Public Funding of Research into Ethnological Activities in Andalusia (Spain): Boosting the Academic Career of Researchers

The advent of democracy in Spain and the establishment of the different autonomous communities marked the beginning of a process to transfer political, economic and other competences over Culture and Cultural Heritage. Following its creation in 1984, the Ministry of Culture of the Andalusian Autonomous Government incorporated a Directorate-General for Cultural Assets into its organisational structure and embarked on an ambitious programme of actions to support Andalusian historical heritage, including creation of a management structure, enactment of a specific heritage law and budget allocations for protection tasks. From the outset, a type of heritage little known until then emerged: ethnological heritage. Dynamic actions were also promoted to fund research into this area, including grants for ethnological activities, financing for publications and funding for ethnological symposiums. This paper analyses the different ethnological activities carried out and their funding, and assesses the extent to which this investment favoured the professional development of teaching staff in the field of Social Anthropology in Andalusia, specifying the marginal effects and differentiating them according to gender and university size using binary choice models (Logit).

Comparing Hedge Funds: Highest Return Strategy

Since 1997, the hedge fund industry has grown at a compounded annual growth rate of 16.07%, resulting in a 26-fold increase from its original value to its present value of $3.1 trillion Assets Under Management. This study researched the varying investment strategies used by hedge funds to determine the strategy that provides the highest returns for its investors. From the previous literature, the study identified Long/Short Equity, Global Macro, Arbitrage, Event Driven, and Cross-Asset Multi-Strategy as viable and relevant investment approaches. Using hedge fund index data from Bloomberg, Hedge Fund Research, Eureka Hedge, Barclay’s, and Credit Suisse, returns for each respective strategy were collected and compared against the Bloomberg Global Hedge Fund (BHEDGE) Index and the S&P 500 Index. Alpha adjusted returns for each strategy were later calculated and plotted against the average weighted returns of each individual strategy. The results of this study show that the L/S Equity strategy provided the highest returns for its investors. Specifically, only the L/S Equity strategy outperformed the BHEDGE Index by a narrow margin, while all other strategies provided negative alpha figures. All hedge fund strategies outperformed the overall equity market on a year-to-date basis, however, provided negative alpha returns when compared to the S&P 500 1-Year market gains. This deficit between hedge funds and the overall equity market can be attributed to the COVID-19 pandemic and its inflationary effects through low interest rates, market stimulus packs, and an increased money supply.

Factors Influencing Internal Audit Fund Sufficiency

This study is motivated by the lack of internal audit (IA) fund research and examines the influence that the following elements have on IA fund sufficiency: IA quality factors (experience, certification and training), the independence and objectivity of Chief Audit Executives (rotation, reporting line and appointment), IA characteristics (IA department size and age), budget changes, and IA risk assessment activities. This study identifies 2,205 Chief Audit Executives and uses logistic regression to examine the impact of internal audit quality, independence, characteristics and activity on IA fund sufficiency. The results show that IA quality variables, independence and objectivity variables, IA size, age and budget changes all contribute to predicting fund sufficiency for the model IA department. The results also demonstrate that the risk assessment variable does not contribute to the model. The value of this study is that it provides empirical evidence regarding identifying factors that influence internal audit fund sufficiency. This study’s evidence has implications for policymakers and practitioners, as the actual issue of IA fund sufficiency has yet to be examined.

The Chinese Model and Chinese Wisdom of Modernization

The Chinese Model and Chinese Wisdom of Modernization 1 Abstract: The Soviet model of socialism and the American model of capitalism are the two major solutions to modernization. Under the guidance of the traditional Chinese Doctrine of the Mean and the Marxist dialectical materialism, the Communist Party of China, by successively learning from these two major solutions and combining with the actual situation of China, has proposed Chinese solutions of socialism with Chinese characteristics to modernization of state governance and thus offered to the world Chinese wisdom beyond the conflicts between two major ideologies, namely, socialism and capitalism. Keywords: State governance. Modernization. Chinese wisdom. Chinese situations. O modelo chinês e a sabedoria chinesa da modernização Resumo: O modelo soviético de socialismo e o modelo americano de capitalismo são as duas principais soluções para a modernização. Sob a orientação da doutrina chinesa tradicional do caminho do meio e do materialismo dialético marxista, o Partido Comunista da China, aprendendo sucessivamente com essas duas soluções principais e combinando-se com a situação atual da China, propôs soluções chinesas de socialismo com características chinesas, modernização da governança do estado e, assim, ofereceu ao mundo a sabedoria chinesa além dos conflitos entre duas grandes ideologias, a saber, socialismo e capitalismo. Palavras-chave: Governança estatal. Modernização. Sabedoria chinesa. Situações chinesas. El modelo chino y la sabiduría china de la modernización Resumen: El modelo soviético del socialismo y el modelo estadounidense del capitalismo son las dos soluciones principales para la modernización. Bajo la guía de la Doctrina tradicional china de la media y el materialismo dialéctico marxista, el Partido Comunista de China, al aprender sucesivamente de estas dos soluciones principales y combinar con la situación actual de China, ha propuesto soluciones chinas del socialismo con características chinas para modernización de la gobernanza estatal y, por lo tanto, ofreció al mundo sabiduría china más allá de los conflictos entre dos ideologías principales, a saber, el socialismo y el capitalismo. Palabras clave: Gobernanza estatal. Modernización. Sabiduría china. Situaciones chinas. 1This paper is related to “the Research of the Relationship between the Thought of the Communist Party of China about state Governance and Excellent Traditional Chinese Culture” supported by Beijing Social Science Fund Research Project Base (Project No. 17JDKDB003) Data de registro: 30/07/2020 Data de aceite: 21/10/2020 1 This paper is related to “the Research of the Relationship between the Thought of the Communist Party of China about state Governance and Excellent Traditional Chinese Culture” supported by Beijing Social Science Fund Research Project Base (Project No. 17JDKDB003).

Predictors and Outcomes of Flares in Chronic Graft-Versus-Host Disease

Introduction: Chronic Graft-versus-Host Disease (cGvHD) frequently requires prolonged immune suppressive therapy (IST) with > 50% still on IST at 5 years. The IST typically involves a slow taper of steroids often with flare of cGvHD, necessitating augmentation of previous therapy or addition of new IST. Studies describing cGvHD flares are limited. We analyzed patients with cGvHD who flared during the treatment with systemic IST, their overall survival (OS) and non-relapse mortality (NRM). Methods: This study included all adult patients with cGvHD (n=145) following an allogeneic transplant (2010 - 2017) from a matched sibling donor peripheral blood stem cell transplant (MSD, n=104 (72%) or double/single umbilical cord blood transplant (UCBT, n=41 (28%). The 2014 NIH Consensus Criteria were used to classify organ/overall cGvHD severity. Flare of cGvHD was defined as progression in cGvHD manifestations (after initial response), which was less severe than at diagnosis. Multivariate regression of flares was based on the Prentice, Williams and Peterson model for ordered multiple events (flares). Time-dependent effects on OS and NRM were analyzed by Cox and Fine and Gray regression with propensity scoring to control for confounding. Results: Flares occurred in 87 patients; the cumulative incidence of flares was 60% (95% CI: 51-70%) at a median of 188 days (range 16-751) after diagnosis of cGvHD. The median dose of prednisone was 1 mg/kg/day (range 0-4.2) at diagnosis of cGvHD. At the diagnosis of flare, 36 (41%) of the patients were off prednisone, 50 (57%) were receiving 0.1-0.5 mg/kg /day, and 2 patients > 0.5 mg/kg /day. Thirty two of the 87 (36%) patients experienced multiple flares (2 to 4). The most common organs involved at cGvHD flare were skin (n=45; 51%), mouth (n=27; 31%), GI tract (n=22; 25%) and liver (n=12; 14%); often in combinations of skin/mouth in 11 cases (13%), skin/GI in 6 (7%) and liver/mouth in 4 (5%) cases. Treatment for flare was mostly increase in dose of prednisone to 0.5 mg/kg/day (range 0.3-1.0) in 77 patients (88%) plus the addition of another line of IST in 48 patients (55%). In multiple regression analysis, only donor type was significant predictor of flare in cGvHD. UCBT was associated with 2-fold lower probability of flaring (HR 0.5; 95% CI: 0.3-0.9; p=0.03) compared to MSD. cGvHD severity, organ involvement, platelet count at diagnosis and type of onset were not significant predictors of cGvHD flares. At 2 years after the initial flare, the OS was 77% (95% CI: 66-84%) and NRM 19% (95% CI: 11-28%). Multiple regression analysis evaluating OS and NRM from onset of cGvHD comparing flare to non-flare were performed using flare as a time dependent variable. Compared to cGvHD patients without flare at 2 years, those with flare of cGvHD had a similar risk of NRM (HR 1.2; 95% CI: 0.2-6.1, p=0.86) and OS (HR 0.9; 95% CI: 0.4-2.3, p=0.85). At 2 years from cGvHD onset, the cumulative incidence of resolved cGvHD (durable discontinuation of steroids for ≥ 6 consecutive months) was 31% (95% CI: 21-41%) in those who flared vs. 86% (95% CI: 75-96%) in those without flare. Conclusions: Though cGvHD patients with flare had similar risk of NRM and OS as those without a flare, patients with flare required extended steroids, along with clinical monitoring and intensified IST. cGvHD after UCBT was associated with significantly lower risk of flaring compared to MSD. The ongoing burden of IST, risk of infection and morbidity of cGvHD is substantial and needs better approaches than chronic slow taper of steroids. Disclosures Weisdorf: Incyte: Research Funding; FATE Therapeutics: Consultancy. Wagner:Novartis: Research Funding; Rocket Pharmaceuticals, Inc.: Consultancy, Current equity holder in publicly-traded company; Magenta Therapeutics: Consultancy, Research Funding; BlueRock: Research Funding; Gadeta: Membership on an entity's Board of Directors or advisory committees. Blazar:Fate Therapeutics Inc.: Research Funding; Childrens' Cancer Research Fund: Research Funding; BlueRock Therapeutics: Research Funding; BlueRock Therapeuetic: Consultancy; Magenta Therapeutics: Consultancy; KidsFirst Fund: Research Funding; Tmunity: Other: Co-founder. MacMillan:Mesoblast: Consultancy; Angiocrine Biosciences, Inc.: Consultancy; Equillium, Inc.: Consultancy; Talaris Therapeutics, Inc: Consultancy; Fate Therapeutics, Inc.: Consultancy. Holtan:Generon: Consultancy; BMS: Consultancy; CSL Behring: Other: Clinical trial data adjudication; Incyte: Consultancy. Brunstein:AlloVir: Other: Advisory board; Gamida: Research Funding; Astex: Research Funding; Magenta: Research Funding. Betts:Patent Pending: Patents & Royalties: Dr. Betts has a pending patent WO2017058950A1: Methods of treating transplant rejection. This includes the use of JAK inhibitors. Neither he nor his institution have received payment related to claims described in the patent.. Bachanova:FATE: Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding. Rashidi:Synthetic Biologics: Other: DSMC member (1 trial) and related honorarium. Arora:Fate Therapeutics: Consultancy; Kadmon: Research Funding; Pharmacyclics: Research Funding; Syndax: Research Funding.

Triple Gene-Modified iPSC-Derived NK Cells Combined with Daratumumab for Targeted Immunotherapy Against AML

Approximately 19,940 new cases of acute myeloid leukemia (AML) will be diagnosed in 2020 with an estimated 11,180 deaths, which has remained steady for 3 decades. We established that allogeneic natural killer (NK) cell infusions have an antileukemic effect and induce remission in 25-40% of relapsed/refractory AML patients. After hundreds of individual donor product infusions, we noted therapeutic limitations to include effector potency, cell numbers,persistence, specificity and exportability. To overcome these barriers, we developed a robust genetic editing and manufacturing platform for the uniform engineering and expansion of high-quality NK cells derived from induced pluripotent stem cells (iPSCs). This manufacturing system allows efficient production of iPSC-derived NK (iNK) cells engineered to enhance persistence and potency, and enables distribution of highly homogenous iNK cells to multiple clinical sites and multi-dosing to treat patients on-demand with advanced cancer. We hypothesized that iNK cells could be combined with the anti-CD38 monoclonal antibody daratumumab (dara) to directly target various tumors and harness their antibody-dependent cellular cytotoxicity (ADCC) potential. Previously, we reported on our ability to effectively target multiple myeloma with our FT538 program (the iNK defined below), now FDA approved for clinical trials. Here we discuss applying these same engineered iNK cells to specifically target and kill AML blasts induced to upregulate CD38 by retinoic acid exposure. We utilized iNK cells expressing a high-affinity, non-cleavable version of CD16 (the Fc receptor that mediates ADCC) termed hnCD16 alone or combined with CD38 knockout (KO) to prevent dara-mediated NK cell fratricide (Fig. 1A). CD38 KO iNK cells had intact calcium flux in response to ionomycin or CD16 crosslinking (Fig. 1B). Adding dara to peripheral blood NK cells or hnCD16 iNK cells triggered ADCC-mediated fratricide, while hnCD16/CD38 KO iNK cells that cannot be targeted by dara were unaffected (Fig 1C). CD38, expressed intracellularly and on the plasma membrane, functions as an NADase, degrading nicotinamide adenine dinucleotide (NAD+) into ADP-ribose and nicotinamide. Because NAD+ levels influence several key metabolic pathways, we assessed the impact of CD38 KO on iNK cell metabolism. We found that, relative to hnCD16 iNK cells, hnCD16/CD38 KO iNK cells had significantly higher intracellular NAD+, NADH, and ATP levels (Fig. 1D). Additionally, hnCD16/CD38 KO iNK cells exhibited elevated mitochondrial oxidative phosphorylation (Fig. 1E) and marked resistance to oxidative stress to hydrogen peroxide exposure (Fig. 1F). Together, these results demonstrate a significant enhancement of NK cell mitochondrial oxidative phosphorylation and redox homeostasis in iNK CD38 KO cells. To enhance hnCD16/CD38 KO iNK cells further, we incorporated a third modification consisting of an IL-15 receptor signaling complex (IL-15RF). This receptor complex is expressed on the cell surface and provides IL-15 signals required for NK cell survival and proliferation independent of exogenous cytokine. To determine the efficacy of hnCD16/CD38 KO/IL-15RF iNK cells combined with dara to target AML, we first assessed CD38 expression on THP-1 cells (an AML cell line) and primary AML blasts incubated with or without retinoic acid. We observed high CD38 expression on both THP-1 cells and primary AML cells further elevated with retinoic acid treatment (Fig. 1G). THP-1 and primary AML cells were labeled with CellTrace dye and used as targets for killing assays using hnCD16/CD38 KO/IL-15RF iNK cells. Compared to hnCD16/CD38 KO/IL-15RF iNK cells cultured with targets alone, adding dara led to higher target cell killing, especially after retinoic acid exposure (Fig. 1H). In 12-hour live imaging experiments testing iNK cell cytotoxicity against THP-1 cells, similar results were observed (Fig. 1I). Collectively, our results show that utilizing the iNK cell platform to uniformly express hnCD16 and IL15RF combined with complete CD38 KO is an effective strategy to promote effective ADCC against CD38+ cells in the absence of fratricide, and that CD38 KO reprograms NK cells for higher oxidative metabolic fitness for improved persistence and anti-tumor function. Furthermore, we have generated proof-of-concept data supporting triple gene-modified iNK cells combined with dara as a novel AML immunotherapy. Disclosures Cichocki: Fate Therapeutics, Inc: Consultancy, Patents & Royalties, Research Funding. Bjordahl:Fate Therapeutics: Current Employment. Bonello:Fate Therapeutics, Inc: Current Employment. Mahmood:Fate Therapeutics, Inc: Current Employment. Rogers:Fate Therapeutics, Inc: Current Employment. Ge:Fate Therapeutics, Inc: Current Employment. Lee:Fate Therapeutics, Inc.: Current Employment. Felices:GT Biopharma: Consultancy. Walcheck:Fate Therapeutics: Consultancy, Research Funding. Blazar:Fate Therapeutics Inc.: Research Funding; KidsFirst Fund: Research Funding; Magenta Therapeutics: Consultancy; Childrens' Cancer Research Fund: Research Funding; BlueRock Therapeutics: Research Funding; BlueRock Therapeuetic: Consultancy; Tmunity: Other: Co-founder. Valamehr:Fate Therapeutics, Inc: Current Employment, Current equity holder in publicly-traded company. Miller:GT Biopharma: Consultancy, Patents & Royalties, Research Funding; Onkimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nektar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics, Inc: Consultancy, Patents & Royalties, Research Funding; Vycellix: Consultancy. OffLabel Disclosure: FT538 is a genetically modified induced pluripotent stem cell derived NK cell product that can be combined with daratumumab to target CD38 on AML after retinoid acid induction.

Plasma Short Chain Fatty Acids As a Predictor of Response to Therapy for Life-Threatening Acute Graft-Versus-Host Disease

Introduction Minnesota High Risk and steroid-refractory acute graft-versus-host disease (aGVHD) are life-threatening complications of allogeneic hematopoietic cell transplantation (HCT). Recent data suggests dysbiosis may relate to GVHD outcomes. Bacteria in the lower gastrointestinal tract (LGI) produce short chain fatty acids (SCFAs) as fuel for enterocytes and modulators of mucosal immunity. LGI damage caused by aGVHD and antibiotic administration may be detrimental to SCFAs production and thus intestinal repair. However, limited data exists on how plasma SCFA levels vary between aGVHD patients who respond to treatment and those who do not. This study examined how aGVHD treatment response relates to plasma levels of five common SCFAs: acetate, propionate, butyrate, isovalerate, and valerate. Patients and Methods Serial plasma samples (n=221) were collected from 49 patients who underwent treatment for Minnesota High Risk or steroid-dependent/refractory aGVHD on NCT02525029 at study baseline and at 7, 14, 28 and 56 days post-treatment initiation. GVHD severity was graded using Minnesota criteria. Patients were categorized by their response to therapy at day 28 (complete/partial response [CR/PR], n=35 versus no response or death [NR], n=14). Plasma SCFA levels were quantified via liquid chromatography and cytokines measured by multiplex cytokine array. Changes in SCFA over time were assessed by repeated measures ANOVA. SCFA levels responders versus non-responders at individual time points were compared using Mann-Whitney testing and principal component analysis (PCA). SCFA, cytokines, and GVHD biomarkers including ST2, REG3a, and AREG were correlated using Spearman's rho with Bonferroni correction for multiple comparisons. Results Patients with CR/PR had higher levels of propionate (p=0.02) and butyrate (p=0.008) in comparison to NR among all samples analyzed (Figure 1a). Only butyrate levels varied significantly over time (p=0.018, with a significant difference in CR/PR vs NR at day 7, Figure 1b). The overall metabolomic profile of CR/PR patients was more stable than NR patients as determined by PCA. Neither initial clinical nor histologic grade of LGI aGVHD were associated with baseline plasma SCFA. Recent Clostridium difficile infection (n=5, p=NS) and total parenteral nutrition use (n=26, p=NS) did not influence baseline SCFA concentrations. Patients with high levels of butyrate also had high propionate (rho 0.9, p<0.001) and valerate (rho 0.84, p<0.001) and low isovalerate (rho -0.34, p<0.001). Plasma levels of interleukin-6 were higher in patients with low propionate and valerate (rho -0.33, p=0.008 and rho -0.36, p=0.002 respectively). Discussion Plasma SCFA profiles in patients with life-threatening GVHD suggest that differences in intestinal commensal microbe-derived SCFA production may relate to response to treatment. Patients responding to therapy have higher levels of plasma propionate and butyrate, especially early in the course of therapy. Patients with NR at day 28 appear to have increasing butyrate over time, possibly due to survival bias and/or stabilization on 2nd line therapy. Patients with higher concentrations of propionate and valerate have lower circulating IL-6 levels, which may indicate reduced systemic inflammation. Figure. (A) Comparison of short chain fatty acid (SCFA) plasma concentrations and clinical response (complete/partial response [CR/PR] vs no response [NR]) among all samples and (B) with butyrate over time. (C) Correlation of plasma SCFA, cytokines, and graft-versus-host disease biomarkers. Disclosures MacMillan: Equillium, Inc.: Consultancy; Mesoblast: Consultancy; Talaris Therapeutics, Inc: Consultancy; Fate Therapeutics, Inc.: Consultancy; Angiocrine Biosciences, Inc.: Consultancy. Rashidi:Synthetic Biologics: Other: DSMC member (1 trial) and related honorarium. Weisdorf:Incyte: Research Funding; FATE Therapeutics: Consultancy. Blazar:Tmunity: Other: Co-founder; Fate Therapeutics Inc.: Research Funding; KidsFirst Fund: Research Funding; Childrens' Cancer Research Fund: Research Funding; BlueRock Therapeutics: Research Funding; BlueRock Therapeuetic: Consultancy; Magenta Therapeutics: Consultancy. Betts:Patent Pending: Patents & Royalties: Dr. Betts has a pending patent WO2017058950A1: Methods of treating transplant rejection. This includes the use of JAK inhibitors. Neither he nor his institution have received payment related to claims described in the patent.. Holtan:Incyte: Consultancy; Generon: Consultancy; CSL Behring: Other: Clinical trial data adjudication; BMS: Consultancy.