Understanding the impact of coatings on the friction performance of carbon fibre ceramic composite brakes

In the railway industry, and premium luxury and super sports sectors of the automotive industry, traditional cast iron brake discs are gradually being replaced with advanced composites such as carbon fibre reinforced carbon silicon carbide (Cf/C-SiC). These materials offer the ability to operate at higher temperatures, whilst displaying improved friction performance, and vastly reduced wear rates. Their primary benefit comes from being approximately one third of the density of the incumbent material used in the industry, grey cast iron (GCI), a cast iron with a high proportion of graphite flakes formed during solidification. This reduced density means that brake discs manufactured from Cf/C-SiC materials are a highly suitable proposition for a future automotive market, where weight saving in an attempt to meet ever restrictive CO2 emissions is a must. The understanding surrounding the friction mechanisms involved with these new materials has been lacking, until recently, with the majority of the international research focused on the manufacturing methods. Research has shown that friction performance, particularly bedding friction, is highly dependent on the successful formation of a friction transfer film (FTF) at the surface of any disc, comprised from wear debris from both the disc and pad. Prior research carried out at Loughborough University has identified that Cf/C-SiC materials do not readily form such a layer, as might be seen on a GCI equivalent, due to the intrinsically heterogeneous nature of the composite material. [Continues.

Application of Active Learning Strategies for Online Delivery in an Occupational Therapy Assistant Program

The COVID-19 pandemic had a significant impact worldwide in every aspect of society including occupational therapy assistant students enrolled in academic coursework. This manuscript examines the unique experience of occupational therapy assistant faculty in a northeast state who were able to quickly modify classroom and lab teaching-learning strategies to a fully online virtual format for two semesters. Since no available information on strategies for online delivery of occupational therapy assistant education were found in the literature, their experiences implementing active learning strategies are described and discussed. Strategies covered include: the flipped classroom model; think-pair-share and jigsaw technique using breakout rooms; polling and student response systems; muddiest point via chat box; lab kits; one-minute paper using discussion forums; and student-generated videos. Twenty students provided feedback through a survey about the helpfulness of each strategy. The breakout room and chat box feature of the synchronous virtual classroom as well as lab kits were perceived as most helpful, whereas student-generated videos and one-minute papers were perceived as least helpful. Implications for continued incorporation of online learning in occupational therapy assistant curricula are outlined

Faculty-Led Virtual Level 1 Community Fieldwork during the COVID-19 Pandemic

Fieldwork is an integral portion of occupational therapy education that ensures students have the opportunity to develop basic competencies in real world practice settings. The national shortage of fieldwork placements, particularly in the area of mental health, in combination with the COVID-19 pandemic, have led to the adoption of increasingly innovative fieldwork models. This retrospective, qualitative study investigates occupational therapy assistant students’ experiences of completing a faculty-led (i.e. where faculty served as the primary fieldwork educator) and virtual (i.e., where services were offered in a virtual environment) Level I fieldwork with a community-based peer led behavioral health agency. Twenty-three students completed a confidential survey describing their experiences in Fall 2020. A secondary analysis of students’ responses was performed using principles of thematic analysis, which yielded results centered on four themes: knowledge, skills, attitudes, and structure. Subcategories highlighted growth across multiple areas including knowledge of occupational therapy’s role in mental health, interpersonal skills, and use of technology and other resources. Students’ preconceived notions of individuals with mental illness were challenged and many reported increased confidence in their abilities to work with these individuals. Both positive and constructive feedback were provided regarding the overall virtual fieldwork experience. The faculty-led virtual fieldwork model was viable in supporting occupational therapy assistant students’ skills to engage people with mental health and substance use challenges in a community setting. The potential use of this model is discussed in light of the anticipated increase of behavioral health problems for many across the lifespan post-COVID-19 pandemic

Evaluating the real-world implementation of the Family Nurse Partnership in England: protocol for a data linkage study.

INTRODUCTION: Almost 20 000 babies are born to teenage mothers each year in England, with poorer outcomes for mothers and babies than among older mothers. A nurse home visitation programme in the USA was found to improve a wide range of outcomes for young mothers and their children. However, a randomised controlled trial in England found no effect on short-term primary outcomes, although cognitive development up to age 2 showed improvement. Our study will use linked routinely collected health, education and social care data to evaluate the real-world effects of the Family Nurse Partnership (FNP) on child outcomes up to age 7, with a focus on identifying whether the FNP works better for particular groups of families, thereby informing programme targeting and resource allocation. METHODS AND ANALYSIS: We will construct a retrospective cohort of all women aged 13-24 years giving birth in English NHS hospitals between 2010 and 2017, linking information on mothers and children from FNP programme data, Hospital Episodes Statistics and the National Pupil Database. To assess the effectiveness of FNP, we will compare outcomes for eligible mothers ever and never enrolled in FNP, and their children, using two analysis strategies to adjust for measured confounding: propensity score matching and analyses adjusting for maternal characteristics up to enrolment/28 weeks gestation. Outcomes of interest include early childhood development, childhood unplanned hospital admissions for injury or maltreatment-related diagnoses and children in care. Subgroup analyses will determine whether the effect of FNP varied according to maternal characteristics (eg, age and education). ETHICS AND DISSEMINATION: The Nottingham Research Ethics Committee approved this study. Mothers participating in FNP were supportive of our planned research. Results will inform policy-makers for targeting home visiting programmes. Methodological findings on the accuracy and reliability of cross-sectoral data linkage will be of interest to researchers

Re-thinking and re-positioning ‘being in the moment’ within a continuum of moments : introducing a new conceptual framework for dementia studies

This article draws upon six social research studies completed by members of the Dementia and Ageing Research Team at The University of Manchester and their associated networks over an eight-year period [2011-2019] with the aim of constructing a definition of ‘being in the moment’ and situating it within a continuum of moments that could be used to contextualise and frame the lived experience of dementia. Using the approach formulated by Pound et al.(2005) to synthesising qualitative studies, we identified this continuum of moments as comprising four sequential and inter-linked steps: i) ‘Creating the moment’, defined as the processes and procedures necessary to enable being in the moment to take place. The time necessary for this to occur can range from fleeting to prolonged; ii) ‘Being in the moment’, which refers to the multi-sensory processes involved in a personal or relational interaction and embodied engagement. Being in the moment can be sustained through creativity and flow; iii) ‘Ending the moment’, defined as when a specific moment is disengaged. This can be triggered by the person(s) involved consciously or subconsciously, or caused by a distraction in the environment or suchlike; and iv) ‘Reliving the moment’, which refers to the opportunity for the experience(s) involved in ‘being in the moment’ to be later remembered and shared, however fragmentary, supported or full the recall

Redefining the Expression and Function of the Inhibitor of Differentiation 1 in Mammary Gland Development

The accumulation of poorly differentiated cells is a hallmark of breast neoplasia and progression. Thus an understanding of the factors controlling mammary differentiation is critical to a proper understanding of breast tumourigenesis. The Inhibitor of Differentiation 1 (Id1) protein has well documented roles in the control of mammary epithelial differentiation and proliferation in vitro and breast cancer progression in vivo. However, it has not been determined whether Id1 expression is sufficient for the inhibition of mammary epithelial differentiation or the promotion of neoplastic transformation in vivo. We now show that Id1 is not commonly expressed by the luminal mammary epithelia, as previously reported. Generation and analysis of a transgenic mouse model of Id1 overexpression in the mammary gland reveals that Id1 is insufficient for neoplastic progression in virgin animals or to prevent terminal differentiation of the luminal epithelia during pregnancy and lactation. Together, these data demonstrate that there is no luminal cell-autonomous role for Id1 in mammary epithelial cell fate determination, ductal morphogenesis and terminal differentiation

The personal benefits of musicking for people living with dementia:a thematic synthesis of the qualitative literature

This review aimed to explore the psychological, social and emotional benefits of music activities for people living with dementia through a systematic review of qualitative literature. Eighteen studies were identified that covered a wide range of music programmes for people with dementia, with the majority of programmes focusing on active musical participation. A thematic synthesis revealed four key benefits of music engagement for people with dementia, namely: Taking Part, Being Connected, Affirming Identity and Immersion “in the moment”. Overall, engaging with music was seen to have a number of psychological, social and emotional benefits for people with dementia. However, only seven studies actively included people with dementia in the research process. Going forward, it would appear essential that people with dementia are encouraged to take a more active role in research exploring musical experiences and that a heightened emphasis is placed upon participatory approaches to knowledge generation. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group

Cyclic adenosine 5′-diphosphate ribose analogs without a southern ribose inhibit ADP-ribosyl cyclase-hydrolase CD38

Cyclic adenosine 5′-diphosphate ribose (cADPR) analogs based on the cyclic inosine 5′-diphosphate ribose (cIDPR) template were synthesized by recently developed stereo- and regioselective <i>N</i>1-ribosylation. Replacing the base <i>N</i>9-ribose with a butyl chain generates inhibitors of cADPR hydrolysis by the human ADP-ribosyl cyclase CD38 catalytic domain (shCD38), illustrating the nonessential nature of the “southern” ribose for binding. Butyl substitution generally improves potency relative to the parent cIDPRs, and 8-amino-<i>N</i>9-butyl-cIDPR is comparable to the best noncovalent CD38 inhibitors to date (IC₅₀ = 3.3 μM). Crystallographic analysis of the shCD38:8-amino-<i>N</i>9-butyl-cIDPR complex to a 2.05 Å resolution unexpectedly reveals an <i>N</i>1-hydrolyzed ligand in the active site, suggesting that it is the <i>N</i>6-imino form of cADPR that is hydrolyzed by CD38. While HPLC studies confirm ligand cleavage at very high protein concentrations, they indicate that hydrolysis does not occur under physiological concentrations. Taken together, these analogs confirm that the “northern” ribose is critical for CD38 activity and inhibition, provide new insight into the mechanism of cADPR hydrolysis by CD38, and may aid future inhibitor design

ELF5 modulates the estrogen receptor cistrome in breast cancer.

Acquired resistance to endocrine therapy is responsible for half of the therapeutic failures in the treatment of breast cancer. Recent findings have implicated increased expression of the ETS transcription factor ELF5 as a potential modulator of estrogen action and driver of endocrine resistance, and here we provide the first insight into the mechanisms by which ELF5 modulates estrogen sensitivity. Using chromatin immunoprecipitation sequencing we found that ELF5 binding overlapped with FOXA1 and ER at super enhancers, enhancers and promoters, and when elevated, caused FOXA1 and ER to bind to new regions of the genome, in a pattern that replicated the alterations to the ER/FOXA1 cistrome caused by the acquisition of resistance to endocrine therapy. RNA sequencing demonstrated that these changes altered estrogen-driven patterns of gene expression, the expression of ER transcription-complex members, and 6 genes known to be involved in driving the acquisition of endocrine resistance. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, and proximity ligation assays, we found that ELF5 interacted physically with members of the ER transcription complex, such as DNA-PKcs. We found 2 cases of endocrine-resistant brain metastases where ELF5 levels were greatly increased and ELF5 patterns of gene expression were enriched, compared to the matched primary tumour. Thus ELF5 alters ER-driven gene expression by modulating the ER/FOXA1 cistrome, by interacting with it, and by modulating the expression of members of the ER transcriptional complex, providing multiple mechanisms by which ELF5 can drive endocrine resistance

'Click cyclic ADP-ribose':A neutral second messenger mimic

Analogues of the potent Ca(2+) releasing second messenger cyclic ADP-ribose (cADPR) with a 1,2,3-triazole pyrophosphate bioisostere were synthesised by click-mediated macrocyclisation. The ability to activate Ca(2+) release was surprisingly retained, and hydrolysis of cADPR by CD38 could also be inhibited, illustrating the potential of this approach to design drug-like signalling pathway modulators