bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial organization of RNA polymerase and its relationship with transcription in
Escherichia coli
Authors: Weng Xiaoli , Bohrer Christopher H. , Bettridge Kelsey , Lagda Arvin Cesar , Cagliero Cedric , Jin Ding Jun , Xiao Jie
Published: September 2019

Recent studies have shown that RNA polymerase (RNAP) is organized into distinct clusters in
Escherichia coli
and
Bacillus subtilis
cells. Spatially organized molecular components in prokaryotic systems imply compartmentalization without the use of membranes, which may offer insights into unique functions and regulations. It has been proposed that the formation of RNAP clusters is driven by active ribosomal RNA (rRNA) transcription and that RNAP clusters function as factories for highly efficient transcription. In this work, we examined these hypotheses by investigating the spatial organization and transcription activity of RNAP in
E. coli
cells using quantitative superresolution imaging coupled with genetic and biochemical assays. We observed that RNAP formed distinct clusters that were engaged in active rRNA synthesis under a rich medium growth condition. Surprisingly, a large fraction of RNAP clusters persisted in the absence of high rRNA transcription activities or when the housekeeping σ
70
was sequestered, and was only significantly diminished when all RNA transcription was inhibited globally. In contrast, the cellular distribution of RNAP closely followed the morphology of the underlying nucleoid under all conditions tested irrespective of the corresponding transcription activity, and RNAP redistributed into dispersed, smaller clusters when the supercoiling state of the nucleoid was perturbed. These results suggest that RNAP was organized into active transcription centers under the rich medium growth condition; its spatial arrangement at the cellular level, however, was not dependent on rRNA synthesis activity and was likely organized by the underlying nucleoid.
Heme binding to human CLOCK affects interactions with the E-box
Authors: Freeman Samuel L. , Kwon Hanna , Portolano Nicola , Parkin Gary , Venkatraman Girija Umakhanth , Basran Jaswir , Fielding Alistair J. , Fairall Louise , Svistunenko Dimitri A. , Moody Peter C. E. , Schwabe John W. R. , Kyriacou Charalambos P. , Raven Emma L.
Published: September 2019

The circadian clock is an endogenous time-keeping system that is ubiquitous in animals and plants as well as some bacteria. In mammals, the clock regulates the sleep–wake cycle via 2 basic helix–loop–helix PER-ARNT-SIM (bHLH-PAS) domain proteins—CLOCK and BMAL1. There is emerging evidence to suggest that heme affects circadian control, through binding of heme to various circadian proteins, but the mechanisms of regulation are largely unknown. In this work we examine the interaction of heme with human CLOCK (hCLOCK). We present a crystal structure for the PAS-A domain of hCLOCK, and we examine heme binding to the PAS-A and PAS-B domains. UV-visible and electron paramagnetic resonance spectroscopies are consistent with a bis-histidine ligated heme species in solution in the oxidized (ferric) PAS-A protein, and by mutagenesis we identify His144 as a ligand to the heme. There is evidence for flexibility in the heme pocket, which may give rise to an additional Cys axial ligand at 20K (His/Cys coordination). Using DNA binding assays, we demonstrate that heme disrupts binding of CLOCK to its E-box DNA target. Evidence is presented for a conformationally mobile protein framework, which is linked to changes in heme ligation and which has the capacity to affect binding to the E-box. Within the hCLOCK structural framework, this would provide a mechanism for heme-dependent transcriptional regulation.
Untapped capacity for resilience in environmental law
Authors: Garmestani Ahjond , Ruhl J. B. , Chaffin Brian C. , Craig Robin K. , van Rijswick Helena F. M. W. , Angeler David G. , Folke Carl , Gunderson Lance , Twidwell Dirac , Allen Craig R.
Published: September 2019

Significance

International and national law have not stemmed the tide of rapidly accelerating environmental change. In response to this challenge, we highlight examples from the United States and the European Union of the untapped capacity of existing laws to enhance social-ecological resilience to these continual changes. The recommendations we advance regarding how to mine existing legal instruments to enhance resilience are agenda-setting, and they represent a far more feasible approach to addressing emerging environmental challenges than proposing politically untenable new laws or major amendments to existing laws. We show that governance can make substantial advances in addressing environmental change in the short term by exploiting those existing untapped capacities, and we offer principles and strategies to guide such initiatives.
Neuromuscular actuation of biohybrid motile bots
Authors: Aydin Onur , Zhang Xiaotian , Nuethong Sittinon , Pagan-Diaz Gelson J. , Bashir Rashid , Gazzola Mattia , Saif M. Taher A.
Published: September 2019

Significance

Biohybrid machines have been developed using muscles to actuate soft robotic structures. We envision that the integration of neurons into the embodiment of such systems can transform them into intelligent machines which, for instance, could use sensory neurons to detect environmental cues then adaptively respond and orchestrate various motor patterns through their neural circuitry. However, achieving such sensory-motor modalities relies on the ability of neural units to command muscle activity, making actuation through motor neurons the first milestone. Here, we achieve this milestone and demonstrate neuromuscular actuation of a biohybrid swimmer. This paves the way for the development of biohybrid embodied platforms as models to gain deeper understanding of motor control, with potentially broad impact in robotics, bioengineering, and health.
Arabidopsis
PP6 phosphatases dephosphorylate PIF proteins to repress photomorphogenesis
Authors: Yu Xiaodan , Dong Jie , Deng Zhaoguo , Jiang Yaping , Wu Chong , Qin Xiaofang , Terzaghi William , Chen Haodong , Dai Mingqiu , Deng Xing Wang
Published: September 2019

The PHYTOCHROME-INTERACTING FACTORs (PIFs) play a central role in repressing photomorphogenesis, and phosphorylation mediates the stability of PIF proteins. Although the kinases responsible for PIF phosphorylation have been extensively studied, the phosphatases that dephosphorylate PIFs remain largely unknown. Here, we report that seedlings with mutations in
FyPP1
and
FyPP3
, 2 genes encoding the catalytic subunits of protein phosphatase 6 (PP6), exhibited short hypocotyls and opened cotyledons in the dark, which resembled the photomorphogenic development of dark-grown
pifq
mutants. The hypocotyls of dark-grown sextuple mutant
fypp1 fypp3
(
f1 f3
)
pifq
were shorter than those of parental mutants
f1 f3
and
pifq
, indicating that PP6 phosphatases and PIFs function synergistically to repress photomorphogenesis in the dark. We showed that FyPPs directly interacted with PIF3 and PIF4, and PIF3 and PIF4 proteins exhibited mobility shifts in
f1 f3
mutants, consistent with their hyperphosphorylation. Moreover, PIF4 was more rapidly degraded in
f1 f3
mutants than in wild type after light exposure. Whole-genome transcriptomic analyses indicated that PP6 and PIFs coregulated many genes, and PP6 proteins may positively regulate PIF transcriptional activity. These data suggest that PP6 phosphatases may repress photomorphogenesis by controlling the stability and transcriptional activity of PIF proteins via regulating PIF phosphorylation.
Photoenhanced metastable c-axis electrodynamics in stripe-ordered cuprate La
1.885
Ba
0.115
CuO
4
Authors: Cremin Kevin A. , Zhang Jingdi , Homes Christopher C. , Gu G. D. , Sun Zhiyuan , Fogler Michael M. , Millis Andrew J. , Basov D. N. , Averitt Richard D.
Published: September 2019

Quantum materials are amenable to nonequilibrium manipulation with light, enabling modification and control of macroscopic properties. Light-based augmentation of superconductivity is particularly intriguing. Copper-oxide superconductors exhibit complex interplay between spin order, charge order, and superconductivity, offering the prospect of enhanced coherence by altering the balance between competing orders. We utilize terahertz time-domain spectroscopy to monitor the c-axis Josephson plasma resonance (JPR) in La
2−x
Ba
x
CuO
4
(x = 0.115) as a direct probe of superconductivity dynamics following excitation with near-infrared pulses. Starting from the superconducting state, c-axis polarized excitation with a fluence of 100 μJ/cm
2
results in an increase of the far-infrared spectral weight by more than an order of magnitude as evidenced by a blueshift of the JPR, interpreted as resulting from nonthermal collapse of the charge order. The photoinduced signal persists well beyond our measurement window of 300 ps and exhibits signatures of spatial inhomogeneity. The electrodynamic response of this metastable state is consistent with enhanced superconducting fluctuations. Our results reveal that La
2−x
Ba
x
CuO
4
is highly sensitive to nonequilibrium excitation over a wide fluence range, providing an unambiguous example of photoinduced modification of order-parameter competition.
Vapor deposition of a nonmesogen prepares highly structured organic glasses
Authors: Bishop Camille , Thelen Jacob L. , Gann Eliot , Toney Michael F. , Yu Lian , DeLongchamp Dean M. , Ediger M. D.
Published: September 2019

Significance

Organic glasses are useful, versatile materials for current and future organic electronic technologies. They are nonequilibrium materials, so a single-component system can be processed in different ways to create a wide range of solids with diverse structural and optical properties. In this work, we use physical vapor deposition to prepare glasses with structure similar to that of an aligned smectic liquid crystal from a molecule that does not have any liquid crystal phases. This shows the potential to create highly structured glasses from a wide range of molecules.
Elevated mutation and selection in wild emmer wheat in response to 28 years of global warming
Authors: Fu Yong-Bi , Peterson Gregory W. , Horbach Carolee , Konkin David J. , Beiles Avigdor , Nevo Eviatar
Published: September 2019

Global warming has been documented to threaten wild plants with strong selection pressures, but how plant populations respond genetically to the threats remains poorly understood. We characterized the genetic responses of 10 wild emmer wheat (Triticum dicoccoidesKoern.; WEW) populations in Israel, sampling them in 1980 and again in 2008, through an exome capture analysis. It was found that these WEW populations were under elevated selection, displayed reduced diversity and temporal divergence, and carried increased mutational burdens forward. However, some populations still showed the ability to acquire beneficial alleles via selection or de novo mutation for future adaptation. Grouping populations with mean annual rainfall and temperature revealed significant differences in most of the 14 genetic estimates in either sampling year or over the 28 y. The patterns of genetic response to rainfall and temperature varied and were complex. In general, temperature groups displayed more temporal differences in genetic response than rainfall groups. The highest temperature group had more deleterious single nucleotide polymorphisms (dSNPs), higher nucleotide diversity, fewer selective sweeps, lower differentiation, and lower mutational burden. The least rainfall group had more dSNPs, higher nucleotide diversity, lower differentiation and higher mutational burden. These characterized genetic responses are significant, allowing not only for better understanding of evolutionary changes in the threatened populations, but also for realistic modeling of plant population adaptability and vulnerability to global warming.
A field experiment on community policing and police legitimacy
Authors: Peyton Kyle , Sierra-Arévalo Michael , Rand David G.
Published: September 2019

Despite decades of declining crime rates, longstanding tensions between police and the public continue to frustrate the formation of cooperative relationships necessary for the function of the police and the provision of public safety. In response, policy makers continue to promote community-oriented policing (COP) and its emphasis on positive, nonenforcement contact with the public as an effective strategy for enhancing public trust and police legitimacy. Prior research designs, however, have not leveraged the random assignment of police–public contact to identify the causal effect of such interactions on individual-level attitudes toward the police. Therefore, the question remains: Do positive, nonenforcement interactions with uniformed patrol officers actually cause meaningful improvements in attitudes toward the police? Here, we report on a randomized field experiment conducted in New Haven, CT, that sheds light on this question and identifies the individual-level consequences of positive, nonenforcement contact between police and the public. Findings indicate that a single instance of positive contact with a uniformed police officer can substantially improve public attitudes toward police, including legitimacy and willingness to cooperate. These effects persisted for up to 21 d and were not limited to individuals inclined to trust and cooperate with the police prior to the intervention. This study demonstrates that positive nonenforcement contact can improve public attitudes toward police and suggests that police departments would benefit from an increased focus on strategies that promote positive police–public interactions.
Mechanical fatigue of human red blood cells
Authors: Qiang Yuhao , Liu Jia , Dao Ming , Suresh Subra , Du E.
Published: September 2019

Significance

The mechanisms underlying degradation of biological cells due to mechanical fatigue are not well understood. Specifically, detrimental effects of fatigue on properties and homeostasis of human red blood cells (RBCs), as they repeatedly deform while traversing microvasculature, have remained largely unexplored. We present a general microfluidics method that incorporates amplitude-modulated electrodeformation to induce static and cyclic mechanical deformation of RBCs. Fatigue of RBCs leads to significantly greater loss of membrane deformability, compared to static deformation under the same maximum load and maximum-load duration. These findings establish unique effects of cyclic mechanical deformation on the properties and function of biological cells. Our work provides a means to assess the mechanical integrity and fatigue damage of RBCs in blood circulation.
Discordance between eNOS phosphorylation and activation revealed by multispectral imaging and chemogenetic methods
Authors: Eroglu Emrah , Saravi Seyed Soheil Saeedi , Sorrentino Andrea , Steinhorn Benjamin , Michel Thomas
Published: September 2019

Significance

Nitric oxide (NO) is synthesized by the endothelial isoform of nitric oxide synthase (eNOS) in vascular endothelial cells. The high reactivity of NO undermines its accurate detection in living cells. The direct detection of the low physiological concentrations of NO that are present in endothelial cells represents a significant analytical challenge. In these studies, we have used powerful biosensors to measure NO and other key signaling molecules in living endothelial cells in real time using fluorescence microscopy. These approaches have provided insights into the mechanisms whereby NO synthesis is regulated and call into question many prior conclusions about the intracellular pathways that regulate eNOS.
Molecular control limiting sensitivity of sweet taste neurons in
Drosophila
Authors: Chen Hsueh-Ling , Stern Ulrich , Yang Chung-Hui
Published: September 2019

Significance

When making feeding decisions for themselves or their progenies, animals must accurately decode both the identity and the quantity of relevant chemicals in potential food options. While much is known about how animals determine the identity of these chemicals, little is known about how they determine whether these chemicals are of relevant quantity. Here, we discover a molecule that limits the sensitivity of
Drosophila
taste neurons: its absence causes flies to exhibit abnormally high interest for very low levels of sucrose and acetic acid—2 nutritive stimuli that can activate
Drosophila
sweet neurons—that normal flies are less interested about. Our work shows that sensitivity for sweet neurons is actively limited and identifies a key regulator responsible for such control.
Agency and technology-mediated task repetition with young learners
Authors: Pinter Annamaria
Published: September 2019

This paper offers a review of the TBLT literature for young learners with an aim to identify some gaps where future research and classroom practice could be targeted. The specific focus of this review is on procedural task repetition for children, arguing that in addition to the linguistic benefits, task repetition is associated with important gains in the affective domain. It is suggested that technology-mediated task repetition, via tablet devices, can further enhance both opportunities for learning and confidence building and enjoyment. Due to the technological affordances, the learners are firmly in charge of creating dynamic, fluid tasks through cycles of reflection and practice, polishing their performance along the way, stretching towards their ‘upper potential’. To date research within TBLT with children has not explored yet what types of tasks children enjoy working with and why and how task repetition is realised when using tablet devices to record their own performances. This paper suggests steps that can be taken in this direction both in research and classroom practice.
Disambiguating recasts with prosodic and extra-linguistic cues in task-based interactions among young
learners
Authors: Kong Amy , Bui Gavin
Published: September 2019

This study investigates the relative effects of enhanced and unenhanced recasts on young learners’ question
development in L2 English, examining whether enhanced recasts can contribute to disambiguation. Forty-six Secondary One students
in Hong Kong were evenly divided into an enhanced recast group and an unenhanced recast group. Each participant participated in a
pretest, followed by three treatment sessions in three consecutive weeks. Participants in the enhanced recast group received
enhanced recasts with prosodic (tonal stress) and extra-linguistic (gestures and facial expressions) cues from the teacher,
whereas those in the unenhanced recast group received normal recasts when they made mistakes when asking questions. After that, an
immediate post-test and a two-week delayed post-test were carried out to examine participants’ progress in L2 question formation.
The results of the immediate post-test showed that both types of recasts contributed to L2 advancement, but the effects of
enhanced recasts were relatively strong as compared with unenhanced recasts. Both groups performed significantly better in the delayed post-test than in the
pretest, indicating the robust effects of recasts (enhanced or unenhanced) on learning L2 question formation. However, the
differences between the two groups were significantly reduced in the delayed post-test. In addition, the enhanced group scored
significantly lower in the delayed post-test than in the immediate post-test, suggesting a greater degenerating effect of enhanced
recasts than unenhanced recasts.
‘It’s like having a test but in a fun way’
Authors: Courtney Louise , Graham Suzanne
Published: September 2019

Assessment is a central challenge within classroom-based early language learning, where there is a need to employ
assessment methods which, as well as being valid and reliable for a range of learners, protect rather than diminish motivation.
The motivational properties of digital or serious games within language learning are increasingly recognised in the literature,
yet the value of digital game-based assessment (DGBA) remains underexplored. This study used a questionnaire to examine how 3437
young language learners of English, Spanish, German, Italian and French perceived a DGBA tool and the extent to which their
perceptions were modulated by age, gender and performance levels on the game.

Learners perceived the DGBA tool as fun to play, worth playing again, helpful for telling them about their
progress and of moderate difficulty level. Girls were more positive than boys about the game but for all learners levels of
positivity were not related to age. There was a significant but weak relationship between positivity and game scores, suggesting
that learners liked the game regardless of their attainment levels. The study’s findings are discussed in relation to theories of
motivation associated with digital game-based tools and their practical implications for the teaching of early language
learners.
16 An Analysis of the Impact of Establishing an Ambulatory Stroke Team
Authors: Menagh Colin , Wilson David , Dynan Kevin , Power Michael , Hull Karen , McCallion Charlotte , Matthews Maureen
Published: September 2019

Background

The South Eastern Trust established an Ambulatory Stroke Team (AST) in October 2017. This consisted of Stroke Nurses and a Specialty doctor with Stroke consultant support. During the initial pilot the AST team worked Monday – Friday 9-5pm. The majority of assessments took place in the emergency department. The overall aims were to improve length of stay for TIAs / stroke mimics and improve the percentage of strokes being admitted directly to the Stroke Unit.

Methods

Using quality improvement methodology we worked through several Plan, Do, Study, Act (PDSA) cycles. The most significant intervention was the introduction of a protected direct to stroke unit bed. A database was kept of all patients seen, including final diagnoses and patients discharged after assessment, preventing admission and saving bed days.

Results

A 6 month period was analysed from April to September 2018. 312 patients were reviewed - 159 (51%) stroke mimics, 108 (35%) strokes and 45 (14%) TIAs. 54 patients were identified for early discharge and appropriate follow-up. Bed days saved was estimated at 110 days. Direct to stroke unit percentage improved from 30% in October 2017 when the AST was introduced to 82% in January 2019.

Conclusion

A dedicated Ambulatory Stroke Team can prevent hospital admissions and save bed days due to rapid identification and specialist assessment of suspected TIAs and strokes. Multidisciplinary team working as part of a quality improvement project can improve the percentage of strokes admitted directly to the stroke unit.
38 Patient and Environmental Factors Influencing Recognition, Response Time, and Treatment of In-Hospital Stroke
Authors: Mello Sarah , Cogan Nicola , Greene Suzanne , Collins Ronan , Ryan Dan
Published: September 2019

Background

Approximately one in ten strokes occur in hospital whilst the patient is hospitalised for another reason. Existing research suggests that delays in recognition of in-hospital stroke (IHS) result in poorer outcomes compared to those with community-onset stroke. We aim to describe the characteristics of an IHS population and to phenotype the patient and/or environmental factors most likely to account for delays in recognition and response times.

Methods

Patients diagnosed with having an ischemic stroke while admitted to hospital for a non-stroke reason were identified through our hospital's stroke registry. We collected patient demographics along with the ward and service they were admitted under and if they underwent any invasive procedures prior to the stroke event. The patient cohort was dichotomised based on patient specific or environmental factors. We then calculated the likelihood of symptom recognition, medical review, and neuroimaging occurring within the 4.5 hour thrombolysis window between the two groups using the chi squared test.

Results

Fifty IHS occurred in the study time period. 52% were male, average age 74 (SD 12.7 years). 34 (68%) were admitted medically, and 16 (32%) surgically. 27 (54%) were assessed within the time frame for thrombolysis. Of these, seven received acute stroke treatment and the remaining 19 had contraindications to treatment. Patients presenting with collapse (67% vs 4%, p=0.011), limb weakness (85% vs 52%, p=0.011) or aphasia (63% vs 9%, p=0.019) were more likely to be recognised. Patients whose symptoms were recognised by a non-staff member (52% vs 78%, p=0.026) and those presenting out of hours (56% vs 70%, p=0.047) or with delirium (85% vs 39%, 0.051) were more likely to be missed.

Conclusion

In-hospital strokes are frequently missed due to the complexities of the patients involved. Education programs targeted at enhancing stroke pickup among hospital staff could potentially decrease delays and improve patient outcomes.
48 Accessing Respite Services for People with Dementia and Their Carers: A Qualitative Study with Multiple Stakeholders
Authors: O'Shea Emma , Timmons Suzanne , O'Shea Eamon , Irving Kate
Published: September 2019

Background

People with dementia and carers do not always access respite services in a timely manner, and in some cases, they do not access respite services at all. While carers’ perspectives on respite access have been explored, other stakeholder perspectives, especially those of people with dementia, are under-represented in the existing literature. The aim of this study was to synthesise multiple stakeholders’ perspectives, including people with dementia, on accessing respite services.

Methods

Purposive sampling was employed. Semi-structured interviews were conducted with 35 key stakeholders, including people with dementia (N=6), carers (N=9), respite front-line staff (N= 4), respite managers (N=8), primary care professionals (N=3) and policy-makers/academics (N=5). Informed consent was obtained from all stakeholders who could give this. Dewing's ‘process consent’ method was employed in relation to people with dementia. Data were interpreted inductively using thematic analysis. We aimed to move beyond the semantic level of meaning, and to interpret patterns of meaning in the data. Reflexivity was considered throughout the research process.

Results

Three themes (‘Service Acceptability’; ‘Navigational Knowledge and Skills’; ‘Constructing and Adjudicating Respite Need’) were identified that relate to how access to respite services is negotiated between service providers and dyads.

Conclusion

A number of the findings support previous research; however novel findings discussed relating to the access negotiation process include 1) the ambiguous legitimacy of respite needs, in a system configured to deliver a biomedical model of care and which considers non-medical care as a family responsibility, and 2) the constraining effects of disparate conceptualisations of ‘respite’ between carers and providers. Future research should interrogate the appropriate boundaries of public responsibility in relation to respite service planning/delivery for dementia, with particular reference to client preferences for community and in-home provision.
65 The Health and Well-Being of Family Carers of Older People: An Exploratory Cross-Sectional Analysis
Authors: O'Donnell Deirdre
Published: September 2019

Background

Family carers are critical to supporting older people to live well in their homes and demand for care at home is projected to increase dramatically into the future.1 The Irish state and health system, therefore, are dependent upon the supply of family care now and into the future. The health and well-being of older family carers, and carers providing care to older people in the community, is under-researched.

Methods

A combination of online and postal survey distribution achieved a convenience sample (N=1102) of carers from the membership and network reach of Ireland’s largest family carer support and advocacy agency.

Results

Of those carers providing care to an older adult (n=341), 30% were aged over 64 and 28% reported mild to moderate carer burden. A further 36% reported moderate to severe burden. The average Zarit burden score for carers caring for an older adult was 44 (CI 42:45) and was 39 (CI 36:43) for family carers aged over 64. Among family carers of older adults, 72% reported diagnosis or treatment for physical illness and 42% reported diagnosis or treatment for mental illness. The most frequently cited source of worry for this group was their own health and wellbeing (73%) followed by lack of appropriate supports/services (68%). GPs were the most frequently cited source of support (64%) followed by a PHN (50%).

Conclusion

The study findings indicate that the lack of appropriate state supports and services for family carers is negatively impacting carer health and well-being. Family carers, including those providing care to older people and those who are themselves aged over 64, need to be consistently identified for intervention by health professionals, particularly GPs and PHNs.
141 Using Random Forest Plots to Examine Predictive and Discriminative Ability of Mobility Measures for Future Falls
Authors: Donoghue Orna , Hernandez Belinda , O'Connell Matthew , Kenny Rose Anne
Published: September 2019

Background

Slow gait speed and Timed Up-and Go (TUG) are often independent predictors of falls in regression analysis, although their ability to discriminate between fallers and non-fallers is questionable. Random forest plots can model complex interactions between predictor variables and have high classification accuracy. We compare the predictive and discriminative ability of UGS and TUG in predicting recurrent falls over 4 years using poisson regression and random forest plots.

Methods

Data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA), a population-based study of community-dwelling adults aged ≥50 years were used. Baseline physical, neuro-cognitive, sensory and behavioural health were assessed. The outcome was recurrent (≥2) falls at Wave 2 or Wave 3. Poisson regression analysis was used to examine associations between UGS, TUG and falls adjusting for covariates. Random forest models were used. Predictive accuracy was calculated using 5 fold cross-validation and as there was class imbalance, the algorithm was trained using under-sampling of the larger class. Classification rate, area under the receiver operating characteristic curve (AUC) and area under the precision recall curve (PRROC) were obtained to assess predictive accuracy.

Results

In poisson regression analysis (n=4918), TUG predicted recurrent falls independent of covariates including UGS (IRR=1.06, 95% CI: 1.01, 1.12, p<0.05). The random forest model predicted 60.82% of participants correctly (61.85% of non-fallers; 55.37% of fallers). AUC was 0.63 and PRROC was 0.28.

Conclusion

Impaired mobility i.e. slower TUG performance, is an independent predictor of future recurrent falls, however it does not discriminate well between fallers and non-fallers. This is highlighted by the PRROC which provides a more conservative estimate of predictive accuracy than AUC as it accounts for the ability to identify both fallers and non-fallers. The analysis highlights the multifactorial nature and complexity of falls, and supports the need for comprehensive falls assessment.
175 A Dyadic Approach to Life-Threatening Illness in Older Adults and their Spouse Carers
Authors: Lyons Karen , Lee Christopher
Published: September 2019

Background

Little research focuses on the older adult with life-threatening illness and their carer simultaneously, nor the role of the interpersonal and familial context around them. The purpose of this study was to identify factors associated with poor mental health and lack of shared appraisal of symptoms.

Methods

Multilevel modeling was used to examine cross-sectional data from 135 older adult-spouse carer dyads with life-threatening illness (59 with congestive heart failure and 76 with lung cancer). This was a secondary analysis of quantitative data from two studies. Data were gathered using established measures of symptoms (dyspnoea, fatigue, pain), depression, concealment, relationship quality and family support with in-person interviews conducted separately for older adults and their carers. Diagnosis and stage of disease were gathered from clinical records.

Results

Older adults with heart failure reported significantly more depressive symptoms than older adults with lung cancer, whereas spouses caring for someone with heart failure reported significantly less depressive symptoms than those caring for someone with lung cancer. Greater levels of spouse depressive symptoms were significantly associated with less shared appraisal of the older adult’s fatigue and pain interference, controlling for the quality of the relationship between them. Finally, risk factors for higher depressive symptoms of older adults included higher levels of concealing symptoms and worries from their spouse, advanced stage of disease, reporting low relationship quality and low levels of support from family. Risk factors for higher depressive symptoms of spouse carers included being younger and reporting low support from family.

Conclusion

Findings highlight the importance of taking a dyadic approach to life-threatening illness in older adults and the role of interpersonal and familial variables on the mental health of both members. Interventions to support and strengthen relationships and communication and address depressive symptoms of both members of the dyad are warranted.
179 Evaluating a Clinical Pharmacist Service in a Residential Care Unit
Authors: Kavanagh Claire , O'Dwyer Eimear , Purcell Róisín , McMahon Niamh , Crowe Morgan , Scott Michael
Published: September 2019

Background

This study assessed the pharmacist role in an 80 bed residential care unit by: Quantifying the number and type of pharmacist interventions made and their acceptance rate.Assessing impact of pharmacist interventions on patient care.Assessing staff attitudes towards the clinical pharmacist service.

Methods

This was a non-blinded, non-comparative evaluation of the existing clinical pharmacist service in the unit. All residents were included. All pharmacist interventions over a 10-week period were recorded, then graded according to the Eadon scale1 by a consultant gerontologist and an experienced pharmacist to assess their impact on patient care.

Results

There were 615 pharmacist interventions. The most common interventions were: Drug Therapy Review, 34% (n=209) Technical Prescription, 26.5% (n=163) Administration, 15.3% (n=94) Drug Interaction, 10.4% (n=64) Medication Reconciliation, 8.5% (n=52)

98% (n=596) of interventions were rated as having significance to patient care, of which: 48.4% (n=298) and 41.8% (n=257) of the interventions rated as ‘significant and resulting in an improvement in the standard of care’1% (n=6) and 0.5% (n=3) rated as ‘very significant and preventing harm’.

There was a statistically significant agreement between the evaluators, κw = 0.231 (95% CI, 0.156 to 0.307), p < .0005. The strength of agreement was fair.

Of interventions requiring acceptance by medical team (n=335), 89.9% (n=301) were accepted.

95% (n=36) of staff who responded agreed or strongly agreed that improved patient safety resulted from the pharmacist’s involvement in multidisciplinary medication reviews.

Over 92% (n=35) agreed or strongly agreed that their experience of the pharmacist was positive.

Conclusion

The pharmacist has an important role in our residential care unit. Their involvement in the medicines optimisation process positively impacts patient outcomes and prevents harm. Staff perceived a positive impact of the clinical pharmacist service provided on patient care and patient safety.
181 Pharmacist Review of Clinical Practice for Crushing Medicines on Two Gerontology Wards in an Acute Hospital
Authors: McGann Ciara , Colthorpe Anna , MacEoin Hanna
Published: September 2019

Background

Older patients frequently have difficulty swallowing, due to acute pathologies or chronic conditions. Tablets are often crushed and administered by various methods.

This alters the licensed status of the medicine and, in some cases, crushing medicines poses iatrogenic risks to both patients and nursing staff.

This study evaluated the prevalence of swallowing difficulties which impact the administration of medicines and assessed current practice in this area.

Methods

On a single day, clinical pharmacists reviewed all patients on two wards. The pharmacists, together with Nurses and Speech and Language Therapists, reviewed each patient.

Patients receiving crushed medicines were identified and the reasons for crushing were established. Each relevant medicine was reviewed to assess suitability for crushing.

STOPP/START criteria were used to assess for potentially inappropriate prescribing and continued need for each medicine.

Results

The study included 48 patients. Six (12.5%) were receiving crushed medicines due to swallowing difficulties/enteral feeding tubes. Prior to the review, the pharmacists were aware that two (33%) of these patients were receiving crushed medicines. The medical teams were not aware that the remaining four patients were receiving crushed medicines.

The six patients were prescribed 48 oral medicines in total. 36 (75%) were being crushed while 12 (25%) were being administered in a suitable licensed formulation (liquid/dispersible tablet).

The pharmacists confirmed that 24 (67%) were appropriate for crushing but recommended adjustment in 12 (33%) instances: 8 (22%) were available in a suitable alternative formulation and crushing was contraindicated in 4 (11%) instances (sustained release/enteric coated preparations).

Additionally, STOPP/START criteria identified 6 (12.5%) of medicines as potentially inappropriate and requiring clinical review.

Conclusion

Administration of medicines in patients with swallowing difficulties was sub-optimal. Clinical pharmacist review of medicines supports appropriate administration in these patients.

A system to promote close communication within the multi-disciplinary team regarding patient’s swallowing ability is needed.
191 A Multi-Country Survey to Explore What Key Stakeholders Consider to be Important in a Model of Dementia Palliative Care
Authors: Fox Siobhan , O'Connor Niamh , Drennan Jonathan , Guerin Suzanne , Kernohan George , Murphy Aileen , Timmons Suzanne
Published: September 2019

Background

The Model for Dementia Palliative Care Project will develop a service delivery model for community-based dementia palliative care in Ireland. This responds to palliative care now being recognised as a priority in care for people with dementia. Various dementia palliative care services exist internationally, however little is known about what the service providers would deem to be the most important aspects of service provision. The aim of this study was to identify what key stakeholders consider to be essential components of a model of dementia palliative care.

Methods

A web-based survey was developed, piloted (n=5), and revised. It was distributed electronically within five healthcare jurisdictions, in the Republic of Ireland, Northern Ireland, England, Scotland, and Wales. The target population was healthcare professionals, policy-makers, and academics, with an interest in dementia and palliative care. Content analysis of open ended questions was used to identify common themes within the data.

Results

Complete surveys were received from 112 stakeholders. The majority of respondents were female (86%). Identified key principles of care incorporated the philosophies of palliative care and good dementia care, with many describing ‘holistic’ and ‘person-centred care’ as core. Important individual components were identified, including support for carers, advanced care planning, information, education and training, activities for ‘meaningful living’, comprehensive disease management, coordinated case management, and linking in with community health services and social activities. Barriers to the model were identified at three levels: ‘(mis)understanding of dementia palliative care’, ‘application of dementia palliative care’ and ‘wider service organisation’.

Conclusion

Numerous components of a ‘good’ model were identified, along with possible barriers to implementation of the model. This study, as part of the larger project, will inform a model of dementia palliative care for the Irish Healthcare system with the potential to improve the experiences of people with dementia and their families.
192 Interleukin-6 and C-Reactive Protein Predict all Cause Death and Poor Functional Outcome after Non-Severe Stroke and Transient Ischaemic Attack
Authors: Coveney Sarah , McCabe John J , Sean Murphy , Belton Orina , Crowe M , Dolan Eamon , Cassidy Tim , De Gaetano Monica , Fitzgibbon Maria , Harbison Joe , Horgan Gillian , Marnane Michael , Merwick Aine , Williams David , Kelly P J
Published: September 2019

Background

Inflammation plays a role in the development of ischaemic cerebrovascular events. High sensitivity C-reactive protein (CRP) is known to predict recurrent events. Little data exists for more upstream serum markers of inflammation.

Methods

BIO-STROKE and BIO-TIA were multicentre prospective biomarker and imaging studies of patients with non-severe stroke, TIA and controls. Exclusion criteria were malignancy, infection, recent trauma / surgery, recurrent stroke before phlebotomy/MRI.

Serum biomarkers analysed included Interleukin (IL) – 6, CRP, IL-1, IL-8, IL10, IL12p70, IFN and TNF.Plasma CRP and IL-6 were measured by mass spectrometry. Additional biomarkers were measured using ELISA. Follow up was performed at 7, 28, 90 days and 1 year.

Results

680 patients (439 strokes, 241 TIAs) and 68 controls were included in the analysis. The median age was 70 for cases. Carotid stenosis was present in 23.6% of cases. Median CRP was 3.75mg/L, 2.36mg/l and 1.87mg/L in the stroke, TIA and control groups (p=<0.001). Median IL-6 was 5.86pg/ml (stroke), 4.25pg/ml (TIA), 3.06pg/ml (control) (p=<0.001).

On multivariate cox regression analysis baseline IL6 and CRP were independent predictors of all cause death at 1 year with a HR of 1.005 (95% CI 1.002-1.007, p<0.001).and 1.005(95% CI 1.002-1.007, p<0.001) per unit increase. Both IL6 and CRP were associated with vascular death at 1 year. In adjusted analyses, IL6 and CRP were associated with poor functional outcome at 1 year (OR of 1.02(CI 1.01 -1.03) and 1.02(CI 1.01-1.03) per unit increase, for IL6 and CRP respectively).

On adjusted analysis, when IL6 was analysed as quartiles, there was a strong association with death at 1 year with an OR 1.87 (95% CI 1.19-2.93).CRP, analysed as quartiles, demonstrated an OR for death at 1 year of 1.64 (1.10-2.46).

Conclusion

IL-6 and CRP may be a useful prognostic factor for the prediction of outcome and death after stroke at 1 year follow up.
196 A Structured Literature Review of Diagnostic Processes and Pathways for People Living with Younger Onset Dementia
Authors: Kilty Caroline , Cahill Suzanne , Cahill Siobhan , Foley Tony , Rock Bernadette , Sweeney Brian , McGowan Rachel , Fox Siobhán
Published: September 2019

Background

Currently, 1 in 10 people diagnosed with dementia in Ireland are aged under 65, this is termed “Younger Onset Dementia” (YOD). Though small in numbers these figures (4000 people) are increasing, and important differences exist between people diagnosed with (PwYOD) and those diagnosed with later onset dementia (LOD). As dementia is normally associated with advancing age, clinicians are not always on the alert for its diagnosis in younger people. Diagnosing YOD can be especially challenging since presentation may be atypical and there is a lack of clinical ownership in this area.

Methods

A structured literature review was conducted to identify optimum models of diagnostic processes and pathways for PwYOD. Two research questions were addressed: (i) what models for the diagnosis of PwYOD exist nationally and internationally, and what evidence supports these and (ii) what are the differences between diagnostic processes and pathways for PwYOD compared with PwLOD. A systematic search strategy was devised to identify all relevant scientific papers. Key databases were used, supplemented by grey literature searches. A narrative synthesis approach was undertaken to assess the literature identified.

Results

Pathways and processes to the diagnosis of YOD are unclear and complex and compared with LOD, diagnosis takes more time. PwYOD are more likely to have multiple referrals to different specialists, have their memory and cognitive complaints misattributed to other factors such as depression and experience longer delays in obtaining a diagnosis.

Conclusion

Few evidence-based best-practice models or guidelines for the diagnosis of YOD exist internationally. Increased awareness of the signs and symptoms of YOD among all healthcare professionals is necessary. There is a need for improved linkages to be developed between Geriatric Medicine, Neurology, Psychiatry, and Primary Care services and in certain instances for suspected cases of YOD to be referred to neurology-led memory clinics.
209 Deprescribing in Frail Older People Approaching End-of-Life: Development and Validation of STOPPFrail Version 2
Authors: Curtin Denis , Gallagher Paul , O'Mahony Denis
Published: September 2019

Background

Older people with advanced frailty are commonly prescribed lengthy, burdensome medication regimens. When life expectancy is likely to be limited, many of the prescribed drugs may be inappropriate. STOPPFrail Criteria were developed in 2016 to assist clinicians with deprescribing decisions in frail older people with limited life expectancy. Due to an expanding evidence base, updating of the criteria was required.

Methods

A focused literature review was performed to reassess the original criteria and propose new criteria. Eight panelists, with expertise in geriatric medicine, general practice, palliative medicine, psychiatry and clinical pharmacology, reviewed and critiqued a new draft of STOPPFrail criteria. The revised list of criteria was then validated using Delphi consensus methodology.

Results

The expert panel agreed a final list of 27 criteria after two Delphi validation rounds. STOPPFrail version 2 proposes a method for identifying older people approaching end-of-life and emphasizes shared decision making in the deprescribing process. New criteria relating to the discontinuation of anti-hypertensive medications, anti-thrombotic therapies and vitamin D are included.

Conclusion

STOPPFrail version 2 has been expanded and updated for the purpose of assisting clinicians with deprescribing decisions in frail older adults approaching end-of-life. The criteria are based on an up-to-date literature review and consensus validation among a panel of experts.