Business process management and supply chain collaboration: effects on performance and competitiveness

Purpose: This study aims to examine the interrelationships among business process management (BPM), supply chain collaboration (SCC), collaborative advantage and organisational performance. Design/methodology/approach: Data were collected from 204 manufacturing firms in Thailand, and the interrelationships proposed in the framework were tested via structural equation modelling. Findings: This study highlights the role of intra- and inter-organisational practices and clearly demonstrates the joint role and impact of BPM and SCC, respectively. The results provide empirical evidence that BPM improves both organisational performance and collaborative activities. Also, SCC and collaborative advantage can have indirect positive impacts on organisational performance. Research limitations/implications: This work could be expanded by adopting a supplementary dyadic or extended supply chain (SC) approach and could also consider contextual factors, which were outside of the scope of this study. Practical implications: The BPM approach has a positive impact on organisational performance, which is essential for collaborative activities between a firm and its SC partners. Further, effective BPM and SCC practices lead to enhanced performance and collaborative benefits. Practitioners should be better able to define and measure specific actions relating to their BPM and SCC practices. Originality value: This paper stresses the need to consider the interrelationships between BPM, SCC, collaborative advantage and organisational performance for both direct and indirect effects. Rather than focusing only on improvement at individual firm level, SCC is vital to compete in the market. Improving the effectiveness of SC allows higher organisational performance levels than those that could be achieved in isolatio

Recent advances in sulfotransferase enzyme activity assays

Sulfotransferases are enzymes that catalyze the transfer of sulfo groups from a donor, for example 3′-phosphoadenosine 5′-phosphosulfate, to an acceptor, for example the amino or hydroxyl groups of a small molecule, xenobiotic, carbohydrate, or peptide. These enzymes are important targets in the design of novel therapeutics for treatment of a variety of diseases. This review examines assays used for this important class of enzyme, paying particular attention to sulfotransferases acting on carbohydrates and peptides and the major challenges associated with their analysis

Control and regulation of S‐Adenosylmethionine biosynthesis by the regulatory β subunit and quinolone‐based compounds

Methylation is an underpinning process of life and provides control for biological processes such as DNA synthesis, cell growth, and apoptosis. Methionine adenosyltransferases (MAT) produce the cellular methyl donor, S‐Adenosylmethionine (SAMe). Dysregulation of SAMe level is a relevant event in many diseases, including cancers such as hepatocellular carcinoma and colon cancer. In addition, mutation of Arg264 in MATα1 causes isolated persistent hypermethioninemia, which is characterized by low activity of the enzyme in liver and high level of plasma methionine. In mammals, MATα1/α2 and MATβV1/V2 are the catalytic and the major form of regulatory subunits, respectively. A gating loop comprising residues 113–131 is located beside the active site of catalytic subunits (MATα1/α2) and provides controlled access to the active site. Here, we provide evidence of how the gating loop facilitates the catalysis and define some of the key elements that control the catalytic efficiency. Mutation of several residues of MATα2 including Gln113, Ser114, and Arg264 lead to partial or total loss of enzymatic activity, demonstrating their critical role in catalysis. The enzymatic activity of the mutated enzymes is restored to varying degrees upon complex formation with MATβV1 or MATβV2, endorsing its role as an allosteric regulator of MATα2 in response to the levels of methionine or SAMe. Finally, the protein–protein interacting surface formed in MATα2:MATβ complexes is explored to demonstrate that several quinolone‐based compounds modulate the activity of MATα2 and its mutants, providing a rational for chemical design/intervention responsive to the level of SAMe in the cellular environment

Business process management and supply chain collaboration: a critical comparison

The link between a firm and supply chain (SC) members has been recognised as one of the key issues for ensuring business success and achieving competitive advantage. Indeed, working across organisational boundaries is required to accomplish effective responses to customers’ needs. Our preliminary research confirmed that there are positive relationships between business process management (BPM), supply chain collaboration (SCC), collaborative advantage and organisational performance. This study is a step further and uses a multiple case design to illuminate the results and gain a greater understanding from extensive discussions about these relationships. By means of semi-structured interviews, the three main issues were identified as: (1) the link between BPM and organisational performance; (2) the link between BPM and SCC; and (3) the contextual factors and benefits achieved from working collaboratively with SC partners. The different scenarios of the link between BPM and SCC were developed in a taxonomy, and the case studies were used to illustrate the experience of intra- and inter-organisational practices in the developing economy of Thailand. The case studies’ results explain in depth that both BPM and SCC are important for improving organisational performance and competitiveness. BPM not only improves organisational performance directly, but also assists with collaborative activities that in turn help to improve internal capabilities. Additionally, the comparisons in issues relating to firm size, industry type, relationship closeness and relationship length were also included in this study

Political connections and corporate financial decision making

This paper investigates whether and how political connections influence managerial financial decisions. Our study reveals that those firms that have a politician on its board of directors are highly leveraged, use more long-term debt, hold large excess cash and are associated with low quality financial reporting compared to their non-connected counterparts. These effects escalate with the strength of the connected politician and whether he or his party is in power. The winning party effect is observed to be stronger than victory by the politician himself. Overall, our paper provides strong evidence that political connection is a two-edged sword. It is indeed a valuable resource for connected firms, but it comes at a cost of higher agency problems

Molecular Evolution of HIV-1 CRF01_AE Env in Thai Patients

BACKGROUND: The envelope glycoproteins (Env), gp120 and gp41, are the most variable proteins of human immunodeficiency virus type 1 (HIV-1), and are the major targets of humoral immune responses against HIV-1. A circulating recombinant form of HIV-1, CRF01_AE, is prevalent throughout Southeast Asia; however, only limited information regarding the immunological characteristics of CRF01_AE Env is currently available. In this study, we attempted to examine the evolutionary pattern of CRF01_AE Env under the selection pressure of host immune responses. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood samples were collected periodically over 3 years from 15 HIV-1-infected individuals residing in northern Thailand, and amplified env genes from the samples were subjected to computational analysis. The V5 region of gp120 showed highest variability in several samples over 3 years, whereas the V1/V2 and/or V4 regions of gp120 also showed high variability in many samples. In addition, the N-terminal part of the C3 region of gp120 showed highest amino acid diversity among the conserved regions of gp120. Chronological changes in the numbers of amino acid residues in gp120 variable regions and potential N-linked glycosylation (PNLG) sites are involved in increasing the variability of Env gp120. Furthermore, the C3 region contained several amino acid residues potentially under positive selection, and APOBEC3 family protein-mediated G to A mutations were frequently detected in such residues. CONCLUSIONS/SIGNIFICANCE: Several factors, including amino acid substitutions particularly in gp120 C3 and V5 regions as well as changes in the number of PNLG sites and in the length of gp120 variable regions, were revealed to be involved in the molecular evolution of CRF01_AE Env. In addition, a similar tendency was observed between CRF01_AE and subtype C Env with regard to the amino acid variation of gp120 V3 and C3 regions. These results may provide important information for understanding the immunological characteristics of CRF01_AE Env

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Financial and corporate social performance in the UK listed firms: the relevance of non-linearity and lag effects

Using environmental, social and governance scores compiled by Reuters Datastream for each company’s corporate social performance (CSP), we examine the relationship between CSP and corporate financial performance (CFP) of 314 UK listed companies over the period 2002–2015. We further evaluate the relationship between prior and subsequent CFP and prior and subsequent CSP. Based on the system-GMM estimation method, we provide direct evidence that suggests that while CFP and CSP can be linked linearly; however, when we examine the impact of CSP on CFP, the association is more non-linear (cubic) than linear. Our results suggest that firms periodically adjust their level of commitment to society, in order to meet their target CSP. The primary contributions of this paper are testing (1) the non-monotonous relationship between CSP and CFP, (2) the lagged relationship between the two and the optimality of CSP levels, and (3) the presence of a virtuous circle. Our results further suggest that CSP contributes to CFP better during post-crisis years. Our findings are robust to year-on-year changes in CFP and CSP, financial versus non-financial firms, and the intensity of corporate social responsibility (CSR) engagement across industries