bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimising the spatial planning of prescribed burns to achieve multiple objectives in a fire‐dependent ecosystem
Authors: Williams Brooke A. , Shoo Luke P. , Wilson Kerrie A. , Beyer Hawthorne L.
Published: April 2017

There is potential for negative consequences for the ecological integrity of fire‐dependent ecosystems as a result of inappropriate fire regimes. This can occur when asset (property) protection is prioritised over conservation objectives in burn programs.

Optimisation of fire management for multiple objectives is rarely undertaken. Here, we use integer linear programming to identify burn scheduling solutions that will cost‐effectively achieve asset protection and conservation objectives.

An approach to burn scheduling that favours a risk‐averse asset protection strategy results in poor conservation outcomes. Conversely, a conservation‐focused approach achieves only modest asset protection benefits. However, when formulated as a multi‐objective problem, good conservation outcomes can be realised with only a small reduction in potential benefits for asset protection.

A conservation‐focused approach resulted in substantially more heterogeneity in burns at multiple spatial scales and a marked reduction in mean time since fire among all forest patches relative to an asset protection scenario. This increase in heterogeneity improves ecological integrity, while the resulting reduction in fuel load is beneficial for asset protection.

Synthesis and applications. Mathematical optimisation is a powerful framework for informing fire management that improves the prioritisation and scheduling of controlled burns to efficiently achieve management objectives. By quantifying the trade‐offs that exist between the two competing objectives of conservation and asset protection, we demonstrate that compromise solutions can be identified that achieve good outcomes for both objectives. In a transparent and equitable manner, we show that conservation value may be improved within a fire‐dependent ecosystem with only modest concession to asset protection performance. Explicitly evaluating trade‐offs among competing objectives enables managers to identify potentially undesirable outcomes, and facilitate development of preferred solutions. Heterogeneous burning under the auspices of conservation also has the potential to reduce overall fuel loads within the ecosystem and thus its value for asset protection is likely underappreciated.
Student perspectives of a Student‐Led Groups Program model of professional practice education in a brain injury rehabilitation unit
Authors: Patterson Freyr , Fleming Jennifer , Marshall Kathryn , Ninness Nadine
Published: April 2017

Background/aim

Professional practice education is a core and essential component of occupational therapy training. With increasing numbers of education programmes and more students requiring professional practice placements, development of innovative models of professional practice education has emerged, but these require investigation. The aim of this study was to investigate student experiences and perceptions of the Student‐Led Groups Program model of professional practice education in an inpatient brain injury rehabilitation unit.

Methods

A qualitative approach, guided by phenomenological theory was used. Participants were 15 students who had completed a professional practice placement in the Student‐Led Groups Program. Data were collected using in‐depth semi‐structured interviews and analysed thematically.

Results

Three over‐arching themes emerged from the data; balance of support and freedom, development of clinical skills and missed opportunities. Students described how the structure of the placement facilitated independent learning and autonomy that was balanced with support from clinicians and student peers. Students perceived that they had developed a breadth of clinical skills and also had missed some learning opportunities in this professional practice placement structure.

Conclusions

Overall student perceptions of the Student‐Led Groups Program were positive, supporting the continued use of this model of professional practice education in this setting. The results highlight the value of structured and consistent approaches for supervision, including the use of formal approaches to peer supervision in the initial stages of learning.
Congenital anomalies of lumbosacral spine: A pictorial review
Authors: Naffaa Lena , Irani Neville , Saade Charbel , Sreedher Gayathi
Published: April 2017

Congenital malformations of the lumbosacral spine include spinal dysraphism and caudal anomalies. Most often, these malformations are discovered prenatally or in early infancy, but some are not diagnosed until late childhood or adulthood. The purpose of this pictorial review is to illustrate the multi‐modality imaging characteristics in these complex anomalies and to provide a systematic radiological approach aiming at improving diagnostic accuracy.
The influence of institutional contexts on the relationship between voluntary carbon disclosure and carbon emission performance
Authors: Luo Le
Published: April 2017

This article examines the relationship between the level of voluntary carbon disclosure (VCD) and carbon emission performance and how the institutional context influences this relationship. Using a sample of Global 500 firms participating in the Carbon Disclosure Project (CDP) over the period 2008–2015, the evidence shows a negative relationship between voluntary carbon disclosure and carbon emission performance, which is consistent with the legitimacy theory that VCD may be undertaken for the purposes of legitimation. However, stringent carbon institutions appear to restrict legitimation attempts and help better reflect underlying performance.
Evaluating fund capacity: issues and methods
Authors: O'Neill Michael J. , Warren Geoffrey J.
Published: April 2017

We examine the issues and methods involved in evaluating the size that an equity fund might attain before it becomes unable to create additional value for investors. We discuss how capacity is defined, identify ten drivers and outline methods for conducting capacity analysis. We detail models that predict capacity, assuming that a fund adjusts the manner in which it trades and constructs portfolios as funds under management grow. We also provide an overview of transaction cost modelling, which is integral to predicting capacity. This study is primarily intended as an aid for investment industry participants who wish to evaluate the capacity associated with a given investment signal.
Suicide among immigrant population in Norway: a national register‐based study
Authors: Puzo Q. , Mehlum L. , Qin P.
Published: April 2017

Objective

To investigate differences in suicide risk among immigrant population in Norway compared with native Norwegians, with respect to associated country group of origin.

Methods

Based on the entire national population, a nested case‐control design was adopted using Norwegian national longitudinal registers to obtain 23 073 suicide cases having occurred in 1969–2012 and 373 178 controls. Odds ratios (ORs) for suicide were estimated using conditional logistic regression analysis adjusting for socio‐economic factors.

Results

Compared with native Norwegians, suicide risk was significantly lower in first‐ and second‐generation immigrants but higher in Norwegian‐born with one foreign‐born parent and foreign‐born individuals with at least one Norwegian‐born parent. When stratifying data by country group of origin, first‐generation immigrants had lower ORs in most of the strata. Subjects born in Asia and in Central and South America with at least one Norwegian‐born parent had a significantly higher risk of suicide. The observed results remained mostly unchanged in the analyses controlled for socio‐economic status.

Conclusions

Suicide risk is lower in first‐ and second‐generation immigrants but higher in subjects born in Norway with one foreign‐born parent and those born abroad with at least one Norwegian‐born parent, with notable differences by country group of origin.
Post‐traumatic stress disorder symptoms in pregnant Australian Indigenous women residing in rural and remote New South Wales: A cross‐sectional descriptive study
Authors: Mah Beth , Weatherall Loretta , Burrows Julie , Blackwell Caroline C. , Gwynn Josephine , Wadhwa Pathik , Lumbers Eugenie R. , Smith Roger , Rae Kym M.
Published: April 2017

Background

Pregnancy can be a stressful time for many women. There is ample evidence of numerous physical and mental health inequities for Indigenous Australians. For those Indigenous women who are pregnant, it is established that there is a higher incidence of poor physical perinatal outcomes when compared with non‐Indigenous Australians. However, little evidence exists that examines stressful events and post‐traumatic stress disorder (PTSD) symptoms in pregnant women who are members of this community.

Aims

To quantify the rates of stressful events and PTSD symptoms in pregnant Indigenous women.

Methods

One hundred and fifty rural and remote Indigenous women were invited to complete a survey during each trimester of their pregnancy. The survey measures were the stressful life events and the Impact of Events Scale.

Results

Extremely high rates of PTSD symptoms were reported by participants. Approximately 40% of this group exhibited PTSD symptoms during their pregnancy with mean score 33.38 (SD = 14.37) significantly higher than a study of European victims of crisis, including terrorism attacks (20.6, SD = 18.5).

Conclusions

The extreme levels of PTSD symptoms found in the women participating in this study are likely to result in negative implications for both mother and infant. An urgent response must be mounted at government, health, community development and research levels to address these findings. Immediate attention needs to focus on the development of interventions to address the high levels of PTSD symptoms that pregnant Australian Indigenous women experience.
Work productivity in rhinitis using cell phones: The MASK pilot study
Authors: Bousquet J. , Bewick M. , Arnavielhe S. , Mathieu‐Dupas E. , Murray R. , Bedbrook A. , Caimmi D. P. , Vandenplas O. , Hellings P. W. , Bachert C. , Anto J. M. , Bergmann K. C. , Bindslev‐Jensen C. , Bosnic‐Anticevich S. , Bouchard J. , Canonica G. W. , Chavannes N. H. , Cruz A. A. , Dahl R. , Demoly P. , De Vries G. , Devillier P. , Fink‐Wagner A. , Fokkens W. J. , Fonseca J. , Guldemond N. A. , Haahtela T. , Hellqvist‐Dahl B. , Just J. , Keil T. , Klimek L. , Kowalski M. L. , Kuna P. , Kvedariene V. , Laune D. , Larenas‐Linnemann D. , Mullol J. , Pereira A. M. , Carreiro‐Martins P. , Melén E. , Morais‐Almeida M. , Nogueira‐Silva L. , O'Hehir R. E. , Papadopoulos N. G. , Passalacqua G. , Portejoie F. , Price D. , Ryan D. , Samolinski B. , Sheikh A. , Simons F. E. R. , Spranger O. , Todo Bom A. , Tomazic P. V. , Triggiani M. , Valero A. , Valovirta E. , Valiulis A. , van Eerd M. , Wickman M. , Young I. , Zuberbier T.
Published: April 2017

Allergic rhinitis often impairs social life and performance. The aim of this cross‐sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS‐global measured), nasal (VAS‐nasal), ocular (VAS‐ocular) and asthma symptoms (VAS‐asthma) as well as work (VAS‐work). A combined nasal‐ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS‐work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS‐work. Symptoms of allergic rhinitis were controlled (VAS‐global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS‐work >50). There was a significant correlation between VAS‐global calculated and VAS‐work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS‐work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof‐of‐concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.
Weak by the machines: muscle motor protein dysfunction – a side effect of intensive care unit treatment
Authors: Friedrich O. , Diermeier S. , Larsson L.
Published: April 2017

Intensive care interventions involve periods of mechanical ventilation, sedation and complete mechanical silencing of patients. Critical illness myopathy (CIM) is an ICU‐acquired myopathy that is associated with limb muscle weakness, muscle atrophy, electrical silencing of muscle and motor proteinopathy. The hallmark of CIM is a preferential muscle myosin loss due to increased catabolic and reduced anabolic activity. The ubiquitin proteasome pathway plays an important role, apart from recently identified novel mechanisms affecting non‐lysosomal protein degradation or autophagy. CIM is not reproduced by pure disuse atrophy, denervation atrophy, steroid‐induced atrophy or septic myopathy, although combinations of high‐dose steroids and denervation can mimic CIM. New animal models of critical illness and ICU treatment (i.e. mechanical ventilation and complete immobilization) provide novel insights regarding the time course of protein synthesis and degradation alterations, and the role of protective chaperone activities in the process of myosin loss. Altered mechano‐signalling seems involved in triggering a major part of myosin loss in experimental CIM models, and passive loading of muscle potently ameliorates the CIM phenotype. We provide a systematic overview of similarities and distinct differences in the signalling pathways involved in triggering muscle atrophy in CIM and isolated trigger factors. As preferential myosin loss is mostly determined from biochemistry analyses providing no spatial resolution of myosin loss processes within myofibres, we also provide first results monitoring myosin signal intensities during experimental ICU intervention using multi‐photon Second Harmonic Generation microscopy. Our results confirm that myosin loss is an evenly distributed process within myofibres rather than being confined to hot spots.
Understanding ethnography through a life course framework: a research journey into alternative spiritual spaces
Authors: Fois Francesca
Published: April 2017

Recently scholars have emphasised the importance of looking at the researcher's experience and how positionality, emotions and embodiment shape the ethnographic fieldwork process. Specifically, feminist contributions have shown how the professional and the personal can be interlinked when conducting ethnographic research and have reconsidered the role of the researcher in the production of knowledge. However, such accounts often lack analytical engagements and/or reveal little about the researcher's experience beyond the fieldwork. By adopting a life course framework and its conceptual categories of social pathways, turning points, and transitions & trajectories, this paper offers an analytical device to read through the ethnographer's own experience. The paper explores a research journey undertaken in the intentional spiritual communities of Damanhur (Italy) and Terra Mirim (Brazil) by the author, which aimed to study the enactment of alternative spaces. By integrating a life course framework, this paper firstly argues the need to consider how social pathways shape the life course positioning and the research trajectory. Secondly, it shows how turning points can affect both the research direction but also the researcher's life course. Thirdly, the paper argues that the fieldwork is only one of the transitional phases of ethnographic research and encourages the researcher to reflect on its long‐term effects. It concludes by discussing how such experience can impact on the life course of the researcher as well as on the research participants.
Marizomib for central nervous system‐multiple myeloma
Authors: Badros Ashraf , Singh Zeba , Dhakal Binod , Kwok Young , MacLaren Ann , Richardson Paul , Trikha Mohit , Hari Parameswaran
Published: April 2017

Marizomib, a natural marine product, is an irreversible proteasome inhibitor currently under investigation in relapsed‐refractory multiple myeloma (RRMM) and malignant glioma. Central nervous system‐multiple myeloma (CNS‐MM) is a rare manifestation of extra‐medullary disease with few therapeutic options, highlighting the unmet clinical need in these patients. Marizomib demonstrated encouraging activity in RRMM and has emerging clinical activity in glioma, making it a potential CNS‐MM therapeutic intervention. Herein, we present two patients with RRMM and CNS involvement who benefited from marizomib‐based therapy. These cases provide the first proof of principle for further exploring marizomib in CNS‐MM patients.
Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome
Authors: Katz Laura , Tripp Dean A. , Carr Lesley K. , Mayer Robert , Moldwin Robert M. , Nickel J. Curtis
Published: April 2017

Objectives

To examine a self‐regulation and coping model for interstitial cystitis/bladder pain syndrome (IC/BPS) that may help us understand the pain experience of patients with chronic IC/BPS.

Patients and Methods

The model tested illness perceptions, illness‐focused coping, emotional regulation, mental health and disability in a stepwise method using factor analysis and structural equation modelling. Step 1, explored the underlying constructs. Step 2, confirmed the measurement models to determine the structure/composition of the main constructs. Step 3, evaluated the model fit and specified pathways in the proposed IC/BPS self‐regulation model. In all, 217 female patients with urologist diagnosed IC/BPS were recruited and diagnosed across tertiary care centres in North America. The data were collected through self‐report questionnaires.

Results

An IC/BPS self‐regulation model was supported. Physical disability was worsened by patient's negative perception of their illness, attempts to cope using illness‐focused coping and poorer emotional regulation. Mental health was supported by perceptions that individuals could do something about their illness, using wellness‐focused behavioural strategies and adaptive emotion regulation.

Conclusions

The results clarify the complex and unique process of self‐regulation in women with IC/BPS, implicating cognitive and coping targets, and highlighting emotional regulation. This knowledge should help clinicians understand and manage these patients’ distress and disability.
Clinicopathological significance of the microRNA‐146a/WASP‐family verprolin‐homologous protein‐2 axis in gastric cancer
Authors: Yao Qunyan , Tu Chuantao , Lu Di , Zou Yanting , Liu Hongchun , Zhang Shuncai
Published: April 2017

Gastric cancer (GC) is one of the most common malignancies, and cancer invasion and metastasis are the leading causes of cancer‐induced death in GC patients. WASP‐family verprolin‐homologous protein‐2 (WASF2), with a role controlling actin polymerization which is critical in the formation of membrane protrusions involved in cell migration and invasion, has been reported to possess cancer‐promoting effects in several cancers. However, data of WASF2's role in GC are relatively few and even contradictory. In this study, we analyzed WASF2 expression in GC tissues and their corresponding adjacent normal tissues. We found that WASF2 was upregulated in GC tissues and high level of WASF2 was associated with lymph node metastasis of GC. Through gain‐ and loss‐of‐function studies, WASF2 was shown to significantly increase GC cells migration and invasion, but had no effect on proliferation in vitro. Importantly, WASF2 was also found to enhance GC metastasis in vivo. Our previous research suggested that WASF2 was a direct target of microRNA‐146a (miR‐146a). Furthermore, we analyzed miR‐146a's level in GC tissues and their corresponding adjacent normal tissues. We found that miR‐146a was downregulated in GC tissues and low miR‐146a level was associated with advanced TNM stage and lymph node metastasis. The level of WASF2 in GC tissues was negatively correlated with miR‐146a expression and had inverse clinicopathologic features. The newly identified miR‐146a/WASF2 axis may provide a novel therapeutic target for GC.
An expedient synthesis of N‐(1‐(5‐mercapto‐4‐((substituted benzylidene)amino)‐4H‐1,2,4‐triazol‐3‐yl)‐2‐phenylethyl)benzamides as jack bean urease inhibitors and free radical scavengers: Kinetic mechanism and molecular docking studies
Authors: Saeed Aamer , Larik Fayaz Ali , Channar Pervaiz Ali , Mehfooz Haroon , Ashraf Mohammad Haseeb , Abbas Qamar , Hassan Mubashir , Seo Sung‐Yum
Published: April 2017

In this study, some new azomethine‐triazole hybrids 5a–5l derived from N‐benzoyl‐L‐phenylalanine were synthesized and characterized. The synthesized compounds showed first‐rate, urease inhibition, and compounds 5c and 5e were found to be most effective inhibitors with 0.0137 ± 0.00082 μm and 0.0183 ± 0.00068 μm, respectively (thiourea 15.151 ± 1.27 μm). The kinetic mechanism of urease inhibition revealed the compounds 5c and 5e to be non‐competitive inhibitors, whereas compounds 5d and 5j were found to be of mixed‐type inhibitors. Docking studies also indicated better interaction patterns with urease enzyme. The results of enzyme inhibition, kinetic mechanism and molecular docking suggest that these compounds can serve as lead compounds in the design of more effective urease inhibitors.
Foundations of Reasoning About Social Dominance
Authors: Pun Anthea , Birch Susan A.J. , Baron Andrew S.
Published: April 2017

Understanding the factors that shape the social landscape is essential for living in a group, where dominant individuals often have greater control over and access to desired resources such as food and mates. Recently, researchers have demonstrated that preverbal infants, similar to their nonhuman primate relatives, already possess the cognitive schemas necessary to represent social dominance in relationships, using ecologically relevant cues such as relative physical size and group size. In this article, we discuss the phylogenetic and ontogenetic origins of infants’ and children's capacity to represent social dominance in relationships and hierarchies, and examine how these initial representations are enriched across early childhood.
A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with TAB2 mutations
Authors: Ritelli M. , Morlino S. , Giacopuzzi E. , Bernardini L. , Torres B. , Santoro G. , Ravasio V. , Chiarelli N. , D'Angelantonio D. , Novelli A. , Grammatico P. , Colombi M. , Castori M.
Published: April 2017

Deletions encompassing TAK1‐binding protein 2 (TAB2) associated with isolated and syndromic congenital heart defects. Rare missense variants are found in patients with a similar phenotype as well as in a single individual with frontometaphyseal dysplasia. We describe a family and an additional sporadic patient with polyvalvular heart disease, generalized joint hypermobility and related musculoskeletal complications, soft, velvety and hyperextensible skin, short limbs, hearing impairment, and facial dysmorphism. In the first family, whole‐exome sequencing (WES) disclosed the novel TAB2 c.1398dup (p.Thr467Tyrfs*6) variant that eliminates the C‐terminal zinc finger domain essential for activation of TAK1 (TGFβ‐activated kinase 1)‐dependent signaling pathways. The sporadic case carryed a ~2 Mb de novo deletion including 28 genes also comprising TAB2. This study reveal an association between TAB2 mutations and a phenotype resembling Ehlers‐Danlos syndrome with severe polyvalvular heart disease and subtle facial dysmorphism. Our findings support the existence of a wider spectrum of clinical phenotypes associated with TAB2 perturbations and emphasize the role of TAK1 signaling network in human development.
Preventing Global Extinction of the Javan Rhino: Tsunami Risk and Future Conservation Direction
Authors: Setiawan Ridwan , Gerber Brian D. , Rahmat Ujang Mamat , Daryan Daryan , Firdaus Asep Yayus , Haryono Mohammad , Khairani Kurnia Okhtavia , Kurniawan Yuyun , Long Barney , Lyet Arnaud , Muhiban Muhiban , Mahmud Rois , Muhtarom Aom , Purastuti Elisabet , Ramono Widodo S. , Subrata Dadan , Sunarto Sunarto
Published: April 2017

The Javan rhino (Rhinoceros sondaicus) is one of the most threatened mammals on Earth. The only remaining individuals live as part of a small population isolated in a single protected area, Ujung Kulon National Park, Java, Indonesia. Despite almost a century of studies, little is known about the factors that affect Javan rhino demography and distribution. National park officials require such information to identify conservation strategies and track the success and failures of these efforts; translocating selected individuals to establish a second population has been considered, but the risks must be weighed. We show that the 2013 global population of Javan rhinos was 62 individuals, which is likely near the site's carrying capacity. Our analysis of rhino distribution indicates that tsunamis are a significant risk to the species in Ujung Kulon, justifying the risks of establishing additional populations. Continued individual‐based monitoring is needed to guide future translocation decisions.
Consistent findings in glycaemic control, body weight and hypoglycaemia with iGlarLixi (insulin glargine/lixisenatide titratable fixed‐ratio combination) vs insulin glargine across baseline HbA1c, BMI and diabetes duration categories in the LixiLan‐L trial
Authors: Wysham Carol , Bonadonna Riccardo C. , Aroda Vanita R. , Puig Domingo Manuel , Kapitza Christoph , Stager William , Yu Christine , Niemoeller Elisabeth , Souhami Elisabeth , Bergenstal Richard M. ,   on behalf of the LixiLan‐L trial investigators
Published: April 2017

Aims

To assess the impact of baseline characteristics on clinical outcomes in the LixiLan‐L trial, a randomized open‐label trial designed to evaluate the efficacy and safety of iGlarLixi, a novel fixed‐ratio combination of insulin glargine 100 U (iGlar) plus lixisenatide, in comparison with iGlar over 30 weeks in a population of patients with type 2 diabetes mellitus (T2DM) inadequately controlled on a previous regimen of basal insulin alone or in combination with 1 or 2 oral glucose‐lowering drugs.

Materials and Methods

In this exploratory analysis of LixiLan‐L (N = 736), efficacy outcomes were assessed within population subgroups derived from the following baseline characteristics: glycated haemoglobin [HbA1c; <8%, ≥8% (<64, ≥64 mmol/mol)]; duration of T2DM (<10, ≥10 years); body mass index (<30, ≥30 kg/m2). Furthermore, the incidence of symptomatic hypoglycaemia with plasma glucose ≤3.9 mmol/L (≤70 mg/dL) was also analysed according to the same subgroups.

Results

Compared with the iGlar treatment group, patients treated with iGlarLixi showed consistently greater reductions in HbA1c during the treatment period, with higher percentages of patients achieving the HbA1c target level of <7% (<53 mmol/mol) in all of the subpopulations tested (P < .0001 for all), having consistent mitigation of body weight gain and with no major differences in the incidence of hypoglycaemia.

Conclusions

iGlarLixi consistently improved glycaemic control compared with iGlar in all baseline characteristic subgroups of patients with T2DM inadequately controlled with insulin, including difficult‐to‐treat subgroups of patients with long duration of diabetes, obesity and high HbA1c.

Clinical trial number: NCT02058160 (clinicaltrials.gov).
Impact of empagliflozin on blood pressure in dipper and non‐dipper patients with type 2 diabetes mellitus and hypertension
Authors: Chilton Robert , Tikkanen Ilkka , Hehnke Uwe , Woerle Hans J. , Johansen Odd Erik
Published: April 2017

In the EMPA‐REG BP trial, empagliflozin significantly reduced systolic and diastolic blood pressure (SBP and DBP) compared with placebo at week 12 in patients with type 2 diabetes mellitus (T2DM) and hypertension. In a post‐hoc analysis, we assessed the effect of empagliflozin on SBP and DBP using 24‐hour ambulatory BP monitoring in patients categorized as dippers (sleep‐time mean SBP ≤ 90% of awake‐time mean; n = 417) or non‐dippers (sleep‐time mean SBP > 90% of awake‐time mean; n = 350). In dippers, adjusted mean (SE) changes from baseline in mean 24‐hour SBP (mm Hg) at week 12 were −0.2 (0.7) with placebo vs −3.8 (0.6) and −3.9 (0.7) with empagliflozin 10 and 25 mg, respectively (both
P
 < .001 vs placebo). In non‐dippers, these changes were 1.0 (0.7) with placebo vs −1.6 (0.7) with empagliflozin 10 mg (
P
 = .013 vs placebo) and −3.8 (0.7) with empagliflozin 25 mg (
P
 < .001 vs placebo). In both dippers and non‐dippers, SBP and DBP patterns over 24 hours were maintained. There were no clinically relevant changes in heart rate with empagliflozin. In conclusion, empagliflozin significantly reduced mean 24‐hour SBP compared with placebo in dippers and non‐dippers.
Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials
Authors: O'Neil Patrick M. , Aroda Vanita R. , Astrup Arne , Kushner Robert , Lau David C. W. , Wadden Thomas A. , Brett Jason , Cancino Ana‐Paula , Wilding John P. H. ,   on behalf of the Satiety and Clinical Adiposity – Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups
Published: April 2017

Aims

Liraglutide, a GLP‐1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally‐acting anti‐obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double‐blind trials with liraglutide 3.0 mg were evaluated post hoc.

Methods

Data from the liraglutide weight‐management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m2 with weight‐related comorbidities were randomized to once‐daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/d deficit diet, plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental‐health questionnaires were prospectively and systematically administered.

Results

In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person‐years) and anxiety (1.9 vs 1.7 events/100 person‐years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire‐9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia‐Suicide Severity Rating Scale.

Conclusions

Results of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no between‐treatment imbalances in suicidal ideation/behaviour or depression were noted through prospective questionnaire assessments.
Examining trends in type 2 diabetes incidence, prevalence and mortality in the UK between 2004 and 2014
Authors: Zghebi Salwa S. , Steinke Douglas T. , Carr Matthew J. , Rutter Martin K. , Emsley Richard A. , Ashcroft Darren M.
Published: April 2017

Aims

Contemporary data describing type 2 diabetes prevalence, incidence and mortality are limited. We aimed to (1) estimate annual incidence and prevalence rates of type 2 diabetes in the UK between 2004 and 2014, (2) examine relationships between observed rates with age, gender, socio‐economic status and geographic region, and (3) assess how temporal changes in incidence and all‐cause mortality rates influence changes in prevalence.

Methods

Type 2 diabetes patients aged ≥16 years between January 2004 and December 2014 were identified using the Clinical Practice Research Datalink (CPRD). Up to 5 individuals without diabetes were matched to diabetes patients based on age, gender and the general practice. Annual incidence, prevalence and mortality rates were calculated per 10 000 person‐years at risk (95% CI). Survival models compared mortality rates in patients with and without type 2 diabetes.

Results

Prevalence rates of type 2 diabetes increased from 3.21% (3.19; 3.22) in 2004 to 5.26% (5.24; 5.29) in 2014. Incidence rates remained stable, overall, throughout the study period. Higher incidence and prevalence rates were related to male gender and deprivation. Individuals with type 2 diabetes were associated with higher risk of mortality (Hazard ratio 1.26 [1.20; 1.32]). Mortality rates declined in patients with and without diabetes throughout the study period. The incidence and prevalence of type 2 diabetes in patients aged 16 to 34 years increased over time.

Conclusions

The rising prevalence of type 2 diabetes in the UK over the last decade is probably explained by patients living longer rather than by increasing incidence of type 2 diabetes.
Maximal systolic excursion of the tricuspid annulus is independent of right atrial size and function in chronic pulmonary hypertension
Authors: Hernandez‐Suarez Dagmar F. , López Menéndez Francisco , López‐Candales Angel
Published: April 2017

Background

Even though the tricuspid annulus (TA) is anatomically and functionally related to right atrioventricular dependence and tricuspid annular plane systolic excursion (TAPSE) is a well‐known measure of right ventricular (RV) systolic function, there is paucity of data regarding the potential impact that right atrial (RA) size and function have on TAPSE. Hence, we sought to determine whether RA volumetric and longitudinal measures affect TAPSE in patients with chronic pulmonary hypertension (cPH).

Methods

In this retrospective study, echocardiographic data from 110 patients were reviewed and the studied population was divided into Group I consisting of 50 patients (50±11 years) without PH and Group II that included 60 patients (55±14 years) with cPH.

Results

Even though RA areas, RA fractional area change, and maximal long‐axis length measurements were abnormal in cPH patients, TA tissue Doppler imaging systolic velocity and RV fractional area change were the only useful variables in identifying patients with abnormal TAPSE (P<.0001 and P=.018, respectively). Additionally, TAPSE was independent of all RA measures, left ventricular ejection fraction, and age (P>.05).

Conclusions

Based on these results, TAPSE does not appear to be influenced by either RA size or function. Additional studies using strain echocardiography to interrogate RA mechanics might now be very useful to advance our understanding of TA motion in cPH patients given recent data showing that RA function accounts for a significantly greater proportion of total right heart function in patients with cPH than in normal subjects.
Thrombus formation in the interrupted segment of the aorta
Authors: Karavelioğlu Yusuf , Kalçık Macit , Yetim Mucahit , Doğan Tolga , Gölbaşı Zehra
Published: April 2017

Interrupted aorta is a very rare heart defect in which there is a gap between the ascending and the descending thoracic aorta. It is usually associated with other cardiac anomalies, including ventricular septal defect, ductus arteriosus, and truncus arteriosus. Severe cases present with serious complications such as hypertension, heart failure, or intracranial hemorrhage. Neurological complications are very rare form of presentation and commonly associated with intracranial aneurysms. We have reported a case of interrupted aorta who presented with transient ischemic attack due to thrombus formation in the interrupted segment of the aorta.
The generalized replication principle and the partitioning of functional diversity into independent alpha and beta components
Authors: Botta‐Dukát Zoltán
Published: April 2017

The replication principle was first proposed by Hill (1973, Ecology 54: 247– 432) as an advantageous property of his family of diversity indices. Later Jost (2007, Ecology 88: 2427– 2439) discovered that diversity measures satisfying this principle allow partitioning of gamma diversity into independent alpha and beta components by simple multiplicative partitioning. Despite the emerging agreement on measuring taxonomic beta‐diversity by multiplicative partitioning of Hill diversity, there is no consensus on how to measure functional beta diversity. Two different generalizations of Hill numbers for measuring functional diversity were proposed by Leinster and Cobbold (2011, Ecology 93: 477– 489) and Chiu and Chao (2014, PLoS One 9: e1000014). Both generalizations attempted to satisfy the generalized replication principle, but they formulate it in different ways. The aims of this paper are 1) to review approaches for measuring functional diversity in units of equivalent numbers without explicit reference to replication principle; 2) to compare the two proposed replication principle and to point out some important differences in the behavior of diversity families derived from the two principles; 3) to explore the conditions necessary for partitioning functional diversity of Leinster and Cobbold into meaningful alpha and beta components; 4) and, finally, to explore how transformation of among‐species distances into similarities influences the sensitivity of functional diversity to the scale parameter.
Learning from the past to prepare for the future: felids face continued threat from declining prey
Authors: Sandom C. J. , Faurby S. , Svenning J.‐C. , Burnham D. , Dickman A. , Hinks A. E. , Macdonald E. A. , Ripple W. J. , Williams J. , Macdonald D. W.
Published: April 2017

Many contemporary species of large‐felids (≥ 15 kg) feed upon prey that are endangered, raising concern that prey population declines (defaunation) will further threaten felids. We assess the threat that defaunation presents by investigating a late Quaternary (LQ), ‘present‐natural’ counterfactual scenario. Our present‐natural counterfactual is based on predicted ranges of mammals today in the absence of any impacts of modern humans Homo sapiens through time. Data from our present‐natural counterfactual are used to understand firstly how megafauna extinction has impacted felid communities to date and secondly to quantify the threat to large‐felid communities posed by further declines in prey richness in the future. Our purpose is to identify imminent risks to biodiversity conservation and their cascading consequences and, specifically, to indicate the importance of preserving prey diversity.

We pursue two lines of enquiry; first, we test whether the loss of prey species richness is a potential cause of large‐felid extinction and range loss. Second, we explore what can be learnt from the large‐scale large‐mammal LQ losses, particularly in the Americas and Europe, to assess the threat any further decline in prey species presents to large‐felids today, particularly in Africa and Asia.

Large‐felid species richness was considerably greater under our present‐natural counterfactual scenario compared to the current reality. In total, 86% of cells recorded at least one additional felid species in our present‐natural counterfactual, and up to 4–5 more large‐felid species in 10% of the cells. A significant positive correlation was recorded between the number of prey species lost and the number of large‐felid species lost from a cell. Extant felids most at risk include lion and Sunda clouded leopard, as well as leopard and cheetah in parts of their range. Our results draw attention to the continuation of a trend of megafauna decline that began with the emergence of hominins in the Pleistocene.
Microsurgical techniques in temporal lobe epilepsy
Authors: Alonso Vanegas Mario A. , Lew Sean M. , Morino Michiharu , Sarmento Stenio A.
Published: April 2017

Temporal lobe resection is the most prevalent epilepsy surgery procedure. However, there is no consensus on the best surgical approach to treat temporal lobe epilepsy. Complication rates are low and efficacy is very high regarding seizures after such procedures. However, there is still ample controversy regarding the best surgical approach to warrant maximum seizure control with minimal functional deficits. We describe the most frequently used microsurgical techniques for removal of both the lateral and mesial temporal lobe structures in the treatment of medically intractable temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (corticoamygdalohippocampectomy and selective amygdalohippocampectomy). The choice of surgical technique appears to remain a surgeon's preference for the near future. Meticulous surgical technique and thorough three‐dimensional microsurgical knowledge are essentials for obtaining the best results.
Subdural grid and depth electrode monitoring in pediatric patients
Authors: Skoch Jesse , Adelson P. David , Bhatia Sanjiv , Greiner Hansel M. , Rydenhag Bertil , Scavarda Didier , Mangano Francesco T.
Published: April 2017

Invasive electroencephalographic monitoring with implantable subdural electrodes and intraparenchymal depth electrodes has become a basic tenet of epilepsy surgery. Improved localization of epileptic foci justifies the secondary procedure and monitoring period in many patients. Informed use of invasive monitoring in conjunction with imaging and functional studies makes epilepsy surgery a smaller, safer, and more effective endeavor. Herein we review the history, indications, implementation, and foreseeable future of grid, strip, and depth electrode use.
WONOEP appraisal: Development of epilepsy biomarkers—What we can learn from our patients?
Authors: Jozwiak Sergiusz , Becker Albert , Cepeda Carlos , Engel Jerome , Gnatkovsky Vadym , Huberfeld Gilles , Kaya Mehmet , Kobow Katja , Simonato Michele , Loeb Jeffrey A.
Published: April 2017

Objective

Current medications for patients with epilepsy work in only two of three patients. For those medications that do work, they only suppress seizures. They treat the symptoms, but do not modify the underlying disease, forcing patients to take these drugs with significant side effects, often for the rest of their lives. A major limitation in our ability to advance new therapeutics that permanently prevent, reduce the frequency of, or cure epilepsy comes from a lack of understanding of the disease coupled with a lack of reliable biomarkers that can predict who has or who will get epilepsy.

Methods

The main goal of this report is to present a number of approaches for identifying reliable biomarkers from observing patients with brain disorders that have a high probability of producing epilepsy.

Results

A given biomarker, or more likely a profile of biomarkers, will have both a quantity and a time course during epileptogenesis that can be used to predict who will get the disease, to confirm epilepsy as a diagnosis, to identify coexisting pathologies, and to monitor the course of treatments.

Significance

Additional studies in patients and animal models could identify common and clinically valuable biomarkers to successfully translate animal studies into new and effective clinical trials.
Heritability of behavioural tolerance to high CO2 in a coral reef fish is masked by nonadaptive phenotypic plasticity
Authors: Welch Megan J. , Munday Philip L.
Published: April 2017

Previous studies have demonstrated limited potential for acclimation of adversely affected olfactory behaviours in reef fishes under elevated CO2, indicating that genetic adaptation will be required to maintain behavioural performance in the future. Adaptation depends on the presence of heritable phenotypic variation in the trait, which may differ between populations and environments. We used parent–offspring regressions to estimate the heritability (h2) of variation in behavioural tolerance to high CO2 (754 μatm) in both field‐collected and laboratory‐reared families of Acanthochromis polyacanthus. Tolerance to elevated CO2 was measured by determining the behavioural response of individuals to chemical alarm cues. Both populations exhibited high heritability of olfactory behaviour phenotype (father–mid‐offspring h2 = 0.56 & 0.65, respectively) when offspring were acutely exposed to high CO2 for 4 days. However, there was no heritability in the behavioural phenotype when juveniles were chronically exposed to high CO2 for 6 weeks in the laboratory‐reared families. Parental exposure to high CO2 during the breeding season did not alter this relationship between heritability and length of juvenile exposure to high CO2. These results demonstrate that variation in behavioural tolerance to high CO2 is heritable, but adaptive potential may be constrained by a loss of phenotypic variation when juveniles permanently experience a high‐CO2 environment, as will occur with rising CO2 levels in the ocean.
Controls on the evolution of Ediacaran metazoan ecosystems: A redox perspective
Authors: Bowyer F. , Wood R. A. , Poulton S. W.
Published: April 2017

A growing number of detailed geochemical studies of Ediacaran (635–541 Ma) marine successions have provided snapshots into the redox environments that played host to the earliest known metazoans. Whilst previous compilations have focused on the global evolution of Ediacaran water column redox chemistry, the inherent heterogeneity evident in palaeogeographically distinct environments demands a more dissected approach to better understand the nature, interactions and evolution of extrinsic controls on the development of early macrobenthic ecosystems. Here, we review available data of local‐scale redox conditions within a palaeogeographic and sequence stratigraphic framework, to explore the mechanisms controlling water column redox conditions and their potential impact on the record of metazoans. The openly connected Laurentian margin, North America (632–540 Ma) and Nama basin, Namibia (550–538 Ma), and the variably restricted Yangtze Block, South China (635–520 Ma), show continued redox instability after the first fossil evidence for metazoans. This may support opportunistic benthic colonisation during periods of transient oxygenation amidst episodic upwelling of anoxic waters beneath a very shallow, fluctuating chemocline. The first skeletal metazoans appeared under conditions of continued redox stratification, such as those which characterise the Dengying Formation of the Yangtze Block and the Kuibis Subgroup of the Nama basin. Current data, however, suggests that successful metazoan reef‐building demanded more persistent oxia. We propose that cratonic positioning and migration throughout the Ediacaran Period, in combination with gradually increasing dissolved oxygen loading, may have provided a first‐order control on redox evolution through regulating circulation mechanisms in the Mirovian Ocean. Some unrestricted lower slope environments from mid‐high latitudes benefited from sustained oxygenation via downwelling, whilst transit of isolated cratons towards more equatorial positions stifled pervasive ventilation either through ineffective surface ocean mixing, Ekman‐induced upwelling, elevated surface ocean productivity or a combination of these processes.