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The article deals with the concept of close-out netting, its role and significance for the stability of the financial market and minimizing the risks of participants in derivatives transactions. The author conducts a research of the procedure for implementing close-out netting based on the provisions of the Model Provisions for derivative transactions on the financial markets as of 2011, the results of which can be used in practice.

Most of the prior studies concentrated on warning letters issued for clinical investigation, Institutional review board, and infringement of promotional claims, no studies assessed the warning letters issued for infringements of Current Good Manufacturing Practice (cGMP) pertaining to medical devices. Hence, there is a need to carry out a crosssectional study of these warning letters. Publically available U.S. Food & Drug Administration (USFDA) letters under the law of the freedom of Information Act sent to the pharmaceutical company were accessed from the USFDA website. A standard data collection tool (Excel Spreadsheet) with all letters of warning issued from January 2008 to July 2018 was developed. Letters have been manually screened. Warning letters related to medical device breaches of cGMP were screened based on the letter's subject and content. Overall, 669 warning letters issued for medical device cGMP violations were reviewed between January 2008 and November 2018. From 2008 to 2013, there was a downward trend in the issuance of warning letters. The number of warning letters issued in 2014 was 101, followed by 106 in 2015, as the USFDA focused more on data integrity issues, while the number decreased to 53, 27, and 19, respectively, in 2016, 2017, and 2018. The highest number of warning letters were issued to manufacturers located in the USA (379), followed by Canada (52), and China (37). Section 820.30 of Title 21 CFR was found to be most violated with 603 infringements. This section represents the design control requirements for cGMP. Class 2 type of medical devices were found to be most violated (82%), followed by Class 3 with 7%. Only 32% of the companies responded to the warning letters although 52% Not Issued the closeout letter followed by 16% of the letters were considered as non-applicable letters. With the time, scientific developments and increased awareness of both regulatory authorities and industries/academic organizations, overall improvement are observed with significant decrease in the number of warning letters.

Background: When implementing e-health solutions, effective integration into a clinic's existing processes is essential to facilitate adoption and sustained usage. Introduction: This article examines the effectiveness of adoption/utilization of an electronic consultation (eConsult) service by primary care providers (PCPs) using a "delegate model," through which referral clerks manage requests on behalf of PCPs, thereby reducing PCPs' administrative burden. Materials and Methods: We conducted a retrospective cross-sectional study of all eConsults submitted between May 1, 2013, and December 31, 2017, by the Bruyere Academic Family Health Team (FHT), after the clinic implemented the service using a delegate model. We assessed system utilization, including monthly volume of submitted eConsults, requested specialties, and impact on PCP referral behavior based on the mandatory closeout surveys. We also conducted a subanalysis to compare the volumes of eConsults per provider between the FHT and all other providers. Results: The Bruyere Academic FHT submitted 3,233 eConsult cases. Volume increased 3.5 fold, from 285 in the first year to 1,016 in the last year. Active Bruyere Academic FHT providers (those who submitted ≥3 cases in 6 months) submitted a median of 25 eConsults (interquartile range [IQR]: 14.75-35.25) versus 14 (IQR 8-24) for all other active users. In 36% of cases, a referral was originally contemplated but avoided based on specialist advice. In 5% of cases, the referral was not originally contemplated but deemed appropriate by the PCP based on specialist advice. Discussion: Our findings show high levels of eConsult use in the clinic utilizing a delegate model, which persisted throughout the study period and was reported to significantly reduce the backlog of traditional referrals at the clinic. Conclusions: The integration of eConsult capability into existing clinic operations was successful in that it allowed the PCPs to request eConsult using a familiar process, avoiding the challenges associated with adopting a new and unfamiliar technology.

Objective To compare the content of traditional faxed referrals and electronic consultations (eConsults) and determine how many questions sent by traditional referral could be successfully addressed using eConsult. Methods We conducted a cross-sectional, qualitative study of eConsults and faxed referrals sent to a tertiary diabetes and endocrinology clinic in Ottawa, Ontario. A convenience sample of 300 faxed referrals sent between March and July 2017 and 300 eConsults submitted between January and December 2017 were selected and coded using an established taxonomy to determine question type. Two endocrinologists reviewed the faxed referrals to assess whether they could have been addressed using eConsult. Responses to a mandatory closeout survey were reviewed for all eConsults, assessing the case’s outcome, impact on decision to refer, and educational value. Results Most faxed consultations were requests for shared care in diabetes mellitus, whereas most eConsults requested help in diagnostic test interpretation. 25–27% of faxed consults were felt to be potentially amenable to eConsult. Referring provider behaviour was changed in 45.3% of eConsult cases through avoidance of face-to-face consultation. Conclusion eConsult is a promising tool for PCPs to improve access to specialist opinion without necessitating a face-to-face visit.

Electronic Data Capture (EDC) has become a common a proven tool for data collection and management in clinical trials. Thus, understanding the principles and methods for EDC use has become a major component of clinical data management (CDM) professional practice. This chapter focuses on using the EDC system and accruing data to support study conduct, maintaining an EDC system during a study, and concluding active data collection through database lock. The regulatory basis for minimum standard and recommended best practices are discussed.

In this paper, we launch a practical modus-operandi for the assessment of potential market risk exposures for financial trading portfolios by providing an investment management perspective from the 2007-2009 global financial crisis. This proposed tactic is based on the renowned concept of Liquidity-Adjusted Value-at-Risk (LVaR) along with the innovation of a risk-engine algorithm that can estimate LVaR for both long and short-sales positions.

Auction is probably the most seasoned method of purchasing and selling merchandise and items. The present world has been changed to the web so closeout has additionally advanced to online.83% of the absolute populace purchase something in the auction.94% of the all-out populace sell items in the bartering. 34% of the complete populace determines the status of the sale. This two-way component is utilized for purchasing and selling items or IAAS. The Internet gave an unbounded commercial center to clients, one in which they can discover anything they need and think about costs without any problem. Distributed computing is the transport of figuring administrations including workers, limit, information bases, coordinating, PC program, examination, and insight over the Web ("the cloud") to offer speedier turn of events, versatile resources, and economies of scale. You usually pay in a manner of speaking for cloud organizations you use, having an effect lower you're working expenses, run your structure all the more capably, and scale your trade needs changes.

This article investigates the applicability and compatibility of project closeout processes defined in traditional project management frameworks in cases of agile-developed IT projects. Based on a literature review analysis of three project management frameworks, the hypothesis is formed that traditional project closeout processes are critical in agile developed IT projects. The developed hypothesis suggests an unclear indication of how to trigger a project closeout, the inapplicability of scope fulfillment for closeout trigger, and critical transitions between closed projects and ongoing agile software improvement and maintenance. All three parts of the hypothesis are then individually evaluated by an online survey with 85 participants. As a result of this survey, all three hypotheses are falsified. For most project management practitioners in agile projects, closeout processes are not critical, scope fulfillment is still the most relevant closeout trigger, and the transition to a continues-improvement and maintenance process is seen as principally uncritical.

Background: Research site monitoring (RSM) is an effective way to ensure compliance with Good Clinical Practice (GCP). However, RSM is not offered to trainees (investigators) at African Institutions routinely. The Makerere University/Uganda Virus Research Institute Centre of Excellence in Infection and Immunity Research and Training (MUII-Plus) introduced internal monitoring to promote the quality of trainees’ research projects. Here, we share our monitoring model, experiences and achievements, and challenges encountered. Methods: We analysed investigators’ project reports from monitoring visits undertaken from April 2017 to December 2019. Monitors followed a standard checklist to review investigator site files and record forms, and toured site facilities. We planned four monitoring visits for each trainee: one at site initiation, two interim, and a closeout monitoring visit. A team of two monitors conducted the visits. Results: We monitored 25 out of the 26 research projects in progress between April 2017 and December 2019. Compliance with protocols, standard operating procedures, GCP, and GCLP improved with each monitoring visit. Median (IQR) compliance rate was 43% (31%, 44%) at site initiation visit for different monitoring items, 70% (54%, 90%) at the 1st interim monitoring visit, 100% (92%, 100%) at 2nd interim monitoring visit and all projects achieved 100% compliance at site closeout. All investigators had good work ethics and practice, and appropriate facilities. Initially, some investigators’ files lacked essential documents, and informed consent processes needed to be improved. We realized that non-compliant investigators had not received prior training in GCP/GCLP, so we offered them this training. Conclusions: Routine monitoring helps identify non-compliance early and improves the quality of research. We recommend continuous internal monitoring for all research studies. Investigators conducting research involving human subjects should receive GCP/GCLP training before commencing their projects. Institutional higher degrees and research ethics committees should enforce this as a requirement for project approvals.

In the recent times, the World Wide web has the drastic effect on the way people used to do the business in a standard way. Individuals can financial institution, oversee ventures, demand various items, and acquire information on an unbounded variety of points on the internet. It is not a good sign that, such a boost to the technique is not contributing to the development and prosperity of the new entrepreneur. It is also disappointing that the pharmacy business failed to take gain of this fortunate ruin to modernize a standard limit —prescription agreement. Various web drug stores provide medium-term delivery, enabling customers to hold a strategic distance from the deferral of regular mail. Web medicate stores can offer protection that is regularly ailing in a standard drug store. In any case, there is need to consider fundamentally the moral standards in the usage of digital drug. The online medical stores has induced administrative and checking activities at the government, and expert affiliation stages. The closeout of e-medicines in the global framework is possibly perilous and needs universal guidelines. Here is an outline of online drug stores, their latent advantages, the affiliations engaged with controlling these destinations, and the enormous discussions including on the web drug stores.

Closeout procedures enable central counterparties (CCPs) to respond to events that challenge the continuity of their normal operations, most frequently triggered by the default of one or more clearing members. The procedures ensure the regularity of the settlement process through the prudent and orderly closeout of the defaulter’s portfolio. Traditional approaches to CCPs’ margin requirements typically assume a simple closeout profile, and do not account for the ‘real-life’ constraints embedded on the management of a default. The paper proposes an approach of evaluating how distinct closeout strategies may expose a CCP to different sets of risk and costs, and consequently could impact the sufficiency of financial resources to cover its risk exposure to a default. The approach is based on a counterfactual simulation, and evaluates a full spectrum of hedging strategies in an exploratory and model-free manner, deriving endogenous and market-dependent risk metrics. Using the trade repository data available to the Bank (as a result of EMIR reporting) on over-the-counter (OTC) interest rate swaps (IRS) and ten years (ie 2005 to 2015) of information on related market risk factors, the paper derives empirically an efficient hedging strategy that minimizes the CCP’s risk exposure to a defaulting clearing member. Endogenous trade-off structures between total risk (market risk plus funding needs) and transaction costs are also established, with marginal sensitivities to individual components of the hedging strategy determined.

To apply final as-built BIM models to facility management (FM) during the operation phase, it is important for owners to obtain an accurate, final as-built model from the general contractors (GCs) following project closeout. Confirming the accuracy of the final as-built BIM model is one of the most important works executed by owners to meet the accuracy requirement of final as-built models for FM. However, many practical problems arise relating to the management of final as-built models such as final as-built model mismatch, the lack of available final as-built models, and the entry of incorrect non-geometric information into the final as-built models. To solve these practical problems, this study develops a Final As-built BIM Model Management (FABMM) system for owners to handle final as-built BIM model inspection, modification, and confirmation (BMIMC) work beyond project closeout. The proposed approach and system can be used to manage the status and results of BMIMC management work for the final as-built BIM model to be performed. The proposed approach and system were applied in a case study in a selected building in Taiwan to verify and demonstrate its practical effectiveness. This study identifies the benefits, limitations, and conclusions of the FABMM system, and presents suggestions for its further application.

Purpose Problems of Malaysian construction industry have often been associated, in part to incompetent construction manager (CM) when managing the construction projects. Although various education and training provisions have been introduced, critics argue that the provisions have not been effective. Central in the debate on the adequacy of the CM education and training offered is the answer to the question of “what constitutes the technical competency of the CM?” The purpose of this paper is to present the study that identifies the technical competencies required by the CM to address the question. Design/methodology/approach Multi-layered thematic analysis of literature was first carried out to identify the technical competency elements. Then, interviews were undertaken to confirm the elements of competencies. It was followed with questionnaire surveys to test the validity of the technical competencies against different contractors’ category and grade/size. Findings The findings suggest that the technical competencies of CM are generic, regardless of the size of construction organisation or the types of projects they undertake. A total of 16 CM technical competencies were identified which include the ability to manage: staff, materials, labour, plant, sub-contractors, safety, money, quality, time, environment, site administration, pre-construction activities, project closeout and handover, third parties, computer literacy, and construction contract. Originality/value The findings suggest that generic education and training is possible to develop technically competent CM. It also provides insights to the CM technical competencies which the industry is expecting.

Purpose The purpose of this paper is to provide an analysis of a post-project review (PPR) method designed to verify the accomplishments of urban disaster risk reduction-neighborhood approach (DRR-NA) projects after at least one year of project closeout. The PPR revisited the essential processes identified during project implementation and analyzed the sustainability of project gains. Design/methodology/approach The first section focuses on a literature review of the evaluation methods after project implementation, and the second describes the urban risk PPR design, its implementation, and findings. Findings The proposed framework for the PPR was clear and uniform and at the same time offered the necessary flexibility to adapt to the different DRR-NA projects and contexts. The PPR methodology sought to determine the conditions of the physical works, social and environmental gains, and progress in institutional arrangements associated with the NA projects. Factors that contribute and impede success in DRR-NA projects were identified. Practical implications Allowing at least one year between the completion of the NA projects and the PPR is both convenient and challenging. On the positive side, this approach allows for the verification of project outcomes after an extended period of time. However, there are also challenges, such as the need to seek additional financial resources to carry out the review; generate new contractual mechanisms; and assign human resources to review a project already closed. Originality/value The changes introduced into the PPR methodology to obtain a participative and self-conducted process resulted in a truly collective learning experience, becoming an act of accountability and social commitment.

Price is a major factor on the demand based on marketing and economic theory. In addition, the demand for perishable products also depends on its freshness. Moreover, it is a well-known fact that increasing stock display (e.g., fresh fruits, vegetables, baked goods) may encourage consumers to purchase more. This paper first proposes an inventory model that stipulates the demand explicitly in a multivariate function of price, freshness, and displayed stocks. It may be profitable to have a closeout sale at a markdown price, and always keep on-hand displayed stocks fresh and plentiful if the demand is freshness-and-stock dependent. Hence, the traditional assumption of zero ending inventories is relaxed to a non-zero ending inventory. As a result, the objective is to determine three decision variables (i.e., unit price, cycle time, and ending-inventory level) in order to maximize the total profit. Then it is demonstrated that the total profit is strictly pseudo-concave in those three decision variables, which reduces the search for solutions to a unique local maximum. Finally, numerical examples to illustrate the theoretical results and to highlight managerial insights are presented.

Background and Objectives: Patients in many countries face poor access to specialist care. Electronic consultation (eConsult) improves access by allowing primary care providers (PCPs) and specialists to communicate electronically. As more countries adopt eConsult services, there has been growing interest in leveraging them as educational tools. Our study aimed to assess PCPs’ perspectives on eConsult’s ability to improve collegiality between providers and serve as an educational tool. Methods: We conducted a qualitative content analysis of free-text comments left by PCPs using the Champlain BASE eConsult service based in Eastern Ontario, Canada. All responses provided between January 1, 2015 and January 31, 2017 that mentioned education or collegiality were included. Results: PCPs completed 16,712 closeout surveys during the study period, of which 3,601 (22%) included free-text comments. Of these, 223 (6%) included references to education or collegiality. Three prominent themes emerged from the data: building provider relationships, teaching incorporated into answer, and prompting further learning. Conclusions: PCPs described eConsult’s ability to foster stronger relationships with specialists, deliver responses that provided teaching in multiple areas of their practice, and support further learning that extended beyond the case at hand and into their overall practice. The Champlain BASE eConsult service has educational value for providers. Further study is underway to explore how questions and replies submitted through eConsult can be used to facilitate reflective learning and promote feedback to providers.

Since the 2008 global financial crisis, the banking industry has been using valuation adjustments to account for default risk and funding costs. These adjustments are computed separately and added together by practitioners as if the valuation equations were linear. This assumption is too strong and does not allow to model market features such as different borrowing and lending rates and replacement default closeout. Hence we argue that the full valuation equations are nonlinear, and this paper is devoted to studying the nonlinear valuation equations introduced in Pallavicini et al (2011). We illustrate all the cash flows exchanged by the parties involved in a derivative contract, in presence of default risk, collateralisation with re-hypothecation and funding costs. Then we show how to obtain semi-linear PDEs or Forward Backward Stochastic Differential Equations (FBSDEs) from present-valuing said cash flows in an arbitrage-free setup, and we study the well-posedness of these PDEs and FBSDEs in a viscosity and classical sense. Moreover, from a financial perspective, we discuss cases where classical valuation adjustments (XVA) can be disentangled. We show how funding costs are offset by treasury valuation adjustments when one takes a whole-bank perspective in the valuation, while the same costs are not offset by such adjustments when taking a shareholder perspective. We show that although we use a risk-neutral valuation framework based on a locally risk-free bank account, our final valuation equations do not depend on the risk-free rate. Finally, we show how to consistently derive a netting set valuation from a portfolio level one.

Summary Identifying biomarkers as surrogates for clinical endpoints in randomized vaccine trials is useful for reducing study duration and costs, relieving participants of unnecessary discomfort, and understanding vaccine-effect mechanism. In this article, we use risk models with multiple vaccine-induced immune response biomarkers to measure the causal association between a vaccine’s effects on these biomarkers and that on the clinical endpoint. In this setup, our main objective is to combine and select markers with high surrogacy from a list of many candidate markers, allowing us to get a more parsimonious model which can potentially increase the predictive quality of the true markers. To address the missing “potential” biomarker value if a subject receives placebo, we utilize the baseline immunogenicity predictor design augmented with a “closeout placebo vaccination” group. We then impute the missing potential marker values and conduct marker selection through a stepwise resampling and imputation method called stability selection. We test our proposed strategy under relevant simulation settings and on (partially simulated) biomarker data from a HIV vaccine trial (RV144).

Background It is well reported that tracking physical activity can lead to sustained exercise routines, which can decrease disease risk. However, most stop using trackers within a couple months of initial use. The reasons people stop using activity trackers can be varied and personal. Understanding the reasons for discontinued use could lead to greater acceptance of tracking and more regular exercise engagement. Objective The aim of this study was to determine the individualistic reasons for nonengagement with activity trackers. Methods Overweight and obese participants (n=30) were enrolled and allowed to choose an activity tracker of their choice to use for 9 weeks. Questionnaires were administered at the beginning and end of the study to collect data on their technology use, as well as social, physiological, and psychological attributes that may influence tracker use. Closeout interviews were also conducted to further identify individual influencers and attributes. In addition, daily steps were collected from the activity tracker. Results The results of the study indicate that participants typically valued the knowledge of their activity level the activity tracker provided, but it was not a sufficient motivator to overcome personal barriers to maintain or increase exercise engagement. Participants identified as extrinsically motivated were more influenced by wearing an activity tracker than those who were intrinsically motivated. During the study, participants who reported either owning multiple technology devices or knowing someone who used multiple devices were more likely to remain engaged with their activity tracker. Conclusions This study lays the foundation for developing a smart app that could promote individual engagement with activity trackers.

Background Fever is an important vital sign and often the first one to be assessed in a sick child. In acutely ill children, caregivers are expected to monitor a child’s body temperature at home after an initial medical consult. Fever literacy of many caregivers is known to be poor, leading to fever phobia. In children with a serious illness, the responsibility of periodically monitoring temperature can add substantially to the already stressful experience of caring for a sick child. Objective The objective of this pilot study was to assess the feasibility of using the iThermonitor, an automated temperature measurement device, for continuous temperature monitoring in postoperative and postchemotherapy pediatric patients. Methods We recruited 25 patient-caregiver dyads from the Pediatric Surgery Department at the Massachusetts General Hospital (MGH) and the Pediatric Cancer Centers at the MGH and the Dana Farber Cancer Institute. Enrolled dyads were asked to use the iThermonitor device for continuous temperature monitoring over a 2-week period. Surveys were administered to caregivers at enrollment and at study closeout. Caregivers were also asked to complete a daily event-monitoring log. The Generalized Anxiety Disorder-7 item questionnaire was also used to assess caregiver anxiety at enrollment and closeout. Results Overall, 19 participant dyads completed the study. All 19 caregivers reported to have viewed temperature data on the study-provided iPad tablet at least once per day, and more than a third caregivers did so six or more times per day. Of all participants, 74% (14/19) reported experiencing an out-of-range temperature alert at least once during the study. Majority of caregivers reported that it was easy to learn how to use the device and that they felt confident about monitoring their child’s temperature with it. Only 21% (4/9) of caregivers reported concurrently using a device other than the iThermonitor to monitor their child’s temperature during the study. Continuous temperature monitoring was not associated with an increase in caregiver anxiety. Conclusions The study results reveal that the iThermonitor is a highly feasible and easy-to-use device for continuous temperature monitoring in pediatric oncology and surgery patients. Trial Registration ClinicalTrials.gov NCT02410252; https://clinicaltrials.gov/ct2/show/NCT02410252 (Archived by WebCite at http://www.webcitation.org/73LnO7hel)

Social processes that change quickly are difficult to study, because they require frequent survey measurement. Weekly, daily, or even hourly measurement may be needed depending on the topic. With more frequent measurement comes the prospect of more complex patterns of missing data. The mechanisms creating the missing data may be varied, ranging from technical issues such as lack of an Internet connection to refusal to complete a requested survey. We examine one approach to mitigating the damage of these missing data - a follow-up or closeout interview that is completed after the frequent measurement. The Relationship Dynamics and Social Life (RDSL) study used this approach. The study asked women weekly about their attitudes and behaviors related to sexual relationships and pregnancy. The surveys were carried out for 130 weeks and concluded with a closeout interview. We explore the patterns of missing data in the RDSL study and then examine associations between the data collected in the closeout survey and key variables collected in the weekly survey. We then assess the extent to which data from the closeout survey are useful in repairing the damage caused by missing data.

This chapter provides regulatory guidance and author insight on how study teams can correctly and efficiently conclude a trial, ensuring regulatory compliance as well as positioning the site for attracting future sponsor and research funding. The chapter provides detailed information on study closeout procedures, including important International Council on Harmonisation Good Clinical Practices (ICH GCP) guidance on Essential Document Retention following the clinical study conclusion. The chapter concludes with recommendations on the procedures for publishing the results of a clinical trial.

The advent of mandatory daily initial and variation margin requirements for non-cleared over-the-counter derivatives transactions has raised many questions regarding the methodology which should be used for computing these margin requirements. Regulatory guidelines require initial margin levels for non-cleared contracts to cover a 99% loss quantile of the netting set over a horizon of 10 days, as opposed to 3 to 5 days for cleared OTC contracts. We discuss the rationale behind this and other features of the proposed framework for bilateral margin requirements and advocate an approach which better reflects the actual exposure during closeout in case of the default of a counter party. We argue that the liquidation horizon should depend on the size of the position relative to the market depth of the asset. This may be achieved by specifying a minimum liquidation horizon for each asset class, associated with an asset-specific size threshold, and scaling the liquidation horizon linearly with position size beyond this threshold. Adopting such a size-dependent liquidation horizon leads to a liquidity-sensitive initial margin, which penalizes large concentrated positions without requiring any ‘liquidity add-on’. We also argue that the IM calculation needs to account for the fact that market participants hedge their exposures to the defaulted counter party once default has been confirmed. As a result, IM should not be based on the exposure of initial position over the entire liquidation horizon but on the exposure over the initial period required to set up the hedge, plus the exposure to the hedged position over the remainder of the liquidation horizon. Based on these remarks, we propose a “four-step approach” for the calculation of IM for over-the-counter derivatives transactions. We argue that this approach yields a more realistic assessment of closeout risk for non-cleared transactions and leads to an outcome which is in general quite different from the risk exposure of the netting set over the liquidation horizon.

The HALT Polycystic Kidney Disease Trials Network consisted of two randomized, double blind, placebo-controlled trials among patients with autosomal dominant polycystic kidney disease. The trials involved 5-8years of participant follow-up with interventions in blood pressure and antihypertensive therapy. We provide a framework for designing and implementing closeout near the end of a trial while ensuring patient safety and maintaining scientific rigor and study morale.We discuss issues and resolutions for determining the last visit, tapering medications, and unblinding of participants to study allocation and results. We also discuss closure of clinical sites and Data Coordinating Center responsibilities to ensure timely release of study results and meeting the requirements of regulatory and funding authorities.Just over 90% of full participants had a 6-month study visit prior to their last visit preparing them for trial closeout. Nearly all patients wanted notification of study results (99%) and treatment allocation (99%). All participants were safely tapered off study and open label blood pressure medications. Within 6months, the trials were closed, primary papers published, and 805 letters distributed to participants with results and allocation. DCC obligations for data repository and clinicaltrials.gov reporting were completed within 12months of the last study visit.Closeout of our trials involved years of planning and significant human and financial resources. We provide questions for investigators to consider when planning closeout of their trials with focus on (1) patient safety, (2) dissemination of study results and (3) compliance with regulatory and funding responsibilities.

Multi-asset class, multimarket central counterparties (CCPs) are becoming less uncommon as a result of merges between specialized (single-asset class, single market) CCPs and market demands for greater capital efficiency. Yet, traditional CCP risk management models often lack the necessary sophistication to estimate potential losses relative to the closeout process of a defaulter’s portfolio in a multi-asset class, multimarket environment. As a result, multi-asset class, multimarket CCPs usually rely on a simplified silo approach for risk calculation which not only fails to deliver efficiency, but may also increase systemic risk. The CORE (Closeout Risk Evaluation) approach, on the other hand, provides conceptual and mathematical tools necessary for robust and efficient central counterparty risk evaluation in multi-asset class and multimarket environments, acknowledging the portfolio dynamics involved in the closeout process as well as important “real life” market frictions.

The endocrinology eConsult service at Mount Sinai Hospital, in New York City, was conceived to simplify and accelerate access to the expertise of endocrinologists. Here we detail how we designed our workflow according to input from primary care providers (PCPs). Additionally, we describe the impact of the pilot phase of our endocrinology eConsult service. In this pilot phase, providers in a Medicaid clinic and those making visits to homebound patients placed eConsult orders within the hospital's EMR using one of 18 original, disease-specific templates and one generic template. The eConsultant sent evidence-based recommendations in a response template, which included a rationale with references. As part of an ongoing quality improvement project, PCPs were asked to complete a two question closeout survey. Seventy percent of PCPs indicated that they got good advice for a new or additional course of action, and 25% answered that they were able to confirm a course of action that they already had in mind. Referral was originally contemplated, but avoided as a result of the eConsult according to 62% of respondents, exceeding rates reported at other academic institutions. Our unique emphasis on providing a detailed rationale for recommendations may have contributed to these outcomes. With a majority of respondents indicating that a formal consultation was averted, an expanded endocrine eConsult service could reduce a significant volume of unnecessary endocrine referrals, expedite more urgent visits, and reduce costs. This outcome is especially significant in light of a nationwide shortage of endocrinologists.

Due to financial crisis many entrepreneurs suffered heavy losses on derivatives, mainly currency options and forward contracts. Tax authorities tend to disallow deduction of those losses from the taxable income. Many cases ended up in administrative courts, resulting in judicature controversies on the issue in question. This paper is the third of four in a cycle. The aim of the whole cycle will be to analyze deeply these controversies and suggest the proper interpretation of the legal provisions, determining whether the expenses on currency options and forward contracts should or should not be regarded as tax-deductible expenses. The aim of this paper is to determine if the rights from the derivatives are being exercised or waived (as the law provides) in case of their early closeout (which allows the deduction as well). The conducted analysis suggests that early derivative closeout realises in exercising the rights from the derivative (as the law provides) which allows the deduction.

Background The ending of a clinical trial may be challenging, particularly if staff are required to withdraw the investigated treatment(s); however, this aspect of trial work is surprisingly under-researched. To address this gap, we explored the experiences of staff involved in closing out a trial that entailed withdrawal of treatment (insulin pumps) from some patients. Methods Interviews were conducted with n = 22 staff, recruited from seven trial sites. Data were analysed thematically. Results Staff described a myriad of ethical and emotional challenges at closeout, many of which had been unforeseen when the trial began. A key challenge for staff was that, while patients gave their agreement to participate on the understanding that pump treatment could be withdrawn, they often found themselves benefitting from this regimen in ways they could not have foreseen. Hence, as the trial progressed, patients became increasingly anxious about withdrawal of treatment. This situation forced staff to consider whether the consent patients had given at the outset remained valid; it also presented them with a dilemma at closeout because many of those who had wanted to remain on a pump did not meet the clinical criteria required for post-trial funding. When deciding whether to withdraw treatment, staff not only had to take funding pressures and patient distress into account, but they also found themselves caught between an ethic of Hippocratic individualism and one of utilitarianism. These conflicting pressures and ethical considerations resulted in staff decision-making varying across the sites, an issue that some described as a further source of ethical unease. Staff concluded that, had there been more advanced planning and discussion, and greater accountability to an ethics committee, some of the challenges they had confronted at closeout could have been lessened or even prevented. Conclusions The same kinds of ethical issues that may vex staff at the beginning of a trial (e.g. patients having unrealistic expectations of trial participation; staff experiencing conflicts between research and clinical roles) may re-present themselves at the end. To safeguard the wellbeing of staff and patients, greater planning, coordination and ethical oversight should go into the closeout of trials involving withdrawal of treatment(s). Trial registration International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ISRCTN61215213. Registered on 11 May 2011 Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1813-y) contains supplementary material, which is available to authorized users.

Background Since 2010, the Champlain BASE (Building Access to Specialist Advice through eConsultation) has allowed primary care providers (PCPs) to submit clinical questions to specialists through a secure web service. The study objectives are to describe questions asked to Infectious Diseases specialists through eConsultation and assess impact on physician behaviors. Methods eConsults completed through the Champlain BASE service from April 15, 2013 to January 29, 2015 were characterized by the type of question asked and infectious disease content. Usage data and PCP responses to a closeout survey were analyzed to determine eConsult response time, change in referral plans, and change in planned course of action. Results Of the 224 infectious diseases eConsults, the most common question types were as follows: interpretation of a clinical test 18.0% (41), general management 16.5 % (37), and indications/goals of treating a particular condition 16.5% (37). The most frequently consulted infectious diseases were as follows: tuberculosis 14.3% (32), Lyme disease 14.3% (32), and parasitology 12.9% (29). Within 24 hours, 63% of cases responded to the questions, and 82% of cases took under 15 minutes to complete. In 32% of cases, a face-to-face referral was originally planned by the PCP but was no longer needed. In 8% of cases, the PCP referred the patient despite originally not planning to make a referral. In 55% of cases, the PCP either received new information or changed their course of action. Conclusions An eConsult service provides PCPs with timely access to infectious disease specialists’ advice that often results in a change in plans for a face-to-face referral.

Display of stock plays an effective role to boost up the demand as it encourages customer to buy more. For perishable good freshness is also an important factor affecting its demand, as consumers look for fresh items. Selling price is also a major factor affecting the demand. This paper proposes an inventory model where demand depends on selling price, freshness of item and displayed stock. The traditional assumption of zero ending inventories is relaxed to a non-zero ending inventory. As it may be profitable to have a closeout sale at a markdown price, and always keep on-hand fresh displayed stocks if the demand is freshness-and- stock dependent. The objective is to maximize the total profit with respect to three decision variables (i.e., unit price, cycle time and ending-inventory level). Numerical examples are presented to validate the model and sensitivity analysis of inventory parameters is done to understand their effect in determining optimal policies.