Статті в журналах з теми "Recurring payments"

PayPal is an international payment gateway allowing businesses and individuals to transfer funds in a secure manner over the Internet. Using PayPal to accept payments has several advantages for online merchants. It is a recognized brand when it comes to Business to Consumer (B2C) transactions, creating a business account with PayPal is easier and faster, and finally, PayPal lends its name to the transaction, so customers may feel more comfortable entering into a transaction with a previously unknown merchant. Besides the mentioned advantages, PayPal’s transaction dispute system requires a tracking number from a shipped package to respond to a customer dispute. If the product is purely electronic (a download or access to a site, for example), one’s response to disputes will be quite limited. The solution for the problem mentioned above is PayPal API. The PayPal API resolves Pay Pal drawback through maintaining card and bank account payment schedules without the liability of warehousing payment data also processing one-time and recurring payments. For the evaluation of Pay Pal API, the authors develop an Event Registration Management System (ERMS). ERMS serves as a platform for users to make registrations for events such as conferences, seminars, and workshops.

The economic fallout of the COVID-19 pandemic prompted many governments to provide emergency payments to citizens. These one-off and recurring payments revealed the shortcomings of existing financial infrastructures even as electronic payments replaced cash for everyday expenses. Delays in getting government payments to citizens in many countries focused attention on the potential benefits of central bank digital currencies (CBDCs). This article outlines the social and economic policy choices involved in designing a CBDC and the consequences of these choices for privacy. Priorities including preventing the criminal abuse of the financial system, geopolitical concerns and private sector innovation compete with, and potentially undermine, privacy. We identify and categorize four key privacy risks as ‘losses’ associated with current CBDC models: loss of anonymity, loss of liberty, loss of individual control, and loss of regulatory control.

AbstractDividend payments are firm events on a recurring and predictable basis. High returns in the period between announcement-date and ex-dividend date are the main driver for the so-called dividend month premium, which are positive abnormal returns in months in which corporations are predicted to issue dividend payments. In our empirical analysis of the German stock market, we find a robust dividend month premium, which is particularly high for stocks with positive dividend surprise. Knowing the dates of dividend announcements and payments enable portfolio managers to exploit the dividend month premium. Also taking into account tracking error and transaction costs, we show that simple portfolio-enhancing strategies lead to highly significant abnormal returns.

The subject of this research is the legislation and practice of its implementation, as well as the legal doctrine of Russia, Germany and Great Britain on the existing special systems of compensation for damage inflicted to health as a result of work accidents and occupational diseases. The author examines the special systems of restitution for occupational damage that represent starkly different versions of implementation of basic models developed in global practice (Bismarck and Beveridge). Attention is focused on the key issues of compensation for occupational damage using the legal means available in the Russian Federation. Analysis is conducted on the existing foreign experience on the matter. The author’s special contribution to the research of the topic consists in the statement that for establishing balance within the system of restitution for occupational damage it is necessary to clearly demarcate the three types of compensations: guaranteed social security paid from the budget funds in terms of obligations assumed by government  to support vulnerable population groups; obligations in tort recovered from the tortfeasor, considering the grounds and limits of civil liability; insurance payments, which represent partial coverage of inflicted damage based on the terms of insurance contract. The scientific novelty lies in determination of the prospects for improving the national special system of restitution for occupational damage. It is substantiated that in such system the distribution of losses between different types of compensations should be based on the criteria of preferred form of compensation (payment in kind or financial compensation); legal nature of separate elements of reparation (incapacitation, occupational disease, etc.); type of payments (recurring or lump sum), purpose of compensation; calculation of payments.

Given that project selection is a vital and recurring strategic decision for construction firms, there is a sizeable collection of studies that examine the factors affecting contractors’ decision to bid (d2b). With the aim to provide a global perspective of factors affecting contractors’ d2b, this study meta-analytically reviews 24 relevant studies published between 1988 and 2021. The results show that that there are 28 critical factors, and the top five factors are (i) project payment terms, (ii) financial capacity of client, (iii) client’s reputation in the industry, (iv) the history of client’s payments in the past projects, and (v) project size. The heterogeneity test results, which show no statistically significant heterogeneity across the included studies, reinforce the generalisability of the findings to a global context. The research findings have practical implications for construction clients in their procurement of construction services, highlighting the importance of good reputation and payment history. For contractors, they now have access to a list of critical factors from a global perspective in facilitating their d2b decision. There are methodological implications for the research community in guiding future efforts in replicating studies.

The aims of this study is understand the meaning of murabahah financing by the BMT practitioners and scholars through intensionalisme hermeneutics. Intensionalisme hermeneutics used by practitioners and scholars to analyse how cultural and historical aspect of practitioners and scholars will murabaha interpretation. There were two informants from BMT Managemen, three informants from BMT customers, and four informants from scholars. The result shows, that scholars perceive murabahah as sale of mutual trust. The managements BMT perceive murabahah as a fair sale credit, mutually beneficial and have social aims. The BMT customers perceive murabahah as sale with recurring payments, easy and also has social objectives.

The aims of this study is understand the meaning of murabahah financing by the BMT practitioners and scholars through intensionalisme hermeneutics. Intensionalisme hermeneutics used by practitioners and scholars to analyse how cultural and historical aspect of practitioners and scholars will murabaha interpretation. There were two informants from BMT Managemen, three informants from BMT customers, and four informants from scholars. The result shows, that scholars perceive murabahah as sale of mutual trust. The managements BMT perceive murabahah as a fair sale credit, mutually beneficial and have social aims. The BMT customers perceive murabahah as sale with recurring payments, easy and also has social objectives

Since the early 1990s, Pakistan’s economy has continued to lose its earlier growth momentum, except for a brief spurt in 2002–06. This has now become cause for considerable concern and urgent policy action is needed to revive the economy and move it to a higher growth trajectory. This slowdown during a period of rapid globalization (at least till 2008) and unprecedented technological advancement has raised fundamental questions as to the growing lack of competitiveness, both at the global level as well as against cheaper and better-quality imports in the domestic economy. In addition, recurring balance-of-payments crises have forced Pakistan to frequently seek IMF assistance and resort to severe contractionary policies to restore macroeconomic stability.

ABSTRACT: This paper examines the implications of tax loss carryback incentives for corporate reporting decisions and capital market behavior. During the 1981 through 2010 sample period, we find that firms increase losses in order to claim a cash refund of recent tax payments before the option to do so expires, and we estimate that firms with tax refund-based incentives accelerate about $64.7 billion in losses. Tax-motivated loss shifting is reflected in both recurring and nonrecurring items and is more evident for financially constrained firms. Analysts do not generally incorporate tax-motivated loss shifting into their earnings forecasts, resulting in more negative analyst forecast errors for firms with tax-based incentives than for firms without. Holding earnings surprises constant, however, investors react less negatively to losses reported by firms with tax loss carryback incentives. Data Availability: Data are available from sources identified in the paper.

E - Commerce allows consumers to electronically exchange goods and services with no barriers of time or distance. Electronic commerce has expanded rapidly over the past five years and is predicted to continue at this rate, or even accelerate. In the near future the boundaries between "conventional" and "electronic" commerce will become increasingly blurred as more and more businesses move sections of their operations onto the Internet. The e-commerce industry in India is growing at a remarkable pace due to high penetration of internet and sophisticated electronic devices. However, the recent growth rate of e-commerce in India is far lagging behind than other developed countries. The advantages of e- commerce are convenience, Time saving, Options, Easy to compare, Easy to find reviews, Coupons and deals, Increasing customer base, Rise in sales, 24/7, 365 days, Expand business reach, Recurring payments made easy, Instant transactions. There are many big problems and challenged on the way of an online merchant. Factors like safety and security of online money transaction being the biggest problem along with others have curbed the smooth expansion of the online industry in the country.

The award of pipeline surveillance contracts (PSCs) to ex-militant commanders has set the basis for a new wave of on-going conflicts in Rivers State. These lucrative PSCs constitute a new arena of ‘do or die’ struggles between and among ex-militant, cult, gang, vigilante groups, violence business people, community organizations, state actors and politicians. This article examined the effects of these PSCs by Transnational Oil Corporations and government agencies on recurring oil-related conflicts in Rivers State from 2009 – 2021. The Marxian political economy approach was employed to guide data collection and analysis. It relied on secondary data collected from libraries, national/international agencies and internet resources. The contents of the secondary data collected were analyzed to describe how the PSCs to ex-militant leaders have generated on-going armed struggles between beneficiaries and non-beneficiaries over the control of oil pipelines in Rivers State. It was observed that the lack of local communities’ partnership in Nigeria’s oil industry necessitated the existence of PSCs to ex-militants as ‘payments for peace’ and to prevent oil sabotage and theft. However, instead of achieving this purpose, existing PSCs have ensued conflicts, pipeline vandalism and oil theft. It was accordingly recommended that, among others: local communities should be involved in pipeline surveillance – they should be given at least 45 % of the PSCs and 55% to professional competent firms. A standing ‘Community-Security Consultative Committee’ comprising all stakeholders should be set up to amicably address and resolve issues.

Background For Malaysia, a nation highly dependent on migrant labour, the large non-citizen workforce presents a unique health system challenge. Although documented migrant workers are covered by mandatory healthcare insurance (SPIKPA), financial constraints remain a major barrier for non-citizen healthcare access. Malaysia recently extended protection for migrant workers under the national social security scheme (SOCSO), previously exclusive to citizens. This study aims to evaluate healthcare financing and social security policies for migrant workers to identify policy gaps and opportunities for intervention. Methods A total of 37 in-depth interviews were conducted of 44 stakeholders from July 2018 to July 2019. A mixed-methods analysis combining major themes from qualitative interviews with policy document reviews was conducted. Descriptive analysis of publicly available secondary data, namely revenues collected at government healthcare facilities, was conducted to contextualise the policy review and qualitative findings. Results We found that migrant workers and employers were unaware of SPIKPA enrolment and entitlements. Higher fees for non-citizens result in delayed care-seeking. While the Malaysian government nearly doubled non-citizen healthcare fees revenues from RM 104 to 182 million (USD 26 to 45 million) between 2014 to 2018, outstanding revenues tripled from RM 16 to 50 million (USD 4 to 12 million) in the same period. SPIKPA coverage is likely inadequate in providing financial risk protection to migrant workers, especially with increased non-citizens fees at public hospitals. Undocumented workers and other migrant populations excluded from SPIKPA contribution to unpaid fees revenues are unknown. Problems described with the previous Foreign Workers Compensation Scheme (FWCS), could be partially addressed by SOCSO, in theory. Nevertheless, questions remain on the feasibility of implementing elements of SOCSO, such as recurring payments to workers and next-of-kin overseas. Conclusion Malaysia is moving towards migrant inclusion with the provision of SOCSO for documented migrant workers, but more needs to be done. Here we suggest the expansion of the SPIKPA insurance scheme to include all migrant populations, while broadening its scope towards more comprehensive coverage, including essential primary care.

When assessing the value of capital investments, they often do not pay due attention to those capital investments that are associated with the formation of a sufficient amount of working capital, focusing on fixed assets. Meanwhile, capital investments in the project working capital formation are necessary to cover the costs of the preparatory process, inventory formation, and the creation of a reserve for the period until payments are received for receivables on products sold. During the period of acquisition of assets, one of the important components of investment costs, along with capital expenditures in fixed assets and intangible assets, is net working capital, which is the cost of increasing working capital (current assets). It should also be noted that when evaluating the effectiveness of real investment projects at the stage of feasibility study, it is neither possible nor necessary to calculate net discounted income for individual periods, since at this stage of analysis, it is unlikely that annual differentiation of costs and results will be provided. Thus, when determining the effectiveness of an investment project at the stage of pre-feasibility study of the main decisions, it is justified to use simplified calculations of operating results based on annuity models. An important problem should be recognized as modeling the mechanism for returning invested amounts. To ensure the adequacy of the algorithm taking into account the reimbursement of non-recurring costs in the calculation of investment performance should take into account the flow of funds sinking Fund (in the form of means for reproduction of fixed assets and the depreciation; or funds that ensures return on investment). In the same section, the organization's assets that remain after the end of the business project should be taken into account. In the article, the authors present the improvement of the model for forming business project indicators at the pre-project stage of evaluating the effectiveness of investments, taking into account all these aspects.

The purpose of writing this paper is to provide an overview of the progress of cloud-based accounting systems that are applied to Student Financial Services (cashiers) at Raharja College. Implementation of this system is due to the existence of good management in college to solve the problem. This recurring scheduling feature in the cloud-based accounting system is a new breakthrough that is useful for paying for lectures that use the installment payment system. Where, students can pay tuition twice in installments, namely the period before the midterm exam and before the final exam. This feature is useful to minimize the existence of human error because it forgets billing input, bills are inputted twice with the same nominal, and sending invoices via email is not monitored. So, with the implementation of this system, the cashier's work on students in the installment system can be more effective and have a positive impact on the cashier's performance. This research was conducted using the literature review research method, to find useful theoretical foundations as a reference for solving problems that occur.

Contemporaries and economic historians have noted several features of medieval and early modern European monetary systems that are hard to analyze using models of centralized exchange. For example, contemporaries complained of recurrent shortages of small change and argued that an abundance/dearth of money had real effects on exchange, especially for the poor. To confront these facts, we build a random-matching monetary model with two indivisible coins with different intrinsic values. The model shows that small change shortages can exist, in the sense that adding small coins to an economy with only large coins is welfare-improving. This effect is amplified by increases in trading opportunities. Further, changes in the quantity of monetary metals affect the real economy and the amount of exchange as well as the optimal denomination size. Finally, the model shows that replacing full-bodied small coins with tokens is not necessarily welfare-improving.

Electronic bill presentment and payment (EBPP) provides an opportunity for firms to decrease their billing costs, while increasing their customer interaction. While many models exist, there is a dearth of information for determining which model would best fit customer characteristics and needs. This article examines the three primary models of EBPP, the characteristics of recurring bills, and customer concerns to develop an exploratory framework for determining which EBPP model a bill generating firm should deploy.

The over-reliance on oil export revenue with little attention to non-oil export has subjected the Nigerian economy to recurring adverse external shocks which further aggravate the problem of balance of payment deficit in Nigeria. Therefore, study set out to examine the impact of non-oil exports on balance of payment disequilibrium in Nigeria. The data used for this study is secondary in nature and it spans from 1970 to 2018. The study employed econometric tools of ARDL Cointegration analysis and ARDL Error Correction Model to explore the long run relationship and the impact of non-oil exports on balance of payment disequilibrium respectively. The result of Wald bound test revealed that there is existence of co-movement between non-oil exports and balance of payment while long run ARDL Error Correction Model results showed that non-oil export has significant negative impact on balance of payment disequilibrium. In the same vein, inflation and interest rate also have negative impact on balance of payment disequilibrium but interest rate is insignificant. Findings from the study also exhibited positive relationship between exchange rate, trade openness and balance of payment. However, the positive impact of exchange rate on balance of payment is significant while that of trade openness is not significant. The study, thus concluded based on the findings that the non-oil export has not been contributing positively to improve the balance of payment position in Nigeria. In line with these findings, the study recommended that government should devise plans and strategies of boost the non-oil export sectors such as agricultural, manufacturing, solid minerals and service sectors in order to build virile and strong non-oil export sectors that can achieve favourable balance of payment. Moreover, the citizens of Nigeria should be motivated by one way or the others to have a taste for locally produced goods.

Abstract Venetoclax induces high rates of response (~80%), including complete remissions (CR) in patients with heavily pre-treated chronic lymphocytic leukemia (CLL) through inhibition of BCL2. Despite achieving deep and durable responses, most patients will eventually experience disease progression on treatment. The molecular mechanisms that mediate clinical resistance to venetoclax in vivo are largely unknown. From a cohort of 67 relapsed CLL patients (Anderson et al, Blood 2017; 129:3362-3370) treated with venetoclax on three early phase clinical trials, we performed focussed genomic evaluation in those with CLL-type progressions (as opposed to large cell Richter's transformation). Targeted amplicon next generation sequencing of a panel of 33 genes recurrently mutated in lymphoid malignancy was performed where suitable pre- and post-progression samples were available. Twenty-one patients experienced CLL progression after a median of 36 months (range 6 - 73). Fifteen patients had paired samples for detailed analyses. A single heterozygous nucleotide variant was detected in BCL2 (NM_000633.2:c.302G>T, p.(Gly101Val)) in progression samples in 7 of 15 patients (Fig 1A). Further investigation using a highly sensitive (limit of detection 0.01%) and specific droplet digital PCR (ddPCR) assay indicated that the Gly101Val mutation was first detected at low variant allele fraction after 19-42 months on venetoclax, up to 25 months earlier than when standard disease progression criteria were met. The Gly101Val was not detected prior to venetoclax treatment in this cohort and was not detected in a series of samples from patients treated at our institution who had not received venetoclax (CLL [n=74], NHL [n=198], myeloma [n=103]) nor has it been described in cancer (COSMIC) or population (gnomAD) databases. To investigate whether Gly101Val directly causes resistance to venetoclax, we expressed it in two B-lineage cell lines (RS4;11 and KMS-PE-12). Gly101Val cells were ~30-fold less sensitive to venetoclax than cells expressing wild-type (WT) BCL2. The Gly101Val mutation conferred a selective advantage during continuous exposure to sublethal concentrations of venetoclax in 3-week cultures. The same phenomena was observed with primary patient Gly101Val mutant cells in both short-term survival assays and when cultured in a bone marrow stromal model (Thijssen et al, Haematologica 2015;100:302-6). On stroma, primary cells bearing the Gly101Val mutation demonstrated markedly increased resistance to venetoclax with concentrations higher than achievable clinically in vivo. In the absence of venetoclax, the Gly101Val mutant demonstrated preserved normal function by protecting cell lines from apoptosis induced by cytotoxics with similar effectiveness to WT BCL2. In binding assays, the capacity for venetoclax to compete in vitro with BIM for binding to the Gly101Val mutant was markedly reduced (~180-fold) compared to WT BCL2. This is most likely explained by the presence of a bulkier valine residue in a region juxtaposed to the venetoclax binding groove (Fig 1B). In cell-based assays, whilst venetoclax readily displaced BAX and BAK from WT BCL2 it was ineffective when these pro-apoptotic molecules were bound to the Gly101Val mutant. We observed that not all CLL cells at progression carried the Gly101Val mutation. One patient harbored distinct subclones with and without the BCL2 Gly101Val mutation at progression. The subclone with exclusively WT BCL2 was observed to have elevated BCL-xL by mass cytometry (CyTOF), while the Gly101Val clone had minimal BCL-xL expression. Together these data indicate that whilst the Gly101Val mutation is sufficient to enable clinical resistance to venetoclax, alternative mechanisms may also mediate resistance in the same patient. In conclusion, we have identified and functionally characterized a novel recurrent BCL2 mutation (Gly101Val) emerging in a cohort of patients with CLL-type progressions treated with venetoclax. The BCL2 Gly101Val impairs binding of venetoclax to BCL2, confers resistance to venetoclax in both patient leukemia cells and engineered cell lines, and provides a selective growth advantage over wild-type cells when maintained in the presence of the drug in vitro. This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse. Figure 1 Figure 1. Disclosures Anderson: Walter and Eliza Hall: Employment, Patents & Royalties; AbbVie, Inc: Research Funding; Genentech: Research Funding. Gong:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Thijssen:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Birkinshaw:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Teh:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Xu:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Flensburg:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Lew:Walter and Eliza Hall: Employment, Patents & Royalties. Majewski:Abbvie: Patents & Royalties: I am an employee of the Walter and Eliza Hall Institute which receives milestone and royalty payments related to venetoclax. Gray:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Tam:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding. Seymour:AbbVie: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Consultancy. Czabotar:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Huang:The Walter and Eliza Hall Institute of Medical Research: Other: Institutional funding for venetoclax including milestone and royalty payments.. Roberts:Walter and Eliza Hall: Employment, Patents & Royalties: Employee of Walter and Eliza Hall Institute of Medical Research which receives milestone and royalty payments related to venetoclax; AbbVie: Research Funding; Genentech: Research Funding; Janssen: Research Funding.

202 Background: Florida is among the states that have highest number of cases and total medical malpractice payments. The aim of the study is to examine the characteristics of cancer-related malpractice cases in Florida. Methods: Cancer-related malpractice claims with payment occurred during Jan. 2005 to Dec. 2015 were identified from the Florida Office of Insurance Regulation (FLOIR) database. The characteristics of malpractice cases examined in the study includes cause of allegation, severity of injury, specialty of healthcare provider, length of delay in diagnosis, settlement stage, and indemnity paid. Results: A total of 811 claims were identified. The most common general cause was delay in diagnosis (49.8% of total claims), followed by failure to interpret test result (9.3%) and failure to perform procedure (9.2%). Among the claims of delay in diagnosis, 22.7% were breast cancer, followed by lung cancer (11.1%), and head and neck cancer (10.9%). About 30% claims reported death caused by malpractice. Radiologist (26.1%) was the most common specialty among all specialties, followed by general practice (12.2%) and internal medicine (11.6%). Radiologists were also more likely to have recurrent malpractice claims. The median payout was $250,000 (mean $277,493). The period from case report to settlement was 1.64 years on average. Conclusions: Delay in diagnosis was the most common cause of cancer-related malpractice suits. Our results aligned with previous reports that radiologists were more likely to be involved in the malpractice claims. This study highlights possible pathways to reduce malpractice litigation, as well as improving quality of care in cancer treatment.

Online transactions are becoming more popular in present situation where the globe is facing an unknown disease COVID-19. Now authorities of several countries have requested people to use cashless transaction as far as possible. Practically, it is not always possible to use it in all transactions. Since number of such cashless transactions has been increasing during lockdown period due to COVID-19, fraudulent transactions are also increasing in a rapid way. Fraud can be analysed by viewing a series of customer transactions data that was done in his/ her previous transactions. Normally banks or other transaction authorities warn their customers about the transaction, if they notice any deviation from available patterns; the authorities consider it as a possibly fraudulent transaction. For detection of fraud during COVID-19, banks and credit card companies are applying various methods such as data mining, decision tree, rule based mining, neural network, fuzzy clustering approach and machine learning methods. The approach tries to find out normal usage pattern of customers based on their former activities. The objective of this paper is to propose a method to detect such fraud transactions during such unmanageable situation of the pandemic. Digital payment schemes are often threatened by fraudulent activities. Detecting fraud transactions during money transfer may save customers from financial loss. Mobile-based money transactions are focused in this paper for fraud detection. A Deep Learning (DL) framework is suggested in the paper that monitors and detects fraudulent activities. Implementing and applying Recurrent Neural Network on PaySim generated synthetic financial dataset, deceptive transactions are identified. The proposed method is capable to detect deceptive transactions with an accuracy of 99.87%, F1-Score of 0.99 and MSE of 0.01.

AbstractThis article considers British society's response to the suspension of cash payments in February 1797. Although this event marked the beginning of the so-called Bank Restriction Period, during which the Bank of England's notes were inconvertible, there have been no detailed studies on the social and political situation surrounding the suspension. This article provides an in-depth examination of the events leading up to and immediately following the suspension. It questions existing accounts of the suspension as a smooth transition into the nationwide use of paper money and describes the complex process that came into play to avert a nationwide financial collapse. The decision to suspend the Bank's cash payments stemmed from deep-rooted financial instability, exacerbated by recurrent invasion scares that heightened after the French attempt on Bantry Bay, Ireland, in December 1796. Under such circumstances, national support for drastic financial measures could not be taken for granted. The article demonstrates that the declaration movement, which was a form of consolidated and visualized trust in the financial system, played a crucial role in the 1797 suspension crisis.

The Construction Contracts Act 2004 provides for security of payment in the construction industry through the use of rapid adjudication processes to determine payment disputes. It further prohibits or modifies certain “unfair” provisions in construction contracts and implies provisions in construction contracts about certain matters if there are no written provisions about these matters in the contract. In 2015 the Minster for Commerce commissioned a review of the Act to determine whether iy is meeting the needs of industry and whether amendment was required. This paper provides a background to the construction industry in Western Australia and the essential provisions of the Act together with the principal findings from the review. The recurring issue throughout the review was the critical need for widespread education and publicity regarding the existence of, and the provisions of the Act. Unless this occurs as a matter of urgency and priority, the Act will not fully achieve its objectives for the benefit of all sections of the construction industry.

ABSTRACT Until 1973 the postwar international payments system was, in large measure, shaped by Keynes’s thesis that flexible exchange rates and free international capital mobility are incompatible with global full employment and rapid economic growth in an era of multilateral free trade (Felix, 1977-8). This resulted in a stable international monetary system that permitted the global economy to experience unparalleled economic growth and prosperity despite widespread capital controls and international financial market regulations. Since 1973, the financial system has grown progressively more fragile with recurrent and increasingly stressful international debt and currency liquidity crises threatening the stability of the global economy.

Occurrence of non-recurrent traffic congestion hinders the economic activity of a city, as travellers could miss appointments or be late for work or important meetings. Similarly, for shippers, unexpected delays may disrupt just-in-time delivery and manufacturing processes, which could lose them payment. Consequently, research on non-recurrent congestion detection on urban road networks has recently gained attention. By analysing large amounts of traffic data collected on a daily basis, traffic operation centres can improve their methods to detect non-recurrent congestion rapidly and then revise their existing plans to mitigate its effects. Space-time clusters of high link journey time estimates correspond to non-recurrent congestion events. Existing research, however, has not considered the effect of travel demand on the effectiveness of non-recurrent congestion detection methods. Therefore, this paper investigates how travel demand affects detection of non-recurrent traffic congestion detection on urban road networks. Travel demand has been classified into three categories as low, normal and high. The experiments are carried out on London’s urban road network, and the results demonstrate the necessity to adjust the relative importance of the component evaluation criteria depending on the travel demand level.

Occurrence of non-recurrent traffic congestion hinders the economic activity of a city, as travellers could miss appointments or be late for work or important meetings. Similarly, for shippers, unexpected delays may disrupt just-in-time delivery and manufacturing processes, which could lose them payment. Consequently, research on non-recurrent congestion detection on urban road networks has recently gained attention. By analysing large amounts of traffic data collected on a daily basis, traffic operation centres can improve their methods to detect non-recurrent congestion rapidly and then revise their existing plans to mitigate its effects. Space-time clusters of high link journey time estimates correspond to non-recurrent congestion events. Existing research, however, has not considered the effect of travel demand on the effectiveness of non-recurrent congestion detection methods. Therefore, this paper investigates how travel demand affects detection of non-recurrent traffic congestion detection on urban road networks. Travel demand has been classified into three categories as low, normal and high. The experiments are carried out on London’s urban road network, and the results demonstrate the necessity to adjust the relative importance of the component evaluation criteria depending on the travel demand level.

Abstract Background: Bruton tyrosine kinase inhibitors (BTKis) are important tools to treat B-cell malignancies. However, duration of treatment may be limited by adverse events (AEs). Zanubrutinib (zanu) is a BTKi approved for mantle cell lymphoma (MCL) and is in development for other hematologic malignancies. Data from phase 3 head-to-head trials of zanu vs ibrutinib (ibr) in pts with Waldenström macroglobulinemia (WM) or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) demonstrated that pts treated with zanu showed lower rates of AEs leading to discontinuation (Blood 2020;136(18):2038-50; EHA 2021 LB1900). Preliminary results from BGB-3111-215 (NCT04116437) show that zanu was well-tolerated in pts who discontinued ibr and/or acalabrutinib (acala) treatment due to AEs (EHA 2021 EP642). Here, we report updated results from the BGB-3111-215 study with a median follow-up of 9 months. Methods: This study is an ongoing US, phase 2, multicenter, single-arm, open-label study. The safety and efficacy of zanu monotherapy (160 mg twice daily or 320 mg once daily) were evaluated in pts with B-cell malignancies who met criteria for continued treatment after having become intolerant to prior BTKi therapy. Pts were divided into cohort 1 (pts who were intolerant to ibr only) and cohort 2 (pts who were intolerant to acala alone/and ibr). Pts with documented progressive disease (PD) on prior BTKi therapy were excluded. Efficacy and safety, including recurrence of intolerant AEs to the prior BTKi, were evaluated. AEs were assessed for severity, seriousness, and relation to zanu; as well as dose reductions, holds, or discontinuations. Response was assessed by investigators based on response criteria for their respective indications (Blood 2008;131:2745; J Clin Oncol 2012;30:2820; J Clin Oncol 2014;32:3059; Br J Haemtol 2013;160:171). Disease parameters from study entry were the baseline for response assessment. Mutational analysis was performed on pts who discontinued treatment, and data will be shared once available. To support clinical findings, kinase selectivity was assessed using Kinome profiling at 100X IC50 (against BTK) for zanu, ibr, acala and its major metabolite, M27 (Reaction Biology Corp). Results: As of 7 June 2021 (data cutoff), 57 pts (n=44 CLL/SLL; n=9 WM; n=2 MCL; n=2 marginal zone lymphoma [MZL]) were enrolled in cohort 1, and 7 pts were enrolled in cohort 2 (n=4 CLL; n=1 WM; n=1 MCL; n=1 MZL). All received ≥1 dose of zanu and were analyzed for safety. The median age was 71 years (range, 49-91) in cohort 1 and 71 years (range, 65-76) in cohort 2; median duration of treatment was 8.7 months (range, 0.6-17.9) in cohort 1 and 8.2 months (range, 6.4-11.4) in cohort 2; median number of prior regimens was 1 (range, 1-12) in cohort 1 and 3 (range, 2-5) in cohort 2. Within cohort 2, 5 pts were intolerant to both ibr and acala. Median number of intolerant events per pt for both cohorts 1 and 2 was 2 (range, 1-5). Overall, 73% of pts did not experience recurrence of their ibr or acala intolerant events and 79% of recurrent events recurred at a lower severity (Figure 1). At cutoff, 54 pts remained on treatment. Reasons for treatment discontinuation were AEs (n=4), PD (n=4), physician's decision (n=1), and consent withdrawal (n=1). Grade ≥3 AEs were reported in 18 pts (28%), and serious AEs occurred in 7 pts (11%). AEs requiring dose interruptions occurred in 17 pts (27%), and AEs leading to dose reduction occurred in 3 pts (5%). One death, due to COVID-19, was reported. Pts demonstrated maintained (41%) and improved (53%) response with zanu treatment from their reported best overall response on prior BTKis for a total disease control rate of 94% (including a 42% partial response rate in pts with CLL/SLL, 30% in pts with WM, and a 20% very good partial response rate in pts with WM). Zanu also demonstrated good selectivity by kinase profiling. It showed >50% inhibition on 7/370 kinases, while ibr, acala, and M27 had more off-target binding (17, 15 and 23 kinases, respectively) at their respective 100X IC50 (BTK) concentrations (Figure 2). Conclusion: In pts with B-cell malignancies intolerant to ibr and/or acala, zanu treatment resulted in continued disease control or improved response. Zanu was well-tolerated, and most AEs that led to discontinuation of previous BTKi therapy did not recur or recurred at a lower grade. In support of clinical findings, differentiation between BTKi selectivity profiles favor zanu over ibr and acala. Figure 1 Figure 1. Disclosures Shadman: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, and Atara Biotherapeutics, Adaptimmune: Consultancy; Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding; Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, and Atara Biotherapeutics, Adaptimmune: Membership on an entity's Board of Directors or advisory committees. Flinn: Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Levy: Epizyme: Consultancy, Other: Promotional speaker; Amgen Inc.: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Other: Promotional speaker; Morphosys: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Beigene: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Novartis: Consultancy, Other: Promotional speaker; Dova: Consultancy, Other: Promotional speaker; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau. Burke: SeaGen: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; MorphoSys: Consultancy; Bristol Myers Squibb: Consultancy; AstraZeneca: Consultancy; Epizyme: Consultancy; Verastem: Consultancy; Kura: Consultancy; Kymera: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Consultancy; Roche/Genentech: Consultancy; X4 Pharmaceuticals: Consultancy. Cultrera: Beigene: Research Funding. Yimer: Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau; Janssen: Speakers Bureau; Beigene: Speakers Bureau; GSK: Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Pharmacyclics: Speakers Bureau; Texas Oncology: Current Employment. Chaudhry: Medical Oncology Associates, PS (dba Summit Cancer Centers): Current Employment; Novartis, Immunomedics: Current holder of individual stocks in a privately-held company. Gandhi: TG Therapeutics: Honoraria; Karyopharm Therapeutics: Honoraria; GlaxoSmithKline: Honoraria. Kingsley: Comprehensive Cancer Centers of Nevada: Current Employment. Tumula: Texas Oncology: Current Employment. Manda: Morphosys: Honoraria; Genmab: Current equity holder in publicly-traded company. Chen: BeiGene: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Cohen: BeiGene: Current Employment, Current equity holder in publicly-traded company, Other: Travel, Accommodations, Expenses. By: BeiGene, Ltd: Current Employment. Xu: Beigene: Current Employment; AstraZeneca: Ended employment in the past 24 months. Liu: BeiGene Co., Ltd: Current Employment, Current equity holder in publicly-traded company. Sharman: TG Therapeutics: Consultancy; Centessa: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an AbbVie Company: Consultancy; BMS: Consultancy; AbbVie: Consultancy; BeiGene: Consultancy; AstraZeneca: Consultancy; Lilly: Consultancy.

Objective: A project designed to improve the quality of health care received by persons with psychosis is described. Methods: A nurse was appointed to provide liaison between the mental health service and general practitioners, and to facilitate general health care of patients. ACT Health offered service agreements to general practices, with quarterly per capita payments. Results: About half of the local general practices participated. The number of patients without a general practitioner was reduced and quality of health care improved compared with the previous year. Recurrent funding has been provided. Conclusions: Improving the general health of persons with psychosis is an important issue for psychiatry. Having a similar project in all mental health services could be valuable.

PURPOSE: Spending for patients with advanced cancer is substantial. Past efforts to characterize this spending usually have not included patients with recurrence (who may differ from those with de novo stage IV disease) or described which services drive spending. METHODS: Using SEER-Medicare data from 2008 to 2013, we identified patients with breast, colorectal, and lung cancer with either de novo stage IV or recurrent advanced cancer. Mean spending/patient/month (2012 US dollars) was estimated from 12 months before to 11 months after diagnosis for all services and by the type of service. We describe the absolute difference in mean monthly spending for de novo versus recurrent patients, and we estimate differences after controlling for type of advanced cancer, year of diagnosis, age, sex, comorbidity, and other factors. RESULTS: We identified 54,982 patients with advanced cancer. Before diagnosis, mean monthly spending was higher for recurrent patients (absolute difference: breast, $1,412; colorectal, $3,002; lung, $2,805; all P < .001), whereas after the diagnosis, it was higher for de novo patients (absolute difference: breast, $2,443; colorectal, $4,844; lung, $2,356; all P < .001). Spending differences were driven by inpatient, physician, and hospice services. Across the 2-year period around the advanced cancer diagnosis, adjusted mean monthly spending was higher for de novo versus recurrent patients (spending ratio: breast, 2.39 [95% CI, 2.05 to 2.77]; colorectal, 2.64 [95% CI, 2.31 to 3.01]; lung, 1.46 [95% CI, 1.30 to 1.65]). CONCLUSION: Spending for de novo cancer was greater than spending for recurrent advanced cancer. Understanding the patterns and drivers of spending is necessary to design alternative payment models and to improve value.

Thinking about solving the problem of high consumption and high cost in the electricity bill, this study proposes to present proposals to increase the energy efficiency of the site. In this sense, it is proposed an energy efficiency analysis of a Public Higher Education Institution in the Municipality of Manaus, Amazonas. A building survey was performed on the appliances and components of the building's electrical system, as well as an assessment of electricity bills to measure consumption. In order to verify voltage, current and power, electric measuring instruments were used to elaborate proposals aiming at increasing the energy efficiency of the site. Through the results obtained during the building survey at the IES, it was possible to observe the anomalies of the systems and indicate proposals for repair or replacement of equipment to increase the energy efficiency of the building. From the results obtained from the invoice it was possible to propose a new value of demand contract and by comparing the collected data, we identified the appliances that make the electric system less efficient, in this case, the air conditioners. Recurring payment problems with overconsumption were encountered. Adhering to the proposal of a new contract value with possible annual savings of R $ 22,543.92 referring to the payment of the demand portion in the electricity bill. It is also proposed to replace current lamps with LED tube lamps, reducing energy consumption by 9,122 kWh / month and saving R $ 3,263.57 per month. As for the proposal presented for the HVAC system, given the exchange of existing appliances for new and energy efficient, was not viable. Despite representing a reduction of 41869.91 kWh / month, the expected investment is not paid.

6611 Background: To address the paucity of data on costs of cancer recurrence, this study estimated medical care costs of patients diagnosed with recurrent breast, colorectal or lung cancer, and compared costs to patients diagnosed with de novo stage IV disease. Methods: Data from patients enrolled in three health plans who were diagnosed with de novo stage IV or recurrent breast (nstage IV = 352; nrecurrent= 765), colorectal (nstage IV = 1072 and nrecurrent= 542) and lung (nstage IV = 4042 and nrecurrent= 339) cancers between 2000-2012 were used to estimate total medical care costs in the 12 months preceding (pre-index), month of index, and 12 months following (post-index) diagnosis/recurrence date. Cancer patients were identified using tumor registry data. Recurrent cancers were validated by medical record abstraction and the RECUR algorithms –innovative tools to detect recurrence using claims and electronic health record data. We used generalized linear repeated measures regression models controlling for demographic and comorbidity variables to estimate costs (2012 US$), stratified by age at diagnosis (ages < 65, ≥65). Results: Medical care cost differences in the pre-index period indicate higher costs for recurrent cancer patients than for stage IV breast (Age < 65:+$2550; Age ≥65: +$1254), colorectal (Age < 65:+$3295; Age ≥65: +$1653), and lung cancer patients (Age < 65:+$3232; Age ≥65: +$2340). Conversely, in the index and post-index periods, costs for stage IV cancers were higher than recurrent cancer costs. Specifically, post-index period cost differences indicate higher costs for stage IV patients than for recurrent breast (Age < 65:+$683; Age ≥65: +$1172), colorectal (Age < 65:+$3104; Age ≥65: +$1557), and lung cancer patients (Age < 65:+$1136; Age ≥65: +$1103). Conclusions: Our study provides medical care cost estimates of recurrent and de novo stage IV cancers. Cost differences between recurrent and stage IV cancers reveal heterogeneity in care patterns that merits further investigation. The reported study costs, measured in capitated care systems using standardized fee-for-service reimbursement coefficients, may serve as a benchmark for stage-specific phase-of-care oncology episode payment models.

Despite the impossibility to, under Brazilian law, as a rule, an insured or aggrieved third party seek payment of insurance indemnity directly from a reinsurer, it is recurrent the inclusion of reinsurers as defendants in lawsuits, especially in cases involving the purchase of facultative civil liability insurance. As a result of legislative, jurisprudential, bibliographical and documentary research, this study aims to shed light on the relationships and obligations established by reinsurance agreements and reject this unlawful practice at once. This is done through an initial dive into the insurance relationship and the facultative civil liability insurance and through the review of the particularities of reinsurance and the features that differ it from insurance, to, ultimately, reinforce the initial statement that served as a premise for this work.

Optimisation of revenue potential in the subnational governments in Kenya is core to meeting the their recurrent and development expenditure needs without overrelying on national government transfers. However, the subnational governments face constraints that limit their potential to enhance their revenue collections. Therefore, this study examines the constraints to own source revenue (OSR) collections in Nairobi City County (NCC), assesses challenges to optimal collection of parking fees, and identifies measures to address the challenges inherent to the collection of single business permits (SBPs) debts in the county. The study employed desk review and survey design targeting 170 key informants from the NCC Government and the Kenya Revenue Authority distributed across the 17 sub-counties. The study found that the major constraints to OSR collection in the NCC are inadequate revenue collection tools, equipment and machines (82%); inadequate capacity of the debt collection unit to follow taxpayers who default or delay in making payments (68%); poor tax education/awareness within the county (63%); below par adoption of information and communications technology systems combined with the prevalence of manual revenue collection in making payments (58%); inadequate staff numbers to collect the fees and charges (53%); and lack of legal framework (policies, rules and regulations) for collection of all the revenue streams (51%). The study also found that the main challenges to optimal collection of parking fees in the NCC are high parking fees; system failure; insecurity; unmarked parking lots; interference by parking boys; lack of parking spaces, among others. The study makes suggestions for addressing the challenges in the collection of SBPs debts and provides comprehensive recommendations on dealing with the identified constraints to revenue optimisation in the NCC, applicable to other subnational governments across sub-Saharan Africa.

A recurrent topic of debate concerns the effects of transfer pricing adjustments for direct tax purposes on the taxable amount for VAT. This topic is currently gaining attention, which is underlined by the recently published VAT Committee working paper on the possible VAT effects of transfer pricing adjustments. Focussing on so-called ‘year-end transfer pricing adjustments’, the authors discuss various fundamental questions concerning the VAT implications of such adjustments. Do year-end adjustments lead to retroactive adjustments to the taxable amounts for VAT of supplies made throughout the year? If any retroactive adjustments need to be made to the taxable amounts for VAT, what are the implications for the VAT returns, EC-Sales lists and interests? What if a year-end adjustment does not lead to an adjustment of the taxable amount for VAT? Can intercompany payments (which follow from year-end adjustments) then be regarded as the remuneration for any service rendered? Or are year-end adjustments merely to be regarded as financial transactions outside the scope of EU VAT after all? These, and other questions are discussed in this article.

Introduction: Pediatric acute myeloid leukemia (AML) is a molecularly heterogeneous group of diseases lacking therapy options that would improve overall survival. Venetoclax (VEN) is an oral inhibitor for selective targeting of B-cell lymphoma 2 (BCL2), which is highly expressed in most patients (pts) with AML and has demonstrated promising efficacy in pediatric pts with AML when combined with chemotherapy (CTx) (Karol SE, et al. Lancet Oncol. 2020;21:551-560). Here, we present safety, efficacy, and preliminary genomic results from pediatric pts with relapsed/refractory (R/R) AML receiving VEN + CTx. Methods: This phase 1 open-label, 2-part, multicenter study (NCT03236857) enrolled pts &lt;25 years with R/R malignancies; here we report on R/R AML. During VEN monotherapy (monoTx), 10 pts received a weight- or age-adjusted adult-equivalent oral daily dose of 800 mg VEN after a 3-day ramp-up to mitigate tumor lysis syndrome risk. Standard of care CTx could be added after 21 days of VEN monoTx at the discretion of the treating physicians. In cohort expansion, 26 pts were enrolled with standard of care CTx allowed after VEN ramp-up. Primary and secondary endpoints included safety and preliminary efficacy of VEN monoTx and VEN + CTx. In addition, exploratory biomarker analyses were performed. For genomic analyses, whole exome sequencing was performed on pretreatment blood or bone marrow samples, and highly recurrent genetic alterations across various functional classifications in AML were analyzed. Previously documented gene fusion data were acquired through site-reported cytogenetic entries at screening. RNA sequencing was performed on pretreatment blood or bone marrow samples and BCL2 family expression was assessed. Results: As of June 2020, 36 pts with R/R AML were enrolled and received VEN monoTx (n=3) and VEN + CTx (n=33: VEN + decitabine [VEN-DEC, n=5], azacitidine [VEN-AZA, n=19], or low- [VEN-LDAC, n=1] or high-dose cytarabine [VEN-HDAC, n=8]) (Table). The primary reason for VEN discontinuation was progressive disease (n=19); median duration of VEN therapy was 3.1 months (range 0.2-9.3). All pts experienced adverse events (AEs); 3 pts (n=1 VEN-DEC, n=2 VEN-AZA) had fatal AEs considered unrelated to VEN. The most common grade 3/4 AEs were febrile neutropenia (58%) and hypokalemia (33%). The overall objective response rate (ORR) was 25% (9/36); median duration of response was 0.8 month (95% CI, 0.5, 3.6). The best ORR was seen with VEN-HDAC (4/8, 50%) with 1 complete response (CR), 1 CR without platelet recovery, 1 CR with incomplete marrow recovery (CRi), and 1 partial response (PR); 2 pts achieved minimal residual disease negativity and 2 pts proceeded to transplant. The ORR with VEN-AZA was 26% (5/19), with 3 CR/CRi and 2 PR. No responses were seen with VEN monoTx or VEN + other CTx. The genomic landscape of biomarker-evaluable pts was highly heterogeneous (Figure A). Mutations of genes involved in epigenetic modification (MYH11, IDH2, ASXL1, SETBP1, TET2, and NSD1) and transcription regulation (GATA1, WT1, RUNX1, and CEBPA) were the most common, in 58% and 48% of pts, respectively. Analysis of the recurring mutations found in ≥2 pts revealed that responses to VEN-AZA were seen in pts with IDH2 (1/4), MYH11 (2/6), RUNX1 (1/3), or FLT3 (1/3) mutations, and responses to VEN-HDAC were seen in pts with JAK2 (1/4) or GATA1 (1/3) mutations. Pts with WT1 (3/6) and PTPN11 (3/4) mutations responded to both regimens. Pts with TP53 (n=2) or ETV6 (n=3) mutations and PML-RARA (n=2) or KMT2A rearrangements (n=8) did not respond to any treatment. Gene expression profiling revealed that BCL-xL expression was significantly higher compared with BCL2;MCL1 levels were the highest (Figure B). There was no association between expression of these genes and response. Mutations were seen in BCL2 and MCL1 (n=1 each), but not in BCL-xL. Conclusions: VEN + CTx was well tolerated in pediatric pts with R/R AML, with no unexpected toxicities. Preliminary efficacy was seen in pts receiving VEN-AZA or VEN-HDAC: ORR 26% and 50%, respectively. VEN + CTx resulted in responses in pts harboring mutations across a range of functional classifications; however, some alterations may confer resistance. Due to the limited number of pts harboring each mutation and the overall heterogeneity of the genomic landscape, these findings need to be evaluated in a larger population, and warrant further investigation. Disclosures Karol: AbbVie Inc.: Other: Unrelated to this study, St. Jude has received a charitable contribution from AbbVie, Inc. The charitable contribution is not being used for clinical or research activities, including any activities related to this study. . Bittencourt:Jazz Pharmaceuticals: Consultancy, Other: travel, accommodations, expenses; Novartis: Consultancy. Morgenstern:EUSA Pharma: Consultancy, Other: travel support; Bayer: Consultancy; Clarity Pharmaceuticals: Consultancy; BMS: Other: Institutional Research Funding; Boehringer Ingelheim: Consultancy; Roche: Consultancy. Macy:Merck: Other: Institutional Research Funding; Pfizer: Other: Institutional Research Funding; Bayer: Other: Institutional Research Funding; AbbVie Inc.: Other: Institutional Research Funding; Roche: Other: Institutional Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company. Khaw:Amgen: Other: Institutional Research Funding; Bristol-Myers Squibb: Other: Institutional Research Funding; AbbVie Inc.: Other: Institutional Research Funding; Novartis: Other: travel, accommodation, expenses; Walter and Eliza Hall Institute of Medical Research.: Patents & Royalties: Recipient of a share in royalty payments . Cooper:Celgene: Other: Spouse was an employee of Celgene (through August 2019). Ramsingh:Genentech: Current Employment, Current equity holder in publicly-traded company; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Tong:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Unnebrink:AbbVie: Current Employment, Other: may hold stock or other options. Vishwamitra:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Dunbar:Abbvie: Current Employment, Current equity holder in publicly-traded company. Prine:AbbVie: Current Employment, Other: may hold stock or other options. Palenski:AbbVie: Current Employment, Other: may hold stock or other options. Place:Novartis: Consultancy, Other: Institutional Research Funding; AbbVie: Consultancy. OffLabel Disclosure: Venetoclax is a BCL-2 inhibitor that is FDA approved for some indications. Venetoclax for treatment of pediatric AML is not an approved indication.

Concebidas como operações para expandir e diversificar mercados, buscando aproveitar oportunidades de negócios, as Fusões e Aquisições (F&A) são consideradas uma das mais recorrentes formas de reestruturação organizacional, cujos impactos atingem os mais variados aspectos, incluindo as decisões estratégicas, a estrutura organizacional e a cultura corporativa. Todos esses aspectos são essenciais para determinar o sucesso ou o fraco de um processo de F&A e não podem ser negligenciados. Sob essa perspectiva, o presente artigo tem como objetivo explorar o processo de aquisição de uma empresa do mercado de pagamentos brasileiro, investigando as principais mudanças e impactos na estratégia e na estrutura organizacional e a percepção e adaptação dos funcionários aos novos elementos culturais desta empresa decorrentes de tal processo. A pesquisa foi conduzida tendo como base, fontes documentais tais quais relatórios e apresentações internas da empresa e; entrevistas com executivos dos níveis operacional, tático e estratégico, que vivenciaram o processo de aquisição tanto na empresa adquirida quanto na adquirente. Os resultados evidenciaram que elementos culturais da instituição financeira adquirente foram rapidamente incorporados à empresa estudada. A estratégia e a estrutura organizacional da empresa sofreram alterações em sua forma de solucionar problemas gerenciais, melhorar indicadores estratégicos de desempenho e aumentar a sinergia entre as duas empresas. Palavras-chave: Estratégia. Estrutura Organizacional. Mercado de Pagamentos. Fusões e Aquisições. AbstractPlanned as operations to expand and diversify markets, in order to take advantage of business opportunities, mergers and acquisitions (M&A) are considered one of the most recurrent forms of organizational changes, whose impacts affect the most varied aspects, including strategic decisions, organizational structure and corporate culture. All these aspects are essential to determine the success or weakness of a M&A process and can not be neglected. In this perspective, this article aims to explore the process of acquiring in a company from the Brazilian payments market, investigating the main changes and impacts in the strategy and organizational structure and the perception and adaptation of the employees to the new cultural elements resulting from such process. The research was carriet out through documentary sources, such as internal reports and presentations, and interviews with executives at the operational, tactical and strategic levels who experienced the acquisition process both in the acquired company and in the acquirer. The results showed that acquirer’s cultural elements were quickly incorporated into the acquired company. The strategy and organizational structure of the acquired company undergone changes as a way to solve managerial problems, improve strategic performance indicators and increase the synergy between the two firms. Keywords: Strategy. Organizational Structure. Payment Market. Mergers and Acquisitions.

Object Despite advances in technology and understanding in spinal physiology, reoperation for symptomatic same-level recurrent stenosis continues to occur. Although revision lumbar surgery is effective, attention has turned to the question of the utility and value of revision decompression and fusion procedures. To date, an analysis of cost and heath state gain associated with revision lumbar surgery for recurrent same-level lumbar stenosis has yet to be described. The authors set out to assess the 2-year comprehensive cost of revision surgery and determine its value in the treatment of same-level recurrent stenosis. Methods Forty-two patients undergoing revision decompression and instrumented fusion for same-level recurrent stenosis–associated leg and back pain were included in this study. Two-year total back-related medical resource utilization, missed work, and health state values (quality-adjusted life years [QALYs], calculated from the EQ-5D with US valuation) were assessed. Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost), and patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). Mean total 2-year cost per QALY gained after revision surgery was assessed. Results The mean (± SD) interval between prior and revision surgery was 4.16 ± 4.64 years. Bone morphogenetic protein was used in 7 cases of revision arthrodesis (16.7%). A mean cumulative 2-year gain of 0.84 QALY was observed after revision surgery. The mean total 2-year cost of revision fusion was $49,431 ± $7583 (surgery cost $21,060 ± $4459; outpatient resource utilization cost $9748 ± $5292; indirect cost $18,623 ± $9098). Revision decompression and extension of fusion was associated with a mean 2-year cost per QALY gained of $58,846. Conclusions In the authors' practice, revision decompression and fusion provided a significant gain in health state utility for patients with symptomatic same-level recurrent stenosis, with a 2-year cost per QALY gained of $58,846. When indicated, revision surgery for same-level recurrent stenosis is a valuable treatment option for patients experiencing back and leg pain secondary to this disease. The authors' findings provide a value measure of surgery that can be compared with the results of future cost-per-QALY-gained studies of medical management or alternative surgical approaches.

The constructions of urban infrastructure are an important sector that provides remarkable ingredients for the economic development of modern cities. However, a large number of transportation infrastructure construction projects are delayed; therefore, those projects always exceed their original time and cost estimates. So construction delay has been considered as a recurring problem in the construction projects of urban infrastructure, and it adversely affects the time, cost, safety, and quality of construction. This paper is committed to investigating the time performance of subway tunnel constructions in China to identify the causes of delay based on the questionnaire surveys of 87 tunnel consultants and 91 contractors, and a total of 49 delay causes of tunnel construction are identified one by one in this study. It can be concluded from this study that the six most severe delay causes are national policy for subway tunnel construction, complicated geological conditions, payment delays by owners, award projects to the lowest bid price, shortage of advanced large equipment, and low productivity of laborers. There is a relatively reliable agreement between the tunnel consultants and contractors of 76.3% on the ranking of different delay causes.

Abstract Objective Amid electronic health records, laboratory tests, and other technology, office-based patient and provider communication is still the heart of primary medical care. Patients typically present multiple complaints, requiring physicians to decide how to balance competing demands. How this time is allocated has implications for patient satisfaction, payments, and quality of care. We investigate the effectiveness of machine learning methods for automated annotation of medical topics in patient-provider dialog transcripts. Materials and Methods We used dialog transcripts from 279 primary care visits to predict talk-turn topic labels. Different machine learning models were trained to operate on single or multiple local talk-turns (logistic classifiers, support vector machines, gated recurrent units) as well as sequential models that integrate information across talk-turn sequences (conditional random fields, hidden Markov models, and hierarchical gated recurrent units). Results Evaluation was performed using cross-validation to measure 1) classification accuracy for talk-turns and 2) precision, recall, and F1 scores at the visit level. Experimental results showed that sequential models had higher classification accuracy at the talk-turn level and higher precision at the visit level. Independent models had higher recall scores at the visit level compared with sequential models. Conclusions Incorporating sequential information across talk-turns improves the accuracy of topic prediction in patient-provider dialog by smoothing out noisy information from talk-turns. Although the results are promising, more advanced prediction techniques and larger labeled datasets will likely be required to achieve prediction performance appropriate for real-world clinical applications.

Object Despite advances in technology and understanding in spinal physiology, reoperation for symptomatic adjacent-segment disease (ASD), same-level recurrent stenosis, and pseudarthrosis in elderly patients continues to occur. While revision lumbar surgery is effective, attention has turned to questions on the utility and value of the revision decompression and fusion procedure. To date, an analysis of the cost and health state gain associated with revision lumbar surgery in elderly patients with symptomatic pseudarthrosis, ASD, or same-level recurrent lumbar stenosis has yet to be performed. The aim of this study was to assess the long-term outcomes and cost-effectiveness of revision surgery in elderly patients with recurrent or persistent back and leg pain. Methods After reviewing their institutional database, the authors found 69 patients 65 years of age and older who had undergone revision decompression and instrumented fusion for back and leg pain associated with pseudarthrosis (17 patients), same-level recurrent stenosis (24 patients), or ASD (28 patients) and included them in this study. Total 2-year back-related medical resource utilization and health state values (quality-adjusted life years [QALYs], calculated from the EQ-5D, the EuroQol-5D health survey, with US valuation) were assessed. Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts. The mean total 2-year cost per QALY gained after revision surgery was assessed. Results The mean (± standard deviation) time between the index surgery and revision surgery was 3.51 ± 3.63 years. A mean cumulative 2-year gain of 0.35 QALY was observed after revision surgery. The mean total 2-year cost of revision surgery was $28,256 ± $3000 (ASD: $28,829 ± $3812, pseudarthrosis: $28,069 ± $2508, same-level recurrent stenosis: $27,871 ± $2375). Revision decompression and extension of fusion was associated with a mean 2-year cost of $80,594 per QALY gained. Conclusions Revision decompression and fusion provided a significant gain in health state utility for elderly patients with symptomatic pseudarthrosis, same-level recurrent stenosis, or ASD, with a mean 2-year cost of $80,594 per QALY gained. When indicated, revision surgery for symptomatic ASD, same-level recurrent stenosis, and pseudarthrosis is a valuable treatment option for elderly patients experiencing persistent back and leg pain. Findings in this study provided a value measure of surgery that can be compared with future cost-per-QALY-gained studies of medical management or alternative surgical approaches.

The Object of the Study: Payment for work in the Rossiykaya Federatsiya The Subject of the Study: The minimum wage rate and dynamics in Rossiya and RF subjectsThe Purpose of the Study: Estimating the minimum wage substance in different periods of the socio-economic development of the country and identifying the reasons for different approaches to the minimum wage setting in regions.The Main Provisions of the Article. Minimum wage is a social guarantee of payment for work of employees that is set according to the tripartite agreement between the State, employers and trade unions representing the interests of employees. In the Rossiyskaya Federatsiya the substantive estimation of the minimum wage is based on its ratio to the amount of the subsistence minimum of able-bodied population. In international comparisons the most common statistical indicator for calculation of the sufficient minimum wage is the minimum wage ratio to median wage (Kaitz index) and average wage.The minimum wage dynamics in Rossiya is analyzed by four periods. Each of them reflects the socio-economic situation in the country. The first period (1992 - 1999) was characterized by formation of market relations accompanied by economic crisis and high inflation. The second one (2000 - mid-2008) – by a gradual normalization of the socio-economic situation and economic growth. During this period were adopted the laws that in subsequent years affected the situation with minimum wages in regions. The third (late 2008 - early 2018) – by periodically recurring crises in the economy. The fourth one started in May 2018 when the wage at the Federal level was set at 100% of the subsistence minimum of the able-bodied population of Rossiya in the second quarter of 2017. The authors consider in detail the situation in these years in the RF subjects with different natural climatic conditions. They conclude by saying that the notion of minimum wage in the legislation should be clearly defined as well as the criterion of its economic substance – subsistence minimum-should be changed.

This paper proposes a new application of the stochastic game model to solve the problem of self- organization of the Hamiltonian cycle of a graph. To do this, at the vertices of the undirected graph are placed game agents, whose pure strategies are options for choosing one of the incident edges. A random selection of strategies by all agents forms a set of local paths that begin at each vertex of the graph. Current player payments are defined as loss functions that depend on the strategies of neighboring players that control adjacent vertices of the graph. These functions are formed from a penalty for the choice of opposing strategies by neighboring players and a penalty for strategies that have reduced the length of the local path. Random selection of players’ pure strategies is aimed at minimizing their average loss functions. The generation of sequences of pure strategies is performed by a discrete distribution built on the basis of dynamic vectors of mixed strategies. The elements of the vectors of mixed strategies are the probabilities of choosing the appropriate pure strategies that adaptively take into account the values of current losses. The formation of vectors of mixed strategies is determined by the Markov recurrent method, for the construction of which the gradient method of stochastic approximation is used. During the game, the method increases the value of the probabilities of choosing those pure strategies that lead to a decrease in the functions of average losses. For given methods of forming current payments, the result of the stochastic game is the formation of patterns of self-organization in the form of cyclically oriented strategies of game agents. The conditions of convergence of the recurrent method to collectively optimal solutions are ensured by observance of the fundamental conditions of stochastic approximation. The game task is extended to random graphs. To do this, the vertices are assigned the probabilities of recovery failures, which cause a change in the structure of the graph at each step of the game. Realizations of a random graph are adaptively taken into account when searching for Hamiltonian cycles. Increasing the probability of failure slows down the convergence of the stochastic game. Computer simulation of the stochastic game provided patterns of self-organization of agents’ strategies in the form of several local cycles or a global Hamiltonian cycle of the graph, depending on the ways of forming the current losses of players. The reliability of experimental studies is confirmed by the repetition of implementations of self-organization patterns for different sequences of random variables. The results of the study can be used in practice for game-solving NP-complex problems, transport and communication problems, for building authentication protocols in distributed information systems, for collective decision-making in conditions of uncertainty.

Using an empirical approach and relying on core media management research theories — strategic management, structural contingency and the economic — for background, this research studied the financial situations of newspapers in Nigeria between 2015 and 2019 to find out how their prolonged financial difficulties interact with their ‘responsibility’ to Nigeria’s democracy. It found that the financial troubles of the newspaper market in Nigeria are manifested in the marked decline of traditional revenue sources, shutting down of bureaus and titles, retrenchment of quality hands as well as poor renumeration and non-payment of journalists’ salaries. Subtly and directly, these have impacts on Nigeria’s democracy, especially when it is considered that newspapers are valued civic engagement and accountability tools in democracy. The recurrent drop in circulation figures, closure of bureaus and retrenchment of quality manpower indicate that newspapers in Nigeria are in a precarious financial state, which affects their capacity to support profound democratic practices in the country.

The main thrust of this study is to investigate the seeming mismatch between resource generation, resource allocation and expenditure management in Nigeria. While an ex-post facto research design was adopted in the investigation; descriptive statistics as well as a least square regression analysis were carried out on a time-series data to ascertain relationships. Real Gross Domestic Product taken as a proxy for economic growth is the dependent variable while capital and recurrent expenditures are the independent variables. Outcome of the study indicates that, the nation’s financing option is skewed towards payment of salaries and personnel emoluments (Recurrent Expenditures) as against the provision of basic infrastructures (Capital Expenditures) that are growth oriented. The trend of disbursements is not appropriately harnessed to create a favorable and positive impact on economic growth. In the short run, the disaggregated components of capital expenditure (CAPEX) indicate that expenses incurred in administration sector and external debt service transfers attracted more than their fare share of public expenditure to the detriment of economic and social community welfare services. The disaggregated component of recurrent expenditures (RECEX) indicate that expense on economic service sector and the lagged value of RGDP taken as an explanatory variable were found to have a positive significant relationship with economic growth in the long run. It is therefore recommended that conscious efforts be made by government to scrutinize and monitor budget implementations. Macroeconomic projections should guide the overall level of expenditures. This should be more realistic, internally consistent and based on more accurate and timely information. Government must embark on a careful estimation and determination of priorities and to emphasize the need for control over revenue and expenditure so as to enhance critical areas of economic growth in Nigeria.

Mobile phones has become very integral part in our day to day life. In the digitalized world most of our day to day activities rely on mobile phone like banking activities, wallet payments, credentials, social accounts etc. Our system works in such a way that if there is an advantage to a technology there also exists a disadvantage. Every users have all their private and sensitive data in their mobile phones and download random applications from different platforms like play store, App store etc. There is a huge possibility that the applications downloaded are malicious applications. The existing system provides a solution for detection of such applications with the help of antivirus which has pre-built signatures that can be used to obtain an already existing malware which can be modified and manipulated by the hacker if they tend to do so. In this project, our purpose is to identify the malicious applications using Machine learning. By combining both static analysis and dynamic analysis we can use a Hybrid approach for analysing and detecting malware threats in android applications using Recurrent Neural Network (RNN). The main aim of this project will be to ensure that the application installed is benign, if it is not, it should block such applications and notify the user.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy and genetic abnormalities contribute to disease heterogeneity and outcome. Primary abnormalities, namely recurrent immunoglobulin (Ig) heavy chain translocations and hyperdiploidy, occur early in disease course. Secondary events, such as MYC abnormalities occur upon progression. Earlier studies showed MYC abnormalities detected by FISH or by capture sequencing were independently associated with poor outcome (Walker, et al., BCJ, 2014), while recent studies using WGS did not support this finding (excluding MYC/IGL) (Mikulasova, et al. Haematologica, 2020; Misund, et al. Leukemia, 2020). We hypothesize these discrepancies are due to differences in methods and sensitivities of detection of MYC abnormalities by FISH vs. WGS. Given that MYC abnormalities often display remarkable genomic heterogeneity with numerous gene partners, reduced detection of MYC abnormalities by FISH is not unexpected. This hypothesis is supported by lower frequencies of MYC abnormalities found by FISH (15%) vs. NGS (30-35%) consistent with ~50% false-negative rate of the MYC FISH probe (Smadbeck, et al. BCJ, 2019). To better understand the role of MYC in myeloma disease outcome, we compared the MYC abnormality subtype identified by FISH or NGS vs. MYC gene expression levels and overall survival. Methods: We performed a retrospective study of newly diagnosed MM patients seen at Mayo Clinic or enrolled in the MMRF CoMMpass trial. For Mayo cases, MYC FISH results (breakapart probe, Abbott) were obtained from the Mayo Clinic Genomics database (N=1342) and mate pair sequencing (MPseq) was performed on 140 cases. For CoMMpass cases, we obtained tumor long-insert whole genome sequencing (WGS), RNA sequencing (RNAseq) for gene expression and clinical outcome data. Overall survival (OS) was defined as time from diagnosis to death from any cause or to last follow up. Survival curves were estimated using Kaplan Meier and compared using the Log-Rank test. Statistical analyses performed using SPSS and JMP with significance determined when P &lt;0.05. Results: We first evaluated the impact of MYC abnormalities on OS when detected by FISH or NGS. In Mayo cases, OS was significantly shorter in patients with MYC abnormalities compared to patients without MYC abnormalities using FISH (5.3 vs. 8.0 years, P&lt;0.001, N=1342). In contrast, there was no significant difference in OS between patients with or without MYC or abnormalities using MPseq or WGS in both the Mayo and CoMMpass cohorts (Mayo: 6.4 vs. and 6.9 years P=0.78, N=140; CoMMpass: 4.9 vs. and 5.1 years P=0.74, N=546). Since FISH-detected MYC abnormalities were associated with poor outcome, we evaluated differences in the types of MYC abnormalities identified FISH and genome sequencing; 270 of 658 CoMMpass cases had a MYC abnormality and 12 abnormality subgroups were identified. In the Mayo cases, FISH preferentially detected translocations and complex abnormalities and missed insertions with flanking duplicating sequences or terminal tandem duplications (TTD) that occur telomeric to MYC. Since the level of MYC expression should be a consequence of the various genomic abnormalities altering the MYC gene region, we compared MYC expression levels in relation to MYC abnormality subgroups. Highest expression was seen with MYC amplification, followed by Ig abnormalities, non-Ig abnormalities, complex deletion/duplications, proximal deletions, non-Ig insertions, terminal deletions, TTD, trisomy 8, no MYC structural variation, monosomy 8 and cases with MAX mutations had the lowest expression. Abnormalities identified by FISH had higher MYC expression (83.5 TPM) compared to cases predicted to be missed by FISH (63.2 TPM). We tested if high MYC expression, irrespective of MYC structural abnormality, was associated with differences in OS. Boxplot analysis was used to categorize MYC expression in 631 CoMMpass patients as top quartile/high MYC expression (Q4≥ 75 TPM, n=159) and bottom quartile/low MYC expression (Q1≤ 16.5 TPM, n= 158) (see Figure). OS was significantly shorter in patients with high MYC expression compared to patients with low MYC expression (4.6 vs. 5.3 years, P &lt;0.038). Conclusion: We show that FISH detects only a subset of the MYC abnormalities detected by genome sequencing, and that FISH-detected MYC abnormalities are associated with higher MYC gene expression and decreased survival. Figure 1 Disclosures Kumar: Kite Pharma: Consultancy, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Dr. Reddy's Laboratories: Honoraria; Cellectar: Other; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Novartis: Research Funding; Tenebio: Other, Research Funding; Carsgen: Other, Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Merck: Consultancy, Research Funding; Genecentrix: Consultancy; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; MedImmune: Research Funding; Adaptive Biotechnologies: Consultancy.

Background: Multiple myeloma (MM) remains an incurable plasma cell (PC) malignancy. Despite improvements in clinical outcomes, variability in treatment response exists. Some patients experience innate resistance, while others develop resistance over the course of treatment. Identifying signatures of treatment response and resistance is essential to predicting effective treatment strategies. Given the phenotypic clonal heterogeneity observed in MM, we hypothesize that resistant and sensitive subpopulations have unique phenotypic signatures. We used mass cytometry (CyTOF) to characterize primary MM samples and correlated their phenotypic signatures with treatment response. Methods: We characterized 102 primary MM samples by CyTOF using 37 antibodies (see figure). Frozen whole BM specimens were thawed, stained with antibodies, barcoded, and analyzed on a Helios mass cytometer. Data was processed using Cytobank or Pathsetter and analyzed using t-distributed stochastic neighbor embedding (t-SNE) algorithm. T-SNE plots for CD45+ cells were created using lineage defining markers. T-SNE plots of neoplastic PCs (CD138+,CD3-,CD16-,CD19-,cytoplasmic kappa or lambda+) were created using all remaining markers. A differential analysis of each sample's clusters was performed against all other events. Z-score values, representing marker changes from the differential analysis, for each cluster were used to group similar clusters across all samples, allowing us to compare sub populations of PCs between patients (see figure). From these groups of clusters with similar changes in markers, we calculated the proportion of cells with increases or decreases in markers for each sample. Results were compared to IMWG 90-day response criteria using a random forest model. Results: We performed mass cytometry on 102 samples from 68 unique MM patients. Median age was 66 years (range 34-95) with a 1.5:1 male:female ratio. 37 (36%) had NDMM, 55 (54%) had RRMM, 2 (2%) had SMM and 8 cases (8%) had unknown status. FISH studies revealed 47 (46%) had hyperdiploidy without a recurrent primary IgH rearrangement, 31 (30%) had t(11;14), 13 (13%) had t(4;14), 5 (5%) had 14;16 or 14;20, 3 (3%) had hyperhaploidy and 3 (3%) had an undefined primary. 54 (53%) had 1q gain/amp, 22 (22%) had TP53 deletion, 22 (22%) had a MYC rearrangement and 71% had high mSMART risk. Nearly all patients received an immunomodulatory compound, a proteasome inhibitor and dexamethasone. 2 (2%) had complete response (CR), 10 (9.8%) very good partial response (VGPR), 36 (35%) had partial response (PR), 14 (14%) had minimal response (MR), 13 (13%) had stable disease (SD) and 17 (17%) had progressive disease (PD). Characterization of CD45+ cells identified a relatively conserved and reproducible map from each patient. Notable differences included an ~2-fold reduction in the percentage of total B cells (CD45+,CD3-,CD19+)/total CD45+ cells in cases with high risk mSMART, RRMM and TP53 deletion compared to cases with standard risk, NDMM or normal TP53 status. Similar B-cell reductions were found in RRMM vs. NDMM samples from matched-patients. In contrast to the conserved t-SNE structure of the CD45+ population, the neoplastic PC population displayed dramatically reduced t-SNE structural consistency. Heterogeneity between patient samples and between the same patient samples over time was observed. We focused our analysis on 22 patients with serial samples. The proportion of each t-SNE group present in each patient sample was calculated and then correlated to the 90-day response metric. We identified a phenotypic group whose proportion increased in relation to disease progression (R2=0.85). This group had elevated BCL-2, pSTAT3, CD56 levels and reduced CD45 and CD81 levels. Evaluating individual markers, we found an increase in the proportion of cells with elevated BCL-2, pS6, Ki67, and IKZF1 levels in relation to disease progression. We also observed an increase in the proportion of cells with reduced pCREB levels and a reduction in the proportion of cells with reduced CD147 levels in relation to disease progression. Conclusions: We have utilized CyTOF to characterize phenotypic and functional markers in MM cells on a single cell level and can identify unique subgroups that change in relation to disease progression. Future analysis will correlate phenotypic signatures with ISS stage, mSMART risk, cytogenetic abnormality and type of treatment. Figure 1 Disclosures Kumar: Kite Pharma: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; MedImmune: Research Funding; Karyopharm: Consultancy; Merck: Consultancy, Research Funding; Carsgen: Other, Research Funding; Cellectar: Other; Novartis: Research Funding; Adaptive Biotechnologies: Consultancy; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Tenebio: Other, Research Funding; BMS: Consultancy, Research Funding; Dr. Reddy's Laboratories: Honoraria.

This study empirically examine the impact of government expenditure on education on human capital development in Kaduna State over the last 15 years (2000-2015) using econometrics model with Ordinary Least Square (OLS) technique.The paper test for presence of stationary between the variables using Augmented Dickey Fuller (ADF) and autocorrelationusing Durbin Watson statistics. The results reveals all the variables were not stationary in levels except capital expenditure (CE) and Primary schools enrolment (PE) while the rest were stationary at second difference. DW shows presence of serial correlation. The regression results indicated that government expenditure on education have significant impact on human capital development in Kaduna State. It could therefore be recommended that the state government should increase its capital and recurrent expenditure on education, ensure proper management and monitory of funds made for the teachers, constant payment of teachers salaries and allowances in a manner that it will raise the state production capacity. The state should construct addition primary and secondary schools across the state, with modern facilities, and employ more teachers.

The additional cost of treating acute care type Victorian private patients as public patients in Victorian public hospitals based on the current public sector payment model and rates was calculated, as was the loss of health fund income to public hospitals. If all private cases became public the net recurrent cost would be $1.05 billion assuming all patients were still treated. If private health insurance (PHI) uptake had declined to 23.3% as was projected without Lifetime Health Cover and the 30% rebate, the additional operating cost and income loss would be $385 million. This compares to the Victorian cost of the 30% rebate for acute hospital cases of $383 million. This takes no account of capital costs and possible public sector access problems. The analysis suggests that 31 extra operating theatres would be needed in the public sector (had the transfer of surgical patients from the public sector to the private sector not occurred). This analysis suggests that without the PHI rebate the current stresses on Victorian public hospitals would be increased, not decreased.

Purpose The sustainable skills that informal manufacturers use in volatile times remain poorly understood. This study explored the skills that the informal manufacturers used to navigate the uncertain business environment during the COVID-19 pandemic. Design/methodology/approach A total of 27 telephone interviews were conducted with informal entrepreneurs who were manufacturers of agricultural machinery at Mbare Magaba and Gaza home industry in Harare, Zimbabwe. Purposive and snow ball sampling were used to identify information rich sources. The authors used thematic analysis in identifying recurrent themes from this study. Findings The study results show that business agility motivated most informal manufacturers to restructure their business to sustain their operations. With the closure of formal companies, the informal manufacturers adopted slowing and narrowing loops through purchasing broken down agricultural machines for repairs or remanufacturing of durable machines for their low-income customer base. Most young and formally trained manufacturers adopted a prospector strategic behaviour as they used digital platforms to network with business associates for supplies, gathering market intelligence, making and receiving electronic payments and establishing virtual distant markets whilst the older manufacturers resorted mostly to a defender strategic behaviour of engaging their usual customers for repair jobs and a few referrals. Originality/value This study offers unique insights with respect to skills required for the sustainable and strategic management of small and medium enterprises during times of crisis.

Since the Belt and Road Initiative (BRI) has been put in practice by the Chinese government, several High-Speed Railways (HSR) have been built by Chinese Engineering Procurement and Construction (EPC) firms. However, many delays have created severe detrimental consequences on the progress of most HSR projects. This study sought to explore the essence of the recurring triggers of delays in international EPC HSR projects under the BRI, and a structured questionnaire survey approach was applied to compile the first-hand dataset from Chinese EPC firms working for BRI infrastructure projects. The data were evaluated, and the Relative Importance Index (RII) was adopted to assess the magnitude of the important delay triggers. The findings suggest that HSR projects are still susceptible to unavoidable delays in global construction infrastructure projects. In the engineering phase, improper management of the design, unsustainable land acquisition, and insufficient use of EPC joint venture are the salient trigger of delays. In the procurement phase, the leading causes of unsuitable procurement, undervalued procurement cost, inefficient logistics in labor and materials, improper planning, unqualified site supervisors, inefficient technical standard management, and inefficient constant payment terms are likely to trigger delays in the construction phase HSR projects. Five critical groups of delay factors are identified by this study, which has an essential primary contribution to the body of knowledge and is helpful to EPC contractors working for HSR projects under BRI.