Degradable emulsion-templated scaffolds for tissue engineering from thiol– ene photopolymerisation

Emulsion templating has been used to prepare highly porous polyHIPE materials by thiol–ene photoinitiated network formation. Commercially available multifunctional thiols and acrylates were formulated into water-in-oil high internal phase emulsions (HIPEs) using an appropriate surfactant, and the HIPEs were photo-cured. The temperature of the HIPE aqueous phase was found to influence the morphology of the resulting materials. In agreement with previous work, a higher aqueous phase temperature (80 °C) gave rise to a larger mean void and interconnect diameter. The influence of temperature on morphology was found to be reduced at higher porosity, but still significant. The Young's modulus of the porous materials was shown to be related to the functionality of the acrylate comonomer used. A mixture of penta- and hexa-acrylate gave rise to a 100-fold increase in modulus, compared to an analogous tri-functional acrylate. The materials could be functionalised conveniently by addition of mono-acrylates or thiols to the organic phase of the precursor HIPE. Degradation was observed to occur at a rate depending on the degradation conditions. Under cell culture conditions at 37 °C, 19% mass loss occurred over 15 weeks. The scaffolds were found to be capable of supporting the growth of keratinocytic cells (HaCaTs) over 11 days in culture. Some penetrative in-growth of the cells into the scaffold was observed

Soil bulk density sampling for neutron gauge calibration

The ASCE Task Committee on Neutron Gauge Calibration met in Logan, Utah in July 1992 to investigate the various methods of soil sampling, installation of access tubes, effect of various parameters on gauge readings, methods of developing field calibration curves and comparison of neutron gauge characteristics. Details of the overall objectives of the study are covered by Stone (1993, this volume). This paper discusses the soil sampling methods and presents a comparative result based on bulk density, time required for sampling and cost of sampling equipment Other papers developed from this study describe the soils, the three sites investigated and the problems related to the tube installation process

Vortices and dynamics in trapped Bose-Einstein condensates

I review the basic physics of ultracold dilute trapped atomic gases, with emphasis on Bose-Einstein condensation and quantized vortices. The hydrodynamic form of the Gross-Pitaevskii equation (a nonlinear Schr{\"o}dinger equation) illuminates the role of the density and the quantum-mechanical phase. One unique feature of these experimental systems is the opportunity to study the dynamics of vortices in real time, in contrast to typical experiments on superfluid $^4$He. I discuss three specific examples (precession of single vortices, motion of vortex dipoles, and Tkachenko oscillations of a vortex array). Other unusual features include the study of quantum turbulence and the behavior for rapid rotation, when the vortices form dense regular arrays. Ultimately, the system is predicted to make a quantum phase transition to various highly correlated many-body states (analogous to bosonic quantum Hall states) that are not superfluid and do not have condensate wave functions. At present, this transition remains elusive. Conceivably, laser-induced synthetic vector potentials can serve to reach this intriguing phase transition.Comment: Accepted for publication in Journal of Low Temperature Physics, conference proceedings: Symposia on Superfluids under Rotation (Lammi, Finland, April 2010

Pre-M Phase-promoting Factor Associates with Annulate Lamellae in Xenopus Oocytes and Egg Extracts

We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates

IMPlementation of an Online Relatives’ Toolkit for Psychosis or Bipolar (IMPART Study): Iterative Multiple Case Study to Identify Key Factors Impacting on Staff Uptake and Use

Background: Despite the potential of digital health interventions to improve the delivery of psychoeducation to people with mental health problems and their relatives, and substantial investment in their development, there is little evidence of successful implementation into clinical practice. We report the first implementation study of a digital health intervention: Relatives Education And Coping Toolkit (REACT), into routine mental healthcare. Our main aim was to identify critical factors affecting staff uptake and use of this online self-management tool for relatives of people with psychosis or bipolar. Methods: A mixed-methods, theory-driven (Normalisation Process Theory), iterative multiple case study approach using qualitative analysis of interviews with staff and quantitative reporting of uptake. Carer researchers were part of the research team. Results: In all, 281 staff and 159 relatives from Early Intervention teams across six catchment areas (cases) in England registered on REACT; 129 staff took part in qualitative interviews. Staff were positive about REACT helping services improve support and meet clinical targets. Implementation was hindered by: high staff caseloads and difficulties prioritising carers; perception of REACT implementation as research; technical difficulties using REACT; poor interoperability with trust computer systems and care pathways; lack of access to mobile technology and training; restricted forum populations; staff fears of risk, online trolling, and replacement by technology; and uncertainty around REACT’s long-term availability

An online supported self-management toolkit for relatives of people with psychosis or bipolar experiences: the IMPART multiple case study

Background Digital health interventions have the potential to improve the delivery of psychoeducation to people with mental health problems and their relatives. Despite substantial investment in the development of digital health interventions, successful implementation into routine clinical practice is rare. Objectives Use the implementation of the Relatives’ Education And Coping Toolkit (REACT) for psychosis/bipolar disorder to identify critical factors affecting uptake and use, and develop an implementation plan to support the delivery of REACT. Design This was an implementation study using a mixed-methods, theory-driven, multiple case study approach. A study-specific implementation theory for REACT based on normalisation process theory was developed and tested, and iterations of an implementation plan to address the key factors affecting implementation were developed. Setting Early-intervention teams in six NHS mental health trusts in England (three in the north and three in the south). Participants In total, 281 staff accounts and 159 relatives’ accounts were created, 129 staff and 23 relatives took part in qualitative interviews about their experiences, and 132 relatives provided demographic data, 56 provided baseline data, 21 provided data at 12 weeks’ follow-up and 20 provided data at 24 weeks’ follow-up. Interventions REACT is an online supported self-management toolkit, offering 12 evidence-based psychoeducation modules and support via a forum, and a confidential direct messaging service for relatives of people with psychosis or bipolar disorder. The implementation intervention was developed with staff and iteratively adapted to address identified barriers. Adaptations included modifications to the toolkit and how it was delivered by teams. Main outcome measures The main outcome was factors affecting implementation of REACT, assessed primarily through in-depth interviews with staff and relatives. We also assessed quantitative measures of delivery (staff accounts and relatives’ invitations), use of REACT (relatives’ logins and time spent on the website) and the impact of REACT [relatives’ distress (General Health Questionnaire-28), and carer well-being and support (Carer Well-being and Support Scale questionnaire)]. Results Staff and relatives were generally positive about the content of REACT, seeing it as a valuable resource that could help services improve support and meet clinical targets, but only within a comprehensive service that included face-to-face support, and with some additional content. Barriers to implementation included high staff caseloads and difficulties with prioritising supporting relatives; technical difficulties of using REACT; poor interoperability with trust information technology systems and care pathways; lack of access to mobile technology and information technology training; restricted forum populations leading to low levels of use; staff fears of managing risk, online trolling, or replacement by technology; and uncertainty around REACT’s long-term availability. There was no evidence that REACT would reduce staff time supporting relatives (which was already very low), and might increase it by facilitating communication. In all, 281 staff accounts were created, but only 57 staff sent relatives invitations. In total, 355 relatives’ invitations were sent to 310 unique relatives, leading to the creation of 159 relatives’ accounts. The mean number of logins for relatives was 3.78 (standard deviation 4.43), but with wide variation from 0 to 31 (median 2, interquartile range 1–8). The mean total time spent on the website was 40.6 minutes (standard deviation 54.54 minutes), with a range of 0–298 minutes (median 20.1 minutes, interquartile range 4.9–57.5 minutes). There was a pattern of declining mean scores for distress, social dysfunction, depression, anxiety and insomnia, and increases in relatives’ well-being and eHealth literacy, but no changes were statistically significant. Conclusions Digital health interventions, such as REACT, should be iteratively developed, evaluated, adapted and implemented, with staff and service user input, as part of a long-term strategy to develop integrated technology-enabled services. Implementation strategies must instil a sense of ownership for staff and ensure that they have adequate training, risk protocols and resources to deliver the technology. Cost-effectiveness and impact on workload and inequalities in accessing health care need further testing, along with the generalisability of our findings to other digital health interventions. Limitations REACT was offered by the same team running the IMPlementation of A Relatives’ Toolkit (IMPART) study, and was perceived by staff and relatives as a time-limited research study rather than ongoing clinical service, which affected engagement. Access to observational data was limited. Trial registration Current Controlled Trials ISRCTN16267685. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 37. See the NIHR Journals Library website for further project information

Signatures of the slow solar wind streams from active regions in the inner corona

Some of local sources of the slow solar wind can be associated with spectroscopically detected plasma outflows at edges of active regions accompanied with specific signatures in the inner corona. The EUV telescopes (e.g. SPIRIT/CORONAS-F, TESIS/CORONAS-Photon and SWAP/PROBA2) sometimes observed extended ray-like structures seen at the limb above active regions in 1MK iron emission lines and described as "coronal rays". To verify the relationship between coronal rays and plasma outflows, we analyze an isolated active region (AR) adjacent to small coronal hole (CH) observed by different EUV instruments in the end of July - beginning of August 2009. On August 1 EIS revealed in the AR two compact outflows with the Doppler velocities V =10-30 km/s accompanied with fan loops diverging from their regions. At the limb the ARCH interface region produced coronal rays observed by EUVI/STEREO-A on July 31 as well as by TESIS on August 7. The rays were co-aligned with open magnetic field lines expanded to the streamer stalks. Using the DEM analysis, it was found that the fan loops diverged from the outflow regions had the dominant temperature of ~1 MK, which is similar to that of the outgoing plasma streams. Parameters of the solar wind measured by STEREO-B, ACE, WIND, STEREO-A were conformed with identification of the ARCH as a source region at the Wang-Sheeley-Arge map of derived coronal holes for CR 2086. The results of the study support the suggestion that coronal rays can represent signatures of outflows from ARs propagating in the inner corona along open field lines into the heliosphere.Comment: Accepted for publication in Solar Physics; 31 Pages; 13 Figure

Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain

A population of >6 million people worldwide at high risk of Alzheimer’s disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome-21-gene BACE2, but prevented by combined chemical β and γ-secretase inhibition. We found that T21-organoids secrete increased proportions of Aβ-preventing (Aβ1-19) and Aβ-degradation products (Aβ1-20 and Aβ1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1-inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in ~30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases

Trends in the Statistical Assessment of Reliability

Changes in technology have had and will continue to have a strong effect on changes in the area of statistical assessment of reliability data. These changes include higher levels of integration in electronics, improvements in measurement technology and the deployment of sensors and smart chips into more products, dramatically improved computing power and storage technology, and the development of new, powerful statistical methods for graphics, inference, and experimental design and reliability test planning. This paper traces some of the history of the development of statistical methods for reliability assessment and makes some predictions about the future