The relation of perceptual factors and speed of handwriting to spelling ability.

Thesis (Ed.M.)--Boston Universit

Design Innovation for Engaging and Accessible Digital Aphasia Therapies: Framework Analysis of the iReadMore App Co-Design Process

Background: iReadMore is a digital therapy for people with acquired reading impairments (known as alexia) caused by brain injury or neurodegeneration. A phase II clinical trial demonstrated the efficacy of the digital therapy research prototype for improving reading speed and accuracy in people with poststroke aphasia (acquired language impairment) and alexia. However, it also highlighted the complexities and barriers to delivering self-managed therapies at home. Therefore, in order to translate the positive study results into real-world benefits, iReadMore required subsequent design innovation. Here, we present qualitative findings from the co-design process as well as the methodology. / Objective: We aimed to present a methodology for inclusive co-design in the redesign of a digital therapy prototype, focusing on elements of accessibility and user engagement. We used framework analysis to explore the themes of the communications and interactions from the co-design process. / Methods: This study included 2 stages. In the first stage, 5 in-person co-design sessions were held with participants living with poststroke aphasia (n=22) and their carers (n=3), and in the second stage, remote one-to-one beta-testing sessions were held with participants with aphasia (n=20) and their carers (n=5) to test and refine the final design. Data collection included video recordings of the co-design sessions in addition to participants’ written notes and drawings. Framework analysis was used to identify themes within the data relevant to the design of digital aphasia therapies in general. / Results: From a qualitative framework analysis of the data generated in the co-design process, 7 key areas of consideration for digital aphasia therapies have been proposed and discussed in context. The themes generated were agency, intuitive design, motivation, personal trajectory, recognizable and relatable content, social and sharing, and widening participation. This study enabled the deployment of the iReadMore app in an accessible and engaging format. Conclusions: Co-design is a valuable strategy for innovating beyond traditional therapy designs to utilize what is achievable with technology-based therapies in user-centered design. The co-designed iReadMore app has been publicly released for use in the rehabilitation of acquired reading impairments. This paper details the co-design process for the iReadMore therapy app and provides a methodology for how inclusive co-design can be conducted with people with aphasia. The findings of the framework analysis offer insights into design considerations for digital therapies that are important to people living with aphasia

Development and validation of risk prediction model for venous thromboembolism in postpartum women: multinational cohort study

Objective: To develop and validate a risk prediction model for venous thromboembolism in the first six weeks after delivery (early postpartum). Design: Cohort study. Setting: Records from England based Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and data from Sweden based registry. Participants: All pregnant women registered with CPRD-HES linked data between 1997 and 2014 and Swedish medical birth registry between 2005 and 2011 with postpartum follow-up. Main outcome measure: Multivariable logistic regression analysis was used to develop a risk prediction model for postpartum venous thromboembolism based on the English data, which was externally validated in the Swedish data. Results: 433 353 deliveries were identified in the English cohort and 662 387 in the Swedish cohort. The absolute rate of venous thromboembolism was 7.2 per 10 000 deliveries in the English cohort and 7.9 per 10 000 in the Swedish cohort. Emergency caesarean delivery, stillbirth, varicose veins, pre-eclampsia/eclampsia, postpartum infection, and comorbidities were the strongest predictors of venous thromboembolism in the final multivariable model. Discrimination of the model was similar in both cohorts, with a C statistic above 0.70, with excellent calibration of observed and predicted risks. The model identified more venous thromboembolism events than the existing national English (sensitivity 68% v 63%) and Swedish guidelines (30% v 21%) at similar thresholds. Conclusion: A new prediction model that quantifies absolute risk of postpartum venous thromboembolism has been developed and externally validated. It is based on clinical variables that are available in many developed countries at the point of delivery and could serve as the basis for real time decisions on obstetric thromboprophylaxis

Expression and regulation of drug transporters in vertebrate neutrophils.

There remains a need to identify novel pro-resolution drugs for treatment of inflammatory disease. To date, there are no neutrophil-specific anti-inflammatory treatments in clinical use, perhaps due to our lack of understanding of how drugs access this complex cell type. Here we present the first comprehensive description and expression of both major classes of drug transporters, SLC and ABC, in resting human blood neutrophils. Moreover, we have studied the expression of these carriers in the tractable model system, the zebrafish (Danio rerio), additionally examining the evolutionary relationship between drug transporters in zebrafish and humans. We anticipate that this will be a valuable resource to the field of inflammation biology and will be an important asset in future anti-inflammatory drug design

CoCREATE: Collaborative Curriculum Reimagining and Enhancement Aiming to Transform Education

The establishment of TU Dublin in January 2019 provided a unique opportunity to create a bespoke curriculum framework for students, staff and stakeholders of TU Dublin, produced by the students, staff and stakeholders of TU Dublin. A curriculum framework is a set of guiding values that inform the design of teaching and learning activities within TU Dublin. A Teaching Fellowship Team, comprising eighteen teaching academics from across the three TU Dublin campuses and supported extensively by the Learning Teaching and Technology Centre (LTTC), was formed to collaboratively craft, in partnership with all stakeholders, a curriculum framework for TU Dublin. Working collaboratively under the project name CoCREATE (Collaborative Curriculum Reimagining and Enhancement Aiming to Transform Education) the Teaching Fellowship Team developed TU Dublin’s CoCREATED Curriculum Framework over eighteen months. The design and development of the CoCREATED Curriculum Framework was informed by consultation with all key stakeholders across all campuses, examination and synthesis of local, national and international best practice and policy, as well as relevant scholarly literature. The framework is underpinned by the core values and mission of TU Dublin, as well as local and national strategic plans. It provides a distinctive but tangible learning philosophy for all at TU Dublin. The framework is both considered, flexible and progressive so as to adapt to the diversity within TU Dublin, including accredited programmes, and is inclusive of all learners across the university. The four curriculum values of the TU Dublin CoCREATED Curriculum Framework are: Step forward and try new things Use all of our talents; everyone has something to learn and something to teach Make our learning experience active, useful and related to the world Create the space and time to do work that matters This new, dynamic and evolving TU Dublin CoCREATED Curriculum Framework characterises an innovative, responsive and caring learning environment for the diversity of our university’s student population across all programme levels. Simultaneously, it developed a synergy between staff, students, professional bodies, industry and community partners through a collaborative design process. It is as inspiring, distinctive and pioneering as Ireland’s first Technological University. The CoCREATED Curriculum Framework will support staff and students to develop a unique approach to teaching and learning, which will characterise a TU Dublin teaching and learning experience, and ultimately a TU Dublin graduate, in a competitive national and international higher education space. Going forward, the TU Dublin CoCREATED Curriculum Framework will empower the judicious creation of rich and diverse curricula across all disciplines and levels within TU Dublin, from apprenticeship, through undergraduate, to structured PhD

Risk of first venous thromboembolism in pregnant women in hospital: population based cohort study from England

Objective: To examine the potential for preventing venous thromboembolism during and after antepartum hospital admissions in pregnant women. Design: Cohort study using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode statistics) care records. Setting: Primary and secondary care centres, England. Participants: 206 785 women aged 15-44 who had one or more pregnancies from 1997 up to 2010. Main outcome measure: Risk of first venous thromboembolism in pregnant women admitted to hospital for one or more days for reasons other than delivery or venous thromboembolism. Risk was assessed by calculating the absolute rate of venous thromboembolism and comparing these rates with those observed during follow-up time not associated with hospital admission using a Poisson regression model to estimate incidence rate ratios. Results: Admission to hospital in pregnancy was associated with an increased risk of venous thromboembolism(absolute rate 1752/100000 person years; incidence rate ratio 17.5, 95% confidence interval 7.69 to 40.0) compared with time outside hospital. The rate of venous thromboembolism was also high during the 28 days after discharge(absolute rate 676; 6.27, 3.74 to 10.5). The rate during and after admission combined was highest in the third trimester (961; 5.57, 3.32 to 9.34) and in those aged ≥35 years (1756; 21.7, 9.62 to 49.0). While the absolute rate in the combined period was highest for those with three or more days in hospital (1511; 12.2, 6.65 to 22.7), there was also a fourfold increase (558; 4.05, 2.23 to 7.38) in the risk of venous thromboembolism for those admitted to hospital for less than three days. Conclusion: The overall risk of first venous thromboembolism in pregnant women increased during admissions to hospital not related to delivery,and remained significantly higher in the 28 days after discharge. During these periods need for thromboprophylaxis should receive careful consideration

A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis

peer-reviewedCystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further

The Far-Ultraviolet "Continuum" in Protoplanetary Disk Systems II: CO Fourth Positive Emission and Absorption

We exploit the high sensitivity and moderate spectral resolution of the $HST$-Cosmic Origins Spectrograph to detect far-ultraviolet spectral features of carbon monoxide (CO) present in the inner regions of protoplanetary disks for the first time. We present spectra of the classical T Tauri stars HN Tau, RECX-11, and V4046 Sgr, representative of a range of CO radiative processes. HN Tau shows CO bands in absorption against the accretion continuum. We measure a CO column density and rotational excitation temperature of N(CO) = 2 +/- 1 $\times$ 10$^{17}$ cm$^{-2}$ and T_rot(CO) 500 +/- 200 K for the absorbing gas. We also detect CO A-X band emission in RECX-11 and V4046 Sgr, excited by ultraviolet line photons, predominantly HI LyA. All three objects show emission from CO bands at $\lambda$ $>$ 1560 \AA, which may be excited by a combination of UV photons and collisions with non-thermal electrons. In previous observations these emission processes were not accounted for due to blending with emission from the accretion shock, collisionally excited H$_{2}$, and photo-excited H2; all of which appeared as a "continuum" whose components could not be separated. The CO emission spectrum is strongly dependent upon the shape of the incident stellar LyA emission profile. We find CO parameters in the range: N(CO) 10$^{18-19}$ cm$^{-2}$, T_{rot}(CO) > 300 K for the LyA-pumped emission. We combine these results with recent work on photo- and collisionally-excited H$_{2}$ emission, concluding that the observations of ultraviolet-emitting CO and H2 are consistent with a common spatial origin. We suggest that the CO/H2 ratio in the inner disk is ~1, a transition between the much lower interstellar value and the higher value observed in solar system comets today, a result that will require future observational and theoretical study to confirm.Comment: 12 pages, 7 figures, 3 tables. ApJ - accepte

Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection