bluuebunny/crossref_metadata_2025_split huggingface dataset:
Euvolemia—A critical target in the management of acute kidney injury
Authors: Colbert Gates B. , Szerlip Harold M. 
Published: November 2018

AbstractIt has been clearly established that critically ill patients with sepsis require prompt fluid resuscitation. The optimal amount of fluid and when to taper this resuscitation is less clear. There is a growing evidence that fluid overload leads to acute kidney injury, and increased morbidity and mortality. A clinician's best intentions in resuscitating a patient can lead to too much of a good thing. Currently, there are several bedside tools to aid in determining a patient's response to a fluid challenge as well as in the assessment of the current volume status. Guidelines are not available on the exact rate of fluid overload removal and what medicinal or mechanical modality is most favorable. We discuss our experience and an examination of the literature on the problems with fluid overload, and how a patient may benefit from forced fluid removal.
Participatory research meets validated outcome measures: Tensions in the co‐production of social care evaluation
Authors: Allen Kerry , Needham Catherine , Hall Kelly , Tanner Denise 
Published: November 2018

AbstractFunding for care service research is increasingly subject to the satisfaction of two requirements: public involvement and adoption of validated outcome tools. This study identifies competing paradigms within these requirements and reveals significant challenges faced by researchers who seek to satisfy them. The focus here is on a study co‐produced between academic researchers and people with experience of adult social care services. It examines to what extent research studies can conduct high‐quality public involvement and genuine co‐production of knowledge, whilst attempting to produce quantifiable outcome scores. Findings add to debate around how to incorporate diverse perspectives in research, which may draw on incommensurate accounts of validity and reliability. Findings also highlight constructive attempts by academic and co‐researchers to make the combination of approaches work in the field. These small scale acts of researcher agency indicate some scope to combine the two approaches in future research studies. However, conclusions foreground the importance of broader awareness of how tensions and power imbalances related to this combination of approaches play out in social policy research practice.
Loss Aversion and Risk Aversion in Wagering on Jeopardy!’s “Daily Double”*
Authors: Simon Curtis M. 
Published: November 2018

ObjectivesThe objective of the study was to test predictions of loss aversion and risk aversion by analyzing contestant wagers in the game show Jeopardy!MethodsThe primary method employed in this article is ordinary least squares regression analysis but the mean wagers of contestants in various player subcategories and stages of the game are also analyzed.ResultsThe results support the core proposition of loss aversion in that the mean wagers of contestants who are behind in the game are greater than are the mean wagers of contestants who are ahead in the game. The results also indicate some differences in the behavior of men and women in risk taking and that contestants make use of frames of reference in making their wagers such as how far ahead or behind they are in points and how much “time” is left in the game at the time of their wager.ConclusionGiven the results of this article and a review of other relevant literature, the suggestion is made that future studies of loss aversion and risk aversion continue to explore complexity and variation in the context of decision making and that future research into possible differences by sex in risk aversion explore scenarios in which choices are grounded in other‐ or community‐oriented situations rather than scenarios centering only on individual gains.
Will donor‐derived neoplasia be problematic after clinical pig organ or cell xenotransplantation?
Authors: Jagdale Abhijit , Iwase Hayato , Klein Edwin , Cooper David K. C. 
Published: November 2018

AbstractThere is an increased incidence of certain tumors and other neoplastic disease in organ allotransplant recipients receiving immunosuppressive therapy. Following clinical pig organ xenotransplantation, will there be a risk of the development of neoplasia in the pig graft or in other tissues transplanted with it, eg, lymph nodes? The incidence of neoplasia in young slaughterhouse pigs is very low (<0.005%), but in older pigs is largely unknown (as most pigs are killed within the first six months of life). However, lymphosarcoma, nephroblastoma, and melanoma have been reported in pigs. These tumors should be readily identified by ultrasound or direct inspection and palpation before an organ is excised for clinical xenotransplantation, and so transfer to the human recipient should be unlikely. Post‐transplant lymphoproliferative disorder (PTLD) has been reported in pigs receiving intensive immunomodulatory therapy, particularly if this includes whole body irradiation, in an effort to induce mixed hematopoietic chimerism and immunological tolerance. However, the pigs used as sources of organs in xenotransplantation should be free of the porcine lymphotropic herpesvirus that is a key causative factor for PTLD in pigs, and so donor‐derived PTLD should not occur. We conclude that the risk of a malignant tumor developing in a transplanted organ from a young pig is small.
Action potential shortening rescues atrial calcium alternans
Authors: Kanaporis Giedrius , Kalik Zane M. , Blatter Lothar A. 
Published: November 2018

Key points
Cardiac alternans refers to a beat‐to‐beat alternation in contraction, action potential (AP) morphology and Ca2+ transient (CaT) amplitude, and represents a risk factor for cardiac arrhythmia, including atrial fibrillation.
We developed strategies to pharmacologically manipulate the AP waveform with the goal to reduce or eliminate the occurrence of CaT and contraction alternans in atrial tissue.
With combined patch‐clamp and intracellular Ca2+ measurements we investigated the effect of specific ion channel inhibitors and activators on alternans. In single rabbit atrial myocytes, suppression of Ca2+‐activated Cl− channels eliminated AP duration alternans, but prolonged the AP and failed to eliminate CaT alternans. In contrast, activation of K+ currents (IKs and IKr) shortened the AP and eliminated both AP duration and CaT alternans.
As demonstrated also at the whole heart level, activation of K+ conductances represents a promising strategy to suppress alternans, and thus reducing a risk factor for atrial fibrillation.
AbstractAt the cellular level alternans is observed as beat‐to‐beat alternations in contraction, action potential (AP) morphology and magnitude of the Ca2+ transient (CaT). Alternans is a well‐established risk factor for cardiac arrhythmia, including atrial fibrillation. This study investigates whether pharmacological manipulation of AP morphology is a viable strategy to reduce the risk of arrhythmogenic CaT alternans. Pacing‐induced AP and CaT alternans were studied in rabbit atrial myocytes using combined Ca2+ imaging and electrophysiological measurements. Increased AP duration (APD) and beat‐to‐beat alternations in AP morphology lowered the pacing frequency threshold and increased the degree of CaT alternans. Inhibition of Ca2+‐activated Cl− channels reduced beat‐to‐beat AP alternations, but prolonged APD and failed to suppress CaT alternans. In contrast, AP shortening induced by activators of two K+ channels (ML277 for Kv7.1 and NS1643 for Kv11.1) abolished both APD and CaT alternans in field‐stimulated and current‐clamped myocytes. K+ channel activators had no effect on the degree of Ca2+ alternans in AP voltage‐clamped cells, confirming that suppression of Ca2+ alternans was caused by the changes in AP morphology. Finally, activation of Kv11.1 channel significantly attenuated or even abolished atrial T‐wave alternans in isolated Langendorff perfused hearts. In summary, AP shortening suppressed or completely eliminated both CaT and APD alternans in single atrial myocytes and atrial T‐wave alternans at the whole heart level. Therefore, we suggest that AP shortening is a potential intervention to avert development of alternans with important ramifications for arrhythmia prevention and therapy.
3D dSTORM imaging reveals novel detail of ryanodine receptor localization in rat cardiac myocytes
Authors: Shen Xin , van den Brink Jonas , Hou Yufeng , Colli Dylan , Le Christopher , Kolstad Terje R. , MacQuaide Niall , Carlson Cathrine R. , Kekenes‐Huskey Peter M. , Edwards Andrew G. , Soeller Christian , Louch William E. 
Published: November 2018

Key points
Using 3D direct stochastic optical reconstruction microscopy (dSTORM), we developed novel approaches to quantitatively describe the nanoscale, 3D organization of ryanodine receptors (RyRs) in cardiomyocytes.
Complex arrangements of RyR clusters were observed in 3D space, both at the cell surface and within the cell interior, with allocation to dyadic and non‐dyadic pools.
3D imaging importantly allowed discernment of clusters overlapping in the z‐axis, for which detection was obscured by conventional 2D imaging techniques. Thus, RyR clusters were found to be significantly smaller than previous 2D estimates.
Ca2+ release units (CRUs), i.e. functional groupings of neighbouring RyR clusters, were similarly observed to be smaller than earlier reports. Internal CRUs contained more RyRs in more clusters than CRUs on the cell surface, and yielded longer duration Ca2+ sparks.
AbstractCardiomyocyte contraction is dependent on Ca2+ release from ryanodine receptors (RyRs). However, the precise localization of RyRs remains unknown, due to shortcomings of imaging techniques which are diffraction limited or restricted to 2D. We aimed to determine the 3D nanoscale organization of RyRs in rat cardiomyocytes by employing direct stochastic optical reconstruction microscopy (dSTORM) with phase ramp technology. Initial observations at the cell surface showed an undulating organization of RyR clusters, resulting in their frequent overlap in the z‐axis and obscured detection by 2D techniques. Non‐overlapping clusters were imaged to create a calibration curve for estimating RyR number based on recorded fluorescence blinks. Employing this method at the cell surface and interior revealed smaller RyR clusters than 2D estimates, as erroneous merging of axially aligned RyRs was circumvented. Functional groupings of RyR clusters (Ca2+ release units, CRUs), contained an average of 18 and 23 RyRs at the surface and interior, respectively, although half of all CRUs contained only a single ‘rogue’ RyR. Internal CRUs were more tightly packed along z‐lines than surface CRUs, contained larger and more numerous RyR clusters, and constituted ∼75% of the roughly 1 million RyRs present in an average cardiomyocyte. This complex internal 3D geometry was underscored by correlative imaging of RyRs and t‐tubules, which enabled quantification of dyadic and non‐dyadic RyR populations. Mirroring differences in CRU size and complexity, Ca2+ sparks originating from internal CRUs were of longer duration than those at the surface. These data provide novel, nanoscale insight into RyR organization and function across cardiomyocytes.
Seasonality in clinical courses of Kawasaki disease
Authors: Shimizu Daisuke , Hoshina Takayuki , Kawamura Masaru , Tomita Yoshie , Hidaka Yasufumi , Kojiro Masumi , Muneuchi Jun , Kamizono Junji , Yamaguchi Kenichiro , Fujino Yoshihisa , Kusuhara Koichi 
Published: November 2018

ObjectiveEpidemics of Kawasaki disease (KD) are well known; however, the seasonal variation in the clinical course of KD is uncertain. The aim of this study was to investigate the seasonality in the clinical course of KD.MethodsThis study included 744 patients who were admitted to six hospitals in Kitakyushu City for KD from 2010 to 2014. We divided the patients into two groups according to the average monthly temperature (warm and cold periods) and compared the clinical courses of KD.ResultsThe clinical courses of 715 patients who were initially treated with intravenous immunoglobulin (IVIG) were investigated. The proportion of patients with resistance to the initial IVIG therapy was significantly higher during the warm period than during the cold period (p=0.016). There was no seasonality in the proportion of patients with coronary artery abnormalities.ConclusionSeasonality was observed in the response to IVIG therapy of patients with KD.
Quantitative analysis of structure–function relationship between ocular motility and superior oblique muscle hypoplasia in unilateral superior oblique palsy
Authors: Lee Ji Eun , Yang Hee Kyung , Kim Jae Hyoung , Hwang Jeong-Min 
Published: November 2018

AimsTo determine the structure–function relationship between the degree of superior oblique (SO) hypoplasia and ocular motility in unilateral SO palsy.MethodsA total of 166 patients with unilateral SO palsy were divided into three groups based on their aetiology and high-resolution MRI findings by an in-plane resolution of 0.25 mm: (1) congenital SO palsy and unilateral trochlear nerve agenesis (absent group, n=79), (2) congenital SO palsy and symmetric trochlear nerves on both sides (present group, n=40) and (3) acquired SO palsy (acquired group, n=47) who all had symmetric trochlear nerves on both sides. The degree of SO hypoplasia was defined as the ratio of SO area between the paretic and nonparetic sides (SOP/N) at the optic nerve–globe junction on MR images. Multivariate analysis was performed to investigate the relationship between SO hypoplasia and ocular motility parameters.ResultsThe degree of SO hypoplasia (SOP/N) showed a weak negative correlation with bilateral head tilt differences in all groups (β=−0.009, p<0.001 in the absent group; β=−0.003, p=0.034 in the present group; β=−0.007, p=0.002 in the acquired group). There was only a weak positive correlation with SOP/N and hypertropia differences between both gazes in the absent group (β=0.009, p<0.001) and the acquired group (β=0.007, p=0.001). In addition, none of the other ocular motility parameters were related to the degree of SO hypoplasia in all groups.ConclusionRegardless of the aetiology of unilateral SO palsy, the structure–function relationship of the paretic SO size and ocular motility examination was weak and almost negligible.
Obstructive sleep apnoea and increased risk of non-arteritic anterior ischaemic optic neuropathy
Authors: Yang Hee Kyung , Park Sang Jun , Byun Seong Jun , Park Kyu Hyung , Kim Jeong-Whun , Hwang Jeong-Min 
Published: November 2018

Background/aimsTo determine whether the development of non-arteritic anterior ischaemic optic neuropathy (NAION) is increased among patients newly diagnosed with obstructive sleep apnoea (OSA) in a large general population.MethodsA 12-year nationwide, population-based, retrospective cohort study including 1 025 340 beneficiaries in the 2002–2013 Korean National Health Insurance Service database was performed. We identified 919 patients newly diagnosed with OSA aged ≥40 years and matched 9190 non-OSA controls using estimated propensity scores in reference to age, sex, demographics, comorbidities and co-medications. We applied Kaplan-Meier curves and Cox proportional hazard models to determine the risk of developing NAION in the OSA group compared with the non-OSA group.ResultsThe 10-year incidence probability of NAION was higher in the OSA group (0.92%; 95% CI 0.88 to 0.97) than the non-OSA group (0.42%; 95% CI 0.41 to 0.44, p=0.002, log-rank test). The OSA group was at increased risk of developing NAION compared with the non-OSA group (HR 3.80; 95% CI 1.46 to 9.90) after adjusting for demographics, comorbidities and co-medications.ConclusionsOur results suggest that patients with newly diagnosed OSA have an increased risk of NAION, although the absolute risk of NAION is low.
Exploring the phase for highest impact on radicality: a cross-sectional study of patient involvement in quality improvement in Swedish healthcare
Authors: Gremyr Ida , Elg Mattias , Smith Frida , Gustavsson Susanne 
Published: November 2018

ObjectivesInvolving patients in quality improvement is often suggested as a critical step for improving healthcare processes. However, this comes with challenges related to resources, tokenism, validity and competence. Therefore, to optimise the use of available resources, there is a need to understand at what stage in the improvement cycle patient involvement is most beneficial. Thus, the purpose of this study was to identify the phase of an improvement cycle in which patient involvement had the highest impact on radicality of improvement.DesignAn exploratory cross-sectional survey was used.Setting and methodsA questionnaire was completed by 155 Swedish healthcare professionals (response rate 34%) who had trained and had experience in patient involvement in quality improvement. Based on their replies, the impact of patient involvement on radicality in various phases of the improvement cycle was modelled using the partial least squares method.ResultsPatient involvement in quality improvement might help to identify and realise innovative solutions; however, there is variation in the impact of patient involvement on perceived radicality depending on the phase in which patients become involved. The highest impact on radicality was observed in the phases of capture experiences and taking action, while a moderate impact was observed in the evaluate phase. The lowest impact was observed in the identify and prioritise phase.ConclusionsInvolving patients in improvement projects can enhance the quality of care and help to identify radically new ways of delivering care. This study shows that it is possible to suggest at what point in an improvement cycle patient involvement has the highest impact, which will enable more efficient use of the resources available for patient involvement.
Are inequalities in cancer diagnosis through emergency presentation narrowing, widening or remaining unchanged? Longitudinal analysis of English population-based data 2006–2013
Authors: Herbert Annie , Abel Gary A , Winters Sam , McPhail Sean , Elliss-Brookes Lucy , Lyratzopoulos Georgios 
Published: November 2018

BackgroundDiagnosis of cancer through emergency presentation is associated with poorer prognosis. While reductions in emergency presentations have been described, whether known sociodemographic inequalities are changing is uncertain.MethodsWe analysed ‘Routes to Diagnosis’ data on patients aged ≥25 years diagnosed in England during 2006–2013 with any of 33 common or rarer cancers. Using binary logistic regression we determined time-trends in diagnosis through emergency presentation by age, deprivation and cancer site.ResultsOverall adjusted proportions of emergency presentations decreased during the study period (2006: 23%, 2013: 20%). Substantial baseline (2006) inequalities in emergency presentation risk by age and deprivation remained largely unchanged. There was evidence (p<0.05) of reductions in the risk of emergency presentations for most (28/33) cancer sites, without apparent associations between the size of reduction and baseline risk (p=0.26). If there had been modest reductions in age inequalities (ie, patients in each age group acquiring the same percentage of emergency presentations as the adjacent group with lower risk), in the last study year we could have expected around 11 000 fewer diagnoses through emergency presentation (ie, a nationwide percentage of 16% rather than the observed 20%). For similarly modest reductions in deprivation inequalities, we could have expected around 3000 fewer (ie, 19%).ConclusionThe proportion of cancer diagnoses through emergency presentation is decreasing but age and deprivation inequalities prevail, indicating untapped opportunities for further improvements by reducing these inequalities. The observed reductions in proportions across nearly all cancer sites are likely to reflect both earlier help-seeking and improvements in diagnostic healthcare pathways, across both easier-to-suspect and harder-to-suspect cancers.
Patterns of BMI development between 10 and 42 years of age and their determinants in the 1970 British Cohort Study
Authors: Viner Russell M , Costa Silvia , Johnson William 
Published: November 2018

BackgroundMixture modelling is a useful approach to identify subgroups in a population who share similar trajectories. We aimed to identify distinct body mass index (BMI) trajectories between 10 and 42 years and investigate how known early-life risk factors are related to trajectories.MethodsSample: 9187 participants in the 1970 British Birth Cohort Study, with BMI observations between 10 and 42 years and data on birth weight, parental BMI, socioeconomic status, breast feeding and puberty. Latent growth mixture modelling in Mplus was used to model age-related BMI trajectories and test associations of risk factors with trajectory membership.ResultsA three latent class model was most credible: (1) normative: 92%: started normal weight but gradually increased BMI to become overweight in adulthood; (2) childhood onset persistent obesity (COP): 4%: persistently high BMI from childhood; (3) adolescent and young adulthood onset obesity (AYAO): 4%: normal weight in childhood but had a steep ascending trajectory. Higher maternal and paternal BMI and early puberty increased the probability of being in either the COP or the AYAO classes compared with the normative class.ConclusionMost individuals gradually increased BMI and became overweight in mid-adulthood. Only 8% demonstrated more severe BMI trajectories. Further research is needed to understand the underlying body composition changes and health risks in the COP and AYAO classes.
Epidemiology of ALS in Korea using nationwide big data
Authors: Jun Kyo Yeon , Park Jinseok , Oh Ki-Wook , Kim Eun Mi , Bae Jong Seok , Kim Inah , Kim Seung Hyun 
Published: November 2018

ObjectiveThis study aimed to determine the incidence, prevalence and survival time of Korean patients with amyotrophic lateral sclerosis (ALS) using National Health Insurance Service (NHIS) data.MethodsUsing NHIS data, the Korean nationwide health dataset, we identified patients with motor neuron diseases who were first diagnosed with a KCD-6 code (G12.20–G12.28; modified from ICD-10 codes) between 2011 and 2015. ALS (G12.21 code) epidemiological characteristics, including annual incidence, prevalence, mortality rates and survival time, were analysed and compared with sociodemographic variables.ResultsNew patients with ALS (n=3049) were enrolled over 5 years. The mean annual incidence was 1.20/100 000, and the sex ratio was 1.60 (male:female). The mean age at the time of diagnosis was 61.4 years. The prevalence rate was 3.43/100 000 in 2015. In this period, riluzole was prescribed to 53.6% of patients with ALS. Furthermore, 20.3% of patients with ALS underwent tracheostomy. When analysed for age and socioeconomic status, ALS prevalence rate was 10.71 in the aged group (≥60) in 2015 and was lowest in the middle-income group compared with that in the high-income and low-income groups. The estimated mean survival time in this population was 50.0 months, and the 3-year and 5-year mortality rates were 52.1% and 63.7%, respectively.ConclusionsThis study is the first nationwide survey for epidemiological characteristics of ALS in Korea using national data. The use of these data substantially advances the understanding of Korean and Asian ALS epidemiology and its relationship with socioeconomic status, age and sex.