bluuebunny/crossref_metadata_2025 huggingface dataset:
Start-ups in entrepreneurial ecosystems: the role of relational capacity
Authors: Gueguen Gaël , Delanoë-Gueguen Servane , Lechner Christian
Published: December 2021

Purpose

Entrepreneurial ecosystems provide the context for start-ups to access resources. The authors investigate the reliance of start-ups on their entrepreneurial ecosystem and the driving factors behind the proportion of local actors (belonging to their entrepreneurial ecosystem) within their overall set of relationships (their business ecosystem). Recognizing the limited relational capacity of firms, the authors focus on three differentiating firm characteristics: size, age and innovation of firms.

Design/methodology/approach

The authors developed a sample of 163 start-ups located in the entrepreneurial ecosystem of Toulouse, France. The authors investigated the characteristics of their relationship sets using regression analysis.

Findings

The results confirm that age is inversely related to the proportion of a start-up's relationships located in its entrepreneurial ecosystem. More surprisingly, for older start-ups, the authors also highlight the presence of a moderating effect of the start-up's size on the relationship between its degree of innovation and the proportion of its relationships in its entrepreneurial ecosystem: Larger and more innovative start-ups appear to rely more on their local entrepreneurial ecosystem.

Originality/value

This research increases the understanding of the characteristics driving the interactions of start-ups with their entrepreneurial ecosystems by adopting a relational capacity approach. The authors introduce digital methods as an innovative approach for uncovering firms' ecosystems. Finally, from a practical point of view, the research should provide public authorities seeking to promote the link between local resources and the development of innovative start-ups in their regions with interesting insights.
Linking workplace spirituality and adaptive performance through a serial mediation of job satisfaction and emotional labor strategies
Authors: Rana Sahar , Ahmed Ishfaq , Shahzadi Gulnaz
Published: December 2021

Purpose

Despite growing interest in workplace spirituality (WPS) and its impact on employee behaviors, there is a dearth of literature discussing an underlying mechanism of how it affects adaptive performance. Against this backdrop, this study aims to develop and test a comprehensive model that examined the effects of WPS on adaptive performance through serial mediation of job satisfaction and emotional labor strategies.

Design/methodology/approach

Using a multi-stage sampling technique, the data is collected from 390 faculty members of the higher education institutions in two-time lags.

Findings

The findings indicate that spirituality practices at the workplace help to increase the adaptive performance of employees through serial mediation of job satisfaction and emotional labor strategies.

Research limitations/implications

This study offers important implications to researchers as well as practitioners and highlights the significance of WPS in increasing the adaptive performance of employees.

Originality/value

This research is among the initial attempts to assess the impact of WPS on adaptive performance through serial mediation.
Sendai virus C protein affects macrophage function, which plays a critical role in modulating disease severity during Sendai virus infection in mice
Authors: Sakuma Ryusuke , Morita Naoko , Tanaka Yukie , Koide Naoki , Komatsu Takayuki
Published: December 2021

Sendai virus (SeV) accessory protein C limits the generation of double‐stranded RNAs, defective interfering RNAs, or both, during viral transcription and replication, thereby limiting interferon‐β production. Our recent in vitro analyses on murine macrophage cell lines demonstrated that this protein also contributes to restricting macrophage function, including the production of nitric oxide (NO) and inflammatory cytokines in addition to interferon‐β, in infected macrophages. This study showed that depletion of airway macrophages by clodronate‐loaded liposomes led to the development of severe viral pneumonia in recombinant C gene‐knockout SeV (SeV∆C)‐infected mice, but did not modulate disease severity in wild‐type SeV‐infected mice. Furthermore, the severe disease observed in macrophage‐depleted, SeV∆C‐infected mice was associated with exacerbated virus replication in the lungs, leading to severe airway inflammation and pulmonary edema, indicating lung injury. These results suggested that the antimacrophage activity of SeV C protein might play a critical role in modulating lung injury and associated diseases caused by SeV.
Stable isotopes unravel the feeding mode–trophic position relationship in trematode parasites
Authors: Sabadel Amandine J. M. , MacLeod Colin D.
Published: December 2021

Stable isotopes have been sporadically used over the last two decades to characterise host–parasite trophic relationships. The main reason for this scarcity is the lack of an obvious pattern in the ratio of nitrogen stable isotope values (δ15N) of parasites in comparison to their host tissues, which would be key to understand any host–parasite system dynamics.

To circumvent this, we focused on a single snail host,Zeacumantus subcarinatus, and three of its trematode parasites.

We used stable isotopes to investigate each host‐trematode trophic relationship and shed light on the mechanisms utilised by the parasite to reroute its hosts' biomass.

All our trematodes were found to be15N‐enriched compared to their host, with theirδ15N values strongly related to their feeding behaviours: passive versus active. It was possible to ‘rank’ these parasite species and assess their ‘relative’ trophic position usingδ15N values. We also demonstrated that including a broader range of samples (e.g. host food and faeces, multiple parasite life stages) helped understand the metabolic mechanisms used by the various participants, and that using carbon stable isotope values and C:N ratios allowed to identify an important lipid requirement of these trematode parasites. Finally, we show how critical it is to not ignore parasitic infections as they can have a great influence on their host's trophic position.

We have shown that by focussing on a single host species and a single taxonomic group of parasites, we can remove a certain amount of variation recorded by broader isotope studies. We hope that these data will ultimately improve our ability to place parasites in food webs, and thus improve our understanding of the connections and interactions that dictate food web dynamics.
Using habitat suitability and landscape connectivity in the spatial prioritization of public outreach and management during carnivore recolonization
Authors: Boudreau Melanie R. , Gantchoff Mariela G. , Ramirez‐Reyes Carlos , Conlee Laura , Belant Jerrold L. , Iglay Raymond B.
Published: December 2021

Despite continued global declines in large carnivore abundance and distribution, some species are recovering. In North America, these recoveries can occur in large areas of suitable habitat in or near areas of human development, increasing the likelihood of human–carnivore conflicts. Understanding the intersection among habitat suitability, connectivity and human–carnivore conflicts can aid in conflict prevention and mitigation.

We used GPS collar data from 97 bears and conflict reports collected from 1991 to 2020 to examine black bear Ursus americanus habitat suitability and landscape connectivity in relation to community‐level human–bear conflict occurrences and conflict rates in Missouri, USA. We used conflict–landscape relationships to predict potential community‐level human–bear conflicts given black bear recolonization.

Suitable habitat for black bears comprised about 29% of Missouri and was predominantly forest and shrub cover with low habitat fragmentation and human density, and greater spring vegetation productivity. Landscape connectivity was greatest in south‐central Missouri with limited connectivity in northern and eastern portions of the state.

Conflict rates were low (61 of 94 communities had 1–2 reported conflicts over 30 years), increased 6.5‐fold from 2000 to 2020, and 75% involved black bear use of anthropogenic food. The presence and rate of conflicts increased with greater amounts of suitable habitat, landscape connectivity and community size, with conflict rate also positively associated with patch density and aggregation and negatively associated with patch area. Of 1,010 communities in Missouri, we identified 99 communities with increased risk of human–bear conflicts based on surrounding landscape characteristics.

Synthesis and applications. Our framework integrating landscape attributes and conflict reports can successfully identify communities at greater potential of human–carnivore conflict. In our Missouri case study, we identified 99 out of 1,010 communities which have increased risk of human–bear conflicts, knowledge which will increase the efficiency of education and mitigation rollouts as black bears re‐establish. This framework allows managers to identify communities at greater risk of conflict for many conflict‐prone species and helps prioritize communities for education and conflict mitigation actions, facilitating long‐term coexistence.
Potential Output in a Commodity‐Exporting Economy*
Authors: Yamout Nadine
Published: December 2021

The surge in global demand for natural resources has driven the terms of trade in commodity‐exporting economies to historically high levels. A critical question is how the upswing in commodity prices influences these economies' potential output. I estimate the potential output and output gap that are consistent with a small open economy model featuring a commodities sector and study the implications of permanent commodity price changes on potential output and output gap. Following a 70 per cent permanent commodity price increase, the output gap improves on impact but deteriorates afterwards, falling to −0.75 per cent in the transition.
Choosing Wisely: An idea worth sustaining
Authors: Kastner Monika , Makarski Julie , Mossman Kathryn , Harris Kegan , Hayden Leigh , Giraldo Manuel , Sharma Deepak , Asalya Marwan , Jussaume Linda , Eisen David , Wintemute Kimberly , Rolko Edith , Shin Phil , Zadravec Jennifer , McRitchie Donna
Published: December 2021

Objectives

To evaluate the sustainability potential of Choosing Wisely (CW) to address unnecessary medical care at Ontario community hospitals.

Data Sources/Study Setting

Ontario community hospitals and their affiliated family health teams (FHTs).

Study Design

A mixed‐methods study involving the administration of a validated sustainability survey to CW implementation teams followed by their participation in focus groups.

Data Collection/Extraction Methods

Survey data were collected using an Excel file with an embedded, automated scoring system. We collated individual survey scores and generated aggregate team scores. We also performed descriptive statistics for quantitative data (frequencies, means). Qualitative data were triangulated with quantitative assessments to support data interpretations using the meta‐matrix method.

Principal Findings

Fifteen CW implementation teams across four Ontario community hospitals and six affiliated primary care FHTs participated. CW priority areas investigated were de‐prescribing of proton pump inhibitors (PPIs) and reducing Pre‐Op testing and BUN/Urea lab testing. Survey results showed steady improvements in sustainability scores from baseline to final follow‐up among most implementation teams: 10% increase for PPI de‐prescribing (six FHTs) and 2% increase (three hospital teams); 18% increase in BUN/Urea lab testing (three hospital teams). Regardless of site or CW priority area, common facilitators were fit with existing processes and workflows, leadership support, and optimized team communication; common challenges were lack of awareness and buy‐in, leadership engagement or a champion, and lack of fit with existing workflow and culture. All teams identified at least one challenge for which they co‐designed and implemented a plan to maximize the sustainability potential of their CW initiative.

Conclusions

Evaluating the sustainability potential of an innovation such as Choosing Wisely is critical to ensuring that they have the best potential for impact. Our work highlights that implementation teams can be empowered to influence implementation efforts and to realize positive outcomes for their health care services and patients.
Rhenium‐Osmium Isotope Constraints on the Origin of the Tianyu Cu‐Ni Deposit in the East Tianshan Orogenic Belt, Xinjiang, NW China
Authors: HAN Chunming , XIAO Wenjiao , AO Songjian , ZHANG Jien , SONG Dongfang , ZHANG Zhiyong , SONG Shuaihua , XIE Mingcai
Published: December 2021

The Tianyu Cu‐Ni sulfide deposit occurs in the north margin of the Central Tianshan Arc in East Tianshan orogenic belt, Xinjiang, NW China. The intrusions consist of gabbro, peridotite, and olivine pyroxenite. The peridotite and pyroxenite are the main host rock for the Cu‐Ni ores. Rhenium and osmium isotopic analyses of Ni‐ and Cu‐bearing sulfide minerals from the deposit have been used to determine the source of osmium, and by inference, the sources of ore metals. Sulfide ore samples have Os and Re concentrations varying in the ranges 1.85 to 4.58 ppb and 93.56 to 146.00 ppb, respectively. An initial 187Os/188Os ratio ranges from 0.86 to 1.23 for the ores and the γOs values from 592 to 2227. Osmium isotopic data suggest that the Tianyu intrusion and associated Cu‐Ni mineralization has derived from crustal‐contaminated mantle melts. The intrusions early show island‐arc geochemical signatures, which indicate that the Hulu mafic–ultramafic intrusions, along with the Cu‐Ni deposit, formed as a result of subduction of oceanic crust in the Early Permian.
Alcohol withdrawal symptoms predict corticostriatal dysfunction that is reversed by prazosin treatment in alcohol use disorder
Authors: Sinha Rajita , Fogelman Nia , Wemm Stephanie , Angarita Gustavo , Seo Dongju , Hermes Gretchen
Published: December 2021

Chronic alcohol use increases risk of alcohol withdrawal symptoms (AW) and disrupts stress biology and resilient coping, thereby promoting excessive alcohol intake. Chronic alcohol intake and multiple alcohol detoxifications are known to impair brain medial prefrontal cortex (mPFC) and striatal functioning, regions involved in regulating stress, craving and alcohol intake. In two related studies, we examined whether AW predicts this functional brain pathology and whether Prazosin versus Placebo treatment may reverse these effects. In Study 1, patients with Alcohol Use Disorder (AUD) (N = 45) with varying AW levels at treatment entry were assessed to examine AW effects on corticostriatal responses to stress, alcohol cue and neutral visual images with functional magnetic resonance imaging (fMRI). In Study 2, 23 AUD patients entering a 12‐week randomised controlled trial (RCT) of Prazosin, an alpha1 adrenergic antagonist that decreased withdrawal‐related alcohol intake in laboratory animals, participated in two fMRI sessions at pretreatment and also at week 9–10 of chronic treatment (Placebo: N = 13; Prazosin: N = 10) to assess Prazosin treatment effects on alcohol‐related cortico‐striatal dysfunction. Study 1 results indicated that higher AW predicted greater disruption in brain mPFC and striatal response to stress and alcohol cues (p < 0.001, family‐wise error [FWE] correction) and also subsequently greater heavy drinking days (HDD) in early treatment (p < 0.01). In Study 2, Prazosin versus Placebo treatment reversed mPFC‐striatal dysfunction (p < 0.001, FWE), which in turn predicted fewer drinking days (p < 0.01) during the 12‐week treatment period. These results indicate that AW is a significant predictor of alcohol‐related prefrontal‐striatal dysfunction, and Prazosin treatment reversed these effects that in turn contributed to improved alcohol treatment outcomes.
Health impacts of a scale‐up of supervised injection services in a Canadian setting: an interrupted time series analysis
Authors: Kennedy Mary Clare , Hayashi Kanna , Milloy M‐J , Compton Miranda , Kerr Thomas
Published: December 2021

Background and Aims

In response to a dramatic rise in overdose deaths due to injection drug use, there was a rapid scale‐up of low‐threshold supervised injection services (SIS), termed ‘overdose prevention sites’ (OPS), in Vancouver, Canada in December 2016. We measured the potential impact of this intervention on SIS use and related health outcomes among people who inject drugs (PWID).

Design

Segmented regression analyses of interrupted time series data from two community‐recruited prospective cohorts of PWID from January 2015 to November 2018 were used to measure the impact of the OPS scale‐up on changes in SIS use, public injection, syringe sharing and addiction treatment participation, controlling for pre‐existing secular trends.

Setting

Vancouver, Canada.

Participants

Of 745 PWID, 292 (39.7%) were women, 441 (59.6%) self‐reported white ancestry and the median age was 47 years (interquartile range = 38, 53) at baseline.

Measurements

Immediate (i.e. step level) and gradual (i.e. slope) changes in the monthly proportion of participants who self‐reported past 6‐month SIS use, public injection, syringe sharing and participation in any form of addiction treatment.

Findings

Post OPS expansion, the monthly prevalence of SIS use immediately increased by an estimated 6.4% [95% confidence interval (CI) = 1.7, 11.2] and subsequently further increased by an estimated 0.7% (95% CI = 0.3, 1.1) per month. The monthly prevalence of addiction treatment participation immediately increased by an estimated 4.5% (95% CI = 0.5, 8.5) following the OPS expansion, while public injection and syringe sharing were estimated to immediately decrease by 5.5% (95% CI = 0.9, 10.0) and 2.5% (95% CI = 0.5, 4.6), respectively. Findings were inconclusive as to whether or not an association was present between the intervention and subsequent gradual changes in public injection, syringe sharing and addiction treatment participation.

Conclusions

Scaling‐up overdose prevention sites in Vancouver, Canada in December 2016 was associated with immediate and continued gradual increases in supervised injection service engagement and immediate increases in related health benefits.
Azizi: Gender, Relationality, and the Embodiment of Mawazo in Tanzania
Authors: Meek Laura A.
Published: December 2021

This piece traces the intercorporeal embodiment of an ailment in Tanzania called mawazo, the Swahili term for “ideas” or “thoughts.” As a condition, mawazo is somewhat akin to stress: a cumulative compounding of many problems (shida nyingi) that leads to confused, muddled, and tangled thoughts, as well as physical symptoms like painful, inflamed eyes. Over my three years of ethnographic fieldwork in Iringa, Tanzania, my female collocutors who suffered from mawazo would often trace its origin to familial and marital problems, including their husbands’ infidelity, abuse, alcoholism, or squandering of money. This fictionalized narrative presents the embodied intensities of mawazo and the ways it congeals diffuse pains, hardships, and injustices, past and present. At the same time, I also show how Tanzanian women empower and support one another across generations, natal and affinal relations, friendships, and communities. The story simultaneously attends to the bodily and affective injuries that gender inequality inflicts—as mawazo and in many other registers—and to the ways that women construct lives filled with joy, care, and love.
How do New Zealand‐trained general surgeons secure a SMO job? Are we effectively retaining our trainees?
Authors: Espiner Emma , MacCormick Andrew D. , Weston Maree
Published: December 2021

Background

In the context of increasing shortages in the New Zealand medical specialist workforce, this research seeks to answer the question ‘Are we effectively retaining our New Zealand‐trained general surgeons?’

Methods

Semi‐structured interviews were undertaken with 16 general surgeons. Participants work in New Zealand and internationally. Interviews were transcribed, coded and themed. Thematic analysis was used to interpret the findings.

Results

This research finds that we are failing to effectively retain New Zealand‐trained general surgeons through haphazard workforce planning and a lack of transparent recruitment processes. General surgeons who choose to take their first SMO role overseas are pushed to do so due to a lack of certainty about job opportunities in New Zealand, bullying, and relative ease of negotiation for job composition and conditions at international hospitals. General surgeons who take their first SMO role in New Zealand feel that securing a job is down to luck, existing relationships with influential people in surgical departments and timing.

Conclusion

The failure to retain New Zealand‐trained general surgeons in the New Zealand specialist workforce is amenable to improvements in workforce planning, improved coordination between clinical and administrative leadership in DHBs, and better career development support for trainees prior to receiving their FRACS and embarking on post‐fellowship subspecialist training. Further research into the experiences of trainees and SMOs in general surgery and other surgical subspecialties is required to build a complete picture of the path from trainee to SMO, and areas where interventions could improve retention of New Zealand‐trained general surgeons.
Genetic deletion or pharmacological blockade of nociceptin/orphanin FQ receptors in the ventral tegmental area attenuates nicotine‐motivated behaviour
Authors: Domi Ana , Lunerti Veronica , Petrella Michele , Domi Esi , Borruto Anna Maria , Ubaldi Massimo , Weiss Friedbert , Ciccocioppo Roberto
Published: December 2021

Background and Purpose

The nociceptin/orphanin FQ (N/OFQ)–nociceptin opioid‐like peptide (NOP) receptor system is widely distributed in the brain and pharmacological activation of this system revealed therapeutic potential in animal models of substance use disorder. Studies also showed that genetic deletion or pharmacological blockade of NOP receptors confer resistance to the development of alcohol abuse. Here, we have used a genetic and pharmacological approach to evaluate the therapeutic potential of NOP antagonism in smoking cessation.

Experimental Approach

Constitutive NOP receptor knockout rats (NOP−/−) and their wild‐type counterparts (NOP+/+) were tested over a range of behaviours to characterize their motivation for nicotine. We next explored the effects of systemic administration of the NOP receptor antagonist LY2817412 (1.0 & 3.0 mg·kg−1) on nicotine self‐administration. NOP receptor blockade was further evaluated at the brain circuitry level, by microinjecting LY2817412 (3.0 & 6.0 μg·μl−1) into the ventral tegmental area (VTA), nucleus accumbens (NAc) and central amygdala (CeA).

Key Results

Genetic NOP receptor deletion resulted in decreased nicotine intake, decreased motivation to self‐administer and attenuation of cue‐induced nicotine reinstatement. LY2817412 reduced nicotine intake in NOP+/+ but not in NOP−/− rats, confirming that its effect is mediated by inhibition of NOP transmission. Finally, injection of LY2817412 into the VTA but not into the NAc or CeA decreased nicotine self‐administration.

Conclusions and Implications

These findings indicate that inhibition of NOP transmission attenuates the motivation for nicotine through mechanisms involving the VTA and suggest that NOP receptor antagonism may represent a potential treatment for smoking cessation.
Review: The effectiveness of musical therapy in improving depression and anxiety symptoms among children and adolescents – a systematic review
Authors: Belski Nikita , Abdul‐Rahman Zein , Youn Eunjae , Balasundaram Vibhash , Diep Dion
Published: December 2021

Background

Depression and anxiety disorders are considered to be among the greatest burdens of disease in children and adolescents. Recent literature has reported music therapy to be a safe and potentially effective intervention for the treatment of depression and anxiety. This systematic review examined the effectiveness of music therapy in reducing the symptom severity of depression and/or anxiety among children and adolescents.

Methods

Randomized controlled trials (RCTs) were obtained from a systematic search of nine major English databases from inception to January 2021. Studies were categorized by outcome, music therapy technique and follow‐up period.

Results

Seven RCTs (n = 589) were included. Four RCTs had some concern of bias, while three had high risk of bias. Statistical pooling was not appropriate due to clinical heterogeneity. Four studies (n = 428) favoured music therapy for improvement of depressive symptoms at short‐ and intermediate‐term follow‐ups compared to control. One study (n = 106) favoured music therapy for improvement of anxiety symptoms at short‐term follow‐up compared to control. No studies favoured any control over music therapy for symptom improvement of depression and/or anxiety.

Conclusion

Limited evidence suggests music therapy is an effective treatment for improving depression and/or anxiety symptom severity in children and adolescents. More high‐quality RCTs are needed to address methodological flaws of current studies.
How percentage‐protected targets can support positive biodiversity outcomes
Authors: Carroll Carlos , Noss Reed F.
Published: December 2021

Global targets for the percentage area of land protected, such as 30% by 2030, have gained increasing prominence, but both their scientific basis and likely effectiveness have been questioned. As with emissions‐reduction targets based on desired climate outcomes, percentage‐protected targets combine values and science by estimating the area over which conservation actions are required to help achieve desired biodiversity outcomes. Protected areas are essential for achieving many biodiversity targets, in part because many species are highly sensitive to human‐associated disturbance. However, because the contribution of protected areas to biodiversity outcomes is contingent on their location, management, governance, threats, and what occurs across the broader landscape matrix, global percentage‐protected targets are unavoidably empirical generalizations of ecological patterns and processes across diverse geographies. Percentage‐protected targets are insufficient in isolation but can complement other actions and contribute to biodiversity outcomes within a framework that balances accuracy and pragmatism in a global context characterized by imperfect biodiversity data. Ideally, percentage‐protected targets serve as anchors that strengthen comprehensive national biodiversity strategies by communicating the level of ambition necessary to reverse current trends of biodiversity loss. If such targets are to fulfill this role within the complex societal process by which both values and science impel conservation actions, conservation scientists must clearly communicate the nature of the evidence base supporting percentage‐protected targets and how protected areas can function within a broader landscape managed for sustainable coexistence between people and nature. A new paradigm for protected and conserved areas recognizes that national coordination, incentives, and monitoring should support rather than undermine diverse locally led conservation initiatives. However, the definition of a conserved area must retain a strong focus on biodiversity to remain consistent with the evidence base from which percentage‐protected targets were originally derived.
Building a systems framework to facilitate adaptive organizational change in state fish and wildlife agencies
Authors: Berl Richard E. W. , Manfredo Michael J. , Gasta Mark , Smith Dean , Sullivan Leeann , Jacobson Cynthia A. , Bishop Chad , Camuso Judy , Eason Thomas , Hayes John P. , Jacobson Rick , Melcher Curt , Newmark Jennifer , Novotny Pete , Pauley Sara Parker , Smith Carter , Sparks Catherine , Stoner Kathryn , Strong J.D. , Ver Steeg Jeff
Published: December 2021

State fish and wildlife agencies in the United States are confronted with the realities of a rapidly changing society. With declines in historical sources of revenue and the growth of diverse voices with values that differ from those emphasized by traditional policies and user groups, agencies are faced with diminishing relevancy and are encountering institutional challenges that inhibit their ability to serve the broader public. Here, in collaboration with a group of fish and wildlife agency leaders from 11 states, conservation professionals, and academics, we employ qualitative methods and concepts from systems theory to develop an integrative model of a state wildlife agency. We use this model to identify leverage points to induce transformational change toward an ideal future state: one driven by a system of shared values toward wildlife and a mission to improve quality of life for all people. Our findings point to the importance of developing interventions that will lead to changes in agency culture, systems of governance, and policy and action, and enhance the accessibility of natural resources and opportunities for diverse publics to engage with and benefit from fish and wildlife. We offer recommendations for state wildlife agencies to engage in adaptive organizational change and for university programs to support agency needs.
A phase I, first‐in‐human, randomized dose‐escalation study of anti‐activated factor XII monoclonal antibody garadacimab
Authors: McKenzie Andrew , Roberts Anthony , Malandkar Sourabh , Feuersenger Henrike , Panousis Con , Pawaskar Dipti
Published: December 2021

Factor XII (FXII) is the principal initiator of the plasma contact system and has proinflammatory and prothrombotic activities. This single‐center, first‐in‐human phase I study aimed to assess the safety and tolerability of single escalating doses of garadacimab, a monoclonal antibody that specifically inhibits activated FXII (FXIIa), in healthy male volunteers. Volunteers were randomized to eight cohorts, with intravenous (i.v.) doses of 0.1, 0.3, 1, 3, and 10 mg/kg and subcutaneous (s.c.) doses of 1, 3, and 10 mg/kg. Six volunteers in each cohort received garadacimab or placebo in a ratio of 2:1. Follow‐up for safety lasted 85 days after dosing. Blood samples were collected throughout for pharmacokinetic/pharmacodynamic analysis. Forty‐eight volunteers were enrolled: 32 received garadacimab and 16 received placebo. Most volunteers experienced at least one treatment‐emergent adverse event (TEAE), predominantly grade 1. No serious TEAEs, deaths, or TEAEs leading to discontinuation were reported. No volunteers tested positive for garadacimab antidrug antibodies. Garadacimab plasma concentrations increased in a dose‐dependent manner. Sustained inhibition of FXIIa‐mediated kallikrein activity beyond day 28 resulted from 3 and 10 mg/kg garadacimab (i.v. and s.c.). A dose‐dependent increase in activated partial thromboplastin time with no change in prothrombin time was demonstrated. Garadacimab (single‐dose i.v. and s.c.) was well‐tolerated in healthy volunteers. Dose‐dependent increases in plasma concentration and pharmacodynamic effects in relevant kinin and coagulation pathways were observed. These results support the clinical development of garadacimab, including in phase II studies in hereditary angioedema and coronavirus disease 2019 (COVID‐19).
A case of cutaneous syncytial myoepithelioma with extensive adipocytic metaplasia: Usefulness of EWSR1‐PBX3 gene fusion analysis
Authors: Shimada Kanade , Ansai Osamu , Katsumi Tatsuya , Deguchi Tokiko , Hayashi Ryota , Yuki Akihiko , Nakamura Mai , Umezu Hajime , Fukumoto Takaya , Ansai Shin‐Ichi , Abe Riichiro
Published: December 2021

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized variant of myoepithelioma characterized by an intradermal syncytial proliferation of spindled, ovoid, and histiocytoid cells. Immunohistochemically, tumor cells usually show strong expression of S‐100 protein and epithelial membrane antigen (EMA). Here we report a case of CSM in the thigh of a 51‐year‐old Japanese woman. Histopathological findings showed a sheet‐like growth of ovoid cells and histiocytoid cells with an eosinophilic syncytial cytoplasm, and adipocytic metaplasia was widely observed in the tumor. Immunohistochemical staining revealed a diffuse, strong pattern for EMA, smooth muscle actin (SMA), and HHF35, and variable expression of S‐100 protein and p63 in ovoid and histiocytoid cells without significant mitotic figures or pleomorphism. In addition, EWSR1‐PBX3 gene fusion, which is characteristic of CSM, was observed in the tumor. Based on these findings, we diagnosed the patient as having CSM. Our case shows that CSM can exhibit extensive adipocytic metaplasia, which could make its histopathological diagnosis challenging.
Legislative, delegated acts, comitology and interinstitutional conundrum in EU law – configuring EU normative spaces
Authors: Türk Alexander H.
Published: December 2021

This article seeks to contribute to The Conference on the Future of Europe by arguing that its debates on substantive policies and democratic foundations cannot be detached from consideration being given to the configuration of the Union's normative spaces in which those policies will be developed and implemented. In its current stage of development, we can find in the Union legal system two competing conceptions for the configuration of its different normative spaces, one that relies on the Member States for resources and legitimacy and another that intends to free itself from those constraints. This article will argue that a uniquely European model of governance will benefit from the integration of both conceptions in the configuration of its normative spaces, not only where they are provided for by the Union Treaties but also where they have developed in the shadow of those official spaces, which they complement and increasingly supplant.
The Effects of Health Consciousness on Environmentally Sustainable Textile Furnishing Product Purchase
Authors: Gam Hae Jin , Yu Ui‐Jeen , Yang Somang
Published: December 2021

The environmental and health issues in using textile furnishing products have grown, but previous studies have not investigated health‐related antecedents that influence consumers’ purchase intentions of environmentally sustainable textile furnishing products (ESTFP). This study examined the antecedent role of health consciousness influencing consumers’ attitudes, subjective norms, perceived behavioral control, and purchase intention regarding ESTFP. Analysis of data from an Internet‐based survey of 302 US shoppers indicated that consumers with a higher level of health consciousness were likely to have more favorable attitudes, stronger subjective norms, greater perceived behavioral control, and consequently stronger purchase intentions toward ESTFP. The results support the effect of consumers’ health consciousness on ESTFP and extend the application of the theory of planned behavior to the purchase of textile furnishing products.
Gross primary productivity and water use efficiency are increasing in a high rainfall tropical savanna
Authors: Hutley Lindsay B. , Beringer Jason , Fatichi Simone , Schymanski Stanislaus J. , Northwood Matthew
Published: December 2021

Despite their size and contribution to the global carbon cycle, we have limited understanding of tropical savannas and their current trajectory with climate change and anthropogenic pressures. Here we examined interannual variability and externally forced long‐term changes in carbon and water exchange from a high rainfall savanna site in the seasonal tropics of north Australia. We used an 18‐year flux data time series (2001–2019) to detect trends and drivers of fluxes of carbon and water. Significant positive trends in gross primary productivity (GPP, 15.4 g C m2 year−2), ecosystem respiration (Reco, 8.0 g C m2 year−2), net ecosystem productivity (NEE, 7.4 g C m2 year−2) and ecosystem water use efficiency (WUE, 0.0077 g C kg H2O−1 year−1) were computed. There was a weaker, non‐significant trend in latent energy exchange (LE, 0.34 W m−2 year−1). Rainfall from a nearby site increased statistically over a 45‐year period during the observation period. To examine the dominant drivers of changes in GPP and WUE, we used a random forest approach and a terrestrial biosphere model to conduct an attribution experiment. Radiant energy was the dominant driver of wet season fluxes, whereas soil water content dominated dry season fluxes. The model attribution suggested that [CO2], precipitation and Tair accounting for 90% of the modelled trend in GPP and WUE. Positive trends in fluxes were largest in the dry season implying tree components were a larger contributor than the grassy understorey. Fluxes and environmental drivers were not significant during the wet season, the period when grasses are active. The site is potentially still recovering from a cyclone 45 years ago and regrowth from this event may also be contributing to the observed trends in sequestration, highlighting the need to understand fluxes and their drivers from sub‐diurnal to decadal scales.
Cross‐sector partnerships: Mapping the field and advancing an institutional approach
Authors: Vogel Rick , Göbel Markus , Grewe‐Salfeld Marit , Herbert Barbara , Matsuo Yuka , Weber Christiana
Published: December 2021

Cross‐sector partnerships (CSPs) addressing economic, social, and environmental issues continue to be a vibrant topic in management research and beyond. However, compared to the exogenous factors that drive collaborative advantage through structures and governance, the endogenous problems of collaborating across different institutional logics, residing at the micro‐level of interactions among partners from the business, government, and nonprofit sectors, have received scant attention. The preoccupation with success factors often leads to a bias toward the problem‐solving capacities of CSPs at the neglect of the considerable barriers to successful collaboration across sectors. This study addresses this shortcoming and extracts an institutional approach of CSPs from an integrative review of the literature combining bibliometric methods with qualitative reviewing. A bibliometric map shows how the literature is divided into several clusters, each addressing a specific type of CSP but not engaging much in exchange with other clusters. Zooming in on the clusters provides a more nuanced picture of how institutional theory has hitherto been applied to CSPs. We build on these pieces of the puzzle and assemble them into a preliminary framework that accounts for inter‐institutional conflicts in CSPs and actor‐level responses to these conflicts. Our framework introduces a new analytical platform that facilitates multi‐level research, bringing the micro‐level of individual actors back in and connecting it with institutional frames at the macro‐level.
Trois mécanismes de gouvernance pour remédier aux déficits de travail décent dans les chaînes de valeur mondiales
Authors: ANNER Mark
Published: December 2021

Gereffi et Lee (2016) distinguent six mécanismes de gouvernance susceptibles de remédier aux déficits de travail décent dans les chaînes de valeur mondiales. En s'appuyant sur des travaux relatifs au Viet Nam, au Honduras et au Bangladesh, l'auteur affirme que, pour être véritablement efficace, la gouvernance en question doit permettre de rééquilibrer le rapport de force entre les partenaires en présence. Trois mécanismes remplissent cette condition: la gouvernance publique, les conventions collectives de large portée et les accords multipartites globaux contraignants. L'option la plus adaptée dépend du régime de relations professionnelles et des caractéristiques et stratégies du mouvement ouvrier dans le pays.
Development of structural descriptors to predict dissolution rate of volcanic glasses: Molecular dynamic simulations
Authors: Gong Kai , Olivetti Elsa A.
Published: December 2021

Establishing the composition–structure–property relationships for amorphous materials is critical for many important natural and engineering processes, including the dissolution of highly complex volcanic glasses. In this investigation, we performed force field molecular dynamics (MD) simulations to generate detailed structural representations for 10 natural CaO–MgO–Al2O3–SiO2–TiO2–FeO–Fe2O3–Na2O–K2O glasses with compositions ranging from rhyolitic to basaltic. Based on the resulting atomic structural representations at 300 K, we have calculated the partial radial distribution functions, nearest interatomic distances and coordination number, which are consistent with the literature data on silicate‐based glasses. Based on these structural attributes and classical bond valence models, we have introduced a novel structural descriptor, that is, average metal–oxygen (M–O) bond strength parameter, which has captured the log dissolution rates of the 10 glasses at both acidic and basic conditions (based on literature data) with R2 values of ∼0.80–0.92 based on linear regression. This structural descriptor is seen to outperform several other structural descriptors also derived from MD simulation results, including the average metal oxide dissociation energy, the average self‐diffusion coefficient of all the atoms at 2000 K, and the energy barrier of self‐diffusion. Furthermore, we showed that the MD‐derived descriptors generally exhibit better predictive performance than the degree of depolymerization parameter commonly used to describe glass and mineral reactivity. The results suggest that the structural descriptors derived from MD simulations, especially the average M–O bond strength parameter, are promising structural descriptors for connecting composition with dissolution rates of highly complex natural glasses.
Production and characterization of naturally occurring antibacterial magnetite nanoparticles from magnetotactic Bacillus sp. MTB17
Authors: Rajalakshmi Arumugam , Ramesh Manickam , Divya Ellappan , Kavitha Kuppuswamy , Puvanakrishnan Rengarajulu , Ramesh Balasubramanian
Published: December 2021

Aims

This study envisaged the isolation and characterization of magnetite nanoparticles (MNPs) from magnetotactic bacteria (MTB) and the evaluation of their antibacterial efficacy.

Methods and Results

MNPs were extracted from 20 motile but morphologically different MTB, and they were subjected to antibacterial activity assay. These MNPs were found to be highly effective against Vibrio cholerae. MTB17 was considered as the potent MTB strain based on the antibacterial activity. The MNPs of MTB17 were isolated and validated by UV-Visible spectroscopy, particle size analysis, FTIR analysis, and PXRD.

Conclusions

Isolation and characterization of ~85 nm MNPs from MTB is reported, and it is highly active against all the gram-positive and gram-negative strains tested.

Significance and Impact of the Study

This study focuses on a novel use of biogenic magnetite MNPs as an antibacterial agent, which can be further explored using in vivo studies.
Effects of water activity, ammonia and Corynebacterium urealyticum on the survival of Salmonella Typhimurium in sterile poultry litter
Authors: Gutierrez Alan , Schneider Keith R.
Published: December 2021

Aims

This study examined the effects of water activity (aw), ammonia and Corynebacterium urealyticum on the survival of Salmonella Typhimurium in sterile poultry litter.

Methods and Results

Sterile poultry litter inoculated with S. Typhimurium was adjusted to pH 9.0, various aw levels (0.84, 0.92 and 0.96), and total ammonia nitrogen levels were increased either by the addition of ammonium sulphate or C. urealyticum inoculation with 1% urea added. All litter treatments were incubated at 30°C and sampled daily for five days. Similar results were observed at each aw level in both experiments. At 0.84 and 0.92 aw, S. Typhimurium populations in litter fell below 1 log CFU g−1 within 5 days, with no significant differences between the controls and increased ammonia treatments. At 0.96 aw, Salmonella populations treated with increased ammonia levels were significantly lower than control treatments on days 1–5.

Conclusions

This study showed that C. urealyticum can produce ammonia in litter at higher aw levels with sufficient available urea and that the antimicrobial efficacy of ammonia is dependent on high aw (~0.96) in litter.

Significance and Impact of the Study

These results provide insights into the production of ammonia in litter, its antimicrobial efficacy in litter and the importance of aw in this interaction.
Population genomics indicates micro‐refuges and riverine barriers for a southern South American grassland nightshade
Authors: Giudicelli Giovanna C. , Turchetto Caroline , Guzmán‐Rodriguez Sebastián , Teixeira Marcelo C. , Petzold Earl , Bombarely Aureliano , Freitas Loreta B.
Published: December 2021

Aim

Pleistocene climate oscillations influenced the species distribution and genetic diversity in grasslands, and such climatic changes promoted expansion and contraction cycles, leading to fragmentation and isolation of evolutionary lineages in refuges. This study aimed to infer the evolutionary processes that most influenced the genetic diversity of a South American nightshade Petunia inhabiting subtropical grasslands under the Pleistocene influence.

Location

Pampa and Chaco.

Taxon

The widely distributed herb Petunia axillaris subsp. parodii (Solanaceae).

Methods

We obtained high‐density genome coverage throughout the geographical distribution of Petunia axillaris subsp. parodii. We estimated the genetic diversity and structure to evaluate population differentiation and applied a model‐based demographic analysis to investigate the scenarios that could have influenced the species' evolutionary history. We evaluated the association between neutral and outlier polymorphisms with environmental variables to distinguish the influence of the geographical distance and environmental differences between populations.

Results

There are three evolutionary lineages in P. axillaris subsp. parodii. The origin and differentiation of these lineages were related to the Pleistocene refuges and rivers acting as barriers to gene flow. We also identified 496 outlier loci related to adaptation to environmental conditions.

Main conclusion

The Pleistocene climate changes drove lineage diversification isolated in micro‐refugia. Rivers and changes in their courses may have also acted on the population divergence, serving as barriers to gene flow or even as corridors for species range expansion. These findings contribute to the knowledge of the evolutionary processes that influenced the lineage diversification of South American subtropical grassland species.