Heterogeneous populations of bone marrow stem cells--are we spotting on the same cells from the different angles?

Accumulated evidence suggests that in addition to hematopoietic stem cells (HSC), bone marrow (BM) also harbors endothelial stem cells (ESC), mesenchymal stem cells (MSC), multipotential adult progenitor cells (MAPC), pluripotent stem cells (PCS) as well as tissue committed stem cells (TCSC) recently identified by us. In this review we discuss the similarities and differences between these cell populations. Furthermore, we will present the hypothesis that all of these versatile BM derived stem cells are in fact different subpopulations of TCSC. These cells accumulate in bone marrow during ontogenesis and being a mobile population of cells are released from BM into peripheral blood after tissue injury to regenerate damaged organs. Furthermore, since BM is a "hideout" for TCSC, their presence in preparations of bone marrow derived mononuclear cells should be considered before experimental evidence is interpreted simply as trans-differentiation or plasticity of HSC. Finally, our observation that the number of TCSC accumulate in the bone marrow of young animals and their numbers decrease during senescence provides a new insight into aging and may explain why the regeneration processes becomes less effective in older individuals

Heterogeneous populations of bone marrow stem cells : are we spotting on the same cells from the different angles?

Accumulated evidence suggests that in addition to hematopoietic stem cells (HSC), bone marrow (BM) also harbors endothelial stem cells (ESC), mesenchymal stem cells (MSC), multipotential adult progenitor cells (MAPC), pluripotent stem cells (PCS) as well as tissue committed stem cells (TCSC) recently identified by us. In this review we discuss the similarities and differences between these cell populations. Furthermore, we will present the hypothesis that all of these versatile BM derived stem cells are in fact different subpopulations of TCSC. These cells accumulate in bone marrow during ontogenesis and being a mobile population of cells are released from BM into peripheral blood after tissue injury to regenerate damaged organs. Furthermore, since BM is a "hideout" for TCSC, their presence in preparations of bone marrow derived mononuclear cells should be considered before experimental evidence is interpreted simply as trans-differentiation or plasticity of HSC. Finally, our observation that the number of TCSC accumulate in the bone marrow of young animals and their numbers decrease during senescence provides a new insight into aging and may explain why the regeneration processes becomes less effective in older individuals

Hindsight and Sequential Rationality of Correlated Play

Driven by recent successes in two-player, zero-sum game solving and playing, artificial intelligence work on games has increasingly focused on algorithms that produce equilibrium-based strategies. However, this approach has been less effective at producing competent players in general-sum games or those with more than two players than in two-player, zero-sum games. An appealing alternative is to consider adaptive algorithms that ensure strong performance in hindsight relative to what could have been achieved with modified behavior. This approach also leads to a game-theoretic analysis, but in the correlated play that arises from joint learning dynamics rather than factored agent behavior at equilibrium. We develop and advocate for this hindsight rationality framing of learning in general sequential decision-making settings. To this end, we re-examine mediated equilibrium and deviation types in extensive-form games, thereby gaining a more complete understanding and resolving past misconceptions. We present a set of examples illustrating the distinct strengths and weaknesses of each type of equilibrium in the literature, and prove that no tractable concept subsumes all others. This line of inquiry culminates in the definition of the deviation and equilibrium classes that correspond to algorithms in the counterfactual regret minimization (CFR) family, relating them to all others in the literature. Examining CFR in greater detail further leads to a new recursive definition of rationality in correlated play that extends sequential rationality in a way that naturally applies to hindsight evaluation.Comment: Technical report for a paper in the proceedings of the thirty-fifth AAAI Conference on Artificial Intelligence (AAAI-21), February 2-9, 2021, Virtual. 26 pages and 15 figure

Theorizing media production: the poverty of political economy

This article argues that the Political Economy of Communication (PEC) has generally failed to develop theories of media production. Such theory as exists has been heavily influenced by accounts of mass production and flexible specialization in Hollywood. Hollywood film production has been viewed as paradigmatic of media production in general, in the same way as Ford was for manufacturing, and these theories continue to influence accounts of production across media and cultural industries. The article tests the mass production/flexible specialization paradigm against both the evidence of the Hollywood case and Ford’s mass production system. An alternative paradigm, the theory of craft media production, is also examined. The article then attempts to show how applying organization theory and media economics can provide a more convincing explanation of media production and of the Hollywood case. Finally, the article briefly attempts to show how we might develop rich theoretical explanations of media production by exploring the relationships between economic, organizational and media-specific cultural elements

Lancet

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation

Retinal pigment epithelium damage enhances expression of chemoattractants and migration of bone marrow-derived stem cells

PURPOSE: To characterize chemoattractants expressed by the retinal pigment epithelium (RPE) after sodium iodate (NaIO3)-induced damage and to investigate whether ocular-committed stem cells preexist in the bone marrow (BM) and migrate in response to the chemoattractive signals expressed by the damaged RPE. METHODS: C57/BL6 mice were treated with a single intravenous injection of NaIO3 (50 mg/kg) to create RPE damage. At different time points real-time RT-PCR, ELISA, and immunohistochemistry were used to identify chemoattractants secreted in the subretinal space. Conditioned medium from NaIO3-treated mouse RPE was used in an in vitro assay to assess chemotaxis of stem cell antigen-1 positive (Sca-1+) BM mononuclear cells (MNCs). The expression of early ocular markers (MITF, Pax-6, Six-3, Otx) in migrated cells and in MNCs isolated from granulocyte colony-stimulating factor (G-CSF) and Flt3 ligand (FL)-mobilized and nonmobilized peripheral blood (PB) was analyzed by real-time RT-PCR. RESULTS: mRNA for stromal cell-derived factor-1 (SDF-1), C3, hepatocyte growth factor (HGF), and leukemia inhibitory factor (LIF) was significantly increased, and higher SDF-1 and C3 protein secretion from the RPE was found after NaIO3 treatment. A higher number of BMMNCs expressing early ocular markers migrated to conditioned medium from damaged retina. There was also increased expression of early ocular markers in PBMNCs after mobilization. CONCLUSIONS: Damaged RPE secretes cytokines that have been shown to serve as chemoattractants for BM-derived stem cells (BMSCs). Retina-committed stem cells appear to reside in the BM and can be mobilized into the PB by G-CSF and FL. These stem cells may have the potential to serve as an endogenous source for tissue regeneration after RPE damage