bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal lactazole scaffold for in vitro production of pseudo-natural thiopeptides
Authors: Vinogradov Alexander A. , Shimomura Morito , Goto Yuki , Ozaki Taro , Asamizu Shumpei , Sugai Yoshinori , Suga Hiroaki , Onaka Hiroyasu
Published: October 2019

Lactazole A is a cryptic thiopeptide from Streptomyces lactacystinaeus, encoded by a compact 9.8 kb biosynthetic gene cluster. Here, we established a platform for in vitro biosynthesis of lactazole A, referred to as the FIT-Laz system, via a combination of the flexible in vitro translation (FIT) system with recombinantly produced lactazole biosynthetic enzymes. Systematic dissection of lactazole biosynthesis revealed remarkable substrate tolerance of the biosynthetic enzymes, and led to the development of the “minimal lactazole scaffold”, a construct requiring only 6 post-translational modifications for macrocyclization. Efficient assembly of such minimal thiopeptides with FIT-Laz enabled access to diverse lactazole analogs with 10 consecutive mutations, 14- to 62-membered macrocycles, and up to 18 amino acid-long tail regions. Moreover, utilizing genetic code reprogramming, we demonstrated synthesis of pseudo-natural lactazoles containing 4 non-proteinogenic amino acids. This work opens possibilities in exploring novel sequence space of pseudo-natural thiopeptides.
Conceptualising patterns of career commitment: the leaving process in hospitality
Authors: Gebbels Maria , Pantelidis Ioannis S. , Goss-Turner Steven
Published: October 2019

Purpose

This paper aims to examine the interplay between self-efficacy and career inheritance and its influence on career commitment in the hospitality sector. High labour turnover, unclear career paths and the transient nature of the work available in hospitality render it a suitable industry context that allows us to explore career commitment patterns.

Design/methodology/approach

Drawing on life history methodology, semi-structured interviews were conducted with hospitality professionals holding a relevant degree but no longer employed in the hospitality industry.

Findings

The findings revealed the interplay between self-efficacy, career inheritance and career commitment, as well as the speed of decline of career commitment, visualised as patterns of the leaving process. Although an infinite number of variations are possible, data unveiled the three main patterns.

Research limitations/implications

The schematic illustrations of the patterns of the leaving process are not representative. The purposive sample comprises only ex-hospitality professionals, and generalisations can be considered in future studies.

Practical implications

This newly conceptualised understanding of career commitment enables researchers to reconsider the fundamental reasons why individuals leave the hospitality industry, whilst also offering hospitality managers deeper insights into how the three identified patterns could inform recruitment and selection.

Originality/value

This paper contributes to the literature through its meaningful theoretical extension in the context of career development studies. The unique concept of the leaving process addresses the prevalent issue of turnover and generates important implications.
Do parents and carers experiencing violent and challenging behaviour from their children fit with safeguarding models of support? Messages from a Facebook study
Authors: Heslop Philip , McAnelly Su , Wilcockson Jane , Newbold Yvonne , Avantaggiato-Quinn Maria , Meredith Cathryn
Published: October 2019

Purpose

This paper reports research findings on the experiences of parents/carers of children with special education needs and disabilities who present violent and challenging behaviour. More specifically, the purpose of this paper is to explore how parents/carers report how their support needs are met by social care services.

Design/methodology/approach

The research is an empirical study which considers the challenging side of parenting children with additional needs. Data were gathered through a national online social media focus group and thematically analysed to identify emerging themes from an overlooked community. The study applied a participatory approach, with researchers and participants collaborating in designing and producing the research.

Findings

Participants reported a multitude of adversities and they experience difficulties in accessing support from professionals. The parents and carers expressed a continued desire to care for their children, often during much adversity and in receipt of little recognition or support from external agencies. An emerging theme was that they are often not assessed in their own right by agencies who focus on safeguarding.

Research limitations/implications

In this online participatory study, participants were self-selecting and the research relied on self-report during online discussions.

Originality/value

This study is original in applying an innovative research methodology using online focus groups with an under researched community. This online focus group generated real time data and offered participants the opportunity to share information in their own environments. The themes emerging from this research have implications for policy and practice for an under reported adult community who experience increasing vulnerabilities.
Evaluation of a psychology graduate internship programme
Authors: Moulton-Perkins Alesia , Wressle Alexandra , Grey Nick , Sired Rebecca
Published: October 2019

Purpose

Applications for clinical psychology training far outstrip places and relevant work experience is key. Paid opportunities are limited and therefore many choose volunteering, with well-connected graduates faring best. To promote equal opportunities a coordinated psychology graduate voluntary internship programme was established in a National Health Service Trust in the South of England. The purpose of this paper is to evaluate intern and supervisor outcomes, equality of access and adherence to governance standards.

Design/methodology/approach

Three cohorts of interns, unappointed applicants and supervisors were surveyed. Between 2013 and 2016, 270 psychology graduates applied, 119 were recruited and 151 either refused a place or were unsuccessful. In total, 91 supervisors provided service-level feedback.

Findings

Interns and applicants were predominantly young, able-bodied white British heterosexual females. Demographic profiles were similar and broadly representative of psychology graduates nationally. While fewer were from Black and Ethnic Minority backgrounds, proportions were greater than the local population. Participants were more socioeconomically privileged than undergraduates nationally. The scheme was popular and well governed according to interns and supervisors. Post-internship employment prospects were improved, with most interns gaining paid mental health roles like assistant psychologist. Most supervisors commented on the positive contribution made by interns to service outcomes.

Originality/value

This study makes a significant contribution to the literature on voluntary psychology graduate posts, an area under-researched until now. Our results suggest that a coordinated, transparent approach can benefit both interns and services by minimising exploitation and maximising developmental opportunities for the new graduate. The programme makes an important contribution to addressing inequalities experienced by psychology graduates attempting to enter mental health careers.
Human rights and the moralities of property
Authors: Holligan Bonnie
Published: October 2019

Purpose

Responding to the Supreme Court’s decision in R (on the application of Mott) v. Environment Agency, the purpose of this study is to explore the interface between property, environment and human rights. It examines the space within human rights jurisprudence for a richer notion of property that can accommodate social and environmental obligation and non-anthropocentric values.

Design/methodology/approach

In this study, a theoretical lens is applied to human rights doctrine. A central question is the extent to which there is room within the discourse on Article 1 of Protocol 1 (A1P1) to the European Convention on Human Rights for a more relational and ecocentric approach. The paper engages with the jurisprudence of the UK courts and that of the European Court of Human Rights, as well as the works of scholars such as Jennifer Nedelsky and Nicole Graham.

Findings

It is concluded that although the judgment in Mott demonstrates the potential for A1P1 to function as a means for rights-holders to obtain a voice in environmental decision-making processes, it highlights the tendency of property to preserve existing structures and arrangements. When assessing whether an individual is asked to bear an excessive burden, great weight was given in Mott to values associated with livelihood. What did not feature in the (brief) judgment was the consideration of the ecological context in which Mr Mott’s rights were embedded and the extent to which this context might have inherently restricted his ability to enjoy his property. The dispute demonstrates the limitations of existing property institutions and discourses in managing ecological conflict and fostering positive relationships and management practices.

Originality/value

This study contributes to the doctrinal literature on A1P1, providing a new perspective on the role of human rights jurisprudence in managing environmental conflict. It is original in its examination of human rights discourse in light of relational and ecocentric theories of property, providing a critique of existing values and paradigms. Evaluating the doctrinal reasoning in Mott with reference to this theoretical framework, it provides fresh insight into the limitations of the Supreme Court’s approach. It points to the need for more explicit incorporation of environmental values and contexts in human rights reasoning.
Business model innovation: a review and research agenda
Authors: Ramdani Boumediene , Binsaif Ahmed , Boukrami Elias
Published: October 2019

Purpose

The aim of this paper is to review and synthesise the recent advancements in the business model literature and explore how firms approach business model innovation.

Design/methodology/approach

A systematic review of business model innovation literature was carried out by analysing 219 papers published between 2010 and 2016.

Findings

Evidence reviewed suggests that rather than taking either an evolutionary process of continuous revision, adaptation and fine-tuning of the existing business model or a revolutionary process of replacing the existing business model, firms can explore alternative business models through experimentation, open and disruptive innovations. It was also found that changing business models encompasses modifying a single element, altering multiple elements simultaneously and/or changing the interactions between elements in four areas of innovation: value proposition, operational value, human capital and financial value.

Research limitations/implications

Although this review highlights the different avenues to business model innovation, the mechanisms by which firms can change their business models and the external factors associated with such change remain unexplored.

Practical implications

The business model innovation framework can be used by practitioners as a “navigation map” to determine where and how to change their existing business models.

Originality/value

Because conflicting approaches exist in the literature on how firms change their business models, the review synthesises these approaches and provides a clear guidance as to the ways through which business model innovation can be undertaken.
Artful praxis: experience, inquiry and consciousness
Authors: Arnold Julie
Published: October 2019

Purpose

The purpose of this paper is to illuminate the way in which pre-service teachers adopt ways of thinking critically about learning and practice. It highlights the unfolding of critical dialogue, knowledge and artful action as a way of “reading the scene” (Pahl and McKenna, 2015). The focus concerns mindshifts that occur while learning to be a teacher. The study sets out to seek factors that contribute towards development as professional practitioner.

Design/methodology/approach

As part of a much larger study involving ten pre-service teachers, this paper focusses on just one participant named Meredith, a pre-service teacher in her fourth year of her teacher education course. The design constructed draws on the data from Meredith’s interview and conversation, art making and gestural activity while painting and communicating her stories. These narratives from interviews exist in this paper as vignettes and privilege of the interplay of art making, interview and gestural responses. Implementing a framework by Denzin (2001) enables a way of reading to note learning and epiphanic moments that exist for Meredith.

Findings

Moment of learning and themes are indicated and suggest that from the original interview there are 11 important moments of epiphanic mindshifts for Meredith.

Originality/value

The method as practice intends to make cogent links to new levels of consciousness by presenting innovative ways in which qualitative research data can be gathered and analysed. Meredith engages in mindshifts that occur as learner and also embraces experiences of praxis as a means of understanding self and teacher identity.
Individual variation in age‐dependent reproduction: Fast explorers live fast but senesce young?
Authors: Dingemanse Niels J. , Moiron Maria , Araya‐Ajoy Yimen G. , Mouchet Alexia , Abbey‐Lee Robin N.
Published: October 2019

Adaptive integration of life history and behaviour is expected to result in variation in the pace‐of‐life. Previous work focused on whether ‘risky’ phenotypes live fast but die young, but reported conflicting support. We posit that individuals exhibiting risky phenotypes may alternatively invest heavily in early‐life reproduction but consequently suffer greater reproductive senescence.

We used a 7‐year longitudinal dataset with >1,200 breeding records of >800 female great tits assayed annually for exploratory behaviour to test whether within‐individual age dependency of reproduction varied with exploratory behaviour. We controlled for biasing effects of selective (dis)appearance and within‐individual behavioural plasticity.

Slower and faster explorers produced moderate‐sized clutches when young; faster explorers subsequently showed an increase in clutch size that diminished with age (with moderate support for declines when old), whereas slower explorers produced moderate‐sized clutches throughout their lives. There was some evidence that the same pattern characterized annual fledgling success, if so, unpredictable environmental effects diluted personality‐related differences in this downstream reproductive trait.

Support for age‐related selective appearance was apparent, but only when failing to appreciate within‐individual plasticity in reproduction and behaviour.

Our study identifies within‐individual age‐dependent reproduction, and reproductive senescence, as key components of life‐history strategies that vary between individuals differing in risky behaviour. Future research should thus incorporate age‐dependent reproduction in pace‐of‐life studies.
The Role of ICT in Modulating the Effect of Education and Lifelong Learning on Income Inequality and Economic Growth in Africa
Authors: Tchamyou Vanessa S. , Asongu Simplice A. , Odhiambo Nicholas M.
Published: October 2019

This study assesses the role of information and communication technologies (ICT) in modulating the impact of education and lifelong learning on income inequality and economic growth. It focuses on a sample of 48 African countries from 2004 to 2014. The empirical evidence is based on the generalized method of moments. The following findings are established. First, mobile phone and internet each interact with primary school education to decrease income inequality. Second, all ICT indicators interact with secondary school education to exert a negative impact on the Gini index. Third, fixed broadband distinctly interacts with primary school education and lifelong learning to have a positive effect on economic growth. Fourth, ICT indicators do not significantly influence inequality and economic growth through tertiary school education and lifelong learning. These main findings are further substantiated. Policy implications are discussed.
Inhibitory Effects of Pectinase‐Treated Prunus Mume Fruit Concentrate on Colorectal Cancer Proliferation and Angiogenesis of Endothelial Cells
Authors: Cho Hyun‐Dong , Kim Jeong‐Ho , Won Yeong‐Seon , Moon Kwang‐Deok , Seo Kwon‐Il
Published: October 2019

Pectinase is a well‐known enzyme used in the food processing industry to produce fruit juice and concentrate. This study evaluated the anticancer and antiangiogenesis activities of pectinase‐treated Prunus mume fruit concentrate (PC) and its phenolic components. PC treatment (250 to 1,000 µg/mL) resulted in decreased proliferation of SW480 human colorectal cancer cells through S‐phase cell cycle arrest; however, equivalent concentrations of PC did not show toxicity toward CRL‐1539 colon normal cells. Furthermore, PC‐induced caspase‐dependent apoptosis in SW480 cells, which was characterized by accumulation of apoptotic cell population, cell shrinkage, formation of apoptotic bodies, upregulation of proapoptotic Bax, cleaved PARP, caspase‐3, caspase‐8, and caspase‐9, and downregulation of antiapoptotic Bcl‐2. Antiangiogenesis effects of PC were assessed using human umbilical vein endothelial cells (HUVECs). We found that PC did not inhibit HUVECs proliferation at concentrations of 500 to 1,500 µg/mL. In addition, treatment with PC at nontoxic concentrations (500 to 1,000 µg/mL) blocked vascular endothelial growth factor induced cell migration, invasion, capillary‐like tube formation, and angiogenesis from rat aortic rings. HPLC‐PDA analysis showed that there were at least four different phenolics including 5‐HMF, neochlorogenic acid, protocatechuic acid, and syringic acid. Taken together, these results indicated that PC could be used as a good source of phenolic compounds with selective anticancer and antiangiogenesis activities.

Practical Application

Pectinases are one of the well‐known enzyme used in the part of food processing. Treatment of pectinase is a useful strategy to reduce viscosity, turbidity, and pulp particles in the production of fruit juice, extract, and concentrate. In the present study, we found that pectinase‐treated P. mume fruit concentrate significantly suppresses colorectal cancer proliferation and angiogenesis of human umbilical vein endothelial cells. The significance of our findings is that pectinase‐treated P. mume concentrate may be used as a commercial functional food material to inhibit colorectal cancer and angiogenesis.
MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations
Authors: Sánchez C. Héctor M. , Wu Sean L. , Bennett Jared B. , Marshall John M.
Published: October 2019

Malaria, dengue, Zika and other mosquito‐borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide‐based tools and antimalarial drugs. The advent of CRISPR/Cas9‐based gene editing and its demonstrated ability to streamline the development of gene drive systems has reignited interest in the application of this technology to the control of mosquitoes and the diseases they transmit. The versatility of this technology has enabled a wide range of gene drive architectures to be realized, creating a need for their population‐level and spatial dynamics to be explored.

We present MGDrivE (Mosquito Gene Drive Explorer): a simulation framework designed to investigate the population dynamics of a variety of gene drive architectures and their spread through spatially explicit mosquito populations. A key strength of the MGDrivE framework is its modularity: (a) a genetic inheritance module accommodates the dynamics of gene drive systems displaying user‐defined inheritance patterns, (b) a population dynamic module accommodates the life history of a variety of mosquito disease vectors and insect agricultural pests, and (c) a landscape module generates the metapopulation model by which insect populations are connected via migration over space.

Example MGDrivE simulations are presented to demonstrate the application of the framework to CRISPR/Cas9‐based homing gene drive for: (a) driving a disease‐refractory gene into a population (i.e. population replacement), and (b) disrupting a gene required for female fertility (i.e. population suppression), incorporating homing‐resistant alleles in both cases. Further documentation and use examples are provided at the project's Github repository.

MGDrivE is an open‐source r package freely available on CRAN. We intend the package to provide a flexible tool capable of modelling novel inheritance‐modifying constructs as they are proposed and become available. The field of gene drive is moving very quickly, and we welcome suggestions for future development.
Cone‐beam computed tomography accuracy in pulp chamber size evaluation: An ex vivo study
Authors: Maddalone Marcello , Citterio Claudio , Pellegatta Alberto , Gagliani Massimo , Karanxha Lorena , Del Fabbro Massimo
Published: October 2019

This study aimed to assess ex vivo the accuracy of cone‐beam computed tomography (CBCT), as compared to operative microscope, for evaluating pulp chamber size. A total of forty teeth were extracted for periodontal reasons and a horizontal section was done at the most apical level of the cement–enamel junction. The pulp chamber was photographed using a digital camera connected to an optical microscope. Then, the tooth was scanned with CBCT and the horizontal slide matching the anatomical section of pulp chamber was digitally stored. The pulp chamber section area was measured through image analysis software. The two methods provided similar results, either for monoradicular (P = 0.14) or multiradicular teeth (P = 0.93). Correlation was statistically significant (P < 0.0001), being the coefficient r = 0.89 and 0.94 for monoradicular and multiradicular teeth, respectively. Conclusively, CBCT is suitable for pulp chamber morphology evaluation. However, it has limitations in detecting the anatomical variability of small branches in root canal system.
Risk factors for periprosthetic femoral fractures around total hip arthroplasty: a systematic review and meta‐analysis
Authors: Deng Yi , Kieser David , Wyatt Michael , Stringer Mark , Frampton Christopher , Hooper Gary
Published: October 2019

Background

Periprosthetic fractures are becoming increasingly common, often leading to poor patient outcomes. The aim of this study was to identify risk factors associated with periprosthetic femoral fractures (PPFFx).

Methods

Two independent reviewers conducted a systematic review of the databases MEDLINE, Embase and Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, from the earliest available date to December 2017. We included all clinical articles reporting more than 100 post‐operative PPFFx around total hip arthroplasty (THA). Outcomes included demographics, fracture type, risk factors and time to fracture.

Results

A total of 12 868 PPFFx were reported across 18 eligible studies; 64% occurred following primary THA and 36% occurred after revision THA, and 66% of all fractures were in females. Vancouver B2 fractures were the most common type (39%). We found the odds of sustaining a PPFFx is significantly lower after a primary THA compared to revision THA (odds ratio 0.31, 95% confidence interval 0.24–0.40, P < 0.00001). The incidence of PPFFx is 2.96 per 1000 person‐years following primary THA compared to 9.08 per 1000 person‐years following revision THA (odds ratio 0.33, 95% confidence interval 0.27–0.40). The time to fracture was 6.03 years following primary THA and 4.08 years following revision THA. Gender and cementation did not significantly affect the odds of fracture.

Conclusion

The odds of sustaining a PPFFx following revision THA is three times greater compared to primary THA. Other risk factors including gender and cementation did not affect the odds of fracture.
Is there life after degeneration? The organizational life cycle of cooperatives under a ‘grow‐or‐die’ dichotomy
Authors: Bretos Ignacio , Errasti Anjel , Marcuello Carmen
Published: October 2019

This article provides an in‐depth, longitudinal analysis combining real‐time and retrospective data on a set of Mondragon's industrial cooperatives that are organized as international groups. We examine the life cycle of these international cooperative groups, which is expected to evolve differently to that of small‐ and medium‐sized cooperatives that operate exclusively on a local scale. The article is theoretically informed by the cooperative life cycle theory, as well as by recent insights from the degeneration and regeneration theses. Our analysis yields an intricate picture of the evolution of cooperatives faced with a ‘grow‐or‐die’ dichotomy. On the one hand, our findings reject the highly simplistic and deterministic view of the degeneration thesis by demonstrating that these cooperatives can mobilize resources to revitalize cooperative values and practices. On the other, we find that regeneration may not occur in a consistent, sequential fashion as the previous literature suggests, but rather degenerative and regenerative tendencies can occur simultaneously, even leading to long‐lasting, unresolvable situations. In light of this, the article asks future research to draw on power‐aware and politically informed approaches for further understanding of how cooperatives manage the tensions at each organizational stage of their life cycle, and of which organizational actors benefit, and how, from reversing some degenerative tendencies while maintaining others intact.
Safety of first year vaccination in children born to mothers with inflammatory bowel disease and exposed in utero to anti‐TNFα agents: a French nationwide population‐based cohort
Authors: Luu Maxime , Benzenine Eric , Barkun Alan , Doret Muriel , Michiels Christophe , Degand Thibault , Quantin Catherine , Bardou Marc
Published: October 2019

Background

Children born to mothers with IBD may be exposed to anti‐TNFα agents antenatally. Current European guidelines recommend postponing live vaccines until after 6 months of life in this population. Data on the safety of live vaccines administration in the first year of life of these children are sparse with one reported fatality following bacillus Calmette‐Guerin (BCG) administration.

Aims

To describe the use and safety of vaccines administered in children born to mothers with IBD and exposed antenatally to anti‐TNFα agents

Methods

Data from children born to mothers with IBD between 2013 and 2014 were collected retrospectively from the French Health Insurance Database. Vaccines recommended before or at 1 year of age were considered.

Results

Among 4741 children, 670 (14.1%) were exposed to anti‐TNFα agents antenatally, with concomitant thiopurines in 16.0% (n = 107) and steroids in 19.3% (n = 214). Among these 670 children, 315 (47%) were exposed up to delivery. Exposed children were less likely than non‐exposed to receive BCG (88/670, 13.1% vs 780/4071, 19.2% respectively, P < .05) and received it later in life (months, mean ± SD, 4.3 ± 3.9 and 2.4 ± 2.9 respectively, P < .001). In exposed children, 64/88 (73%) received BCG vaccination before 6 months of age, but with no BCG‐related severe adverse event observed during the first year. Uptake of other vaccines recommended before 6 months was above 85% in both groups.

Conclusion

In children exposed antenatally to anti‐TNFα agents, vaccinations are often not postponed in keeping with the recommendations, but no BCG‐related severe adverse events were reported in children vaccinated before 6 months of life.
Adverse events related to low dose corticosteroids in autoimmune hepatitis
Authors: van den Brand Floris F. , van der Veen Koen S. , Lissenberg‐Witte Birgit I. , de Boer Ynto S. , van Hoek Bart , Drenth Joost P. H. , Verdonk Robert C. , Vrolijk Jan M. , van Nieuwkerk Carin M. J. , Bouma Gerd ,   the Dutch Autoimmune Hepatitis Study Group
Published: October 2019

Background

Autoimmune hepatitis requires long‐term therapy, and systemic corticosteroids are the backbone of therapeutic management. Prolonged use of corticosteroids may lead to adverse events but data from long‐term studies are mainly derived from studies in rheumatic diseases.

Aim

To assess cataract, diabetes and fractures in relation to corticosteroid doses in the long‐term maintenance treatment of patients with autoimmune hepatitis.

Methods

We retrospectively collected data on 476 patients (77% women) with an established diagnosis of autoimmune hepatitis. Binary logistic regression with a generalised estimating equation was used to analyse the association between current corticosteroid use and the incidence of cataract, diabetes and fractures with onset after autoimmune hepatitis diagnosis. We corrected for sex, age, cirrhosis at diagnosis and predniso(lo)ne use in the prior 3 years to account for possible ongoing effects.

Results

A total of 6634 years, with a median of 13 (range 1‐40) per patient were recorded. The median age at diagnosis was 44 years (range 2‐88). Adverse events were documented in 120 (25%) patients. Low‐dose predniso(lo)ne (0.1‐5.0 mg/d) increased the odds of fractures whereas higher doses (>5.0 mg/d) increased the odds of cataracts and diabetes. Budesonide increased the odds of cataract and fractures; this effect was independent of predniso(lo)ne use in the prior 1, 2 or 3 years.

Conclusions

Even low doses of corticosteroids frequently lead to substantial adverse events refuting the assumption that adverse events are prevented by administering low doses.
Cariprazine in the treatment of Bipolar Disorder: A systematic review and meta‐analysis
Authors: Pinto Jairo Vinícius , Saraf Gayatri , Vigo Daniel , Keramatian Kamyar , Chakrabarty Trisha , Yatham Lakshmi N.
Published: October 2019

Objectives

Cariprazine is a partial agonist at D2/D3 receptors that has been approved for the treatment of mania associated with bipolar disorder (BD). This meta‐analysis aimed to assess the efficacy and tolerability of cariprazine in the treatment of BD.

Methods

Randomized controlled trials investigating the efficacy of cariprazine in BD were included. Of the 391 studies yielded by search, 7 were included. The PRISMA protocol was followed and a set of analyses involving random‐effects model with restricted maximum‐likelihood estimator were used to synthesize effect sizes.

Results

Cariprazine was associated with a moderate and significant reduction of manic symptoms based on YMRS change scores (SMD: −0.52; 95%CI: −0.82 to −0.21; P = .018). Cariprazine resulted in significantly higher remission (OR: 2.05; 95%CI: 1.61‐2.61; P = .006) and response rates (OR: 2.31; 95%CI: 1.35‐3.95; P = .021) for manic and mixed episodes compared with placebo. Both cariprazine 1.5 mg and 3 mg doses were associated with small but significant reduction in depressive symptoms assessed with MADRS scores (SMD: −0.26, 95%CI: −0.49 to −0.02; P = .040) (SMD: −0.21, 95%CI: −0.41 to −0.01; P = .045), respectively. Cariprazine was significantly associated with the development of adverse effects but not with dropouts due to these adverse effects, when compared to placebo.

Conclusion

Cariprazine appears to be safe and efficacious in the treatment of acute mania and mixed episodes associated with BD. Cariprazine at doses of 1.5‐3 mg/day is efficacious in acute bipolar depression but the effect sizes were smaller. Controlled studies evaluating its efficacy for prophylaxis are needed.
Progress bias versus status quo bias in the ethics of emerging science and technology
Authors: Hofmann Bjørn
Published: October 2019

How should we handle ethical issues related to emerging science and technology in a rational way? This is a crucial issue in our time. On the one hand, there is great optimism with respect to technology. On the other, there is pessimism. As both perspectives are based on scarce evidence, they may appear speculative and irrational. Against the pessimistic perspective to emerging technology, it has been forcefully argued that there is a status quo bias (SQB) fuelling irrational attitudes to emergent science and technology and greatly hampering useful development and implementation. Therefore, this article starts by analysing the SQB using human enhancement as a case study. It reveals that SQB may not be as prominent in restricting the implementation of emergent technologies as claimed in the ethics literature, because SQB (a) is fuelled by other and weaker drivers than those addressed in the literature, (b) is at best one amongst many drivers of attitudes towards emergent science and technology, and (c) may not be a particularly prominent driver of irrational decision‐making. While recognizing that SQB can be one driver behind pessimism, this article investigates other and counteracting forces that may be as strong as SQB. Progress bias is suggested as a generic term for the various drivers of unwarranted science and technology optimism. Based on this analysis, a test for avoiding or reducing this progress bias is proposed. Accordingly, we should recognize and avoid a broad range of biases in the assessment of emerging and existing science and technology in order to promote an open and transparent deliberation.
Visualizing Dynamics of Urban Regions Through a Geo‐Semantic Graph‐Based Method
Authors: Wang Yunzhe , Baciu George , Li Chenhui
Published: October 2019

In urban analysis, it is desirable to find regions where a primary socio‐economic activity dominates as a key endeavour. This can be accomplished by aggregating neighbouring locations where similar activities take place. However, people move and their activities change over time. Furthermore, the boundaries of regions are not stationary. Thus, it is challenging to update region divisions and track their evolution. Geo‐textual data embody geographical information and activity descriptions. We obtain changes in regional boundaries by iteratively applying a community detection process to a sequence of latent graphs that are constructed from geo‐textual data. Region characteristics are interpreted by topics learned by the latent Dirichlet allocation model. We also propose a matching algorithm to expose region transformations between different timestamps. Interesting patterns of evolution emerge after clustering the migration trajectories of region centroids. In our visual system, users can explore the evolution of regions through animations and linked snapshots. To facilitate visual comparisons, we represent regions by hexagonal tiling that better construct arbitrary regional shapes. The effectiveness of our method is evaluated on two case studies using real‐world datasets, and a user study shows that our visual analytics system is highly effective in performing studies on such regional maps.
Bedside approach in the diagnosis obstructive sleep apnea using postprandial oximetry testing: A comparative study with polysomnography
Authors: Sarıçam Ersin , Yalcinkaya Esin , Basay Nihal
Published: October 2019

Introduction

Due to the availability and cost issues in developing countries of polysomnography (PSG), there is a need for outpatient test for an initial assessment of the patients with suspected obstructive sleep apnea (OSA).

Objectives

Epworth sleepiness scale (ESS) is a widely used and best‐validated scale for assessing daytime sleepiness, including dozing when sitting quietly after a lunch (no alcohol). This study introduces a novel screen test called postprandial oximetry test (POT) used during daytime.

Methods

This single‐center prospective study included 101 patients (80 patients with suspected OSA and 21 patients without OSA suspicion). Berlin Questionnaire was used to determine the score/pretest probability of OSA patients, all chosen randomly. First, all the patients underwent POT in laboratory. Then we performed PSG. After lunch, while sleeping, the patients were monitored for 1 hour with pulse oximetry and standard electroencephalographic system. The oximetry saturation classification events with SpO2 was divided into two groups as normal or mild obstructive sleep apnea syndrome (OSAS), and moderate‐to‐severe OSAS. Below 90% SpO2 drops in a postprandial oximetry recordings were accepted as moderate‐to‐severe.

Results

The mean lowest oxygen saturation in PSG was 82.34 ± 5.99, while it in POT were 87.42 ± 1.39. A positive correlation was found between POT‐ and PSG‐derived Apnoea–Hypopnoea Index (AHIs). The sensitivity and specificity in postprandial oximetry were 85% and 85.7%, respectively. The accuracy was 0.903 for POT.

Conclusion

POT may be useful as an outpatient test in the initial assessment of the patients with suspected OSA, serving as a gatekeeper for PSG.
Costarting sitagliptin with metformin is associated with a lower likelihood of disease progression in newly treated people with type 2 diabetes: a cohort study
Authors: Campbell S. A. , Light P. E. , Simpson S. H.
Published: October 2019

Aim

To examine whether early addition of sitagliptin to metformin is associated with a delay in type 2 diabetes progression.

Methods

Administrative health records from Alberta, Canada, for the period April 2008 to March 2015, were used to conduct a retrospective cohort study in new metformin users. People who started sitagliptin on the same day they initiated metformin therapy were compared with those who added sitagliptin later. Insulin initiation served as a surrogate marker for diabetes progression, and multivariable logistic regression models were used to evaluate the association with sitagliptin addition (costart vs later use). A mixed‐effects linear regression model was used to examine the effect of timing of sitagliptin addition on HbA1c change over 1 year.

Results

The mean (sd) age of the 8764 people who used sitagliptin was 52.1 (11.1) years, 5665 (64.6%) were men, and 1153 (13.2%) started sitagliptin on the same day as metformin. Insulin was added to the therapy of 173 (15.0%) costarters and 1453 (19.1%) later sitagliptin users. The adjusted odds ratio for adding insulin was 0.76 (95% CI 0.64 to 0.90) in favour of costarting sitagliptin. HbA1c levels decreased in both groups 1 year after starting sitagliptin, with costarters having a significantly greater reduction [absolute between‐group difference of 0.5% (95% CI 0.3 to 0.7)] compared with later sitagliptin users.

Conclusion

Costarting drug therapy with sitagliptin and metformin was associated with a lower likelihood of disease progression in people with type 2 diabetes compared with adding sitagliptin later.
A novel exploration of the support needs of people initiating insulin pump therapy using a social network approach: a longitudinal mixed‐methods study
Authors: Reidy C. , Foster C. , Rogers A.
Published: October 2019

Aims

To establish what practical and emotional means of support are required on initiation of insulin pump therapy and how needs change over time, using GENIE, a social network intervention.

Methods

The study's longitudinal design used semi‐structured interviews, surveys (PAID, CLARKE) and HbA1c values at time of pump initiation, and at 3 and 6 months. Interviews used GENIE to capture participants’ expectations and experiences of pump therapy and associated support and resources. Thematic analysis was used with sequential, time‐ordered matrices.

Results

A total of 16 adults undertook 47 interviews. A total of 94 services, resources and activities were acquired, while tally, frequency and value of network members increased over time. The novelty of pump therapy impacted on participants’ self‐management needs. Key themes included: 1) the independent nature of managing diabetes; 2) overcoming the challenges and illness burden associated with pump use; 3) the need for responsive and tailored emotional and practical support; and 4) useful resources when incorporating pump therapy. GENIE was thought to be novel and beneficial.

Conclusions

A social network approach determined what resources and support people with diabetes require when incorporating a new health technology. Visualisation of support networks using concentric circles enabled people to consider and mobilise support and engage in new activities as their needs changed. The novelty of pump therapy creates new illness‐related work, but mobilisation of personally valued flexible, tailored support can improve the process of adaptation.
Species range shifts along multistressor mosaics in estuarine environments under future climate
Authors: Lauchlan Shannon S. , Nagelkerken Ivan
Published: October 2019

Range shifts are a key mechanism that species employ in response to climate change. Increasing global temperatures are driving species redistributions to cooler areas along three main spatial axes: increasing latitudes, altitudes and water depths. Climate‐mediated range shift theory focuses on temperature as the primary ecological driver, but global change alters other environmental factors as well, and these rarely work in isolation. Ecosystems are often characterized as mosaics of overlapping environmental stressors, resulting in temporal and spatial heterogeneity which differs between stable, low complexity mosaics (e.g. open ocean) and highly variable, highly complex mosaic environments (e.g. estuaries). We propose a multistressor mosaic of climate‐mediated species range shift across abiotic environmental gradients, typical for mobile species (e.g. fish) in variable coastal environments. We conceptualize how climate‐driven changes in salinity, temperature, dissolved oxygen and pH can drive redistribution of estuarine species in a future world. Non‐thermal drivers are a critical component of species range shifts and when not considered, underestimate the impact of global change on species populations and ecosystem services.
A guide to sample delivery systems for serial crystallography
Authors: Zhao Feng‐Zhu , Zhang Bin , Yan Er‐Kai , Sun Bo , Wang Zhi‐Jun , He Jian‐Hua , Yin Da‐Chuan
Published: October 2019

Crystallography has made a notable contribution to our knowledge of structural biology. For traditional crystallography experiments, the growth of crystals with large size and high quality is crucial, and it remains one of the bottlenecks. In recent years, the successful application of serial femtosecond crystallography (SFX) provides a new choice when only numerous microcrystals can be obtained. The intense pulsed radiation of X‐ray free‐electron lasers (XFELs) enables the data collection of small‐sized crystals, making the size of crystals no longer a limiting factor. The ultrafast pulses of XFELs can achieve ‘diffraction before destruction’, which effectively avoids radiation damage and realizes diffraction near physiological temperatures. More recently, the SFX has been expanded to serial crystallography (SX) that can additionally employ synchrotron radiation as the light source. In addition to the traditional ones, these techniques provide complementary opportunities for structural determination. The development of SX experiments strongly relies on the advancement of hardware including the sample delivery system, the X‐ray source, and the X‐ray detector. Here, in this review, we categorize the existing sample delivery systems, summarize their progress, and propose their future prospectives.
Multi‐scale integration of tree recruitment and range dynamics in a changing climate
Authors: Copenhaver‐Parry Paige E. , Carroll Charles J. W. , Martin Patrick H. , Talluto Matthew V.
Published: October 2019

Aim

The rate and magnitude of climate‐induced tree range shifts may be influenced by range‐wide variation in recruitment, which acts as a bottleneck in tree range dynamics. Here, we compare range predictions made using standard species distribution models (SDMs) and an integrated metamodelling approach that assimilates data on adult occurrence, seedling recruitment dynamics, and seedling survival under both current and future climate, and evaluate the degree to which information provided by seedling data can improve predictions of range dynamics.

Location

The interior west region of the United States.

Time period

1990–2015.

Major taxa studied

Five widespread conifer tree species.

Methods

We used a previously published metamodelling framework to combine information from SDMs of adult tree occurrence and sub‐models describing seedling recruitment dynamics and seedling survival into a single set of predictions for the probability of occurrence for each species. The integrated framework links sub‐models to a SDM to generate cohesive predictions that consider information and uncertainty contained in all datasets. We then compared predictions from the integrated model to SDM predictions.

Results

Integration of seedling information served primarily to improve characterization of model uncertainty, particularly in regions where recruitment may be limited by temperatures that exceed seedling tolerance. Integration constrained response curves very slightly across most climate gradients, particularly across temperature gradients. These differences were primarily attributable to the isolated effects of temperature on seedling survival and not to recruitment dynamics.

Main conclusions

Our results indicate that range‐wide variation in recruitment both now and in the future is most uncertain along the edges of occupied regions, which increases uncertainty in projections of future species occurrence along range margins. Overall, the broad‐scale climatic dependence of the regeneration niche appears weaker than that of the adult climatic niche, and this enhances uncertainty in predicting range‐wide responses of these species to climate change.
Is Helicobacter pylori associated with Behçet's syndrome? A meta‐analysis
Authors: Yu Ye , Yao Xin , Liang Junyu , Lu Chao , Yan Tianlian , Lin Jin
Published: October 2019

Background

Preceding studies have reported the relationship between Helicobacter pylori (H pylori) and Behçet's syndrome (BS), but there still exists controversy. In this study, we firstly conducted a meta‐analysis to clarify the relationship of these two diseases.

Methods

Articles published until July 1, 2019, in the PubMed, MEDLINE, and Embase databases with restriction of English‐language studies were searched and reviewed. According to the inclusion criteria, relevant statistical data were extracted and analyzed.

Results

Six articles were finally included. The result showed that BS individuals were 1.39 times more susceptible to H pylori infection (OR = 1.39, 95% CI = (1.03, 1.87)). In addition, it found that oral ulceration (OR = 27.98, 95% CI = (3.49, 224.49)), genital ulceration (OR = 3.15, 95% CI = (1.51, 6.56)), and cutaneous lesions (OR = 4.29, 95% CI = (2.14, 8.61)) were alleviated after H pylori eradication. Publication bias and sensitivity analysis showed no statistical heterogeneity.

Conclusions

BS patients had higher rate of H pylori infection, and clinical symptoms including oral ulceration, genital ulceration, and cutaneous lesions can be improved after H pylori eradication. The results indicated that H pylori may be an etiological factor to BS.