bluuebunny/crossref_metadata_2025 huggingface dataset:
Pigeonholing or learning instrument?
Authors: Lundgren Henriette , Kroon Brigitte , Poell Rob F.
Published: January 2019

Purpose

While factors that influence test takers’ reactions to personality testing in selection contexts have been well researched, little empirical research evidence exists to determine whether these factors also apply to test takers’ reactions in the context of management development (MD). The purpose of this study is, therefore, to explore what explains different test takers’ reactions in the context of MD programs.

Design/methodology/approach

A qualitative longitudinal approach with three phases of data collection was used, resulting in participatory workshop observations and 11 semi-structured interviews with participants from two different contexts. Data were analyzed using Qualitative Comparative Analysis (QCA).

Findings

The findings show that test takers’ reactions vary; some are more accepting, others are more neutral or rejecting, where perceived usefulness, clarity of purpose and perceived respectfulness are identified as distinguishing factors. Individuals also differ in terms of their awareness of assumptions and their perceived emotional safety, two emerging factors that are relevant in the MD context.

Research limitations/implications

Data were collected during the MD workshops and three months after, but no records of immediate test takers’ reactions were included, which could be an addition for future research.

Practical implications

The findings of this study suggest that human resource development (HRD) professionals have significant impact on test takers’ reactions when it comes to encouraging self-reflection and learning along personality tests.

Originality/value

This study adds to existing research by offering insights into factors in MD settings where participants are concerned about aspects of fairness, learning and behavioral change.
Affective value of game items: a mood management and selective exposure approach
Authors: Bae Joonheui , Kim Sang Jin , Kim Kyung Hoon , Koo Dong-Mo
Published: January 2019

Purpose

The purpose of this paper is to investigate the relationship between game items and mood management to show the affective value of game items. Specifically, the study examines the impact of interaction between two negative mood states (stress vs boredom) and types of game items (functional vs decorative) on the purchasing intention of game items.

Design/methodology/approach

Two experiments were conducted to predict the outcomes of using game items.

Findings

Game users effectively manage their level of arousal and mood valence using game items. The selective exposure theory provides additional understanding of different purchasing behaviors, suggesting that stressed users are more likely to purchase decorative items while bored users purchase functional items to manage their mood.

Research limitations/implications

The study results show the affective role of game items in mood management. While previous studies focused on the cognitive and functional aspects of purchasing game items, this study extends the value of game items as augmented products.

Practical implications

When launching new games, companies should provide game users free game items for mood management. In addition, to increase intervention potential and behavioral affinity, marketers need to develop and launch more game item types.

Originality/value

This study extends the understanding of affective value of game items by applying mood management and selective exposure theories to explain the purchase intention of game items.
Dark aerobic sulfide oxidation by anoxygenic phototrophs in anoxic waters
Authors: Berg Jasmine S. , Pjevac Petra , Sommer Tobias , Buckner Caroline R.T. , Philippi Miriam , Hach Philipp F. , Liebeke Manuel , Holtappels Moritz , Danza Francesco , Tonolla Mauro , Sengupta Anupam , Schubert Carsten J. , Milucka Jana , Kuypers Marcel M.M.
Published: January 2019

Anoxygenic phototrophic sulfide oxidation by green and purple sulfur bacteria (PSB) plays a key role in sulfide removal from anoxic shallow sediments and stratified waters. Although some PSB can also oxidize sulfide with nitrate and oxygen, little is known about the prevalence of this chemolithotrophic lifestyle in the environment. In this study, we investigated the role of these phototrophs in light‐independent sulfide removal in the chemocline of Lake Cadagno. Our temporally resolved, high‐resolution chemical profiles indicated that dark sulfide oxidation was coupled to high oxygen consumption rates of ~9 μM O2·h−1. Single‐cell analyses of lake water incubated with 13CO2 in the dark revealed that Chromatium okenii was to a large extent responsible for aerobic sulfide oxidation and it accounted for up to 40% of total dark carbon fixation. The genome of Chr. okenii reconstructed from the Lake Cadagno metagenome confirms its capacity for microaerophilic growth and provides further insights into its metabolic capabilities. Moreover, our genomic and single‐cell data indicated that other PSB grow microaerobically in these apparently anoxic waters. Altogether, our observations suggest that aerobic respiration may not only play an underappreciated role in anoxic environments but also that organisms typically considered strict anaerobes may be involved.
Physiological responses of the freshwater N2‐fixing cyanobacterium Raphidiopsis raciborskii to Fe and N availabilities
Authors: Fu Qing‐Long , Yeung Anna C. Y. , Fujii Manabu , Neilan Brett A. , Waite T. David
Published: January 2019

The cyanobacterium Raphidiopsis raciborskii is of environmental and social concern in view of its toxicity, bloom‐forming characteristics and increasingly widespread occurrence. However, while availability of macronutrients and micronutrients such as N and Fe are critically important for the growth and metabolism of this organism, the physiological response of toxic and non‐toxic strains of R. raciborskii to varying Fe and N availabilities remains unclear. By determining physiological parameters as a function of Fe and N availability, we demonstrate that R. raciborskii growth and N2‐fixing activity are facilitated at higher Fe availability under N2‐limited conditions with faster growth of the CS‐506 (cylindrospermopsin‐producing) strain compared with that of CS‐509 (the non‐toxic) strain. Radiolabelled Fe uptake assays indicated that R. raciborskii acclimated under Fe‐limited conditions acquires Fe at significantly higher rates than under Fe replete conditions, principally via unchelated Fe(II) generated as a result of photoreduction of complexed Fe(III). While N2‐fixation of both strains occurred during both day and night, the CS‐506 strain overall exhibited higher N2‐fixing and Fe uptake rates than the CS‐509 strain under N‐deficient and Fe‐limited conditions. The findings of this study highlight that Fe availability is of significance for the ecological advantage of CS‐506 over CS‐509 in N‐deficient freshwaters.
Risk analysis of the supply chain of a tools manufacturer in Puebla, Mexico
Authors: Cano‐Olivos Patricia , Hernández‐Zitlalpopoca Ricardo , Sánchez‐Partida Diana , Caballero‐Morales Santiago‐Omar , Martínez‐Flores José‐Luis
Published: January 2019

Risk management has taken considerable importance in the supply chain. Much research has been focused on this area to improve quality and competitiveness within organisations. This paper is focused on the identification, analysis, and evaluation of risks associated to materials/purchasing departments through the failure mode and effect analysis (FMEA) and analytic hierarchy process (AHP). This integrated analysis led to prioritise the potential risks that generate downtime and financially impact of the supply chain. Having a unique supply source was identified as the main risk, and restriction on the contract's length was determined to be a suitable solving approach. The identified risks should also be quantified considering the negative effects on cost, time, and quality‐functionality to provide immediate or long‐term solutions.
Improving emergency department trauma care in Fiji: Implementing and assessing the trauma call system
Authors: Raj Lavinesh Kumar , Creaton Anne , Phillips Georgina
Published: January 2019

Objective

The trauma team process was recently implemented at the Colonial War Memorial (CWM) Hospital, Suva. This study audits the trauma call procedure at the hospital over a period of 12 months.

Method

Retrospective descriptive study of trauma calls from August 2015 to July 2016 at CWM Hospital. Data relating to patient demographics, time of presentation, time to team assembly and time to computed tomography (CT) scan were extracted from the ED trauma call database. Disposition from the ED and status at hospital discharge was extracted from the hospital patient information system.

Results

There were 38 trauma calls for 46 patients. Seventy‐two per cent were male. Eighty‐two per cent occurred when the CT radiographer was off site (16.00–08.00 h), including 47% that occurred between midnight and 08.00 h. Fifty‐two per cent of patients were intubated, 43% went to ICU, 26% went directly to the operating theatre, and 37% died. Benchmarks for time to trauma team assembly and time to CT scan were met in 50% of cases.

Conclusion

This was a severely injured cohort of patients with a high mortality rate. The rate of missed calls was not assessed in this study. Time to CT scan could be improved with an onsite radiographer. Time to team assembly could be improved with trauma team training and early notification from pre‐hospital providers. There is a need to continue to monitor and refine the trauma call process and to extend data capture to measure injury severity and outcomes.
Variables associated with completeness of medical record documentation in the emergency department
Authors: Lai Fiona WY , Kant Joyce A , Dombagolla Mahesha HK , Hendarto Andreas , Ugoni Antony , Taylor David McD
Published: January 2019

Objective

The completeness of ED medical record documentation is often suboptimal. We aimed to determine the variables associated with documentation completeness in a large, tertiary referral ED.

Methods

We audited 1200 randomly selected medical records of patients who presented with either abdominal pain, cardiac chest pain, shortness of breath or headache between May–July 2013 and May–July 2016. Data were collected on patient and treating doctor variables. Documentation completeness was assessed using a 0–10 point scoring tool designed for the study. A maximum score was achieved if each of 10 pre‐determined important items, specific to the presenting complaint, were documented (five medical history items, five physical examination items). Data were analysed using multivariate regression.

Results

The presenting year, day and time, patient age and gender, preferred language, interpreter requirement, discharge destination and doctor gender were not associated with documentation completeness (P > 0.05). Patients with triage category 3 or pain score of 6–7 had higher documentation scores (P < 0.05). Compared to interns, registrars (effect size −0.72, 95% CI −1.02 to −0.42, P < 0.01) and consultants (−1.62, 95% CI −1.95 to −1.29, P < 0.01) scored significantly less. The headache patient subgroup scored significantly less than the other patient subgroups (−0.35, 95% CI −0.63 to −0.08, P = 0.01). For all presenting complaint subgroups, examination findings were less well documented than history items (P < 0.001).

Conclusion

Documentation completeness is less among senior doctors, headache patients and for examination findings. Research should determine if the supervision responsibilities of senior doctors affects documentation and if medico‐legal and patient care implications exist.
Learning strategies and the social brain: Missing elements in the link between developmental stress, song and cognition?
Authors: KRIENGWATANA Buddhamas Pralle
Published: January 2019

Bird songs may advertise aspects of cognition because song learning and learning speed in cognitive tasks are both affected by early‐life environments. However, such relationships remain ambiguous in the literature. Here, I discuss 2 lines of research that may help to demystify links between song learning and cognition. First, learning strategies should be considered when assessing performance to ensure that individual differences in learning ability are not masked by individual differences in learning strategies. Second, song characteristics should be associated with social behavior because songs have a social purpose and, consequently, should be strongly related at functional and neural levels. Finally, if song learning and cognitive abilities are correlated because they develop concurrently and/or share or compete for the same resources, I discuss ways glucocorticoids may link early‐life stress, song learning and cognitive ability, focusing particularly on oxidative stress as a potential mechanism.
The Many Meanings of Quality Education: Politics of Targets and Indicators in SDG4
Authors: Unterhalter Elaine
Published: January 2019

The formulation of the SDG education targets was more inclusive than the processes linked with the MDGs. Key constituencies making representations through the Open Working Group and other consultative processes succeeded in formulating targets that stressed inclusion, quality and equality in all phases of education. However, the development of the global indicators for SDG4, has resulted in metrics that miss many of the values of the targets, most notably with regard to quality and free education and substantive, not simply distributive, meanings of equality. The article analyses why some of these slippages took place, and what potential there may be to mobilise for metrics that better depict the key tenets of the education goal and targets. The analysis thus considers ways forward for exploring measurement of the many meanings of quality and equalities in education, reflecting on numbers as instruments that impose power and hierarchy, and the possibility of using reflections on numbers and indicators for critical dialogue and an enhancement of participation, accountability, and work to change injustices in education.
The Contested Discourse of Sustainable Agriculture,
Authors: McNeill Desmond
Published: January 2019

The article critically analyses how the transformative ambition of the SDGs may be threatened in the process of moving from vision, through goals and targets to indicators. This is exemplified by a case study concerning sustainable agriculture, and most specifically indicator 2.4.1, where two contrasting approaches – industrial agriculture and agro‐ecology – stand in opposition, each with its associated discourse and interests. The process is analysed in great detail, noting the complex interplay of political and technical considerations. FAO has played a central role in establishing a compromise with regard to the wording of indicator 2.4.1 which papers over the disagreements and does not explicitly promote either of the two competing approaches. And the organisation has facilitated a technical process which, instead of one simple indicator, has led to a composite, multidimensional version with nine sub‐indicators, as a result of which it has been relegated to ‘Tier III’ status, implying that it will not be used for global monitoring purposes. The article concludes that – owing to a combination of political and technical factors – the transformative potential of the SDGs may, in this instance, be lost.
Political Thriller Exposes the Underbelly of Global Goals
Authors: Burke Sara , Rürup Bettina Luise
Published: January 2019

This commentary characterizes the SDG indicator framework as a ‘political thriller’ in which the power struggles are hidden behind the veil of technocratic expertise. Like a Trojan horse, each indicator conceals the theories of change and development that lie within, exerting their interpretive influence. Where the politics will ultimately lead to by 2030 – in shaping policy priorities, power structures, and knowledge about development – is for now unknown and unpredictable.
Acarbose improves health and lifespan in aging HET3 mice
Authors: Harrison David E. , Strong Randy , Alavez Silvestre , Astle Clinton Michael , DiGiovanni John , Fernandez Elizabeth , Flurkey Kevin , Garratt Michael , Gelfond Jonathan A. L. , Javors Martin A. , Levi Moshe , Lithgow Gordon J. , Macchiarini Francesca , Nelson James F. , Sukoff Rizzo Stacey J. , Slaga Thomas J. , Stearns Tim , Wilkinson John Erby , Miller Richard A.
Published: January 2019

To follow‐up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log‐rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%–11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2‐(2‐hydroxyphenyl) benzothiazole (HBX), and INT‐767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose‐control drugs in humans.
The LMA® ProtectorTM in anaesthetised, non‐paralysed patients: a multicentre prospective observational study
Authors: Zaballos M. , Zaballos J. , López S. , Fernández‐Dïez A. I. , Lluch‐Oltra A. , Mexedo C. , López A.
Published: January 2019

We evaluated the LMA® ProtectorTM in 280 ASA physical status 1–3 patients aged 18–75 years by assessing the ease of insertion, insertion time, oropharyngeal leak pressure, ease of gastric tube passage and complications. First‐attempt and overall insertion success was 234/280 (84; 95%CI 79–88%) and 274/280 (98; 95–99%). Median (IQR [range]) insertion time was 17 (12–25 [5–44]) s, and manoeuvres to facilitate insertion were required in 56 (50–63)% of patients. Median oropharyngeal leak pressure was 31 (26–36 [14–40]) cmH2O. Multivariate analysis identified two risk factors for oropharyngeal leak pressure < 25 cmH2O: male sex (OR 2.44; 1.01–5.91, p = 0.048) and the insertion of a LMA size different to that recommended by weight (OR 1.98; 0.97–4.03, p = 0.06). Gastric tube insertion was possible in 256 out of 274 patients (93%). On fibreoptic view, vocal cords were visible in 86% of patients. During maintenance, 14 patients (5%) required airway manipulation. There were no episodes of regurgitation or aspiration. Blood staining on LMA removal was present in 70 out of 280 patients (25%). Use of the LMA Protector appears safe and is associated with a high success rate, provision of a highly effective seal and low rates of clinical complications. These attributes would suggest considerable potential for use during anaesthesia.
Novel frequency analysis of signal‐averaged electrocardiograms is predictive of adverse outcomes in implantable cardioverter defibrillator patients
Authors: Chow Ryan , Hashemi Javad , Torbey Sami , Siu Johnny , Glover Benedict , Baranchuk Adrian M. , Abdollah Hoshiar , Simpson Christopher , Akl Selim , Redfearn Damian P.
Published: January 2019

Background

Current noninvasive risk stratification methods offer limited prediction of arrhythmic events when selecting patients for ICD implantation. Our laboratory has recently developed a signal processing metric called Layered Symbolic Decomposition frequency (LSDf) that quantifies the percentage of hidden QRS wave frequency components in signal‐averaged ECG (SAECG) recordings. The purpose of this pilot study was to determine whether LSDf can be predictive of ventricular arrhythmia or death in an ICD patient cohort.

Methods and Results

Fifty‐two ICD patients were recruited from 2008 to 2009. These were followed for a mean of 8.5 ± 0.4 years for the primary outcome of first appropriately treated ventricular arrhythmia (VT/VF) or death. Thirty‐four subjects met the primary outcome. LSDf was significantly lower, and 12‐lead QRS duration was significantly greater in patients meeting the primary outcome (12.14 ± 3.97% vs. 16.45 ± 3.73%; p = 0.001) and (111.59 ± 14.96 ms vs. 97.69 ± 13.51 ms; p = 0.012) respectively. A 13.25% LSDf threshold (0.74 sensitivity and 0.85 specificity) was selected based on an ROC curve. Kaplan–Meier survival analysis was conducted; patients above the 13.25% threshold demonstrated significantly better survival outcomes (log‐rank p < 0.001). In Cox multivariate regression analysis, the LSDf threshold (13.25%) was compared to LVEF (28.5%), 12‐lead QRSd (100 ms), age, % male sex, NYHA classification, and antiarrhythmic usage. LSDf was a predictor of the primary outcome (p = 0.005) and an independent predictor for solely ventricular arrhythmia (p = 0.002).

Conclusion

Layered Symbolic Decomposition frequency analysis in SAECG recordings may be a viable predictor of negative ICD survival outcomes.
Whole genome sequencing of breast cancer
Authors: Rossing Maria , Sørensen Claus Storgaard , Ejlertsen Bent , Nielsen Finn Cilius
Published: January 2019

Breast cancer was the first to take advantage of targeted therapy using endocrine therapy, and for up to 20% of all breast cancer patients a further significant improvement has been obtained by HER2‐targeted therapy. Greater insight in precision medicine is to some extent driven by technical and computational progress, with the first wave of a true technical advancement being the application of transcriptomic analysis. Molecular subtyping further improved our understanding of breast cancer biology and has through a new tumor classification enabled allocation of personalized treatment regimens. The next wave in technical progression must be next‐generation‐sequencing which is currently providing new and exciting results. Large‐scale sequencing data unravel novel somatic and potential targetable mutations as well as allowing the identification of new candidate genes predisposing for familial breast cancer. So far, around 15% of all breast cancer patients are genetically predisposed with most genes being factors in pathways implicated in genome maintenance. This review focuses on whole‐genome sequencing and the new possibilities that this technique, together with other high‐throughput analytic approaches, provides for a more individualized treatment course of breast cancer patients.
Letter: impact of Epstein‐Barr virus serological status on clinical outcomes in adult patients with inflammatory bowel disease
Authors: Ahmed Tehmina , Brown Francesca , Ahmed Ruhina , Shah Ash , Whitehead Simon , Steed Helen , Brookes Matthew J.
Published: January 2019

Linked Content

This article is linked to de Francisco et al and de Francisco et al papers. To view these articles, visit https://doi.org/10.1111/apt.14933 and https://doi.org/10.1111/apt.15125.
Solving the paradox – (further) evidence for a quadratic relationship between in‐group centrality and group‐based guilt
Authors: Masson Torsten , Barth Markus
Published: January 2019

Previous research on the relationship between strength of in‐group identification and collective guilt about an in‐group's wrongdoing is mixed, providing evidence for both a negative and a positive relationship. One possible way to reconcile these findings is to explore non‐linear (quadratic) functions. Correlational data (Study 1) and experimental data (Study 2) from two questionnaire studies (Ntotal = 311) were in line with a quadratic relationship between self‐centrality of the in‐group and collective guilt (inverted U‐shaped function). Collective guilt about a group's transgression was highest at medium levels of in‐group centrality and lower for low and high levels of centrality, respectively. Additionally, defensive in‐group beliefs (i.e., beliefs restoring a positive in‐group image) were also associated non‐linearly with in‐group centrality (cubic relation relationship). Our findings call for a more detailed look on possible non‐linear relationships between in‐group identification and collective guilt or in‐group defensiveness.
Holocene environmental history in high‐Arctic North Greenland revealed by a combined biomarker and macrofossil approach
Authors: Kusch Stephanie , Bennike Ole , Wagner Bernd , Lenz Matthias , Steffen Ilona , Rethemeyer Janet
Published: January 2019

In this study, we use a combined biomarker and macrofossil approach to reconstruct the Holocene climate history recorded in Trifna Sø, Skallingen area, eastern North Greenland. Chronological information is derived from comparison of lithological, biogeochemical and macrofossil characteristics with a well‐dated record from nearby Lille Sneha Sø. Following local deglaciation aroundc. 8 cal. ka BP, the local peak warmth occurred betweenc. 7.4 and 6.2 cal. ka BPas indicated by maximum macrofossil abundances of warmth‐demanding plants (Salix arcticaand Dryas integrifolia) and invertebrates (Daphnia pulexand Chironomidae). Warm conditions were dominated by terrestrial organic matter (OM) sedimentation as implied by the alkane‐based Paqratio, but increased aquatic productivity is indicated when temperature was highest around 6.5 cal. ka BP. Then‐C29/n‐C31alkane ratio shows that vegetation in the catchment was dominated by shrubs after deglaciation, but shifted towards relatively more grassy/herbaceous vegetation during peak warmth. After 5.4 cal. ka BP, the disappearance of warmth‐demanding plant and invertebrate macrofossils indicates cooling in the Skallingen area. This cooling was characterized by a significant shift towards dominance of aquaticOMsedimentation in Trifna Sø as implied by high Paqratios. Cooling was also associated with a shift in vegetation type from dwarf‐shrub heaths towards relatively more herbaceous vegetation in the catchment, stronger erosion and more oligotrophic conditions in the lake. Our data show that mean air temperatures inferred using branched glycerol dialkyl glycerol tetraethers (brGDGTs) do not seem to accurately reflect the local climatic history. Irrespective of calibration, methylation of branched tetraethers (MBT) palaeothermometry cannot be reconciled with the macrofossil evidence and seems to be biased by either changing brGDGTsources (in situvs. soil‐derived) or changing species assemblages and/or an unknown physiological response to changing environmental conditions at high latitude.
Debate: Fomenting controversy regarding pediatric bipolar disorder
Authors: Goldstein Benjamin I. , Post Robert M. , Birmaher Boris
Published: January 2019

Read the Editors’ introduction at: doi: 10.1111/camh.12315

Read the core debate at: doi: 10.1111/camh.12231; doi: 10.1111/camh.12243; doi: 10.1111/camh.12296; doi: 10.1111/camh.12306

Read more perspectives in this debate at: doi: 10.1111/camh.12317; doi: 10.1111/camh.12316; doi: 10.1111/camh.12313; doi: 10.1111/camh.12310; doi: 10.1111/camh.12314
Editorial: The job of an editor
Authors: Ougrin Dennis
Published: January 2019

The job of an editor is exciting, fraught with difficulties, friend‐making, enemy‐making, time‐eating, time‐saving, but above all, it is exciting. I took over from Jane Barlow in November 2018. First, I would like to thank her for her work. I do not just say this: Jane has made my work easy in many ways. She has steered the journal to become a recognisable presence in our field, with an impact factor, a growing number of downloads and high aspirations of participation in PubMed Central. The job of an editor is also to extend the success of previous editors. The way I see it is that CAMH should continue to grow to become one of the leading sources for clinically relevant knowledge worldwide. I would like you, our readers, to think of CAMH whenever you need clinical advice.
Deubiquitinase ubiquitin‐specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells
Authors: Lu Qin , Lu Dayun , Shao Zhi‐Ming , Li Da‐Qiang
Published: January 2019

The E3 ubiquitin ligase ring finger protein 115 (RNF115) is overexpressed in more than half of human breast tumors and is implicated in the pathogenesis and progression of breast cancer. However, the mechanism behind RNF115 overexpression in breast tumors remains largely unknown. Here we report that ubiquitin‐specific protease 9X (USP9X), a substrate‐specific deubiquitinating enzyme, stabilizes RNF115 and thereby regulates its biological functions in breast cancer cells. Immunoprecipitation and GST pull‐down assays showed that USP9X interacted with RNF115. Depletion of RNF115 by siRNAs or overexpression of RNF115 did not significantly affect USP9X expression. In contrast, knockdown of USP9X in breast cancer cells by siRNAs reduced RNF115 protein abundance, which was partially restored following treatment with proteasome inhibitor MG‐132. Moreover, depletion of USP9X reduced the half‐life of RNF115 and increased its ubiquitination. Conversely, overexpression of USP9X resulted in an accumulation of RNF115 protein, accompanied by a decrease in its ubiquitination. RNF115 mRNA levels were unaffected by overexpression or knockdown of USP9X. Furthermore, USP9X protein expression levels correlated positively with RNF115 in breast cancer cell lines and breast tumor samples. Importantly, reintroduction of RNF115 in USP9X‐depleted cells partially rescued the reduced proliferation, migration, and invasion of breast cancer cells by USP9X knockdown. Collectively, these findings indicate that USP9X is a stabilizer of RNF115 protein and that the USP9X‐RNF115 signaling axis is implicated in the breast cancer malignant phenotype.
Gender, prick test size and rAra h 2 sIgE level may predict the eliciting dose in patients with peanut allergy: Evidence from the Mirabel survey
Authors: Elegbede Chabi Fabrice , Papadopoulos Alexandra , Just Jocelyne , Moneret‐Vautrin Denise Anne , Deschildre Antoine , Crépet Amélie
Published: January 2019

Background

Peanut allergy management is based on active avoidance and access to emergency treatment including self‐injectable adrenaline. Knowing the dose at which a patient is likely to react is crucial for risk assessment and could significantly improve management by integrating a personalized approach.

Objective

To develop a threshold dose distribution curve model from routinely collected data.

Methods

The MIRABEL survey is an observational study of 785 patients with peanut allergy/sensitization conducted in France, Belgium and Luxemburg. The current analysis included the 238 participants for whom medical and oral food challenge data were available. Several statistical models (Kaplan‐Meier, Cox model, Weibull and Lognormal with predictive factors, basic Weibull and Lognormal) were compared to select the best model and predictive factor combination associated with the threshold doses. Inferences were made with a Bayesian approach.

Results

Patients were mainly children (mean age: 9 years [IQR: 6‐11]; 87% < 16 years) and males (62%). Median Ara h2 s IgE was of 8kUA/L [IQR: 1‐55] and median skin prick test size of 10 mm [IQR: 7‐13]. OFC was positive in 204 patients (86%). The median threshold dose was of 67 mg of peanut protein [IQR: 16‐244]. The dose at which 1% of the patients are likely to react with objective symptoms was 0.26 [0.03; 2.24] mg of peanut protein. Gender, size of the skin prick test (SPT) and Ara h 2 specific IgE level had a significant impact on the threshold dose distribution curve. The Cox model was the most effective to predict threshold doses with this combination of factors. Girls react to lower doses than boys with a beta coefficient associated to the risk and a 95% credible interval of 0.44 [0.04; 0.77]. The higher the size of the SPT and the Ara h 2 specific IgE level are, the higher the risk of reacting to a small amount of peanut, with beta coefficients associated to the risk and 95% credible intervals of 0.05 [0.02; 0.08] and 0.01 [0.01; 0.02], respectively.

Conclusion and clinical relevance

According to the model, routinely collected data could be used to estimate the threshold dose. The consequences could be the identification of high‐risk patients who are susceptible to react to small amounts of peanut and a personalized management of peanut allergy integrating the risk of allergic reaction. Limitations of this study are that assessors of OFC outcome were aware of SPT and Arah2 results, and a further validation study is required to confirm the predictive value of these parameters.
Impaired immunoregulatory network of the CD4 T lymphocytes in refractory asthma
Authors: Fernandes Jamille S. , Araujo Maria Ilma , de Almeida Tarcísio V. V. S. , Andrade Lorena S. , Lopes Diego M. , de Mello Luane M. , Carvalho Edgar M. , Cruz Álvaro A. , Cardoso Luciana S.
Published: January 2019

Background

The immunopathogenesis of severe asthma has been associated with an inefficient regulatory response. There are a few studies about the CD4 T cells profile among individuals with severe asthma refractory to treatment.

Objective

To evaluate the CD4 T lymphocyte profile from individuals with severe asthma according to their response to treatment, relating to their atopy status and age of asthma onset.

Methods

We evaluated nineteen individuals with severe asthma refractory to treatment (SAR), 21 with well‐controlled or partly controlled severe asthma (CSA) and 23 with mild‐to‐moderate asthma (MMA). Lymphocytes were obtained from PBMC, and the frequency of expression of different molecules in this population was assessed using the flow cytometry.

Results

We observed the frequency of CD4+IFN‐γ+T cells was higher in atopic individuals with SAR than with CSA. In addition, among the atopic and early‐onset asthma (EOA), the frequency of CD4+CTLA‐4+T cells was lower in the SAR group than the CSA group. In relation to non‐atopic and late‐onset asthma (LOA) phenotypes, we noted the frequency of CD4+FoxP3+T cells was lower in individuals with SAR than with CSA. We also observed among the LOA patients, the frequency of CD4+TGF‐β+ T cells was decreased in SAR group than the in CSA group.

Conclusion and Clinical Relevance

Our data suggest that refractoriness to treatment in asthma is associated with a lower expression of distinct regulatory molecules by CD4 T cells between those who are atopic and have EOA and those who are non‐atopic and have LOA. Thus, these results may contribute to the identification of new regulatory strategies to treat asthma according to their phenotypes.
Lessons from seabird conservation in Alaskan longline fisheries
Authors: Melvin Edward F. , Dietrich Kimberly S. , Suryan Robert M. , Fitzgerald Shannon M.
Published: January 2019

Although bycatch of seabirds and other long‐lived species is a critical conservation issue in world fisheries, case studies documenting significant reductions in the mortality of these low‐productivity species in a fishery are rare. We studied progress toward seabird conservation in the Alaskan longline fisheries, one of the largest and most diverse demersal fisheries. We generated annual seabird bycatch rates in 4 target fisheries and all fisheries combined from 23 years of fisheries observer data. We used 0‐inflated negative binomial models to evaluate variables influencing seabird bycatch per unit effort (BPUE) in 2 target fisheries. Following adoption of streamer lines, at first voluntarily and then mandatorily, seabird BPUE was reduced by 77–90%, preventing mortality of thousands of birds per year. Despite this, BPUE increased significantly in 2 of 4 target fisheries since streamer lines were adopted. Although night setting yielded significant reductions (74–97%) in seabird BPUE and significant increases (7–11%) in fish catch per unit effort over daytime setting, nighttime setting increased the BPUE of Northern Fulmar (Fulmarus glacialis) by 40% and nontarget fish species by 5–17%. Thus, best practices to prevent seabird mortalities in longline fisheries varied by species assemblage and fishery. Our results inform global efforts toward fisheries bycatch reduction by illustrating that successful conservation requires fishery‐specific solutions, strong industry support, constant vigilance in analysis and reporting observer data, and ongoing outreach to fleets, especially to vessels with anomalously high BPUE.
A systematic review of outcomes after salvage abdominoperineal resection for persistent or recurrent anal squamous cell cancer
Authors: Ko G. , Sarkaria A. , Merchant S. J. , Booth C. M. , Patel S. V.
Published: January 2019

Aim

Up to 30% of patients with squamous cell cancer of the anus (SCCA) will require a salvage abdominoperineal resection (APR) for either persistent or recurrent disease. The objective of this study was to assess cancer‐related outcomes in patients with (i) persistent or (ii) recurrent SCCA.

Method

Embase and MEDLINE were searched. Publications were included if they assessed overall survival (OS), disease‐free survival (DFS) and locoregional recurrence or metastatic disease after salvage APR for persistent or recurrent SCCA.

Results

A total of 28 retrospective case series (study size ranged from nine to 111) met our inclusion criteria. The median time to salvage APR was 2.6 months [interquartile range (IQR) 2.6–5.0 months, six studies] for persistent disease and 27.6 months (IQR 15.0–32.7 months, five studies) for recurrent disease. The median 5‐year OS from the time of salvage APR was 45.0% (IQR 32.0%–52.3%, 10 studies) for persistent disease and 51.0% (IQR 36.0%–60.9%, 11 studies) for recurrent disease. The median 5‐year DFS following salvage APR was 44.0% (IQR 29.5%–53.0%, 10 studies) for all patients. Following salvage APR, the median locoregional recurrence rate was 23.5% (IQR 15.8%– 46.9%, 19 studies) and 9.0% (IQR 6.4%–13.3%, 16 studies) of patients developed metastatic disease after salvage APR.

Conclusion

Our review characterizes the best evidence for outcomes following salvage APR for patients with persistent or recurrent SCCA. The evidence is limited by the quality of included studies, as many were single centre case series.
Identifying a potential biomarker for primary focal segmental glomerulosclerosis and its association with recurrence after transplantation
Authors: Harel Efrat , Shoji Jun , Abraham Vivek , Miller Loan , Laszik Zoltan , Thurison Tine , King Andrew , Olshen Adam , Leung Joey , Szabo Gyula , Hann Byron , Høyer‐Hansen Gunilla , Craik Charles S. , Vincenti Flavio
Published: January 2019

Background

We investigated circulating levels of individual soluble urokinase plasminogen activation receptor (suPAR) forms to determine if specific circulating fragments of suPAR (II‐III) and (I) can better serve as clinical biomarkers for focal segmental glomerulosclerosis (FSGS) and the risk of recurrence after transplantation.

Materials and Methods

Serum levels of intact suPAR and its cleaved forms were measured with two assays, ELISA and TR‐FIA.

Results

suPAR levels in healthy controls were significantly lower than those who had glomerular diseases but were not significantly different between FSGS patients and glomerular controls. Intact suPAR (I‐II‐III) levels were noted to be elevated in glomerular diseases including FSGS. uPAR fragment (I) levels measured with the TR‐FIA 4 assay were significantly higher in FSGS (695.4 + 91.29 pMol/L) than glomerular controls (239.1 + 40.45 pMol/L, P = 0.001). However, suPAR(I) levels were not significantly different between recurrent FSGS and nonrecurrent FSGS patients.

Conclusion

Our analysis of suPAR using the ELISA assay used in all previous studies does not appear to be a useful marker for FSGS nor serve as a predictor for its recurrence after transplantation. The TR‐FIA assay results suggest that uPAR(I) is a potential biomarker for FSGS but not of its recurrence.
The ethical conundrum: Conflicting advocacy positions in advanced heart failure therapy
Authors: Dudzinski Denise M. , Mahr Claudius , Bjelkengren Jason , Mokadam Nahush A.
Published: January 2019

It is estimated that nearly 6.5 million Americans over the age of 20 suffer from heart failure. Heart failure is the leading cause of hospitalization in patients over 65 years of age, and carries with it a 5‐year mortality of nearly 50%. Despite advances in medical therapy, treatment for medically refractory end‐stage, advanced heart failure is limited to heart transplant, mechanical circulatory support (MCS), or palliative care only. Patient selection in advanced heart failure (AHF) therapy is complex. Not only are the patients medically complicated, but providers are biased by their individual and collective experience with similar and dissimilar patients. Clinicians caring for AHF patients balance competing clinical and ethical demands, which appropriately leads to professional debate and disagreement. These debates are constructive because they clarify ethical and professional commitments and help to ensure fair and equitable treatment of AHF patients.
Biliary interventions using single‐operator cholangioscopy
Authors: Navaneethan Udayakumar , Moon Jong Ho , Itoi Takao
Published: January 2019

Cholangioscopy provides an opportunity to directly visualize the bile duct for diagnosing biliary lesions and for therapeutic interventions. Although there are different cholangioscopy techniques available, single‐operator cholangioscopy has gained widespread acceptance as the standard technique for interventions in the biliary system because of its ease of use and widespread availability. Single‐operator cholangioscopy can be used for both diagnostic and therapeutic indications in the biliary tract. Diagnostic cholangioscopy is used for direct evaluation of indeterminate bile duct strictures with biopsies, diagnosing filling defects in the bile ducts observed during endoscopic retrograde cholangiography (ERC) imaging, preoperative mapping of the precise location and extension of tumors of the biliary tract, and diagnosis of intraductal neoplasms. Therapeutic cholangioscopy is used for visually guided treatment of biliary stones that have failed extraction with conventional ERC techniques, residual or impacted stones by using intraductal lithotripsy, ablation of biliary tumors and for facilitation of guidewire advancement into selective intrahepatic ducts for adequate biliary drainage. In this review, we will focus on advances in the single‐operator cholangioscopy techniques in the diagnosis and management of biliary disorders.
Saving and Bequest in China: An Analysis of Intergenerational Exchange
Authors: Almås Ingvild , Freddi Eleonora , Thøgersen Øystein
Published: January 2019

Particularly high saving rates among the elderly in both rural and urban China call for an investigation of the involved bequest motive. Utilizing unique survey data from a diverse group of Chinese households, we document that the magnitude of the bequest from parent to child is associated with the level of personal assistance from child to parent. Moreover, we find indicative evidence that both bequest and assistance are increasing in the parent's income and decreasing in the child's income. Comparing with the predictions from a stylized intergenerational model, these findings are consistent with an exchange‐based bequest motive. Our findings have potential implications for how public policies and transfer schemes should be designed in order to contribute to the Chinese government objective of increased private consumption. Our results are conditional on the inclusion of housing wealth as part of the bequest, which indicates that transfer of housing is key to understanding the intergenerational assistance and bequest motives, and subsequently the high saving levels among the elderly in China.
Aripiprazole compared with placebo for auditory verbal hallucinations in youth with borderline personality disorder: Protocol for the VERBATIM randomized controlled trial
Authors: Chanen Andrew M. , Betts Jennifer , Jackson Henry , McGorry Patrick , Nelson Barnaby , Cotton Sue M. , Bartholomeusz Cali , Jovev Martina , Ratheesh Aswin , Davey Christopher , Pantelis Christos , McCutcheon Louise , Francey Shona , Bhaduri Amit , Lowe Danielle , Rayner Victoria , Thompson Katherine
Published: January 2019

Aim

Up to half of patients with borderline personality disorder report auditory verbal hallucinations that are phenomenologically indistinguishable from those in schizophrenia, occur early in the course of the disorder, and are enduring, distressing and disabling. In clinical practice, this symptom is widely assumed to be unresponsive to treatment with antipsychotic medication and early intervention is rarely offered. The Verbal Experiences Response in Borderline personality disorder to Aripiprazole TrIal Medication (VERBATIM) study aims to be the first controlled trial to investigate the effectiveness of conventional pharmacotherapy for this symptom in this patient group.

Method

VERBATIM is a 12‐week, triple‐blind, single‐centre, parallel groups randomised controlled trial, with a 27‐week follow‐up period. Participants between the ages of 15 and 25 years receive either aripiprazole or placebo daily, commencing at 2 mg and increasing to 10 mg by day 15. Further dose escalations (up to 30 mg) may occur, as clinically indicated. This trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry ACTRN12616001192471 on 30/08/2016.

Results

The primary outcome is severity of auditory verbal hallucinations assessed using the Psychotic Symptom Rating Scale. Secondary outcomes include the severity of general psychopathology, borderline personality pathology, social and occupational functioning and change in brain resting state connectivity. The primary endpoint is week 12 and secondary endpoint is week 39.

Conclusion

The results will inform treatment decisions for individuals with borderline personality disorder who present with auditory verbal hallucinations.
Principles of the animal molecular clock learned from Neurospora
Authors: Loros Jennifer J.
Published: January 2019

Study of Neurospora, a model system evolutionarily related to animals and sharing a circadian system having nearly identical regulatory architecture to that of animals, has advanced our understanding of all circadian rhythms. Work on the molecular bases of the Oscillator began in Neurospora before any clock genes were cloned and provided the second example of a clock gene, frq, as well as the first direct experimental proof that the core of the Oscillator was built around a transcriptional translational negative feedback loop (TTFL). Proof that FRQ was a clock component provided the basis for understanding how light resets the clock, and this in turn provided the generally accepted understanding for how light resets all animal and fungal clocks. Experiments probing the mechanism of light resetting led to the first identification of a heterodimeric transcriptional activator as the positive element in a circadian feedback loop, and to the general description of the fungal/animal clock as a single step TTFL. The common means through which DNA damage impacts the Oscillator in fungi and animals was first described in Neurospora. Lastly, the systematic study of Output was pioneered in Neurospora, providing the vocabulary and conceptual framework for understanding how Output works in all cells. This model system has contributed to the current appreciation of the role of Intrinsic Disorder in clock proteins and to the documentation of the essential roles of protein post‐translational modification, as distinct from turnover, in building a circadian clock.