AI revolution in healthcare and medicine and the (re-)emergence of inequalities and disadvantages for ageing population

AI systems in medicine and healthcare are being extensively explored in prevention, diagnosis, novel drug designs and after-care. The application of AI technology in healthcare systems promises impressive outcomes such as equalising healthcare, reducing mortality rate and human error, reducing medical costs, as well as reducing reliance on social services. In the light of the WHO “Decade of Healthy Ageing”, AI applications are designed as digital innovations to support the quality of life for older persons. However, the emergence of evidence of different types of algorithmic bias in AI applications, ageism in the use of digital devices and platforms, as well as age bias in digital data suggests that the use of AI might have discriminatory effects on older population or even cause harm. This paper addresses the issue of age biases and age discrimination in AI applications in medicine and healthcare systems and try to identify main challenges in this area. It will reflect on the potential of AI applications to amplify the already existing health inequalities by discussing two levels where potential negative impact of AI on age inequalities might be observed. Firstly, we will address the technical level of age bias in algorithms and digital datasets (especially health data). Secondly, we will discuss the potential disparate outcomes of automatic decision-making systems (ADMs) used in healthcare on the older population. These examples will demonstrate, although only partially, how AI systems may create new structures of age inequalities and novel dimensions of exclusion in healthcare and medicine

Sediment features at the grounding zone and beneath Ekström Ice Shelf, East Antarctica, imaged using on-ice vibroseis

The grounding zone, where an ice sheet becomes a floating ice shelf, is known to be a key threshold region for ice flow and stability. A better understanding of ice dynamics and sediment transport across such zones will improve knowledge about contemporary and palaeo ice flow, as well as past ice extent. Here we present a set of seismic reflection profiles crossing the grounding zone and continuing to the shelf edge of Ekström Ice Shelf, East Antarctica. Using an on-ice vibroseis source combined with a snowstreamer we have imaged a range of sub-glacial and sub-shelf sedimentary and geomorphological features; from layered sediment deposits to elongated flow features. The acoustic properties of the features as well as their morphology allow us to draw conclusions as to their material properties and origin. These results will eventually be integrated with numerical models of ice dynamics to quantify past and present interactions between ice and the solid Earth in East Antarctica; leading to a better understanding of future contributions of this region to sea-level rise

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Case Report: Graft Versus Tumor Effect After Non-Myeloablative Allogeneic Stem-Cell Transplantation in a Patient With Brentuximab-Vedotin Refractory Sezary Syndrome

Sezary Syndrome (SS) is a rare leukemic variant of primary cutaneous T-cell lymphoma. Relapsed or refractory disease is generally considered incurable by conventional therapeutic approaches, although durable responses can be achieved with novel monoclonal antibodies. Allogeneic hematopoietic stem cell transplantation (alloHSCT) may have potential value by inducing graft vs-lymphoma (GvL) effects, but there is currently no consensus regarding the timing of alloHSCT or type of conditioning regimen. Here we present the case of a male patient who achieved a complete remission (CR) of primary refractory SS after non-myeloablative alloHSCT. Patient: Two years prior to HSCT, the patient had been refractory to CHOEP-based chemotherapy, interferon, extracorporeal photopheresis (ECP), and bexarotene. Directly prior to alloHSCT brentuximab-vedotin (BV) was applied resulting in a partial remission of the skin compartment and overall in a stable disease. Prior to HSCT, flow cytometry of the bone marrow and peripheral blood showed an infiltration with T-cells positive for CD5, CD4, low CD3, low CD2 and negative for CD7, CD38, HLA-DR and CD8. The trephine biopsy showed a 7% infiltration of SS cells. The CD4:CD8 ratio in peripheral blood (pb) was massively increased at 76.67, with 63.5% of white blood cells expressing a SS immune phenotype. The conditioning regimen included 30 mg/m2 fludarabine on days -5, -4 and -3 and total body irradiation with 2 Gy on day -1. Immunosuppression consisted of cyclosporine A from day-1 and mycophenolate mofetil from day 0. The patient received 6.55x106 CD34+ cells and 1.11x108 CD3+ cells/kg body weight. Bone marrow evaluation on day 28 still showed persistent SS cells by flow cytometry. After tapering immunosuppression until day 169, the CD4:CD8 ratio in pb normalized. CR was documented on day 169 after alloHSCT and is now ongoing for almost 3 years after alloHSCT. Conclusions: We confirm that an alloHSCT can be a curative option for refractory patients with SS. The achievement of a CR after tapering the immunosuppressive therapy indicates a significant role of the GvL effect. In present treatment algorithms for patients with SS, the timing of an alloHSCT and the intensity of conditioning should be further explored

Relevance of field observations as boundary conditions for understanding ice-sheet-ocean interactions

The direct contact of warm ocean water with the front and base of ice shelves is the main driver for accelerated mass loss of the Antarctic ice sheet. We present a compilation of observations from various projects and methodological approaches applied over the last decade along the Dronning Maud Land coast and highlight their importance for understanding the ice-ocean interactions. With a focus on the Ekström ice shelf, these include spatially continuous seismic observations in combination with airborne gravity inversion to yield sub-shelf bathymetry and geomorphological evidence of past ice-flow activity; ice-dynamic numerical modelling to investigate the role of seafloor/subglacial substrate characteristics to enhance or reduce ice-sheet extent and advance/retreat rates; sub-shelf CTD measurements to determine ocean properties driving basal melting; satellitebased remote sensing to determine ice-shelf height changes and spatially-distributed basal melting; and point measurements of basal melt with surface-based phase-sensitive radar to determine ocean-driven melt and validate remote-sensing products. As the Dronning Maud Land coast plays a critical role in preconditioning the water mass of the coastal current before it enters the Filcher ice-shelf cavity, we argue that a coordinated inter- and transdisciplinary observational network is required to facilitate monitoring a potential ice-sheet mass loss in this part of Antarctica

A human in vitro neuronal model for studying homeostatic plasticity at the network level

Mechanisms that underlie homeostatic plasticity have been extensively investigated at single-cell levels in animal models, but are less well understood at the network level. Here, we used microelectrode arrays to characterize neuronal networks following induction of homeostatic plasticity in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons co-cultured with rat astrocytes. Chronic suppression of neuronal activity through tetrodotoxin (TTX) elicited a time-dependent network re-arrangement. Increased expression of AMPA receptors and the elongation of axon initial segments were associated with increased network excitability following TTX treatment. Transcriptomic profiling of TTX-treated neurons revealed up-regulated genes related to extracellular matrix organization, while down-regulated genes related to cell communication; also astrocytic gene expression was found altered. Overall, our study shows that hiPSC-derived neuronal networks provide a reliable in vitro platform to measure and characterize homeostatic plasticity at network and single-cell levels; this platform can be extended to investigate altered homeostatic plasticity in brain disorders.The work was supported by funding from the European Community’s Horizon 2020 Programme (H2020/2014–2020) under grant agreement no. 728018 (Eat2beNICE) (to B.F.); ERA-NET NEURON-102 SYNSCHIZ grant (NWO) 013-17-003 4538 (to D.S.); China Scholarship Council 201906100038 (to X.Y.); ISCIII /MINECO (PT17/0009/0019) and FEDER (to A.E.C.); and M.M. was supported by an internal grant from the Donders Centre for Medical Neurosciences of the Radboud University Medical Center

Salvage Therapy With Polatuzumab Vedotin, Bendamustine, and Rituximab Prior to Allogeneic Hematopoietic Transplantation in Patients With Aggressive Lymphomas Relapsing After Therapy With Chimeric Antigen Receptor T-Cells—Report on Two Cases

Up to 60% of patients with aggressive B-cell lymphoma who receive chimeric antigen receptor (CAR) T-cell therapy experience treatment failure and subsequently have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a potentially curative approach for patients in this situation. Induction of a deep response prior to alloHSCT is crucial for long-term outcomes, but the optimal bridging strategy following relapse after CAR T-cell therapy has not yet been established. Polatuzumab vedotin, an antibody drug conjugate targeting CD79b, is a novel treatment option for use in combination with rituximab and bendamustine (Pola-BR) in relapsed or refractory disease. Patients: We report two heavily pretreated patients with primary refractory diffuse large Bcell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) respectively who relapsed after therapy with CAR T-cells with both nodal and extranodal manifestations of the disease. After application of three courses of Pola-BR both patients achieved a complete metabolic remission. Both patients underwent alloHSCT from a human leukocyte antigen (HLA)-mismatched donor following conditioning with busulfan and fludarabine and are disease free 362 days and 195 days after alloHSCT respectively. We conclude that Pola-BR can be an effective bridging therapy before alloHSCT of patients relapsing after CAR T-cell therapy. Further studies will be necessary to define the depth and durability of remission of this salvage regimen before alloHSCT

On-ice Vibroseis: What lie beneath Ekström Ice Shelf, East Antarctica?

Between 2010-2018 an extensive grid of seismic reflection data were collected across the grounding line and on the Ekström ice-shelf, using an on-ice vibroseis source and snowstreamer. Here they are used to investigate current ice dynamics and reconstruct the glaciological history of this region. These data show the ice-shelf thickness ranges from 170 m, near the ice-shelf front, to ~600 m near the grounding line. Relic crevasses are seen at the ice base, in the Western part of the ice shelf, which can be tracked back to a current crevasse field at the grounding line. There is also evidence of an ice-shelf basal channel, with a corresponding surface depression. Beneath the sea floor the outcrop and sub-ice extent of the volcanic Explora Wedge (generated through Jurassic rifting and seafloor spreading) is clearly imaged. The wedge is overlain by a sequence of truncated, dipping marine-sediment layers. The sediment layers were likely truncated by former ice advance and subsequent retreat; which has also left evidence in the form topographic over-deepening and glacial debris deposits at the sea floor. The debris deposits range from elongated bedforms in a topographic trough (indicating probable former ice-stream flow) to layered sediment wedges at the current ice-shelf front (indicating the likely former extent of grounded ice). The vibroseis method is fast and effective allowing for a high volume of data collection. For example, in the 2016/17 season ~280 km of multi-fold seismic reflection data were collected over a 25-day period. Future integration of these results with numerical models will provide a better understanding of past and present interactions between the ice sheet and the solid Earth in Dronning Maud Land, which will in turn improve understanding of future contributions of this region to sea-level rise

Media ethnography

Contents Editorial Thematic Focus: Media Ethnography Media Ethnography and Participation in Online Practices / David Waldecker, Kathrin Englert, Wolfgang Ludwig-Mayerhofer, Oliver Schmidtke The Story is Everywhere. Dispersed Situations in a Literary Role Play Game / Wolfgang Reißmann Co-operation and/as Participant Observation: Reflections on Ethnographic Fieldwork in Morocco / Simon Holdermann Ethnomethodological Media Ethnography: Exploring Everyday Digital Practices in Families with Young Children / Clemens Eisenmann, Jan Peter, Erik Wittbusch Cooperation and Difference. Camera Ethnography in the Research Project ‘Early Childhood and Smartphone’ / Bina E. Mohn, Pip Hare, Astrid Vogelpohl, Jutta Wiesemann Reports Coordinations, or Computing is Work / Sebastian Gießman