalized service.

Objectives: This study evaluates the availability of perioperative nutritional care protocols and the practices of bariatric registered dietitians in Saudi Arabia. The primary outcomes of the study were conducted using an adapted American survey “with permission.” Methods: A cross-sectional survey of a selected 32 dietitians providing bariatric services completed a self-administered online questionnaire from 12 hospitals in Jeddah, Saudi Arabia. Results: All surveyed dietitians were females, mainly Saudi nationals (93.9%, n = 30), and accredited by the Saudi Commission for Health Specialties (93.8%, n = 30). Only 37.5% (n = 6) of the dietitians were specialized in bariatric surgery. Perioperative common practices of dietitians included a conduct of screening for nutrition risk before (44%, n = 14) and after surgery (62.5%, n = 20) and applied a nutrition management protocol that is mainly based on the application of nutrition care process (62.5%, n = 20). Dietitians (81%, n = 26) reported the importance of having standardized protocols for nutritional management of patients undoing bariatric surgery, where 69% (n = 22) confirmed the availability of pre-operative written protocols in hospitals and 75% (n = 24) confirmed the existence of post-operative protocols. Pre-operative practices included using approaches for weight loss before surgery, for example, very low and low-calorie diet. Dietitians (25%, n = 8) see two to ten patients per month. The sleeve gastrectomy procedure is the most often performed surgery. Conclusion: This is the first study to evaluate the perioperative nutrition care protocols and practices related to bariatric surgery in Saudi Arabia. Perioperative bariatric protocols are available, but some dietitians are not aware of their availability and contents. Researchers emphasize the importance of creating national protocols by the Saudi Credentials Body to standardize practices within the field.

International oil and gas companies have poured significant resources into building social licence since the 1990s. Despite this extensive effort at a local community level adjacent to operations, social licence has not been consistently gained and broad-based community trust in the industry is lacking. This paper argues that social licence has not been achieved globally, because oil and gas companies have failed to respond directly and appropriately to the concerns of all stakeholders. We argue that while international oil and gas companies have largely been successful in achieving and communicating the benefits they bring at a local level, in terms of royalties, local community investment, jobs and even in environmental credentials, they have not achieved social licence because it is no longer granted by only local communities. It extends to a potentially more powerful group of largely urban dwelling broader society, enabled by technology, especially social media. A new way of communicating and operating is required if oil and gas companies want to avoid the loss of social licence in future. This article contends three distinct opportunities to strengthen social licence in today’s context: 1. Understand and use social media to proactively address the concerns of all of your stakeholders. This includes responding to societal and global issues, which no longer centre on the ‘jobs, taxes and philanthropy’ dialogue that has been the mainstay of oil and gas industry communications; 2. Stress the role gas has as an enabler of renewable energy development and penetration; and 3. Review your investment strategy in light of the scientific reality of climate change. To gain social licence in future, action will be required to follow the lead of some fossil fuel majors who have already moved to build a new world, decarbonised portfolio of the future.

Abstract We have recently established mosaic analysis by dual recombinase-mediated cassette exchange (MADR), which permits stable labeling of mutant cells expressing transgenic elements from precisely defined chromosomal loci. MADR provides a toolkit of elements for combinatorial labeling, inducible/reversible transgene manipulation, VCre recombinase expression, and genetic manipulation of human cells. Further, we have demonstrated the versatility of MADR by creating glioma models with mixed, reporter-identified zygosity or with “personalized” driver mutations from pediatric glioma. For example, introducing H3f3a (aka H3.3) mutation variants with MADR regulates the spatiotemporal profile of glioma, and single-cell RNA and ATAC sequencing analysis demonstrates a recapitulation of developmental hierarchy seen in K27M mutant human glioma. Moreover, we have generated novel models of H3.3 WT glioma, H3.3 G34R glioma, and supratentorial ependymoma using patient-derived oncofusion transgenes. These models display a high degree of phenotypic fidelity and we now compare these models on a single-cell level with our previous models, mouse single-cell RNA glioma datasets from other studies, and human tumor cell transcriptomes. Our multi-omics approach includes integration of ChIP-seq/Cut&Tag datasets, single-cell ATAC, and single-cell Cut&Tag datasets. Moreover, we have engineered a novel methodology for inducible gain- and loss-of function perturbation studies in vivo. Using ETS transcription factors as a proof-of-principle, we overlay these genetic perturbations on the glioma atlas to examine the gene networks altered by precise molecular manipulations. We hope that these combined approaches will enable researchers to discover disease mechanisms with increased resolution and test therapeutics in credentialed pre-clinical disease models.

Abstract On June 9th, 2015, ACME Oil Company’s rig suffered a dynamic positioned ‘run-off’. The mobile drilling unit lost its station above the wellhead and a loss of well control was experienced. “A massive environmental emergency unfolded…affecting pristine coastline and masses of wildlife”. Incident Management and Field Response Teams were activated in a multi-agency operation, bringing together 200 personnel from 16 oil and gas companies and 18 government agencies and third party providers. Source control, aerial, offshore, nearshore, shoreline and oiled wildlife response capabilities were deployed and national/international support was utilised. Jointly managed by the Australian Marine Oil Spill Centre (AMOSC), the Australian Maritime Safety Authority (AMSA), the Federal Department of Industry and Science, and the Western Australian Department of Transport -Exercise Westwind was a successful multi-faceted marine spill response, demonstrating Australia’s collective Industry/Government capacity to respond to a large, offshore loss of well control incident in a remote and isolated location. ACME Oil Company was a fictitious company formed to enable the amalgamation of Australian petroleum companies to exercise industry arrangements under one ‘banner’ during the exercise period. ACME Oil Company had its own set of credentials, company website and Oil Pollution Emergency Plan. The company also held real time memberships with a number of service providers including AMOSC, Oil Spill Response Ltd, Trendsetter Engineering International, Oceaneering Australia and addenergy. Representing an innovative approach to spill response exercising, ACME Oil Company was a valuable and critical aspect to industry and governments participation under a non-attributable banner. Additionally, it enabled safe, widespread lessons to be observed, allowed for real-time testing of arrangements and provided a safe environment for regulators, stakeholder and industry interplay. The exercise was an efficient and practical solution for Industry titleholders and their third party supporting organisations, to test shared response resources and to ensure Industry arrangements for responding to oil pollution are in accordance with the Offshore Petroleum and Greenhouse Gas Storage (Environment) Regulations 2009. This paper will discuss the development program behind the exercise and the experience of managing an exercise of this nature. It will highlight the successes including the creation and implementation of a fictitious company and the extensive collaboration between the industry and government personnel involved. It will also look forward – where are we 11-months later? Can the history of exercising and/or response help us improve for the future-implementation of change and continued testing is critical in furthering our oil spill response capability and capacity.Exercise Westwind – Operational Phase TwoExercise Westwind – Operational Phase Two

Background Case studies suggest that late hiring timelines are common in large urban school districts and result in the loss of qualified teachers to surrounding suburbs. To date, however, there has been no large-scale quantitative investigation of the relationship between the timing of teacher hires and teacher qualifications. Purpose This study examines the pervasiveness of late teacher hiring in urban and suburban school districts and explores the association between the timing of teacher hires and teacher qualifications, including certification, master's degree, and selectivity of undergraduate institution. Research Design Nationally representative cross-sectional data collected by the National Center for Education Statistics are used. Data Analysis The study uses data on school districts, public schools, and teachers from the 1999–2000 Schools and Staffing Survey. Secondary data are analyzed using multiple regression, including labor market fixed effects, to estimate the relationship between the timing of teacher hires and teacher qualifications. Results On average, districts hire 45% of their new teachers late—during the second half of summer and once the school year has already begun. Late hiring is more pervasive in urban and low-socioeconomic-status districts where over half of new hires take place during this late period. In urban districts, fully one fifth of new hires are made once the school year has already begun. The proportion of teachers hired late, however, does not predict the Barron's ratings of teachers’ undergraduate institutions, certification, or master's degree. Conclusions Although descriptive results indicate that late hiring is pervasive and more pronounced in urban districts, analyses do not provide evidence supporting the notion that earlier hiring is associated with hiring better credentialed teachers. Despite these null results, it is important to remember that late hires are still likely to cause problems for students, as well as for teachers, schools, and districts.

Abstract In the present article, we demonstrate the utility of Open Badge certifications in documenting ESP, EAP and EMI courses. Open Badges are online records of achievement which document field-specific, soft and technical skills. They consist of a visual image and a set of embedded metadata, they are endorsed by the institution which issues them and are recognized at an international level. The information packaged within the badge image file is provided in an open source format and can be shared on social media platforms, as part of an online e-portfolio, as a link on an electronic CV, and on the platform which hosts the Badge. As of 2019, Turin University Language Centre offers Badges in “English for the Social Services” (B1 and B2), “English for Administrative Purposes” (A2, B1 and B2), “Academic Writing and Presentation Skills” (B2 and C1) and “English Medium Instruction” (B2 and C1). We will argue that Open Badge certifications are particularly suited to ESP, since they provide a record of specific hard and soft skills and of innovative teaching and learning practices which go undocumented in conventional certifications and on academic transcripts. We will emphasize the “glocal” quality of these certifications, inasmuch as they are internationally recognized awards tailored by local providers in response to local demands. We will suggest that this perspective is valuable for ESP training. Although ESP learners need to be able to share their credentials on international platforms, using a common language, it is important that we do not lose sight of the specific characteristics of professional activities at a local level. We will further argue that the University Language Centre is, in many ways, ideally suited to issue these kinds of certification.

Abstract Introduction: Within the Military Health System (MHS), facilities have struggled to meet minimum recommended volume thresholds for certain procedures. Understanding variations in complication rates and cost can help policymakers tailor policy to target improvement. Our objective was to quantify the variation in bariatric surgery complication rates and costs across a sample of military hospitals. Materials and Methods: We study a retrospective cohort of 38 military surgeons practicing in 21 military treatment facilities from 2007 to 2014 who performed 1,277 bariatric surgeries. Data from the Centralized Credentials and Quality Assurance System, which provides education and training characteristics of physicians, were linked to patient encounter data from the MHS Data Repository. Physicians were included if they performed at least five bariatric surgeries over the study period. Patients were included if they had a diagnosis of obesity (body mass index &gt; 30) and underwent a bariatric weight loss surgery. We calculated and summarized inpatient costs and complication rates across both surgeons and facilities using multivariable mixed-effects linear or logistic models. We used these models to calculate adjusted complication rates and average costs across both providers and hospitals to characterize variation in bariatric outcomes within the MHS. This study was considered exempt by the Uniformed Services University Institutional Review Board. Results: We find evidence of large variations in both complication rates and costs per admission. Overall, we found a 15.5% complication rate across the sample. When comparing averages across facilities, we find large variation in complications (49.4% coefficient of variation [CV]) and procedure costs (25.9% CV). Controlling for patient comorbidities, BMI, and year attenuates much of the variation (12.6% CV complications, 4.4% CV cost), but cannot completely explain differences across facilities. Our model suggests that complications cost 32% more than complication-free surgeries on average suggesting that quality improvement efforts could potentially yield large savings. Conclusions: We find large variations in complication rates even after controlling for patient health. Furthermore, surgical complications are a significant determinant of cost. Policymakers should target efforts to improve surgical quality across facilities and physicians. Surgical quality improvement initiatives could produce savings to the MHS through reduced complications and improved surgical readiness.

Purpose This paper aims to explore how stolen Indian antiquities were purchased by a major Australian collecting institution, despite cultural protection policies designed to prevent such inappropriate acquisitions. Using the acquisition of the Dancing Shiva as a case study, the purpose of this paper is to examine how collecting institutions such as the National Gallery of Australia experience difficulty when determining legal title through provenance research. The impact of incautious provenance research produces significant risk to the institution including damaging its social responsibility credentials and reputation when the acquisition is discovered to be stolen. Design/methodology/approach This research applies a qualitative case study method and analysis of sourced official policy documents, personal communication with actors involved with the case, media reports and published institutional statements. Findings This work identifies four contributing factors that resulted in the National Gallery of Australia’s acquisition of stolen Indian artefacts: a misguided level of trust of the art dealer based on his professional reputation; a problematic motivation to expand the gallery’s Asian art collection; a less transparent and judicious acquisition process; and a collaboration deficiency with cultural institutions in India. Crime preventative methods would appear to be a strategic priority to counter art crime of this nature. Research limitations/implications Additional research into how collecting institutions can be effectively supported to develop and implement crime preventative methods, especially less-resourced institutions, can potentially further enhance cultural heritage protection. Practical implications Fostering a higher degree of transparency and institutional collaboration can enhance cultural heritage protection, develop a greater level of institutional ethics and social responsibility and identify any potential criminal activity. Changing the culture of “owning” to “loaning” may provide a long-term solution for cultural heritage protection, rather than incentivising a black market with lucrative sums of money paid for artefacts. Social implications Art crime involving the illegal trade of antiquities is often misinterpreted as a victimless crime with no real harm to individuals. The loss of a temple deity statue produces significant spiritual anguish for the Indian community, as the statue is representative not only of their God but also of place. Collecting institutions have a social responsibility to prioritise robust provenance policy and acquisition practices above collection priorities. Originality/value Art crime is a relatively new area within criminology. This work examines issues involving major collecting institutions acquiring stolen cultural heritage artefacts and the impact art crime has on institutions and communities. This paper unpacks how motivations for growing more prestigious collections can override cultural sensibilities and ethical frameworks established to protect cultural heritage. It highlights the liabilities associated with purchasing antiquities without significant due diligence regarding provenance research and safeguarding cultural heritage. It also emphasises the importance for collecting institutions to establish robust acquisition policies to protect the reputation of the institutions and the communities they represent.

The concept of a standalone production system on the seabed with automated wellbore construction and production processes has been an industry goal for a long time. Electrification of subsea facilities and of wellbore and reservoir equipment offers many opportunities to improve operational efficiency, reduce life-of-field capital and operating expenses, and reduce carbon footprint, among other benefits. Talk of a subsea electrification revolution being “just around the corner” has been ongoing for more than 20 years. And, millions of dollars in investments and numerous joint industry projects (JIPs) over the past decade have moved the vision closer to fruition (Fig. 1). But the upstream industry continues to lag others in replacing hydraulics with electrics. The reasons echo those for slow uptake of other new technologies and methodologies—fear of change, the unknown, and failure. Now, recent events are stirring up interest and expectations. “Four to five years ago, only a very small percentage of the buying community were making big noises about the future state of the electrified subsea or subsurface,” said John Kerr, subsea production systems and technology director for Baker Hughes, in a recent interview. “During the past 18 months the narrative has increased rapidly with many more operators looking at electrification as the base case for subsea solutions. We’ve seen a groundswell of interest to the point that we now see 3-, 5-, and 7-year lookaheads with electric solutions as the base case design concept,” Kerr said. What has changed? “Electrification of subsea devices has always been a solution to solve specific technical needs,” said Kerr. “The predominant one was extreme long-distance stepouts, where once you get to 250 miles or so, the ability to pump hydraulic fluids through small umbilicals presented so much pressure loss that it became impractical to implement a hydraulic solution, so all-electric became the solution of choice. Now we are seeing much more understanding of what electrification can deliver in the commercial and operational sense. “During the last 2 years, there has also been rapid adoption of dialogue around the aspect of increased carbon credentials and carbon reduction as an advantage,” Kerr continued. “The interest is much more comprehensive, driving different behavior in concept selection for operators.” Has the pandemic played a role? The consensus of participants in a subsea electrification panel at the virtual 2020 SPE Annual Technical Conference and Exhibition (ATCE) was that unless you’re surrounded by a crisis, you’re not encouraged to change. “The moment you put someone in a crisis situation, they understand that they have to change,” said Rory Mackenzie, leader for subsea electrical technologies at Total. “2020—the pandemic, oil price collapse, and environmental issues—this created a crisis. People are now much more open to considering change.” The panelists included Alvaro Arrazola, completions engineer, Chevron, North America Upstream; Glenn-Roar Halvorsen, project manager subsea all-electric, Equinor; Christina Johansen, managing director, Norway, TechnipFMC; Samantha McClean, intelligent wells technical advisor, BP; Rory Mackenzie, head of subsea electrical technologies, Total R&D; and Thomas Scott, global product line director, intelligent production systems and reservoir information, Baker Hughes. Edward O’Malley, director of strategy and portfolio, oilfield services, Baker Hughes, moderated the session.

Abstract The Hallmarks of Cancer provided a framework that has guided cancer research since it was first published. Although Hanahan and Weinberg highlighted the role of the tumor microenvironment, the existing hallmarks should be expanded to include another crucial aspect of the tumor microenvironment—the tumor-neural interaction. Traditionally, the nervous and immune systems have been viewed as functionally and anatomically distinct, even though they share a critical common task: to detect and respond to internal and external threats, whether physical, chemical, or biological. While the role of the immune system is well established in cancer, and both immune evasion and tumor-promoting inflammation are considered hallmarks of cancer, the nervous system is typically viewed as a tissue affected by cancer and as a conduit for the transmission of cancer-related pain and perineural invasion. Recent work by us and others has shown that the nervous system plays several important roles in promoting tumor initiation, progression, and metastasis. By comparing the transcriptomes of cancer-associated trigeminal sensory neurons with those of endogenous neurons in mouse models of oral cancer, we identified an adrenergic differentiation signature. We showed that loss of TP53 leads to adrenergic transdifferentiation of tumour-associated sensory nerves through loss of the microRNA miR-34a. Tumor growth was inhibited by sensory denervation or pharmacological blockade of adrenergic receptors, but not by chemical sympathectomy of pre-existing adrenergic nerves. A retrospective analysis of samples from oral cancer revealed that p53 status was associated with nerve density, which was in turn associated with poor clinical outcomes. This crosstalk between cancer cells and neurons represents one mechanism by which tumor-associated neurons are reprogrammed towards an adrenergic phenotype that can stimulate tumor progression and is a potential target for anticancer therapy. These studies suggest that newly formed nerve fibers support both cancer cells and the tumor microenvironment. However, despite increasing recognition of tumor-associated neurogenesis—the formation of new nerve fibers—this topic has been relatively understudied. In the last decade, emerging technologies have enabled us to bridge the gaps between cancer research and neuroscience and to take a glimpse into the roles of nerves and their supporting cells like Schwann cells, in cancer. Specifically, the development of spatial imaging and in vivo neural tracing and recording techniques removed some of the obstacles that impeded cancer neuroscience research, namely, our ability to capture phenotypes and functions in the tumor microenvironment (i.e., dendrites and axons, far away from the neuron cell body or soma) using high-dimensional labeling techniques (e.g., mass cytometry and multiplex immunofluorescence). Using these techniques, it has been shown that in many types of cancer, ablation of different portions of the nervous system prevents cancer development and progression. This process is similar to another microenvironmental hallmark of cancer—tumor angiogenesis, whereby tumors induce the growth of new blood vessels to supply them with oxygen and blood-borne nutrients. Importantly, neuromodulation with both genetic and pharmacologic approaches has been shown to affect not only tumor growth but also the antitumor immune response. Neurogenesis should be recognized as a hallmark of cancer for two important reasons. First, doing so would establish the neo-neurogenic process as a highly relevant therapeutic target for both the prevention and treatment of cancer. Second, it would foster interdisciplinary crosstalk between two fields that traditionally have progressed along parallel paths. We have credentialed the neoneurogenic process as a highly relevant therapeutic target for both the prevention and treatment of cancer; hopefully, in the next decade we will see more clinical trials targeting the neural microenvironment of cancer aiming to prevent tumor’s development and progression and improve patient’s quality of life. Citation Format: Moran Amit. Neural regulation of tumors and their microenvironment: Novel, actionable, hallmark of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY12-02.

Objective – To examine the human resources environment in Canadian libraries in order to assess readiness to accommodate change and to identify opportunities for human resources planning. The “8Rs” of the study were defined as recruitment, retirement, retention, remuneration, repatriation, rejuvenation, re-accreditation, and restructuring. Design – This study was undertaken in three phases over nearly three years through the use a variety of methods including literature review, analyses of existing data (Statistics Canada and library school graduate data), telephone interviews (with senior library administrators), focus groups (with representatives from Canadian Association of Research Libraries, Canadian Urban Libraries Council and Alberta Association of Library Technicians), print surveys (library institutions) and web-based surveys (of professional librarians and paraprofessional library staff). Setting – Canadian libraries that are not component branches of a system, and that employ professional librarians. Subjects – Stage I: 17 senior library administrators participated in telephone interviews and three focus groups were conducted. Stage II: Surveyed library administrators representing institutions. A multi-stage stratified random sampling technique was used to ensure geographical representation from each of Canada’s provinces and territories. Full census participation was conducted for members of the Canadian Association of Research Libraries and the Canadian Urban Libraries Council. The print survey instrument was distributed to 1,357 subjects; 461 completed surveys were returned (response rate of 34% with results for the total sample accurate within plus or minus 3.8 per centage points, 95 times out of 100). Stage III: Surveyed professional librarians and paraprofessional staff. Multi-stage random sampling was used to ensure representation of library staff from all library sectors and sufficient sub-sample sizes. Of the 12,472 individuals in the sampling frame, 8,626 were notified of their selection to participate in the web-based survey. Corrections were made to e-mail addresses and 7,569 e-mail invitations with the survey URL were sent successfully. Of the 8,626 potential respondents, 3,148 librarians and paraprofessionals participated (for a response rate of 37%). A non-random Canada-wide call for participation was distributed to library staff who had not been represented in the sampling frame via the listservs of 56 library associations. This provided an additional 1,545 respondents and the total sample size increased to 4,693 for a confidence interval of plus or minus 1.2%, 95 times out of 100. The non-random data from the Canada-wide call was kept in a separate dataset file. Methods – Stage I began with a literature review and analysis of existing Statistics Canada and library school graduate data. Three focus group sessions with representatives from Canadian Association of Research Libraries, Canadian Urban Libraries Council and Alberta Association of Library Technicians were held and in-depth telephone interviews were conducted in May 2003 with 17 senior library administrators. Transcripts were thematically coded and summarised. The interview guide is available as Appendix E of the report. The results of Stage I were used to inform the design of the two survey instruments (Stages II and III). Stage II was a 17-page print survey informed by insights gathered in Stage I and was sent to library directors in the summer of 2003. The print mail-out of the institutional survey was sent to libraries that employed at least one librarian and were not a component branch of another system. A copy of the institutional survey is available as Appendix C of the report. Stage III was a web-based survey of librarians and paraprofessional library staff undertaken in the summer of 2004 using random and non-random sampling methods. This survey was developed from insights gathered in Stages I and II. A copy of the individual survey is available as Appendix D of the report. Main results – The analytical focus of the 275-page report is on the broad Canadian library sector. Data and analysis are provided by type of library, type of staff, and by geographical regions where sufficient response rates have allowed reporting. Although the role of the paraprofessional is examined in many sections of the report, the principal focus is on the professional librarian. Nine sections of the report present results, analysis and strategic human resource planning implications. Highlights for the broad Canadian library environment are briefly described below. Each section of the report provides further breakdown by library sector, type of position, career stage and other variables that provide significant insight. Workplace Demographic Characteristics (Section C) This section provides demographic information about those in supervisory or management roles (62% of librarians), union density (67% of librarians and 79% of paraprofessional staff), longevity in career, part-time employment, and gender, along with other characteristics. Results conclude that visible minorities and Aboriginal staff are under-represented across all types of libraries and that few libraries recognise the credentials of immigrant librarians. Recruitment to the Profession and to the Organization (Section D) Positive exposure to libraries and librarians is the best predictor of librarianship as a career choice and there were no significant differences in the original motivations for choosing the professional librarian career between new professionals and senior librarians. In response to the open-ended question about motivation for choosing librarianship, none of the librarian respondents (n=1,823) indicated leadership, managing libraries or supervising others as their reason (p. 52). Many respondents indicated reasons for choosing the profession that are in alignment with the values of librarianship, but few indicated reasons that reflect the real nature of the librarians’ role. The average age of new librarian recruits is 37 (with little variation between sectors). Thirty per cent of paraprofessionals are interested in pursuing an MLIS degree; 29 per cent are not interested because they are satisfied with their current role. The major barriers for paraprofessionals wishing to pursue the MLIS degree are inadequate or unrecognised credentials (21% - although 45% of paraprofessionals have an undergraduate degree), geographic distance (33%), lack of money (48%), and lack of time (49%). Eighty per cent of libraries report that the major barrier to recruiting is budget constraints; other barriers include small size of library (60%), organizational hiring freeze (54%), inadequate librarian pay (54%), geographic location (52%), inadequate pool of qualified candidates (51%), and inadequate pool of interested candidates (50%). The ten most important and difficult-to-fill competencies when recruiting varied significantly for each sector: leadership potential, ability to respond flexibly to change, and ability to handle high-volume workload were the three highest-ranked competencies across all libraries. Retirement (Section E) Canadian libraries experienced librarian retirements (11% of total current workforce) and paraprofessional retirements (7% of total current workforce) between 1997 and 2002. During this period, 79 per cent of librarians retired before age 65. Forty per cent of librarians over age 50 estimate that they will retire between 55 and 60. Only 9 per cent of libraries have a succession plan. Staff Retention: Inter- and Intra-organizational Mobility (Section F) Librarians are satisfied with their work and stay in their organization because they like the job (85%), co-workers (84%), and workplace (79%). Seventy-seven per cent of senior librarians and 87% of senior paraprofessionals have been at their current library for more than 10 years. Sixty-nine per cent of librarians believe they are qualified to move to higher level positions, but 69% of institutions state that limited librarian turnover contributes to a lack of promotional opportunities. Education (Section G) Seventy-five per cent library administrators agree that MLIS programs equip graduates with needed competencies, but 58% recommended that the programs provide more management, business and leadership training. Seventy-six per cent of administrators believe that they have little or no input into curriculum content of MLIS programs. Overall evaluation of MLIS education by recent librarian entrants is not positive. Only forty-four per cent indicated that the program provided a realistic depiction of the job, while only 36% said the program provided a realistic expectation of work in their library sector. Recent librarian entrants (67%) were satisfied with the overall quality of their MLIS program, but few indicated that their program provided them with the necessary management skills (25%), leadership skills (20%), or business skills (12%) for their position. Recent library technician entrants were more satisfied (81%) with their programs’ success in providing general skills (87%), and providing a realistic depiction of the job (72%). Continuing Education (Section H) New librarians (72%) need a significant amount of ongoing training, but only 56% believe that their institution provides sufficient training opportunities. Only 30% of libraries have a routine method for determining training needs of librarians and fewer (13 %) have an evaluation method for training outcomes. In most cases, about half of those who received training reported that it improved their job performance. Quality of Work and Job Satisfaction (Section I) Librarians and paraprofessionals are satisfied with their jobs (79% for each) and librarians (72%) and paraprofessionals (61%) agree that their salary is fair. Most libraries offer a wide range of benefits to their employees, including life insurance (95%), pension plan (92%), and medical benefits (88%). Librarians (80%) and paraprofessionals (70%) are satisfied with their benefits. Although a low percentage of librarians agreed that they have little job stress (24%) and only 39% found their workload to be manageable, 62% of librarians agree that their work allows work, family and personal life balance. The statistics are slightly more positive for paraprofessionals. There is a gap between the desire to be treated with respect (98% for all workers) and the perception that respect is conveyed (77% of librarians and 75% of paraprofessionals). A similar gap exists between desire to be involved in decision-making and actual involvement. The two most important factors for job satisfaction for all library workers are respectful treatment and a job that allows them to learn new skills and grow. Numerical Librarian Demand-Supply Match (Section J) Libraries hired more librarians than they lost in 2002, for a net three per cent increase. Many library administrators believe that there will be a five-year increased demand for librarians (77%) and paraprofessionals (81%). The short-term supply (next 5 years) of new librarians to replace departures due to retirements is predicted to have the capacity to fill 98 per cent of the current librarian positions; the capacity to replace library technicians is 99 per cent. The long-term supply (next 10 years) of new librarians to replace departures due to retirements is predicted to have the capacity to fill 89 per cent of the current librarian positions; the capacity to fill technician positions is identical. These predictions are based on no growth in the number of positions in the future. Match Between Organizational Job Function Demand and Individual Staff Supply of Skills, Abilities, Talents, Interests (Section K) Libraries report that increased use of information technologies (87%) and re-engineering (61%) have contributed the greatest change in the roles of librarians. Libraries report that more librarians have been required to perform a wider variety of tasks in the past five years (93%) and that this trend will continue over the coming five years (94%). A high percentage of libraries (86%) reported that over the past five years librarians have been expected to perform more management functions and 56% of mid-career and senior librarians believed this had occurred. Libraries (88%) believe that this trend will continue; only 44% of librarians indicate interest in performing management functions. Mid-career and senior librarians report that job stress has increased over five years ago. Requirements to work harder (55%), perform more difficult tasks (56%), perform a wider variety of tasks (69%), and perform more managerial functions (56%) are the contributing factors. The performance of a wider variety of tasks and more difficult tasks was significantly related to the assessment by librarians that their jobs were more enjoyable, interesting, rewarding and challenging. Institutions (78%) reported the increased need for paraprofessionals to perform librarian tasks over the past five years and believe that this will continue (77%). Only 28% of paraprofessionals believe they are currently required to perform more librarian tasks. Conclusion – The need to confirm the existence and magnitude of the crisis that will be created by upcoming retirements in Canadian libraries was a primary motivator for this study. Conclusive results were obtained that should inform each sector and geographic area in Canada. The percentages of staff over the age of 55 (librarians: 25%; paraprofessionals: 21%) is much greater than that of the Canadian workforce (11%). If there is no growth in the number of positions needed, there will be no short-term supply-demand crisis to fill the gaps left by retirements. There will be a librarian and technician shortage in ten years (a shortfall of 11% of the current supply) and a more significant crisis if the predicted growth in staffing is factored in. Recruitment to the librarian and technician professions is critical and the paraprofessional staff may be a potential pool of future MLIS candidates if the accessibility issues associated with the programs are addressed. Only nine per cent of organizations have a succession plan in place. There is great opportunity for the development of strategic solutions. In response to the open-ended question about motivation for choosing librarianship, no respondent indicated leadership, managing libraries or supervising others as their reason. This is of concern when 62% of librarians today work in a managerial role. Management and leadership skills are a significant concern for recent graduates, administrators, and librarians, with all indicating that the workplace needs are greater than the current preparedness. More cooperation with MLIS programs and professional associations is essential to ensure that leadership and management skill development are supported through the curricula and continuing education planning. Organizations must also develop and support a culture where leadership is encouraged and expected, and recognised. There is a need for further development of continuing education opportunities, and training needs assessment and outcome assessment programs may be beneficial. Paraprofessionals and new librarians are less satisfied with the workplace training opportunities available to them than librarians in later stages of their careers. Role change will continue in libraries and planning will be essential to ensure that restructuring reflects the competencies that will be needed in the new mix. Workload and job stress appear to be rising and will require careful monitoring. There may be opportunity to define roles for “other” professionals in libraries. Library staff have a tendency to stay in their institution for much of their career, making decisions in the recruitment and hiring processes of critical importance. Loss of employees due to turnover is not a problem for most libraries, but the lack of turnover has affected the promotional opportunities for those who desire upward mobility. An interesting recommendation was made that two or more libraries may realise both cost savings and benefits through the sharing of staffing resources. If issues surrounding credentials can be addressed, there may be a potential pool of future immigrant librarians.

Executive Summary 1 This report analyzes the US Refugee Admissions Program (USRAP), leveraging data from a national survey of resettlement stakeholders conducted in 2020. 2 The survey examined USRAP from the time that refugees arrive in the United States. Its design and questionnaire were informed by three community gatherings organized by Refugee Council USA in the fall and winter of 2019, extensive input from an expert advisory group, and a literature review. This study finds that USRAP serves important purposes, enjoys extensive community support, and offers a variety of effective services. Overall, the survey finds a high degree of consensus on the US resettlement program’s strengths and objectives, and close alignment between its services and the needs of refugees at different stages of their settlement and integration. Because its infrastructure and community-based resettlement networks have been decimated in recent years, the main challenges of subsequent administrations, Congresses, and USRAP stakeholders will be to rebuild, revitalize, and regain broad and bipartisan support for the program. This article also recommends specific ways that USRAP’s programs and services can be strengthened. Among the study’s findings: 3 Most refugee respondents identified USRAP’s main purpose(s) as giving refugees new opportunities, helping them to integrate, offering hope to refugees living in difficult circumstances abroad, and saving lives. High percentages of refugees reported that the program allowed them to support themselves soon after arrival (92 percent), helped them to integrate (77 percent), and has a positive economic impact on local communities (71 percent). Refugee respondents also reported that the program encourages them to work in jobs that do not match their skills and credentials (56 percent), does not provide enough integration support after three months (54 percent), does not offer sufficient financial help during their first three months (49 percent), and reunites families too slowly (47 percent). Respondents identified the following main false ideas about the program: refugees pose a security risk (84 percent), use too many benefits and drain public finances (83 percent), and take the jobs of the native-born (74 percent). Refugee respondents reported using public benefits to meet basic needs, such as medical care, food, and housing. Non-refugee survey respondents believed at high rates that former refugees (69 percent) and refugee community advocate groups (64 percent) should be afforded a voice in the resettlement process. Non-refugee respondents indicated at high rates that the program’s employment requirements limit the time needed for refugees to learn English (65 percent) and limit their ability to pursue higher education (59 percent). Eighty-six percent of non-refugee respondents indicated that the Reception and Placement program is much too short (56 percent) or a little too short (30 percent). Respondents identified a wide range of persons and institutions as being very helpful to refugees in settling into their new communities: these included resettlement staff, friends, and acquaintances from refugees’ country of origin, members of places of worship, community organizations led by refugees or former refugees, and family members. Refugee respondents identified finding medical care (61 percent), housing (52 percent), and a job (49 percent) as the most helpful services in their first three months in the country. Refugees reported that the biggest challenge in their first year was to find employment that matched their educational or skill levels or backgrounds. The needs of refugees and the main obstacles to their successful integration differ by gender, reflecting at least in part the greater childcare responsibilities borne by refugee women. Refugee men reported needing assistance during their first three months in finding employment (68 percent), English Language Learning (ELL) courses (59 percent), and orientation services (56 percent), while refugee women reported needing orientation services (81 percent) and assistance in securing childcare (64 percent), finding ELL courses (53 percent), and enrolling children in school (49 percent). To open-response questions, non-refugee respondents identified as obstacles to the integration of men: digital literacy, (lack of) anti–domestic violence training, the need for more training to improve their jobs, the new public benefit rule, transportation to work, low wages, the need for more mental health services, cultural role adjustment, and lack of motivation. Non-refugee respondents identified as obstacles to the integration of women: lack of childcare and affordable housing, the different cultural roles of women in the United States, lack of affordable driver’s education classes, a shortage of ELL classes for those with low literacy or the illiterate, digital literacy challenges, difficulty navigating their children’s education and school systems, transportation problems, poorly paying jobs, and lack of friendships with US residents. Non-refugee respondents report that refugee children also face unique obstacles to integration, including limited funding or capacity to engage refugee parents in their children’s education, difficulties communicating with refugee families, and the unfamiliarity of teachers and school staff with the cultures and backgrounds of refugee children and families. LGBTQ refugees have many of the same basic needs as other refugees — education, housing, employment, transportation, psychosocial, and others — but face unique challenges in meeting these needs due to possible rejection by refugees and immigrants from their own countries and by other residents of their new communities. Since 2017, the number of resettlement agencies has fallen sharply, and large numbers of staff at the remaining agencies have been laid off. As a result, the program has suffered a loss in expertise, institutional knowledge, language diversity, and resettlement capacity. Resettlement agencies and community-based organizations (CBOs) reported at high rates that to accommodate pre-2017 numbers of refugees, they would need higher staffing levels in employment services (66 percent), general integration and adjustment services (62 percent), mental health care (44 percent) and medical case management (44 percent). Resettlement agencies indicated that they face immense operational and financial challenges, some of them longstanding (like per capita funding and secondary migration), and some related to the Trump administration’s hostility to the program. Section I introduces the article and provides historic context on the US refugee program. Section II outlines the resettlement process and its constituent programs. Section III describes the CMS Refugee Resettlement Survey: 2020. Section IV sets forth the study’s main findings, with subsections covering USRAP’s purpose and overall strengths and weaknesses; critiques of the program; the importance of receiving communities to resettlement and integration; the effectiveness of select USRAP programs and services; integration metrics; and obstacles to integration. The article ends with a series of recommendations to rebuild and strengthen this program.

Abstract: Neuron homeostasis is crucial for the organism, and its maintenance is multifactorial, including autophagy. The turnover of aberrant intracellular components is a fundamental pathogenetic mechanism for cell aging. Autophagy is involved in the acceleration of the neurocyte aging process and the modification of cell longevity. Neurocyte aging is a process of loss of cell identity through cellular and subcellular changes that include molecular loss of epigenetics, transcriptomic, proteomic, and autophagy dysfunction. Autophagy dysfunction is the hallmark of neurocyte aging. Cell aging is the credential feature of neurodegenerative diseases. Pathophysiologically, aged neurocytes are characterized by dysregulated autophagy and subsequently neurocyte metabolic stress, resulting in accelerated neurocyte aging. In particular, chaperone-mediated autophagy perturbation results in upregulated expression of aging and apoptosis genes. Aged neurocytes are also characterized by the down-regulation of autophagy-related genes, such as ATG5-ATG12, LC3-II / LC3-I ratio, Beclin-1, and p62. Slowing aging through autophagy targeting is sufficient to improve prognosis in neurodegenerative diseases. Three primary anti-senescent molecules are involved in the aging process: mTOR, AMPK, and Sirtuins. Autophagy therapeutic effects can be applied to reverse and slow aging. This article discusses current advances in the role of autophagy in neurocyte homeostasis, aging, and potential therapeutic strategies to reduce aging and increase cell longevity.

AbstractAccurate prediction of future sea level rise requires models that accurately reproduce and explain the recent observed dramatic ice sheet behaviours. This study presents a new multi-phase, multiple-rheology, scalable and extensible geofluid model of the Greenland ice sheet that shows the credential of successfully reproducing the mass loss rate derived from the Gravity Recovery and Climate Experiment (GRACE), and the microwave remote sensed surface melt area over the past decade. Model simulated early 21st century surface ice flow compares satisfactorily with InSAR measurements. Accurate simulation of the three metrics simultaneously cannot be explained by fortunate model tuning and give us confidence in using this modelling system for projection of the future fate of Greenland Ice Sheet (GrIS). Based on this fully adaptable three dimensional, thermo-mechanically coupled prognostic ice model, we examined the flow sensitivity to granular basal sliding, and further identified that this leads to a positive feedback contributing to enhanced mass loss in a future warming climate. The rheological properties of ice depend sensitively on its temperature, thus we further verified modelâŹs temperature solver against in situ observations. Driven by the NCEP/NCAR reanalysis atmospheric parameters, the ice model simulated GrIS mass loss rate compares favourably with that derived from the GRACE measurements, or about −147 km3/yr over the 2002–2008 period. Increase of the summer maximum melt area extent (SME) is indicative of expansion of the ablation zone. The modeled SME from year 1979 to 2006 compares well with the cross-polarized gradient ratio method (XPGR) observed melt area in terms of annual variabilities. A high correlation of 0.88 is found between the two time series. In the 30-year model simulation series, the surface melt exhibited large inter-annual and decadal variability, years 2002, 2005 and 2007 being three significant recent melt episodes.

Abstract Sociologists have long used credential inflation theory to explain the devaluation of tertiary education degrees as the consequence of the excessive supply of educated personnel. However, the literature has inadequately examined two fundamental conditions: the combination of degrees/skills that individuals possess and the level of degrees. In this article, cross-country multilevel regressions reveal lower-level degrees (i.e. short-cycle tertiary) are devalued due to the larger extent of lower-level tertiary expansion in a society, regardless of degree holders’ skills level. This is consistent with the concept of credential inflation. In contrast, alongside the proliferation of higher-level tertiary education (i.e. bachelor and above), individuals with such degrees are penalized only when they lack high skills. Put differently, higher-level degree holders retain their rewards despite their diminishing scarcity as long as they possess high skills. Meanwhile, high skills unaccompanied by tertiary degrees lose their premium merely in connection with lower-level tertiary expansion. These results suggest credentialism is intensified and credential inflation operates in societies where the extent of lower-level tertiary expansion is relatively large, whereas ‘decredentialization’ emerges along with the larger extent of higher-level tertiary expansion in a way that devalues credentials as such whilst relatively enhancing the role of skills in reward allocation.

Chimeric antigen receptor (CAR) T cell immunotherapies targeting CD19 or CD22 induce remissions in the majority of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), although relapse due to target antigen loss or downregulation has emerged as a major clinical dilemma. Accordingly, great interest exists in developing CAR T cells directed against alternative leukemia cell surface antigens that may help to overcome immunotherapeutic resistance. The fms-like tyrosine kinase 3 receptor (FLT3) is constitutively activated via FLT3 mutation in acute myeloid leukemia (AML) or wild-type FLT3 overexpression in KMT2A (lysine-specific methyltransferase 2A)-rearranged B-acute lymphoblastic leukemia (ALL), which are associated with poor clinical outcomes in children and adults. We developed monovalent FLT3-targeted CAR T cells (FLT3CART) and bispecific CD19xFLT3CART and assessed their anti-leukemia activity in preclinical models of FLT3-mutant AML and KMT2Arearranged infant ALL. We report robust in vitro FLT3CART-induced cytokine production and cytotoxicity against AML and ALL cell lines with minimal cross-reactivity against normal hematopoietic and non-hematopoietic tissues. We also observed potent in vivo inhibition of leukemia proliferation in xenograft models of both FLT3-mutant AML and KMT2A-rearranged ALL, including a post-tisagenlecleucel ALL-to-AML lineage switch patient-derived xenograft model pairing. We further demonstrate significant in vitro and in vivo activity of bispecific CD19xFLT3CART against KMT2A-rearranged ALL and posit that this additional approach might also diminish potential antigen escape in these high-risk leukemias. Our preclinical data credential FLT3CART as a highly effective immunotherapeutic strategy for both FLT3-mutant AML and KMT2A-R ALL that is poised for further investigation and clinical translation.