From supply chain risk to system-wide disruptions: research opportunities in forecasting, risk management and product design

Purpose Supply chains must rebuild for resilience to respond to challenges posed by systemwide disruptions. Unlike past disruptions that were narrow in impact and short-term in duration, the Covid pandemic presented a systemic disruption and revealed shortcomings in responses. This study outlines an approach to rebuilding supply chains for resilience, integrating innovation in areas critical to supply chain management. Design/methodology/approach The study is based on extensive debates among the authors and their peers. The authors focus on three areas deemed fundamental to supply chain resilience: (1) forecasting, the starting point of supply chain planning, (2) the practices of supply chain risk management and (3) product design, the starting point of supply chain design. The authors’ debated and pooled their viewpoints to outline key changes to these areas in response to systemwide disruptions, supported by a narrative literature review of the evolving research, to identify research opportunities. Findings All three areas have evolved in response to the changed perspective on supply chain risk instigated by the pandemic and resulting in systemwide disruptions. Forecasting, or prediction generally, is evolving from statistical and time-series methods to human-augmented forecasting supplemented with visual analytics. Risk management has transitioned from enterprise to supply chain risk management to tackling systemic risk. Finally, product design principles have evolved from design-for-manufacturability to design-for-adaptability. All three approaches must work together. Originality/value The authors outline the evolution in research directions for forecasting, risk management and product design and present innovative research opportunities for building supply chain resilience against systemwide disruptions

Caracterização do ciclo estral de vacas e novilhas curraleiras Pé-Duro.

1 CD-ROM

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

TH17-driven inflammation is present in all clinical forms of multiple sclerosis; disease quiescence is associated with gata3-expressing cells

Multiple Sclerosis (MS) presents in a variety of clinical forms associated with a diverse grade of neurological impairment, different prognosis and, possibly, multiple pathogenic mechanisms. Thus, whereas relapsing-remitting (RR) MS appears to be largely driven by inflammatory processes, neurodegeneration, partially independent from inflammation, drives primary progressive (PP) and secondary progressive (SP) MS. An extensive analysis of neuroinflammation in the different forms of MS was performed by evaluating immunophenotypic and functional parameters in MBP-stimulated T lymphocytes of 103 MS patients (26 benign (BE) MS, 30 RRMS, 33 SPMS and 14 PPMS) and 40 healthy controls (HC). Results showed that: i) IL-17-producing and RORC/\u3b3t-expressing CD4+ T cells (TH17 lymphocytes), as well as IL-6 expressing CD14+ cell were augmented in all patients; ii) IL-22-expressing cells were increased in all forms of MS with the exception of PPMS; iii) TGF-\u3b2-expressing B cells were increased only in RRMS; and iv) GATA3-, NFATc-1, IL-13-, and IL-25-expressing cells (TH2 lymphocytes) were augmented in RRMS and BEMS patients alone. Data herein indicate a pivotal pathogenic role of TH17-driven inflammation in all clinical forms of MS and suggest that control over disease (RRMS and BEMS) is associated not with lack of inflammation per se, but rather with the activation of immune-mediated anti-inflammatory mechanisms. These results could help the design of novel diagnostic and therapeutic approaches

Outcomes of Elderly Patients with ST-Elevation or Non-ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Introduction: Acute coronary syndromes (ACS) have been classified according to the finding of ST-segment elevation on the presenting electrocardiogram, with different treatment strategies and practice guidelines. However, a comparative description of the clinical characteristics and outcomes of acute coronary syndrome elderly patients undergoing percutaneous coronary intervention during index admission has not been published so far. Methods: Retrospective cohort study of patients enrolled in the Elderly ACS-2 multicenter randomized trial. Main outcome measures were crude cumulative incidence and cause-specific hazard ratio (cHR) of cardiovascular death, noncardiovascular death, reinfarction, and stroke. Results: Of 1443 ACS patients aged >75 years (median age 80 years, interquartile range 77-84), 41% were classified as ST-elevation myocardial infarction (STEMI), and 59% had non-ST-elevation ACS (NSTEACS) (48% NSTEMI and 11% unstable angina). As compared with those with NSTEACS, STEMI patients had more favorable baseline risk factors, fewer prior cardiovascular events, and less severe coronary disease, but lower ejection fraction (45% vs 50%, P <.001). At a median follow-up of 12 months, 51 (8.6%) STEMI patients had died, vs 39 (4.6%) NSTEACS patients. After adjusting for sex, age, and previous myocardial infarction, the hazard among the STEMI group was significantly higher for cardiovascular death (cHR 1.85; 95% confidence interval [CI], 1.02-3.36), noncardiovascular death (cHR 2.10; 95% CI, 1.01-4.38), and stroke (cHR 4.8; 95% CI, 1.7-13.7). Conclusions: Despite more favorable baseline characteristics, elderly STEMI patients have worse survival and a higher risk of stroke compared with NSTEACS patients after percutaneous coronary intervention

Immanuel Kant. Il tempo interno del miglioramento: un paradigma del progresso storico?

Il soggetto kantiano, per sapersi morale, deve potersi pensare come un soggetto che non ha fine nel tempo sensibile: per pensarsi secondo questa forma dell’intelligibile egli postula una durata infinita della sua personalità. Con ciò si apre un orizzonte di senso immaginabile soltanto in un ‘futuro aperto’ e dilatato all’infinito: in questa dimensione temporale specifica trova senso l’esercizio morale di ogni individuo. La designazione temporale dell’immortalità dell’anima come durata infinita (unendliche Dauer) e il progresso intelligibile che è connesso al postulato mostrano un’interessante processualità inerente alla dimensione intelligibile - non spazio-temporalmente condizionata - dell’esistenza di ogni personalità morale. Seppure non tematizzato esplicitamente da Kant, attraverso questo postulato si indica un peculiare svolgimento - temporale - esclusivo del noumeno. Presenteremo l’aspetto contraddittorio della processualità infinita argomentata da Kant: com’è possibile, all’interno del sistema trascendentale, un tempo ascrivibile - paradossalmente - al noumeno? Il problema del tempo nella filosofia morale di Kant, e in particolare il riferimento non ordinario ad una temporalità riconducibile all’ordine noumenico, è un tema molto complesso: nel fornire uno spunto di riflessione e un primo avvicinamento a questa tematica, peraltro poco trattata dalla letteratura kantiana, ripercorriamo in questa sede gli studi che hanno mostrato e discusso quest’interessante paradosso, ipotizzando nel tempo interno del miglioramento un paradigma della comprensione della storia dalla prospettiva della filosofia critica