bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective 20‐year longitudinal follow‐up of dementia in persons with Down syndrome
Authors: McCarron M. , McCallion P. , Reilly E. , Dunne P. , Carroll R. , Mulryan N. 
Published: June 2017

AbstractGoalTo examine dementia characteristics, age at onset and associated co‐morbidities in persons with Down syndrome.MethodA total of 77 people with Down syndrome aged 35 years and older were followed up from 1996 to 2015. The diagnosis of dementia was established using the modified ICD 10 Criteria and a combination of objective and informant‐based tests. Cognitive tests included the Test for Severe Impairment and the Down Syndrome Mental Status Examination; adaptive behaviour was measured using the Daily Living Skills Questionnaire, and data from the Dementia Questionnaire for People with Intellectual Disabilities have been available since 2005.ResultsOver the 20‐year period, 97.4% (75 of 77) persons developed dementia with a mean age of dementia diagnosis of 55 years (SD = 7.1, median = 56 years). Clinical dementia was associated with cognitive and function decline and seizure activity. Risk for dementia increased from 23% in those aged 50 years to 80% in those aged 65 years and above. There were no differences by level of ID.ConclusionThe previously reported high risk levels for dementia among people with Down syndrome were confirmed in this data as was the relationship with late onset epilepsy. The value of the instruments utilised in tracking decline and helping to confirm diagnosis is further highlighted.
Between the military government and the minority affairs ministry: The construction of the Palestinian minority as a security threat during the first years of the existence of Israel
Authors: Korn Alina 
Published: June 2017

AbstractThis study examines correspondence and documents on various matters handled by Israel's Ministry of Minority Affairs during its brief period of operation. The extensive correspondence illuminates aspects relating to the distress faced by Palestinian citizens as a result of the 1948 War and the restrictions imposed on them by the military government, as well as the nature of the emerging relationship between the State and the minority population during the crucial first year following the establishment of Israel. We argue that the construction of the Palestinian minority as a security threat was not a product of the war circumstances, but rather an outcome of interests and political considerations. This construction grew gradually, along with the developing of practices of supervision and means of control, peaking with the subjugation of the Arab population to military government.
The PKR regulatory subunit of protein kinase A (PKA) is involved in the regulation of growth, sexual and asexual development, and pathogenesis in Fusarium graminearum
Authors: Li Chaoqun , Zhang Yonghui , Wang Huan , Chen Lingfeng , Zhang Ju , Sun Manli , Xu Jin‐Rong , Wang Chenfang 
Published: June 2017

SummaryFusarium graminearum is a causal agent of wheat scab disease and a producer of deoxynivalenol (DON) mycotoxins. Treatment with exogenous cyclic adenosine monophosphate (cAMP) increases its DON production. In this study, to better understand the role of the cAMP–protein kinase A (PKA) pathway in F. graminearum, we functionally characterized the PKR gene encoding the regulatory subunit of PKA. Mutants deleted of PKR were viable, but showed severe defects in growth, conidiation and plant infection. The pkr mutant produced compact colonies with shorter aerial hyphae with an increased number of nuclei in hyphal compartments. Mutant conidia were morphologically abnormal and appeared to undergo rapid autophagy‐related cell death. The pkr mutant showed blocked perithecium development, but increased DON production. It had a disease index of less than unity and failed to spread to neighbouring spikelets. The mutant was unstable and spontaneous suppressors with a faster growth rate were often produced on older cultures. A total of 67 suppressor strains that grew faster than the original mutant were isolated. Three showed a similar growth rate and colony morphology to the wild‐type, but were still defective in conidiation. Sequencing analysis with 18 candidate PKA‐related genes in three representative suppressor strains identified mutations only in the CPK1 catalytic subunit gene. Further characterization showed that 10 of the other 64 suppressor strains also had mutations in CPK1. Overall, these results showed that PKR is important for the regulation of hyphal growth, reproduction, pathogenesis and DON production, and mutations in CPK1 are partially suppressive to the deletion of PKR in F. graminearum.
Phage Therapy Approaches to Reducing Pathogen Persistence and Transmission in Animal Production Environments: Opportunities and Challenges
Authors: Colavecchio Anna , Goodridge Lawrence D. 
Published: June 2017

ABSTRACTThe era of genomics has allowed for characterization of phages for use as antimicrobials to treat animal infections with a level of precision never before realized. As more research in phage therapy has been conducted, several advantages of phage therapy have been realized, including the ubiquitous nature, specificity, prevalence in the biosphere, and low inherent toxicity of phages, which makes them a safe and sustainable technology for control of animal diseases. These unique qualities of phages have led to several opportunities with respect to emerging trends in infectious disease treatment. However, the opportunities are tempered by several challenges to the successful implementation of phage therapy, such as the fact that an individual phage can only infect one or a few bacterial strains, meaning that large numbers of different phages will likely be needed to treat infections caused by multiple species of bacteria. In addition, phages are only effective if enough of them can reach the site of bacterial colonization, but clearance by the immune system upon introduction to the animal is a reality that must be overcome. Finally, bacterial resistance to the phages may develop, resulting in treatment failure. Even a successful phage infection and lysis of its host has consequences, because large amounts of endotoxin are released upon lysis of Gram-negative bacteria, which can lead to local and systemic complications. Overcoming these challenges will require careful design and development of phage cocktails, including comprehensive characterization of phage host range and assessment of immunological risks associated with phage treatment.
Vitreoretinal interface abnormalities in middle-aged adults with visual impairment in the UK Biobank study: prevalence, impact on visual acuity and associations
Authors: McKibbin Martin , Farragher Tracey , Shickle Darren 
Published: June 2017

ObjectiveThe aim of this study was to determine the prevalence of vitreoretinal interface abnormalities (VRIA), the degree of visual impairment and associations with VRIA among adults, aged 40–69 years, in the UK Biobank study.Methods and analysisColour fundus photographs and spectral domain optical coherence tomography images were graded for 25% of the 8359 UK Biobank participants with mild visual impairment or worse (LogMAR >0.3 or Snellen <6/12) in at least one eye. The prevalence and contribution of VRIA to visual impairment was determined and multinomial logistic regression models were used to investigate association with known risk factors and other predetermined socioeconomic, biometric, lifestyle and medical variables for cases and matched controls.ResultsThe minimum prevalence of any VRIA was 17.6% and 8.1% in the eyes with and without visual impairment, respectively. VRIA were identified as the primary cause of visual impairment in 3.6% of eyes. Although epiretinal membrane and vitreomacular traction were the most common VRIA, the degree of visual impairment was typically milder with these than with other VRIA. Visual impairment with a VRIA was positively associated with increasing age (relative risk ratio (RRR) 1.22 (95% CI 1.07 to 1.40)), female gender (RRR 1.28; 1.08 to 1.52) and Asian or Asian British ethnicity (RRR 1.60; 1.10 to 2.32).ConclusionsVRIA are common in middle-aged adults in the UK Biobank study, especially in eyes with visual impairment. VRIA were considered to be the primary cause of visual impairment in 3.6% of all eyes with visual impairment, although there was variation in the degree of visual impairment for each type of VRIA.
Oral administration of the 11β-hydroxysteroid-dehydrogenase type 1 inhibitor RO5093151 to patients with glaucoma: an adaptive, randomised, placebo-controlled clinical study
Authors: Schwab Dietmar , Sturm Carolina , Portron Agnès , Fuerst-Recktenwald Sabine , Hainzl Dominik , Jordan Paul , Stewart William C , Tepedino Michael E , DuBiner Harvey 
Published: June 2017

Background/aimsCortisol is involved in the regulation of intraocular pressure (IOP). This study aimed to assess the effect of 11β-hydroxysteroid-dehydrogenase type 1 (11βHSD1) inhibition by oral administration of RO5093151 on IOP.MethodsThe exposure of key ocular compartments following oral administration was assessed in rabbits. An adaptive, randomised, placebo-controlled study gated by a Bayesian decision criterion was performed in 35 patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). Following a 7-day placebo-controlled run-in period, 200 mg twice daily RO5093151 or placebo (4:1) were administered for 7 days. The extent of 11βHSD1 inhibition was assessed by the ratio of urinary tetrahydrocortisol (5α and 5β)/tetrahydrocortisone (THF/THE). Time-matched IOP assessments were performed.ResultsA high distribution of RO5093151 into the rabbit eye was observed. In humans, a high and sustained inhibition of 11βHSD1 was shown by the decrease of THF/THE from 0.9 at baseline to 0.18 on day 7. There was no statistically significant difference in change of IOP from baseline. In the ‘worse eye’, the adjusted least square mean change from baseline was −2.7 mm Hg (95% CI −4.2 to –1.2) and −2.9(95% CI −5.9 to 0.1) in the RO5093151 and placebo group, respectively.ConclusionsDespite high inhibition of 11βHSD1 and expected moderate to high tissue distribution in ocular tissues, a 7-day treatment with a high oral dose of RO5093151 did not result in a clinically meaningful effect on IOP in patients with POAG or OHT.
Determinants of hospital death in haematological cancers: findings from a qualitative study
Authors: McCaughan Dorothy , Roman Eve , Smith Alexandra G , Garry Anne , Johnson Miriam , Patmore Russell , Howard Martin , Howell Debra A 
Published: June 2017

ObjectivesCurrent UK health policy promotes enabling people to die in a place they choose, which for most is home. Despite this, patients with haematological malignancies (leukaemias, lymphomas and myeloma) are more likely to die in hospital than those with other cancers, and this is often considered a reflection of poor quality end-of-life care. This study aimed to explore the experiences of clinicians and relatives to determine why hospital deaths predominate in these diseases.MethodsThe study was set within the Haematological Malignancy Research Network (HMRN—www.hmrn.org), an ongoing population-based cohort that provides infrastructure for evidence-based research. Qualitative interviews were conducted with clinical staff in haematology, palliative care and general practice (n=45) and relatives of deceased HMRN patients (n=10). Data were analysed for thematic content and coding and classification was inductive. Interpretation involved seeking meaning, salience and connections within the data.ResultsFive themes were identified relating to: the characteristics and trajectory of haematological cancers, a mismatch between the expectations and reality of home death, preference for hospital death, barriers to home/hospice death and suggested changes to practice to support non-hospital death, when preferred.ConclusionsHospital deaths were largely determined by the characteristics of haematological malignancies, which included uncertain trajectories, indistinct transitions and difficulties predicting prognosis and identifying if or when to withdraw treatment. Advance planning (where possible) and better communication between primary and secondary care may facilitate non-hospital death.
Outcome after percutaneous edge-to-edge mitral repair for functional and degenerative mitral regurgitation: a systematic review and meta-analysis
Authors: Chiarito Mauro , Pagnesi Matteo , Martino Enrico Antonio , Pighi Michele , Scotti Andrea , Biondi-Zoccai Giuseppe , Latib Azeem , Landoni Giovanni , Mario Carlo Di , Margonato Alberto , Maisano Francesco , Feldman Ted , Alfieri Ottavio , Colombo Antonio , Godino Cosmo 
Published: June 2017

ObjectivesDifferences in terms of safety and efficacy of percutaneous edge-to-edge mitral repair between patients with functional and degenerative mitral regurgitation (MR) are not well established. We performed a systematic review and meta-analysis to clarify these differences.MethodsPubMed, EMBASE, Google scholar database and international meeting abstracts were searched for all studies about MitraClip. Studies with <25 patients or where 1-year results were not delineated between MR aetiology were excluded. This study is registered with PROSPERO.ResultsA total of nine studies investigating the mid-term outcome of percutaneous edge-to-edge repair in patients with functional versus degenerative MR were included in the meta-analysis (n=2615). At 1 year, there were not significant differences among groups in terms of patients with MR grade≤2 (719/1304 vs 295/504; 58% vs 54%; risk ratio (RR) 1.12; 95% CI: 0.86 to 1.47; p=0.40), while there was a significantly lower rate of mitral valve re-intervention in patients with functional MR compared with those with degenerative MR (77/1770 vs 80/818; 4% vs 10%; RR 0.60; 95% CI: 0.38 to 0.97; p=0.04). One-year mortality rate was 16% (408/2498) and similar among groups (RR 1.26; 95% CI: 0.90 to 1.77; p=0.18). Functional MR group showed significantly higher percentage of patients in New York Heart Association class III/IV (234/1480 vs 49/583; 16% vs 8%; p<0.01) and re-hospitalisation for heart failure (137/605 vs 31/220; 23% vs 14%; p=0.03). No differences were found in terms of single leaflet device attachment (25/969 vs 20/464; 3% vs 4%; p=0.81) and device embolisation (no events reported in both groups) at 1 year.ConclusionsThis meta-analysis suggests that percutaneous edge-to-edge repair is likely to be an efficacious and safe option in patients with both functional and degenerative MR. Large, randomised studies are ongoing and awaited to fully assess the clinical impact of the procedure in these two different MR aetiologies.
First and recurrent ischaemic heart disease events continue to decline in New Zealand, 2005–2015
Authors: Grey Corina , Jackson Rod , Wells Susan , Wu Billy , Poppe Katrina , White Harvey , Chan Wing Cheuk , Kerr Andrew J 
Published: June 2017

ObjectivesTo examine recent trends in first and recurrent ischaemic heart disease (IHD) deaths and hospitalisations.MethodsUsing anonymous patient-linkage of routinely collected data, all New Zealanders aged 35–84 years who experienced an International Statistical Classification of Diseases and Related Health Problems I(CD)-coded IHD hospitalisation and/or IHD death between 1 January 2005 and 31 December 2015 were identified. A 10-year look-back period was used to differentiate those experiencing first from recurrent events. Age-standardised hospitalisation and mortality rates were calculated for each calendar year and trends compared by sex and age.Results160 109 people experienced at least one IHD event (259 678 hospitalisations and 35 548 deaths) over the 11-year study period, and there was a steady decline in numbers (from almost 24 000 in 2005 to just over 16 000 in 2015) and in age-standardised rates each year. With the exception of deaths in younger (35–64 years) women with prior IHD, there was a significant decline in IHD events in men and women of all ages, with and without a history of IHD. The decline in IHD mortality was greater for those experiencing a first rather than recurrent IHD event (3.8%–5.2% vs 0%–3.7% annually on average). In contrast, the decline in IHD hospitalisations was greater for those experiencing a recurrent compared with a first IHD event (5.6%–7.3% vs 3.2%–5.7% annually on average).ConclusionsThe substantial decline in IHD hospitalisations and mortality observed in New Zealanders with and without prior IHD between 2005 and 2015 suggests that primary and secondary prevention efforts have been effective in reducing the occurrence of IHD events.
Structures in the diffraction cone: The “break” and “dip” in high-energy proton–proton scattering
Authors: Jenkovszky László , Szanyi István 
Published: June 2017

Anticipating forthcoming publication by the TOTEM collaboration of low-[Formula: see text] elastic scattering data at [Formula: see text] = 13 and 2.76 TeV, hereby we emphasize the correlation between two prominent structures seen upon the otherwise exponential diffraction cone, namely a “break” staying fixed around [Formula: see text]0.1 GeV2 and a dip moving with energy logarithmically inwards; while at the ISR, the two structures are separated by a distance of about 1 GeV2, at the LHC, the dip comes close to the periphery of the “break”, thus affecting its parametrization. An unbiased disentangling and identification of the “break” at the LHC should account for this correlation.
Cataloguing tsunami events in the UK
Authors: Long Dave 
Published: June 2017

Abstract
Tsunami catalogues provide important datasets in assessing the risk from infrequent but potentially high-impact events. Although the UK is located away from subduction zones (the most common origin of tsunamis), tsunamis have struck its shores, most notably those triggered by the prehistoric Storegga submarine landslide and the 1755 Lisbon earthquake. Since the major events of 2004 (Indian Ocean) and 2011 (Japan) tsunamis are in the public psyche, even if the risks to UK coasts are not. Due to this heightened awareness, many reported events are claimed to be tsunamis and the potential for tsunamis is increasingly included in risk planning; understanding the true frequency of tsunamis is therefore important. Within the UK, the evidence for tsunamis includes tide gauge readings, reported visual observations and interpretation of sedimentological features. Catalogues need to consider whether the event is a true tsunami in order to avoid a plethora of claims that confound risk assessments; for example, recent well-documented events generated by weather systems (meteotsunamis) provide a possible explanation for some historical events. A detailed examination of the impact of tsunamis upon the UK coast is provided, including examples of events triggered by the three primary causes of tsunamis: seismicity, submarine landslides and coastal landslides.
Generating Obligations, Assertions and Tests from UI Models
Authors: Bowen Judy , Reeves Steve 
Published: June 2017

Model-based development of interactive systems provides a number of benefits which can support the creation of robust and correct systems, particularly important when the interactive systems are safety-critical. Many different approaches have been proposed which target the models at different aspects of the development process (for example task analysis, interface layouts, functional behaviours etc.) and which can be used in different ways (verification of correctness, plasticity, usability).
One of the aims for any modelling method should be simplicity - we are after all trying to hide complexity via abstraction in order to make reasoning about systems more tractable than working at the programming level. One of the challenges that exists however we do our modelling is ensuring the consistency between the model of the interface and interactivity and model of the functional behaviour of the system. This is primarily due to the different types of models that most naturally describe these different elements. In this paper we propose a method of tightening the integration of models of these different components of the system by generating obligations which explicitly describe the coupling of functional behaviour with interactive elements. We then show how these obligations can be used to support the development process during the programming and testing of the system.
Ly6C
high
Monocytes Oscillate in the Heart During Homeostasis and After Myocardial Infarction—Brief Report
Authors: Schloss Maximilian J. , Hilby Michael , Nitz Katrin , Guillamat Prats Raquel , Ferraro Bartolo , Leoni Giovanna , Soehnlein Oliver , Kessler Thorsten , He Wenyan , Luckow Bruno , Horckmans Michael , Weber Christian , Duchene Johan , Steffens Sabine 
Published: June 2017

Objective—
Circadian regulation of neutrophil homeostasis affects myocardial infarction (MI) healing. It is unknown whether diurnal variations of monocyte counts exist in the heart and whether this affects their cardiac infiltration in response to MI.

Approach and Results—

Murine blood and organs were harvested at distinct times of day and analyzed by flow cytometry. Ly6C
high
monocyte surface expression levels of chemokine receptors (CCR) were ≈2-fold higher at the beginning of the active phase, Zeitgeber Time (ZT) 13 compared with ZT5. This was because of enhanced receptor surface expression at ZT13, whereas no significant changes in total cellular protein levels were found. Most blood Ly6C
high
monocytes were CCR2
high
, whereas only a minority was CCR1
high
and CCR5
high
. We also found diurnal changes of classical monocyte blood counts in humans, being higher in the evening, while exhibiting enhanced CCR2 surface expression in the morning. In support of monocyte oscillations between blood and tissue, murine cardiac Ly6C
high
monocyte counts were highest at ZT13, accompanied by an upregulation of cardiac CC chemokine ligand 2 mRNA. Mice subjected to MI at ZT13 had an even higher upregulation of CCR2 surface expression on circulating monocytes compared with noninfarcted mice and more elevated cardiac CC chemokine ligand 2 protein expression and more pronounced Ly6C
high
monocyte infiltration compared with ZT5-infarcted mice. Concomitantly, CCR2 antagonism only inhibited the excessive cardiac Ly6C
high
monocyte infiltration after ZT13 MI but not ZT5 MI.

Conclusions—

CCR2 surface expression on Ly6C
high
monocytes changes in a time-of-day–dependent manner, which crucially affects cardiac monocyte recruitment after an acute ischemic event.
The value of systems and complexity sciences for healthcare: a review
Authors: Anwar Fozia , Yousafzai Afifa , Niazi Muaz A. 
Published: June 2017

Book detailsEditor: Joachim P. SturmbergThe Value of Systems and Complexity Sciences for Healthcare.Berlin: Springer Publishers; 2016.285 pages; ISBN: 978-3-319-26219-2, ISBN (eBook): 978-3-319-26221-5
Words and Deeds: Presidential Discussion of Minority Health, Public Policies, and Minority Perceptions
Authors: Gillion Daniel Q. 
Published: June 2017

Abstract
What are the different rhetorical approaches presidents used to address minority health inequality? More importantly, how have the efforts of presidents impacted minorities' perceptions of health? I offer a historical perspective that describes the three major periods of presidential engagement in discussions of minority health since the 1960s. I couple this historical overview with an empirical assessment that introduces a novel and extensive dataset of every presidential discussion of minority health spanning five decades (1960–2016). This study finds that, since the early 1990s, presidents have transported their discussion of minority health beyond the confines of Washington, DC, traveling to speak to local communities throughout the nation that have a disproportionate number of blacks and Latinos. Moreover, a presidential discussion of minority health leads to greater salience on this issue and thus increases public health awareness. This work suggests that presidential messaging on minority health provides a framework for minority groups to understand and discuss the health disparities that may plague their communities.