Bott--Kitaev periodic table and index theory

We consider topological insulators and superconductors with discrete symmetries and clarify the relevant index theory behind the periodic table proposed by Kitaev. An effective Hamiltonian determines the analytical index, which can be computed by a topological index. We focus on the spatial dimensions one, two and three, and only consider the bulk theory. In two dimensions, the $\mathbb{Z}$-valued invariants are given by the first Chern number. Meanwhile, $\mathbb{Z}_2$-valued invariants can be computed by the odd topological index and its variations. The Bott-Kitaev periodic table is well-known in the physics literature, we organize the topological invariants in the framework of KR-theory.Comment: 37 page

Existing and Evolving Bioethical Dilemmas, Challenges, and Controversies in Vascularized Composite Allotransplantation: An International Perspective From the Brocher Bioethics Working Group

Early results of hand and face transplants and other grafts such as those of uterus, penis, trachea, larynx, or abdominal wall have confirmed the potential for vascularized composite allotransplantation (VCA) to restore appearance, anatomy, function, independence, and social integration in patients suffering from devastating tissue deficits untreatable by conventional treatment options. Despite such promise, these novel and complex procedures face challenges and controversies that remain open to discussion and debate. Indeed, many barriers to clinical advancement and negative stakeholder perceptions still exist. The bioethical challenges surrounding VCA include but are not limited to justice and vulnerability of subjects, and their experiences with risks, benefits and outcomes, provider economy of fame, public awareness and attitudes toward transplantation, and policy and regulatory issues shaping progress of the field. The First International Workshop on Bioethical Challenges in Reconstructive Transplantation was organized by the Brocher Foundation in Hermance, Switzerland. VCA professionals representing teams from across the world examined bioethical issues in VCA related to standards for safety, efficacy, feasibility, privacy, confidentiality, and equitability. Key discussion topics from the workshop were included in a survey questionnaire implemented across VCA professionals attending the 13th Congress of International Society of VCA held in Salzburg, Austria. The insights from the Brocher workshop and International Society of VCA survey as presented here could help inform the future development of clinical practice and policy strategies in VCA to ensure value, accessibility, and acceptance of these procedures by potential donors, potential or actual recipients and their families, and providers and payers

Sensorimotor neural plasticity following hand transplantation measured with magnetoencephalography: A case study

This is a single case study that investigated brain connectivity (coherence) using Magnetoencephalography (MEG) in a twenty-four-year-old male who underwent hand transplantation of his right hand at 18 months after a traumatic injury. We examined the neuromagnetic fields of the whole brain during resting state. There is little research on brain reorganization and connectivity within the brain following transplantation, specifically, during resting state. Our findings revealed increased coherence within sensory cortices of the Default Mode Network (DMN) during the early phase of recovery while enhanced coherence in motor cortical regions became apparent in the later phase of recovery

The Role of Imaging in Patient Selection, Preoperative Planning, and Postoperative Monitoring in Human Upper Extremity Allotransplantation

Objective. To describe the role of imaging in vascular composite allotransplantation based on one institution’s experience with upper extremity allotransplant patients. Methods. The institutional review board approved this review of HIPAA-compliant patient data without the need for individual consent. A retrospective review was performed of imaging from 2008 to 2011 on individuals undergoing upper extremity transplantation. This demonstrated that, of the 19 patients initially considered, 5 patients with a mean age of 37 underwent transplantation. Reports were correlated clinically to delineate which preoperative factors lead to patient selection versus disqualification and what concerns dictated postoperative imaging. Findings were subdivided into musculoskeletal and vascular imaging criterion. Results. Within the screening phase, musculoskeletal exclusion criterion included severe shoulder arthropathy, poor native bone integrity, and marked muscular atrophy. Vascular exclusion criterion included loss of sufficient arterial or venous supply and significant distortion of the native vascular architecture. Postoperative imaging was used to document healing and hardware integrity. Postsurgical angiography and ultrasound were used to monitor for endothelial proliferation or thrombosis as signs of rejection and vascular complication. Conclusion. Multimodality imaging is an integral component of vascular composite allotransplantation surgical planning and surveillance to maximize returning form and functionality while minimizing possible complications

Characteristics and Immunomodulating Functions of Adipose-Derived and Bone Marrow-Derived Mesenchymal Stem Cells Across Defined Human Leukocyte Antigen Barriers

BackgroundVascularized composite allotransplantation opens new possibilities in reconstructive transplantation such as hand or face transplants. Lifelong immunosuppression and its side-effects are the main drawbacks of this procedure. Mesenchymal stem cells (MSCs) have clinically useful immunomodulatory effects and may be able to reduce the burden of chronic immunosuppression. Herein, we assess and compare characteristics and immunomodulatory capacities of bone marrow- and adipose tissue-derived MSCs isolated from the same human individual across defined human leukocyte antigen (HLA) barriers.Materials and methodsSamples of omental (o.) adipose tissue, subcutaneous (s.c.) adipose tissue, and bone marrow aspirate from 10 human organ donors were retrieved and MSCs isolated. Cells were characterized by flow cytometry and differentiated in three lineages: adipogenic, osteogenic, and chondrogenic. In mixed lymphocyte reactions, the ability of adipose-derived mesenchymal stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (BMSCs) to suppress the immune response was assessed and compared within individual donors. HLA mismatched or mitogen stimulations were analyzed in co-culture with different MSC concentrations. Supernatants were analyzed for cytokine contents.ResultsAll cell types, s.c.ASC, o.ASC, and BMSC demonstrated individual differentiation potential and cell surface markers. Immunomodulating effects were dependent on dose and cell passage. Proliferation of responder cells was most effectively suppressed by s.c.ASCs and combination with BMSC resulted in highly efficient immunomodulation. Immunomodulation was not cell contact-dependent and cells demonstrated a specific cytokine secretion.ConclusionWhen human ASCs and BMSCs are isolated from the same individual, both show effective immunomodulation across defined HLA barriers in vitro. We demonstrate a synergistic effect when cells from the same biologic system were combined. This cell contact-independent function underlines the potential of clinical systemic application of MSCs

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

PURPOSE OF REVIEW Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. RECENT FINDINGS Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SUMMARY Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA

Emerging Implications for Extracellular Matrix-Based Technologies in Vascularized Composite Allotransplantation

Despite recent progress in vascularized composite allotransplantation (VCA), limitations including complex, high dose immunosuppression regimens, lifelong risk of toxicity from immunosuppressants, acute and most critically chronic graft rejection, and suboptimal nerve regeneration remain particularly challenging obstacles restricting clinical progress. When properly configured, customized, and implemented, biomaterials derived from the extracellular matrix (ECM) retain bioactive molecules and immunomodulatory properties that can promote stem cell migration, proliferation and differentiation, and constructive functional tissue remodeling. The present paper reviews the emerging implications of ECM-based technologies in VCA, including local immunomodulation, tissue repair, nerve regeneration, minimally invasive graft targeted drug delivery, stem cell transplantation, and other donor graft manipulation

Hand Allotransplantation

In the past decade, more than 100 different composite tissue allotransplantation (CTA) procedures have been performed around the world including more than 50 hand and 8 facial transplants with encouraging graft survival and excellent functional outcomes. Broader clinical application of CTA, however, continues to be hampered by requirement for long-term, high-dose, multidrug maintenance immunosuppression to prevent graft rejection mediated particularly by composite tissue allograft's highly immunogenic skin component. Medication toxicity could result in severe adverse events including metabolic and infectious complications or malignancy. Notably, unlike in solid organs, clinical success is dictated not only by graft acceptance and survival but also by nerve regeneration, which determines ultimate functional outcomes. Novel strategies such as cellular and biologic therapies that integrate the concepts of immune regulation with those of nerve regeneration have shown promising results in small and large animal models. Clinical translation of these insights to reconstructive transplantation and CTA could further minimize the need of immunosuppression and optimize functional outcomes. This will enable wider application of such treatment options for patients in need of complex reconstructive surgery for congenital deformities or devastating injuries that are not amenable to standard methods of repair