Re-ordering policies for inventory systems with a fluctuating economic environment–Using economic descriptors to model the demand process

Customer demand is highly dependent on external environmental factors that are mainly economic in nature. We build on the financial literature to identify two key economic factors that impact the demand process, which are the gross domestic product (GDP) and the economic policy uncertainty (EPU). We accordingly categorize the economic environment into states that jointly capture different realizations of the GDP and EPU. We resort to data from the technology, automotive and oil industries to further validate the state categorizations by illustrating the relationship/dependency between the economic states and the demand process. We utilize a regularization technique to capture the fluctuation in the economic environment by a continuous time Markov Chain. We observe that the demand rates are dependent on the economic environment and accounting for this dependency improves the performance of the inventory system, especially in the technology industry. We numerically investigate the impact of the fluctuations on inventory control systems with continuous (s, S) inventory control policies. Algorithmic approaches, based on matrix representations of the system, are presented to compute the inventory performance measures. Our numerical study shows that savings are highest for the technology industry where the demand process is highly dependent on fluctuations in the economic environment. © Operational Research Society 2022

Prodrug Strategy for PSMA-targeted Delivery of TGX-221 to Prostate Cancer Cells

TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit. Recent studies showed that TGX-221 has anti-proliferative activity against PTEN-deficient tumor cell lines including prostate cancers. The objective of this study was to develop an encapsulation system for parenterally delivering TGX-221 to the target tissue through a prostate-specific membrane aptamer (PSMAa10) with little or no side effects. In this study, PEG-PCL micelles were formulated to encapsulate the drug, and a prodrug strategy was pursued to improve the stability of the carrier system. Fluorescence imaging studies demonstrated that the cellular uptake of both drug and nanoparticles were significantly improved by targeted micelles in a PSMA positive cell line. The area under the plasma concentration time curve of the micelle formulation in nude mice was 2.27-fold greater than the naked drug, and the drug clearance rate was 17.5-fold slower. These findings suggest a novel formulation approach for improving site-specific drug delivery of a molecular-targeted prostate cancer treatment

Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells

We thank Anna-Lena Berg (AstraZeneca, Lund) and Cheryl Scudamore (MRC, Harwell, UK) for histological analysis, Julie Foster (Barts Cancer Institute, London) for CT scans, Johan Swinnen and Frank Claessens (Leuven University, Belgium) for discussion and AR-luciferase reporter plasmids, Florian Guillou (INRA, CNRS, Université de Tours, France) for the AMH-Cre mouse line and Laura Milne (MRC Centre for Reproductive Health, The University of Edinburgh) for technical support. We thank the members of the Cell Signalling group for critical input.International audienceThe organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interac

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Determinants of credit spread changes for the financial sector

Purpose: Most of the credit spread literature deals with the determinants of credit spread changes for individual bonds. The purpose of this paper is to investigate the explanatory power of credit spread changes and their determinants for portfolios. Design-methodology-approach: Using ordinary least squares (OLS) regressions and monthly data from 1990 to 1997, this paper tests several new potential determinants (e.g. portfolio diversification) and expectations (and realizations) for some previously identified determinants (e.g. gross domestic product (GDP)) of credit spread changes for portfolios of financials as derived from spot curves. Findings: Strong empirical support is reported that default risk and undiversified risk are priced in credit spreads. The paper finds that forecasts for GDP and inflation are better determinants of credit spread changes than the realized values previously used in the literature, which is consistent with the notion that term structures convey expectations about future interest rates. Research limitations-implications: Interesting issues for future research include the sensitivity of the results to the use of other procedures for deriving zero-coupon spot rates, and whether forecasts of macrovariables (such as GDP) are better determinants of credit spreads for other industrial categories, such as utilities and industrials. Practical implications: The findings provide guidance for the management of risk for fixed income portfolios, for the pricing of fixed income securities differentiated by the difficulties encountered in achieving well-diversified portfolios, and for assessing the performance of credit spread portfolios managed by financial institutions. Originality-value: The empirical model, which achieves substantial explanatory power while being parsimonious, is the first to support the usage of forecasts instead of realized values in determining credit spreads, and to show that undiversifiable risk is an important component of the credit spreads of portfolios. © Emerald Group Publishing Limited

Impact of bond index revisions

This appears to be the first investigation of the impact of bond index additions and deletions on the returns of bonds and stocks of the underlying issuers using various unconditional and conditional return-generating models. The effect of additions and deletions is symmetric for each asset class, and robust across various return-generating models. While bond returns are positively (negatively) affected by bond index inclusions (exclusions), stock returns are unaffected by these bond index revisions. These results suggest that, although bond index additions and deletions materially affect bond values when measured at market, equity investors do not perceive any material change in financial risk from such changes

The January effect for individual corporate bonds

We examine the presence, magnitude and determinants of a January effect for individual corporate bonds. Our results provide empirical evidence of positive and statistically (but not economically) significant abnormal returns in January across different event windows and models. Our results suggest that, in the addition to the term and default factors, the excess stock returns, size and book-to-market factors are priced for individual bond returns. We investigate a number of determinants of the January abnormal returns for individual bonds. Our findings suggest that the reversal and tax-loss selling effects are important determinants of the abnormal returns on individual bonds. © 2013 Elsevier Inc.Al-Khazali Osama M., 2001, REV FINANCIAL EC, V10, P71; Loughran T, 1997, J FINANC QUANT ANAL, V32, P249, DOI 10.2307-2331199; Avramov D, 2013, J FINANC ECON, V108, P139, DOI 10.1016-j.jfineco.2012.10.005; Bao J, 2011, J FINANC, V66, P911, DOI 10.1111-j.1540-6261.2011.01655.x; Barnhill Jr Theordore M., 2000, J EMPIR FINANC, V7, P57; BERGES A, 1984, J FINANC, V39, P185, DOI 10.2307-2327675; Bessembinder H, 2006, J FINANC ECON, V82, P251, DOI 10.1016-j.jfineco.2005.10.002; Bessembinder H, 2009, REV FINANC STUD, V22, P4219, DOI 10.1093-rfs-hhn105; BHARDWAJ RK, 1992, J FINANC, V47, P553, DOI 10.2307-2329115; BRANCH B, 1977, J BUS, V50, P198, DOI 10.1086-295930; BROWN P, 1983, J FINANC ECON, V12, P105, DOI 10.1016-0304-405X(83)90030-2; Chang Eric C., 1990, J FINANCIAL QUANTITA, V25, P323; Chen H., 2004, J FINANC RES, V27, P351, DOI 10.1111-j.1475-6803.2004.00095.x; Chen Haiwei, 2011, FINANCIAL REV, V46, P703; CHO DC, 1987, J FINANC, V42, P1195, DOI 10.2307-2328522; Cooper Rick A, 1994, FINANCIAL ANAL J, V50, P61; DeRosa-Farag Sam, 1996, 1995 HIGH YIELD MARK; DIMSON E, 1979, J FINANC ECON, V7, P197, DOI 10.1016-0304-405X(79)90013-8; D'Mello R, 2003, J FINANC MARK, V6, P73, DOI 10.1016-S1386-4181(02)00023-X; Dyl Edward A, 1977, J FINANC, V32, P165; Edwards AK, 2007, J FINANC, V62, P1421, DOI 10.1111-j.1540-6261.2007.01240.x; Elton J. E., 2001, J FINANC, V56, P247; Fama Eugene F., 1989, JOURNAL OF FINANCIAL, V25, P23; Fama F., 1993, J FINANC ECON, V33, P3; Fama F., 1973, J POLITICAL EC, V81, P607; Fridson Martin, 1995, THIS WEEK HIGH YIELD, V47, P4; Fridson Martin, 1995, THIS WEEK HIGH YIELD, V47, P1; Gebhardt William R., 2005, J FINANC ECON, V75, P85; GIVOLY D, 1983, J FINANC, V38, P171, DOI 10.2307-2327645; Granger Clive W. J., 2000, J FORECASTING, V19, P537; GULTEKIN MN, 1983, J FINANC ECON, V12, P469, DOI 10.1016-0304-405X(83)90044-2; Haug Mark, 2005, WORKING PAPER; JONES CP, 1987, J FINANC, V42, P453, DOI 10.2307-2328262; Jordan Susan D, 1991, J FINANCIAL QUANTITA, V26, P269; KASHYAP AK, 1994, Q J ECON, V109, P565, DOI 10.2307-2118414; Keim Donald B., 1983, J FINANC ECON, V12, P12; Kothari S. P., 2006, HDB EMPIRICAL CORPOR, V1, P3; LEITCH G, 1991, AM ECON REV, V81, P580; Maxwell William F, 1998, FINANC MANAGE, V27, P18; Moosa Imad A., 2007, INT RES J FINANCE EC, V7, P92; Morey Matthew R., 2006, J FINANC RES, V29, P325; Petersen MA, 2009, REV FINANC STUD, V22, P435, DOI 10.1093-rfs-hhn053; Pinegar Michael J., 1986, J FINANC ECON, V17, P391; Reinganum Marc R., 1983, J FINANC ECON, V12, P89; RITTER JR, 1988, J FINANC, V43, P701, DOI 10.2307-2328193; RITTER JR, 1989, J FINANC, V44, P149, DOI 10.2307-2328280; ROLL R, 1983, J FINANC ECON, V12, P371, DOI 10.1016-0304-405X(83)90055-7; SCHNEEWEIS T, 1979, J FINANC QUANT ANAL, V14, P939, DOI 10.2307-2330299; SMIRLOCK M, 1985, J PORTFOLIO MANAGE, V11, P42, DOI 10.3905-jpm.1985.409009; Starks LT, 2006, J FINANC, V61, P3049, DOI 10.1111-j.1540-6261.2006.01011.x; Tinic Seha M., 1987, J FINANCIAL QUANTITA, V22, P51; WHITED TM, 1992, J FINANC, V47, P1425, DOI 10.2307-2328946; Wilcox Jarrod W., 1993, FINANCIAL ANAL J, V49, P77; Wilcox Jarrod W., 1993, FINANCIAL ANAL J, V49, P45; Wilson Jack W., 1990, FINANCIAL REV, V25, P550

Coordinating a three-level supply chain with delay in payments and a discounted interest rate

Both researchers and practitioners recognize the importance of the interactions between financial and inventory decisions in the development of cost effective supply chains. Moreover, achieving effective coordination among the supply chain players has become a pertinent research issue. This paper considers a three-level supply chain, consisting of a capital-constrained supplier, a retailer, and a financial intermediary (bank), coordinating their decisions to minimize the total supply chain costs. Specifically, we consider a retailer managing its cash through the supplier's bank, in return for permissible delay in payments from the supplier. The bank, benefiting from increasing its cash holdings with the retailer's cash deposits, offers the supplier a discount on its borrowing rate. We show that the proposed coordination mechanism achieves significant cost reduction, by up to 26.2percent, when compared to the non-coordinated model. We also find that, with coordination, the retailer orders in larger quantities than its economic order quantity, and that a higher return on cash for the retailer leads to a higher order quantity. Furthermore, we empirically validate our proposed coordination mechanism, by showing that banks, retailers, and suppliers have much to gain through collaboration. Thus, using COMPUSTAT datasets for the years 1950 through 2012, we determine the most important factors that affect the behavior of the retailers and suppliers in granting and receiving trade credit. Our results indicate that engaging into such a coordination mechanism is a win-win situation to all parties involved. © 2013 Elsevier Ltd. 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Does gender affect innovation? Evidence from female chief technology officers

202206 bcfcNot applicableOthersProject of Strategic Importance at the Hong Kong Polytechnic University (No. ZE2J)Published36 month