bluuebunny/crossref_metadata_2025 huggingface dataset:
Crossing the boundary between physical and digital: the role of boundary objects
Authors: Corsaro Daniela
Published: June 2018

Purpose

Digitalization is one of the most important phenomena that characterize the last decade – not only in business-to-consumer markets but also in business-to-business as well. The advent of digital technologies has multiplied the number and type of touchpoints between actors, thus generating new spaces of interaction where cross-boundary movements are frequent and traverse physical and digital contexts. All these elements, in turn, produce a higher need for coordination in business relationships. By using the concept of boundary objects, the purpose of this paper is to understand the main functions of boundary objects to coordinate business relationships across digital and physical contexts.

Design/methodology/approach

The empirical research is based on two case studies where the role of boundary objects is particularly emphasized: Salesforce.com and 3DiTALY. 27 qualitative interviews with key referents have been carried out. To analyze data, the authors applied a constructionist perspective based on Carlile’s (2004) framework of transferring, translating and transforming knowledge across boundaries.

Findings

The study will identify six functions that boundary objects play in coordinating business relationships across physical and digital contexts. It will also show the relevance of a mental network space of shared understanding to enable changes in the relational network space.

Practical implications

This study makes concrete the abstract idea of boundary objects. Therefore, it sheds light on the opportunity of managing strategically boundary objects in order to improve their effectiveness in digital environments.

Originality/value

The study will contribute to IMP research on b-to-b relationships by showing that, in digital contexts, boundary objects are key to coordinate interaction in space and cross-boundary movements. The study will show that once considering a digital context, the traditional functions of boundary objects in terms of transfer, translation, and transformation can be further declined into sub-functions. The study will also provide important managerial implications on how boundary objects can be strategically used by companies to increase the effectiveness of their business relationships.
The development of a collaborative framework for commissioning health and social care
Authors: Nelson Kayleigh M. , McKinnon Aimee I. , Farr Angela , Rance Jaynie Y. , Phillips Ceri J.
Published: June 2018

Purpose

The purpose of this paper is to present an evaluation of a collaborative commissioning approach to improve quality and experience and reduce cost within integrated health and social care.

Design/methodology/approach

A multi-method approach is used involving qualitative interviews, documentary analysis and non-participant observation.

Findings

The findings suggest that the approach provides a suitable framework for the collaborative commissioning of integrated health and social care services.

Research limitations/implications

Further research is now needed to provide a definitive evaluation of its value outside of Wales.

Practical implications

With the significant scrutiny on health systems, the approach demonstrates effectiveness in securing quality improvements, achievement of recognised care standards and patient outcomes, while providing scope for financial gains and a goal for stakeholders to engage in effective communication.

Originality/value

This research presents an innovative method for collaborative commissioning and reveals activities that appear to contribute to more effective commissioning processes.
Real exchange rate volatility and domestic consumption in Ghana
Authors: Njindan Iyke Bernard , Ho Sin-Yu
Published: June 2018

Purpose

This paper aims to examine the effects of exchange rate volatility on consumption by focusing on a small open sub-Saharan Africa (SSA) country, Ghana, which has experienced exchange rate volatility frequently.

Design/methodology/approach

The authors used annual data covering the period 1980-2015, the annualised variance of the real exchange rate as a measure of exchange rate volatility and a technique that is able to separate short-run effects from long-run effects.

Findings

The authors found that exchange rate volatility has negative effects on domestic consumption in the short run, which is passed on as negative long-run effects. This conclusion is unaffected by an alternative measure of exchange rate volatility and the choice of lag restrictions.

Research limitations/implications

The authors’ finding suggests that policymakers should seek to reduce or prevent exchange rate volatility by pursuing various policies including limiting foreign currency transactions within the country and promoting quality exports.

Originality/value

The extant studies have examined the effects of exchange rate volatility on consumption by considering countries in regions other than SSA. This paper focuses on a small open SSA country which has experienced exchange rate volatility frequently. Unlike most studies, this paper differentiates short-run effects from long-run effects.
Emerging trends in food packaging
Authors: Sharma Rajan , Ghoshal Gargi
Published: June 2018

Purpose

The purpose of this study is to review the recent approaches in food packaging trends to address the preferences of the modern world.

Design/methodology/approach

Recent studies in all the emerging food packaging technologies have been discussed with the examples of commercially available products.

Findings

Advanced food packaging solutions have acquired much appreciation from food industries to address the preferences of the modern world. This paper attempts to describe the current practices in food packaging with examples of commercially available products. Significant emphasis has been given on the technical aspects of the intelligent packaging components, namely, barcodes, radio frequency identification, sensors and indicators. Another distinctive area of packaging focused in this review is the importance of bioplastics due to non-degradable nature of synthetic polymers. Three major categories of biodegradable polymers, namely, polysaccharide-based materials, protein-based materials and lipid-based materials, have been discussed along with an insight about sustainable packaging and edible films and coatings.

Originality/value

Changes in the industrial & retail matters and increasing demand for fresh, safe, nutritious food are the factors owing to the new innovations in the packaging sector. Imminent packaging technologies aim at value addition involving the extension of shelf life, prevention of microbial attack, proper moisture barrier, use of carbon dioxide scavengers/emitters, ethylene scavengers, flavor absorbers, freshness indicators, biosensors and release of bioactive compounds during storage.
Evaluation of processing variables in polymer projection sintering
Authors: Nussbaum Justin , Crane Nathan B.
Published: June 2018

Purpose

Projection sintering, a system for selectively sintering large areas of polymer powder simultaneously with a high-power projector is introduced. This paper aims to evaluate the suitability of laser sintering (LS) process parameters for projection sintering, as it uses substantially lower intensities, longer exposure times and larger areas than conventional LS.

Design/methodology/approach

The tradeoffs in sintering outcomes are evaluated by creating single layer components with varied exposure times and optical intensities. Some of these components were cross-sectioned and evaluated for degree of densification, while the single-layer thickness and the maximum tensile force was measured for the rest.

Findings

Shorter exposure times and higher intensities can create thicker and therefore stronger parts than when equal energy is applied over longer exposures. This is different from LS in which energy input (Andrew’s Number) is accepted as a reliable process variable. This difference is likely because significant thermal energy is lost from the sintering region during the exposure time – resulting in reduced peak temperatures. These thermal losses can be offset by imparting additional energy through increased exposure time or light intensity.

Practical implications

Most methods for evaluating LS process parameters, such as the energy melt ratio and Andrew’s Number, estimate energy input from basic process parameters. These methods do not account for thermal losses and assume that the powder absorbs all incident light. These methods become increasingly inaccurate for projection sintering with visible light where exposure times are much higher (>1s) and a larger portion of the light is reflected from the power’s surface. Understanding the appropriate sintering criteria is critical for the development of long-exposure sintering.

Originality/value

A new method of selectively sintering large areas is introduced that could sinter a wider variety of materials by enabling longer sintering times and may increase productivity relative to LS. This work shows that new processing parameters are required for projection sintering as traditional LS process parameters are inadequate.
Inducing effects of cellulosic hydrolysate components of lignocellulose on cellulosome synthesis in Clostridium thermocellum
Authors: Li Renmin , Feng Yingang , Liu Shiyue , Qi Kuan , Cui Qiu , Liu Ya‐Jun
Published: June 2018

Cellulosome is a highly efficient supramolecular machine for lignocellulose degradation, and its substrate‐coupled regulation requires soluble transmembrane signals. However, the inducers for cellulosome synthesis and the inducing effect have not been clarified quantitatively. Values of cellulosome production capacity (CPC) and estimated specific activity (eSA) were calculated based on the primary scaffoldin ScaA to define the stimulating effects on the cellulosome synthesis in terms of quantity and quality respectively. The estimated cellulosome production of Clostridium thermocellum on glucose was at a low housekeeping level. Both Avicel and cellobiose increased CPCs of the cells instead of the eSAs of the cellulosome. The CPC of Avicel‐grown cells was over 20‐fold of that of glucose‐grown cells, while both Avicel‐ and glucose‐derived cellulosomes showed similar eSA. The CPC of cellobiose‐grown cells was also over three times higher than glucose‐grown cells, but the eSA of cellobiose‐derived cellulosome was 16% lower than that of the glucose‐derived cellulosome. Our results indicated that cello‐oligosaccharides played the key roles in inducing the synthesis of the cellulosome, but non‐cellulosic polysaccharides showed no inducing effects.
Risk factors for developing diabetes after 3 years among community‐dwelling elderly with impaired fasting glucose
Authors: Zhang Wen , Yang Xiaolong , Han Peipei , Ma Yixuan , Fu Liyuan , Jia Liye , Yu Hairui , Chen Xiaoyu , Wang Lu , Hou Lin , Yu Xing , Kohzuki Masahiro , Guo Qi
Published: June 2018

Background

The aim of the present study was to examine the risk factors for developing diabetes after 3 years in an elderly Chinese suburban population with impaired fasting glucose (IFG).

Methods

The study population comprised residents of the Hangu area of Tianjin, China, with IFG, aged ≥60 years, who joined the national free physical examination program (n = 328; mean [±SD] age 68.0 ±6.1 years; 48.2% men). Diabetes was defined by self‐report of a physician's diagnosis or fasting plasma glucose (FPG) ≥7.0 mmol/L; IFG was defined as FPG ≥5.6 and < 7.0 mmol/L. Risk factors of incident diabetes at the 3‐year follow‐up were analyzed individually using logistic regression analysis.

Results

Between baseline and the 3‐year follow‐up, 56 subjects with IFG at baseline had developed diabetes. After multivariate adjustment for demographic and clinical factors, the incidence of diabetes increased with higher FPG (odds ratio [OR] 9.30, 95% confidence interval [CI] 2.84–30.48), but decreased with the grip strength/weight ratio (OR 0.88, 95% CI 0.82–0.94). Moreover, the combination of higher FPG and lower grip strength/weight was associated with a higher incidence of diabetes than higher FPG only or lower grip strength/weight (P < 0.05).

Conclusion

The present study indicates that higher FPG and lower muscle strength are associated with glycemic deterioration among subjects with IFG after 3 years. The results suggest that not only glucose levels, but also physical performance may be useful markers of the risk of diabetes in this population.
Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice
Authors: Yoshida Shohei , Yamahara Kosuke , Kume Shinji , Koya Daisuke , Yasuda‐Yamahara Mako , Takeda Naoko , Osawa Norihisa , Chin‐Kanasaki Masami , Adachi Yusuke , Nagao Kenji , Maegawa Hiroshi , Araki Shin‐ichi
Published: June 2018

Extending healthy lifespan is an emerging issue in an aging society. This study was designed to identify a dietary method of extending lifespan, promoting renoprotection, and preventing muscle weakness in aged mice, with a focus on the importance of the balance between dietary essential (EAAs) and nonessential amino acids (NEAAs) on the dietary restriction (DR)‐induced antiaging effect. Groups of aged mice were fed ad libitum, a simple DR, or a DR with recovering NEAAs or EAAs. Simple DR significantly extended lifespan and ameliorated age‐related kidney injury; however, the beneficial effects of DR were canceled by recovering dietary EAA but not NEAA. Simple DR prevented the age‐dependent decrease in slow‐twitch muscle fiber function but reduced absolute fast‐twitch muscle fiber function. DR‐induced fast‐twitch muscle fiber dysfunction was improved by recovering either dietary NEAAs or EAAs. In the ad libitum‐fed and the DR plus EAA groups, the renal content of methionine, an EAA, was significantly higher, accompanied by lower renal production of hydrogen sulfide (H2S), an endogenous antioxidant. Finally, removal of methionine from the dietary EAA supplement diminished the adverse effects of dietary EAA on lifespan and kidney injury in the diet‐restricted aged mice, which were accompanied by a recovery in H2S production capacity and lower oxidative stress. These data imply that a dietary approach could combat kidney aging and prolong lifespan, while preventing muscle weakness, and suggest that renal methionine metabolism and the trans‐sulfuration pathway could be therapeutic targets for preventing kidney aging and subsequently promoting healthy aging.
Skeletal unit construction of rat mandible based on the masticatory muscle anatomy and double microcomputed tomography
Authors: Kim Hak‐Jin , Park Kyeong‐Mee , Tak Hye‐Jin , Choi Ji Wook , Kang Sang‐Hoon , Park Wonse , Bertin Helios , Corre Pierre , Lee Sang‐Hwy
Published: June 2018

This study aimed to divide the mandible into skeletal units based on three‐dimensional (3D) muscular anatomy with microcomputed tomography (micro‐CT) of Sprague–Dawley rat. Five normal rats were micro‐CT scanned at 12 weeks of age before and after contrast enhancements for the masticatory muscles. Three‐dimensional reconstruction of the mandible was performed from the initial micro‐CT images, followed by segmentation of the masticatory muscles using the second enhanced micro‐CT data. Bone and muscle models were superimposed based on the teeth and bony structures to evaluate muscular orientation and attachment. The mandible was divided into skeletal units using the bony structures and muscle attachments. The mandibular foramen and mental foramen were adopted as the reference points based on their anatomical and developmental significance. The skeletal units consisted of the condylar, coronoid, angular, body and symphyseal units. Further evaluation of these units in relation to development, growth, and other biology and medicine will be helpful in elucidating their biological identities.
Earnings Management by Non‐profit Organisations: Evidence from UK Charities
Authors: Nguyen Tam , Soobaroyen Teerooven
Published: June 2018

Informed by stakeholder theory and resource dependence theory, this paper investigates whether UK charities are engaged in earnings management practices. Based on a sample of 1414 charities over a five‐year period (2008–2012) the study firstly finds that UK charities use discretionary accruals to drive their financial results towards a zero surplus/deficit; this result also reveals that the distribution of reported earnings around zero is prevalent amongst UK charities. In addition, in contrast to prior findings, the empirical results point to a significant association between leverage and earnings management behaviour by charities. Lastly, this study finds that the practice of earnings management is influenced by non‐profit organisational size.
Character definition and tempus optimum in comparative chondrocranial research
Authors: Werneburg Ingmar , Yaryhin Oleksandr
Published: June 2018

Here, we define a research program using primordial skull characters for broad scale phylogenetic comparisons, particularly for amniotes. There are many chondrocranium descriptions in the literature, encompassing many clades of vertebrates. The definition of a comparable “tempus optimum” for fully formed chondrocrania, as developed herein, will enable discrete character definition in the sense of phylogenetic systematics. The “tempus optimum” is a time period in which the nose region shows full chondrification and the basicranium has not yet changed in its anatomy by ossification processes. For studies on heterochrony, changes in the developmental timing through evolution, the available data in the literature are insufficient. Anatomical standardizations, traceable methodological approaches and clear definitions of comparable developmental stages are needed. Moreover, for profound homology assertions of chondrocranial structures, ontogeny needs to be traced from early mesenchymal condensation, through several stages of cartilage development, up to postnatal stages, in which ossifications are already present. A holistic observation, including hard and soft tissue anatomy, is of paramount importance to generate hypotheses of homology with much explanatory power and to derive conclusions on functional morphology. For that, traditional histological methodology is needed. We exemplify the suggested approach in two case studies on the disputed laterosphenoid in turtles and crocodiles and on the homology of pila antotica in a pleurodire turtle, and, using here defined criteria, we formulate hypotheses on their homology.
Prescription patterns of angiotensin‐converting enzyme inhibitors for various indications: A UK population‐based study
Authors: Mahmoudpour Seyed Hamidreza , Asselbergs Folkert W. , Souverein Patrick C. , de Boer Anthonius , Maitland‐van der Zee Anke H.
Published: June 2018

Aim

Angiotensin‐converting enzyme inhibitors (ACEIs) are widely prescribed for several cardiovascular indications. This study investigated patterns of ACEI use for various indications.

Methods

A descriptive, retrospective population‐based study was conducted using data from the UK Clinical Practice Research Datalink. Patients starting ACEIs (2007–2014) were selected and ACEI indications were retrieved from electronically recorded medical records. Stratified by indication, we distinguished between persistent and nonpersistent ACEI use, considering a 6‐month interval between two prescription periods as a maximum for persistent use. Five‐year persistence rates for various indications were calculated using the Kaplan–Meier method and compared in a log‐rank test. Nonpersistent users were subdivided into three groups: (i) stop; (ii) restart; and (iii) switch to an angiotensin II‐receptor blocker. Patients who received ACEIs for hypertension who switched to other classes of antihypertensive medications were further investigated.

Results

In total, 254 002 ACEI initiators were identified with hypertension (57.6%), myocardial infarction (MI; 4.2%), renal disease (RD; 3.7%), heart failure (HF; 1.5%), combinations of the above (17.2%) or none of the above (15.8%). Five‐year persistence rates ranged from 43.2% (RD) to 68.2% (MI; P < 0.0001). RD and HF patients used ACEIs for the shortest time (average 23.6 and 25.0 months, respectively). For the nonpersistent group, the percentage of switchers to angiotensin II‐receptor blockers ranged from 27.6% (RD) to 42.2% (MI) and the restarters ranged from 15.0% (HF) to 18.1% (group without indication).

Conclusions

Depending on the indication, there are various rates of ACEI nonpersistence. Patients with RD are most likely to discontinue treatment.
Activating the pregnane X receptor by imperatorin attenuates dextran sulphate sodium‐induced colitis in mice
Authors: Liu Meijing , Zhang Guohui , Zheng Chunge , Song Meng , Liu Fangle , Huang Xiaotao , Bai Shasha , Huang Xinan , Lin Chaozhan , Zhu Chenchen , Hu Yingjie , Mi Suiqing , Liu Changhui
Published: June 2018

Background and Purpose

Activation of the human pregnane X receptor (PXR; NR1I2) has potential therapeutic uses for inflammatory bowel disease (IBD). Imperatorin (IMP), a naturally occurring coumarin, is the main bioactive ingredient of Angelica dahurica Radix, which is regularly used to treat the common cold and intestinal disorders. However, there are no data on the protective effects of IMP against IBD.

Experimental Approach

The effects of IMP on PXR‐modulated cytochrome P450 3A4 (CYP3A4) expression were assessed using a PXR transactivation assay, a mammalian two‐hybrid assay, a competitive ligand‐binding assay, analysis of CYP3A4 mRNA and protein expression levels and measurement of CYP3A4 activity using a cell‐based reporter gene assay and in vitro model. The inhibitory effects of IMP on NF‐κB activity were evaluated by a reporter assay and NF‐κB p65 nuclear translocation. The anti‐IBD effects of IMP were investigated in a dextran sulphate sodium (DSS)‐induced colitis mouse model. Colon inflammatory cytokines were assessed by elisa.

Key Results

IMP activated CYP3A4 promoter activity, recruited steroid receptor coactivator 1 to the ligand‐binding domain of PXR and increased the expression and activity of CYP3A4. PXR knockdown substantially reduced IMP‐induced increase in CYP3A4 expression. Furthermore, IMP‐mediated PXR activation suppressed the nuclear translocation of NF‐κB and down‐regulated LPS‐induced expression of pro‐inflammatory genes. Nevertheless, PXR knockdown partially reduced the IMP‐mediated inhibition of NF‐κB. IMP ameliorated DSS‐induced colitis by PXR/NF‐κB signalling.

Conclusions and Implications

IMP acts as a PXR agonist to attenuate DSS‐induced colitis by suppression of the NF‐κB‐mediated pro‐inflammatory response in a PXR/NF‐κB‐dependent manner.
Digital third parties: Understanding the technological challenge to Canada's third party advertising regime
Authors: Small Tamara A.
Published: June 2018

Some scholars proclaim that social media can make third party advertising regulations “technologically obsolete.” Since social media are essentially free, financial resources are no longer an obstacle to the participation in elections. These claims, however, lack empirical consideration. Using original data on third party election advertising from 2004 ‐ 2015, this article argues that digital technologies have not made advertising regulations obsolete. Analysis shows that third parties are increasingly engaged in paid internet advertising. For many third parties, money matters in the digital age as it did in the broadcast age.
Policy versus practice: Third party behaviour in Canadian elections
Authors: Lawlor Andrea , Crandall Erin
Published: June 2018

Third party campaigners are widely noted to have the power to change the landscape of an election. Yet, in Canada, we know little about whether there is consistency behind third parties' motivations, expectations and strategies, or how these motivations parse with those of the legislators who are attempting to regulate their behaviour. This article explores these factors using data from Canadian federal elections from 2004 to 2015. Merging qualitative interviews and survey data of third parties with quantitative evaluations of third party and political party campaign spending, we assess whether the strategic motivations of third parties reflect the intentions and design of campaign policies that regulate their actions. The United Kingdom regulatory regime is briefly reviewed as an example of an alternative policy approach.
Third party political participation and anti‐collusion rules
Authors: Pal Michael
Published: June 2018

One of the enduring questions regarding third parties is how to prevent collusion between them and political parties. Collusion raises the spectre of third parties being used as vehicles to evade the spending and contribution limits imposed on political parties. I will argue in this article that federal election laws are inadequate at deterring collusion. The episode involving the “HarperPAC” and similar groups around the 2015 election helped to shine a spotlight on the vulnerabilities of the Canada Elections Act. I argue that the model deployed by the U.S. Federal Election Commission to regulate independent expenditures represents a promising path for reform if carefully adapted to the Canadian context.
Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer
Authors: Dong Dong , Jia Li , Zhang Lufang , Ma Na , Zhang Aimin , Zhou Yunli , Ren Li
Published: June 2018

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.9), the most frequently used biomarker for PDAC, is not sensitive and specific enough for the detection of the disease. This study aimed to evaluate serum periostin (POSTN) and CA242 as potential diagnostic biomarkers complementing CA19.9 in detecting pancreatic cancer. Blood samples were from 362 participants, including 213 patients with different stages of PDAC, 75 patients with benign pancreatic disease, and 74 healthy individuals. All samples were randomly divided into a training set and a validation set. Carbohydrate antigen 19.9, CA242, POSTN, as well as carcinoembryonic antigen, were measured by ELISA or automated immunoassay. The receiver operating characteristic curve analysis revealed that the performance of CA19.9 in the validation group were improved by the marker panel composed of CA19.9, POSTN, and CA242, to discriminate early stage PDAC not only from healthy controls (area under the curve [AUC]CA19.9 = 0.94 vs AUCCA19.9 + POSTN + CA242 = 0.98, P < .05) but also from benign conditions (AUCCA19.9 = 0.87 vs AUCCA19.9 + POSTN + CA242 = 0.90, P < .05). In addition, POSTN retained significant diagnostic capabilities to distinguish PDAC CA19.9‐negative from healthy controls (AUCPOSTN = 0.87) as well as from benign conditions (AUCPOSTN = 0.84) in the whole set. This study suggested that POSTN and CA242 are potential diagnostic serum biomarkers complementing CA19.9 in detecting early pancreatic cancer.
Interindividual differences in the clinical effectiveness of liraglutide in Type 2 diabetes: a real‐world retrospective study conducted in Spain
Authors: Gomez‐Peralta F. , Lecube A. , Fernández‐Mariño A. , Alonso Troncoso I. , Morales C. , Morales‐Pérez F. M. , Guler I. , Cadarso‐Suárez C.
Published: June 2018

Aims

To study the response of clinical variables (HbA1c, body weight, lipid profile and blood pressure) over 24 months of liraglutide treatment in a real‐world clinical setting, and to describe the evolution of HbA1c and body weight reduction in response to liraglutide treatment by employing generalized additive mixed models (GAMMs).

Methods

We included people aged ≥ 18 years with Type 2 diabetes mellitus that initiated liraglutide treatment between November 2011 and May 2015. Demographic and clinical data were retrieved retrospectively over 24 months from electronic medical records with a median duration of observation of 7.0 (IQR 3.0–12.0) months.

Results

Individuals that initiated liraglutide therapy were obese (BMI 39.1 kg/m2), with inadequate HbA1c (68 mmol/mol [8.4%]), blood pressure and lipid levels. Upon liraglutide treatment, HbA1c, body weight, mean systolic and diastolic blood pressure, and lipid levels decreased gradually. GAMMs demonstrated that longer treatment with liraglutide was a predictor of improved HbA1c response, whereas higher baseline HbA1c, longer Type 2 diabetes duration and treatment with insulin were predictors of worse HbA1c response. Higher baseline weight, longer treatment with liraglutide and the interaction between metformin and time were predictors of improved weight response.

Conclusions

In this real‐world study, we showed the effectiveness of liraglutide in improving body weight, HbA1c, mean systolic and diastolic blood pressure, and lipid levels. GAMMs indicated that baseline HbA1c and weight, time of treatment with liraglutide, diabetes duration and the use of metformin or insulin are predictors of clinical response to liraglutide.
Plasma levels of free fatty acids correlate with type 2 diabetes mellitus
Authors: Spiller Sandro , Blüher Matthias , Hoffmann Ralf
Published: June 2018

Aims

Free fatty acids (FFA) mediate adverse metabolic effects such as downregulated carbohydrate metabolisms, providing causal links between obesity and the development of type 2 diabetes mellitus (T2DM). Here, we investigated the plasma concentrations of FFA alone and in combination with protein glycation as potential diagnostic and prognostic biomarkers of T2DM.

Materials and methods

EDTA‐plasma obtained from 48 newly diagnosed male T2DM patients, 48 long‐term controlled (24 male and 24 female) T2DM patients, 20 prediabetic male T2DM patients and two age‐matched control cohorts (48 non‐diabetic (ND) men; 24 male and 24 female ND partipants) were analysed for a set of clinical parameters including FFA. Glycation sites were quantified after tryptic digestion using tandem mass spectrometry.

Results

Median plasma concentrations of FFA were almost three‐fold higher in samples obtained from newly diagnosed (long‐term controlled) T2DM patients than in those obtained from the control group, providing diagnostic sensitivity (SN) of 92% (85%) and specificity (SP) of 90% (88%). When combined with the glycation level of lysine‐141 of haptoglobin, diagnostic accuracy improved further for newly diagnosed (SN, 94%; SP 96%) and long‐term controlled (SN, 85%; SP, 94%) T2DM patients (HbA1c: SN, 88%; SP, 96%). A prospective pilot study evaluating the prognostic value revealed initially low FFA levels for pre‐diabetic patients that increased in the following four years in patients whose prediabetic state worsened or who developed T2DM.

Conclusions

FFA levels are elevated in newly diagnosed and long‐term controlled T2DM patients, providing high diagnostic accuracy of 87% and 91%, respectively, which improved further when combined with the glycation degree of lysine‐141 in haptoglobin. Additionally, FFA showed higher mean fold‐changes than HbA1c or FPG in subjects developing T2DM, indicating higher sensitivity towards the progression of the disease.
Left atrial function: Correlation with left ventricular function and contractile reserve in patients with hypertension
Authors: Fung Matle J. , Thomas Liza , Leung Dominic Y.
Published: June 2018

Aims

Alterations in left atrial (LA) and left ventricular (LV) function have been documented in hypertensive patients. However, the correlation of LA with LV functional changes has not been established. Using normotensive controls, we examined LA functional changes in hypertensive patients by strain deformation analysis, and their relationship to LV functional changes including contractile reserve (CR).

Methods

One hundred and sixteen patients (61 men, aged 57.6 ± 9.1 years, 67 with hypertension) underwent dobutamine echocardiography. Patients with significant coronary or valvular disease, previous myocardial infarction or coronary revascularization, and diabetes were excluded. LA reservoir (Ɛs), conduit (Ɛe), and atrial contractile (Ɛa) strain were measured at rest. LV global longitudinal strain (GLS) and ejection fraction (LVEF) were measured at rest and at low‐dose dobutamine. LV CR was calculated as the difference in GLS and LVEF between the low dose and their corresponding resting values.

Results

Hypertensive patients, compared with controls, had significantly impaired LA Ɛs (30.7 ± 3.9% vs 42.4 ± 4.9%), Ɛe (16.2 ± 4.1% vs 22.5 ± 5.5%), and Ɛa (14.5 ± 4.1% vs 19.9 ± 5.0%, all P < .001) strain. All LA phasic strain correlated with LV GLS at rest, at low‐dose dobutamine, and LV CR. There was no correlation between LA strain and LVEF or LV CR assessed by LVEF. LV GLS and LAVImax were the strongest independent determinants for LA Ɛs/Ɛe and LA Ɛa, respectively.

Conclusion

Compared to controls, hypertensive patients had impaired LA strain, which correlated with LV GLS and CR. LV GLS and LAVImax were the strongest independent determinants for LA Ɛs/Ɛe and LA Ɛa, respectively, independent of BP and LVMi.
Accumulation of NO2− during periods of drying stimulates soil N2O emissions during subsequent rewetting
Authors: Liu S. , Schloter M. , Brüggemann N.
Published: June 2018

Rewetting of soil might contribute considerably to the annual production of nitrous oxide (N2O) in ecosystems subjected to long dry periods. Therefore, it is crucial to elucidate the most important factors responsible for large pulses of N2O with rewetting. In this study, we carried out a series of rewetting experiments with soil samples collected from upland and riparian forest, grassland and arable land. We analysed the dynamics of ammonium (NH4+), nitrite (NO2−), nitrate (NO3−) and dissolved organic matter (DOM) of air‐dried soil samples after rewetting. We also analysed the effects of sterilization of soil samples by γ‐irradiation on N2O production with rewetting. Furthermore, we explored the effects of rewetting and sterilization on the isotopic composition of N2O in the different soil samples. The grassland soil produced the largest amount of N2O (64.1 μg N kg−1) in 1 hour on rewetting, followed by upland forest soil, whereas it was least for soils from riparian forest and arable land. Gamma irradiation, however, decreased soil N2O production from forest soil samples by 30–90% after rewetting, but increased N2O production in grassland and arable land soils three‐fold and two‐fold, respectively. Correlation analysis revealed that NO2− concentration in the soil samples at the time of rewetting was the most relevant factor that explained soil N2O production after rewetting. Furthermore, the addition of NO2− before rewetting increased N2O production during rewetting more than with additions of NO3− and NH4+ in all soil samples. The 15N site preference values of N2O produced after rewetting were close to 0‰, indicating a denitrification‐related production process according to the classical view. However, additional abiotic processes responsible for soil N2O production during rewetting cannot be excluded.

Highlights

Mechanisms responsible for large N2O production during rewetting of soil are not well understood.

Nitrite content in dry soil was strongly correlated with N2O production after rewetting.

The 15N site preference of the N2O produced was close to 0‰ after rewetting.

Additional abiotic processes could have contributed to N2O formation from NO2−.
Digital ITEMS Module 1: Reliability in Classical Test Theory
Authors: Lewis Charlie , Chajewski Michael , Rupp André A.
Published: June 2018

In this ITEMS module, we provide a two‐part introduction to the topic of reliability from the perspective of classical test theory (CTT). In the first part, which is directed primarily at beginning learners, we review and build on the content presented in the original didactic ITEMS article by Traub and Rowley (1991). Specifically, we discuss the notion of reliability as an intuitive everyday concept to lay the foundation for its formalization as a reliability coefficient via the basic CTT model. We then walk through the step‐by‐step computation of key reliability indices and discuss the data collection conditions under which each is most suitable. In the second part, which is directed primarily at intermediary learners, we present a distribution‐centered perspective on the same content. We discuss the associated assumptions of various CTT models ranging from parallel to congeneric, and review how these affect the choice of reliability statistics. Throughout the module, we use a customized Excel workbook with sample data and basic data manipulation functionalities to illustrate the computation of individual statistics and to allow for structured independent exploration. In addition, we provide quiz questions with diagnostic feedback as well as short videos that walk through sample exercises within the workbook.
Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus
Authors: Strzelczyk Adam , Kay Lara , Bauer Sebastian , Immisch Ilka , Klein Karl Martin , Knake Susanne , Kowski Alexander , Kunz Rhina , Kurlemann Gerhard , Langenbruch Lisa , Möddel Gabriel , Müller‐Schlüter Karen , Reif Philipp S. , Schubert‐Bast Susanne , Steinhoff Bernhard J. , Steinig Isabel , Willems Laurent M. , von Podewils Felix , Rosenow Felix
Published: June 2018

Objective

The objective of this study was to evaluate effectiveness, retention, and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in clinical practice.

Methods

A multicenter, retrospective cohort study recruiting all patients that started BRV in 2016 and 2017.

Results

A total of 61 patients (mean age = 29.8, range = 9‐90 years, 41 female [67%]) were treated with BRV. They were difficult to control, with 2.4 failed antiepileptic drugs (AEDs) in the past, taking 1.9 AEDs on average at baseline. The length of exposure to BRV ranged from 7 days to 24 months, with a mean retention time of 7.9 months, resulting in a total exposure time to BRV of 483 months. The retention rate was 82% at 3 months and 69% at 6 months. Efficacy at 3 months was 36% (50% responder rate), with 25% seizure‐free for 3 months. Patients with juvenile myoclonic epilepsy showed a responder rate of 60%, with 40% being free of any seizures. Long‐term 50% responder rate was present in 17 patients (28%; 11 seizure‐free [18%]) for >6 months and in 14 patients (23%; 10 seizure‐free [16%]) for >12 months. Treatment‐emergent adverse events were observed in 26% of the patients, with the most common being somnolence, ataxia, and psychobehavioral adverse events. Use of intravenous BRV with bolus injection of 200‐300 mg in two females with absence status epilepticus was well tolerated, but did not result in cessation of status epilepticus.

Significance

Use of BRV in GGE is well tolerated, and 50% responder rates are similar to those observed in the regulatory trials for focal epilepsies. An immediate switch from levetiracetam (LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV, and a switch to BRV can be considered in patients with LEV‐induced adverse events.
Why are female color polymorphisms rare in territorial damselflies?
Authors: Cabezas Castillo María Beatriz , Grether Gregory F.
Published: June 2018

In nonterritorial damselflies, females often come in multiple color morphs, perhaps because females with rare colors experience reduced sexual harassment, and thus have a frequency‐dependent fitness advantage, compared to females of the most common color morph, but such polymorphisms are rare in territorial species. We consider three hypotheses to explain the rarity of female color polymorphisms in territorial species: (a) misdirected male aggression, (b) poor male mate recognition, and (c) low mating harassment rates. The first hypothesis has some empirical support, and can account for the absence of andromorphs (i.e., females that resemble males), but does not explain the absence of multiple heteromorphs. We tested the second hypothesis by presenting females of two novel color morphs (green‐ or red‐banded abdomens) to territorial male Hetaerina capitalis. Females of both novel color morphs elicited fewer sexual responses than control females, and the red morph occasionally elicited aggressive responses. These results indicate that novel female color morphs would experience reduced mating harassment in this species, contradicting the hypothesis that male mate recognition is too poorly developed to reduce harassment of novel female morphs. By process of elimination, the third hypothesis, that harassment rates are too low in territorial species to provide rare female morphs a fitness advantage, is favored, but remains untested. Our findings also suggest that the common practice of color‐marking odonates for behavioral research is likely to interfere with mate choice, as has long been known to be the case in birds.
The catalytic effect of internationalization on innovation
Authors: Chang Ching‐Hsing , Chang Ching‐Hung , Hsu Pi‐Kun , Yang Sheng‐Yung
Published: June 2018

This paper examines how internationalization spurs corporate innovation. Internationalization heightens the competitive environment of firms, while increasing financial flexibility. The increased competition reduces agency problems and motivates innovation projects which are supported by improved financial flexibility. We obtain robust evidence with the difference‐in‐differences and instrumental variable approaches. The passage of antitakeover laws and the 1989 Loma Prieta earthquake are treated as exogenous variations to corporate governance; shocks on firm capital supply measured by mutual fund redemptions are also considered. A less positive finding is that internationalization motivates firms to focus on the appropriability of innovation rather than on basic research.
The viability and necessity of APRN‐led care models in the clinical management of haemophilia and other inherited bleeding and clotting disorders
Authors: Federizo A. , Shullick M. , Witkop M.
Published: June 2018

A growing and ageing haemophilia treatment centre (HTC) population, as well as a glaring shortage of adult haematologists available for the clinical management of persons with haemophilia (PWH), has resulted in significant care gaps in the United States. In response, various advanced practice registered nurse (APRN)‐based models have been adopted across the country to counteract a deficit in haematologist resources for adult PWH. These models in the management of PWH have demonstrated competency and efficiency in the care of patients with haemophilia, offering a viable solution in areas where haematologist resources are limited and assure quality care provision, most notably in rural areas. The available literature indicates equivalence in terms of clinical outcomes, patient satisfaction and elements of healthcare service utilization. With continued support in current clinical guidelines and institutional contributions in the form of residency and fellowship programmes, the robust successes of APRN models for the clinical management of PWH can be maintained and expanded well into the foreseeable future.
Strength in diversity: Phenotypic, functional, and molecular heterogeneity within the memory B cell repertoire
Authors: Good‐Jacobson Kim L.
Published: June 2018

The vast majority of vaccines exploit antibody memory to induce lasting immunity. Memory B cells are generated during the initial response to infection, but persist long after the infection has cleared. Immune memory success relies on its adaptability: in response to different pathogens, variants of a single pathogen, and in balancing persistence with reactivation and plasma cell differentiation. This is likely achieved by producing a B cell memory population that is highly diverse, and recent work has highlighted the importance of memory B cell subsets in mediating the dichotomous roles of the population. This review will detail the characterization, function and both intrinsic and extrinsic regulation of different memory B cell subsets: memory B cell precursors within the germinal center, phenotypic, and functional heterogeneity of the memory B cell population, and memory B cell subsets that reside in tissues. In particular, understanding the genetic and epigenetic regulation of memory B diversity may be critical for gaining insight into B cell memory responses to pathogens that have evaded effective vaccine design. Therefore, there is a vital need to understand the mechanisms underlying the origin, function and translational potential of the heterogeneity within the memory B cell population.
Human adaptive immune receptor repertoire analysis—Past, present, and future
Authors: Nielsen Sandra C. A. , Boyd Scott D.
Published: June 2018

The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane‐bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in human biology because they are generated by combinatorial rearrangement of the genomic DNA. The diversity of receptors so generated in populations of lymphocytes enables the human immune system to recognize antigens expressed by pathogens, but also underlies the pathological specificity of autoimmune diseases and the mistargeted immunity in allergies. Several recent technological developments, foremost among them the invention of high‐throughput DNA sequencing instruments, have enabled much deeper and thorough evaluation of clones of human B cells and T cells and the antigen receptors they express during physiological and pathogenic immune responses. The evolutionary struggles between host adaptive immune responses and populations of pathogens are now open to greater scrutiny, elucidation of the underlying reasons for successful or failed immunity, and potential predictive modeling, than ever before. Here we give an overview of the foundations, recent progress, and future prospects in this dynamic area of research.
Bohemian T cell receptors: sketching the repertoires of unconventional lymphocytes
Authors: Schattgen Stefan A. , Thomas Paul G.
Published: June 2018

Over the last several decades, novel populations of unconventional T cells have been identified; defined by an invariant (or nearly invariant) T cell receptor (TCR) with a fixed specificity to non‐canonical antigens and major histocompatibility (MHC) molecules, they form large, functionally monoclonal populations tasked with surveying for their specific antigens. With residence in both lymphoid and non‐lymphoid tissues coupled with their ability to rapidly produce a spectrum of cytokines and effector molecules, the unconventional T cells are poised as some of the first responders to infection/damage and are thought to provide critical coverage before more focused, conventional T cell responses are mobilized. However, new technologies for the measurement and characterization of TCR repertoires have identified an underappreciated amount of TCR diversity in the unconventional T cells. In many cases, the specificities of these diverse TCRs converge on the same or similar antigens as their invariant counterparts, while others have yet to be defined. Here, we will review the current knowledge of the TCR repertoires of unconventional T cells and discuss how repertoires might be used as a framework for their organization, and further our understanding of their role not only during an immune response, but also their contribution in maintaining homeostasis.