bluuebunny/crossref_metadata_2025 huggingface dataset:
CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1
Authors: Li Shu , Xue Jingyi , Sun Zhipeng , Liu Tiantian , Zhang Lane , Wang Limin , You Hongjie , Fan Zheng , Zheng Yuanyuan , Luo Dali
Published: April 2018

Background/Aims: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a regulator of SOCE, but how CaMKII regulates SOCE remains obscure. Methods: Using Fura2, confocal microscopy, co-immunoprecipitation, specific blocker and overexpression/knockdown approaches, we evaluated STIM1 aggregation and its interaction with Orai1, and SOCE upon Ca2+ store depletion in thapsigargin (TG) treated HEK293 and HeLa cells. Results: Overexpression of CaMKIIδ enhanced TG-induced STIM1 co-localization and interaction with Orai1 as well as SOCE. In contrast, CaMKIIδ knockdown and a specific inhibitor of CaMKII suppressed them. In addition, overexpression or knockdown of CaMKIIδ in TG treated cells exhibited increased or reduced STIM1 clustering and plasmalemma redistribution, respectively. Conclusion: CaMKII up-regulates SOCE by increasing STIM1 aggregation and interaction with Orai1. This study provides an additional insight into SOCE regulation and a potential mechanism for CaMKII involvement in some pathological situations through crosstalk with SOCE.
Transcriptome, Biochemical and Growth Responses of the Marine Phytoplankter Phaeodactylum Tricornutum Bohlin (Bacillariophyta) to Copepod Grazer Presence
Authors: Li Si , Ismar Stefanie M.H.
Published: April 2018

Background/Aims: As a model organism for a pleiomorphic marine planktonic primary producer, Phaeodactylum tricornutum has been studied on a molecular level under diverse cultural conditions. But little is known about its morphological, nutritional or transcriptomic responses under grazing stress. Methods: To assess microalgal molecular and cellular responses to grazer presence, we conducted transcriptome profiling in combination with growth rate, biovolume, fatty acid content, carbon and nitrogen content measurements in the model diatom Phaeodactylum tricornutum. RNA-sequencing was used to evaluate the transcriptomic response to grazing stress for P. tricornutum strain CCAP 1055/1. Results: Among the differentially expressed genes, we found down-regulation of genes involved in pathogen resistance, and in fatty acid biosynthesis pathways, while mitosis-involved genes were up-regulated. Experimentally testing morphological and biochemical responses in five strains of the species, we detected strain-specific significant effects of simulated grazing pressure in altered growth rates, biovolume and nutritional composition. Conclusion: Our research reveals the associated molecular and cellular responses to grazing effects in P. tricornutum and extends the understanding of co-evolutionary roles in regulating grazing defence between P. tricornutum and its grazer.
Characterization of the σ-Pore in Mutant hKv1.3 Potassium Channels
Authors: Tyutyaev Pavel , Grissmer Stephan
Published: April 2018

Background/Aims: The replacement of the amino acid valine at position 388 (Shaker position 438) in hKv1.3 channels or at the homologue position 370 in hKv1.2 channels resulted in a channel with two different ion conducting pathways: One pathway was the central, potassium-selective α-pore, that was sensitive to block by peptide toxins (CTX or KTX in the hKv1.3_V388C channel and CTX or MTX in the hKv1.2_V370C channel). The other pathway (σ-pore) was behind the central α-pore creating an inward current at potentials more negative than -100 mV, a potential range where the central α-pore was closed. In addition, current through the σ-pore could not be reduced by CTX, KTX or MTX in the hKv1.3_V388C or the hKv1.2_V370C channel, respectively. Methods: For a more detailed characterization of the σ-pore, we created a trimer consisting of three hKv1.3_V388C α-subunits linked together and characterized current through this trimeric hKv1.3_V388C channel. Additionally, we determined which amino acids line the σ-pore in the tetrameric hKv1.3_V388C channel by replacing single amino acids in the tetrameric hKv1.3_V388C mutant channel that could be involved in σ-pore formation. Results: Overexpression of the trimeric hKv1.3_V388C channel in COS-7 cells yielded typical σ-pore currents at potentials more negative than -100 mV similar to what was observed for the tetrameric hKv1.3_V388C channel. Electrophysiological properties of the trimeric and tetrameric channel were similar: currents could be observed at potentials more negative than -100 mV, were not carried by protons or chloride ions, and could not be reduced by peptide toxins (CTX, MTX) or TEA. The σ-pore was mostly permeable to Na+ and Li+. In addition, in our site-directed mutagenesis experiments, we created a number of new double mutant channels in the tetrameric hKv1.3_V388C background channel. Two of these tetrameric double mutant channels (hKv1.3_V388C_T392Y and hKv1.3_V388C_Y395W) did not show currents through the σ-pore. Conclusions: From our experiments with the trimeric hKv1.3_V388C channel we conclude that the σ-pore exists in hKv1.3_V388C channels independently of the α-pore. From our site-directed mutagenesis experiments in the tetrameric hKv1.3_V388C channel we conclude that amino acid position 392 and 395 (Shaker position 442 and 445) line the σ-pore.
Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC
Authors: Zeng Bing , Lin Zewei , Ye Huilin , Cheng Di , Zhang Guangtao , Zhou Jindu , Huang Zhifeng , Wang Meng , Cai Canfeng , Zeng Jun , Tang Chaoming , Liu Jikui
Published: April 2018

Background/Aims: Long noncoding RNAs (lncRNAs) are key regulators of cancer initiation and progression. In this study, we investigated the clinical value and functional role of LncRNA DQ786243 (LncDQ) in the pathogenesis of hepatocellular carcinoma (HCC). Methods: To investigate the expression level of LncDQ in HCC, we performed quantitative real-time PCR using total RNA extracted from HCC tumor tissues and their matched non-neoplastic counterparts, as well as from the serum of HCC patients and healthy volunteers. The correlation of LncDQ expression with clinicopathologic features and prognosis was analyzed. The functional role of LncDQ in cell proliferation, migration, and invasion were evaluated by MTT cell viability, wound healing, and transwell assays in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays were performed to analyze the potential mechanism of LncDQ in HCC cells. Results: LncDQ was upregulated in both HCC tissue samples and serum and was correlated with low survival rate and adverse clinical pathological characteristics. Multivariate analysis demonstrated that LncDQ expression was an independent prognostic factor for HCC. The area under the receiver operating characteristic curve was 0.804 with a sensitivity of 0.72 and a specificity of 0.8. Knockdown of LncDQ induced inhibition of cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, LncDQ regulated the epithelial–mesenchymal transition pathway by interacting with EZH2, to epigenetically repress the expression of E-cadherin in HCC cells. Conclusions: Taken together, the results of our study indicate that LncDQ plays a critical role in HCC progression, and may serve as a potential diagnostic and prognostic biomarker for HCC.
Endoplasmic Reticulum Chaperone GRP78 Protects Heart From Ischemia/Reperfusion Injury Through Akt Activation
Authors: Bi Xukun , Zhang Guangyu , Wang Xiaoding , Nguyen Chau , May Herman I. , Li Xiaoting , Al-Hashimi Ali A. , Austin Richard C. , Gillette Thomas G. , Fu Guosheng , Wang Zhao V. , Hill Joseph A.
Published: April 2018

Rationale:

Restoration of coronary artery blood flow is the most effective means of ameliorating myocardial damage triggered by ischemic heart disease. However, coronary reperfusion elicits an increment of additional injury to the myocardium. Accumulating evidence indicates that the unfolded protein response (UPR) in cardiomyocytes is activated by ischemia/reperfusion (I/R) injury. Xbp1s (spliced X-box binding protein 1), the most highly conserved branch of the unfolded protein response, is protective in response to cardiac I/R injury. GRP78 (78 kDa glucose-regulated protein), a master regulator of the UPR and an Xbp1s target, is upregulated after I/R. However, its role in the protective response of Xbp1s during I/R remains largely undefined.

Objective:

To elucidate the role of GRP78 in the cardiomyocyte response to I/R using both in vitro and in vivo approaches.

Methods and Results:

Simulated I/R injury to cultured neonatal rat ventricular myocytes induced apoptotic cell death and strong activation of the UPR and GRP78. Overexpression of GRP78 in neonatal rat ventricular myocytes significantly protected myocytes from I/R-induced cell death. Furthermore, cardiomyocyte-specific overexpression of GRP78 ameliorated I/R damage to the heart in vivo. Exploration of underlying mechanisms revealed that GRP78 mitigates cellular damage by suppressing the accumulation of reactive oxygen species. We go on to show that the GRP78-mediated cytoprotective response involves plasma membrane translocation of GRP78 and interaction with PI3 kinase, culminating in stimulation of Akt. This response is required as inhibition of the Akt pathway significantly blunted the antioxidant activity and cardioprotective effects of GRP78.

Conclusions:

I/R induction of GRP78 in cardiomyocytes stimulates Akt signaling and protects against oxidative stress, which together protect cells from I/R damage.
Impacts of Prediabetes Mellitus Alone or Plus Hypertension on the Coronary Severity and Cardiovascular Outcomes
Authors: Liu Hui-Hui , Cao Ye-Xuan , Li Sha , Guo Yuan-Lin , Zhu Cheng-Gang , Wu Na-Qiong , Gao Ying , Dong Qiu-Ting , Zhao Xi , Zhang Yan , Sun Di , Li Jian-Jun
Published: April 2018

Whether prediabetes mellitus (Pre-DM) alone or combined with hypertension is an independent risk factor for cardiovascular disease has not been fully clarified. This study aimed to further confirm whether the relation of Pre-DM to cardiovascular disease differs between individuals with or without hypertension. A total of 7121 consecutive patients with angina-like chest pain who received coronary angiography were evaluated and 4193 patients with angiography-proven stable, new-onset coronary artery disease were enrolled into the study. They were divided into 3 groups according to diabetes mellitus status and further stratified by hypertension. The severity of coronary artery disease was assessed by number of diseased vessels and Gensini score. All subjects were regularly followed up for the occurrence of the composite end points. Comparisons of coronary artery disease severity and outcomes were performed among these groups. During an average of 11 338 patient-years of follow-up, 434 (10.35%) cardiovascular events occurred. No significant difference was observed in coronary severity and composite end point events between Pre-DM and normal glucose regulation groups (both
P
>0.05). However, when hypertension was also incorporated as a stratifying factor, cardiovascular disease risk, assessed by coronary severity and clinical prognosis, was significantly elevated in Pre-DM plus hypertension and diabetes mellitus plus hypertension groups, compared with the reference group with normal glucose regulation and normal blood pressure (all
P
<0.05). The present study indicated that among patients with stable, new-onset coronary artery disease, the increased cardiovascular risk with Pre-DM is largely driven by the coexistence of hypertension rather than Pre-DM per se.
Alkaline Phosphatase and Outcomes in Patients With Preserved Renal Function
Authors: Zong Lixia , Wang Xianwei , Li Zixiao , Zhao Xingquan , Liu Liping , Li Hao , Meng Xia , Wang Yilong , Wang Yongjun
Published: April 2018

Background and Purpose—

Alkaline phosphatase (ALP) is associated with risk of adverse cardiovascular events in patients with kidney failure. However, there is little data about effects of ALP on stroke outcomes in patients with preserved kidney function. The study aimed to explore the association between serum ALP level and clinical outcomes after stroke in patients with preserved kidney function.

Methods—

We included 16 367 stroke patients with preserved kidney function from the China National Stroke Registry for current analysis. Serum ALP levels were tested by automated enzymatic method using unfrozen samples in each center. Participants were divided into 5 groups according to ALP quintiles. Composite end point comprised of recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Poor functional outcome is defined as modified Rankin Scale score of 3 to 6. Multivariable logistic regression was used to evaluate the independent association of serum ALP with 1-year all-cause mortality, recurrent stroke, composite end point, and poor functional outcome.

Results—

The mean age of the included 16 367 patients was 63.9 years, and 63.3% of them were men. Among the top ALP quintile (>98.0 U/L), 1-year incidences of all-cause mortality, recurrent stroke, composite end point, and poor functional outcome were 12.6%, 5.7%, 14.4%, and 27.0%, respectively. Compared with the lowest ALP quintile (≤59.0 U/L), the adjusted odds ratios of the top quintile were 1.36 (1.10–1.68) for all-cause mortality, 1.45 (1.11–1.90) for stroke recurrence, 1.35 (1.12–1.63) for composite end point, and 1.36 (1.17–1.60) for poor functional outcome. There was no significant interaction between age, sex, or alcohol consumption and ALP (
P
for interaction ≥0.10) for all outcomes.

Conclusions—

In patients with preserved kidney function, ALP may be an independent predictor of all-cause mortality, stroke recurrence, composite end point, and poor functional outcome after stroke.
The Reflective Mind: Examining Individual Differences in Susceptibility to Base Rate Neglect with fMRI
Authors: Vartanian Oshin , Beatty Erin L. , Smith Ingrid , Blackler Kristen , Lam Quan , Forbes Sarah , De Neys Wim
Published: April 2018

Performance on heuristics and bias tasks has been shown to be susceptible to bias. In turn, susceptibility to bias varies as a function of individual differences in cognitive abilities (e.g., intelligence) and thinking styles (e.g., propensity for reflection). Using a classic task (i.e., lawyer–engineer problem), we conducted two experiments to examine the differential contributions of cognitive abilities versus thinking styles to performance. The results of Experiment 1 demonstrated that the Cognitive Reflection Test (CRT)—a well-established measure of reflective thinking—predicted performance on conflict problems (where base rates and intuition point in opposite directions), whereas STM predicted performance on nonconflict problems. Experiment 2 conducted in the fMRI scanner replicated this behavioral dissociation and enabled us to probe their neural correlates. As predicted, conflict problems were associated with greater activation in the ACC—a key region for conflict detection—even in cases when participants responded stereotypically. In participants with higher CRT scores, conflict problems were associated with greater activation in the posterior cingulate cortex (PCC), and activation in PCC covaried in relation to CRT scores during conflict problems. Also, CRT scores predicted activation in PCC in conflict problems (over and above nonconflict problems). Our results suggest that individual differences in reflective thinking as measured by CRT are related to brain activation in PCC—a region involved in regulating attention between external and internal foci. We discuss the implications of our findings in terms of PCC's possible involvement in switching from intuitive to analytic mode of thought.
It's the Other Way Around! Early Modulation of Sensory Distractor Processing Induced by Late Response Conflict
Authors: Pastötter Bernhard , Frings Christian
Published: April 2018

Understanding the neural processes that maintain goal-directed behavior is a major challenge for the study of attentional control. Although much of the previous work on the issue has focused on prefrontal brain areas, little is known about the contribution of sensory brain processes to the regulation of attentional control. The present EEG study examined brain oscillatory activities invoked in the processing of response conflict in a lateralized Eriksen single-flanker task, in which target letters were presented at fixation and single distractor letters were presented either left or right to the targets. Distractors were response compatible, response incompatible, or neutral in relation to the responses associated with the targets. The behavioral results showed that responses to targets in incompatible trials were slower and more error prone than responses in compatible trials. The electrophysiological results revealed an early sensory lateralization effect in (both evoked and induced) theta power (3–6 Hz) that was more pronounced in incompatible than compatible trials. The sensory lateralization effect preceded in time a midfrontal conflict effect that was indexed by an increase of (induced) theta power (6–9 Hz) in incompatible compared with compatible trials. The findings indicate an early modulation of sensory distractor processing induced by response conflict. Theoretical implications of the findings, in particular with respect to the theory of event coding and theories relating to stimulus–response binding [Henson, R. N., Eckstein, D., Waszak, F., Frings, C., & Horner, A. Stimulus-response bindings in priming. Trends in Cognitive Sciences, 18, 376–384, 2014; Hommel, B., Müsseler, J., Aschersleben, G., & Prinz, W. The theory of event coding (TEC): A framework for perception and action planning. Behavioral and Brain Sciences, 24, 849–878, 2001], are discussed.
CO2 Transport, Variability, and Budget over the Southern California Air Basin Using the High-Resolution WRF-VPRM Model during the CalNex 2010 Campaign
Authors: Park Changhyoun , Gerbig Christoph , Newman Sally , Ahmadov Ravan , Feng Sha , Gurney Kevin R. , Carmichael Gregory R , Park Soon-Young , Lee Hwa-Woon , Goulden Mike , Stutz Jochen , Peischl Jeff , Ryerson Tom
Published: April 2018

To study regional-scale carbon dioxide (CO2) transport, temporal variability, and budget over the Southern California Air Basin (SoCAB) during the California Research at the Nexus of Air Quality and Climate Change (CalNex) 2010 campaign period, a model that couples the Weather Research and Forecasting (WRF) Model with the Vegetation Photosynthesis and Respiration Model (VPRM) has been used. Our numerical simulations use anthropogenic CO2 emissions of the Hestia Project 2010 fossil-fuel CO2 emissions data products along with optimized VPRM parameters at “FLUXNET” sites, for biospheric CO2 fluxes over SoCAB. The simulated meteorological conditions have been validated with ground and aircraft observations, as well as with background CO2 concentrations from the coastal Palos Verdes site. The model captures the temporal pattern of CO2 concentrations at the ground site at the California Institute of Technology in Pasadena, but it overestimates the magnitude in early daytime. Analysis of CO2 by wind directions reveals the overestimate is due to advection from the south and southwest, where downtown Los Angeles is located. The model also captures the vertical profile of CO2 concentrations along with the flight tracks. The optimized VPRM parameters have significantly improved simulated net ecosystem exchange at each vegetation-class site and thus the regional CO2 budget. The total biospheric contribution ranges approximately from −24% to −20% (daytime) of the total anthropogenic CO2 emissions during the study period.
Assessment of Community Pediatric Providers’ Approach to a Child With Celiac Disease and Available Serological Testing Associated With a Large Tertiary Care Center
Authors: Alrabadi Leina S. , Porto Anthony F.
Published: April 2018

An evidence-practice gap for use of celiac disease testing can lead to poor resource utilization. False positive tests may lead to unnecessary diet changes, gastroenterology consults, parental/patient concern, and additional testing and expenses complicated by varied available celiac bundles. An understanding of pediatric provider practices according to guideline recommendations further improves this gap.
“Assurdo napoletano”: Eduardo anni Quaranta
Authors: Taffon Giorgio
Published: April 2018

Il presente contributo vuol riprendere alcune mie riflessioni sulla svolta drammaturgica, tematica e teatrale di Eduardo De Filippo negli anni Quaranta, espresse in particolare in due volumi, Scritture per la scena, del 2001 (coautore Marco Ariani), e Maestri drammaturghi nel teatro italiano del ‘900, del 2005. Intenzione di chi scrive è quella di mettere ulteriormente a fuoco, anche sulla scorta di altri interventi critici e interpretativi più recenti, i modi in cui, partendo da una cultura tradizionale, dialettale, anche “bassa”, e da tipiche basi etnoantropologiche cronotopiche, Eduardo De Filippo ha saputo allinearsi su posizioni di cultura “alta”, fin europea, portando il neorealismo esemplare di Napoli milionaria! all’altezza di autori europei: Camus, Beckett, anche Pinter. E inventando un “assurdo napoletano”.
Impact of Pharmacy Student–Driven Postdischarge Telephone Calls on Heart Failure Hospital Readmission Rates: A Pilot Program
Authors: Plakogiannis Roda , Mola Ana , Sinha Shreya , Stefanidis Abraham , Oh Hannah , Katz Stuart
Published: April 2018

Background: Heart failure (HF) hospitalization rates have remained high in the past 10 years. Numerous studies have shown significant improvement in HF readmission rates when pharmacists or pharmacy residents conduct postdischarge telephone calls. Objective: The purpose of this retrospective review of a pilot program was to evaluate the impact of pharmacy student–driven postdischarge phone calls on 30- and 90-day hospital readmission rates in patients recently discharged with HF. Methods: A retrospective manual chart review was conducted for all patients who received a telephone call from the pharmacy students. The primary endpoint compared historical readmissions, 30 and 90 days prior to hospital discharge, with 30 and 90 days post discharge readmissions. For the secondary endpoints, historical and postdischarge 30-day and 90-day readmission rates were compared for patients with a primary diagnosis of HF and for patients with a secondary diagnosis of HF. Descriptive statistics were calculated in the form of means and standard deviations for continuous variables and frequencies and percentages for categorical variables. Results: Statistically significant decrease was observed for both the 30-day ( P = .006) and 90-day ( P = .007) readmission periods. Prior to the pharmacy students’ phone calls, the overall group of 131 patients had historical readmission rates of 24.43% within 30 days and 38.17% within 90 days after hospital discharge. After the postdischarge phone calls, the readmission rates decreased to 11.45%, for 30 days, and 22.90%, for 90 days. Conclusion: Postdischarge phone calls, specifically made by pharmacy students, demonstrated a positive impact on reducing HF-associated hospital readmissions, adding to the growing body of evidence of different methods of pharmacy interventions and highlighting the clinical impact pharmacy students may have in transition of care services.
Changes in Lubricant Properties of Used Synthetic Oils Based on the Total Acid Number
Authors: Wolak Artur
Published: April 2018

This article describes the processes of degradation of five engine oils belonging to the same SAE (Society of Automotive Engineers) viscosity class but launched by different manufacturers. The direction and intensity of changes in the total acid number have been analyzed. As part of the experiment, the changes in engine oils occurring during operation have been examined. The operating conditions throughout the test can be described as “severe,” that is, frequent starting of the engine, short distance driving, and extended engine idling. All engine oils were operated in passenger cars of a uniform fleet of 25 vehicles. The total acid number was determined in accordance with the ASTM D664. The obtained results have led to the development of a statistical model enabling to calculate average predictive values of the total acid number for a given mileage. The results may facilitate decision-making regarding the service life of engine oils.
Women’s agency freedom through empowerment against domestic violence: Evidence from Nepal
Authors: Kim Hee Jin , Atteraya Madhu Sudhan , Yoo Ho Yeol
Published: April 2018

Agency freedom is the process through which women can obtain power and control over making decisions about their own life choices. In this study, women’s agency freedom was measured based on women’s ability to make decisions and their help-seeking practices against domestic violence. We examined how women’s higher agency freedom prevented them from being victims of domestic violence. The study analyzed 3373 women from the 2011 Nepal Demographic and Health Survey (NDHS). The results revealed that women’s decision-making participation and help-seeking practices had a negative relationship with domestic violence. Women’s help-seeking practice had moderating effects on the relationship between women’s decision-making participation and domestic violence.
Being a ‘good’ mother: Immigrant mothers of disabled children
Authors: Kim Kyung Mee , Hwang Se Kwang
Published: April 2018

In South Korea, disability and immigration are hidden and invisible phenomena. This article examines how immigrant mothers experience the intersection of immigrant status and mothering a disabled child. Through semi-structured interviews with 16 immigrant mothers, this study found that the values of Confucian familism regarding motherhood and gender roles influenced how these immigrant mothers behaved. The study also found that immigrant mothers faced multiple forms of stigma and discrimination as a result of negative socio-cultural views of disability and immigration. Therefore, the article suggests a need for inter-professional, anti-oppression work strategies to support immigrant mothers of disabled children, along with education for social workers about these issues.
Hybrid networks, everyday life and social control: Electricity access in urban Kenya
Authors: Smith Shaun
Published: April 2018

This article examines electricity access in Kisumu and Kitale, Kenya, through the mediation of land tenure relations. Despite a reported rapid expansion of formal network connectivity, various everyday practices have emerged, including piecemeal electricity purchase and communal meter sharing, which mean electricity access is controlled and mediated at various social scales. It is argued that such practices represent hybridised forms of electricity access and that landlord–tenant relations alter the socio-technical electricity network and how access is lived and experienced.
A Strong Woman: A Psychodynamic Perspective on Religion and Culture in a Grieving Mother
Authors: Doghor Osarumen Nicole , Marshall Francia Latoya
Published: April 2018

This is a case report that depicts spiritual integration in grief psychotherapy with a culture-sensitive perspective. Topics addressed by this article include: 1) The impact of death of a neonate on an individual’s faith; 2) The role of psychosocial development and factors on the process of grieving; 3) Therapist self-disclosure as a tool in working with resistance.
Is use of homeopathy associated with poor prescribing in English primary care? A cross-sectional study
Authors: Walker Alex J , Croker Richard , Bacon Seb , Ernst Edzard , Curtis Helen J , Goldacre Ben
Published: April 2018

Objectives

Prescribing of homeopathy still occurs in a small minority of English general practices. We hypothesised that practices that prescribe any homeopathic preparations might differ in their prescribing of other drugs.

Design

Cross-sectional analysis.

Setting

English primary care.

Participants

English general practices.

Main outcome measures

We identified practices that made any homeopathy prescriptions over six months of data. We measured associations with four prescribing and two practice quality indicators using multivariable logistic regression.

Results

Only 8.5% of practices (644) prescribed homeopathy between December 2016 and May 2017. Practices in the worst-scoring quartile for a composite measure of prescribing quality (>51.4 mean percentile) were 2.1 times more likely to prescribe homeopathy than those in the best category (<40.3) (95% confidence interval: 1.6–2.8). Aggregate savings from the subset of these measures where a cost saving could be calculated were also strongly associated (highest vs. lowest quartile multivariable odds ratio: 2.9, confidence interval: 2.1–4.1). Of practices spending the most on medicines identified as ‘low value’ by NHS England, 12.8% prescribed homeopathy, compared to 3.9% for lowest spenders (multivariable odds ratio: 2.6, confidence interval: 1.9–3.6). Of practices in the worst category for aggregated price-per-unit cost savings, 12.7% prescribed homeopathy, compared to 3.5% in the best category (multivariable odds ratio: 2.7, confidence interval: 1.9–3.9). Practice quality outcomes framework scores and patient recommendation rates were not associated with prescribing homeopathy (odds ratio range: 0.9–1.2).

Conclusions

Even infrequent homeopathy prescribing is strongly associated with poor performance on a range of prescribing quality measures, but not with overall patient recommendation or quality outcomes framework score. The association is unlikely to be a direct causal relationship, but may reflect underlying practice features, such as the extent of respect for evidence-based practice, or poorer stewardship of the prescribing budget.
Backstepping-based output regulation of ordinary differential equations cascaded by wave equation with in-domain anti-damping
Authors: Gu Jianjun , Wei Chunqiu , Wang Junmin
Published: April 2018

Output regulation is considered in this paper for ordinary differential equations cascaded by a wave equation, in which both the body equations and the uncontrolled end are subject to disturbances. The disturbances are generated by an exosystem. A backstepping state-feedback regulator is first designed to force the output to track the reference signal. The design is based on solving cascaded regulator equations, and the solvability condition of the equations is characterized in terms of a transfer function and the eigenvalues of the exosystem. An observer-based output-feedback regulator is then designed to solve the output regulation problem. Finally, the regulator tracking performance is illustrated through numerical simulations.
A thousand healths: Jean-Luc Nancy and the possibility of democratic biopolitics
Authors: Prozorov Sergei
Published: April 2018

This article addresses the relationship between ontology and politics in Jean-Luc Nancy’s theory of democracy by probing the implications of his latest ontological innovation, the concept of struction. We argue that Nancy’s democracy is a mode of politics that makes the radical pluralism of struction legitimate, opening and guarding a political space for the coexistence of the incommensurable. From this perspective, and despite Nancy’s own skepticism about the concept of biopolitics, the notion of struction opens a pathway for theorizing democracy in a biopolitical key as the regime of coexistence of radically incommensurable forms of life in the absence of any coordinating principle. We nonetheless take issue with Nancy’s prescription for democracy to remain devoid of any political affirmation of its own. Instead, we suggest that the prescriptive content of democracy consists in the affirmation of the contingency of all the forms of life that coexist in it, which implies their freedom, equality, and community. In this manner, democracy makes the incommensurability of struction both legitimate and enjoyable.
Hayek’s vicarious secularization of providential theology
Authors: Christiaens Tim
Published: April 2018

Friedrich Hayek’s defense of neoliberal free market capitalism hinges on the distinction between economies and catallaxies. The former are orders instituted via planning, whereas the latter are spontaneous competitive orders resulting from human action without human design. I argue that this distinction is based on an incomplete semantic history of “economy.” By looking at the meaning of “ oikonomia” in medieval providential theology as explained by Giorgio Agamben and Joseph Vogl, I argue how Hayek’s science of catallactics is itself a secularization of providential theology. This exposes Hayek to three criticisms: (1) he unjustifiably neglects the possibility of tendencies toward spontaneous disorder in free markets, (2) he condemns the “losers” of neoliberal competition to being providential waste on the road to general prosperity, and (3) he imposes on people the duty to consent to a neoliberal order that hinders them from cultivating their inoperativity.
“Already/Not Yet”
Authors: Paipais Vassilios
Published: April 2018

This paper interrogates some prominent post-Marxist engagements with St Paul’s messianism by reading them in the theological context of the anti-historicist revival of Pauline eschatology in the twentieth century. In both readings, the means through which the critique of historicism is delivered is the revival of the eschatological core of Paul’s proclamation. Paul is read as inaugurating a “new world” of freedom, love and redemptive hope as opposed to the “old world” of oppression, sorrow, death and despair. And yet, it is exactly in such an apocalyptic reading of Pauline eschatology that both philosophical and theological critiques of historicism, despite protestations to the contrary, remain prisoners to the aporias of a historicist temporality. The symptom of the philosophers’ residual parasitism on historicism is expressed as antinomian negativism, while in the case of the theologians it can take the form of a self-assured Church triumphalism.
How family caregivers help older relatives navigate statutory services at the end of life: A descriptive qualitative study
Authors: Williams Lisa Ann , Moeke-Maxwell Tess , Wiles Janine , Black Stella , Trussardi Gabriella , Kerse Ngaire , Gott Merryn
Published: April 2018

Background:

A key challenge in meeting the palliative care needs of people in advanced age is the multiple healthcare and social service agencies typically involved in their care. The ‘patient navigator’ model, originally developed in cancer care, is the professional solution most often recommended to address this challenge. However, little attention has been paid, or is known, about the role that family carers play in enabling their dying relatives to negotiate service gaps.

Aim:

To explore the role family caregivers play in helping people dying in advanced old age navigate health services at the end of life.

Design:

Qualitative study using semi-structured interviews and analysed via thematic analysis.

Setting/participants:

A total of 58 interviews were conducted in New Zealand with the family caregivers of 52 deceased older relatives who had been participants in Life and Living in Advanced Age: a Cohort Study in New Zealand.

Results:

Fragmentation of services was the key concern, causing distress both for the older person and their family caregivers. Carers identified and engaged with appropriate services in order to facilitate care and treatment. Their involvement was not always met by healthcare professionals with respect or regard to their knowledge of the older person’s needs.

Conclusion:

Family caregivers are trying to help their older relatives overcome the limitations of fragmented health systems at the end of life. They are doing so at times by stepping in to perform patient navigator tasks usually conceptualised as a role for statutory services to carry out. Programmes and services need to be implemented that will better support family carers who are acting as care navigators.
Blood neutrophil-to-lymphocyte ratio is associated with prognosis in advanced gastrointestinal stromal tumors treated with imatinib
Authors: Rutkowski Piotr , Teterycz Paweł , Klimczak Anna , Bylina Elżbieta , Szamotulska Katarzyna , Lugowska Iwona
Published: April 2018

Introduction:

Neutrophil-to-lymphocyte ratio (NLR) was shown to be prognostic in several solid malignancies. There are limited data about predictive/prognostic value of NLR during targeted therapy of patients with advanced gastrointestinal stromal tumors (GIST). The aim of this study was to asses a clinical value of this ratio in patients with advanced GIST.

Methods:

Between 2001 and 2016, 385 patients with metastatic/unresectable GIST treated initially with imatinib were included in the analysis. In all patients, the NLR was assessed at the baseline, after 3 months of treatment, and upon disease progression (or last observation). The cutoff values for NLR were set at 2.7 and 5.4. Kaplan-Meier survival probability estimation with log-rank test and Cox proportional hazards model were used for analysis.

Results:

Median progression-free survival (PFS) on imatinib treatment was 44.8 months, 5-year rate 43%; median overall survival (OS) 87.2 months, 10-year rate 36.3%. NLR >2.7 at baseline was significantly associated with poorer OS and PFS: median OS was 89.3 months (95% confidence interval [CI] 80.2-115) for NLR ratio ≤2.7 vs 59.4 months (95% CI 48.6-82) for NLR >2.7 ( p < .001); median PFS was 59.4 vs 32.7 ( p < .001), respectively. In multivariate model adjusted for mitotic index and driver mutation in the tumor ( KIT exon 11 mutation versus other), NLR ratio was proven to be statistically significant (hazard ratio 1.09; 95% CI 1.01-1.19; p = .030). Among patients with disease progression, NLR >2.7 assessed at the third month of treatment was linked with significantly shorter median time to progression (7.5 vs 19 months).

Conclusions:

Our results demonstrate the usefulness of NLR as a prognostic and predictive marker as well as a marker for treatment monitoring in patients with advanced GIST treated with imatinib.
223Ra-chloride therapy in men with hormone-refractory prostate cancer and skeletal metastases: Real-world experience
Authors: Boni Giuseppe , Mazzarri Sara , Cianci Claudia , Galli Luca , Farnesi Azzurra , Borsatti Eugenio , Bortolus Roberto , Fratino Lucia , Gobitti Carlo , Lamaj Elda , Ghedini Pietro , Rizzini Elisa Lodi , Massari Francesco , Dionisi Valeria , Fanti Stefano , Volterrani Duccio , Monari Fabio
Published: April 2018

Background:

Radium-223 (223Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of 223Ra therapy in routine clinical practice.

Methods:

A total of 83 patients with metastatic CRPC were treated with 223Ra at 3 Italian centers between August 2013 and August 2016. 223Ra-chloride (55 kBq/kg) was administered every 4 weeks for a total of 6 cycles. Primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included toxicity, pain evaluation using numeric rating scale (NRS), symptomatic skeletal-related events and biomarkers response.

Results:

Patients had a median age of 75 (range 53–89) years. The majority of men showed a Gleason score of 7, 8, or 9. Forty-one patients completed 6 treatment cycles; 33 stopped treatment before completing 6 cycles. Nine were still receiving therapy at the time of data collection. At the end of therapy, NRS pain scores significantly improved ( p < .000001). OS was a mean of 10.1 months, while median OS had not been attained. According to Kaplan-Meier estimation, OS and PFS were 17.5 and 7.7 months, respectively. There was a significant correlation between OS and PFS with the number of 223Ra cycles; patients receiving all 6 cycles experienced the major benefit from the therapy. 223Ra was well-tolerated.

Conclusions:

223Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.
Reducing Transportation Greenhouse Gas Emissions Through the Development of Policies Targeting High-Emitting Trips
Authors: Tu Ran , Kamel Islam , Abdulhai Baher , Hatzopoulou Marianne
Published: April 2018

Traffic emission inventories have been under development for decades, often relying on data from traffic assignment models, ranging from macroscopic models generating average link speeds, to more detailed microscopic models with instantaneous speed profiles. Policy testing within such frameworks has often focused on identifying changes in total emissions, or in emissions aggregated at a zonal or street level. Emissions from specific trips or trajectories are seldom analyzed, although reductions in greenhouse gas (GHG) emissions can be achieved more efficiently when targeting high emitters. In this paper, we propose a different approach to reducing transportation GHG emissions, by catering policies to specific trips based on their emission burden. We focus on the City of Toronto downtown. Using second-by-second speed data for entire trajectories, GHGs (in CO2eq) and nitrogen oxides (NOx) emissions were estimated. We observe that the destinations attracting the highest trip emissions tend to be in the hospital and financial districts. Trips originating and ending in the downtown area are responsible for a small share of total emissions, although they have high emission intensity. Removing trips with high total emissions and high emission intensity led to significant reductions in CO2eq and NOx emissions, whereas removing shorter trips, did not have a significant influence on total emissions nor emission intensities.
Use of Placebo in Clinical Trials of Psychotropic Medication
Authors: Hasnain Mehrul , Rudnick Abraham , Bonnell Weldon S. , Remington Gary , Lam Raymond W.
Published: April 2018

This position paper has been substantially revised by the Canadian Psychiatric Association’s Research Committee and approved for republication by the CPA’s Board of Directors on March 31, 2017. The original position paper1 was developed by the Scientific and Research Council and approved by the Board of Directors on October 4, 1996.
Support to triage and public risk perception considering long-term response to a Cs-137 radiological dispersive device scenario
Authors: Andrade Cristiane PS , Souza Cláudio J , Camerini Eduardo SN , Alves Isabela S , Vital Hélio C , Healy Matthew JF , Ramos De Andrade Edson
Published: April 2018

A radiological dispersive device (RDD) spreads radioactive material, complicates the treatment of physical injuries, raises cancer risk, and induces disproportionate fear. Simulating such an event enables more effective and efficient utilization of the triage and treatment resources of staff, facilities, and space. Fast simulation can give detail on events in progress or future events. The resources for triage and treatment of contaminated trauma victims can differ for pure exposure individuals, while discouraging the “worried well” from presenting in the crisis phase by media announcement would relieve pressure on hospital facilities. The proposed methodology integrates capabilities from different platforms in a convergent way composed of three phases: (a) scenario simulation, (b) data generation, and (c) risk assessment for triage focused on follow-up epidemiological assessment. Simulations typically indicate that most of the affected population does not require immediate medical assistance. Medical triage for the few severely injured and the radiological triage to diminish the contamination with radioactivity will always be the priority. For this study, however, higher priorities should be given to individuals from radiological “warm” and “hot” zones as required by risk criteria. The proposed methodology could thus help to (a) filter and reduce the number of individuals to be attended, (b) optimize the prioritization of medical care, (c) reduce or prepare for future costs, (d) effectively locate the operational triage site to avoid possible contamination on the main facility, and (e) provide the scientific data needed to develop an adequate approach to risk and its proper communication.
Current Weight Management Approaches Used by Primary Care Providers in Six Multidisciplinary Healthcare Settings in Ontario
Authors: Aboueid Stephanie , Jasinska Monika , Bourgeault Ivy , Giroux Isabelle
Published: April 2018

Background

Obesity management in primary care has been suboptimal due to lack of access to allied health professionals, time, and resources.

Purpose

To understand the weight management approaches used by primary care providers working in team-based settings and how they assess the most suitable approach for a patient.

Methods

A total of 20 primary care providers (13 nurse practitioners and 7 family physicians) working in 6 multidisciplinary clinics in Ontario were interviewed. All interviews were recorded, transcribed verbatim, and coded using NVivo qualitative software. Conventional content analysis was used to inductively elucidate codes, which were then clustered into categories.

Results

A referral to on-site programming was the most frequent weight management approach used. The pharmacological approach was underutilized due to adverse side effects and cost to patients. Primary care providers assessed the most suitable weight management approach based on patients’: preference, level of motivation, income status and access to resources, body mass index and comorbidities, and previous weight loss attempts. Primary care providers perceived that referring to health professionals and educational resources were the approaches preferred by patients.

Conclusions

The team-based nature of these clinics allowed for referrals to various on-site professionals and/or programs. Some barriers to pursuing weight management avenues with patients were patient dependent.
Hyperinflation of Isoproterenol
Authors: D’Ambrosi Julie , Amin Nilesh
Published: April 2018

The hyperinflation of isoproterenol, a 75-year-old drug, in early 2015 was unbelievable. The attention of health-care professionals, health system administrators, legislators, and the general public was quickly focused on Valeant Pharmaceuticals, purchaser of several generics solely to raise their price. With isoproterenol easily launched toward the top of drug expenditures, pharmacists in many hospitals were forced to engage stakeholders in the investigation and implementation of alternatives, explore utilization and optimize inventory, reduce cost through sterile product preparation, where possible, restrict use to settings that were beneficial to their budget, and become legislative advocates. The alternatives drugs and strategies will be reviewed.