Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration

Background: recent approaches have sought to harness the potential of stem cells to regenerate bone that is lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of osteoprogenitors for such applications. However, previous studies indicated that the concentration of osteoprogenitors present in BMA is less than required for robust bone regeneration. We provide further evidence for the importance of BMA enrichment for skeletal tissue engineering strategies using a novel acoustic wave-facilitated filtration strategy to concentrate BMA for osteoprogenitors, clinically applicable for intraoperative orthopedic use.Methods: femoral BMA from 15 patients of an elderly cohort was concentrated for the nucleated cell fraction against erythrocytes and excess plasma volume via size exclusion filtration facilitated by acoustic agitation. The effect of aspirate concentration was assessed by assays for colony formation, flow cytometry, multilineage differentiation and scaffold seeding efficiency.Results: BMA was filtered to achieve a mean 4.2-fold reduction in volume with a corresponding enrichment of viable and functional osteoprogenitors, indicated by flow cytometry and assays for colony formation. Enhanced osteogenic and chondrogenic differentiation was observed using concentrated aspirate and enhanced cell-seeding efficiency onto allogeneic bone graft as an effect of osteoprogenitor concentration relative specifically to the concentration of erythrocytes in the aspirate.Conclusions: these studies provide evidence for the importance of BMA nucleated cell concentration for both cell differentiation and cell seeding efficiency and demonstrate the potential of this approach for intraoperative application to enhance bone healin

Optical one-way quantum computing with a simulated valence-bond solid

One-way quantum computation proceeds by sequentially measuring individual spins (qubits) in an entangled many-spin resource state. It remains a challenge, however, to efficiently produce such resource states. Is it possible to reduce the task of generating these states to simply cooling a quantum many-body system to its ground state? Cluster states, the canonical resource for one-way quantum computing, do not naturally occur as ground states of physical systems. This led to a significant effort to identify alternative resource states that appear as ground states in spin lattices. An appealing candidate is a valence-bond-solid state described by Affleck, Kennedy, Lieb, and Tasaki (AKLT). It is the unique, gapped ground state for a two-body Hamiltonian on a spin-1 chain, and can be used as a resource for one-way quantum computing. Here, we experimentally generate a photonic AKLT state and use it to implement single-qubit quantum logic gates.Comment: 11 pages, 4 figures, 8 tables - added one referenc

Internet-based cognitive and behavioural therapies for post-traumatic stress disorder (PTSD) in adults

Background Therapist‐delivered trauma‐focused psychological therapies are effective for post‐traumatic stress disorder (PTSD) and have become the accepted first‐line treatments. Despite the established evidence‐base for these therapies, they are not always widely available or accessible. Many barriers limit treatment uptake, such as the number of qualified therapists available to deliver the interventions; cost; and compliance issues, such as time off work, childcare, and transportation, associated with the need to attend weekly appointments. Delivering Internet‐based cognitive and behavioural therapy (I‐C/BT) is an effective and acceptable alternative to therapist‐delivered treatments for anxiety and depression. Objectives To assess the effects of I‐C/BT for PTSD in adults. Search methods We searched MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials to June 2020. We also searched online clinical trial registries and reference lists of included studies and contacted the authors of included studies and other researchers in the field to identify additional and ongoing studies. Selection criteria We searched for RCTs of I‐C/BT compared to face‐to‐face or Internet‐based psychological treatment, psychoeducation, wait list, or care as usual. We included studies of adults (aged over 16 years), in which at least 70% of the participants met the diagnostic criteria for PTSD, according to the Diagnostic and Statistical Manual (DSM) or the International Classification of Diseases (ICD). Data collection and analysis Two review authors independently assessed abstracts, extracted data, and entered data into Review Manager 5. The primary outcomes were severity of PTSD symptoms and dropouts. Secondary outcomes included diagnosis of PTSD after treatment, severity of depressive and anxiety symptoms, cost‐effectiveness, adverse events, treatment acceptability, and quality of life. We analysed categorical outcomes as risk ratios (RRs), and continuous outcomes as mean differences (MD) or standardised mean differences (SMDs), with 95% confidence intervals (CI). We pooled data using a fixed‐effect meta‐analysis, except where heterogeneity was present, in which case we used a random‐effects model. We independently assessed the included studies for risk of bias and we evaluated the certainty of available evidence using the GRADE approach; we discussed any conflicts with at least one other review author, with the aim of reaching a unanimous decision

Undetected post-traumatic stress disorder in secondary-care mental health services:systematic review

Comorbid post-traumatic stress disorder (PTSD) is associated with poorer outcomes of other disorders, but is treatable. To estimate the frequency of clinically undetected PTSD in secondary care. A systematic review of studies that screened for PTSD and reported on PTSD documentation in clinical records. Frequency of undetected PTSD was estimated, and reasons for heterogeneity explored. The median proportion of participants with undetected PTSD (29 studies) was 28.6% (interquartile range 18.2–38.6%). There was substantial heterogeneity, with studies conducted in the USA and those with the highest proportions of in-patients and patients with psychotic disorder reporting higher frequencies of undetected PTSD. Undetected PTSD is common in secondary care, even if the true value is at the lower limit of the estimates reported here. Trials examining the impact of routine screening for PTSD are required to determine whether such programmes should be standard procedure for all mental health services

Biofabrication of nanocomposite-based scaffolds containing human bone extracellular matrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair. However, they fail to provide long-term clinical resolution, necessitating a functional biomimetic tissue engineering alternative. The use of native human bone tissue for synthesizing a biomimetic material ink for three-dimensional (3D) bioprinting of skeletal tissue is an attractive strategy for tissue regeneration. Thus, human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. In this study, we engineered a novel material ink (LAB) by blending human bone-ECM (B) with nanoclay (L, Laponite® ) and alginate (A) polymers using extrusion-based deposition. The inclusion of the nanofiller and polymeric material increased the rheology, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane (CAM) model. The inclusion of bone morphogenetic protein-2 (BMP-2) with the HBMSCs further enhanced vascularization and mineralization after only seven days. This study demonstrates the synergistic combination of nanoclay with biomimetic materials (alginate and bone- ECM) to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair

Evidence for a Mass Dependent Step-Change in the Scaling of Efficiency in Terrestrial Locomotion

A reanalysis of existing data suggests that the established tenet of increasing efficiency of transport with body size in terrestrial locomotion requires re-evaluation. Here, the statistical model that described the data best indicated a dichotomy between the data for small (<1 kg) and large animals (>1 kg). Within and between these two size groups there was no detectable difference in the scaling exponents (slopes) relating metabolic (Emet) and mechanical costs (Emech, CM) of locomotion to body mass (Mb). Therefore, no scaling of efficiency (Emech, CM/Emet) with Mb was evident within each size group. Small animals, however, appeared to be generally less efficient than larger animals (7% and 26% respectively). Consequently, it is possible that the relationship between efficiency and Mb is not continuous, but, rather, involves a step-change. This step-change in the efficiency of locomotion mirrors previous findings suggesting a postural cause for an apparent size dichotomy in the relationship between Emet and Mb. Currently data for Emech, CM is lacking, but the relationship between efficiency in terrestrial locomotion and Mb is likely to be determined by posture and kinematics rather than body size alone. Hence, scaling of efficiency is likely to be more complex than a simple linear relationship across body sizes. A homogenous study of the mechanical cost of terrestrial locomotion across a broad range of species, body sizes, and importantly locomotor postures is a priority for future research

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

De Novo Design of Functional Co-Assembling Organic-Inorganic Hydrogels for Hierarchical Mineralization and Neovascularization

Synthetic nanostructured materials incorporating both organic and inorganic components offer a unique, powerful and versatile class of materials for widespread applications due to the distinct, yet complementary, nature of the intrinsic properties of the different constituents. We report a supramolecular system based on synthetic nanoclay (Laponite™, Lap) and peptide amphiphiles (PAs, PAH3) rationally designed to co-assemble into nanostructured hydrogels with high structural integrity and a spectrum of bioactivities. Spectroscopic and scattering techniques and molecular dynamic simulation approaches were harnessedto confirm that PAH3 nanofibers electrostatically adsorbed and conformed to the surface of Lapnanodisks. Electron and atomic force microscopies also confirmed an increase in diameter and surface areaof PAH3nanofibers after co-assembly with Lap. Dynamic oscillatory rheology revealed that the co-assembled PAH3-Laphydrogels displayed high stiffness and robust self-healing behaviour while gas adsorption analysis confirmed a hierarchical and heterogeneous porosity. Furthermore, this distinctive structure within the three-dimensional matrix(3D) provided spatial confinement for the nucleation and hierarchical organization of high-aspect ratio hydroxyapatite nanorods into well-defined spherical clusters within the 3Dmatrix. Applicability of the organic-inorganic PAH3-Laphydrogels was assessed in vitrousing human bone marrow-derived stromal cells(hBMSCs) and ex vivousing a chick chorioallantoic membrane (CAM) assay. The results demonstrated that the organic-inorganic PAH3-Laphydrogels promote human skeletal cell proliferation and, upon mineralization, integrate with the CAM, are infiltrated by blood vessels, stimulate extracellular matrix production, and facilitate extensive mineral deposition relative to the controls