bluuebunny/crossref_metadata_2025 huggingface dataset:
83 Trip Versus Slip: Implication of the Triggers of Falls on Physiological Fall Risk
Authors: Lam Freddy M H , Choy Dicky T K , Leung Jason C S , Kwok Timothy C Y
Published: December 2019

Introduction

Early identification of fallers with intrinsic fall risk factors could facilitate the delivery of timely and appropriate treatment. This study aims to see if the two most common triggers of falls – trip and slip, have an implication on the physiological profile of older fallers.

Methods

One thousand one hundred and forty-one community-dwelling older adults aged 60 years or above who had a fall in the past year were recruited in Hong Kong. Details on the falls experienced by the elderly were recorded in an interview. Physiological fall risk of the participants was measured by the short-form Physiological Profile Assessment (PPA). It assesses vision, reaction time, proprioception, balance, and knee extension strength. Mobility was assessed by the 10-meter walk test at comfortable speed. Analysis of Co-variance (ANCOVA) was used to compare the assessment results between those who only experienced trip and falls (n=378; 316 female; mean age=70.4±7.2) and those who only experienced slip and falls (n=204; 159 female; mean age=70.1±7.1) while adjusting for gender proportion. Chi-square test was used to evaluate the difference in the proportion of recurrent fallers across groups.

Results

Elderly who experienced only trip and falls have a significantly lower knee extension strength (22.9±8.3kg) compare with those who experienced only slip and falls (25.0±9.18 kg; p=0.031). They also tend to take longer to complete the 10-meter walk test (Trip only: 10.17±2.88; Slip only: 9.72±2.63; p=0.085). A higher percentage of those who tripped were recurrent fallers but the difference was insignificant (Trip only: 11.6%; Slip only: 8.3%; p=0.214). No other outcome measure was found to be significantly different across groups (p≥0.418).

Conclusion

Elderly who tripped and fell have worse physical ability than those who slipped. They are potentially better candidates for fall prevention exercise intervention.
90 Falls Efficacy Related Instruments for Community-Dwellig Older Adults – Development and Content Validity: A Cosmin-Based Systematic Review
Authors: Soh Shawn Leng-Hsien , Tan Chee-Wee , Judith Lane , Gleeson Nigel , Xu Tim
Published: December 2019

Background

Falls efficacy is a widely-studied latent construct in community-dwelling older adults. Various self-reported instruments have been used to measure falls efficacy. Empirical evidence is needed to justify the selection of a specific instrument to measure the intended construct.

Objectives

To summarize evidence on the development, content validity and structural validity of instruments measuring falls efficacy in community-dwelling older adults using Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist.

Study Design and Setting

MEDLINE, Web of Science, PsychINFO, SCOPUS, CINAHL were searched (May 2019). Records on development of instruments and studies assessing content validity or structural validity of falls efficacy related scales were included. COSMIN methodology guided the review of eligible studies and methodological quality. Evidence of content validity: relevance, comprehensiveness and comprehensibility and unidimensionality for structural validity were synthesized. A modified GRADE approach was applied to evidence synthesis.

Results

35 studies on 18 instruments were included in the review. High quality evidence showed that modified Falls-Efficacy Scale (FES)–13 items (mFES-13) is relevant but not comprehensive for measuring falls efficacy. Moderate quality evidence supported the FES-10 had sufficient relevance and the mFES-14 had sufficient comprehensibility. Only the Activities-specific Balance Confidence (ABC) Scale–Simplified (ABC-15) had sufficient relevance of moderate quality evidence to measure balance confidence. Low to very low quality evidence underpinned content validity of other instruments. High quality evidence supported sufficient unidimensionality for eight instruments (FES-10, mFES-14, ABC-6, ABC-15, ABC-16, Iconographical FES (Icon-FES), FES–International (FES-I) and Perceived Ability to Prevent and Manage Fall Risks (PAPMFR)).

Conclusion

Content validity of the instruments to measure falls efficacy is understudied. Structural validity is sufficient for a number of widely-used instruments. Measuring balance confidence is a subset of falls efficacy. Further work is needed to investigate the broader continuum of falls efficacy.
95 Associated Factors and Outcomes of Falls in Acute Elderly Inpatients
Authors: Spiegel Carmen , Warren Diane , McCall Denise , Berry Kristine , Khoo Tien K
Published: December 2019

Introduction

It is thought that more than 1:3 individuals ≥65 years old fall at least once per year. With an increasing number of elderly inpatients in an ageing Australian population, falls prevention is now part of patient safety. We aimed to characterise associated factors of inpatient falls and patient outcomes in an acute medical ward in a regional hospital.

Methodology

Inpatient falls for a 12-month duration (January-December 2018) were identified through a mandatory incident reporting system. Identifiable cases were included in the study with medical records reviewed retrospectively to ascertain active medical issues. Individuals with recurrent falls in the same admission were only counted once. Statistical analyses were performed in cases which completed an Ontario Modified Stratify (Sydney Scoring) Falls Risk Screen (OMS) during admission. An OMS score of ≥9 was indicative of high falls risk (HFR). Active issues were categorised based on major diagnostic categories.

Results

A total of 77 falls occurred during the 12-month period. Fifty three events fulfilled criteria for further analyses. This comprised of 24 (45.3%) males and 29 (54.7%) females once recurrent fallers were accounted. The mean cohort age was 80.2 years (SD 13.6) with a mean OMS score of 14.3 (SD 8.6) whereby 63.0% were deemed HFR.

The top six categories of active issues experienced in this group were history of fall(s) contributing to admission (47.2%), cognitive impairment/ delirium/ dementia (43.4%), infection (43.4%), significant orthopaedic/ rheumatological disorders (39.6%), ischaemic heart disease/ heart failure/ valvulopathy (34%) and hypertension (34%).

Medical admission outcomes for inpatient fallers were as follows; 58.5% discharged, 22.6% transferred to subacute care, 3.8% interhospital transfer and 15.1% death.

Conclusion

Recommended cut-off scores for the OMS are likely suboptimal in multimorbid elderly acute medical inpatients. Based on the limited sample size, elderly inpatients who experienced in-hospital falls are at higher risk of mortality.
99 What is the Attitude and Knowledge of Malaysian Nurses Towards Falls in the Hospital?
Authors: Chong Elizabeth G M , Ramli Roslawati , Ramli Fadhilah , Yau Weng Keong , Abdullah Che Ku Mohd Fairuz Che Ku
Published: December 2019

Background

Fall prevention programs are multidisciplinary, but nursing care plays a central and important role. However, management of falls are not addressed in the nursing clinical training curriculum in Malaysia.

Methodology

This study was conducted in Hospital Kuala Lumpur in the month of April and May 2019. A structured questionnaire with 10 questions on attitudes of a nurse in the management of falls and 10 questions on knowledge of falls in the hospital were distributed randomly to nurses of the Medical and Oncology departments.

Results

There were 260 participants: Medical (73%) and Oncology (27%). Among all the subjects, 84% were female. 17% of the subjects were junior nurses (less than 1 year of service) and 15.2% were seniors (>10 years of service). Majority only had a basic diploma in nursing (97%).

The average score of the nurses’ attitude towards falls was 9 points, where 85.4% had a score of 8 or more, representing a good attitude towards the understanding of their role as a nurse in the management of falls.

In view to knowledge, the average score was 8 and 19% scored full marks. Those who had worked for longer for the organisation and nurses from the medical department had more respondents scoring full marks. The nurses with poorer attitude are reflected by their lower average knowledge score of 6, 2 marks lower than those with a good attitude.

Conclusion

The study showed that the Malaysian nurses have a very good attitude towards the management and prevention of falls. This study showed that attitude of the nurse in the prevention of falls is correlated to their knowledge about falls. Therefore, nursing management of falls should be routinely introduced into the nursing curriculum.

References

1. MH Kim, HW Jeon, MY Chon, Study on the Knowledge and Attitudes of Falls and Awareness of Fall Risk Factors Among Nursing Students, Indian Journal of Science and Technology, Vol 8(S1), 74-80, 2015

2. M Ganabathi. Knowledge, Attitude and Practices (KAP) on fall prevention among nurses at King Abdulaziz Hospital, Saudi Arabia, J Nurs Care 2017, 6:5 (Suppl)
The essential histogram
Authors: Li Housen , Munk Axel , Sieling Hannes , Walther Guenther
Published: December 2019

The histogram is widely used as a simple, exploratory way of displaying data, but it is usually not clear how to choose the number and size of the bins. We construct a confidence set of distribution functions that optimally deal with the two main tasks of the histogram: estimating probabilities and detecting features such as increases and modes in the distribution. We define the essential histogram as the histogram in the confidence set with the fewest bins. Thus the essential histogram is the simplest visualization of the data that optimally achieves the main tasks of the histogram. The only assumption we make is that the data are independent and identically distributed. We provide a fast algorithm for computing the essential histogram and illustrate our method with examples.
African sunbirds predominantly pollinate plants useful to humans
Authors: Newmark William D , Mkongewa Victor J , Amundsen Debra L , Welch Chad
Published: December 2019

Birds provide multiple ecological services that benefit humans including pollination. In Africa, sunbirds are the dominant vertebrate pollinator. Here we present a species-level assessment for African sunbirds of the number and relative frequency of their food plants that have useful properties to humans. We conducted this analysis by compiling and integrating known sunbird food plants with useful tropical plant and tropical cultivated plant databases. Across Africa, 68% of the 329 genera and 44% of the 468 species of sunbirds’ known food plants are used by humans for medicine, food, building materials, or other uses. Yet most genera and species of useful plants are visited by a small number of sunbird species. The median number of sunbird species that visit a useful genus and species of plant is two and one, respectively. Of the 409 genera and 308 species of useful plants that are sunbird pollinated across one or more of the six predominant habitats for sunbirds, 67% of genera and 71% of species are pollinated by sunbird species that are forest or woodland dependent. Additionally, 58% of all genera and 83% of all species of useful plants pollinated by sunbirds are non-cultivated. In Africa, non-cultivated sunbird-pollinated useful plants are almost entirely collected, used, and traded locally rather than regionally or internationally. Our results indicate that African sunbirds provide important ecological services as pollinators that benefit humans, and these services are provided largely at a local scale. Given the decline of invertebrate and vertebrate pollinators both globally and in Africa, sunbirds are important to the long-term conservation of many useful plants in Africa and hence human well-being.
A Rare, Recently Discovered Nematode, Oscheius onirici (Rhabditida: Rhabditidae), Kills Drosophila suzukii (Diptera: Drosophilidae) Within Fruit
Authors: Foye Shane , Steffan Shawn A
Published: December 2019

The spotted-wing drosophila, Drosophila suzukii Matsumura, is an exotic species in North America and represents a major threat to fruit production. Efforts to manage D. suzukii have focused primarily on insecticides, but such controls may, at times, be unreliable, given that D. suzukii larvae are often ensconced within fruit. The fruit interior, however, may represent suitable foraging substrates for carnivorous/entomopathogenic nematodes. In preliminary trials, a rare nematode species, Oscheius onirici Torrini et al., was shown to be highly virulent against D. suzukii when the nematodes were applied directly to fly larvae. To address the more important question of whether this nematode would be as virulent when applied to fruit, we set up assays in which blueberries were infested with D. suzukii larvae and then sprayed with O. onirici infective juveniles (IJs). Across two laboratory trials, O. onirici IJs suppressed D. suzukii puparia by 78.2%. Oscheius onirici IJs were able to search effectively within fruit substrates, find the fly larvae therein, and kill the flies before they could pupariate. Oscheius onirici, therefore, may represent a viable new bio-control agent for D. suzukii management and should be field-tested across a broader diversity of cropping systems.
Dependence of sperm structural and functional integrity on testicular calcineurin isoform PPP3R2 expression
Authors: Liu Yue , Zhang Chujun , Wang Shiyao , Hu Yanqin , Jing Jia , Ye Luyao , Jing Ran , Ding Zhide
Published: December 2019

After leaving the testis, mammalian sperm undergo a sequential maturation process in the epididymis followed by capacitation during their movement through the female reproductive tract. These phenotypic changes are associated with modification of protein phosphorylation and membrane remodeling, which is requisite for sperm to acquire forward motility and induce fertilization. However, the molecular mechanisms underlying sperm maturation and capacitation are still not fully understood. Herein, we show that PPP3R2, a testis-specific regulatory subunit of protein phosphatase 3 (an isoform of calcineurin in the testis), is essential for sperm maturation and capacitation. Knockout of Ppp3r2 in mice leads to male sterility due to sperm motility impairment and morphological defects. One very noteworthy change includes increases in sperm membrane stiffness. Moreover, PPP3R2 regulates sperm maturation and capacitation via (i) modulation of membrane diffusion barrier function at the annulus and (ii) facilitation of cholesterol efflux during sperm capacitation. Taken together, PPP3R2 plays a critical role in modulating cholesterol efflux and mediating the dynamic control of membrane remodeling during sperm maturation and capacitation.
Interference of M-protein on Thrombin Time Test: A Case Report
Authors: Njegovan Milena , Margetić Sandra , Tešija Kuna Andrea , Đerek Lovorka , Ćelap Ivana , Pavičić Tomislav , Čaržavec Dubravka , Gaćina Petar
Published: December 2019

Objective

A case of interference of monoclonal protein (M-protein) on thrombin time (TT) test in a 39-year-old Caucasian male patient is presented.

Methods

Coagulation screening tests were performed where altered results only for TT result (>150 seconds) and activated partial thromboplastin time (aPTT) result (36 seconds) were measured. Further specific coagulation testing included measurement of individual coagulation factors FII, FV, FVII, FVIII, FIX, FX, FXI, and FXII. Diagnostic steps in detection and identification of monoclonal protein included serum protein electrophoresis and immunofixation (both serum and urine specimen).

Results

Monoclonal protein immunoglobulin G kappa detection and identification in serum and urine clarified the situation.

Conclusion

Unexpectedly altered results of screening coagulation tests without any appropriate clinical signs and symptoms in a patient without any anticoagulant therapy needs to be critically considered in the context of extended next diagnostic steps in order to clarify the cause of pathological test results.
The Association between Serum Retinol-Binding Protein 4 Levels and Cardiovascular Events in Patients with Chronic Kidney Disease
Authors: Su Yuhao , Huang Ying , Jiang Ying , Zhu Meilan
Published: December 2019

Objective

The study aimed to assess whether serum retinol-binding protein 4 (RBP4) is associated with a risk of cardiovascular (CV) events in chronic kidney disease (CKD) patients.

Methods

One hundred sixty-nine patients with CKD were followed for a mean of 36 months (range, 5–39 months). Serum RBP4 and other laboratory indicators were measured at baseline. The relationship between RBP4 and the risk of CV events was evaluated by using Cox regression analysis.

Results

Patients with higher serum RBP4 levels had a higher rate of CV events and a higher mortality in a univariate analysis (P < 0.001). The multivariate Cox proportional hazard analysis revealed that RBP4 (hazard ratio, 2.259; 95% confidence interval, 2.067–5.489; P = 0.002) is an independent prognostic factor for CV events in patients with CKD. Kaplan-Meier analysis demonstrated that patients with RBP4 above the median value (>33.86 mg/L) had a higher rate of CV events than did patients with RBP4 at or below the median value (≤33.86 mg/L; P < 0.001).

Conclusion

RBP4 levels are associated with CV events in patients with CKD. Elevated serum RBP4 levels may indicate an increased risk of CV complications in CKD patients.
Forward Surgical Team Procedural Burden and Non-operative Interventions by the U.S. Military Trauma System in Afghanistan, 2008–2014
Authors: Staudt Amanda M , Suresh Mithun R , Gurney Jennifer M , Trevino Jennifer D , Valdez-Delgado Krystal K , VanFosson Christopher A , Butler Frank K , Mann-Salinas Elizabeth A , Kotwal Russ S
Published: December 2019

Introduction

No published study has reported non-surgical interventions performed by forward surgical teams, and there are no current surgical benchmarks for forward surgical teams. The objective of the study was to describe operative procedures and non-operative interventions received by battlefield casualties and determine the operative procedural burden on the trauma system.

Methods

This was a retrospective analysis of data from the Joint Trauma System Forward Surgical Team Database using battle and non-battle injured casualties treated in Afghanistan from 2008–2014. Overall procedure frequency, mortality outcome, and survivor morbidity outcome were calculated using operating room procedure codes grouped by the Healthcare Cost and Utilization Project classification. Cumulative attributable burden of procedures was calculated by frequency, mortality, and morbidity. Morbidity and mortality burden were used to rank procedures.

Results

The study population was comprised of 10,992 casualties, primarily male (97.8%), with a median age interquartile range of 25.0 (22.0–30.0). Affiliations were non-U.S. military (40.0%), U.S. military (35.1%), and others (25.0%). Injuries were penetrating (65.2%), blunt (32.8), and burns (2.0%). Casualties included 4.4% who died and 14.9% who lived but had notable morbidity findings. After ranking by contribution to trauma system morbidity and mortality burden, the top 10 of 32 procedure groups accounted for 74.4% of operative care, 77.9% of mortality, and 73.1% of unexpected morbidity findings. These procedure groups included laparotomy, vascular procedures, thoracotomy, debridement, lower and upper gastrointestinal procedures, amputation, and therapeutic procedures on muscles and upper and lower extremity bones. Most common non-operative interventions included X-ray, ultrasound, wound care, catheterization, and intubation.

Conclusions

Forward surgical team training and performance improvement metrics should focus on optimizing commonly performed operative procedures and non-operative interventions. Operative procedures that were commonly performed, and those associated with higher rates of morbidity and mortality, can set surgical benchmarks and outline training and skillsets needed by forward surgical teams.
How stellar rotation shapes the colour−magnitude diagram of the massive intermediate-age star cluster NGC 1846
Authors: Kamann S , Bastian N , Gossage S , Baade D , Cabrera-Ziri I , Da Costa G , de Mink S E , Georgy C , Giesers B , Göttgens F , Hilker M , Husser T-O , Lardo C , Larsen S S , Mackey D , Martocchia S , Mucciarelli A , Platais I , Roth M M , Salaris M , Usher C , Yong D
Published: December 2019

We present a detailed study of stellar rotation in the massive 1.5 Gyr old cluster NGC 1846 in the Large Magellanic Cloud. Similar to other clusters at this age, NGC 1846 shows an extended main-sequence turn-off (eMSTO), and previous photometric studies have suggested it could be bimodal. In this study, we use MUSE integral-field spectroscopy to measure the projected rotational velocities (vsin i) of around $1400$ stars across the eMSTO and along the upper main sequence of NGC 1846. We measure vsin i values up to $\sim 250\, {\rm km\, s^{-1}}$ and find a clear relation between the vsin i of a star and its location across the eMSTO. Closer inspection of the distribution of rotation rates reveals evidence for a bimodal distribution, with the fast rotators centred around $v\sin i=140\, {\rm km\, s^{-1}}$ and the slow rotators centred around $v\sin i=60\, {\rm km\, s^{-1}}$. We further observe a lack of fast rotating stars along the photometric binary sequence of NGC 1846, confirming results from the field that suggest that tidal interactions in binary systems can spin-down stars. However, we do not detect a significant difference in the binary fractions of the fast and slowly rotating sub-populations. Finally, we report on the serendipitous discovery of a planetary nebula associated with NGC 1846.
Measuring the temperature and profiles of Ly α absorbers
Authors: Garzilli Antonella , Theuns Tom , Schaye Joop
Published: December 2019

The distribution of the absorption line broadening observed in the Ly α forest carries information about the temperature, T, and widths, λF, of the filaments in the intergalactic medium (IGM), and the background hydrogen photoionization rate, $\Gamma _{\rm H\, \small {I}}$. In this work, we present and test a new method for inferring T and λF and $\Gamma _{\rm H\, \small {I}}$ from combining the distribution of the absorption line broadening and the median flux. The method accounts for any underlying degeneracies. We apply our method to mock spectra from the reference model of the EAGLE cosmological simulation, and we demonstrate that we are able to reconstruct the IGM properties.
The impact of the environment of white dwarf mergers on fast radio bursts
Authors: Kundu Esha , Ferrario Lilia
Published: December 2019

Fast radio bursts (FRBs) are transient intense radio pulses with duration of milliseconds. Although, the first FRB was detected more than a decade ago, the progenitors of these energetic events are not yet known. The currently preferred formation channel involves the formation of a neutron star (NS)/magnetar. While these objects are often the end product of the core-collapse (CC) explosion of massive stars, they could also be the outcome of the merging of two massive white dwarfs. In the merger scenario the ejected material interacts with a constant-density circumbinary medium and creates supersonic shocks. We found that when a radio pulse passes through these shocks the dispersion measure (DM) increases with time during the free expansion phase. The rotation measure (RM) displays a similar trend if the power-law index, n, of the outer part of the ejecta is >6. For n = 6, the RM remains constant during this phase. Later, when the ejecta move into the Sedov–Taylor phase while the DM still increases, however, with a different rate, the RM reduces. This behaviour is somewhat similar to that of FRB 121102 for which a marginal increase of DM and a 10 per cent decrease of RM have been observed over time. These features are in contrast to the CC scenario, where the DM and RM contributions to the radio signal always diminish with time.
The emergence of sequence-dependent structural motifs in stretched, torsionally constrained DNA
Authors: Shepherd Jack W , Greenall Robert J , Probert Matt I J , Noy Agnes , Leake Mark C
Published: December 2019

The double-helical structure of DNA results from canonical base pairing and stacking interactions. However, variations from steady-state conformations resulting from mechanical perturbations in cells have physiological relevance but their dependence on sequence remains unclear. Here, we use molecular dynamics simulations showing sequence differences result in markedly different structural motifs upon physiological twisting and stretching. We simulate overextension on different sequences of DNA ((AA)12, (AT)12, (CC)12 and (CG)12) with supercoiling densities at 200 and 50 mM salt concentrations. We find that DNA denatures in the majority of stretching simulations, surprisingly including those with over-twisted DNA. GC-rich sequences are observed to be more stable than AT-rich ones, with the specific response dependent on the base pair order. Furthermore, we find that (AT)12 forms stable periodic structures with non-canonical hydrogen bonds in some regions and non-canonical stacking in others, whereas (CG)12 forms a stacking motif of four base pairs independent of supercoiling density. Our results demonstrate that 20–30% DNA extension is sufficient for breaking B-DNA around and significantly above cellular supercoiling, and that the DNA sequence is crucial for understanding structural changes under mechanical stress. Our findings have important implications for the activities of protein machinery interacting with DNA in all cells.
Human adipose-derived mesenchymal stem cells accelerate decellularized neobladder regeneration
Authors: Moreno-Manzano Victoria , Mellado-López Maravillas , Morera-Esteve Maria Jose , Alastrue-Agudo Ana , Bisbal-Velasco Viviana , Forteza-Vila Jerónimo , Serrano-Aroca Ángel , Vera-Donoso César David
Published: December 2019

Decellularized natural bladder matrices (neobladders) represent an exciting means to regenerate the bladder following bladder cancer-associated cystectomy. In this study, we compare the evolution of decellularized matrices with recellularized matrices by seeding it with human adipose-derived mesenchymal stem cells (ADSC) after implantation following partial cystectomy in rats. We discovered significant anatomical differences since 10 days after neobladder implantation with the ADSC-containing matrices promoting a significant recovery of mature p63- and cytokeratin 7-positive urothelium. We also discovered significantly induced expression of the vimentin mesoderm marker in the submucosal layer in ADSC-seeded matrices. Interestingly, we found a higher expression of smooth muscle actin in transversal and longitudinal smooth muscle layers with ADSC-seeded matrices. Furthermore, ADSC also showed increased vascularization and nerve innervation of the neobladder as determined by the distribution of CD31 and S100β reactivity, respectively. We believe that ADSC and their paracrine-acting pro-regenerative secretome within decellularized matrices represent an efficient bladder substitution strategy; however, we require a fuller understanding of the mechanisms involved before clinical studies can begin.
The Authorship of Donne’s Verse Letters to the Countess of Huntingdon
Authors: May Steven W
Published: December 2019

Donne’s verse letter to the Countess of Huntingdon beginning ‘That unripe side of earth’ was first printed in the second edition of Donne’s Poems (1635), and was reprinted as his in subsequent editions until 1912, when H. J. C. Grierson demoted it to a merely ‘attributed’ poem. Donne’s authorship, fully supported by the seventeenth-century printed editions, was contradicted by three manuscript copies of the poem that unanimously attributed it to the courtier and diplomat Sir Walter Aston. Scholars and editors since Grierson have wavered on their acceptance of this verse letter as reliably Donne’s work. The Donne Variorum edition of the verse letters (2018) classifies it as a ‘Poem of Disputed Canonicity’. I argue in this essay that textual, stylistic, and biographical evidence establish beyond reasonable doubt that Donne wrote this verse letter to Lady Huntingdon, and that Aston’s name became attached to it through an understandable error in scribal transmission of the poem.
Interpretable Deep Temporal Structure Learning Model for Early Detection of Alzheimer’s Disease
Authors: Wang Xiaoqian , Shen Dinggang , Huang Heng
Published: December 2019

In Alzheimer’s research, Mild Cognitive Impairment (MCI) is an important intermediate stage between normal aging and Alzheimer’s disease. How to distinguish MCI samples that finally convert to AD from those do not is an essential problem in the prevention and diagnosis of Alzheimer’s. Traditional methods use various classification models to distinguish MCI converters from non-converters, while the performance is usually limited by the small number of available data. Moreover, previous methods only use the data at baseline time for training but ignore the longitudinal information at other time points along the disease progression. To tackle with these problems, we propose a novel deep learning framework that uncovers the temporal correlation structure of the longitudinal neuroimaing data in the disease progression. In the meantime, we formulate our new deep learning model in an interpretable style such that it provides insights on the important features Alzheimer’s research. We conduct extensive experiments on the ADNI cohort and outperform the related methods with significant margin.
Image Processing in DNA
Authors: Pan Chao , Tabatabaei Yazdi S. M. Hossein , Tabatabaei S Kasra , Hernandez Alvaro G. , Schroeder Charles , Milenkovic Olgica
Published: December 2019

The main obstacles for the practical deployment of DNA-based data storage platforms are the prohibitively high cost of synthetic DNA and the large number of errors introduced during synthesis. In particular, synthetic DNA products contain both individual oligo (fragment) symbol errors as well as missing DNA oligo errors, with rates that exceed those of modern storage systems by orders of magnitude. These errors can be corrected either through the use of a large number of redundant oligos or through cycles of writing, reading, and rewriting of information that eliminate the errors. Both approaches add to the overall storage cost and are hence undesirable. Here we propose the first method for storing quantized images in DNA that uses signal processing and machine learning techniques to deal with error and cost issues without resorting to the use of redundant oligos or rewriting. Our methods rely on decoupling the RGB channels of images, performing specialized quantization and compression on the individual color channels, and using new discoloration detection and image inpainting techniques. We demonstrate the performance of our approach experimentally on a collection of movie posters stored in DNA.
A Late Cretaceous Lonchodectid?
Authors: Albuquerque Carlos
Published: December 2019

A pterosaur ulnar specimen (NZMS CD 467) from the Mangahouanga Stream of New Zealand’s North Island has been first described by Wiffen et al 1988. Assumed to belong to a“Santanadactylus-like” pterosaur, this taxon has not since been extensively described, with only a few tentative claims that it represents an azhdarchid. Here, I re-examine the specimen and compare it to other pterodactyloid taxa, noting peculiar features such as its plug-like (obdurate) ulnar end. ChristenedParirau ataroa, this taxon is found to be a lonchodectid, which alongside the North AmericanNavajodactylus boereiextends this clade into the world’s youngest pterosaur faunas.
An integrated deep mutational scanning approach provides clinical insights onPTENgenotype-phenotype relationships
Authors: Mighell Taylor L. , Thacker Stetson , Fombonne Eric , Eng Charis , O’Roak Brian J.
Published: December 2019

Germline variation inPTENresults in variable clinical presentations, including benign and malignant neoplasia and neurodevelopmental disorders. Despite decades of research, it remains unclear howPTENgenotype is related to clinical outcomes. In this study, we combined two recent deep mutational scanning (DMS) datasets probing the effects of single-amino acid variation on enzyme activity and steady-state cellular abundance with the largest well-curated clinical cohort ofPTEN-variant carriers. We sought to connect variant-specific molecular phenotypes to the clinical outcomes of individuals withPTENvariants. We found that DMS data partially explain quantitative clinical traits, including head circumference and Cleveland Clinic (CC) score, which is a semi-quantitative surrogate of disease burden. We built a logistic regression model using DMS and CADD scores to separate clinicalPTENvariation from gnomAD control-only variation with high accuracy (AUC = 0.892). Using a survival-like analysis, we identified molecular phenotype groups with differential risk of early-onset as well as lifetime risk of cancer. Finally, we identified classes of DMS-defined variants with significantly different risk levels for classical hamartoma-related features (odds ratios range of 4.1-102.9). In stark contrast, the risk for developing autism or developmental delay does not significantly change across variant classes (odds ratios range of 5.4-12.4). Together, these findings highlight the potential impact of combining DMS datasets with rich clinical data, and provide new insights that may guide personalized clinical decisions forPTEN-variant carriers.
Estimation of Quasi-Continuous Blood Pressure based on Harmonic Phase-Shifts in Signals using Non-Invasive Photoplethysmographic Measurements
Authors: Kern Fabian , Bernhard Stefan
Published: December 2019

According to the guidelines of the European Society of Hypertension International Protocol revision 2010, the requirements for long time blood pressure measurement (BPM) are: simple handling, robustness against movements, accuracy of better than ± 5 mmHg, and, above all, that the patient’s motion should not be restricted during measurement. These requirements are in particular important for a reliable interpretation of the blood pressure (BP) of hypertensive patients, because such a diagnosis will usually be confirmed by long-term measurement. Moreover, to be able to correlate the patient’s BP with his normal daily activity, non-obstructive non-invasive methods are desired to reduce the patient’s load.

The main concern of this paper is to present a novel method for estimating non-invasive continuous blood pressure (CBP) from a single photoplethysmography (PPG) signal. In contrast to the pulse transit time (PTT) method, our approach is based on the assumption that the phase-velocities of the fundamental and higher harmonics depend on the (non-linear) elastic properties of the arteries. Consequently, phase velocity varies as a function of a vessel’s instantaneous dilation and can be effectively utilised for CBP estimation.

In addition to its numerous advantages for a simplified measurement setup, we could show that the method achieves a high degree of correlation for a reliable BP estimation from PPG data. Comparison with state-of-the-art PTT methods was carried out using a dataset from the PhysioBank Database comprising a reference invasive blood pressure (IBP) signal measured at the radial artery, a PPG signal measured at the fingertip and a standard ECG signal.

The correlation values obtained from the long-time estimation of the systolic blood pressure (SBP) were as high as r = 0.8945, while the value for the diastolic blood pressure (DBP) was found to be r = 0.9082 and the correlation of the mean blood pressure (MBP) was r = 0.9322. These results were achieved by analysing the dataset in a beat-to-beat manner and regarding several post-processing procedures like coherent averaging (CA) and zero padding with quasi-continuous frequency domain estimation and artificially refined frequency resolution.
The effects of polygenic risk for psychiatric disorders and smoking behaviour on psychotic experiences in UK Biobank
Authors: García-González Judit , Ramírez Julia , Howard David M. , Brennan Caroline H , Munroe Patricia B. , Keers Robert
Published: December 2019

While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n=2 067), hallucinations (n=6 689), and any psychotic experience (delusions or hallucinations; n=7 803) in 157 366 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), bipolar disorder (PRSBP), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in 144 818 UK Biobank participants of European ancestry to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were associated with psychotic experiences (p<1.77×10-5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p<1.99×10-3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD (but not PRSSCZ or PRSBP) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p<0.002). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.
Immunologic and epidemiologic drivers of norovirus transmission in daycare and school outbreaks
Authors: Havumaki Joshua , Eisenberg Joseph NS , Mattison Claire P , Lopman Benjamin A , Ortega-Sanchez Ismael R , Hall Aron J , Hutton David W , Eisenberg Marisa C
Published: December 2019

1

Background

Norovirus outbreaks are notoriously explosive, with dramatic symptomology and rapid disease spread. Children are particularly vulnerable to infection and drive norovirus transmission due to their high contact rates with each other and the environment. Despite the explosive nature of norovirus outbreaks, attack rates in schools and daycares remain low with the majority of students not reporting symptoms.

Methods

We explore immunologic and epidemiologic mechanisms that may underlie epidemic norovirus transmission dynamics using a disease transmission model. Towards this end, we compared different model scenarios, including innate resistance and acquired immunity (collectively denoted ‘immunity’), stochastic extinction, and an individual exclusion intervention. We calibrated our model to daycare and school outbreaks from national surveillance data.

Results

Recreating the low attack rates observed in daycare and school outbreaks required a model with immunity. However, immunity alone resulted in shorter duration outbreaks than what was observed. The addition of individual exclusion (to the immunity model) extended outbreak durations by reducing the amount of time that symptomatic people contribute to transmission. Including both immunity and individual exclusion mechanisms resulted in simulations where both attack rates and outbreak durations were consistent with surveillance data.

Conclusions

The epidemiology of norovirus outbreaks in daycare and school settings cannot be well described by a simple transmission model in which all individuals start as fully susceptible. Interventions should leverage population immunity and encourage more rigorous individual exclusion to improve venue-level control measures.
Forecasting Cycles of Seizure Likelihood
Authors: Karoly Philippa J. , Cook Mark J. , Maturana Matias , Nurse Ewan S. , Payne Daniel , Brinkmann Ben , Grayden David B. , Dumanis Sonya B. , Richardson Mark P. , Worrell Greg , Schulze-Bonhage Andreas , Kuhlmann Levin , Freestone Dean R.
Published: December 2019

Objective

Seizure unpredictability is rated as one of the most challenging aspects of living with epilepsy. Seizure likelihood can be influenced by a range of environmental and physiological factors that are difficult to measure and quantify. However, some generalizable patterns have been demonstrated in seizure onset. A majority of people with epilepsy exhibit circadian rhythms in their seizure times and many also show slower, multiday patterns. Seizure cycles can be measured using a range of recording modalities, including self-reported electronic seizure diaries. This study aimed to develop personalized forecasts from a mobile seizure diary app.

Methods

Forecasts based on circadian and multiday seizure cycles were tested pseudo-prospectively using data from 33 app users (mean of 103 seizures per subject). Individual’s strongest cycles were estimated from their reported seizure times and used to derive the likelihood of future seizures. The forecasting approach was validated using self-reported events and electrographic seizures from the Neurovista dataset, an existing database of long-term electroencephalography that has been widely used to develop forecasting algorithms.

Results

The validation dataset showed that forecasts of seizure likelihood based on self-reported cycles were predictive of electrographic seizures. Forecasts using only mobile app diaries allowed users to spend an average of 62.8% of their time in a low-risk state, with 16.6% of their time in a high-risk warning state. On average, 64.5% of seizures occurred during high-risk states and less than 10% of seizures occurred in low-risk states.

Significance

Seizure diary apps can provide personalized forecasts of seizure likelihood that are accurate and clinically relevant for electrographic seizures. These results have immediate potential for translation to a prospective seizure forecasting trial using a mobile diary app. It is our hope that seizure forecasting apps will one day give people with epilepsy greater confidence in managing their daily activities.
Detection of transient neurotransmitter response using personalized neural networks
Authors: Klyuzhin Ivan S. , Bevington Connor W. J. , Cheng Ju-Chieh (Kevin) , Sossi Vesna
Published: December 2019

Abstract

Measurement of stimulus-induced dopamine release and other types of transient neurotransmitter response (TNR) from dynamic PET images typically suffers from limited detection sensitivity and high false positive rates. Measurement of TNR of a voxel-level can be particularly problematic due to high image noise. In this work, we perform voxel-level TNR detection using artificial neural networks (ANN) and compare their performance to previously used standard statistical tests. Different ANN architectures were trained and tested using simulated and real human PET imaging data, obtained with the tracer [11C]raclopride (a D2 receptor antagonist). A distinguishing feature of our approach is the use of “personalized” ANNs that are designed to operate on the image from a specific subject and scan. Training of personalized ANNs was performed using simulated images that have been matched with the acquired image in terms of the signal and noise.

In our tests of TNR detection performance, the F-test of the linear parametric neurotransmitter PET (lp-ntPET) model fit residuals was used as the reference method. For a moderate TNR magnitude, the areas under the receiver operating characteristic curves in simulated tests were 0.64 for the F-test and 0.77–0.79 for the best ANNs. At a fixed false positive rate of 0.01, the true positive rates were 0.6 for the F-test and 0.8–0.9 for the ANNs. When applied to a real image, the ANNs identified a TNR cluster missed by the F-test. The newly found cluster was verified to contain TNR by direct lp-ntPET model fitting. These results demonstrate that personalized ANNs may offer a greater detection sensitivity of dopamine release and other types of TNR compared to previously used methods.
Attenuation of cGAS/STING Activity During Mitosis
Authors: Uhlorn Brittany L. , Gamez Eduardo R. , Li Shuaizhi , Campos Samuel K.
Published: December 2019

The innate immune system recognizes cytosolic DNA associated with microbial infections and cellular stress via the cGAS/STING pathway, leading to activation of phospho-IRF3 and downstream IFN-I and senescence responses. To prevent hyperactivation, cGAS/STING is presumed to be non-responsive to chromosomal self DNA during open mitosis, though specific regulatory mechanisms are lacking. Given a role for the Golgi in STING activation, we investigated the state of the cGAS/STING pathway in interphase cells with artificially vesiculated Golgi and in cells arrested in mitosis. We find that while cGAS activity is impaired through interaction with mitotic chromosomes, Golgi integrity has little effect on the enzyme’s production of cGAMP. In contrast, STING activation in response to either foreign DNA (cGAS-dependent) or exogenous cGAMP is impaired by a vesiculated Golgi. Overall our data suggest a secondary means for cells to limit potentially harmful cGAS/STING responses during open mitosis via natural Golgi vesiculation.