A Commons-Compatible Implementation of the Sharing Economy: Blockchain-Based Open Source Mediation

The network economical sharing economy, with direct exchange as a core characteristic, is implemented both, on a commons and platform economical basis. This is due to a gain in importance of trust, collaborative consumption and democratic management as well as technological progress, in the form of near zero marginal costs, open source contributions and digital transformation. Concurrent to these commons-based drivers, the grey area between commerce and private exchange is used to exploit work, safety and tax regulations by central platform economists. Instead of central intermediators, the blockchain technology makes decentralized consensus finding, using Proof-of-Work (PoW) within a self-sustaining Peer-to-Peer network, possible. Therefore, a blockchain-based open source mediation seems to offer a commons-compatible implementation of the sharing economy. This thesis is investigated through a qualitative case study of Sardex and Interlace with their blockchain application, based on expert interviews and a structured content analysis. To detect the most commons-compatible implementation, the different implementation options through conventional platform intermediators, an open source blockchain with PoW as well as Interlaces' permissioned blockchain approach, are compared. The following confrontation is based on deductive criteria, which illustrates the inherent characteristics of a commons-based sharing economy

Retrospective audit of antibiotic use in a university general pediatrics department using hospital pharmacy dispensing data

Antibiotics are among the most frequently prescribed drugs in children’s hospitals, which is why regular monitoring of antibiotic use in hospitals is of great importance. This retrospective audit (60 months, January 2014 – December 2018) analyzes the antibiotic consumption at a university inpatient department of general pediatrics including neonatal and pediatric intensive care based on pharmacy dispensing data in units of grams per 100 patient days and in Defined Daily Doses per 100 patient days. The results provide potential targets for Antibiotic Stewardship interventions. Conversely, this audit elicits methodological limitations of the method of antibiotic surveillance in pediatrics recommended by the Robert Koch Institute, Berlin

Outbreak of Burkholderia cepacia complex infections associated with contaminated octenidine mouthwash solution, Germany, August to September 2018

Three German patients developed nosocomial pneumonia after cardiac surgery and had Burkholderia cepacia complex detected in respiratory specimens. Two patients died of septic multi-organ failure. Wholegenome sequencing detected genetically identical B. cepacia complex strains in patient samples, from a batch of octenidine mouthwash solution, which had been used for nursing care, as well as in samples obtained from the manufacturer during production. Contamination of medical products during manufacturing may lead to international outbreaks

ABCC Multidrug Transporters in Childhood Neuroblastoma: Clinical and Biological Effects Independent of Cytotoxic Drug Efflux

Background Although the prognostic value of the ATP-binding cassette, subfamily C (ABCC) transporters in childhood neuroblastoma is usually attributed to their role in cytotoxic drug efflux, certain observations have suggested that these multidrug transporters might contribute to the malignant phenotype independent of cytotoxic drug efflux. Methods A v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN)-driven transgenic mouse neuroblastoma model was crossed with an Abcc1-deficient mouse strain (658 hMYCN1/−, 205 hMYCN+/1 mice) or, alternatively, treated with the ABCC1 inhibitor, Reversan (n = 20). ABCC genes were suppressed using short interfering RNA or overexpressed by stable transfection in neuroblastoma cell lines BE(2)-C, SH-EP, and SH-SY5Y, which were then assessed for wound closure ability, clonogenic capacity, morphological differentiation, and cell growth. Real-time quantitative polymerase chain reaction was used to examine the clinical significance of ABCC family gene expression in a large prospectively accrued cohort of patients (n = 209) with primary neuroblastomas. Kaplan-Meier survival analysis and Cox regression were used to test for associations with event-free and overall survival. Except where noted, all statistical tests were two-sided. Results Inhibition of ABCC1 statistically significantly inhibited neuroblastoma development in hMYCN transgenic mice (mean age for palpable tumor: treated mice, 47.2 days; control mice, 41.9 days; hazard ratio [HR] = 9.3, 95% confidence interval [CI] = 2.65 to 32; P < .001). Suppression of ABCC1 in vitro inhibited wound closure (P < .001) and clonogenicity (P = .006); suppression of ABCC4 enhanced morphological differentiation (P < .001) and inhibited cell growth (P < .001). Analysis of 209 neuroblastoma patient tumors revealed that, in contrast with ABCC1 and ABCC4, low rather than high ABCC3 expression was associated with reduced event-free survival (HR of recurrence or death = 2.4, 95% CI = 1.4 to 4.2; P = .001), with 23 of 53 patients with low ABCC3 expression experiencing recurrence or death compared with 31 of 155 patients with high ABCC3. Moreover, overexpression of ABCC3 in vitro inhibited neuroblastoma cell migration (P < .001) and clonogenicity (P = .03). The combined expression of ABCC1, ABCC3, and ABCC4 was associated with patients having an adverse event, such that of the 12 patients with the "poor prognosis” expression pattern, 10 experienced recurrence or death (HR of recurrence or death = 12.3, 95% CI = 6 to 27; P < .001). Conclusion ABCC transporters can affect neuroblastoma biology independently of their role in chemotherapeutic drug efflux, enhancing their potential as targets for therapeutic interventio

Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated

Population differentiation of Southern Indian male lineages correlates with agricultural expansions predating the caste system

Christina J. Adler, Alan Cooper, Clio S.I. Der Sarkissian and Wolfgang Haak are contributors to the Genographic ConsortiumPrevious studies that pooled Indian populations from a wide variety of geographical locations, have obtained contradictory conclusions about the processes of the establishment of the Varna caste system and its genetic impact on the origins and demographic histories of Indian populations. To further investigate these questions we took advantage that both Y chromosome and caste designation are paternally inherited, and genotyped 1,680 Y chromosomes representing 12 tribal and 19 non-tribal (caste) endogamous populations from the predominantly Dravidian-speaking Tamil Nadu state in the southernmost part of India. Tribes and castes were both characterized by an overwhelming proportion of putatively Indian autochthonous Y-chromosomal haplogroups (H-M69, F-M89, R1a1-M17, L1-M27, R2-M124, and C5-M356; 81% combined) with a shared genetic heritage dating back to the late Pleistocene (10–30 Kya), suggesting that more recent Holocene migrations from western Eurasia contributed, <20% of the male lineages. We found strong evidence for genetic structure, associated primarily with the current mode of subsistence. Coalescence analysis suggested that the social stratification was established 4–6 Kya and there was little admixture during the last 3 Kya, implying a minimal genetic impact of the Varna(caste) system from the historically-documented Brahmin migrations into the area. In contrast, the overall Y-chromosomal patterns, the time depth of population diversifications and the period of differentiation were best explained by the emergence of agricultural technology in South Asia. These results highlight the utility of detailed local genetic studies within India, without prior assumptions about the importance of Varna rank status for population grouping, to obtain new insights into the relative influences of past demographic events for the population structure of the whole of modern India.GaneshPrasad ArunKumar, David F. Soria-Hernanz, Valampuri John Kavitha, Varatharajan Santhakumari Arun, Adhikarla Syama, Kumaran Samy Ashokan, Kavandanpatti Thangaraj Gandhirajan, Koothapuli Vijayakumar, Muthuswamy Narayanan, Mariakuttikan Jayalakshmi, Janet S. Ziegle, Ajay K. Royyuru, Laxmi Parida, R. Spencer Wells, Colin Renfrew, Theodore G. Schurr, Chris Tyler Smith, Daniel E. Platt, Ramasamy Pitchappan, The Genographic Consortiu

NASH limits anti-tumour surveillance in immunotherapy-treated HCC.

Hepatocellular carcinoma (HCC) can have viral or non-viral causes1-5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment