bluuebunny/crossref_metadata_2025 huggingface dataset:
Keeping it private: financial reporting by large proprietary companies in Australia
Authors: Potter Brad , Pinnuck Matthew , Tanewski George , Wright Sue
Published: January 2019

Since 2010, proprietary companies have had a choice of preparing three types of financial reports that vary in scope. We find that between 2010 and 2015, most proprietary companies in our random sample chose the lowest scope option, with very low quality financial reports. Few adopted the new option provided by AASB 1053 Application of Tiers of Australian Accounting Standards. The characteristics of the firms that adopted each type of report are consistent with the regulator's intention. Our findings should provide a better understanding of how accounting standards impact practice, and should assist regulators to reform private company financial reporting.
How Government Reactions to Violence Worsen Social Welfare: Evidence from Peru
Authors: Sexton Renard , Wellhausen Rachel L. , Findley Michael G.
Published: January 2019

Dissident violence inflicts many costs on society, but some of the longest‐lasting consequences for civilians may be indirect, due to the government's response. We explore how government policy responses affect social welfare, specifically through budgetary shifts. Using subnational violence and budgeting data for Peru, we demonstrate that attacks on soldiers during the budget negotiation period drive a shift from local social services, especially health, to defense. One soldier fatality implies a 0.13 percentage point reduction in the local health budget share (2008–12). Health budget cuts due to a single soldier fatality result in 76 predicted additional infant deaths 2 years later. We show that the effect on health budgeting operates through decreases in women's use of health facilities and postnatal services. We offer evidence that Peru's coercive response indirectly harms civilians due to butter‐to‐guns budgetary shifts. Our results identify a budgetary mechanism that translates dissident violence into a deterioration in social welfare.
Rural versus urban women: An examination of anthropometry and body composition
Authors: Tan Miriam , Brown Leanne J. , Mathews Kimberly I. , Whatnall Megan C. , Hutchesson Melinda J. , MacDonald‐Wicks Lesley K. , Patterson Amanda J.
Published: January 2019

Objective

To describe and compare body composition and fat distribution of Australian women 18–44 years from an urban and rural location.

Design

Cross‐sectional survey and collection of anthropometric and body composition measurements.

Setting

Newcastle and Tamworth in New South Wales.

Participants

Convenience sample of women recruited through media and community.

Main outcome measures

Weight, height, waist and hip girths, visceral fat area, body fat (kg and %) and skeletal muscle mass.

Results

Of the total sample (n = 254), 53% resided in an urban area and the mean age was 28.0 (7.6) years. The mean age of rural women was significantly higher than for urban women. The majority of women (66.5%) had a Body Mass Index within the healthy range (18.5–24.9 kg m−2) and there was no significant difference in mean Body Mass Index between rural and urban women. Measures of central fat distribution, waist circumference and waist‐to‐hip ratio were significantly higher in rural residents. Visceral fat area was significantly higher among rural women. After adjustment for age, differences in waist circumference, waist‐to‐hip ratio and visceral fat area were no longer statistically significant.

Conclusion

While we did not find statistically significant differences in body composition among urban and rural women, these results highlight the dramatic effect of age on measures of central adiposity. Population surveillance needs to incorporate measures of excess central adiposity, particularly visceral fat area, to better investigate changes in body composition among women in their 20s and 30s.
Siglec‐7 on peripheral blood eosinophils: Surface expression and function
Authors: Legrand Fanny , Landolina Nadine , Zaffran Ilan , Emeh Robert O. , Chen Elizabeth , Klion Amy D. , Levi‐Schaffer Francesca
Published: January 2019

Background

Siglec‐7 is an inhibitory receptor (IR) expressed on human blood eosinophils. Whereas activation of other IRs, including Siglec‐8 and CD300a, has been shown to downregulate eosinophil function, little is known about the role of Siglec‐7 on human eosinophils.

Objective

To examine Siglec‐7 expression and function in eosinophils from normal (ND) and eosinophilic (EO) donors.

Methods

Eosinophil expression of Siglec‐7 was quantified by flow cytometry and quantitative PCR. Soluble Siglec‐7 (sSiglec‐7) levels were measured by ELISA in serum. The effect of Siglec‐7 on eosinophil viability and degranulation was assessed in vitro by AnnexinV‐FITC/7‐AAD staining and by measuring GM‐CSF‐induced mediator release in culture supernatants. Signal transduction was studied by Western blot.

Results

Siglec‐7 was expressed ex vivo on blood eosinophils from all eosinophilic and normal individuals studied. Siglec‐7 surface, but not SIGLEC‐7mRNA expression, was correlated with absolute eosinophil count (AEC). Siglec‐7 was upregulated on purified eosinophils after in vitro stimulation with GM‐CSF or IL‐5. Serum sSiglec‐7 was detectable in 133/144 subjects tested and correlated with AEC. Siglec‐7 cross‐linking inhibited GM‐CSF‐induced release of eosinophil peroxidase, TNF‐α, and IL‐8 (n = 7–8) but did not promote eosinophil apoptosis (n = 5). Finally, Siglec‐7 cross‐linking on GM‐CSF‐activated eosinophils induced phosphorylation of SHP‐1 and de‐phosphorylation of ERK1/2 and p38.

Conclusions

Siglec‐7 is constitutively expressed on human eosinophils and downmodulates eosinophil activation. Targeting of Siglec‐7 on eosinophils might enhance treatment efficacy in eosinophil‐driven disorders. Conversely, therapeutic interventions that inhibit Siglec‐7 could have unanticipated consequences and promote eosinophilic inflammation.
Retinal blood oxygen saturation and aqueous humour biomarkers in early diabetic retinopathy
Authors: Tayyari Faryan , Khuu Lee‐Anne , Sivak Jeremy M. , Flanagan John G. , Singer Shaun , Brent Michael H. , Hudson Christopher
Published: January 2019

Purpose

The aim of this study was to assess the relationship between retinal blood oxygen saturation (SO2) and specific aqueous humour (AH) concentrations of proangiogenic biomarkers in diabetic patients with nonproliferative diabetic retinopathy (NPDR) and to compare them with those of matched control subjects.

Methods

The sample comprised 14 participants with mild‐to‐moderate NPDR (69.1 ± 6.6 years) and 17 age‐matched healthy controls (69.7 ± 6.3 years); all participants were previously scheduled for routine cataract extraction with intraocular lens implantation. Multiplex cytokine analyses of specific biomarkers, including vascular endothelial growth factor A (VEGF‐A), angiopoietin2 (Ang2), epidermal growth factor (EGF), hepatocyte growth factor (HGF) and interleukin‐8 (IL‐8) were performed by BioPlex 200 system. Six non‐invasive hyperspectral retinal images were acquired.

Results

Mean SO2 was significantly higher in both arterioles (94.4 ± 1.9 versus 93.0 ± 1.6) and venules (64.4 ± 5.6 versus 55.9 ± 4.8) of NPDR than in the healthy controls (p < 0.001). AH levels of HGF (p = 0.018), Ang2 (p = 0.005) and IL‐8 (p = 0.034) were significantly higher, and EGF (p = 0.030) was significantly lower in NPDR subjects. The study demonstrated a correlation between venular retinal blood oxygen saturation and proangiogenic factors HGF (r = 0.558, p = 0.038), Ang2 (r = 0.556, p = 0.039) and EGF (r = −0.554, p = 0.040), but did not find any correlation for IL‐8 (r = 0.330, p = 0.249) even though this biomarker was significantly higher in the diabetic group.

Conclusion

To our knowledge, the present study is the first report considering the association between SO2 and AH concentrations of protein biomarkers in diabetic retinopathy. The biomarkers of interest have been shown to participate in cell death, which may explain higher oxygen saturation in NPDR.
Effects of lentivirus‐mediated astrocyte elevated gene‐1 overexpression on proliferation and apoptosis of human retinoblastoma cells
Authors: Bai Haixia , Chang Ying , Li Bin , Mao Ying , Jonas Jost B.
Published: January 2019

Purpose

To investigate the effect of astrocyte elevated gene‐1 (AEG‐1) overexpression on the biological behaviour of human retinoblastoma (RB) cells and its possible mechanism.

Methods

Three human RB cell lines (SO‐RB50, Y79 and WERI‐RB1) were infected with AEG‐1‐GFP recombinant lentiviral vectors to induce AEG‐1 overexpression, while the cells infected with negative lentiviral vectors and cells without any intervention formed control groups.

Results

All three RB cell lines showed an overexpression of AEG‐1 after lentivirus infection (p < 0.001 for all three cell lines). The survival rate of RB cells increased (all p < 0.001) in the AEG‐1 overexpressed groups when compared with the control groups. There was a decrease in G0/G1 cell cycle phase arrest and an accumulation in G2/M cell cycle phase in all three RB cell lines (p < 0.001), with an induction in the S phase in WERI‐RB1 cells. It was paralleled by a downregulation of p21 and p27 proteins and an upregulation of the Cdc2 protein. The apoptosis rate of RB cells declined (p < 0.001) when AEG‐1 was overexpressed, in association with an upregulation of Bcl‐2 protein and a downregulation of Bax protein and cleaved caspase‐3 proteins.

Conclusions

A lentivirus‐mediated AEG‐1 overexpression in RB cells led in vitro to a growth promotion and an apoptosis inhibition of human RB cells, associated with an upregulation of the Bcl‐2 protein, a downregulation of the Bax protein and of cleaved caspase‐3 proteins, and with alterations of the cell cycle. AEG‐1 may be involved in the development and progression of RB.
Ultrasound evaluation of small intestinal thickness and a comparison to body weight in normal chickens (Gallus gallus domesticus)
Authors: Garrett K , Milne M , Doneley R , Perkins N
Published: January 2019

Background

Ultrasound in avian patients is useful for identifying abnormalities within the coelomic cavity. A correlation between sonographic evaluation of jejunal thickness and body weight has been reported in mammals, but not the chicken (Gallus gallus domesticus). The purpose of this study was to prospectively assess the normal values of jejunal thickness in the chicken and compare this to body weight.

Methods

Coelomic ultrasound was performed on 89 clinically normal chickens with no history or signs of gastrointestinal disease. Two populations of hens (commercial layers and backyard purebred and mixed‐breed hens) were used. Breed and ultrasonographically measured jejunal wall thickness were recorded in all hens. Body weight was recorded in 45 of the hens (mixed‐breed and purebred backyard chickens).

Results and conclusion

There was no statistically significant correlation between body weight and ultrasonographically measured jejunal wall thickness. The mean thickness of the jejunal wall in healthy chickens was 2.1 ± 0.08 mm. Further studies comparing jejunal thickness in chickens with and without signs of GI disease would be useful.
Pilot study of Australian veterinarians and their perceptions and experiences related to online pet health information
Authors: Kogan LR , Oxley JA , Hazel SJ
Published: January 2019

Objective

Investigate Australian veterinarians’ perceptions of clients’ use of the internet to find pet health information.

Methods

An anonymous online survey was distributed using social media, e‐newsletters and veterinary magazines.

Results

A total of 85 complete responses were obtained from Australian veterinarians. Most (80%) reported believing that > 80% of their clients have access to the internet at home or work, but 68% thought that the majority of their clients do not understand what they read online. Attitudes regarding the impact of online pet health information on the veterinarian–client relationship were mixed (56% reported negative impact and 33% a positive impact), as well as for clients’ use of the internet for information on companion animal health (47% reported negative impact and 38% a positive impact). When asked how often they suggest specific websites to their clients (‘information prescriptions’), the majority of veterinarians reported that this is done infrequently.

Conclusion

This pilot study highlighted the perception of Australian veterinarians of their clients’ use of the internet to find pet health information. It also highlighted the need for a large‐scale, detailed survey of Australian veterinarians and their views in relation to pet owners and their use of online information. This should include evaluation of information prescriptions and their potential benefits for clients and patients.
Relationship between allograft cyclosporin concentrations and P‐glycoprotein expression in the 1st month following renal transplantation
Authors: Sallustio Benedetta C. , Noll Benjamin D. , Coller Janet K. , Tuke Jonathan , Russ Graeme , Somogyi Andrew A.
Published: January 2019

The immunosuppressant cyclosporin is a P‐glycoprotein (P‐gp) substrate whose impaired function has been associated with an increased risk of cyclosporin‐induced nephrotoxicity following renal transplantation. This study investigated the relationship between blood and allograft cyclosporin concentration, and the effect of P‐gp expression. Fifty biopsy samples were obtained from 39 renal transplant recipients who received cyclosporin as part of maintenance immunosuppression. Blood cyclosporin concentrations (2 hours postdose) were obtained from clinical records, matching allograft cyclosporin concentrations were measured in frozen biopsy tissue by liquid chromatography–tandem mass spectrometry, and allograft P‐gp expression was assessed by immunohistochemistry. Blood and allograft cyclosporin concentrations in the 1st month post‐transplantation ranged from 505–2005 μg/L and 0.01–16.7 ng/mg tissue, respectively. Dose was the only significant predictor of allograft cyclosporin concentrations (adjusted R2 = .24, F‐statistic = 11.52, P = .0019), with no effect of P‐gp expression or blood cyclosporin concentrations. P‐gp expression is not the major determinant of allograft cyclosporin concentrations.
An analysis of digital competence as expressed in design patterns for technology use in teaching
Authors: Rolf Elisabeth , Knutsson Ola , Ramberg Robert
Published: January 2019

Teachers cannot presume that their learners have the competence to use the technology brought to the classroom. Therefore, the learners’ abilities to use technology may be a concern for teachers. This paper reports on digital competence through an analysis of designs for learning in design patterns, written by upper secondary teachers. Learning activities found in the design patterns were analysed with the aim to understand how teachers perceive the learners’ digital competence when using technology. A framework that compromises digital competence was utilised for inferring the digital competencies. The qualitative analysis of these learning activities reveals that competences of information and data literacy, and of communication and collaboration predominate. By analysing the characteristics of learning activities and hence the teachers’ ideas of technology use in teaching, it is concluded that design patterns can be used to identify the competences teachers believe are relevant for the learners to acquire. The result therefore involves aspects of how teachers perceive learners’ digital competence when using technology in teaching.
Advanced care planning 5 years on: An observational study of multi‐centred service development for children with life‐limiting conditions
Authors: Martin Alice E. , Beringer Antonia J.
Published: January 2019

Aim

The purpose of this study was to compare how planning has developed over the 5 years across a range of children's health care services in a single U.K. city.

Background

Advanced planning for end of life care (EOLC) is an essential component of care for children with life‐limiting and life‐threatening (LLLT) conditions. We report the findings of a follow‐up study (R2) completed 5 years after the initial review (R1). Documented advanced care planning (ACP) was measured against published children's palliative care standards.

Method

We used a manual retrospective review of health care records, using focused data collection. Inclusion criteria were children who died before the age of 18 years, as a consequence of an LLLT condition, over an 18‐month period and had lived locally to a regional children's hospital.

Results

The first review (R1) included 48 patients with 114 health care records: median age at death 0 years (range 0 to 18 years). The follow‐up review (R2) included 47 patients, with 80 health care records: median age at death 2 years (range 0 to 17 years). The proportion of records containing evidence of a prognostic discussion had risen from 73% (R1) to 91% (R2), p < 0.005. The proportion of health care records with ACP was consistent between R1 and R2 (75% and 72%, respectively). An ACP tool was found to be in regular use in R2 compared with no examples in R1. The acute hospital trust plans were more detailed in R2 than R1. The proportion of cases where preferred location of death matched actual location was stable, around half.

Conclusions

EOLC conversations increased over the 5 years studied. In the acute hospital trust, there is evidence of a better quality ACP although quantity is stable: enabled by the implementation of an ACP tool and education programme. Challenges remain in engaging children and young people in advanced planning.
An Australian perspective on rewilding
Authors: Sweeney Oisín F. , Turnbull John , Jones Menna , Letnic Mike , Newsome Thomas M. , Sharp Andy
Published: January 2019

Rewilding is increasingly recognized as a conservation tool but is often context specific, which inhibits broad application. Rewilding in Australia seeks to enhance ecosystem function and promote self‐sustaining ecosystems. An absence of large‐bodied native herbivores means trophic rewilding in mainland Australia has focused on the restoration of functions provided by apex predators and small mammals. Because of the pervasive influence of introduced mesopredators, predator‐proof fences, and establishment of populations on predator‐free islands are common rewilding approaches. This sets Australian rewilding apart from most jurisdictions and provides globally relevant insights but presents challenges to restoring function to broader landscapes. Passive rewilding is of limited utility in arid zones. Although increasing habitat extent and quality in mesic coastal areas may work, it will likely be necessary to undertake active management. Because much of Australia's population is in urban areas, rewilding efforts must include urban areas to maximize effectiveness. Thus rewilding is not synonymous with wilderness and can occur over multiple scales. Rewilding efforts must recognize human effects on other species and benefit both nature and humans. Rewilding in Australia requires development of a shared vision and strategy and proof‐of‐concept projects to demonstrate the benefits. The repackaging of existing conservation activities as rewilding may confuse and undermine the success of rewilding programs and should be avoided. As elsewhere, rewilding in Australia should be viewed as an important conservation tool.
Transforming ecology and conservation biology through genome editing
Authors: Phelps Michael P. , Seeb Lisa W. , Seeb James E.
Published: January 2019

As the conservation challenges increase, new approaches are needed to help combat losses in biodiversity and slow or reverse the decline of threatened species. Genome‐editing technology is changing the face of modern biology, facilitating applications that were unimaginable only a decade ago. The technology has the potential to make significant contributions to the fields of evolutionary biology, ecology, and conservation, yet the fear of unintended consequences from designer ecosystems containing engineered organisms has stifled innovation. To overcome this gap in the understanding of what genome editing is and what its capabilities are, more research is needed to translate genome‐editing discoveries into tools for ecological research. Emerging and future genome‐editing technologies include new clustered regularly interspaced short palindromic repeats (CRISPR) targeted sequencing and nucleic acid detection approaches as well as species genetic barcoding and somatic genome‐editing technologies. These genome‐editing tools have the potential to transform the environmental sciences by providing new noninvasive methods for monitoring threatened species or for enhancing critical adaptive traits. A pioneering effort by the conservation community is required to apply these technologies to real‐world conservation problems.
Mirror movements in children with unilateral cerebral palsy due to perinatal stroke: clinical correlates of plasticity reorganization
Authors: Riddell Madison , Kuo Hsing‐Ching , Zewdie Ephrem , Kirton Adam
Published: January 2019

Aim

We aimed to determine if the mirror movements that often result in children with unilateral cerebral palsy (CP) after perinatal stroke represent a clinical biomarker of developmental plasticity.

Method

This was a prospective, controlled cohort study. Mirror movements in children with unilateral CP from a population‐based cohort were compared to those of typically developing controls. The population with stroke was assessed further via electromyography (EMG), motor function, and corticospinal organization investigations. Mirror movements were quantified (0–5) bidirectionally. EMG mirror movements were quantified during voluntary contraction. Motor function was quantified by validated measures including the Assisting Hand Assessment (AHA). Corticospinal organization was categorized as ipsilateral or contralateral using transcranial magnetic stimulation (TMS). The relationships between mirror movements, function, and corticospinal organization were assessed (t‐tests, Pearson rank correlation coefficients).

Results

Ninety‐two participants were scored (55 males, 37 females, mean [SD] 12y [5y 6mo], range 4–17y), 63 with complete motor outcomes and 39 with TMS data. EMG ratios correlated with clinical mirror movements (r=0.562, p=0.008). Mild mirror activity in controls declined with age (r=−0.459, p<0.001). Mirroring was stronger with tasks performed by the affected hand (p<0.001). Mirror movements correlated with AHA scores (r=−0.255, p=0.04) and poor motor outcome (p<0.001). Unaffected hand mirror activity was higher in children with ipsilateral corticospinal tract arrangements (p<0.001).

Interpretation

Clinical mirror movements correlate with disability and corticospinal organization in children with unilateral CP with perinatal stroke. This simple bedside biomarker could facilitate patient selection for personalized rehabilitation.

What this paper adds

Mirror movements are a clinical indicator of corticospinal organization in children with unilateral cerebral palsy with perinatal stroke.

Mirroring is strongest in children with ipsilateral corticospinal tract reorganization.

The concept of a ‘directionality factor’ to mirror movements highlights additional, clinically relevant functional correlations.
Motivation to learn languages other than English: A critical research synthesis
Authors: Mendoza Anna , Phung Huy
Published: January 2019

The primary purpose of this investigation was to put forward critical research synthesis as a qualitative alternative to meta‐analysis in second language acquisition using as a case example studies published from 2005 to 2018 applying the L2 Motivational Self System (L2MSS) to learners of languages other than English (LOTEs). Since L2MSS research is methodologically diverse and meta‐analysis necessarily excludes literature that cannot be subjected to its parameters, a qualitative synthetic approach with the systematicity and transparency of meta‐analysis is warranted. This study synthesizes 30 L2MSS studies on LOTEs in three world regions—Europe, Inner Circle English‐speaking countries, and Asia—and examines substantive and methodological features of the literature, including (1) the diversity of languages and educational contexts, (2) common issues of interest and findings in each world region, and (3) the strengths and limitations of quantitative and qualitative L2MSS studies. Suggestions for improving the diversity and quality of research on motivation to learn LOTEs are offered.
Domestic gardens play a dominant role in selecting alien species with adaptive strategies that facilitate naturalization
Authors: Guo Wen‐Yong , van Kleunen Mark , Pierce Simon , Dawson Wayne , Essl Franz , Kreft Holger , Maurel Noëlie , Pergl Jan , Seebens Hanno , Weigelt Patrick , Pyšek Petr
Published: January 2019

Aim

Horticulture has been recognized as the main pathway of plant invasions worldwide. The selection of ornamental garden plants is not random, and certain plant characteristics related to adaptive plant strategies are preferred by horticulture and may promote invasion. We examined the direct and indirect interactions between horticultural use, species adaptive strategies (competitive (C), stress‐tolerant (S), and ruderal (R)), native range size and naturalization success.

Location

Global.

Time period

From 1492 to the present.

Major taxa studied

Vascular plants.

Methods

We compiled a dataset of 3,794 plant species including their C‐, S‐ and R‐scores, native range size, cultivation in botanic and domestic gardens and whether the species is naturalized in at least one region globally (naturalization incidence). For the 1,711 naturalized species, we also calculated naturalization extent, that is, the number of regions where the species has naturalized. We used phylogenetic path analysis to disentangle the direct and indirect effects of all variables on both naturalization incidence and extent, and the relationships between variables.

Results

Approximately 87 and 94% of the 1,711 naturalized species were cultivated in botanic or domestic gardens, respectively, compared toc. 55 and 50% of the 2,083 non‐naturalized species, respectively. We found a cascading structure among the examined variables: (a) species exhibiting C‐ or R‐selected strategies and having large native ranges tended to be cultivated in domestic and botanic gardens, became naturalized outside their native ranges and occupied more regions in their naturalized ranges; (b) C‐, S‐ and R‐scores also had indirect effects on naturalization success, which were mediated by horticultural use and native range size; and (c) cultivation in domestic gardens was the strongest factor examined that could explain plant species’ naturalization success.

Main conclusions

We show that horticulture is not only the major introduction pathway of alien plants, but also that in particular domestic gardens select species predisposed to invade and naturalize.
Parent’s report on oral health‐related quality of life of children with haemophilia
Authors: Yazicioglu Iffet , Deveci Ceren , Çiftçi Volkan , Antmen Bülent , Doğan Muharrem C.
Published: January 2019

Introduction

Among children with haemophilia and their caregivers; problems arising from the teeth and the surrounding tissues have an important role in the treatment of this disease and it affects the quality of life of children and their parents.

Aim

Aim of this study is to evaluate the oral health‐related quality of life of children with haemophilia from the perspective of their parents.

Methods

Paediatric oral health‐related quality of life (POQL) instrument was used in this cross‐sectional study for quality of life measurement. The research data collected by the questionnaire form were coded for scale items and personal information questions and transferred to SPSS, a multivariate statistical analysis program for social sciences. SPSS 23.0 (IBM Corp, Armonk, NY) package program was used for statistical analysis of the data.

Results

Primary dentition dmft scores of patients with haemophilia are higher than the control group; mean value of haemophilic group is 3.5 vs control group are 2.6, respectively (P = 0.034). In spite of higher dmft scores, the haemophilia and control groups have shown no significant difference in oral health‐related quality of life scores; median scores were 63.9 in haemophilic group and 85.3 in control group (P = 0.336), respectively.

Conclusion

In spite of lower oral health measures, children with haemophilia and their parents reported no difference in oral health‐related quality of life from their healthy counterparts.
Tissue factor pathway inhibitor is the main determinant of thrombin generation in haemophilic patients
Authors: Chelle Pierre , Montmartin Aurélie , Damien Pauline , Piot Michèle , Cournil Michel , Lienhart Anne , Genre‐Volot Fabienne , Chambost Hervé , Morin Claire , Tardy‐Poncet Brigitte
Published: January 2019

The thrombin generation (TG) assay evaluates haemostatic balance, which is influenced by the levels of many coagulation factors and inhibitors. Our objective was to identify the determinant factors of TG in haemophilia A (HA) and haemophilia B (HB) patients and to compare them to those in healthy controls. Coagulation factor and inhibitor levels, and TG, were measured in platelet‐poor plasma from 40 patients with HA, 32 patients with HB and 40 healthy subjects. Data were analysed using multiple regression models. In HA patients, factor VIII was a positive determinant of endogenous thrombin potential (ETP) and peak, whereas tissue factor pathway inhibitor (TFPI) and factor V were negative determinants of ETP and peak. In HB patients, FIX was a positive determinant of ETP and peak, FVII being a positive determinant of peak. Antithrombin and protein S (PS) were negative determinants of ETP while FX was a negative determinant of peak. Above all, in HB patients, TFPI was a negative determinant of ETP and peak. In healthy subjects, FVIII was a positive determinant of ETP and peak, whereas FX and protein S were negative determinants of these parameters. TFPI was not a negative determinant of either peak or ETP. In haemophilic patients, the determinant factors of TG are all implicated in FXa generation and inhibition, the crucial determinant factor being TFPI whatever the type of haemophilia, A or B. These findings contribute to the rationale that recently place TFPI as a target for innovative therapies of haemophilia.
Relapse pattern and long‐term outcomes in subjects with acquired haemophilia A
Authors: Mizrahi Terry , Doyon Karine , Dubé Evemie , Bonnefoy Arnaud , Warner Margaret , Cloutier Stéphanie , Demers Christine , Castilloux Jean‐François , Rivard Georges‐Etienne , St‐Louis Jean
Published: January 2019

Introduction

Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by neutralizing antibodies against factor VIII (FVIII). Despite significant initial morbidity and mortality, most patients achieve remission with immunosuppressive therapy.

Aim

Long‐term follow‐up data from the Quebec Reference Centre for Inhibitors (QRCI) were analysed to identify factors predictive of AHA relapse and the influence of relapse on survival.

Methods

Criteria used to define AHA were levels of FVIII <0.3 IU/mL and FVIII inhibitor titres ≥0.6 Bethesda Units (BU). Complete remission was defined as FVIII >0.5 IU/mL and/or FVIII inhibitor titres <0.6 BU while not on immunosuppression.

Results

Between 2000 and 2012, 111 subjects met the inclusion criteria and were followed for a median of 25.6 months. Ninety per cent of them reached remission on immunosuppression in a median time of 45 days. Fourteen patients presented one or more relapses in a median time of 13.4 months. Most relapse episodes were successfully treated. Associated lymphoproliferative syndromes (LPS) were predictive of relapse, whereas FVIII activity and inhibitor titres at initial diagnosis or immunosuppressive regimens were not. The overall survival (OS) was the same, with or without relapse.

Conclusion

Among the recognized potential risk factors for relapse, only LPS was statistically significant. The long‐term follow‐up of our patients also showed that late or multiple relapses may occur, but that relapse is not associated with a worse OS. Thus, long‐term follow‐up is important for optimal management of AHA.
Eosinophilic infiltration: an under‐reported histological finding in urticarial vasculitis
Authors: Kamyab Kambiz , Ghodsi Seyedeh Zahra , Ghanadan Alireza , Taghizadeh Jafar , Karimi Shiva , Nasimi Maryam
Published: January 2019

Background

Urticarial vasculitis (UV) is a clinicopathologic entity in which skin lesions resemble urticaria clinically but last more than 24 hours and resolve with residual purpura. In this study, we evaluated distinguishing histological features of UV from common urticaria to differentiate between these two entities.

Methods

During 1 year, 55 urticaria and 245 UV samples were assessed. The selection criteria for UV included: (1) samples that the histological diagnosis was confirmed by two independent dermatopathologists, (2) the histological diagnosis of UV was inconsistent with the first clinical impression and lesion characteristics.

Results

Of our 245 UV patients, 96% had endothelial swelling, 18% had red blood cell (RBC) extravasation, neutrophilic infiltration was seen in 46.7%, and perivascular, interstitial, and perineural eosinophilic infiltration in 198 (81.8%), 181 (74.2%), and 118 (48.1%), respectively. Among different histological findings, endothelial cell swelling as well as neutrophil around vessels and eosinophilic infiltrations were statistically different between two groups (P‐value ˂ 0.001). Both urticaria and UV samples showed a predominantly lymphocytic infiltration more than 10 cells per high power field (HPF) (98.2% of urticaria, 98.8% of UV), and only two patients (0.8%) with UV had predominant neutrophilic infiltration (more than 10 cells/HPF).

Conclusion

We have found that both urticaria and UV showed a predominantly lymphocytic infiltration along with RBC extravasation, endothelial cell swelling, and fibrin deposition in UV. Moreover, significant perineural, perivascular, and interstitial infiltration of eosinophil in UV lesions compared to urticaria was another point that indicates special contribution of these cells in UV pathogenesis.
Patterns of immunotherapy use and management of toxicities in regional and tertiary settings
Authors: Hamilton Brett , Xu Kay , Honeyball Florian , Balakrishnar Bavanthi , Zielinski Rob
Published: January 2019

Background

The introduction of the cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and programmed cell death protein 1 (PD‐1) immune checkpoint inhibitors and their subsequent listing on the Pharmaceutical Benefits Scheme for use in metastatic melanomas, renal cell carcinomas and non‐small‐cell lung cancers has resulted in routine use of these agents in oncology practices, including in regional areas. Although immunotherapeutic agents generally have a favourable toxicity profile compared to chemotherapy, they can provoke immune‐related adverse effects (irAE) caused by an unregulated and hyperstimulated immune response. Some of these effects can be serious and life‐threatening.

Aims

To compare the utilisation of immunotherapy and the rates, management and outcomes of irAE between a regional oncology service and a tertiary service.

Methods

We reviewed the medical records for all patients treated with immunotherapy in the participating services for the 5‐year period from 31 July 2012 to 31 July 2017.

Results

Data demonstrated that rates of immunotherapy use are both similar and increasing across the tertiary and regional services. The rates, types and severity of irAE are equivalent and in concordance with pre‐existing literature. Immune‐related adverse events appear to be identified and treated earlier in the regional service with the corresponding reduction in the duration of immunosuppression and requirement for inpatient management.

Conclusion

The use of immunotherapy in a regional setting is safe and equivalent to that of a tertiary centre.
Predictors of acute hospital mortality and length of stay in patients with new‐onset atrial fibrillation: a first‐hand experience from a medical emergency team response provider
Authors: Thein Paul M. , Ong Julia , Crozier Tim M. , Nasis Arthur , Mirzaee Sam , Tan Sean X. , Junckerstorff Ralph
Published: January 2019

Background

Atrial fibrillation (AF) occurs frequently following cardiothoracic surgery and treatment decisions are informed by evidence‐based clinical guidelines. Outside this setting there are few data to guide clinical management.

Aim

To describe the characteristics, management and outcomes of hospitalised adult patients with new‐onset AF.

Methods

The medical emergency team (MET) database was utilised to identify patients who had a ‘MET call’ activated for tachycardia between 2015 and 2016. Patients with sinus tachycardia, pre‐existing AF/atrial flutter or other known tachyarrhythmia were excluded. Primary outcomes were length of hospital stay and in‐hospital mortality.

Results

New‐onset AF was identified in 137 patients: 68 medically managed; 38 non‐cardiothoracic post‐operative; and 31 cardiothoracic post‐operative. Mean age was 74 ± 11.6 years and 72 (53%) were male. Of 79 patients who underwent echocardiography, 80% had left atrial dilatation and 14% had reduced left ventricular ejection fraction (LVEF). Mean length of stay (LOS) was 12 days and in‐hospital mortality rate was 11%. On multivariable analysis, the odds of death during acute hospitalisation was 7.4 times higher in patients with heart failure with reduced LVEF (odds ratio 7.4, 95% confidence interval (CI) 1.23–44.8, P = 0.028). Length of acute hospital stay increased by 36% if the duration of AF was longer than 48 h (beta coefficient 0.36, 95% CI −0.015 to 0.74, P = 0.059).

Conclusion

Left ventricular systolic dysfunction in hospitalised patients with new‐onset AF is associated with increased all‐cause mortality whereas lower serum potassium levels are associated with an increased LOS. A prospective study is planned to compare outcomes based on in‐hospital treatment strategies.
Direct and indirect genetic effects on reproductive investment in a grasshopper
Authors: Chakrabarty Anasuya , van Kronenberg Philipp , Toliopoulos Nikolaos , Schielzeth Holger
Published: January 2019

A fundamental part of the quantitative genetic theory deals with the partitioning of the phenotypic variance into additive genetic and environmental components. During interaction with conspecifics, the interaction partner becomes a part of the environment from the perspective of the focal individual. If the interaction effects have a genetic basis, they are called indirect genetic effects (IGEs) and can evolve along with direct genetic effects. Sexual reproduction is a classic context where potential conflict between males and females can arise from trade‐offs between current and future investments. We studied five female fecundity traits, egg length and number, egg pod length and number and latency to first egg pod, and estimated the direct and IGEs using a half‐sib breeding design in the grasshopper Chorthippus biguttulus. We found that the male IGEs were an order of magnitude lower than the direct genetic effects and were not significantly different from zero. However, there was some indication that IGEs were larger shortly after mating, consistent with the idea that IGEs fade with time after interaction. Female direct heritabilities were moderate to low. Simulation shows that the variance component estimates can appear larger with less data, calling for care when interpreting variance components estimated with low power. Our results illustrate that the contribution of male IGEs is overall low on the phenotypic variance of female fecundity traits. Thus, even in the relevant context of sexual conflict, the influence of male IGEs on the evolutionary trajectory of female reproductive traits is likely to be small.
DO FIRMS SEEK A TARGET BOARD STRUCTURE? EVIDENCE FROM THE POST‐SOX PERIOD
Authors: Chung Chune Young , Liu Chang , Paul Donna L.
Published: January 2019

We investigate whether firms restructure board composition to align with changes in their contracting environment. Board size and independence increase with firm complexity, consistent with theoretical predictions. However, the hypothesized negative relation between board independence and information costs is evident only for firms completing acquisitions. Furthermore, board independence increases to offset increases in CEO power in a sample of firms making acquisitions, but decreases when CEO power increases in a large cross‐section of firms. We conclude that after the Sarbanes–Oxley Act of 2002, firms face constraints adjusting to target board structure, but these constraints can be mitigated by a shock to the contracting environment via acquisition.
The 5Ts: Preliminary Development of a Framework to Support Inclusion of Older Adults in Research
Authors: Bowling C. Barrett , Whitson Heather E. , Johnson Theodore M.
Published: January 2019

Background/Objectives

To address the underrepresentation of older adults in clinical research, the National Institutes of Health will require investigators to include individuals across the lifespan. As investigators from other fields endeavor to recruit participants who are more representative of the patient population, geriatricians may have the opportunity to influence a broad range of research studies in older adults. Our aims were to elicit challenges to inclusion of older adults in clinical research and to develop a preliminary framework for communicating these challenges to non–geriatrics‐trained researchers.

Design

Communication framework development.

Setting

Academic hospital and Veterans Affairs Medical Center.

Participants

Nongeriatrician researchers and staff, aging research experts.

Measurements

Interviews were used to elicit challenges nongeriatrician investigators and research staff experience when conducting research that includes older adults and then solicit experienced aging researchers' responses to these challenges.

Results

Challenges described by nongeriatrician investigators included lack of knowledge, rigid study structures, and a disease‐focused approach. Responses from our geriatrics experts included communicating practical advice for avoiding common pitfalls. Our resulting framework is the 5Ts: Target Population, Team, Tools, Time, and Tips to Accommodate. This tool complements the 5Ms (Mind, Mobility, Medications, Multicomplexity, and Matters Most to Me) model for geriatric care and emphasizes representation of the Target Population, building research Teams that include aging expertise, incorporating appropriate Tools for function and patient‐reported outcomes, anticipating Time for longer study visits, and accommodating common needs with practical Tips. Limitations include convenience sampling and lack of formal qualitative thematic analysis.

Conclusion

Communicating with nongeriatrician researchers using the 5Ts may offer a practical approach to avoiding barriers to inclusion of older adults in research and complements an existing framework for communicating the value of geriatric medicine. Next steps in developing the 5Ts will be to include additional stakeholders (eg, national samples of nongeriatrician investigators, older adults and their families) and evaluating the impact of its implementation. J Am Geriatr Soc 67:342–346, 2019.
Anti‐inflammatory potential of a carvedilol gel in the pulpal tissue of rats after dental bleaching: A histopathological evaluation
Authors: Louzada Lidiane M. , Briso André L. F. , Benetti Francine , Vieira Letícia B. , de Castilho Jacinto Rogério , Dezan‐Júnior Elói , Cintra Luciano T. A.
Published: January 2019

Aim

Carvedilol is an antioxidant that decreases inflammation in periodontitis. The hydrogen peroxide (H2O2) of bleaching gel causes inflammation and necrosis of the dental pulp. In the present study, we evaluated the anti‐inflammatory potential of carvedilol in the pulp of rats after bleaching.

Methods

The right upper molars of rats received 35% H2O2 (1× 30 minutes), and the left upper molars were used as the control. Half of the rats received carvedilol gel (1× 10 minutes), forming the following groups: bleached, bleached followed by carvedilol (bleached+carvedilol), and control. After 2 and 30 days (N = 7 hemi‐maxillae/group), the rats were killed for histological evaluation, and statistical tests were performed (P < 0.05).

Results

After 2 days, the bleached group showed necrosis in the occlusal third of the coronal pulp, and in the bleached+carvedilol group, severe inflammation (P > 0.05), both different from the control (P < 0.05). In the middle third, the bleached group showed severe inflammation, and the bleached+carvedilol group showed moderate inflammation (P > 0.05), with the only difference between the bleached and control groups (P < 0.05). In the cervical third, the bleached group showed moderate inflammation, and the bleached+carvedilol group showed mild inflammation (P > 0.05). The difference again was only between the bleached and control groups (P < 0.05). At 30 days, there was no inflammation and a marked amount of tertiary dentin in bleached teeth (P > 0.05).

Conclusion

Carvedilol gel has the potential of minimizing H2O2 damage, especially in deep regions of the dental pulp of rats after bleaching.
ON THE SECOND STAGE OF THE CAMBRIDGE CAPITAL CONTROVERSY
Authors: Fratini Saverio M.
Published: January 2019

The second stage of the Cambridge capital controversy concerns the neo‐Walrasian theory of value and distribution. Since production is not understood in this theory as employing factors of production but rather commodities, that is goods and services with date and place of delivery, some scholars maintained that it is not affected by the problems that emerged, during the first stage of the controversy, as regards the conception of capital as a factor of production and the rate of interest as the price for its use. The reply of the ‘neo‐Ricardians’ was based on two arguments. The first regarded the relevance of the new notions of equilibrium adopted in the neo‐Walrasian approach, with particular reference to temporary and Arrow–Debreu equilibria, and the second the possibility that the phenomena of re‐switching and reverse capital deepening, by affecting the working of the saving‐investment market, could cause equilibrium multiplicity and instability also in a neo‐Walrasian framework.