bluuebunny/crossref_metadata_2025 huggingface dataset:
Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism
Authors: Lezzerini Marco , Penzo Marianna , O’Donohue Marie-Françoise , Marques dos Santos Vieira Carolina , Saby Manon , Elfrink Hyung L , Diets Illja J , Hesse Anne-Marie , Couté Yohann , Gastou Marc , Nin-Velez Alexandra , Nikkels Peter G J , Olson Alexandra N , Zonneveld-Huijssoon Evelien , Jongmans Marjolijn C J , Zhang GuangJun , van Weeghel Michel , Houtkooper Riekelt H , Wlodarski Marcin W , Kuiper Roland P , Bierings Marc B , van der Werff ten Bosch Jutte , Leblanc Thierry , Montanaro Lorenzo , Dinman Jonathan D , Da Costa Lydie , Gleizes Pierre-Emmanuel , MacInnes Alyson W
Published: November 2019

Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene variants are also linked to a variety of phenotypes, including malignancy, in individuals with no anemia. Here we report an individual diagnosed with DBA carrying a variant in the 5′UTR of RPL9 (uL6). Additionally, we report two individuals from a family with multiple cancer incidences carrying a RPL9 missense variant. Analysis of cells from these individuals reveals that despite the variants both driving pre-rRNA processing defects and 80S monosome reduction, the downstream effects are remarkably different. Cells carrying the 5′UTR variant stabilize TP53 and impair the growth and differentiation of erythroid cells. In contrast, ribosomes incorporating the missense variant erroneously read through UAG and UGA stop codons of mRNAs. Metabolic profiles of cells carrying the 5′UTR variant reveal an increased metabolism of amino acids and a switch from glycolysis to gluconeogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools. These findings indicate that variants in the same RP gene can drive similar ribosome biogenesis defects yet still have markedly different downstream consequences and clinical impacts.
Severe alcohol intoxication among Canadian Youth: A 2-year surveillance study
Authors: Acker Amy , Norris Mark L , Coo Helen , Santos Alexandre , Allain Dominic , Dow Kimberly
Published: November 2019

Purpose

To obtain data on Canadian youth, aged 11 to 15 years, presenting to paediatric emergency departments, with severe alcohol intoxication and to describe demographics, presentations to hospital, concurrent substance use, comorbidities, and short-term outcomes of admission to emergency departments.

Methods

Between March 2013 and February 2015, through the established methodology of the Canadian Paediatric Surveillance Program, Canadian paediatricians and paediatric subspecialists were surveyed monthly to identify cases of young adolescents presenting to paediatric emergency departments across Canada with severe alcohol intoxication. Those that identified cases were subsequently sent a detailed questionnaire. The detailed questionnaires were then screened to ensure the reported cases met the study’s inclusion criteria.

Results

A total of 39 cases (18 females and 21 males) were included in the final analysis. Overall, results indicate over 90% of presenting youth had consumed spirits, 39% had concurrent substance use and 46% experienced serious medical morbidity. Almost two-thirds of youth were admitted to hospital for a period ranging from 10 hours to 5 days; 12 youth required intubation. Follow-up referrals were provided to two-thirds of youth, with variable supports given. No statistically significant differences between sexes were noted for blood alcohol level or concurrent substance use.

Conclusion

Although rates of alcohol use in adolescents have been steadily decreasing, results from this surveillance study suggest that severe intoxication arising from the use of alcohol alone, and with concurrent substance use, results in significant immediate health consequences in young adolescents. Results from this study also highlight characteristics of patients, initial treatments and initial referrals across Canadian paediatric healthcare facilities, the results of which highlight variability and may aid in the guidance of a future longitudinal study, prevention strategies, and public health messaging.
Employment in the neighborhoods of Barcelona: health effects of an active labor market program in Southern Europe
Authors: González-Marín Patricia , Puig-Barrachina Vanessa , Bartoll Xavier , Cortés-Franch Imma , Malmusi Davide , Clotet Eva , Cardona Africa , Artazcoz Lucía , Borrell Carme
Published: November 2019

Background

The aim of this study was to analyze the changes in self-perceived health status and mental health among participants in an active labour market policy (ALMP) of Barcelona, and to assess whether the results differed according to the participants’ social characteristics and their program trajectories.

Methods

A pre–post intervention study was designed, including unemployed people participating in a return-to-work ALMP in 13 deprived neighborhoods of Barcelona; using one survey upon entering the program (pre), and another 1 year later (post). We assessed the prevalence of poor self-perceived health status and poor mental health (Goldberg-12 questionnaire) in both periods of time. We fit five Poisson regression models using generalized estimating equations (GEE) to measure changes in self-perceived health and mental health between pre- and post-intervention.

Results

About 696 individuals (48% women) participated in the study, mainly manual workers. In both sexes, mental health improved (prevalence ratio [PR]—comparing post- and pre-periods for women: 0.49, 95% confidence interval [CI]: 0.39–0.61 and men: PR: 0.41, 95% CI: 0.32–0.53), whereas self-perceived health status remained stable or worsened. Men who remained unemployed reported poorer self-perceived health status, while no such association was observed among women.

Conclusions

This study shows a mental health improvement among male and female participants.
Validity of the Cold Pressor Test and Pain Sensitivity Questionnaire via online self-administration
Authors: McIntyre Matthew H. ,   23andMe Research Team, Kless Achim , Hein Peter , Field Mark , Tung Joyce Y.
Published: November 2019

To determine the feasibility of complex home-based phenotyping, 1,876 research participants from the customer base of 23andMe participated in an online version of a Pain Sensitivity Questionnaire (PSQ) as well as a cold pressor test (CPT) which is used in clinical assessments of pain. Overall our online version of the PSQ performed similarly to the original pen-and-paper version. Construct validity of the PSQ total was demonstrated by internal consistency and consistent discrimination between more and less painful items. Criterion validity was demonstrated by correlation with pain sensitivity as measured by the cold pressor test. Within the same cohort we performed a cold pressor test using a layperson description and household equipment. Comparison with published reports from controlled studies revealed similar distributions of cold pain tolerance times (i.e., time elapsed before removing the hand from the water). Of those who elected to participate in the CPT, a large majority of participants did not report issues with the test procedure or noncompliance to the instructions (97%). We confirmed a large sex difference in CPT thresholds in line with published data, such that women removed their hands from the water at a median of 54.2 seconds, with men lasting for a median time of 82.7 seconds (Kruskal-Wallis statistic, p < 0.0001), but other factors like age or current pain treatment were at most weakly associated, and inconsistently between men and women. We introduce a new paradigm for performing pain testing, called testing@home, that, in the case of cold nociception, showed comparable results to studies conducted under controlled conditions and supervision of a health care professional.

Research paradigms employing home-based phenotyping are feasible, with both questionnaires and self-administration of a well-established experimental human pain model yielding similar results compared to controlled settings.
Step-downs reduce workers’ compensation payments to encourage return to work. Are they effective?
Authors: Lane Tyler J , Sheehan Luke R , Gray Shannon E , Beck Dianne , Collie Alex
Published: November 2019

Objective

To determine whether step-downs, which cut the rate of compensation paid to injured workers after they have been on benefits for several months, are effective as a return to work incentive.

Methods

We aggregated administrative claims data from seven Australian workers’ compensation systems to calculate weekly scheme exit rates, a proxy for return to work. Jurisdictions were further subdivided into four injury subgroups: fractures, musculoskeletal, mental health, and other trauma. The effect of step-downs on scheme exit was tested using a regression discontinuity design. Results were pooled into meta-analyses to calculate combined effects and the proportion of variance attributable to heterogeneity.

Results

The combined effect of step-downs was a 0.86 percentage point (95% CI -1.45 to -0.27) reduction in the exit rate, with significant heterogeneity between jurisdictions (I2= 68%,p= .003). Neither timing nor magnitude of step-downs was a significant moderator of effects. Within injury subgroups, only fractures had a significant combined effect (-0.84, 95% CI -1.61 to -0.07). Sensitivity analysis indicated potential effects within mental health and musculoskeletal conditions as well.

Conclusions

The results suggest some workers’ compensation recipients anticipate step-downs and exit the system early to avoid the reduction in income. However, the effects were small and suggest step-downs have marginal practical significance. We conclude that step-downs are generally ineffective as a return to work policy initiative.

Key messages

1.

What is already known about this subject?

A number of workers’ compensation systems around the world reduce payments to injured workers after they have been in the system for several months. In Australia, where each state, territory, and Commonwealth system employs step-downs, the stated policy objective is to increase the rate of return to work through financial incentives. However, there is little empirical evidence to either support or reject this claim.

2.

What are the new findings?

The rate at which claimants exited workers’ compensation systems increased ahead of step-downs taking effect, suggesting an anticipatory effect. However, the effect was relatively small, changing the exit rate by less than a percentage point overall, with substantial heterogeneity between systems.

3.

How might this impact on policy or clinical practice in the foreseeable future?

While statistically significant, the findings suggest that step-downs provide workers’ compensation claimants little incentive to return to work. Policymakers may need to reconsider step-downs as a component of scheme design, or justify them according to their original purpose, which was to save costs.
Limited Capacity for Ipsilateral Secondary Motor Areas to Support Hand Function Post-Stroke
Authors: Wilkins Kevin B. , Yao Jun , Owen Meriel , Karbasforoushan Haleh , Carmona Carolina , Dewald Julius P.A.
Published: November 2019

Recent findings have shown connections of ipsilateral cortico-reticulospinal tract (CRST), predominantly originating from secondary motor areas, to not only proximal but also distal portions of the arm. In unilateral stroke, CRST from the ipsilateral side is intact and thus has been proposed as a possible backup system for post-stroke rehabilitation even for the hand. We argue that although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements due to its extensive branching compared to contralateral corticospinal tract. To address this issue, we combined MRI, high-density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age-matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher gray matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity while participants attempted to generate hand opening either supported on a table or while lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability while lifting the arm due to involuntary coupling between the shoulder and wrist/finger flexors. Together, this evidence implicates a compensatory role for ipsilateral (i.e., contralesional) secondary motor areas post-stroke, but with limited capacity to support hand function.
Novel meta-analysis pipeline of heterogeneous high-throughput gene expression datasets reveals dysregulated interactions and pathways in asthma
Authors: Guo Brandon , Kaushik Abhinav , Nadeau Kari C.
Published: November 2019

Introduction

Asthma is a complex and chronic inflammatory disorder with varying degrees of airway inflammation. It affects ∼235 million people worldwide, and about 8% of the United States population. Unlike single-gene disorders, asthma phenotypes are guided by a highly variable combination of genotypes, making it a complex disease to study computationally. Recently, several independent high-throughput gene expression studies in bioinformatics have identified and proposed numerous molecular drivers involved in asthma initiation and progression. However, there is a poor consensus in our understanding of the molecular factors involved in the mechanism of this disease due to inherent genetic heterogeneity. Such an uncertainty in bioinformatics studies have led to a “reproducibility crisis” in the field, where similar analyses can often yield greatly varying results. In this study, we seek to harness heterogeneity in asthma by applying a meta-analysis that explores varying tissue environments.

Methods

We use three publicly-available microarray gene expression datasets, belonging to different tissues in asthma patients, from NCBI’s Gene Expression Omnibus (GEO). As a meta-analysis, we apply a mixed-model effect size test to determine differentially expressed (DE) genes across all three studies. Then, The datasets are pre-processed and subjected to Weighted Gene Co-expression Network Analysis (WGCNA) for identification of functional modules. Using module preservation, we determine modules in asthma that were not preserved in the healthy condition, then combine the three with a Fisher’s test for a set of asthma-unique modules. These modules are explored using functional analysis (i.e. GO term analysis). Using the DE genes as well as known transcription factors, we re-construct Gene Regulatory Networks (GRNs) for each of our shortlisted modules. We then studied the topology of these GRNs using hive plots to reveal underlying dysregulations, paving the way for future analyses.

Results

Our analysis reveals a novel perspective to a key interaction in asthma inflammatory regulation, the CHD4-CCL26 transcription relation. Our hive plot analysis is able to explore this gene interaction beyond the typical “over-expression, under-expression” results from typical bioinformatics studies. We reveal that CCL26, an important regulator of asthma, appears to increase in expression and topological degree in asthma, but loses connection to CHD4, which seems to be characteristic to the asthma disease. Such analysis suggests that the topology of gene networks, above simply expression values, may be key to understanding the nuanced interactions between fundamental biomarkers and drug targets in complex diseases like asthma.
Vascular Territory, White Matter Connections and the Neuroanatomical Basis of Memory Impairment after Stroke
Authors: Wright Paul , O’Sullivan Michael J.
Published: November 2019

Objective

To investigate neuroanatomical correlates of memory impairment 30-90 days after stroke, including the role of white matter connections in the core circuit for episodic memory.

Methods

A cohort of 179 patients with first symptomatic ischaemic stroke were enrolled into a longitudinal cognitive study, STRATEGIC. Verbal and visual memory were assessed at 50±19 (range 22-109) days. Lesion topography was defined by imaging (n=152). In a representative subgroup (n=53), 3T MRI and tractography was used to define patterns of tract injury and microstructure of uninjured tracts.

Results

Lesion location, defined by arterial territory, was associated with verbal memory impairment (F(12,164)=2.62, p=0.003), independent of other factors such as age, risk factor status and lesion volume. Independent lesion symptom mapping identified regions of the left posterior temporal white matter, within the left posterior cerebral artery territory, associated specifically with verbal recall. Visual recognition memory was associated with microstructure of the uninjured fornix but not with lesion location.

Conclusions

Infarct location strongly influenced verbal recall performance 50 days after stroke. Damage in two locations underpinned this relationship: the thalamus; and within the left PCA territory, where disconnection of parahippocampal white matter projections contributed to verbal memory impairment in some cases. The correlates of early cognitive prognosis were domain-specific with a different pattern of associations with executive function. The association between microstructure of the uninjured fornix and visual memory might reflect the effects of comorbid pathology on hippocampal circuits.
The rice pentatricopeptide repeat protein PPR756 is involved in pollen development by affecting multiple RNA editing in mitochondria
Authors: Zhang Qiannan , Xu Yanghong , Huang Jishuai , Zhang Kai , Xiao Haijun , Qin Xiaojian , Zhu Linlin , Zhu Yingguo , Hu Jun
Published: November 2019

In land plants, the pentatricopeptide repeat (PPR) proteins form a large family involved in post-transcriptional processing of RNA in mitochondria and chloroplasts, which is critical for plant development and evolutionary adaption. Although studies showed a number of PPR proteins generally influence the editing of organellar genes, few of them were characterized in detail in rice. Here, we report a PLS-E subclass PPR protein in rice, PPR756, loss of function of which led to the abolishment of RNA editing events among three mitochondrial genes including atp6, ccmC, and nad7. Their defective C-to-U transformation then resulted in improper amino acid retention which could cause abortive pollen development. Furthermore, PPR756 could bind to the three target genes directly and interact with three OsMORFs (multiple organellar RNA editing factors): OsMORF1, OsMORF8-1, and OsMORF8-2. The knock-out plants of PPR756 exhibited retarded growth and greener leaves during the early vegetative stages, along with sterile pollen and lower seed setting at the reproductive stage. These results established a role for PPR756 in rice development, participating in RNA editing of three various transcripts and cooperating with OsMORFs via an editosome manner in rice.
Crystal and molecular structure of jatrophane diterpenoid (2R,3R,4S,5R,7S,8S,9S,13S,14S,15R)-2,3,8,9-tetraacetoxy-5,14-bis(benzoyloxy)-15-hydroxy-7-(isobutanoyloxy)jatropha-6(17),11(E)-diene
Authors: Yang Hequn , Zhao Jiangyu , Talipov Samat , Izotova Lidiya , Aisa Haji Akber , Ibragimov Bakhtiyar
Published: November 2019

The structure of the jatrophane diterpenoid (ES2), C46H56O15, has orthorhombic (P212121) symmetry. The absolute configuration in the crystal has been determined as 2R,3R,4S,5R,7S,8S,9S,13S,14S,15R [the Flack parameter is −0.06 (11)]. The molecular structure features intramolecular O—H...O and C—H...O hydrogen bonding. In the crystal, C—H...O hydrogen bonds link the molecules into supramolecular columns parallel to the a axis. One of the acetoxy substituents is disordered over two orientations in a 0.826 (8):0.174 (8) ratio.
Crystal structure of tris[bis(2,6-diisopropylphenyl) phosphato-κO]pentakis(methanol-κO)europium methanol monosolvate
Authors: Kalugin Alexey E. , Lyssenko Konstantin A. , Minyaev Mikhail E. , Roitershtein Dmitrii M. , Puntus Lada N. , Varaksina Evgenia A. , Nifant'ev Ilya E.
Published: November 2019

The mononuclear title complex, [Eu(C24H34O4P)3(CH4O)5]·CH4O, (1), has been obtained as a minor product in the reaction between EuCl3(H2O)6 and lithium bis(2,6-diisopropylphenyl) phosphate in a 1:3 molar ratio in a methanol medium. Its structure exhibits monoclinic (P21/c) symmetry at 120 K and is isostructural with the La, Ce and Nd analogs reported previously [Minyaev et al. (2018a). Acta Cryst. C74, 590–598]. In (1), all three bis(2,6-diisopropylphenyl) phosphate ligands display the terminal κ1
O-coordination mode. All of the hydroxy H atoms are involved in O—H...O hydrogen bonding, exhibiting four intramolecular and two intermolecular hydrogen bonds. Photophysical studies have demonstrated luminescence of (1) with a low quantum yield.
Molecular replacement using structure predictions from databases
Authors: Simpkin Adam J. , Thomas Jens M. H. , Simkovic Felix , Keegan Ronan M. , Rigden Daniel J.
Published: November 2019

Molecular replacement (MR) is the predominant route to solution of the phase problem in macromolecular crystallography. Where the lack of a suitable homologue precludes conventional MR, one option is to predict the target structure using bioinformatics. Such modelling, in the absence of homologous templates, is calledab initioorde novomodelling. Recently, the accuracy of such models has improved significantly as a result of the availability, in many cases, of residue-contact predictions derived from evolutionary covariance analysis. Covariance-assistedab initiomodels representing structurally uncharacterized Pfam families are now available on a large scale in databases, potentially representing a valuable and easily accessible supplement to the PDB as a source of search models. Here, the unconventional MR pipelineAMPLEis employed to explore the value of structure predictions in the GREMLIN and PconsFam databases. It was tested whether these deposited predictions, processed in various ways, could solve the structures of PDB entries that were subsequently deposited. The results were encouraging: nine of 27 GREMLIN cases were solved, covering target lengths of 109–355 residues and a resolution range of 1.4–2.9 Å, and with target–model shared sequence identity as low as 20%. The cluster-and-truncate approach inAMPLEproved to be essential for most successes. For the overall lower quality structure predictions in the PconsFam database, remodelling withRosettawithin theAMPLEpipeline proved to be the best approach, generating ensemble search models from single-structure deposits. Finally, it is shown that theAMPLE-obtained search models deriving from GREMLIN deposits are of sufficiently high quality to be selected by the sequence-independent MR pipelineSIMBAD. Overall, the results help to point the way towards the optimal use of the expanding databases ofab initiostructure predictions.
Collision detection and force control based on the impedance approach and dynamic modelling
Authors: Wang Pengcheng , Zhang Dengfeng , Lu Baochun
Published: November 2019

Purpose

This paper aims to address the collision problem between robot and the external environment (including human) in an unstructured situation. A new collision detection and torque optimization control method is proposed.

Design/methodology/approach

Firstly, when the collision appears, a second-order Taylor observer is proposed to estimate the residual value. Secondly, the band-pass filter is used to reduce the high-frequency torque modeling dynamic uncertainty. With the estimate information and the torque value, a variable impedance control approach is then synthesized to guarantee that the collision is avoided or the collision will be terminated with different contact models and positions. However, in terms of adaptive linear force error, the variation of the thickness of the boundary layer is controlled by the new proximity function.

Findings

Finally, the experimental results show the better performance of the proposed control method, realizing the force control during the collision process.

Originality/value

Origin approach and origin experiment.
Overcoming the capital investment hurdle in worker-controlled firms
Authors: Major Guy , Preminger Jonathan
Published: November 2019

Purpose

Both the academic literature and practitioners have long noted the need for an equity investment mechanism for worker-controlled firms that alleviates investor anxieties without undermining internal workplace democracy. The purpose of this paper is to outline one such possible mechanism.

Design/methodology/approach

The proposal locks together the interests of workers and external investors, via non-voting shares with dividends set by a pre-agreed value-added sharing formula. Each worker is paid a base wage, with the average across the firm being a pre-defined multiple of the national minimum wage. Any additional surplus is split into a number of equal “slices”, with each share receiving one slice as its dividend, and the average worker receiving a pre-agreed number of slices as a bonus.

Findings

Workers have an incentive to maximise their own incomes, and in so doing, will also automatically maximise the dividends received by investors, obviating the need for the shares to have normal voting rights. Working on this principle of aligned interests, the authors also discuss reinvestment, worker ownership of non-voting shares and possibilities for a secondary share market. The authors show how this proposal will be a significant step in aligning the interests of investors with owner-workers in a democratic, negotiated way that shares both risk and returns, thus making worker-controlled firms more attractive to equity investment.

Originality/value

In light of the recognised problem of underinvestment in worker-controlled firms and the risk of their degeneration, this paper will interest both academics and practitioners in employee ownership, co-operatives and various forms of workplace democracy.
A two-stage structural equation modeling-neural network approach for understanding and predicting the determinants of m-government service adoption
Authors: Talukder Shamim , Chiong Raymond , Dhakal Sandeep , Sorwar Golam , Bao Yukun
Published: November 2019

Purpose

Despite the widespread use of mobile government (m-government) services in developed countries, the adoption and acceptance of m-government services among citizens in developing countries is relatively low. The purpose of this study is to explore the most critical determinants of acceptance and use of m-government services in a developing country context.

Design/methodology/approach

The unified theory of acceptance and use of technology (UTAUT) extended with perceived mobility and mobile communication services (MCS) was used as the theoretical framework. Data was collected from 216 m-government users across Bangladesh and analyzed in two stages. First, structural equation modeling (SEM) was used to identify significant determinants affecting users' acceptance of m-government services. In the second stage, a neural network model was used to validate SEM results and determine the relative importance of the determinants of acceptance of m-government services.

Findings

The results show that facilitating conditions and performance expectancy are the two important precedents of behavioral intention to use m-government services, and performance expectancy mediates the relationship between MCS, mobility and the intention to use m-government services.

Research limitations/implications

Academically, this study extended and validated the underlying concept of UTAUT to capture the adoption behavior of individuals in a different cultural context. In particular, MCS might be the most critical antecedent towards mobile application studies. From a practical perspective, this study may provide valuable guidelines to government policymakers and system developers towards the development and effective implementation of m-government systems.

Originality/value

This study has contributed to the existing, but limited, literature on m-government service adoption in the context of a developing country. The predictive modeling approach is an innovative approach in the field of technology adoption.
Rap1‐mediated nucleosome displacement can regulate gene expression in senescent cells without impacting the pace of senescence
Authors: Song Shufei , Perez Javier V. , Svitko William , Ricketts M. Daniel , Dean Elliot , Schultz David , Marmorstein Ronen , Johnson F. Brad
Published: November 2019

Cell senescence is accompanied, and in part mediated, by changes in chromatin, including histone losses, but underlying mechanisms are not well understood. We reported previously that during yeast cell senescence driven by telomere shortening, the telomeric protein Rap1 plays a major role in reprogramming gene expression by relocalizing hundreds of new target genes (called NRTS, for new Rap1 targets at senescence) to the promoters. This leads to two types of histone loss: Rap1 lowers histone level globally by repressing histone gene expression, and it also causes local nucleosome displacement at the promoters of upregulated NRTS. Here, we present evidence of direct binding between Rap1 and histone H3/H4 heterotetramers, and map amino acids involved in the interaction within the Rap1 SANT domain to amino acids 392–394 (SHY). Introduction of a point mutation within the native RAP1 locus that converts these residues to alanines (RAP1SHY), and thus disrupts Rap1‐H3/H4 interaction, does not interfere with Rap1 relocalization to NRTS at senescence, but prevents full nucleosome displacement and gene upregulation, indicating direct Rap1‐H3/H4 contacts are involved in nucleosome displacement. Consistent with this, the histone H3/H4 chaperone Asf1 is similarly unnecessary for Rap1 localization to NRTS but is required for full Rap1‐mediated nucleosome displacement and gene activation. Remarkably, RAP1SHY does not affect the pace of senescence‐related cell cycle arrest, indicating that some changes in gene expression at senescence are not coupled to this arrest.
A Multifaceted Intervention to Improve Patient Knowledge and Safe Use of Opioids: Results of the ED EMC2 Randomized Controlled Trial
Authors: McCarthy Danielle M. , Curtis Laura M. , Courtney D. Mark , Cameron Kenzie A. , Lank Patrick M. , Kim Howard S. , Opsasnick Lauren A. , Lyden Abbie E. , Gravenor Stephanie J. , Russell Andrea M. , Eifler Morgan R. , Hur Scott I. , Rowland Megan E. , Walton Surrey M. , Montague Enid , Kim Kwang‐Youn A. , Wolf Michael S.
Published: November 2019

Objectives

Despite increased focus on opioid prescribing, little is known about the influence of prescription opioid medication information given to patients in the emergency department (ED). The study objective was to evaluate the effect of an Electronic Medication Complete Communication (EMC2) Opioid Strategy on patients’ safe use of opioids and knowledge about opioids.

Methods

This was a three‐arm prospective, randomized controlled pragmatic trial with randomization occurring at the physician level. Consecutive discharged patients at an urban academic ED (>88,000 visits) with new hydrocodone‐acetaminophen prescriptions received one of three care pathways: 1) usual care, 2) EMC2 intervention, or 3) EMC2 + short message service (SMS) text messaging. The ED EMC2 intervention triggered two patient‐facing educational tools (MedSheet, literacy‐appropriate prescription wording [Take‐Wait‐Stop]) and three provider‐facing reminders to counsel (directed to ED physician, dispensing pharmacist, follow‐up physician). Patients in the EMC2 + SMS arm additionally received one text message/day for 1 week. Follow‐up at 1 to 2 weeks assessed “demonstrated safe use” (primary outcome). Secondary outcomes including patient knowledge and actual safe use (via medication diaries) were assessed 2 to 4 days and 1 month following enrollment.

Results

Among the 652 enrolled, 343 completed follow‐up (57% women; mean ± SD age = 42 ± 14.0 years). Demonstrated safe opioid use occurred more often in the EMC2 group (adjusted odds ratio [aOR] = 2.46, 95% confidence interval [CI] = 1.19 to 5.06), but not the EMC2 + SMS group (aOR = 1.87, 95% CI = 0.90 to 3.90) compared with usual care. Neither intervention arm improved medication safe use as measured by medication diary data. Medication knowledge, measured by a 10‐point composite knowledge score, was greater in the EMC2 + SMS group (β = 0.57, 95% CI = 0.09 to 1.06) than usual care.

Conclusions

The study found that the EMC2 tools improved demonstrated safe dosing, but these benefits did not translate into actual use based on medication dairies. The text‐messaging intervention did result in improved patient knowledge.
Institutions, banking structure and the cost of debt: new international evidence
Authors: Álvarez‐Botas Celia , González Víctor M.
Published: November 2019

This paper analyses the effect of institutions and the structure of the banking system on the cost of debt for a sample of firms from 37 countries. The cost of debt decreases with the rule of law, the protection of creditors’ rights and the weight of banks in the economy. Bank financing and bank concentration have a positive differential effect on the cost of debt in those countries where the financial difficulties of banks are greater. Legal enforcement, the protection of creditors’ rights and the weight of bank financing have a greater influence in countries with a lower degree of economic development.
CEO characteristics: a review of influential publications and a research agenda
Authors: Shen Yun
Published: November 2019

This paper provides a systematic review of literature pertaining to CEO characteristics and firm performance. The CEO of a firm provides critical leadership, social capital, and legitimacy, and as such exerts significant influence on firm performance. By using a bibliographic mapping approach, we identify the fifty‐one most influential publications on CEO characteristics. This field has developed from a few Upper Echelon Theory publications into four distinct categories. We review each of these to identify the main contributions to this research area and to outline research gaps and future research trends.
Peter the great and cataract surgery
Authors: Grzybowski Andrzej , Zimin Igor , Leffler Christopher T.
Published: November 2019

Tsar Peter Alekseyevich Romanov (1672–1725), often called Peter the Great, modernized Russia in many areas, including in the field of medicine. Peter I attended medical lectures and demonstrations and may have even performed some medical procedures himself. In Paris, he witnessed a cataract couching performed by Englishman John Thomas Woolhouse (1664–1733/4) and requested that Woolhouse train a Russian student in ophthalmology.
Climate severity and land‐cover transformation determine plant community attributes in Colombian dry forests
Authors: González‐M. Roy , Norden Natalia , Posada Juan M. , Pizano Camila , García Hernando , Idárraga‐Piedrahita Álvaro , López‐Camacho René , Nieto Jhon , Rodríguez-M Gina M. , Torres Alba M. , Castaño‐Naranjo Alejandro , Jurado Rubén , Franke‐Ante Rebeca , Galindo-T Robinson , Hernández R. Elkin , Barbosa Adriana , Salgado‐Negret Beatriz
Published: November 2019

Tropical dry forests (TDF) are known to be resource‐limited due to a marked seasonality in precipitation. However, TDF are also shaped by factors such as solar radiation, wind speed, soil fertility, and land‐cover transformation. Together, these factors may determine different gradients of environmental harshness that are likely to drive changes in plant community attributes. Here, we evaluated the effects of environmental harshness on plant community diversity and structure of Colombian TDF, based on floristic and environmental data from 15 1‐ha permanent plots. We also analyzed these effects on legumes species only (including both deciduous and non‐deciduous species), deciduous species only (including both legumes and non‐legumes species), and on the whole community excluding either legumes or deciduous separately. Drier conditions and higher land‐cover transformation had the strongest negative effects on species diversity, basal area (BA), and canopy height. Soil fertility, on the contrary, did not have a significant effect on any of the evaluated response variables. Interestingly, legumes maintained their diversity and BA along the climatic gradient, while deciduous species were negatively affected by drier conditions and by an increase in secondary vegetation at the landscape level. Our results suggest that although TDF are limited by water availability, land‐cover transformation strongly increases environmental harshness. Yet, both legumes and deciduous species were differentially impacted by climatic and land transformation variables. Thus, to better understand TDF plant community attributes, it is necessary to consider these gradients and to disentangle their effects on different plant functional groups.

Abstract in Spanish is available with online material.
Engaging Children in Meaningful Charity: Opening‐up the Spaces within Which Children Learn to Give
Authors: Body Alison , Lau Emily , Josephidou Jo
Published: November 2019

This paper presents qualitative evidence from an in‐depth, participative action research project with 150 children aged 4–8 years old, exploring their experiences, perceptions and preferences regarding charitable giving. Most children positively engage in charitable giving through home, school and their community; however, less than 20% are aware of the cause area they are being asked to support, and most have little decision‐making in their giving. Children’s willingness to engage increases when they critically examine the cause area and are facilitated to lead on giving decisions, often resulting in increased and sustained efforts to support cause areas that matter to them.
Ecological change in dynamic environments: Accounting for temporal environmental variability in studies of ocean change biology
Authors: Kroeker Kristy J. , Bell Lauren E. , Donham Emily M. , Hoshijima Umihiko , Lummis Sarah , Toy Jason A. , Willis‐Norton Ellen
Published: November 2019

The environmental conditions in the ocean have long been considered relatively more stable through time compared to the conditions on land. Advances in sensing technologies, however, are increasingly revealing substantial fluctuations in abiotic factors over ecologically and evolutionarily relevant timescales in the ocean, leading to a growing recognition of the dynamism of the marine environment as well as new questions about how this dynamism may influence species' vulnerability to global environmental change. In some instances, the diurnal or seasonal variability in major environmental change drivers, such as temperature, pH and seawater carbonate chemistry, and dissolved oxygen, can exceed the changes expected with continued anthropogenic global change. While ocean global change biologists have begun to experimentally test how variability in environmental conditions mediates species' responses to changes in the mean, the extensive literature on species' adaptations to temporal variability in their environment and the implications of this variability for their evolutionary responses has not been well integrated into the field. Here, we review the physiological mechanisms underlying species' responses to changes in temperature,pCO2/pH (and other carbonate parameters), and dissolved oxygen, and discuss what is known about behavioral, plastic, and evolutionary strategies for dealing with variable environments. In addition, we discuss how exposure to variability may influence species' responses to changes in the mean conditions and highlight key research needs for ocean global change biology.
Diagnostic accuracy of a novel cuffless self‐blood pressure monitor for atrial fibrillation screening in the elderly
Authors: Kyriakoulis Konstantinos G. , Kollias Anastasios , Anagnostopoulos Ioannis , Gravvani Areti , Kalogeropoulos Petros , Destounis Antonios , Stergiou George S.
Published: November 2019

Blood pressure (BP) monitors equipped with atrial fibrillation (AF) detection algorithm are attractive screening tools for AF in elderly hypertensives. This study assessed the diagnostic accuracy of a novel cuffless pocket‐size self‐BP monitor (Freescan, Maisense) equipped with an AF detection algorithm, which displays results for the detection of “AF” or “Arrhythmia” during routine BP measurement. Subjects aged >65 years or 60‐65 years with hypertension, diabetes, or cardiovascular disease were subjected to BP measurements using the Freescan device with simultaneous continuous Holter electrocardiography (ECG) monitoring. Readings with device notification “Instability” (29%) or “Error” (20%) were discarded. Data from 136 subjects with five valid Freescan BP measurements were analyzed (age 73.8 ± 7.1 years, males 63%, treated hypertensives 88%, AF in ECG 21%). Analysis of 680 Freescan readings vs ECG revealed specificity 99%, sensitivity 67%, and diagnostic accuracy 93% for AF diagnosis. When the “Arrhythmia” notification was considered as AF diagnosis, the sensitivity was improved (93%, 96%, and 93%, respectively). Analysis of AF diagnosis in subjects (diagnosis defined as at least three of five readings indicating “AF” or “Arrhythmia”) revealed specificity, sensitivity, and diagnostic accuracy for AF detection at 94%, 100%, and 95%, respectively. These data suggest that the Freescan cuffless device could be used as a useful screening tool for AF detection during routine self‐measurement of BP in the elderly.
Stocking rate and organic waste type affect development of three Chrysomya species and Lucilia sericata (Diptera: Calliphoridae): Implications for bioconversion
Authors: Parry Nina Jennifer , Pieterse Elsje , Weldon Christopher William
Published: November 2019

Fly larvae can be used effectively to reduce various organic waste types and produce value‐added products, including protein as an ingredient in livestock feeds and oil for biodiesel production. However, fly development on different waste types may cause differences in growth rate and the body composition, which can further be influenced by fly species and their stocking rate. This study explored the impact of different waste types (kitchen waste, abattoir waste and swine manure) and larval stocking rate on growth and body composition of four blowfly species, Chrysomya chloropyga (Wiedemann), Chrysomya megacephala (Fabricius), Chrysomya putoria (Wiedemann) and Lucilia sericata (Meigen). First‐instar larvae (20, 50 or 100), less than 3 hr old, were placed on 100 g of each waste type. Pre‐pupal mass at commencement of post‐feeding larval dispersal, time to onset of dispersal, survival and nutrient reserves were determined for each species, stocking rate and waste type. Our results revealed that larvae fed kitchen and abattoir waste had significantly higher dry mass, crude protein and lipid content compared with those fed swine manure. Higher survival rate was observed with increasing larval stocking rate. We provide important information to guide the mass production of high‐quality nutrient‐rich larvae and recommend C. putoria, which is versatile and effective on a range of waste products, as well as high in protein and lipids. The implications for waste management are discussed.
Valuations and dynamics of negotiations
Authors: Gomes Armando
Published: November 2019

This paper analyzes three‐party negotiations in the presence of externalities. We obtain a closed‐form solution for the Markov perfect equilibrium of a multilateral non‐cooperative bargaining model, yielding an equilibrium value and dynamics of negotiations that are supported by experimental studies. Players’ values are monotonically increasing (or decreasing) in the amount of negative (or positive) externalities that they impose on others. Moreover, players’ values are continuous and piecewise linear on the worth of bilateral coalitions, and are inextricably related to their negotiation strategies: the equilibrium value is the Nash bargaining solution when no bilateral coalitions form; the Shapley value when all bilateral coalitions form; or the nucleolus, when either one bilateral coalition among “natural partners” or two bilateral coalitions including a “pivotal player” form.
Pharmacological characterization of high-affinity σ1 receptor ligands with spirocyclic thienopyran and thienofuran scaffold
Authors: Schepmann Dirk , Neue Christina , Westphälinger Stefanie , Müller Christoph , Bracher Franz , Lange Carsten , Bednarski Patrick , Almansa Carmen , Friedland Kristina , Räbiger Vivien , Düfer Martina , Wünsch Bernhard
Published: November 2019

Objectives

In this study, the pharmacological properties of six spirocyclic piperidines 1–6 showing very high σ1 receptor affinity (Ki = 0.2–16 nm) were investigated.

Methods

In vitro receptor binding studies, retinal ganglion assay and in vivo capsaicin assay were used to determine the affinity, selectivity and activity. Influence on human tumour cell growth (cell lines A427, LCLC-103H, 5637 and DAN-G) was determined in different assays. The effect on the ergosterol and cholesterol biosynthesis was determined by GLC/MS analysis.

Key findings

Receptor binding studies demonstrated high selectivity for the σ1 receptor. The increased Ca2+ influx mediated by 2 and the analgesic activity of 1, 4, 5 and 6 confirm σ1 receptor antagonistic activity. Inhibition of human tumour cell growth further supports the σ1 antagonistic effects. Treatment of A427 tumour cells with 2 led to cell detachment and cell degradation. Whereas the ergosterol biosynthesis was not affected, the sterol C14-reductase, a key enzyme in the cholesterol biosynthesis, was weakly inhibited.

Conclusions

Due to the high selectivity, off-target effects are not expected. The antiallodynic activity underlines the clinical potential of the spirocyclic piperidines for the treatment of neuropathic pain. Due to the antiproliferative activity, the spirocyclic σ1 antagonists represent promising antitumour agents.
Potential effect of the microbial fermented feed utilization on physicochemical traits, antioxidant enzyme and trace mineral analysis in rabbit meat
Authors: Shah Assar Ali , Liu Zhiwei , Qian Chen , Wu Juanzi , Sultana Nighat , Zhong Xiaoxian
Published: November 2019

The study investigated the potential effect of the microbial fermented feed utilization on physicochemical traits, antioxidant enzyme and trace mineral analysis in rabbit meat. A total of 72 six‐week‐old male rabbits were weighed and randomly divided into four groups (1) (SRKC) control; (2) (SRKP) Lactobacillus plantarum 1 × 106 cfu/g fresh weight (FW); (3) (SRKG) Pediococcus acidilactici 1 × 106cfu/g FW and (4) (SRKPG) P. acidilactici + L. plantarum 1 × 106 cfu/g FW. Performance characteristic, weekly body weight, was positively (p < .05) enhanced, while daily feed intake (DFI) and feed convention ratio (FCR) were not influenced in treatments group as compared to untreated. The water, protein, water holding capacity (WHC) and dry matter (DM) concentration were positively (p < .05) influenced, while ash, pH, lightness, redness and yellowness were not influenced in treated group as compared to untreated. The concentration of glutathione peroxidase (Gpx), superoxide dismutase (SOD) and aspartate aminotransferase (AST) was positively (p < .05) influenced in treatments group as compared to control. Regarding trace minerals, copper (Cu), iron (Fe), manganese (Mn) and zinc (Zn) were positively (p > .05) reduced in treated group as compared to untreated. It is concluded that the addition of lactic acid bacteria (L. plantarum and P. acidilactici) in Hybrid pennisetum silage had a constructive influence on rabbit health performance and meat biochemistry.