Outsourcing of humanitarian logistics to commercial logistics service providers: An empirical investigation

Purpose – The purpose of this paper is to empirically explore the potential of outsourcing of humanitarian logistics activities to commercial logistics service providers (LSPs) throughout the different disaster phases. The authors identify incentives for initiating outsourcing of humanitarian logistics activities to commercial logistics providers, humanitarian logistics activities to be outsourced and selection criteria for partners. Design/methodology/approach – This study is based on empirical data collected by interviewing 12 practitioners from commercial LSPs and 12 practitioners from humanitarian organizations (HOs). A review of related literature guided this research. Findings – This research shows that incentives for initiating outsourcing engagements, partner selection criteria and activities to be outsourced are changing throughout the different disaster phases. A number of research propositions are presented. Research limitations/implications – This research constitutes a first step towards the goal of a comprehensive analysis of humanitarian logistics outsourcing throughout the different disaster phases. The authors collected data from practitioners and large organizations based mainly in Europe and the USA. Hence, insights from national and local organizations of other parts of the world are missing. Practical implications – This research provides a deeper understanding of outsourcing of humanitarian logistics activities. As the main implication for practice, the research suggests a strategic use of outsourcing during the three disaster phases. The authors acknowledge that business objectives, risks, stakeholder agendas and requirements, as well as costs play a vital and changing role for outsourcing decision-making during the three disaster stages. The managerial implications arising from the research can provide support to commercial LSPs and HOs that initiate or develop strategic outsourcing relationships. Originality/value – This study covers the gap in the humanitarian literature related to context-specific factors of outsourcing in humanitarian logistics by empirically investigating the phenomenon. This is one of the first studies that empirically investigate the potential of outsourcing of humanitarian logistics activities throughout the disaster phases

Digitizing the field: designing ERP systems for Triple-A humanitarian supply chains

Purpose: The purpose of this study is to explore what design principles need to be considered in Enterprise Resource Planning (ERP) systems for humanitarian organizations (HOs) to enable agile, adaptive and aligned (Triple-A) humanitarian supply chain capabilities and digitize humanitarian operations. Design/methodology/approach: This study follows an embedded case study approach with ahumanitarian medical relief organization, Medecins Sans Frontieres (MSF), which engaged in a multiyear ERP design at its humanitarian field missions. Findings: This research shows that ERP systems for humanitarian organizations should be designed asunique systems addressing humanitarian organizations' challenges and unique missions, their valuegeneration processes, and resource base in an effort to improve organizational performance. This study presents 12 general design principles that are unique for humanitarian organizations. These design principle sprovide a high-level structure of guidance under which specific requirements can be further defined and engineered to achieve success. Research limitations/implications: The results of this study are based on a single case study limiting generalizability. However, the case study was analyzed and presented as an embedded case study with five autonomous subunits using different business processes and following different adoption and implementation approaches. Therefore, the findings are derived based on considerable variance reflective of humanitarian organizations beyond MSF. Practical implications: This study recognizes that HOs have unique routines that standard commercial ERP packages do not address easily at the field level. The primary contribution of this research is a set of design principles that consider these unique routines and guide ERP development in practice. National and international HOs that are planning to implement information systems, private companies that are trading partners of HOs as well as vendors of ERP systems that are looking for new opportunities would all benefitfrom this research. Originality/value: This study fills the gap in the humanitarian literature regarding the design of ERPsystems for humanitarian organizations that enable Triple–A supply chain capabilities and it advances the knowledge of the challenges of ERP design by HOs in the context of humanitarian operations

Disaster relief inventory management: horizontal cooperation between humanitarian organizations

Cooperation among humanitarian organizations has attracted increasing attention to enhance effectiveness and efficiency of relief supply chains. Our research focuses on horizontal cooperation in inventory management which is currently implemented in the United Nations Humanitarian Response Depot (UNHRD) network. The present work follows a two-step research approach, which involves collection of empirical data and quantitative modeling to examine and overcome the coordination challenges of the network. Our interviews with members of the network identified several managerial issues for sustainable cooperative inventory management that the UNHRD network pursues. Using a newsvendor model in the context of non-cooperative game theory, our research has explored member humanitarian organizations' incentive of joining the network, a coordination mechanism which achieves system optimality, and impacts of members' decisions about stock rationing. Our results indicate that behaviors of member HOs do not necessarily align with the UNHRD's expectation. Our results suggest that for system optimality, a system coordinator should carefully assess the circumstances, including demand coefficient and stock rationing. Our research also proposes a policy priority for the first-best system optimal inventory management

An ATM/CHK2 Signaling Pathway Induces Nuclear Translocation of SRPK2 in Cisplatin-Treated HeLa Cells

Chemotherapeutic agents are frequently used to treat various cancers, but the mechanisms mediating the cellular response to the drugs are still not fully understood. We previously reported that the nuclear translocation of serine/arginine protein kinases (SRPKs), triggered by the exposure of cells to DNA damage-inducers, plays a pivotal role in drug responsiveness. Here, we investigated the mechanism linking the nuclear accumulation of SRPK2 to the cisplatin treatment of HeLa cells. We present experimental evidence that nuclear SRPK2 acts downstream of Chk2 in the ATM/Chk2 cascade. The inhibition of ATM or Chk2 kinase activity by specific low-molecular-weight inhibitors restricted SRPK2 to the cytoplasm and conferred tolerance to cisplatin treatment. A similar effect was achieved by treating cells with SRPIN340, a selective SRPK1/2 inhibitor, thus confirming previous findings that kinase activity is indispensable for the nuclear import of SRPKs. These data add to previous findings that support a decisive role of SRPKs in coordinating cellular response to DNA damage

The role of nitric oxide in the resistive breathing induced cytokine production from the respiratory muscles

[...] Σκοπός της παρούσας μελέτης είναι να διερευνήσει το ρόλο των MAPKs και του NF-kB στην αυξημένη έκφραση κυτταροκινών από το διάφραγμα συνέπεια της εισπνοής μέσα από αντιστάσεις. Επιπρόσθετα να διερευνήσει το ρόλο του μονοξειδίου του αζώτου ως ερέθισμα για την αυξημένη ενδιοδιαφραγματική έκφραση κυτταροκινών και τη δράση του μονοξειδίου του αζώτου στα μονοπάτια που ελέγχουν την έκφραση των κυτταροκινών στο διάφραγμα συνέπεια αυξημένης ενεργοποίησης. [...

Η επίδραση της ηλικίας στην κλινική εμφάνιση της αποφρακτικής υπνικής άπνοιας στους άνδρες

Η συχνότητα του συνδρόμου αποφρακτικής υπνικής άπνοιας (ΣΑΥ) αυξάνεται με την ηλικία. Εντούτοις τα δεδομένα που έχουμε προέρχονται κυρίως από νεαρής και μέσης ηλικίας ασθενείς, ενώ τα δεδομένα για τους ηλικιωμένους ασθενείς είναι λίγα. ΣΚΟΠΟΣ: να μελετήσουμε τις διαφορές στην κλινική εμφάνιση των ανδρών με ΣΑΥ με βάση την ηλικία ΜΕΘΟΔΟΣ: Μελετήθηκαν αναδρομικά όλοι οι άνδρες ασθενείς που εξετάστηκαν στο ιατρείο ύπνου και υπεβλήθησαν σε μελέτη ύπνου σε διάστημα 4 μηνών. Χωρίστηκαν σε 3 κατηγορίες βάση ηλικίας: Α) έως 44 ετών Β) 45-64 ετών και Γ) ≥65 ετών. Καταγράφηκαν τα συμπτώματα και η αιτία προσέλευσης, η συννοσηρότητα και ο υπνοαπνοϊκός δείκτης (ΑΗΙ). Για την σύγκριση των ποιοτικών παραμέτρων χρησιμοποιήθηκε το Chi square test και των ποσοτικών one way ANOVA -όριο στατιστικής σημαντικότητας το p<0.05. ΑΠΟΤΕΛΕΣΜΑΤΑ: 275 άνδρες με μέση ηλικία 53 έτη (15-86) συμπεριελήφθησαν στη μελέτη-ομάδα Α:28,4%, Β:52%, Γ:19.6%. Οι ασθενείς της ομάδας Γ προσέρχονταν στο ιατρείο κυρίως μετά από παραπομπή από ιατρική ειδικότητα, ενώ των ομάδων Α και Β λόγω συμπτωμάτων. Ως προς τα συμπτώματα όπως τα αναφέρουν ως πρόβλημα οι ίδιοι οι ασθενείς, η ομάδα Γ ανέφερε σε μικρότερο βαθμό ροχαλητό και κόπωση. Ως προς τα συμπτώματα όπως τα ρωτούσε ο ιατρός της εξέτασης, οι ασθενείς της ομάδας Γ, ανέφεραν συχνότερα νυκτουρία και διαταραχές μνήμης και σε μικρότερο βαθμό κόπωση και γαστροοισοφαγική παλινδρόμηση. Οι ασθενείς της ομάδας Α ανέφεραν συχνότερα καρηβαρία. Οι συννοσηρότητες αυξάνονταν με την ηλικία. Το ΒΜΙ, η υπνηλία και το ΑΗΙ δεν διέφεραν μεταξύ των ομάδων. Από τους ασθενείς της ομάδας Γ, αυτοί που επισκέφθηκαν το ιατρείο ύπνου μετά από ιατρική παραπομπή συγκρινόμενοι με αυτούς που προσήλθαν λόγω συμπτωμάτων, ανέφεραν συχνότερα πνιγμονή, πρωινή κεφαλαλγία και κόπωση. ΣΥΜΠΕΡΑΣΜΑ: Η ηλικία επηρεάζει την κλινική εμφάνιση του ΣΑΥ στους άνδρες και την αιτία προσέλευσης τους στο ιατρείο ύπνου. Οι ηλικιωμένοι άνδρες ασθενείς αποτελούν το μικρότερο ποσοστό των ασθενών που υποβάλλονται σε μελέτη ύπνου. Συνήθως προσέρχονται μετά από παραπομπή από θεράποντα ιατρό, παρότι έχουν συμπτωματολογία συμβατή με υπνική άπνοια.Obstructive sleep apnea (OSA) shows increasing prevalence with age. Existing data comes mainly from young and middle age patients. Data from older patients is lacking PURPOSE: to investigate the age specific differences in clinical presentation of male adults with OSA. METHODS: Retrospective study of all male adult patients visited our sleep unit and submitted in sleep study during a 4-month period. Patients were stratified in age-groups, A: up to 44-year-old (YO) B: 45-64 YO and C:≥65 YO. Patients symptoms, comorbidity, reason for referral and Apnea Hypopnea Index (AHI) were recorded. Chi-square test and one-way ANOVA were used for statistics-p<0.05. RESULTS: 275 men with median age 53 (15-86) were included–group A-28.4%, B-52%, C-19.6%. More patients in group C visited the hospital following doctor’s referral, whereas groups A and B presented mainly due to symptoms. In terms of symptoms self-reported by the patients, group C reported less frequent snoring and fatigue. When doctor asked for symptoms group C reported more nocturia and memory disturbances but less fatigue and gastroesophageal reflux. Patients of group A complaint more for heavy-head. Comorbidity increased with aging. BMI, sleepiness and AHI did not differ between age groups. Among patients of group C, those that visited sleep unit following doctor’s referral reported higher prevalence of chocking, morning headaches, heavy head and fatigue compared to those that were self-referred due to symptoms. CONCLUSION: Age influences the clinical presentation of OSA in males. Older patients represent the minority of patients undergoing sleep study. They visit sleep unit mainly following specialty doctor referral although they are highly symptomatic

Studies of the biological function of SRPK1 protein kinase - effects of small molecular compounds

Alternative splicing plays a critical role in cancer as its mechanism is disturbed in cancer cells. Among the kinases that regulate splicing, of major importance is SRPK1 which phosphorylates serine/arginine dipeptides motifs. The expression levels of SRPK1 appear widely disturbed in various tumors, with conflicting roles. Glioblastoma is the most frequent and aggressive malignant cancer of primary brain tumors. SRPK1 is expressed in the mammalian central nervous system in a neuron-specific manner and glial cells are practically devoid of SRPK1. Immunohistochemical analysis revealed that malignant glioma cells express SRPK1, while significant association between SRPK1 expression and patients’ survival was observed. Elevated SRPK1 expression was also detected in the cytoplasm of three glioma cell lines U87, T98 and U251. Small interfering RNA-mediated downregulation of SRPK1, using shRNAs, had little effect on cell viability and resulted in somehow enhanced sensitivity to cisplatin and temozolomide, while no such combinatorial effect was observed with 5-FU, since 5-FU dramatically reduces the protein levels of SRPK1, as opposed to the other two chemotherapeutics. Searching for additional specific inhibitors of SRPK1, 17 newly synthesized compounds, based on the structure of SRPIN340, were tested using in vitro phosphorylation assays but they showed minimal inhibitory activity as compared to SRPIN340. In the context of testing small molecular compounds, lynamicin D, a newly synthesized bisindole pyrrole, exhibited a minor effect on HeLa, A549 and T98G cell viability. However, this compound was able to modulate both constitutive and alternative splicing of reporter mini-genes, mainly by upregulating SRPK1 expression levels. In the last part of this study, we investigated the regulatory mechanisms that modulate the subcellular localization of SRPK1. Indirect immunofluorescence assays revealed that treatment of HeLa cells with various stress-causing agents resulted in the formation of γ-H2AX foci, the concentration of which was proportional to the nuclear accumulation of SRPK1. As the phosphorylated histone H2AX is strictly associated with the presence of double strand breaks (DSBs) on DNA, it is possible that the nuclear translocation of SRPK1, following DNA lesions, is closely associated with the repair mechanism. Next, we confirmed that mutation of two potential phosphorylation sites of SRPK1, threonine 326 and serine 408 to alanine, abolished the nuclear translocation of the kinase, upon treatment of Hela cells with Η2Ο2. Interestingly, the localization of the corresponding phosphomimetic mutants, resulting by substitution of threonine 326 and serine 408 with aspartic acid, was highly cytoplasmic, suggesting that while phosphorylation of the SRPK1 molecule is probably an indispensable post-translational modification for nuclear translocation an additional modification is also required. As such, we tested ubiquitination, based on the UbPred specific predictor of ubiquitination sites. However, mutation of lysine residues 329 and 377, which showed the greatest probability of being ubiquitinated, to arginine did not impair the nuclear translocation of SRPK1 after treatment of HeLa cells with H2O2. Thus, these two lysine residues do not play a critical role in the subcellular localization of SRPK1.Κυρίαρχη θέση στη ρύθμιση του ματίσματος, κατέχει η SRPK1, η οποία φωσφορυλιώνει σερίνες που αποτελούν μέρος διπεπτιδίων σερίνης/αργινίνης, μοτίβο το οποίο φέρουν και οι SR παράγοντες ματίσματος. Η έκφραση της SRPK1 στους διάφορους όγκους, εμφανίζεται διαταραγμένη χωρίς ο ρόλος της να είναι ταυτόσημος σε όλους τους καρκίνους. Το γλοιοβλάστωμα είναι ο πιο συχνά εμφανιζόμενος και επιθετικός κακοήθης καρκίνος των πρωτογενών εγκεφαλικών όγκων. Η SRPK1 εκφράζεται μόνο στους νευρώνες και όχι στα νευρογλοιακά κύτταρα, σε αντίθεση με τους όγκους γλοιοβλαστώματος, στους οποίους παρατηρήθηκε έκφραση της SRPK1, ενώ τα επίπεδα της συσχετίστηκαν με την επιβίωση των ασθενών. Περαιτέρω διερεύνηση του βιολογικού ρόλου της SRPK1 στις τρεις γλοιωματικές κυτταρικές σειρές, U87MG, T98G, και U251MG αρχικά επιβεβαίωσε την έκφρασή της όπως και την κυτταροπλασματική εντόπισή της. Η αναστολή της έκφρασης της SRPK1 με shRNA, είχε περιορισμένη επίδραση στη βιωσιμότητα των κυττάρων ενώ οδήγησε σε μικρή αύξηση της ευαισθησίας των κυττάρων στην cis-πλατίνη και την τεμοζολομίδη. Δεν παρατηρήθηκε κανένα συνδυαστικό αποτέλεσμα στην περίπτωση του 5-FU, καθώς το 5-FU μειώνει δραματικά τα επίπεδα έκφρασης της κινάσης, σε αντίθεση με τα άλλα δύο χημειοθεραπευτικά. Στα πλαίσια του ελέγχου της ανασταλτικής δράσης μικρομοριακών ενώσεων απέναντι στην SRPK1, συντέθηκαν 17 νέες ενώσεις με βάση τη δομή του γνωστού αναστολέα SRPIN340 και ελέγχθηκαν σε in vitro πειράματα φωσφορυλίωσης, τα αποτελέσματα των οποίων έδειξαν ότι δεν εμφάνιζαν ανασταλτική δράση συγκρίσιμη με του SRPIN340. Επίσης βρέθηκε ότι το φυσικά προερχόμενο διινδολικό πυρρόλιο, λυναμικίνη D δεν είχε ουσιαστική επίδραση στη βιωσιμότητα των καρκινικών σειρών HeLa, Α549 και T98G. Επηρέαζε όμως τόσο το ιδιοσύστατο όσο και το εναλλακτικό μάτισμα μινι-γονιδίων αναφοράς, κυρίως μέσω της αύξησης των επιπέδων έκφρασης της SRPK1. Διερευνώντας τους τρόπους ρύθμισης της υποκυτταρικής εντόπισης της SRPK1 με δοκιμασίες έμμεσου ανοσοφθορισμού, παρατηρήθηκε μετατόπιση της κινάσης από το κυτταρόπλασμα στον πυρήνα, μετά από επίδραση στρεσογόνων για τα HeLa κύτταρα ουσιών. Μέσω της ανίχνευσης της φωσφορυλιωμένης ιστόνης H2AX, η οποία σχετίζεται με την παρουσία δίκλωνων σπασιμάτων στο DNA, βρέθηκε ότι η μετακίνηση της SRPK1 στον πυρήνα μετά από επίδραση διαφόρων παραγόντων ήταν ανάλογη της φωσφορυλίωσης της H2AX και κατά συνέπεια των δίκλωνων σπασιμάτων που προκαλούσαν οι συγκεκριμένοι παράγοντες στο DNA. Είναι λοιπόν πιθανόν η SRPK1 να εμπλέκεται στο μηχανισμό επιδιόρθωσης των βλαβών του DNA. Στην αναζήτηση των πιθανών μηχανισμών οι οποίοι διέπουν τη μετακίνηση της SRPK1 στον πυρήνα, επιβεβαιώθηκε ότι η φωσφορυλίωση των δύο πιθανών θέσεων φωσφορυλίωσης της θρεονίνης 326 και της σερίνης 408, αποτελεί μια αναγκαία μετα-μεταφραστική τροποποίηση του μορίου της, καθώς μεταλλάγματα αυτών των θέσεων σε αλανίνη, αδυνατούσαν να εισέλθουν στον πυρήνα υπό την επίδραση Η2Ο2. Τα αντίστοιχα όμως φωσφομιμητικά μεταλλάγματα σε ασπαραγινικό οξύ, υπό φυσιολογικές συνθήκες δεν εμφάνιζαν πυρηνική εντόπιση, οδηγώντας στο συμπέρασμα ότι απαιτείται κάποια συμπληρωματική τροποποίηση. Ο αλγόριθμος πρόβλεψης θέσεων ουβικιτίνωσης, UbPred έδωσε μεγάλη πιθανότητα ουβικιτίνωσης στις λυσίνες 329 και 377 και κατασκευάστηκαν μεταλλάγματα στα οποία οι συγκεκριμένες λυσίνες αντικαταστάθηκαν με αργινίνη. Τα μεταλλάγματα αυτά δεν απώλεσαν την ικανότητά τους να εισέρχονται στον πυρήνα με H2O2, αναιρώντας την αρχική υπόθεση της ουβικιτίνωσης των θέσεων Lys329 ή Lys377, ως προϋπόθεση για την είσοδο της κινάσης στον πυρήνα

Incentivizing at-risk production capacity building for COVID-19 vaccines

Funding Information: Our analysis reveals that the two opposing effects of a higher unit outsourcing price (or unit penalty cost) on the two parties’ interests under the outsourcing mode lead to managerial guideline 1(ii). The results also indicate that the developer's cost‐sharing funding would partially mitigate the possible insufficient at‐risk capacity building under the outsourcing mode, but it is not a perfect remedy. When the outsourcing mode results in a lower at‐risk capacity level than the integrated model, one cannot expect the developer to provide sufficient cost‐sharing funding to help achieve the optimal at‐risk capacity level under the integrated mode. To overcome the possible insufficient at‐risk capacity building under the outsourcing mode, financial support from a third party (e.g., public or private fund sources) is necessary to supplement the developer's insufficient cost‐sharing funding. Publisher Copyright: © 2021 Production and Operations Management SocietyOur study analyzes capacity management for promising vaccine candidates before regulatory approval (i.e., at-risk capacity building) in the presence of production outsourcing and different operational challenges: misaligned interests, possible ex post negotiations, asymmetric information between developers and manufacturers, and government involvement. We develop analytical models to compare two vaccine production modes: (1) the integrated mode (a single company determines the at-risk capacity and produces in-house) and (2) the outsourcing mode (a manufacturer determines the at-risk capacity and a developer determines a funding level to share the capacity-building cost). Our study reveals that outsourcing can achieve a higher at-risk capacity only if it can achieve sufficient cost savings compared to the integrated mode. Our research also proves that both vaccine production modes tend to underinvest in the at-risk capacity. Following this, we suggest measures to improve the at-risk capacity building in both vaccine production modes. Our signaling game model reveals that a developer with high competence cannot always send credible signals of its true competence level to the manufacturer. Our incomplete contract model verifies that the relative performance of the two vaccine production modes is robust when ex post negotiation occurs under the outsourcing mode; however, the two parties may show incompatible preferences for the ex post negotiation. Our study also analyzes the optimal allocation of government financial support to development funding and capacity funding to incentivize at-risk capacity building. We present comprehensive guidelines for the different stakeholders to collectively contribute to ramping up the at-risk capacity of promising vaccines.Peer reviewe

Mitigating personal protective equipment (PPE) supply chain disruptions in pandemics - a system dynamics approach

Purpose The coronavirus disease (COVID-19) pandemic has emerged as an unprecedented health crisis worldwide and heavily disrupted the healthcare supply chain. This study focuses on analysing the different types of disruptions occurring in personal protective equipment (PPE) supply chains during the COVID-19 pandemic and on proposing mitigation strategies that are fit to the global scale and many interdependencies that are characteristic for this pandemic. The authors construct a conceptual system dynamics model (SD) based on the literature and adjusted with the use of empirical data (interviews) to capture the complexity of a global supply chain and identify leverage points (mitigation strategies). Design/methodology/approach This research follows a mix-methods approach. First, the authors developed a conceptual framework based on four types of disruptions that usually occur during health emergencies (direct effect, policy, supply chain strategy, and behaviourally induced disruptions). Second, the authors collected and analysed data from interviews with experts in the PPE supply chain. Based on the interviews data, the authors developed a conceptual system dynamics (SD) model that allows to capture the complex and dynamic interplay between the elements of the global supply chain system, by highlighting key feedback loops, delays, and the way the mitigation strategies can impact on them. From this analysis, the authors developed four propositions for supply chain risk management (SCRM) in global health emergencies and four recommendations for the policy and decision makers. Findings The SD model highlights that without a combination of mitigation measures, it is impossible to overcome all disruptions. As such, a co-ordinated effort across the different countries and sectors that experience the disruptions is needed. The SD model also shows that there are important feedback loops, by which initial disruptions create delays and shortages that propagate through the supply chain network. If the co-ordinated mitigation measures are not implemented early at the onset of the pandemic, these disruptions will be persistent, creating potential shortages of PPE and other critical equipment at the onset of a pandemic - when they are most urgently needed. Originality/value This research enriches the understanding of the disruptions of PPE supply chains on the systems level and proposes mitigation strategies based on empirical data and the existing literature