bluuebunny/crossref_metadata_2025 huggingface dataset:
Broker-dealers need to respond to recent focus on cybersecurity threats
Authors: Petron David , Wolk Michael , McNicholas Edward
Published: August 2014

Purpose

– To alert broker-dealers to several regulatory developments relating to cybersecurity threats.

Design/methodology/approach

– Reviews four regulatory developments in the cybersecurity area and provides several steps broker-dealers should undertake to review and improve their cybersecurity and information technology protocols and practices.

Findings

– While FINRA’s new cybersecurity sweep appears to be an exploratory and learning exercise to obtain regulatory knowledge and intelligence, firms should be cognizant of the fact that both FINRA and the SEC have imposed significant sanctions against Firms when it has found inadequate cyber security policies and procedures.

Practical implications

– Broker-dealers should review the White House’s recent Framework for Improving Critical Infrastructure Cybersecurity and evaluate their own cybersecurity preparedness under the key areas of the Framework.

Originality/value

– Practical guidance from experienced privacy and securities regulatory lawyers that consolidates several recent developments in one piece.
Identifying upstream factors using the community readiness model
Authors: J. Kelly Kathleen , Stanley Linda
Published: August 2014

Purpose

– The purpose of this paper is to, with increasing recognition of the importance of upstream factors in individual behavior, provide an example of how the Community Readiness Model (CRM) was used as a tool to understand the barriers within the broader environment to achieving reductions in the use of alcohol by college students and how this resulted in identifying upstream social marketing strategies. Downstream social marketing approaches have been broadly implemented on college campuses to curb alcohol use and binge drinking, with mixed results.

Design/methodology/approach

– Using the CRM protocol, assessments to measure the community readiness to address issues related to college alcohol use were conducted for each of 12 campuses belonging to a Midwestern state university. Six key informants at each campus were interviewed. Interviews were scored for each of six dimensions, and they were also analyzed for themes. Results were then used in a workshop to develop action plans based on social marketing principles.

Findings

– All campuses received high scores for the efforts dimension and, to a lesser extent, resources. However, leadership readiness levels varied significantly across campuses, while community climate and knowledge of the issue readiness levels were relatively low. Top leadership and faculty were identified by campuses as specific areas to target using social marketing principles.

Originality/value

– The CRM is an accessible and inexpensive method for gathering data on upstream factors related to social issues, such as college drinking. It can be used in conjunction with other data gathering tools (e.g. prevalence surveys) to better understand the macroenvironment in which behavior takes place.
Changes in TCR of amorphous Ni–P resistive films as a function of thermal stabilization parameters
Authors: Kowalik P. , Pruszowski Z. , Kulawik J. , Czerwiński Andrzej , Pluska Mariusz
Published: August 2014

Purpose

– This paper aims to select parameters such as temperature thermal stability and temperature coefficient of resistance (TCR) for Ni–P resistive alloys obtained by electroless metallization. Ni–P alloys are used in the manufacture of precision resistors characterized by TCR in the range of ± 10 ppm/K. The correlation of the technological parameters with the electrical properties of resistors enables the accurate prediction of the TCR resistors.

Design/methodology/approach

– The Ni–P layers were obtained by a continuous process at about 373 K in a solution with the acidity of pH = 2 and then dried for two hours at 393 K. Subsequently, the Ni–P layer was stabilized for two hours in the temperature range of 453-533 K. Resistance was measured with an accuracy of 1 mΩ. TCR was determined with an accuracy of 1 ppm/K in the temperature range 298-398 K. In the next stage of the investigation, the increase in TCR of the Ni–P alloy was correlated with the increase in stabilization temperature. Scanning electron microscope images of the alloy surface were studied to assess grain sizes and to relate the average grain size with TCR values of resistive alloys. The X-ray diffraction analysis was performed to determine the crystallization temperature of Ni–P alloy.

Findings

– The conducted investigation showed that the TCR increase in alloy is a linear function of stabilization temperature in the temperature range in which transition from amorphous phase to crystalline phases did not occur. TCR increase in Ni–P alloy arises from the increase of average size of grains resulting in decrease of scattering of electrons on grain boundaries. The analysis of alloy composition in chosen fragments of surface shows inhomogeneity growing with decreasing analyzed surface dimensions which proves that, before the stabilization, the structural arrangement of alloy is inconsiderable.

Originality/value

– The obtained results are the first attempt to relate the morphology of surface with TCR of alloy and demonstration of linear dependence between an increase in TCR of amorphic Ni–P alloy and stabilization temperature of resistive layer. Such correlations are not described in available literature.
Influence of disk brake friction on the dynamic behaviour of a directly coupled spur gear transmission
Authors: Khabou M.T. , Ksentini O. , Jarraya A. , Abbes M.S. , Chaari F. , Haddar M.
Published: August 2014

Purpose

– The purpose of this paper is to study the influence of friction phenomenon generated by a disc brake on the dynamic behaviour of a one-stage spur gear.

Design/methodology/approach

– A theoretical model is proposed and is based on both theories of Coulomb and Dahl in order to analyse the influence of disc brake friction phenomenon on the dynamic behaviour of one-stage spur gear transmission.

Findings

– The influence of brake friction on the dynamic behaviour of the transmission is investigated using the proposed model and leads to observe higher vibration levels when the braking is occurring as well as the emergence of significant efforts at the gear teeth.

Originality/value

– A new numerical model based on the implicit numerical integration technique of Newmark coupled with Newton-Raphson method is proposed to study the influence of friction phenomenon of a disc brake on the dynamic behaviour of one-stage spur gear.
Introducing a new medical waste tracking and classification system for Jordan
Authors: Y. Ammary Bashaar
Published: August 2014

Purpose

– The purpose of this paper is to introduce a cradle to grave manifest system for medical waste in Jordan. As part of this program, medical waste classification, generation rates, and tracking in different parts of the world and in Jordan are described.

Design/methodology/approach

– After reviewing different classification systems, the program adopted the World Health Organization definition with minor modification to be used with the proposed manifest, as it is very similar to the current bylaw regulating medical waste in Jordan. In addition, the generation rates of hazardous medical waste in 11 public hospitals and one governmental university hospital in the northern part of Jordan were calculated. These were based on the weights of these wastes that were transferred to the sole incinerator used by these hospitals over a 12-month period. These weights were obtained through interviews with personnel in charge of the medical waste incinerator.

Findings

– This project has devised a manifest form to be used for medical waste transport. In addition, the generation rate was found to vary from 0.88 to 3.05 kg/bed/day based on 100 percent occupancy rates. The generation weight was found to be different for different months of the year.

Originality/value

– Management of waste disposal and treatment, including medical waste is very important in a water poor country like Jordan. The introduction of a manifest system and the adoption of a medical classification system, in addition to the calculation of the generation rates are very important for sustainable development in the country.
Environmental perturbation, grazing pressure and soil wetness jointly drive mountain tundra toward divergent alternative states
Authors: Saccone Patrick , Pyykkonen Tuija , Eskelinen Anu , Virtanen Risto
Published: August 2014

Plant communities are structured by complex interactions between multiple factors, which veil our understanding of the effects of environmental changes on communities and ecosystems. Besides the relative role of biotic and abiotic factors as community‐structuring processes, addressing how they jointly affect the ecological resilience and resistance of plant communities is crucial to understand better the long‐term response of communities facing global changes.

Here, we used the results from a long‐term (23 years) perturbation experiment set up in Fennoscandian mountain tundra to test these mechanisms. The experiment consisted of a transplantation of twenty blocks of Vaccinium myrtillus heath vegetation including upper soil layer from a lower elevation tundra heath habitat to a snowbed habitat 150 m higher in elevation where V. myrtillus lies at its upper limit. In the snowbed with contrasting levels of soil wetness, half of the transplanted blocks were protected from mammalian herbivores.

Our results revealed that in addition to the important role of environmental conditions as a structuring force, the joint effects of multiple drivers resulted in divergent patterns in both plant functional composition and species diversity among transplanted communities. Under environmental perturbation (i.e. transplantation to snowbed), the heath vegetation was altered by grazing pressure that reduced the cover of shrubs (especially V. myrtillus). In grazed dry snowbed, a species‐rich community with high functional type evenness and diversity developed. Reversely, in dry exclosures, V. myrtillus gained high dominance associated with only few graminoids and forbs. In wet snowbed conditions, shrubs tended to decline both in grazed plots and exclosures whereas bryophytes attained high abundance. Grazing promoted species richness while soil waterlogging tended to promote among‐plot heterogeneity (β‐diversity) which was highest in wet exclosures.

Synthesis. Our long‐term experiment reveals that environmental perturbation, grazing and soil wetness exhibit joint effects that induce divergent trajectories of tundra plant communities. We suggest that a strong environmental perturbation triggers mountain tundra heath community to move away from its equilibrium state. The outcome of this shift depends on the interplay between grazing pressure and soil wetness that drive tundra plant communities toward divergent alternative states.
Literacy profiles of at‐risk young adults enrolled in career and technical education
Authors: Mellard Daryl F. , Woods Kari L. , Lee Jae Hoon
Published: August 2014

A latent profile analysis of 323 economically and academically at‐risk adolescent and young adult learners yielded two classes: an average literacy class (92%) and a low literacy class (8%). The class profiles significantly differed in their word reading and math skills, and in their processing speeds and self‐reported learning disabilities. The class profiles did not significantly differ in their language comprehension and cognitive processing/working memory abilities. These findings suggest targeted instructional interventions to overcome deficits, leading to overall improvements in literacy and numeracy among this important population.
Within‐year changes in Chinese secondary school students' perceived reading instruction and intrinsic reading motivation
Authors: Lau Kit‐ling
Published: August 2014

This study aimed to expand on existing research about motivational change by investigating within‐year changes of adolescents' intrinsic reading motivation and perceived reading instruction among students from different grades and achievement levels. Six hundred and ninety five students from 10 secondary schools in Hong Kong voluntarily completed a questionnaire that measured these two variables at the beginning and near the end of a school year. The study's findings indicated that students' intrinsic reading motivation was generally stable over a school year. A significant increase in the perceived degree of mastery goal structure in reading instruction was observed near the end of the school year. Students' perception of instruction remained a strong and positive predictor of intrinsic motivation after controlling their prior motivation and other background variables. Different factors affecting students' motivational change are discussed to provide insights for promoting their reading motivation and counter the prevalent trend of motivational decline.
First European data from the network of severe allergic reactions (NORA)
Authors: Worm M. , Moneret‐Vautrin A. , Scherer K. , Lang R. , Fernandez‐Rivas M. , Cardona V. , Kowalski M. L. , Jutel M. , Poziomkowska‐Gesicka I. , Papadopoulos N. G. , Beyer K. , Mustakov T. , Christoff G. , Bilò M. B. , Muraro A. , Hourihane J. O. B. , Grabenhenrich L. B.
Published: August 2014

Background

Occurrence, elicitors and treatment of severe allergic reactions are recognized and reported differently between countries. We aimed to collect standardized data throughout Europe on anaphylaxis referred for diagnosis and counselling.

Methods

Tertiary allergy, dermatology and paediatric units in 10 European countries took part in this pilot phase of the first European Anaphylaxis Registry, from June 2011 to March 2014. An online questionnaire was used to collect data on severe allergic reactions based on the medical history and diagnostics.

Results

Fifty‐nine centres reported 3333 cases of anaphylaxis, with 26.7% below 18 years of age. Allergic reactions were mainly caused by food (children and adults 64.9% and 20.2%, respectively) and insect venom (20.2% and 48.2%) and less often by drugs (4.8% and 22.4%). Most reactions occurred within 30 min of exposure (80.5%); a delay of 4+ hours was mainly seen in drug anaphylaxis (6.7%). Symptom patterns differed by elicitor, with the skin being affected most often (84.1%). A previous, usually milder reaction to the same allergen was reported by 34.2%. The mainstay of first‐line treatment by professionals included corticoids (60.4%) and antihistamines (52.8%). Only 13.7% of lay‐ or self‐treated reactions to food and 27.6% of insect anaphylaxis received on‐site adrenaline.

Conclusion

This pilot phase of a pan‐European registry for severe allergic reactions provides for the first time data on anaphylaxis throughout Europe, demonstrates its potential functionality and allows a comparison of symptom patterns, elicitors and treatment habits between referral centres and countries.
How French paediatric emergency departments manage painful vaso‐occlusive episodes in sickle cell disease patients
Authors: Galeotti Caroline , Courtois Emilie , Carbajal Ricardo
Published: August 2014

Aim

The most common manifestation of sickle cell disease (SCD) is painful vaso‐occlusive episodes (PVOE), and inappropriate treatment leads to unnecessary suffering and potentially fatal complications. This study describes how French paediatric emergency departments (EDs) manage PVOE and their knowledge, and implementation of the French National Authority for Health recommendations on the management of sickle cell patients.

Methods

A questionnaire on managing PVOE was sent to all the 111 French paediatric EDs.

Results

We received responses from 81 (72.9%) of the EDs. Of those who responded to each individual question, 85% said that they had read the national recommendations, 71.6% said they used nalbuphine for moderate PVOE, and 85% used intravenous morphine for severe PVOE. The majority (91.7%) of EDs thought that intravenous morphine provided relief for severe PVOE, but only 30.9% thought that intravenous nalbuphine did. A 50:50 nitrous oxide/oxygen mix was used by 71.3% of departments to relieve procedural pain and by 48% to enhance analgesia when morphine was insufficient for severe pain.

Conclusions

Most French EDs follow the national recommendations for PVOE. Nalbuphine was the most commonly used opioid for moderate PVOE and morphine for severe PVOE. A nitrous oxide/oxygen mixture was widely used for PVOE.
Atopy does not affect the frequency of adenotonsillar hypertrophy and sleep apnoea in children who snore
Authors: Alexopoulos Emmanouel I. , Bizakis John , Gourgoulianis Konstantinos , Kaditis Athanasios G.
Published: August 2014

Aim

Viral respiratory infections and atopy have been implicated in the pathogenesis of adenotonsillar hypertrophy and obstructive sleep apnoea (OSA), but the role of atopy is controversial. We aimed to test our hypothesis that atopy, expressed as physician‐diagnosed eczema, was associated with adenotonsillar hypertrophy and OSA among children who snored.

Methods

Data on children who snored and were referred for polysomnography were reviewed. The primary outcome measures were adenotonsillar hypertrophy and OSA.

Results

We analysed data on 855 children with a mean age (±standard deviation) of 6.3 (±2.5) years and median obstructive apnoea–hypopnea index of 2.1 episodes per hour. Of the 855 subjects, 133 (15.6%) had physician‐diagnosed eczema, 591 (69.1%) had adenoidal hypertrophy, 605 (70.8%) had tonsillar hypertrophy, 219 (25.6%) were obese and 470 (55%) had OSA. Eczema was not related to adenoidal or tonsillar hypertrophy after adjustment for gender and age, with odds ratios (OR) of 1.00 (95% confidence interval 0.67–1.49; p = 0.98) and 0.88 (95% confidence interval 0.59–1.32; p = 0.54), respectively. Similarly, eczema did not affect OSA frequency after adjustment for adenoidal and tonsillar hypertrophy, obesity, gender and age, with an adjusted OR of 0.82 (0.56–1.21; p = 0.32).

Conclusions

Atopy was not related to adenotonsillar hypertrophy or OSA in children who snore.
Observation is a valid way of assessing common variables in typical babbling and identifies infants who need further support
Authors: Lieberman Marion , Lohmander Anette
Published: August 2014

Aim

It is important to identify speech and language difficulties in children as early as possible. This study investigated the validity of observing babbling structure and consonant articulation.

Methods

We focused on the language capabilities of children, with and without cleft palates, at 12 months of age (n = 29) and 18 months of age (n = 38), comparing observations made by speech and language pathologists on babbling structure and consonant articulation to audio recordings phonetically transcribed by experts blinded to the aim of the study. Descriptive cross‐tabs, sensitivity, specificity and predictive values were analysed to investigate the validity of agreement between the methods.

Results

We found high mean agreement between the two methods (94%) and within the observation (100%) and transcription (88.5%) teams when it came to canonical babbling, high‐pressure/oral stop consonants and anterior placement of bilabial and dental/alveolar consonants. The observations had high specificity and negative predictive values (0.90–1) at both ages, with low to moderate sensitivity (0–0.86). However, there was low agreement, between and within the groups, on the number of consonant types and the unproven predictive variable glottal place of articulation.

Conclusion

Previously suggested predictive measures of babbling were shown to be valid and observation is a reliable method of identifying children who need further support.
High doses of benzodiazepine predict analgesic and sedative drug withdrawal syndrome in paediatric intensive care patients
Authors: Amigoni A , Vettore E , Brugnolaro V , Brugnaro L , Gaffo D , Masola M , Marzollo A , Pettenazzo A
Published: August 2014

Aim

Critically ill children can develop withdrawal syndrome after prolonged analgesia and sedation in a paediatric intensive care unit (PICU), when treatment is stopped abruptly or reduced quickly. The aim of this study was to evaluate the incidence of withdrawal syndrome in patients after three or more days of analgesic or sedative drug therapy, using a validated scale. We also analysed the association between withdrawal syndrome and the patients’ outcome and factors related to analgesia and sedation treatment.

Methods

This prospective observational study analysed 89 periods of weaning from analgesia and sedation in 60 children between October 2010 and October 2011. Of these, 65% were less than six months old and 45% were admitted to the PICU after heart surgery. Withdrawal syndrome was assessed using the Withdrawal Assessment Tool‐1 (WAT‐1) scale.

Results

The incidence of withdrawal syndrome was 37%, and the only variable that predicted its presence was the highest administered dose of benzodiazepine. The duration of weaning, Sophia Observational Withdrawal Symptom scale score and nurse judgment were also associated with positive WAT‐1 scores.

Conclusion

Withdrawal syndrome should be considered after three or more days of analgesic or sedative treatment. A high dose of benzodiazepine increases the risk of developing withdrawal symptoms.
Galla Chinensis Attenuates Cigarette Smoke‐associated Lung Injury by Inhibiting Recruitment of Inflammatory Cells into the Lung
Authors: Lee Hyojung , Yu Seung‐Ryeol , Lim Dahae , Lee Hyejung , Jin Eun‐Young , Jang Young‐Pyo , Kim Jinju
Published: August 2014

Inflammation is a common feature in the pathogenesis of cigarette smoke (CS)‐associated diseases. In this study, we investigated the effects of Galla Chinensis (GC) extract on pulmonary inflammatory responses in a CS‐exposed mouse model. In vitro studies showed that GC extract reduced MCP‐1 production in a dose‐dependent manner. In addition, the recruitment of inflammatory cells into the lung was significantly inhibited in the bronchoalveolar lavage fluid (BALF) of the GC‐treated mice after 3 weeks of daily CS exposure. GC treatment down‐regulated TNF‐α, IL‐6 and MCP‐1 mRNA expression levels in lung tissue. Finally, GC‐treated mice showed less emphysematous change of alveolar compared to mice only exposed to CS. Our results show that GC extract reduces lung inflammation and emphysematous change by inhibiting the infiltration of inflammatory cells to the lung. These data indicate that GC extract is a therapeutic candidate for CS‐induced lung injury.
Medical burden in bipolar disorder: findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE)
Authors: Sylvia Louisa G , Shelton Richard C , Kemp David E , Bernstein Emily E , Friedman Edward S , Brody Benjamin D , McElroy Susan L , Singh Vivek , Tohen Mauricio , Bowden Charles L , Ketter Terence A , Deckersbach Thilo , Thase Michael E , Reilly‐Harrington Noreen A , Nierenberg Andrew A , Rabideau Dustin J , Kinrys Gustavo , Kocsis James H , Bobo William V , Kamali Masoud , McInnis Melvin G , Calabrese Joseph R
Published: August 2014

Objectives

Individuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity.

Methods

The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six‐month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM‐IV‐TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non‐cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence).

Results

We found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high‐density lipoprotein and abnormal triglycerides.

Conclusions

There appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients.
A lower intensity of treatment may underlie the increased risk of thrombosis in young patients with masked polycythaemia vera
Authors: Lussana Federico , Carobbio Alessandra , Randi Maria L. , Elena Chiara , Rumi Elisa , Finazzi Guido , Bertozzi Irene , Pieri Lisa , Ruggeri Marco , Palandri Francesca , Polverelli Nicola , Elli Elena , Tieghi Alessia , Iurlo Alessandra , Ruella Marco , Cazzola Mario , Rambaldi Alessandro , Vannucchi Alessandro M. , Barbui Tiziano
Published: August 2014

In patients who do not meet the World Health Organization (WHO) criteria for overt polycythaemia vera (PV), a diagnosis of masked PV (mPV) can be determined. A fraction of mPV patients may display thrombocytosis, thus mimicking essential thrombocythaemia (ET). No previous studies have examined clinical outcomes of mPV among young JAK2‐mutated patients. We analysed a retrospective cohort of 538 JAK2‐mutated patients younger than 40 years, after a re‐assessment of the diagnosis according to the haemoglobin threshold for mPV. In this cohort of patients, 97 (18%) met the WHO criteria for PV, 66 patients (12%) were classified as mPV and 375 (70%) as JAK2‐mutated ET. Surprisingly, a significant difference in the incidence of thrombosis was found when comparing mPV versus overt PV patients (P = 0·04). In multivariate analysis, the only factor accounting for the difference in the risk of thrombosis was the less frequent use of phlebotomies and cytoreduction in mPV patients compared to those with overt PV. Thus, we emphasize the need for the identification of mPV in young JAK2‐mutated patients in order to optimize their treatments.
Characterizing pharmacological ligands to study the long‐chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4
Authors: Milligan G , Alvarez‐Curto E , Watterson K R , Ulven T , Hudson B D
Published: August 2014

The free fatty acid receptors (FFA) 1 (previously designated GPR40) and FFA4 (previously GPR120) are two GPCRs activated by saturated and unsaturated longer‐chain free fatty acids. With expression patterns and functions anticipated to directly or indirectly promote insulin secretion, provide homeostatic control of blood glucose and improve tissue insulin sensitivity, both receptors are being studied as potential therapeutic targets for the control of type 2 diabetes. Furthermore, genetic and systems biology studies in both humans and mouse models link FFA4 receptors to diabetes and obesity. Although activated by the same group of free fatty acids, FFA1 and FFA4 receptors are not closely related and, while the basis of recognition of fatty acids by FFA1 receptors is similar to that of the short‐chain fatty acid receptors FFA2 and FFA3, the amino acid residues involved in endogenous ligand recognition by FFA4 receptors are more akin to those of the sphingosine 1 phosphate receptor S1P1. Screening and subsequent medicinal chemistry programmes have developed a number of FFA1 receptor selective agonists that are effective in promoting insulin secretion in a glucose concentration‐dependent manner, and in lowering blood glucose levels. However, the recent termination of Phase III clinical trials employing TAK‐875/fasiglifam has caused a setback and raises important questions over the exact nature and mechanistic causes of the problems. Progress in the identification and development of highly FFA4 receptor‐selective pharmacological tools has been less rapid and several issues remain to be clarified to fully validate this receptor as a therapeutic target. Despite this, the ongoing development of a range of novel ligands offers great opportunities to further unravel the contributions of these receptors.

Linked Articles

This article is part of a themed section on 5th BPS Focused Meeting on Cell Signalling. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐13
The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases
Authors: Zhang Xiao‐Jing , Jiang Ding‐Sheng , Li Hongliang
Published: August 2014

The family of interferon regulatory factors (IRFs) consists of nine members (IRF1–IRF9) in mammals. They act as transcription factors for the interferons and thus exert essential regulatory functions in the immune system and in oncogenesis. Recent clinical and experimental studies have identified critically important roles of the IRFs in cardiovascular diseases, arising from their participation in divergent and overlapping molecular programmes beyond the immune response. Here we review the current knowledge of the regulatory effects and mechanisms of IRFs on the immune system. The role of IRFs and their potential molecular mechanisms as novel stress sensors and mediators of cardiovascular diseases are highlighted.

Linked Articles

This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
Calcium affects OX1 orexin (hypocretin) receptor responses by modifying both orexin binding and the signal transduction machinery
Authors: Putula Jaana , Pihlajamaa Tero , Kukkonen Jyrki P
Published: August 2014

Background and Purpose

One of the major responses upon orexin receptor activation is Ca2+ influx, and this influx seems to amplify the other responses mediated by orexin receptors. However, the reduction in Ca2+, often used to assess the importance of Ca2+ influx, might affect other properties, like ligand−receptor interactions, as suggested for some GPCR systems. Hence, we investigated the role of the ligand−receptor interaction and Ca2+ signal cascades in the apparent Ca2+ requirement of orexin‐A signalling.

Experimental Approach

Receptor binding was assessed in CHO cells expressing human OX1 receptors with [125I]‐orexin‐A by conventional ligand binding as well as scintillation proximity assays. PLC activity was determined by chromatography.

Key Results

Both orexin receptor binding and PLC activation were strongly dependent on the extracellular Ca2+ concentration. The relationship between Ca2+ concentration and receptor binding was the same as that for PLC activation. However, when Ca2+ entry was reduced by depolarizing the cells or by inhibiting the receptor‐operated Ca2+ channels, orexin‐A‐stimulated PLC activity was much more strongly inhibited than orexin‐A binding.

Conclusions and Implications

Ca2+ plays a dual role in orexin signalling by being a prerequisite for both ligand−receptor interaction and amplifying orexin signals via Ca2+ influx. Some previous results obtained utilizing Ca2+ chelators have to be re‐evaluated based on the results of the current study. From a drug discovery perspective, further experiments need to identify the target for Ca2+ in orexin‐A−OX1 receptor interaction and its mechanism of action.
PEG Mediated Synthesis and Biological Evaluation of Asymmetrical Pyrazole Curcumin Analogues as Potential Analgesic, Anti‐Inflammatory and Antioxidant Agents
Authors: Jadhav Shravan Y. , Bhosale Raghunath B. , Shirame Sachin P. , Patil Sandeep B. , Kulkarni Suresh D.
Published: August 2014

The new series of asymmetrical pyrazole curcumin analogues 4a–g were synthesized by using polyethylene glycol (PEG‐400) as a green reaction medium and evaluated for their in vivo analgesic and in vitro antioxidant (H2O2, DPPH, Ferrous reducing power and Nitric oxide scavenging activity) and anti‐inflammatory activities. All the compounds synthesized 4a–g showed the potential to demonstrate analgesic activity as compared to the standard ibuprofen. Among the tested series, compounds 4e and 4b exhibited good hydrogen peroxide scavenging activity as compared to the standard butylated hydroxy toluene (BHT). Compounds 4b, 4d, 4f, and 4g showed good DPPH free radical scavenging activity. Compounds 4b, 4c, 4d, 4e and 4g showed excellent ferrous‐reducing power activity, whereas all the compounds showed better nitric oxide scavenging activity than standard ascorbic acid. Additionally, all the synthesized compounds were also screened for their in vitro anti‐inflammatory activity. Compounds 4b, 4d, 4f and 4g showed good anti‐inflammatory activity as compared to standard diclofenac sodium.
Development of Category‐Based Induction and Semantic Knowledge
Authors: Fisher Anna V. , Godwin Karrie E. , Matlen Bryan J. , Unger Layla
Published: August 2014

Category‐based induction is a hallmark of mature cognition; however, little is known about its origins. This study evaluated the hypothesis that category‐based induction is related to semantic development. Computational studies suggest that early on there is little differentiation among concepts, but learning and development lead to increased differentiation based on taxonomic relatedness. This study reports findings from a new task aimed to (a) examine this putative increase in semantic differentiation and (b) test whether individual differences in semantic differentiation are related to category‐based induction in 4‐ to 7‐year‐old children (N = 85). The results provide the first empirical evidence of an age‐related increase in differentiation of representations of animal concepts and suggest that category‐based induction is related to increased semantic differentiation.
Interparental Violence and Childhood Adjustment: How and Why Maternal Sensitivity Is a Protective Factor
Authors: Manning Liviah G. , Davies Patrick T. , Cicchetti Dante
Published: August 2014

This study examined sensitive parenting as a protective factor in relations between interparental violence (IPV) and children's coping and psychological adjustment. Using a multimethod approach, a high‐risk sample of 201 two‐year‐olds and their mothers participated in three annual waves of data collection. Moderator analyses revealed that sensitive parenting buffered the risk posed by IPV on children's changes in externalizing and prosocial development over a 2‐year period. Tests of mediated moderation further indicated that sensitive parenting protected children from the vulnerability of growing up in a violent home through its association with lower levels of children's angry reactivity to interparental conflict. Results highlight the significance of identifying the mechanisms that mediate protective factors in models of family adversity.
Effects of lifestyle modification and metformin on irisin and FGF21 among HIV‐infected subjects with the metabolic syndrome
Authors: Srinivasa Suman , Wong Kimberly , Fitch Kathleen V. , Wei Jeffrey , Petrow Eva , Cypess Aaron M. , Torriani Martin , Grinspoon Steven K.
Published: August 2014

Objective

Few studies have investigated irisin and FGF21 to elucidate the role of these hormones to regulate ‘beiging’ in HIV‐infected patients.

Design

Fifty HIV‐infected subjects with the metabolic syndrome were previously recruited and randomized to receive lifestyle modification (LSM) and/or metformin over 12 months. In the current study, we assessed FGF21 and irisin at baseline and after intervention. In addition, we assessed circulating FGF21 and irisin in relationship to brown adipose tissue (BAT) gene expression in dorsocervical subcutaneous fat biopsies from 13 HIV‐infected subjects.

Results

At baseline, prior to intervention, HIV‐infected subjects demonstrated increased log FGF21 (2·13 ± 0·06 vs 1·98 ± 0·05 pg/ml, P = 0·05) and log irisin (0·33 ± 0·02 vs 0·17 ± 0·04 μg/ml, P = 0·003) compared with healthy controls well matched based on waist circumference. After 12 months, HIV‐infected subjects randomized to LSM demonstrated a relative reduction in FGF21 compared with those not randomized to LSM (−10 [−35,22] vs 40 [0,94] %change, P = 0·01). Changes in FGF21 were inversely associated with improved parameters of energy homoeostasis, including increased REE (ρ = −0·34, P = 0·046) and max VO2 (ρ = −0·38, P = 0·02), and reduced RQ (ρ = 0·40, P = 0·02) among all HIV‐infected subjects. Increased UCP‐1 (r = 0·75, P = 0·003), DIO2 (r = 0·58, P = 0·04) and CideA (r = 0·73, P = 0·01) gene expression in dorsocervical fat was significantly associated with FGF21 in HIV‐infected subjects.

Conclusion

HIV‐infected subjects with metabolic complications demonstrate increases in FGF21 in relationship to BAT gene expression. Relative reductions in FGF21 in those receiving long‐term LSM relate to overall improvements in energy expenditure parameters. In contrast, irisin levels are elevated in HIV‐infected subjects, but are not influenced by LSM nor associated with BAT gene expression.
CD8+ tumour‐infiltrating lymphocytes and COX2 expression may predict relapse in differentiated thyroid cancer
Authors: Cunha Lucas Leite , Marcello Marjory Alana , Nonogaki Suely , Morari Elaine Cristina , Soares Fernando Augusto , Vassallo José , Ward Laura Sterian
Published: August 2014

Background/objective

There is an increasing rate of papillary thyroid carcinomas that may never progress to cause symptoms or death. Predicting outcome and determining tumour aggressiveness could help diminish the number of patients submitted to aggressive treatments. We aimed to evaluate whether markers of the immune system response and of tumour‐associated inflammation could predict outcome of differentiated thyroid cancer (DTC) patients.

Design

Retrospective cohort study.

Patients

We studied 399 consecutive patients, including 325 papillary and 74 follicular thyroid carcinomas.

Measurements

Immune cell markers were evaluated using immunohistochemistry, including tumour‐associated macrophages (CD68) and subsets of tumour‐infiltrating lymphocytes (TIL), such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the presence of concurrent lymphocytic infiltration characterizing chronic thyroiditis.

Results

Concurrent lymphocytic infiltration characterizing chronic thyroiditis was observed in 29% of the cases. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0·001) and expression of COX2 (P =0·01) were associated with recurrence. A multivariate model analysis identified CD8+ TIL/COX2 as independent risk factor for recurrence. A multivariate analysis using Cox's proportional‐hazards model adjusted for the presence of concurrent chronic thyroiditis demonstrated that the presence of concurrent chronic thyroiditis had no effect on prognostic prediction mediated by CD8+ TIL and COX2.

Conclusion

In conclusion, we suggest the use of a relatively simple pathology tool to help select cases that may benefit of a more aggressive approach sparing the majority of patients from unnecessary procedures.
Genetic, molecular and physiological mechanisms involved in human obesity: Society for Endocrinology Medal Lecture 2012
Authors: Farooqi Sadaf I.
Published: August 2014

The health consequences of obesity represent one of the major public health challenges of our time. Whilst the role of environmental drivers such as reduced physical activity and increased food intake is widely acknowledged, the importance of biological factors which influence individual variation in weight is less readily recognised. Considerable evidence suggests that genetic factors influence a person's weight in a given environment and that these genetic influences are more potent at the extremes of the body mass index (BMI) distribution. The discovery that genetic disruption of certain pathways can lead to severe obesity has informed our current understanding of how body weight is regulated by brain circuits that regulate appetite and energy expenditure. These studies provide a framework for investigating patients and ultimately may guide the development of more rational‐targeted therapies for genetically susceptible individuals with severe obesity.
Quantification and genotyping of lipoprotein lipase in patients with diabetic lipaemia
Authors: Radhakutty A. , Shen J. , Hooper A. J. , Miller S. A. , Burnett J. R. , Mah P. M. , Burt M. G. , Doogue M. P.
Published: August 2014

Aims

To determine if diabetic lipaemia is caused by loss of function mutations in the lipoprotein lipase gene, LPL.

Methods

We conducted a case–control study over 2 years in two tertiary care hospitals in South Australia. Six patients with a history of diabetic lipaemia and 12 control subjects, with previous diabetic ketoacidosis and peak triglyceride concentrations < 2.4 mmol/l were included. Participants were well at the time of study investigations.

Results

Only one patient with lipaemia had a loss of function mutation in LPL and no functional mutations in APOC2 or GPIHBP1 were identified. The mean lipoprotein lipase concentration was lower in patients with diabetic lipaemia than in control subjects (306 vs 484 μg/l, P = 0.04). The mean fasting C‐peptide concentration was higher in patients with diabetic lipaemia than in control subjects (771 vs 50 pmol/l; P = 0.001).

Conclusions

Lipoprotein lipase deficiency in patients with a history of diabetic lipaemia was predominantly quantitative, rather than secondary to mutations in LPL, APOC2 or GPIHBP1. The majority of patients with severe hypertriglyceridaemia in diabetic ketoacidosis may have ketosis‐prone Type 2, rather than Type 1, diabetes.
Depression, anxiety and self‐care behaviours of young adults with Type 2 diabetes: results from the International Diabetes Management and Impact for Long‐term Empowerment and Success (MILES) Study
Authors: Browne J. L. , Nefs G. , Pouwer F. , Speight J.
Published: August 2014

Aim

Young adults with Type 2 diabetes have higher physical morbidity and mortality than other diabetes sub‐groups, but differences in psychosocial outcomes have not yet been investigated. We sought to compare depression and anxiety symptoms and self‐care behaviours of young adults with Type 2 diabetes with two matched control groups.

Methods

Using cross‐sectional survey data from the Australian and Dutch Diabetes Management and Impact for Long‐term Empowerment and Success (MILES) studies, we matched 93 young adults (aged 18–39 years) with Type 2 diabetes (case group) with: (i) 93 older adults ( ≥ 40 years) with Type 2 diabetes (Type 2 diabetes control group; matched on country, gender, education, diabetes duration and insulin use) and (ii) 93 young adults with Type 1 diabetes (Type 1 diabetes control group; matched on country, gender, age and education). Groups were compared with regard to depression symptoms (nine‐item Patient Health Questionnaire), anxiety symptoms (seven‐item Generalised Anxiety Disorder questionnaire) and frequency of selected self‐care behaviours (single item per behaviour).

Results

Participants in the case group had higher depression scores (Cohen's d = 0.40) and were more likely to have clinically meaningful depressive symptoms (Cramer's V = 0.23) than those in the Type 2 diabetes control group. Participants in the case group had statistically equivalent depression scores to the Type 1 diabetes control group. The groups did not differ in anxiety scores. Those in the case group were less likely than both control groups to take insulin as recommended (Cramer's V = 0.24–0.34), but there were no significant differences between the groups in oral medication‐taking. The case group were less likely than the Type 2 diabetes control group to eat healthily (Cramer's V  = 0.16), and less likely than the Type 1 diabetes control group to be physically active (Cramer's V = 0.15).

Conclusions

Our results suggest that Type 2 diabetes is as challenging as Type 1 diabetes for young adults and more so than for older adults. Young adults with Type 2 diabetes may require more intensive psychological and self‐care support than their older counterparts.
Reversal of Type 2 diabetes after bariatric surgery is determined by the degree of achieved weight loss in both short‐ and long‐duration diabetes
Authors: Steven S. , Carey P. E. , Small P. K. , Taylor R.
Published: August 2014

Aim

To define the impact of duration of diabetes and extent of weight loss on the reversibility of Type 2 diabetes after bariatric surgery.

Methods

Complete data were collated from 89 individuals with Type 2 diabetes mellitus undergoing any bariatric surgical procedure in a specialist bariatric centre. People with a preoperative HbA1c < 43 mmol/mol (6.1%) were excluded. Diabetes duration was defined as: short, < 4 years; medium, 4–8 years; and long, > 8 years.

Results

An HbA1c of <43mmol/mol (6.1%) was achieved by 62% of patients in the short‐duration group and 26% of patients in the long‐duration group. Normoglycaemia was rarely achieved in the long‐duration group if weight loss was < 25kg. In the whole cohort there was a clear relationship of greater weight loss with lower HbA1c levels (Rs = −0.53; P < 0.0001).

Conclusions

The study shows that the degree of achieved weight loss is the major determinant of return to normal blood glucose levels after bariatric surgery. Normoglycaemia can be achieved in long‐duration Type 2 diabetes, but a greater degree of weight loss is required than for short‐duration diabetes.
Similarity between generic and brand‐name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population‐based study
Authors: Corrao Giovanni , Soranna Davide , Merlino Luca , Mancia Giuseppe
Published: August 2014

Background

Although generic and earlier brand‐name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern.

Objective

To compare effectiveness of generic and brand‐name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes.

Design and subjects

A population‐based, nested case–control study was carried out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand‐name agents.

Results

There was no evidence that patients who started on generics experienced different CV risk than those on brand‐name product (OR 0·86; 95% CI 0·63–1·17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand‐name agents (OR 1·19; 95% CI 0·86–1·63). Compared with patients who kept initial brand‐name therapy, those who experienced brand‐to‐generic or generic‐to‐brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1·18 (0·96–1·47), 0·87 (0·63–1·21) and 1·08 (0·80–1·46).

Conclusions

Our findings do not support the notion that brand‐name antihypertensive agents are superior to generics for preventing CV outcomes in the real‐world clinical practice.