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IntroductionMost people living with dementia want to remain living in their own homes, and are supported to do so by family carers and homecare workers. There are concerns that homecare is often unable to meet the needs of this client group, with limited evidence regarding effective interventions to improve it for people living with dementia. We have developed a training and support programme for homecare workers (NIDUS-Professional) to be delivered alongside support sessions for people living with dementia and their family carers (NIDUS-Family). We aim to assess (1) its acceptability among homecare workers and employing agencies, and (2) the feasibility of homecare workers, people living with dementia and their family carers completing the outcomes of intervention in a future randomised controlled trial.Methods and analysisThis is a cluster-randomised (2:1) single-blind, multisite feasibility trial. We aim to recruit 60-90 homecare workers, 30-60 clients living with dementia and their family carers through 6-9 English homecare agencies. In the intervention arm, homecare staff will be offered six group sessions on video call over three months, followed by monthly group sessions over the subsequent three-month period. Outcome measures will be collected at baseline and at six months.Ethics and disseminationThe study received ethical approval on 7 January 2020 from the Camden & King's Cross Research Ethics Committee. Study reference: 19/LO/1667. Findings will be disseminated through a peer-reviewed journal, conference presentation and blog to research and clinical audiences; we will attend forums to present findings to participating homecare agencies and their clients.Trial registration numberISRCTN15757555.

Introduction This process evaluation was conducted in parallel to the randomised controlled feasibility trial of NIDUS-Professional, a manualised remote dementia training intervention for homecare workers (HCWs), delivered alongside an individualised intervention for clients living with dementia and their family carers (NIDUS-Family). The process evaluation reports on: (i) intervention reach, dose and fidelity; (ii) contexts influencing agency engagement and (iii) alignment of findings with theoretical assumptions about how the intervention might produce change. Methods We report proportions of eligible HCWs receiving any intervention (reach), number of sessions attended (dose; attending ≥4/6 main sessions was predefined as adhering), intervention fidelity and adherence of clients and carers to NIDUS-Family (attending all 6–8 planned sessions). We interviewed HCWs, managers, family carers and facilitators. We integrated and thematically analysed, at the homecare agency level, qualitative interview and intervention recording data. Results 32/141 (23%) of eligible HCWs and 7/42 (17%) of family carers received any intervention; most who did adhered to the intervention (89% and 71%). Intervention fidelity was high. We analysed interviews with 20/44 HCWs, 3/4 managers and 3/7 family carers, as well as intervention recordings involving 32/44 HCWs. All agencies reported structural challenges in supporting intervention delivery. Agencies with greater management buy-in had higher dose and reach. HCWs valued NIDUS-Professional for enabling group reflection and peer support, providing practical, actionable care strategies and increasing their confidence as practitioners. Conclusion NIDUS-Professional was valued by HCWs. Agency management, culture and priorities were key barriers to implementation; we discuss how to address these in a future trial. [ABSTRACT FROM AUTHOR]

Background: Self-management, autonomy, and quality of life are key constructs in enabling people to live well with dementia. This population often becomes isolated following diagnosis, but it is important for them to feel encouraged to maintain their daily activities and stay socially active. Promoting Independence in Dementia (PRIDE) fosters social inclusion and greater dementia self-management through an interactive handbook. Objective: This study aimed to develop a paper-based PRIDE manual on a web-based platform. Methods: Two overarching stages were used to create the web-based version of PRIDE. The first was Preliminary Development, which encompassed tendering, preliminary development work, consultations, beta version of the website, user testing and consultation on beta version, and production of the final web-based prototype. The second stage was Development of the Final PRIDE App, which included 2 sprints and further user testing. Results: Through a lengthy development process, modifications were made to app areas such as the log-in process, content layout, and aesthetic appearance. Feedback from the target population was incorporated into the process to achieve a dementia-friendly product. The finished PRIDE app has defined areas for reading dementia-related topics, creating activity plans, and logging these completed activities. Conclusions: The PRIDE app has evolved from its initial prototype into a more dementia-friendly and usable program that is suitable for further testing. The finished version will be tested in a reach, effectiveness, adoption, implementation, and maintenance study, with its potential reach, effectiveness, and adoption explored. Feedback gathered during the reach, effectiveness, adoption, implementation, and maintenance study will lead to any further developments in the app to increase its applicability to the target audience and usability. [ABSTRACT FROM AUTHOR]

Most people living with dementia want to continue living in their own home for as long as possible and many rely on support from homecare services to do so. There are concerns that homecare often fails to meet the needs of clients with dementia, but there is limited evidence regarding effective interventions to improve its delivery for this client group. We aimed to assess whether a co‐designed, 6‐session dementia training intervention for homecare workers (NIDUS‐professional) was acceptable and feasible. Facilitated training sessions were delivered over 3 months, followed by 3, monthly implementation meetings to embed changes in practice. Two trained and supervised facilitators without clinical qualifications delivered the intervention via group video‐calls during Oct 2020–March 2021 to a group of seven homecare workers from one agency in England. Participants provided qualitative feedback 3‐ and 6‐months post intervention. Qualitative interview data and facilitator notes were integrated in a thematic analysis. Adherence to the intervention and fidelity of delivery were high, indicating that it was acceptable and feasible to deliver in practice. Thirty of a possible 42 (71.4%) group sessions were attended. In our thematic analysis we report one over‐arching theme: 'Having time and space to reflect is a rare opportunity'. Within this we identified four subthemes (Having time to reflect is a rare opportunity; Reflecting with peers enhances learning; Reflection and perspective taking can improve care; Recognising skills and building confidence) through which we explored how participants valued the intervention to discuss their work and learn new skills. Attendance was lower for the implementation sessions, perhaps reflecting participants' lack of clarity about their purpose. We used our findings to consider how we can maintain positive impacts of the manualised sessions, so that these are translated into tangible, scalable benefits for people living with dementia and the homecare workforce. A randomised feasibility trial is underway. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.11.047 Byline: Catalina Ruiz-Canada (1), Daniel J. Kelleher (1), Reid Gilmore (1) Keywords: CELLBIO; PROTEINS Abstract: Asparagine-linked glycosylation of polypeptides in the lumen of the endoplasmic reticulum is catalyzed by the hetero-oligomeric oligosaccharyltransferase (OST). OST isoforms with different catalytic subunits (STT3A versus STT3B) and distinct enzymatic properties are coexpressed in mammalian cells. Using siRNA to achieve isoform-specific knockdowns, we show that the OST isoforms cooperate and act sequentially to mediate protein N-glycosylation. The STT3A OST isoform is primarily responsible for cotranslational glycosylation of the nascent polypeptide as it enters the lumen of the endoplasmic reticulum. The STT3B isoform is required for efficient cotranslational glycosylation of an acceptor site adjacent to the N-terminal signal sequence of a secreted protein. Unlike STT3A, STT3B efficiently mediates posttranslational glycosylation of a carboxyl-terminal glycosylation site in an unfolded protein. These distinct and complementary roles for the OST isoforms allow sequential scanning of polypeptides for acceptor sites to insure the maximal efficiency of N-glycosylation. Author Affiliation: (1) Department of Biochemistry and Molecular Pharmacology University of Massachusetts Medical School, Worcester, MA 01605, USA Article History: Received 23 June 2008; Revised 17 October 2008; Accepted 25 November 2008 Article Note: (miscellaneous) Published: January 22, 2009

Background and objectives: We engaged people living with dementia, family carers and health and social care professionals in co-designing two dementia care interventions: for family carers and people living with dementia (New Interventions for Independence in Dementia Study (NIDUS)-family and home-care workers (NIDUS-professional training programme). Research design and methods: Over October 2019–March 2020, we invited public and patient (PPI) and professional members of our NIDUS co-design groups to complete the PPI Engagement Evaluation Tool (designed to assess engagement activities), and non-professional PPI members to participate in qualitative telephone interviews. We thematically analysed and integrated mixed-methods findings. Results: Most (15/20; 75%) of the PPI members approached participated. We identified four themes: (1) Creating the right atmosphere: participants found group meetings positive and enabling, though one health professional was unsure how to position themselves within them; (2) Participants influencing the outcome: while most members felt that they had some influence, for one carer consultation seemed too late to influence; (3) Having the right information: several carers wanted greater clarity and more regular updates from researchers; (4) Unique challenges for people living with dementia: memory problems presented challenges in engaging with substantial information, and within a large group. Discussion and implications: We reflect on the importance of providing accessible, regular updates, managing power imbalances between co-design group members with lived and professional experiences; and ensuring needs and voices of people living with dementia are prioritised. We encourage future studies to incorporate evaluations of co-design processes into study design. [ABSTRACT FROM AUTHOR]

Research has been conducted on the oligosaccharyltransferase which utilizes the fully assembled dolichol-linked oligosaccharide. The proteoliposome assay system that consist of the purified yeast enzyme has been used in investigating the steady-state kinetic properties of the oligosaccharyltransferase and the results are described.

To examine the feasibility and acceptability of NIDUS-Family, a 6–8 session manualised, individually tailored, modular intervention supporting independence at home for people with dementia; and explore participants' and facilitators' experiences of the intervention. In this single group multi-site feasibility study, trained, supervised non-clinically qualified graduates (facilitators) delivered NIDUS-Family to family carer and people living with dementia dyads. We recruited participants from GP practices and memory services in London and Bradford. We completed quantitative outcomes pre- and post-intervention; and conducted qualitative interviews with participants and facilitators. Our pre-specified main outcomes were proportion of potential participants approached who agreed to participate, intervention adherence and acceptability to family carers, and facilitator fidelity to the manual. We recruited 16 dyads (57% of those approached); 12 (75%) completed the intervention. Of 12 participants rating intervention acceptability, 9 (75%) agreed or strongly agreed that it had helped; 2 (18%) neither agreed nor disagreed and 1 (8%) disagreed. Mean facilitator fidelity was high (81.5%). Dyads set on average 3.9 goals; these most commonly related to getting out and about and increasing activity/hobby participation (n = 10); carer wellbeing (n = 6), managing physical complaints (n = 6); meal preparation/cooking (n = 5); and reducing irritability, frustration or aggression (n = 5). Almost all secondary outcomes changed in a direction indicating improvement. In our qualitative analysis we identified three overarching themes; relationships facilitate change, goal-focused versus manualised approach and balancing the needs of carers and people with dementia. NIDUS-Family was feasible and acceptable to participants. Following refinements, testing in a pragmatic trial is underway. [ABSTRACT FROM AUTHOR]

Protein sequence analysis and mutational analysis help study the OST1 gene of Saccharomyces cerevisiae, which encodes the alpha-subunit of oligosaccharyltransferase. Vegetative growth of yeast requires the presence of the Ost1 protein, which is similar to mammalian ribophorin 1. Ost1 mutants exhibit pleiotropic undeglycosylation of glycoproteins that are free or bound to the membrane under different growth temperatures. The transfer of high mannose oligosaccharide to an acceptor tripeptide at the glycosylation site is reduced in microsomal membranes from ost1 mutants.

Objective To share the challenges of recruiting people with dementia to studies, using experiences from one recently completed trial as an exemplar. Background Research publications always cite participant numbers but the effort expended to achieve the sample size is rarely reported, even when the study involved recruiting a hard to reach population. A multisite study of a psychosocial intervention for people with dementia illustrates the challenges. This study recruited 468 ‘dyads’ (a person with dementia and a family carer together) from 15 sites but the time taken to achieve this was longer than originally estimated. This led to a study extension and the need for additional sites. Recruitment data revealed that certain sites were more successful than others, but why? Can the knowledge gained be used to inform other studies? Methods Secondary analysis of routinely collected recruitment data from three purposefully selected sites was examined to understand the strategies used and identify successful approaches. Findings At all three sites, the pool of potential recruits funnelled to a few participants. It took two sites 18 months longer than the third to achieve recruitment numbers despite additional efforts. Explanations given by potential participants for declining to take part included ill health, reporting they were ‘managing’, time constraints, adjusting to a diagnosis of dementia and burden of study procedures. Conclusions Successful recruitment of people with dementia to studies, as one example of a hard to reach group, requires multiple strategies and close working between researchers and clinical services. It requires a detailed understanding of the needs and perspectives of the specific population and knowledge about how individuals can be supported to participate in research. Experiences of recruitment should be disseminated so that knowledge generated can be used to inform the planning and implementation of future research studies. [ABSTRACT FROM AUTHOR]

We develop a general framework on Dirichlet spaces to prove a weak form of the Bakry-Émery estimate and study its consequences. This estimate may be satisfied in situations, like metric graphs, where generalized notions of Ricci curvature lower bounds are not available. [ABSTRACT FROM AUTHOR]

We prove Barlow-Bass type resistance estimates for two random walks associated with repeated barycentric subdivisions of a triangle. If the random walk jumps between the centers of triangles in the subdivision that have common sides, the resistance scales as a power of a constant ρ which is theoretically estimated to be in the interval 5=4 ≤ ρ ≤ 3=2, with a numerical estimate ρ ≈ 1:306. This corresponds to the theoretical estimate of spectral dimension dS between 1.63 and 1.77, with a numerical estimate dS 1:74. On the other hand, if the random walk jumps between the corners of triangles in the subdivision, then the resistance scales as a power of a constant ρT = 1=ρ, which is theoretically estimated to be in the interval 2=3 ≤ ρT ≤ 4=5. This corresponds to the spectral dimension between 2.28 and 2.38. The difference between ρ and ρT implies that the the limiting behavior of random walks on the repeated barycentric subdivisions is more delicate than on the generalized Sierpinski Carpets, and suggests interesting possibilities for further research, including possible non-uniqueness of self-similar Dirichlet forms. [ABSTRACT FROM AUTHOR]

We give an explicit construction of a magnetic Schrödinger operator corresponding to a field with flux through finitely many holes of the Sierpinski Gasket. The operator is shown to have discrete spectrum accumulating at ∞ and it is shown that the asymptotic distribution of eigenvalues is the same as that for the Laplacian. Most eigenfunctions may be computed using gauge transformations corresponding to the magnetic field and the remainder of the spectrum may be approximated to arbitrary precision by using a sequence of approximations by magnetic operators on finite graphs. [ABSTRACT FROM AUTHOR]

Much is known in the analysis of a finitely ramified self-similar fractal when the fractal has a harmonic structure: a Dirichlet form which respects the self-similarity of a fractal. What is still an open question is when such a structure exists in general. In this paper, we introduce two fractals, the fractalina and the pillow, and compute their resistance scaling factor. This is the factor which dictates how the Dirichlet form scales with the self-similarity of the fractal. By knowing this factor one can compute the harmonic structure on the fractal. The fractalina has scaling factor , and the pillow fractal has scaling factor . [ABSTRACT FROM AUTHOR]

We explore the relationship between the limit spaces of contracting self-similar groups and self-similar structures. We give the condition on a contracting group such that its limit space admits a self-similar structure, and also the condition such that this self-similar structure is post-critically finite (p.c.f.). We then give necessary and sufficient conditions for a p.c.f. self-similar structure to be the limit space of a contracting self-similar group. When these conditions hold we give a construction of the contracting group. Finally, we illustrate our results with several examples. [ABSTRACT FROM AUTHOR]

The brain is one of the most studied and highly complex systems in the biological world. While much research has concentrated on studying the brain directly, our focus is the structure of the brain itself: at its core an interconnected network of nodes (neurons). A better understanding of the structural connectivity of the brain should elucidate some of its functional properties. In this paper we analyze the connectome of the nematode Caenorhabditis elegans. Consisting of only 302 neurons, it is one of the better-understood neural networks. Using a Laplacian Matrix of the 279-neuron "giant component" of the network, we use an eigenvalue counting function to look for fractal-like self similarity. This matrix representation is also used to plot visualizations of the neural network in eigenfunction coordinates. Small-world properties of the system are examined, including average path length and clustering coefficient. We test for localization of eigenfunctions, using graph energy and spacial variance on these functions. To better understand results, all calculations are also performed on random networks, branching trees, and known fractals, as well as fractals which have been "rewired" to have small-world properties. We propose algorithms for generating Laplacian matrices of each of these graphs. [ABSTRACT FROM AUTHOR]

The traditional method of discovering natural law is described. This method is used to suggest laws of psychic science, conservation laws, symmetry laws, and field equations. The psychic faculty of perceiving in three dimensions of time is postulated to be a requirement for receiving information psychically. Six dimensions, three of length and three of time, are suggested to describe the psychic field. [ABSTRACT FROM AUTHOR]

The objective is to make progress in psychic science. Reality is a vast number of interlocking phenomena including sense data, memories, physical features, emotional features, spiritual foundations, and mostly unknown entities which humans cannot sense or even comprehend. As scientists study this set of unknown phenomena and changing mental constructs, how can we exclude psychic phenomena from study? Thus in the interest of progress, hypotheses are proposed to describe psychic phenomena. A method of calculating the differences in six dimensional co-ordinates between psychic events is derived. A call to progress in psychic science is made. [ABSTRACT FROM AUTHOR]

An objective of this article is to prove the feasibility of formulating laws and hypotheses of psychic science by physicists, psychologists and neuroscientists. Another objective is to introduce the mental constructs of a second dimension of time as psychic phenomena with mathematical descriptions. The article also discusses how psychical science is shunned by most practitioners of psychology, physics, and neuroscience. [ABSTRACT FROM AUTHOR]

This article describes a psychic theory of life and death proposed by Tibetan researchers. Long ago, the Tibetans used a systematic, pragmatic approach to study the psychic event of death and rebirth. Although it is not considered a scientific approach, it produced a detailed description of these psychic phenomena. This article proposes to explain the Tibetan research with an expansion of the experience of time. Guidance to this expanded experience of time is through mathematics, through certainty, not skepticism, after comprehending the expanded dimensions of time mathematically. An intelligible and mathematical description is presented of the time dimensions in three psychic states, Nirmanakaya, Sambhogakaya, and Dharmakaya. Then, expanding the psychic awareness by following the method of the enlightened Buddha, the reader will also gain the experience of the Nirmanakaya state and its use of two dimensions of time. [ABSTRACT FROM AUTHOR]

Oligosaccharyltransferase (OST) is an integral membrane protein that catalyzes N-linked glycosylation of nascent proteins in the lumen of the endoplasmic reticulum. Although the yeast OST is an octamer assembled from nonhomologous subunits (Ost1p, Ost2p, Ost3p/Ost6p, Ost4p, Ost5p, Wbp1p, Swp1p, and Stt3p), the composition of the vertebrate OST was less well defined. The roles of specific OST subunits remained enigmatic. Here we show that genomes of most multicellular eukaryotes encode two homologs of Stt3p and mammals express two homologs of Ost3p. The Stt3p and Ost3p homologs are assembled together with the previously described mammalian OST subunits (ribophorins I and II, OST48, and DAD1) into complexes that differ significantly in enzymatic activity. Tissue and cell type-specific differences in expression of the Stt3p homologs suggest that the enzymatic properties of oligosaccharyltransferase are regulated in eukaryotes to respond to alterations in glycoprotein flux through the secretory pathway and may contribute to tissue-specific glycan heterogeneity. [Copyright &y& Elsevier]

The dolichol-linked oligosaccharide donor (Glc3Man9GlcNAc2-PP-Dol)for N-linked glycosylation of proteins is assembled in a seriesof reactions that initiate on the cytoplasmic face of the roughendoplasmic reticulum and terminate within the lumen. The biochemicalanalysis of the oligosaccharyltransferase and the glycosyltransferases thatmediate assembly of dolichol-linked oligosaccharides (OS-PP-Dol)has been hindered by the lack of structurally homogeneous substratepreparations. We have developed an improved method for the preparative-scaleisolation of dolichol-linked oligosaccharides from vertebrate tissues andyeast cells. Preparations that were highly enriched in either Glc3Man9GlcNAc2-PP-Dolor Man9GlcNAc2-PP-Dol were obtained from porcinepancreas and a Man5GlcNAc2-PP-Dol preparationwas obtained from an Δalg3 yeast culture.Chromatography of the OS-PP-Dol preparations on an aminopropyl silicacolumn was used to obtain dolichol-linked oligosaccharides withdefined structures. A single chromatography step could achieve near-baselineresolution of dolichol-linked oligosaccharides that differed byone sugar residue. A sensitive oligosaccharyltransferase endpointassay was used to determine the concentration and composition ofthe OS-PP-Dol preparations. Typical yields of Glc3Man9GlcNAc2-PP-Dol,Man9GlcNAc2-PP-Dol, and Man5GlcNAc2-PP-Dolranged between 5 and 15 nmol per chromatographic run. The homogeneityof these preparations ranged between 85 and 98% with respectto oligosaccharide composition. Purification of dolichol-linkedoligosaccharides from cultures of alg mutant yeast strainsprovides a general method to obtain authentic OS-PP-Dol assemblyintermediates of high purity. The analytical methods described herecan be used to accurately evaluate the steady-state dolichol-linkedoligosaccharide compositions of wild-type and mutant cell lines. [ABSTRACT FROM PUBLISHER]

N-Glycans of Entamoeba histolytica, the protist that causes amebic dysentery and liver abscess, are of great interest for multiple reasons. E. histolytica makes an unusual truncated N-glycan precursor (Man5GlcNAc2), has few nucleotide sugar transporters, and has a surface that is capped by the lectin concanavalin A. Here, biochemical and mass spectrometric methods were used to examine N-glycan biosynthesis and the final N-glycans of E. histolytica with the following conclusions. Unprocessed Man5GlcNAc2, which is the most abundant E. histolytica N-glycan, is aggregated into caps on the surface of E. histolytica by the N-glycan-specific, anti-retroviral lectin cyanovirin-N. Glc1Man5GlcNAc2, which is made by a UDP-Glc: glycoprotein glucosyltransferase that is part of a conserved N-glycan-dependent endoplasmic reticulum quality control system for protein folding, is also present in mature N-glycans. A swainsonine-sensitive a-mannosidase trims some N-glycans to biantennary Man3GlcNAc2. Complex N-glycans of E. histolytica are made by the addition of al,2-linked Gal to both arms of small oligomannose glycans, and Gal residues are capped by one or more Glc. In summary, E. histolytica N-glycans include unprocessed Man5GlcNAc2, which is a target for cyanovirin-N, as well as unique, complex N-glycans containing Gal and Glc. [ABSTRACT FROM AUTHOR]

Routine electroencephalogram (EEG) is an important test in aiding the diagnosis of patients with suspected epilepsy. These recordings typically last 20-40 minutes, during which signs of abnormal activity (spikes, sharp waves) are looked for in the EEG trace. It is essential that events of short duration are detected during the routine EEG test. The work presented in this paper examines the effect of changing a range of input values to the detection system on its ability to distinguish between normal and abnormal EEG activity. It is shown that the length of analysis window in the range of 0.5s to 1s are well suited to the task. Additionally, it is reported that patient specific systems should be used where possible due to their better performance.