Territorial Intelligence and Governance.

International audienceAs with European experiments, in various regions in France, territorial intelligence projects have been initiated since 2003. (see the regions of Lower Normandy, Lorraine, Réunion Island, the Aquitaine region, etc.).The objective of these is to gather and exploit information which is not confined to particular sectors and the collective processing of which can contribute to durable development. Apart from institutions, civil society and the inhabitants of the territory, it is observed that companies and in particular small and medium sized enterprises are natural partners who show interest in such initiatives. Both the different economic chains and the participating organizations thus derive considerable benefit in terms of the anticipation of threats and in the reaffirmation of the territory as a common resource worth defending. Above and beyond the information processing systems operating within these organizations or economic chains, the articulation of internal actions to generate informational capital in terms of local territorial intelligence, produces a leverage effect with visibility of European or even worldwide visibility (Herbaux, 2007)52. Nonetheless these experiments lead to widely differing results, of which the progressive abandonment of the project by the companies involved is one of the most commonly observed. To support a theoretical contribution as a thread for this communication, we report on the results of a Delphi type survey completed in 2006 and covering 53 companies in the Nord- Pas de Calais region involved in a process of territorial intelligence since 2003. This revealed that 43 companies out of the 53 concerned had not followed through on their internal information sharing project and contented themselves, by default, with the results by economic sector derived from public regional surveillance Beyond this apparent disengagement from the process initiated, we may be curious about this apparent discretion of a group of actors concerning local government. This work nonetheless did generate a consensus around certain observations among the actors questioned, particularly as regards an initiative for which they did not deny the final utility but for which the requirements necessitated a significant modification to their internal culture. After the initial conventional responses: "security of patrimonial data, new choices in investment of time, lack of means, different priorities, etc.", repeated and differentiated questioning of those concerned revealed that the progressive abandonment of these practices and commitments bore a relationship with a number of human factors of relational and cognitive nature, thus depriving the project of its founding principles. This observation echoed that of the implication suggested by Girardot en 200553 on the theme of multi-level governance. Although the financial aspect is a factor in the long term survival of regular investments of man-hours, this criterion appeared progressively more marginal to the general project among the actors surveyed, as against several positions cited as prerequisites. Based on a synthesis of the results of the study, we propose five key success factors to promote within organizations to promote the logic of information sharing. To this effect, our proposal for a model named in French "CADIE" (Communication, Appui, Durée, Implication, Ecoute - or, in English, Communication, Support, Duration, Attentiveness) suggests several attitudes to which organizations must adhere to develop long-term integration in a territorial intelligence network. The limitations of our proposal arise from the small size of the sample at our disposal and the regional limits of our data gathering. This experimentation, duplicated in various European regions would benefit from a multi-cultural gloss and thus would provide the template for a preliminary European approach to the logic of territorial intelligence

On the economics of interpersonal relationships: three essays on social capital, social norms and social identity

For decades, economic theories have been mostly based on rational choices made by selfish individuals to maximize their utility, while sociology spent a lot of efforts describing the environment of individuals and explaining how this environment shapes theirs decisions. However, the last thirty years have seen many sociological concepts appear in the economic literature. For example, behavioral economics introduces things such as envy or altruism in economic theories. Other notions such as social capital, social norms, trust or community became more and more present in economic papers. The objective of this new strand of literature is to engage into sort of socioeconomic approach and to shed some light on interpersonal relationships. This thesis belongs to this socioeconomic approach, and tries to explore new aspects of various concepts. The two first papers are theoretical. In the first one, we explore the negative side of social capital, which has not been studied extensively, by investigating the effect of a norm on consumers when moving is costly. In the second one, we introduce a sociological concept, namely social identity, in a classic economic model in order to show how social interactions modifies its results, and hence, the importance of taking such interpersonal relationships into account. The third and final paper is an empirical case study of social capital in Belgium, an exercise that has not been done before, with the objective of comparing the level of social capital between the various regions of the country. <p><p>In the first paper, The Tyranny of Social Norms on Individual Behavior, we study the negative effect of the existence of a norm and moving cost inside a community. Because of deviation cost (such as social shame or peer pressure for example), consumers inside a given community may not reach their ideal consumption, that is the consumption they would have without social constraint. On the other hand, moving to another community may be too expensive (in terms of social assets needed to be part of the new community). Hence, agents may get stuck in their community, being forced to consume something they do not want to. One example of such behavior is the underinvestment in education in some neighborhood. We show that such equilibria are possible and that they may be socially suboptimal equilibria as well as Pareto inferior equilibria. We also show that state intervention can correct those “bad” equilibria by operating transfers between agents in order to lower the moving cost.<p><p>In the second paper, Social Identity, Advertising and Market Competition, we use a particular approach of a sociological concept, namely Social Identity, which focuses on the fact that people want to signal who they are to others. We assume that this is done by choosing a specific consumption (think of fashion market for example). We show that under this assumption, the classical result of Bertrand Price Competition does not hold anymore, and that prices and profits are positive, meaning that social identity creates market power for firms. Moreover, if the number of goods is limited, groups will be formed, and there will be multiple equilibria, each one corresponding to a particular partition of the consumers. We then add the possibility for firms to use advertising. This allows consumers to have a coordination tool, but increases also market powers for firms. We investigate the various equilibria that arise and their impact in term of welfare.<p><p>In the third paper, Social Capital in Belgium, we construct an index of social capital using the European Social Survey, and we show that this index can be decomposed in three aspects: Trust, Social Activities and Social Network. We then study whether there is a difference in social capital between Belgium’s regions or not. We show that indeed, such difference exists, even when controlling for socioeconomic variables. In a third part, we investigate whether the level of social capital is higher or lower in Belgium than in other European countries, and we analyze European regional differences in term of social capital.<p>Doctorat en Sciences économiques et de gestioninfo:eu-repo/semantics/nonPublishe

Unpredictability of hip behavior in Dyggve-Melchior-Clausen syndrome: A mid-term assessment of siblings

SummaryDyggve-Melchior-Clausen syndrome is a rare spondylo-epiphyseal disease, which almost constantly leads to both bilateral hip degeneration and dislocation. Few authors have reported to date the surgical management of this orthopaedic disorder. We present two new cases affecting siblings. One brother was treated by unilateral triple pelvic osteotomy combined with varus osteotomy of the proximal femur; the other was treated by bilateral Pemberton osteotomies with varus osteotomy of the proximal femur. At a respective 5-year and 3-year follow-up delay, both cases had evolved towards progressive subluxation recurrence along with severe hip degeneration. Based on both our experience and literature review, it seems that one should avoid operating these hips unless pain renders surgery mandatory. Total hip arthroplasty seems the only reliable surgical solution at the adult age and paediatric surgeons should keep in mind that previous femoral osteotomies will make it more challenging for adult orthopaedic surgeons to implant on a remodeled anatomy

Combined inhibition of Wee1 and Chk1 as a therapeutic strategy in multiple myeloma

Multiple myeloma (MM) is a hematological malignancy characterized by an abnormal clonal proliferation of malignant plasma cells. Despite the introduction of novel agents that have significantly improved clinical outcome, most patients relapse and develop drug resistance. MM is characterized by genomic instability and a high level of replicative stress. In response to replicative and DNA damage stress, MM cells activate various DNA damage signaling pathways. In this study, we reported that high CHK1 and WEE1 expression is associated with poor outcome in independent cohorts of MM patients treated with high dose melphalan chemotherapy or anti-CD38 immunotherapy. Combined targeting of Chk1 and Wee1 demonstrates synergistic toxicities on MM cells and was associated with higher DNA double-strand break induction, as evidenced by an increased percentage of γH2AX positive cells subsequently leading to apoptosis. The therapeutic interest of Chk1/Wee1 inhibitors’ combination was validated on primary MM cells of patients. The toxicity was specific of MM cells since normal bone marrow cells were not significantly affected. Using deconvolution approach, MM patients with high CHK1 expression exhibited a significant lower percentage of NK cells whereas patients with high WEE1 expression displayed a significant higher percentage of regulatory T cells in the bone marrow. These data emphasize that MM cell adaptation to replicative stress through Wee1 and Chk1 upregulation may decrease the activation of the cell-intrinsic innate immune response. Our study suggests that association of Chk1 and Wee1 inhibitors may represent a promising therapeutic approach in high-risk MM patients characterized by high CHK1 and WEE1 expression

Reinstated p53 response and high anti-T-cell leukemia activity by the novel alkylating deacetylase inhibitor tinostamustine

Non peer reviewe

Sociospatial structure explains marked variation in brucellosis seroprevalence in an Alpine ibex population

International audienceIn a context of (re)emerging infectious diseases with wildlife reservoirs, understanding how animal ecology shapes epidemiology is a key issue, particularly in wild ungulates that share pathogens with domestic herbivores and have similar food requirements. For the first time in Europe, brucellosis (Brucella melitensis), a virulent zoonosis, persisted in an Alpine ibex (Capra ibex) population and was transmitted to cattle and humans. To better understand disease dynamics, we investigated the relationships between the spatial ecology of ibex and the epidemiology of brucellosis. Combining home range overlap between 37 GPS-collared individuals and visual observations of 148 visuallymarked individuals monitored during the 2013-2016 period, we showed that females were spatially segregated in at least 4 units all year round, whereas males were more prone to move between female units, in particular during the rutting period. In addition to ibex age, the spatial structure in females largely contributed to variation in seroprevalence in the whole population. These results suggest that non-sexual routes are the most likely pathways of intraspecific transmission, crucial information for management. Accounting for wildlife spatial ecology was hence decisive in improving our ability to better understand this health challenge involving a wildlife reservoir

Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma

Altres ajuts: This study was supported by Bristol-Myers Squibb, Princeton, NJ.Urelumab, a fully human, non-ligand binding, CD137 agonist IgG4 monoclonal antibody, enhances T-cell and natural killer-cell antitumor activity in preclinical models, and may enhance cytotoxic activity of rituximab. Here we report results in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other B-cell lymphomas, in phase 1 studies evaluating urelumab alone (NCT01471210) or combined with rituximab (NCT01775631). Sixty patients received urelumab (0.3 mg/kg IV Q3W, 8 mg IV Q3W, or 8 mg IV Q6W); 46 received urelumab (0.1 mg/kg, 0.3 mg/kg, or 8 mg IV Q3W) plus rituximab 375 mg/m 2 IV QW. The maximum tolerated dose (MTD) of urelumab was determined to be 0.1 mg/kg or 8 mg Q3W after a single event of potential drug-induced liver injury occurred with urelumab 0.3 mg/kg. Treatment-related AEs were reported in 52% (urelumab: grade 3/4, 15%) and 72% (urelumab + rituximab: grade 3/4, 28%); three led to discontinuation (grade 3 increased AST, grade 4 acute hepatitis [urelumab]; one death from sepsis syndrome [urelumab plus rituximab]). Objective response rates/disease control rates were 6%/19% (DLBCL, n = 31), 12%/35% (FL, n = 17), and 17%/42% (other B-cell lymphomas, n = 12) with urelumab and 10%/24% (DLBCL, n = 29) and 35%/71% (FL, n = 17) with urelumab plus rituximab. Durable remissions in heavily pretreated patients were achieved; however, many were observed at doses exceeding the MTD. These data show that urelumab alone or in combination with rituximab demonstrated manageable safety in B-cell lymphoma, but the combination did not enhance clinical activity relative to rituximab alone or other current standard of care

Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström’s Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study

[Purpose]: The double-blind, randomized, placebo-controlled phase III iNNOVATE study showed sustained efficacy of ibrutinib-rituximab in Waldenström's macroglobulinemia (WM). Here, we present the final analysis from iNNOVATE. [Methods]: Patients had confirmed symptomatic WM, either previously untreated or previously treated; patients with prior rituximab had at least a minor response to their last rituximab-based regimen. Patients were randomly assigned to once-daily ibrutinib 420 mg plus rituximab or placebo plus rituximab (n = 75 per arm). The primary end point was progression-free survival (PFS). Secondary end points included response rate, time to next treatment, hemoglobin improvement, overall survival, and safety. [Results]: With a median follow-up of 50 (range, 0.5-63) months, median (95% CI) PFS was not reached (57.7 months to not evaluable) with ibrutinib-rituximab versus 20.3 months (13.0 to 27.6) with placebo-rituximab (hazard ratio, 0.250; P < .0001). PFS benefit was regardless of prior treatment status, MYD88 and CXCR4 mutation status, or key patient characteristics. Higher response rates (partial response or better) were observed with ibrutinib-rituximab (76% v 31% with placebo-rituximab; P < .0001) and were sustained over time. Median time to next treatment was not reached with ibrutinib-rituximab versus 18 months with placebo-rituximab. More patients receiving ibrutinib-rituximab versus placebo-rituximab had sustained hemoglobin improvement (77% v 43%; P < .0001). Median overall survival was not reached in either arm. Ibrutinib-rituximab maintained a manageable safety profile; the prevalence of grade ≥ 3 adverse events of clinical interest generally decreased over time. [Conclusion]: In the final analysis of iNNOVATE with a median follow-up of 50 months, ibrutinib-rituximab showed ongoing superiority across clinical outcomes in patients with WM regardless of MYD88 or CXCR4 mutation status, prior treatment, and key patient characteristics.Supported by Pharmacyclics LLC, an AbbVie Company. Pharmacyclics LLC sponsored and designed the study.Peer reviewe

The BLM helicase is a new therapeutic target in multiple myeloma involved in replication stress survival and drug resistance

Multiple myeloma (MM) is a hematologic cancer characterized by accumulation of malignant plasma cells in the bone marrow. To date, no definitive cure exists for MM and resistance to current treatments is one of the major challenges of this disease. The DNA helicase BLM, whose depletion or mutation causes the cancer-prone Bloom’s syndrome (BS), is a central factor of DNA damage repair by homologous recombination (HR) and genomic stability maintenance. Using independent cohorts of MM patients, we identified that high expression of BLM is associated with a poor outcome with a significant enrichment in replication stress signature. We provide evidence that chemical inhibition of BLM by the small molecule ML216 in HMCLs (human myeloma cell lines) leads to cell cycle arrest and increases apoptosis, likely by accumulation of DNA damage. BLM inhibition synergizes with the alkylating agent melphalan to efficiently inhibit growth and promote cell death in HMCLs. Moreover, ML216 treatment re-sensitizes melphalan-resistant cell lines to this conventional therapeutic agent. Altogether, these data suggest that inhibition of BLM in combination with DNA damaging agents could be of therapeutic interest in the treatment of MM, especially in those patients with high BLM expression and/or resistance to melphalan

Plain Language Summary of the iNNOVATE study: ibrutinib plus rituximab is well-tolerated and effective in people with Waldenström's macroglobulinemia

This article provides a short summary of 5-year results from the iNNOVATE trial. The original paper was published in the Journal of Clinical Oncology in October 2021. People with Waldenström's macroglobulinemia (WM) were randomly divided into two groups of 75 people each. One group received a combination treatment composed of two drugs, ibrutinib plus rituximab, and the other group took placebo (“sugar pill”) plus rituximab. Ibrutinib (also known by the brand name Imbruvica®) is a drug that reduces cancer cells' ability to multiply and survive. Ibrutinib is an FDA-approved drug for the treatment of WM. Rituximab is a drug that helps the immune system find and kill cancer cells. Participants in the trial were treated and their health monitored for up to 5 years (63 months).Editorial support for development of this summary was provided by Cindi A. Hoover, PhD, and was funded by Pharmacyclics LLC, an AbbVie Company.Peer reviewe