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Background The mixture of different metallic nanoparticles released from intended and unintended wearing of orthopaedic implants such as the Co/Cr cup and head, Co/Cr sleeves or tapers and their interface with Ti stems in the case of hip prostheses are a leading cause of adverse inflammatory responses and cytotoxicity to the host. Methods This study assessed the in vitro cytotoxic effects of three metallic nanoparticles (Co, Cr and Ti) separately and in combination on macrophages. The in vivo effects were also evaluated after peri-tibial soft tissue injection in mice. Results The results demonstrated that Co, Cr, and Ti nanoparticles and their combination were phagocytosed by macrophages both in vitro and in vivo. High doses of nanoparticles from each individual metal caused a variable rate of cell death in vitro. However, the mixture of Co/Cr/Ti nanoparticles was more toxic than the Co, Cr or Ti metals alone at low doses. Intracellular distribution of Co, Cr, and Ti in the combined group was heterogeneous and associated with distinct morphological features. The results from in vivo experiments showed a significant increase in the mRNA levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α in peri-tibial soft tissue following the administration of Co alone as well as the combination of nanoparticles. Conclusion This study demonstrated that the combination of Co/Cr/Ti nanoparticles was more cytotoxic than any of the individual metals in vitro and induced higher expression of genes encoding pro-inflammatory cytokines than single metals in vivo. The in vivo model utilised in this study might provide a useful tool for rapid assessment of the effects of unintended release of metal nanoparticles from implants in pre-/post-marketing studies. Translational potential of this article This study highlights the importance of preclinical assessments of potential nanoparticles produced by wear and tear of metal implants using macrophages and animal models, in particular their combinational toxicity in addition to the assessments of the bulk metallic materials.
This systematic review is part of a broader evidence synthesis which aims to produce two systematic reviews to address a significant gap in the evidence base identified by Luchenski et al. (2018) and by (White, 2018). The first review (which is the subject of this protocol) will use meta‐analysis to examine the effectiveness of different psychosocial interventions in (1) reducing problematic substance use; (2) improving mental health; and (3) improving housing stability for adults experiencing homelessness. The second review (which is covered by a separate title registration and protocol) will be of the experiences of adults experiencing homelessness when accessing or using psychosocial interventions, and will be a qualitative evidence synthesis using thematic synthesis (Thomas & Harden, 2008).
Background Understanding and improving access to essential services in (post)-conflict settings requires paying particular attention to the actors who occupy the space left ‘empty’ by weak or deficient State institutions. Religious institutions often play a fundamental role among these actors and typically benefit from high trust capital, a rare resource in so-called ‘fragile’ states. While there is a literature looking at the role faith organisations play to mobilise and sensitise communities during emergencies, our focus is on a different dimension: the reconfiguration of the relationship between religion and health authorities impelled by health crises. Methods We analyse observations, interviews, and focus group discussions with 21 leaders from eight different religious groups in Ituri province in 2020–2021. Results Faith institutions handled the Covid-19 lockdown period by using and redeploying structures at the grassroots level but also by responding to health authorities’ call for support. New actors usually not associated with the health system, such as revivalist churches, became involved. The interviewed religious leaders, especially those whose congregations were not previously involved in healthcare provision, felt that they were doing a favour to the State and the health authorities by engaging in community-level awareness-raising, but also, crucially, by ‘depoliticising’ Covid-19 through their public commitment against Covid-19 and work with the authorities in a context where the public response to epidemics has been highly contentious in recent years (particularly during the Ebola outbreak). The closure of places of worship during the lockdown shocked all faith leaders but, ultimately, most were inclined to follow and support health authorities. Such experience was, however, often one of frustration and of feeling unheard. Conclusion In the short run, depoliticization may help address health emergencies, but in the longer run and in the absence of a credible space for discussion, it may affect the constructive criticism of health system responses and health system strengthening. The faith leaders are putting forward the desire for a relationship that is not just subordination of the religious to the imperatives of health care but a dialogue that allows the experiences of the faithful in conflict zones to be brought to the fore.
Child maltreatment has detrimental social and health effects for individuals, families and communities. The ERICA project is a pan-European training programme that equips non-specialist threshold practitioners with knowledge and skills to prevent and detect child maltreatment. This paper describes and presents the findings of a rapid review of good practice examples across seven participating countries including local services, programmes and risk assessment tools used in the detection and prevention of child maltreatment in the family. Learning was applied to the development of the generic training project. A template for mapping the good practice examples was collaboratively developed by the seven participating partner countries. A descriptive data analysis was undertaken organised by an a priori analysis framework. Examples were organised into three areas: programmes tackling child abuse and neglect, local practices in assessment and referral, risk assessment tools. Key findings were identified using a thematic approach. Seventy-two good practice examples were identified and categorised according to area, subcategory and number. A typology was developed as follows: legislative frameworks, child health promotion programmes, national guidance on child maltreatment, local practice guidance, risk assessment tools, local support services, early intervention programmes, telephone or internet-based support services, COVID-19 related good practices. Improved integration of guidance into practice and professional training in child development were highlighted as overarching needs. The impact of COVID-19 on safeguarding issues was apparent. The ERICA training programme formally responded to the learning identified in this international good practice review.
Improved accessibility to the microkelvin temperature regime is important for future research in quantum materials, for quantum information science, and for applications of quantum sensors. Here, we report the design and performance of a microkelvin platform based on a nuclear-demagnetization stage, engineered and well optimized for operation on a standard cryogen-free dilution refrigerator. PrNi5 is used as the dominant refrigerant. The platform provides a large area for mounting experiments in an ultralow-temperature low-electromagnetic-noise environment. The performance is characterized using current-sensing noise thermometry. Temperatures as low as 395μK are reached and a protocol is established in which it is possible to operate experiments below 1 mK for 95% of the time, providing an efficient cryogen-free microkelvin environment for a wide range of science applications.
This paper is a cross-comparative examination of how tropical forested islands were populated by humans. It first describes the unique ecological conditions of these environments, how they fluctuated during glacial cycles, and the challenges and affordances they provided people. The paper then explores the global archaeological record, classifying modes of colonisation that led insular tropical forests to be populated. These modes include terrestrial colo-nisation followed by insularisation (Mode A), maritime colonisation followed by major landmass reconfiguration (Mode B), maritime colonisation of uninhab-ited islands that always remained insular (Mode C), and maritime colonisation of already inhabited islands (Mode D). Finally, the paper discusses how, amongst Homo sapiens, ongoing dynamism between human adaptive behaviours and environmental flux stimulated processes of diversification, speciali-sation, and connectivity in these crucial ecologies; by contrast, archaic hominins like Homo erectus, Homo floresiensis, and Homo luzonensis may have found changes associated with forest expansion and insularity extremely challenging.
Comparison of Exodus 22.19 with the later legislation of Leviticus 20.15–16 raises a number of difficulties as to how the former text should be interpreted. It is suggested that this sole sexual crime in the Book of the Covenant was designed to prevent a physical union with Yahweh through intercourse with a sacrificial animal.
Light-induced microbial electron transfer has potential for efficient production of value-added chemicals, biofuels and biodegradable materials owing to diversified metabolic pathways. However, most microbes lack photoactive proteins and require synthetic photosensitizers that suffer from photocorrosion, photodegradation, cytotoxicity, and generation of photoexcited radicals that are harmful to cells, thus severely limiting the catalytic performance. Therefore, there is a pressing need for biocompatible photoconductive materials for efficient electronic interface between microbes and electrodes. Here we show that living biofilms of Geobacter sulfurreducens use nanowires of cytochrome OmcS as intrinsic photoconductors. Photoconductive atomic force microscopy shows up to 100-fold increase in photocurrent in purified individual nanowires. Photocurrents respond rapidly (<100 ms) to the excitation and persist reversibly for hours. Femtosecond transient absorption spectroscopy and quantum dynamics simulations reveal ultrafast (~200 fs) electron transfer between nanowire hemes upon photoexcitation, enhancing carrier density and mobility. Our work reveals a new class of natural photoconductors for whole-cell catalysis.
In this quarterly column, Helen Cowan sheds some light on the lesser known area of cardiac nursing in care homes, looking at nurse-led diagnosis and management of cardiac conditions.
MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> superconducting wires hold the advantage over traditional NbTi wires of higher temperature operation, at lower cost than high temperature superconductors, and allowing the use of existing winding techniques. The adoption of MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> wires into large-scale applications requires a robust production process yielding long length wires with consistent performance. Bekaert and Epoch wires have developed a scalable powder-in-tube technique capable of producing MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> wires in km lengths. Demonstrating practical current density in a solenoid coil is an essential step towards larger demonstration assemblies and coils, in wind-and-react or react-and-wind configurations. Here, we report on the performance of a compact wind-and-react solenoid coil wound from Bekaert/Epoch wires 1+6 MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> cable, made up of unstabilized, monocore 0.4 mm MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> wires. The coil was tested in a He-vapor cooled VTI inside a 10 T Cryofree magnet, between 10 K and 20 K, and at up to 3 T background field. The coil reached 384 A at 15 K in zero external field, generating a self-field of 1.88 T without quench. The coil was quenched multiple times without damage.
Homelessness is a major social and public health concern. It is a traumatic experience, and can have a devastating effect on those experiencing it. People who are homeless often face significant barriers when accessing public services, and those experiencing more visible and extreme forms of homelessness have often faced adverse childhood events, extreme social disadvantage, physical, emotional and sexual abuse, neglect, low self‐esteem, poor physical and mental health, and much lower life expectancy compared to the general population. Problematic substance use is disproportionately high amongst people experiencing homelessness, with many using drugs and alcohol to deal with the stress of living on the street, to keep warm, or to block out memories of previous abuse or trauma. Drug overdose is a major cause of death for people experiencing street homelessness. Substance dependency can also create barriers to successful transition to stable housing. There is ongoing policy interest in the effectiveness of different interventions that aim to stop, reduce or prevent problematic substance use, and there is specific interest in the relative effectiveness of interventions that adopt harm reduction or abstinence‐based approaches. The objective of this review is to understand the effectiveness of different substance use interventions. The review will consider the effectiveness of harm reduction‐based interventions, and abstinence‐based interventions, for adults experiencing homelessness. The focus of the review is on high‐income countries. The primary source of studies for potential inclusion in this review is the Homelessness Effectiveness Studies Evidence and Gaps Maps (EGM). The first of these was published in 2018, with updates published in 2019 and 2020. A further update is due to be published in the summer of 2022. It is this update that provides the final list of studies from which this review will draw. The search for this update (EGM 4th edition) was completed in September 2021. Other potential studies will be identified through a call for grey evidence and hand‐searching key journals. Eligible studies will be impact evaluations with designs at levels, 3, 4 and 5 of the Maryland Scientific Methods scale. This therefore includes all studies categorised as either ‘Randomised Controlled Trials’ or ‘nonexperimental designs with a comparison group’ from the studies which form the basis of the Homelessness Effectiveness Studies Evidence and Gap Maps (EGM) created by CHI and the Campbell Collaboration. We are interested in studies that examine the effect of interventions on substance use outcomes. Studies to be excluded are those with designs at levels 1 and 2 of the Maryland Scientific Methods scale, for example, studies without a control or comparison group, ‘before vs. after’ designs (without an untreated comparison group), and cross‐sectional regressions. Descriptive characteristics and statistical information in included studies will be coded and checked by at least two members of the review team. Studies selected for the review will be assessed for confidence in the findings using a critical appraisal tool for determining confidence in primary studies. Standardised effect sizes will be calculated and, if a study does not provide sufficient raw data for the calculation of an effect size, we will attempt to contact the author(s) to obtain this data. We will aim to use random‐effects meta‐analysis and robust‐variance estimation procedures to synthesise effect sizes. If a study includes multiple effects, we will carry out a critical assessment to determine (even if only theoretically) whether the effects are likely to be dependent. Where we suspect dependent effects, we will determine whether we can account for these by robust variance estimation. We will explore the moderating influence of participant and study characteristics, such as gender, race, substances targeted and length of follow‐up. Where effect sizes are converted from a binary to continuous measure (or vice versa), we will undertake a sensitivity analysis to investigate the effect of the inclusion of studies with a converted effect size in the meta‐analysis by running an additional analysis with these studies omitted. We will also assess the sensitivity of results to inclusion of non‐randomised studies and studies classified as low confidence in findings. All analyses will include an assessment of statistical heterogeneity. Finally, we will undertake analysis to assess whether publication bias is likely to be a factor in our findings.
Additive manufactured (AM) metal alloys normally exhibit very diverse grain size distributions. The size measured by electron backscatter diffraction (EBSD) is generally smaller than that from optical microscope (OM) due to better resolution, but proper scan setup must be chosen to reveal the existing fine grains. In this work, we compared these two widely applied techniques and investigated the effects of different parameters on the resulting average diameter d. Regarding the discrepancies of parameters in the literatures, a standard EBSD setup is suggested, so that > 99% of the total grain area should be detected. The grain distribution characteristics for AM fabricated alloys were also illustrated. A simply modified Hall-Petch equation is proposed by considering the grain size distributions using grains covering >99% of the measured area. It gives remarkable agreement between predicted strength and experimental values for almost all the AM alloy systems we tested, which possess very diverse grain size distributions. This revised model can extend to other AM alloys with heterogeneous microstructures and is very practical for engineering approach.
This richly illustrated and beautifully produced volume explores the role of Bohemian culture in late fourteenth-century England. John Gower wrote of the ‘newe guise of Beawme’ in his Confessio Amantis, and Alfred Thomas convincingly explores the wider implications of these influences. Richard II married Anne of Bohemia in 1382, and she died in 1394. Anne was the daughter of Charles IV, Holy Roman Emperor, who had been brought up at the French royal court and who transformed the court at Prague into a centre of art and architecture; her siblings were Elisabeth of Bohemia and Wenceslas IV of Bohemia (also of Germany and Luxembourg). Her grandfather was the cosmopolitan John, count of Luxembourg, king of Bohemia and patron of the poet Guillaume Machaut, and her aunt was Bonne of Luxembourg, who married the man who would become King John II of France; her uncle was the duke of Brabant and, famously, the patron of the poet and chronicler Jean Froissart. One could continue listing these cosmopolitan cultural connections for many lines. As presented here, Anne embodied a truly European culture, stretching from Bohemia to Germany to Italy and France. Thomas is principally interested here in the influence of the flourishing and cosmopolitan Bohemian court, the model of French courtly life, and the imperial connections. He argues that Anne embodied a set of cultural influences which were intertwined with Richard III’s wider political goals: he was interested in imperial claims, worked on the presentation of a form of sacral kingship, and was more interested in culture than war. These observations about Richard’s reign are insightful, though perhaps a little too starkly drawn: the claim that a king might be interested in culture rather than war (repeated for Charles V of France on p. 24) is unnecessarily reductive; Richard’s interest in sacral kingship also has a longer, distinctively English history. Reminding the reader that these were not zero-sum games would not in any way weaken the argument.
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