bluuebunny/crossref_metadata_2025 huggingface dataset:
A study on automotive drivetrain transient response to ‘clutch abuse’ events
Authors: Bingham Philip , Theodossiades Stephanos , Saunders Tim , Grant Edward , Daubney Richard
Published: December 2015

The optimal design of driveline components in passenger vehicles requires detailed knowledge of the effects that load case scenarios introduce into the system. In many cases the latter are difficult to obtain, since a large number of tested cases are required experimentally. Excessive torque loading often occurs during driveline ‘clutch abuse’ events, where the clutch is suddenly engaged and a transient power wave is transmitted across the driveline. This work details the development and validation of a numerical tool, which can be used to simulate such abuse scenarios. The scenario examined consists of a sudden clutch engagement in first gear in a stationary vehicle. The numerical model is validated against experimentally measured torque data, showing fairly good agreement. A set of parametric studies is also carried out using a numerical tool in order to determine the driveline parameters of interest, which affect the generated torque amplitudes.
Prediction of the in-service performance of a railway hydraulic damper
Authors: Wang Wenlin , Yu Dingsong , Xu Rui
Published: December 2015

In this study, an improved physical parametric model with key in-service parameters was established and experimentally validated for a high-speed railway hydraulic damper. A subtle variable oil property model was built and coupled into the full model to address the dynamic flow losses and the relief-valve system dynamics. Experiments were conducted to evaluate the accuracy and robustness of the full damper model and simulation, which determined the damping characteristics over an extremely wide range of excitation speeds. Further simulations with in-service conditions and excitations were performed using the validated model, and the results revealed that improper key in-service parameters, such as improper rubber attachment stiffness, entrained air ratios and small mounting clearances, can greatly degrade the damping capability of a hydraulic damper. The obtained physical model includes all the influential factors that have an impact on the damping characteristics, so it will serve as a useful basic theory in the prediction of in-service performance, optimal specification and product design optimization of hydraulic dampers for modern high-speed rail vehicles.
Strict Slaves of Slogans
Authors: Epstein William M.
Published: December 2015

The corruption of the social work enterprise is not simply episodic but systemic and long-standing including education, research, governance, and practice. Reform is unlikely since the constituency within the field and outside of it that wishes to change the situation is small and ineffective. The corruption of social work reflects the unfortunate social values of the nation that refuses to allocate sufficient resources to address deep social problems, notably economic and social inequality. Social work should severely cut back: eliminate bachelor of social work programs and reduce master’s education to no more than 20 programs that also offer doctorates but only jointly with social science departments. There are too many social workers and not enough good ones.
A Comparison of Parenting Dimensions Between Deaf and Hearing Children
Authors: Ekim Ayfer , Ocakci Ayse Ferda
Published: December 2015

Effective parenting is vital for intellectual, physical, social, and emotional development of a child. This study examined the differences between the parenting dimensions of deaf children and healthy ones. The sample of the study consisted of 292 children and their parents (146 of them deaf children and 146 of them healthy ones). Dimensions of parenting (warmth, rejection, structure, chaos, autonomy, and coercion) were measured using the Parent as Social Context Questionnaire. The mean scores of the positive parenting dimensions of warmth and autonomy of deaf children were significantly lower; however, the mean scores of the negative dimensions of chaos and coercion of deaf children were significantly higher than those of healthy ones. Deaf children can become successful adults with the help of their parents. Our results regarding parenting dimensions will be a guide for future nursing interventions planned to develop the relationships between deaf children and their parents.
Team Adaptiveness in Dynamic Contexts
Authors: Lei Zhike , Waller Mary J. , Hagen Jan , Kaplan Seth
Published: December 2015

Previous research asserts that teams working in routine situations pass through performance episodes characterized by action and transition phases, while other evidence suggests that certain team behaviors significantly influence team effectiveness during nonroutine situations. We integrate these two areas of research—one focusing on the temporal nature of team episodic performance and the other on interaction patterns and planning in teams—to more fully understand how teams working in dynamic settings successfully transition across routine and nonroutine situations. Using behavioral data collected from airline flight crews working in a flight simulator, we find that different interaction pattern characteristics are related to team performance in routine and nonroutine situations, and that teams engage in more contingency, in-process planning behavior during routine versus nonroutine situations. Moreover, we find that the relationship between this in-process planning and subsequent team adaptiveness is curvilinear (inverted U-shaped). That is, team contingency or in-process planning activity may initially increase team adaptiveness, but too much planning has adverse effects on subsequent performance.
Unusual Sertoli Cell Tumor Associated With Sex Cord Tumor With Annular Tubules in Peutz-Jeghers Syndrome
Authors: Ravishankar Sanjita , Mangray Shamlal , Kurkchubasche Arlet , Yakirevich Evgeny , Young Robert H.
Published: December 2015

We report the case of an 11-year-old girl with Peutz-Jeghers syndrome and a unilateral ovarian tumor most consistent with Sertoli cell tumor associated with sex cord tumor with annular tubules. The ovary was replaced by a lobular, solid, yellow tumor. Microscopic examination showed 2 components that focally merged. The first was composed of uniform, cytologically bland cells arranged mostly in diffuse sheets and focally in tubules. The second showed typical sex cord tumor with annular tubules with extensive calcification. The predominant component of the tumor clearly fell in the sex cord category and most closely resembled Sertoli cell tumor. This case adds to the limited information on ovarian sex cord tumors, other than typical sex cord tumor with annular tubules, arising in association with Peutz-Jeghers syndrome, a topic reviewed herein.
Luis, From Ex-Prisoner to Neighborhood Representative and Interlocutor With Public Administrations
Authors: Melgar Patricia
Published: December 2015

As an ex-prisoner from a ghetto in Albacete (Spain), Luis’s aspirations were constrained to either obtaining a seasonal job when possible or resigning to becoming a permanent user of social services. However, his participation in dialogic spaces such as Dialogic Literary Gatherings (DLG) made him dream that a different life was possible, not only for him but also for his children. In the DLG, he began a process of personal transformation that allowed him to become one of the most appreciated representatives of his neighborhood and a core interlocutor with several public administrations. The authors consider how dialogic spaces such as the DLG become sources of hope and sense-making to people such as Luis and note the elements that enable them to overcome social exclusion while inspiring them to fight for the achievement of social justice in their communities.
A Qualitative Examination of Situational Risk Recognition Among Female Victims of Physical Intimate Partner Violence
Authors: Sherrill Andrew M. , Bell Kathryn M. , Wyngarden Nicole
Published: December 2015

Little is known about intimate partner violence (IPV) victims’ situational risk recognition, defined as the ability to identify situational factors that signal imminent risk of victimization. Using semi-structured interviews, qualitative data were collected from a community sample of 31 female victims of IPV episodes involving substance use. Thirteen themes were identified, the most prevalent being related to the partner’s verbal behavior, tone of voice, motor behavior, alcohol or drug use, and facial expression. Participants reporting at least some anticipation of physical aggression (61.3% of the sample) tended to identify multiple factors ( M = 3.47), suggesting numerous situational features often contribute to situational risk recognition.
Transfemoral Transcatheter Aortic Valve Replacement for Mixed Aortic Valve Disease in Child’s Class C Liver Disease Prior to Orthotopic Liver Transplantation
Authors: Wilkey Barbara J. , Hanson Ross , Reece T. Brett , Forman Lisa , Burton James R. , Messenger John C. , Kim Michael S. , Cleveland Joseph C. , Fiegel Matt J. , Nydam Trevor L. , Mandell M. Susan
Published: December 2015

The American Association for the Study of Liver Diseases practice guidelines list severe cardiac disease as a contraindication to liver transplantation. Transcatheter aortic valve replacement has been shown to decrease all-cause mortality in patients with severe aortic stenosis who are not considered candidates for surgical aortic valve replacement. We report our experience of liver transplantation in a patient with severe aortic stenosis and moderate aortic insufficiency who underwent transcatheter aortic valve replacement with Child-Pugh Class C disease at a Model For End-Stage Liver Disease score of 29. The patient had a difficult post procedure course that was successfully medically managed. After liver transplantation the patient was discharged to home on postoperative day 11. The combination of cardiac disease and end stage liver disease is challenging but these patients can have a successful outcome despite very severe illness.
Ambulatory electrocardiogram recordings in cats with primary asymptomatic hypertrophic cardiomyopathy
Authors: Hanås Sofia , Tidholm Anna , Holst Bodil S
Published: December 2015

Objectives

The aims of the study were to determine the heart rate, rhythm, number of ventricular premature complexes (VPCs) and atrial premature complexes (APCs) in unsedated cats with asymptomatic hypertrophic cardiomyopathy (HCM), using 24 h ambulatory electrocardiogram (ECG) (Holter) in the home environment and to compare the results with those from healthy control cats.

Methods

Fifteen privately owned cats with asymptomatic HCM entered the study. Data from 23 healthy cats, previously published by our group, were used as the control. Clinical examination, measurement of blood pressure, echocardiographic examination, Holter recordings and biochemical analyses were performed in all cats. Holter recordings were obtained in the home environment.

Results

Three-lead ECGs of good quality were obtained from 15 cats with HCM. The median heart rate was 145 (interquartile range [IQR] 137–184) beats per minute for the cats with HCM. All cats with HCM presented with normal sinus rhythm; 60% of cats had intermittent sinus arrhythmia. Median number of VPCs was 3 (IQR 1–17). Three cats had APCs and three cats had both escape beats and intermittent sinus arrhythmia.

Conclusions and relevance

Asymptomatic cats with HCM had few VPCs and APCs on 24 h ambulatory ECG in the home environment. Intermittent sinus arrhythmia was observed in 60% of cats with HCM. The present study shows that the heart rate and the number of VPCs and APCs in cats with asymptomatic HCM are similar to that found in healthy control cats.
The experience of couples being given an oxygen concentrator to use at home: A longitudinal interpretative phenomenological analysis
Authors: Thomson Ross , Martin Jennifer L , Sharples Sarah
Published: December 2015

This longitudinal study explores the lived experience of four couples where one person from each couple is prescribed an oxygen concentrator to use at home. Transcripts were analysed using interpretative phenomenological analysis. The findings reported here focus on two super-ordinate themes: ‘the journey of acceptance’ and ‘negotiating changing relationships’. Participants described a gradual process of accepting the device into their lives, the impact on couple’s relationships and the role that expectations have in mediating that process. These themes suggest that patient education that considers the psychological and social issues may prove useful in facilitating the acceptance process.
Lay knowledge, social movements and the use of medicines: Personal reflections
Authors: Britten Nicky , Maguire Kath
Published: December 2015

This article consists of two personal reflections about the changing status of lay knowledge over the last 20 years. The first reflection is by Nicky Britten from the perspective of a sociologist working in medical schools whose interest in this topic was motivated by my own personal experience of health care and of teaching general practitioners. Starting with the problematic deficit model of ‘ignorant patients’, I trace the literature on patient-centredness, shared decision-making, lay knowledge, public involvement in research and social movements. Looking at medicines use in particular, I deplore the continued hegemony of the concept of compliance in the face of extensively documented problems with the licensing, regulation, prescribing and monitoring of medicines. I argue that lay knowledge is now taken more seriously, not so much because of advocacy by clinicians and academics, but because of social movements and social action. We may have moved from ‘anecdotes’ to ‘lived experience’ but there is still a way to go, particularly when it comes to medicines use. I end with a possible future scenario. The second reflection is by Kath Maguire and is a response from the perspective of someone who came to work in this field with the express purpose of improving engagement with lay knowledge. It questions my own ‘layness’ and explores the issues raised by Nicky Britten using the lens of lived experience. Finally, it questions the paradigm of social movements and highlights the importance of developing different ways of listening.
Social TV and the Participation Dilemma in NBC’s The Voice
Authors: van Es Karin
Published: December 2015

In this article, I explore the perks and perils of social TV as a strategy for networks to drive tune-in to episodes as they air and to strengthen audience engagement. I do so by examining reality singing competitions in the United States, and specifically the NBC show The Voice. In analyzing the development of social media use in the program over the course of its first seven seasons, I identify a participation dilemma. This dilemma results from the fact that in giving viewers influence over aspects of the production to create an emotional investment, producers relinquish control over the contents of the show, which needs to appeal to large audiences. In addition, I classify the applications of social media: promotional, affective, functional, and phatic. In discussing these examples, I show how the “new” strategies of social TV hark back to “old” strategies that predate their use.
Prescribing a Healthy Lifestyle Polypill With High Therapeutic Efficacy in Many Shapes and Sizes
Authors: Arena Ross , Lavie Carl J. , Guazzi Marco
Published: December 2015

The paradigm allowing for a lifestyle immersed in unhealthy behaviors to perpetuate to a point where a non-communicable disease (NCD) is eminent or manifests, and then initiating health care interventions, is deeply flawed, results in poor outcomes, and is unsustainable. This paradigm describes the current predominant healthcare model in many countries around the world and has resulted in the continual increase in unhealthy lifestyle patterns that have led to the global NCD epidemic. It is now broadly recognized that rapid integration of a new healthcare model, one heavily focused on primordial and primary NCD prevention, is needed. Being physically active, eating healthy and nutritious foods, not smoking and minimizing second-hand exposure, and maintaining an appropriate body weight are central to this new prevention model. Combined, these four characteristics can be viewed as the key ingredients for the “healthy lifestyle polypill”. Recently, the American Heart Association (AHA), European Society of Cardiology (ESC), European Association for Cardiovascular Prevention and Rehabilitation (EACPR), and American College of Preventive Medicine (ACPM) came together to publish, in both the Mayo Clinic Proceedings and European Heart Journal, a policy statement entitled “Healthy Lifestyle Interventions to Combat Non-Communicable Disease: A Novel Non-Hierarchical Connectivity Model for Key Stakeholders”. We hope the AHA-ESC-EACPR-ACPM healthy lifestyle policy statement prompts a massive increase in production of the healthy lifestyle polypill. Regulatory approval is not needed to start manufacturing and distributing this medication. The polypill can take many forms and have differing ingredients and dosages while still maintaining high therapeutic efficacy.
An industry-scale modeling for the turbulence agglomeration of fine particles
Authors: Xu Jiyun , Shen Hongwei , Wang Hao
Published: December 2015

Turbulence-induced agglomeration of fine particles/droplets in aerosol is important in various industrial and natural processes. Despite abundant theoretical and numerical studies on turbulent collision kernels, convincing numerical methods for industry-scale applications are still lacking. In this work, we develop a mixed Eulerian–Lagrangian model for the modeling of turbulence-induced agglomeration of fine particles/droplets. As advantages over Sommerfeld’s model, the present model searches for real collision pairs based on a new mesh-independent method and uses appropriate turbulent collision kernels to calculate the collision frequencies. Benchmark simulations are carried out and compared with the results provided by the well-characterized experiment by Duru et al.
Stochastic time-dependent vehicle routing problem: Mathematical models and ant colony algorithm
Authors: Duan Zhengyu , Sun Shichao , Sun Shuo , Li Weifeng
Published: December 2015

This article addresses the stochastic time-dependent vehicle routing problem. Two mathematical models named robust optimal schedule time model and minimum expected schedule time model are proposed for stochastic time-dependent vehicle routing problem, which can guarantee delivery within the time windows of customers. The robust optimal schedule time model only requires the variation range of link travel time, which can be conveniently derived from historical traffic data. In addition, the robust optimal schedule time model based on robust optimization method can be converted into a time-dependent vehicle routing problem. Moreover, an ant colony optimization algorithm is designed to solve stochastic time-dependent vehicle routing problem. As the improvements in initial solution and transition probability, ant colony optimization algorithm has a good performance in convergence. Through computational instances and Monte Carlo simulation tests, robust optimal schedule time model is proved to be better than minimum expected schedule time model in computational efficiency and coping with the travel time fluctuations. Therefore, robust optimal schedule time model is applicable in real road network.
Design of pilot-assisted load control valve with load velocity control ability and fast opening feature
Authors: Xie Haibo , Liu Jianbin , Yang Huayong , Hu Liang , Fu Xin , Fan Yurun
Published: December 2015

This article presents a design of pilot-assisted load control valve with load velocity control ability and fast opening feature based on static and dynamic modeling. Traditional load control valves do not have the load velocity control ability and its opening feature is very poor because the high spring stiffness comes along with the pressure–spring balance–based principle. Some improvement has been done by employing a two-stage pressure–pressure balance principle to make a load control valve to achieve load velocity control ability while the opening feature was not improved much. In this design, another pressure–pressure balance principle is proposed to make the load control valve achieve load velocity control ability and fast opening closing feature at the same time. Static modeling method based on force balance and Bernoulli orifice pressure-flow equation is used to design the load velocity control ability of the valve. Dynamic modeling method based on Newton’s second law and fluid continuity equation is used to optimize the parameters to give the proposed load control valve a fast opening feature. An actual load control valve was developed according to the above methods and the test results show both good load velocity control ability and fast opening feature of the design, which validates the potentiality of the proposed design in many applications.
The fluid control mechanism of bionic structural heterogeneous composite materials and its potential application in enhancing pump efficiency
Authors: Tian Limei , Jin E , Li Ziyuan , Mei Haoran , Wang Yinci , Shang Yangeng
Published: December 2015

Studies have shown that the structure of dolphin skin controls fluid media dynamically. Gaining inspiration from this phenomenon, a kind of bionic structural heterogeneous composite material was designed. The bionic structural heterogeneous composite material is composed of two materials: a rigid metal base layer with bionic structures and an elastic polymer surface layer with the corresponding mirror structures. The fluid control mechanism of the bionic structural heterogeneous composite material was investigated using a fluid–solid interaction method in ANSYS Workbench. The results indicated that the bionic structural heterogeneous composite material’s fluid control mechanism is its elastic deformation, which is caused by the coupling action between the elastic surface material and the bionic structure. This deformation can decrease the velocity gradient of the fluid boundary layer through changing the fluid–solid actual contact surface and reduce the frictional force. The bionic structural heterogeneous composite material can also absorb some energy through elastic deformation and avoid energy loss. The bionic structural heterogeneous composite material was applied to the impeller of a centrifugal pump in a contrast experiment, increasing the pump efficiency by 5% without changing the hydraulic model of the impeller. The development of this bionic structural heterogeneous composite material will be straightforward from an engineering point of view, and it will have valuable practical applications.
Computer-aided process planning in prismatic shape die components based on Standard for the Exchange of Product model data
Authors: Khan Awais Ahmad , Hussein Hussein Mohamed , Abouel Nasr Emad Samir , Al-Ahmari Abdulrahman
Published: December 2015

Insufficient technologies made good integration between the die components in design, process planning, and manufacturing impossible in the past few years. Nowadays, the advanced technologies based on Standard for the Exchange of Product model data are making it possible. This article discusses the three main steps for achieving the complete process planning for prismatic parts of the die components. These three steps are data extraction, feature recognition, and process planning. The proposed computer-aided process planning system works as part of an integrated system to cover the process planning of any prismatic part die component. The system is built using Visual Basic with EWDraw system for visualizing the Standard for the Exchange of Product model data file. The system works successfully and can cover any type of sheet metal die components. The case study discussed in this article is taken from a large design of progressive die.
A Case of Heel Cord Pain After Repair of Acute Achilles Tendon Rupture
Authors: Lui Tun Hing
Published: December 2015

The causes of heel cord pain after repair of acute rupture of the Achilles tendon are unclear. The proposed etiologies include nonabsorbable suture granuloma formation, alteration of the pain receptors threshold in the tendon, and distension of the paratenon by the hypertrophied tendon, underlying tendinopathy, postrepair neovascularization, and peritendinous fibrous adhesion. We present an endoscopic technique of adhesiolysis of the Achilles tendon to deal with the various possible causes of postrepair heel cord pain.

Levels of Evidence: Therapeutic, Level 4: Case report
Complex Meniscus Tears Treated with Collagen Matrix Wrapping and Bone Marrow Blood Injection
Authors: Piontek Tomasz , Ciemniewska-Gorzela Kinga , Naczk Jakub , Jakob Roland , Szulc Andrzej , Grygorowicz Monika , Slomczykowski Michal
Published: December 2015

Objective

To collect and analyze the 2-year follow-up clinical and MRI results of patients treated with an arthroscopic technique of collagen membrane-based meniscus repair.

Design

53 consecutive patients with combined (horizontal and radial or longitudinal component) and complex meniscal tears (tear extended through avascular zones or/and composed with two or more morphological tear pattern) were treated with an “all-inside” arthroscopic suture of meniscus and wrapping with a collagen membrane (Chondro-Gide) technique with bone marrow blood injection. The IKDC 2000 subjective score, IKDC 2000 clinical evaluation score, Lysholm score and Barret clinical criteria of meniscal healing were recorded. All patients were examinated by MRI 2 years postoperatively, using modified WORMS criteria for meniscal integrity.

Results

The 2 year follow-up was achieved in 50 cases. Of these, 2 patients were excluded from the evaluation due to incomplete data and 2 patients underwent partial meniscectomy and were classified as failures. In 46 patients (86.8% of the intended to treat cases), a statistically significant improvement in IKDC 2000 subjective, Lysholm scores and IKDC 2000 clinical assessment between preoperative and the 2-year follow-up time points were obsereved. Barret criteria demonstrated an improved clinical outcome between pre- and post-operative values. MRI revealed a non-homogeneous signal without meniscal tear (WORMS grade 1) in 76% of the operated menisci (13% WORMS grade 2).

Conclusions

The 2-year follow-up data demonstrate that this technique is safe and can offer an additional tool to save the meniscus in the patients otherwise scheduled for meniscal removal. Level of evidence IV
Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid–Induced Colitis in Rats
Authors: Rashidian Amir , Roohi Parnia , Mehrzadi Saeed , Ghannadi Ali Reza , Minaiyan Mohsen
Published: December 2015

Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid–induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid–induced colitis.
Bonding and Abandoning
Authors: Kissane Rebecca Joyce , Winslow Sarah
Published: December 2015

Using data on 396 fantasy sports participants, we explore how fantasy sports participation impacts players’ perceptions of their relationships with others, with attention to how and why outcomes are sexed and gendered. We find male players are more likely than female players to report bonding with friends through their participation, particularly via highly masculinized bragging and “smack talk” with others in their male-dominated leagues. Female players also discuss fantasy sports as a means of relationship building or strengthening, particularly with friends in their leagues or men in their lives; but our analyses suggest they may trade off social connections, as women who are highly involved in other groups are less likely to use fantasy sports to connect with others. Finally, male players, more so than their female counterparts, indicate fantasy sports participation strains relationships with their partners and families, an effect seemingly attributable to their greater emotional and mental investment in fantasy sports.
Book Review: Ziyā Baranī, Tārī

kh

-i Fīrozshāhī
Authors: Habib Irfan
Published: December 2015

Ziyā Baranī, Tārīkh-i Fīrozshāhī (earlier version), facsimile edition of MS in Raza Library, 1913, Rampur, with an introduction by Professor S.M. Azizuddīn Husain (Rampur: Raza Library), text, pp. 344 + introduction, pp. 104.
Second-line combination therapies in nonsmall cell lung cancer without known driver mutations
Authors: Bluthgen Maria-Virginia , Besse Benjamin
Published: December 2015

In advanced nonsmall cell lung cancer (NSCLC) patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies.

In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.
Challenges in pulmonary hypertension: managing the unexpected
Authors: Olsson Karen M. , Palazzini Massimiliano
Published: December 2015

The diverse challenges associated with diagnosis and management of patients with pulmonary hypertension are illustrated in this case-based review. Case 1 describes a patient diagnosed with pulmonary arterial hypertension (PAH) with right heart failure and active systemic lupus erythematosus who was effectively treated with an up-front triple combination of PAH therapies and immunosuppressive therapy. In case 2, a diagnosis of pulmonary veno-occlusive disease was reached after a combined approach of clinical suspicion, physical examination, and invasive and noninvasive tests. Cautious PAH therapy and high-dose diuretics provided clinical benefit in this patient and served as a bridge to lung transplantation. These cases highlight the need for ongoing follow-up of patients with PAH, comprising frequent assessment of treatment success and continued diagnostic evaluation.
Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension
Authors: Lang Irene M. , Gaine Sean P.
Published: December 2015

Pulmonary arterial hypertension (PAH) is a severe disease characterised by increased pulmonary vascular resistance, which leads to restricted pulmonary arterial blood flow and elevated pulmonary arterial pressure. In patients with PAH, pulmonary concentrations of prostacyclin, a prostanoid that targets several receptors including the IP prostacyclin receptor, are reduced. To redress this balance, epoprostenol, a synthetic prostacyclin, or analogues of prostacyclin have been given therapeutically. These therapies improve exercise capacity, functional class and haemodynamic parameters. In addition, epoprostenol improves survival among patients with PAH. Despite their therapeutic benefits, treatments that target the prostacyclin pathway are underused. One key factor is their requirement for parenteral administration: continuous intravenous administration can lead to embolism and thrombosis; subcutaneous administration is associated with infusion-site pain; and inhalation is time consuming, requiring multiple daily administrations. Nevertheless, targeting the prostacyclin pathway is an important strategy for the management of PAH. The development of oral therapies for this pathway, as well as more user-friendly delivery devices, may alleviate some of the inconveniences. Continued improvements in therapeutic options will enable more patients with PAH to receive medication targeting the prostacyclin pathway.
Hsp90 and hepatobiliary transformation during sea lamprey metamorphosis
Authors: Chung-Davidson Yu-Wen , Yeh Chu-Yin , Bussy Ugo , Li Ke , Davidson Peter J. , Nanlohy Kaben G. , Brown C. Titus , Whyard Steven , Li Weiming
Published: December 2015

Background

Biliary atresia (BA) is a human infant disease with inflammatory fibrous obstructions in the bile ducts and is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult. Therefore, sea lamprey liver metamorphosis may serve as an etiological model for human BA and provide pivotal information for hepatobiliary transformation and possible therapeutics.

Results

We hypothesized that liver metamorphosis in sea lamprey is due to transcriptional reprogramming that dictates cellular remodeling during metamorphosis. We determined global gene expressions in liver at several metamorphic landmark stages by integrating mRNA-Seq and gene ontology analyses, and validated the results with real-time quantitative PCR, histological and immunohistochemical staining. These analyses revealed that gene expressions of protein folding chaperones, membrane transporters and extracellular matrices were altered and shifted during liver metamorphosis. HSP90, important in protein folding and invertebrate metamorphosis, was identified as a candidate key factor during liver metamorphosis in sea lamprey. Blocking HSP90 with geldanamycin facilitated liver metamorphosis and decreased the gene expressions of the rate limiting enzyme for cholesterol biosynthesis, HMGCoA reductase (hmgcr), and bile acid biosynthesis, cyp7a1. Injection of hsp90 siRNA for 4 days altered gene expressions of met, hmgcr, cyp27a1, and slc10a1. Bile acid concentrations were increased while bile duct and gall bladder degeneration was facilitated and synchronized after hsp90 siRNA injection.

Conclusions

HSP90 appears to play crucial roles in hepatobiliary transformation during sea lamprey metamorphosis. Sea lamprey is a useful animal model to study postembryonic development and mechanisms for hsp90-induced hepatobiliary transformation.
Chloroplast phylogenomic analysis of chlorophyte green algae identifies a novel lineage sister to the Sphaeropleales (Chlorophyceae)
Authors: Lemieux Claude , Vincent Antony T. , Labarre Aurélie , Otis Christian , Turmel Monique
Published: December 2015

Background

The class Chlorophyceae (Chlorophyta) includes morphologically and ecologically diverse green algae. Most of the documented species belong to the clade formed by the Chlamydomonadales (also called Volvocales) and Sphaeropleales. Although studies based on the nuclear 18S rRNA gene or a few combined genes have shed light on the diversity and phylogenetic structure of the Chlamydomonadales, the positions of many of the monophyletic groups identified remain uncertain. Here, we used a chloroplast phylogenomic approach to delineate the relationships among these lineages.

Results

To generate the analyzed amino acid and nucleotide data sets, we sequenced the chloroplast DNAs (cpDNAs) of 24 chlorophycean taxa; these included representatives from 16 of the 21 primary clades previously recognized in the Chlamydomonadales, two taxa from a coccoid lineage (Jenufa) that was suspected to be sister to the Golenkiniaceae, and two sphaeroplealeans. Using Bayesian and/or maximum likelihood inference methods, we analyzed an amino acid data set that was assembled from 69 cpDNA-encoded proteins of 73 core chlorophyte (including 33 chlorophyceans), as well as two nucleotide data sets that were generated from the 69 genes coding for these proteins and 29 RNA-coding genes. The protein and gene phylogenies were congruent and robustly resolved the branching order of most of the investigated lineages. Within the Chlamydomonadales, 22 taxa formed an assemblage of five major clades/lineages. The earliest-diverging clade displayedHafniomonas laevisand theCrucicarteria,and was followed by theRadicarteriaand then by theChloromonadinia. The latter lineage was sister to two superclades, one consisting of theOogamochlamydiniaandReinhardtiniaand the other of theCaudivolvoxaandXenovolvoxa. To our surprise, theJenufaspecies and the two spine-bearing green algae belonging to theGolenkiniaandTreubariagenera were recovered in a highly supported monophyletic group that also included three taxa representing distinct families of the Sphaeropleales (Bracteacoccaceae, Mychonastaceae, and Scenedesmaceae).

Conclusions

Our phylogenomic study advances our knowledge regarding the circumscription and internal structure of the Chlamydomonadales, suggesting that a previously unrecognized lineage is sister to the Sphaeropleales. In addition, it offers new insights into the flagellar structures of the founding members of both the Chlamydomonadales and Sphaeropleales.
High major histocompatibility complex class I polymorphism despite bottlenecks in wild and domesticated populations of the zebra finch (Taeniopygia guttata)
Authors: Newhouse Daniel J. , Balakrishnan Christopher N.
Published: December 2015

Background

Two subspecies of zebra finch,Taeniopygia guttata castanotisandT. g. guttataare native to Australia and the Lesser Sunda Islands, respectively. The Australian subspecies has been domesticated and is now an important model system for research. Both the Lesser Sundan subspecies and domesticated Australian zebra finches have undergone population bottlenecks in their history, and previous analyses using neutral markers have reported reduced neutral genetic diversity in these populations. Here we characterize patterns of variation in the third exon of the highly variable major histocompatibility complex (MHC) class I α chain. As a benchmark for neutral divergence, we also report the first mitochondrial NADH dehydrogenase 2 (ND2) sequences in this important model system.

Results

Despite natural and human-mediated population bottlenecks, we find that high MHC class I polymorphism persists across all populations. As expected, we find higher levels of nucleotide diversity in the MHC locus relative to neutral loci, and strong evidence of positive selection acting on important residues forming the peptide-binding region (PBR). Clear population differentiation of MHC allele frequencies is also evident, and this may be due to adaptation to new habitats and associated pathogens and/or genetic drift. Whereas the MHC Class I locus shows broad haplotype sharing across populations, ND2 is the first locus surveyed to date to show reciprocal monophyly of the two subspecies.

Conclusions

Despite genetic bottlenecks and genetic drift, all surveyed zebra finch populations have maintained high MHC Class I diversity. The diversity at the MHC Class I locus in the Lesser Sundan subspecies contrasts sharply with the lack of diversity in previously examined neutral loci, and may thus be a result of selection acting to maintain polymorphism. Given uncertainty in historical population demography, however, it is difficult to rule out neutral processes in maintaining the observed diversity. The surveyed populations also differ in MHC Class I allele frequencies, and future studies are needed to assess whether these changes result in functional immune differences.
A robust potency assay highlights significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended radio-resistance
Authors: Ketterl Nina , Brachtl Gabriele , Schuh Cornelia , Bieback Karen , Schallmoser Katharina , Reinisch Andreas , Strunk Dirk
Published: December 2015

The inherent immunomodulatory capacity of mesenchymal stem/progenitor cells (MSPCs) encouraged initiation of multiple clinical trials. Release criteria for therapeutic MSPCs cover identity, purity and safety but appropriate potency assessment is often missing. Reports on functional heterogeneity of MSPCs created additional uncertainty regarding donor and organ/source selection. We established a robust immunomodulation potency assay based on pooling responder leukocytes to minimize individual immune response variability. Comparing various MSPCs revealed significant potency inconsistency and generally diminished allo-immunosuppression compared to dose-dependent inhibition of mitogenesis. Gamma-irradiation to block unintended MSPC proliferation did not prohibit chondrogenesis and osteogenesis in vivo, indicating the need for alternative safety strategies.
The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy
Authors: Zhang Jun , Huang Xiaowen , Wang Haijun , Liu Xiaoyan , Zhang Tao , Wang Yunchuan , Hu Dahai
Published: December 2015

Mesenchymal stem cells (MSCs) are ideal for cell-based therapy in various inflammatory diseases because of their immunosuppressive and tissue repair properties. Moreover, their immunosuppressive properties and low immunogenicity contribute to a reduced or weakened immune response elicited by the implantation of allogeneic MSCs compared with other cell types. Therefore, implantation of allogeneic MSCs may be a promising cell-based therapy. In this review, we first summarize the unique advantages of allogeneic MSCs for therapeutic applications. Second, we critically analyze the factors influencing their therapeutic effects, including administration routes, detection time-points, disease models, differentiation of MSCs in vivo, and timing and dosage of MSC administration. Finally, current approaches to allogeneic MSC application are discussed. In conclusion, allogeneic MSCs are a promising option because of their low immunogenicity and immunosuppressive and tissue repair capabilities. Further investigations are needed to enhance the consistency and efficacy of MSCs when used as a cell-based therapy in inflammatory diseases as well as for tissue repair.
$C^{\ast}$-Algebra-valued b-metric spaces and related fixed point theorems
Authors: Ma Zhenhua , Jiang Lining
Published: December 2015

Based on the concept and properties of $C^{\ast}$

C
∗

-algebras, the paper introduces a concept of $C^{\ast}$

C
∗

-algebra-valued b-metric spaces which generalizes the concept of $C^{\ast}$

C
∗

-algebra-valued metric spaces and gives some basic fixed point theorems for self-map with contractive condition on such spaces. As applications, existence and uniqueness results for a type of operator equation and an integral equation are given.
The effect of transdermal nitroglycerin on pain control in diabetic patients with peripheral neuropathy
Authors: Taheri Arman , Farbood Arash , Heshmat Ramin , Samadi Afshin , Khashayar Patricia , Qorbani Mostafa , Ghorbani Mohammad , Ebrahimi Khaneqah Ghazaleh
Published: December 2015

Background

Despite high prevalence of diabetic peripheral neuropathy there is no definite treatment for the condition. The present study was conducted to assess the efficacy of transdermal nitroglycerin patch in pain control of patients with DPN.

Methods

This randomized, double-blind, crossover study was conducted on 30 patients with symmetric distal peripheral neuropathy and good glycemic control. The patients were randomly assigned to receive nitroglycerin transdermal and placebo patches in two 4-week stages. The severity of pain and other neuropathic sensory symptoms were assessed at the end of each course.

Results

Mean reduction of pain severity was more prominent in the NTG group compared to placebo group of the study (p = 0.048) at least during the first phase of the study. Except for mood and sleep, a significant reduction in all Brief Pain Inventory scores was noted in the drug group (all corrected p < 0.05). SF-MPQ also showed the drug patch to be effective in improving different aspects of pain measured using McGill Pain Questionnaire, except for Role–emotional.

Conclusions

It could be concluded that nitroglycerin plasters can effectively help alleviate pain in patients with diabetic neuropathy.

Trial registration

IRCT201308223213N1
Local molecular analysis of indeterminate thyroid nodules
Authors: Gill Mandeep S. , Nayan Smriti , Kocovski Linda , Cutz Jean-Claude , Archibald Stuart D. , Jackson Bernard S. , Young James E. M. , Gupta Michael K.
Published: December 2015

Background

Thyroid nodules are common but only a minority are malignant. Molecular testing can assist in helping determine whether indeterminate nodules are suspicious for malignancy or benign. The objective of the study was to determine if the analysis of mutations (BRAF, NRAS, KRAS and HRAS) using readily available molecular techniques can help better classify indeterminate thyroid nodules.

Methods

A retrospective cohort of consecutive patients undergoing diagnostic thyroid surgery were analyzed for the presence or absence of specific mutations known to be associated with thyroid malignancy in FNA samples. Markers chosen were BRAF, NRAS, KRAS and HRAS. All were locally available and currently in use at our centre for other clinical indications. Results from the molecular analysis were then compared to the histopathology from thyroidectomy specimens to determine the sensitivity and specificity of these molecular techniques to classify indeterminate thyroid nodules.

Results

Sixty consecutive patients with indeterminate FNAs were recruited. Twenty-three patients had malignant tumors while 37 specimens were benign. Multiple different mutations were identified in the FNA samples. Overall 18 cases had a positive mutation (10 malignant and 8 benign). The sensitivity of BRAF, HRAS, KRAS, and NRAS was 8.7, 8.7, 8.7, and 17.4 respectively while the specificity was100, 83.7, 100 and 94.6.

Conclusion

While molecular analysis remains promising, it requires further refinement. Several markers showed promise as good “rule-in” tests.
Provision of neuropsychiatry services: variability and unmet need
Authors: Agrawal Niruj , Bhattacharya Rahul , Rickards Hugh
Published: December 2015

Aims and method

Neuropsychiatry services remain underdeveloped and underprovided. Previous studies have shown variability in service provision in the UK. In this survey we approached all mental health and neuropsychiatric service providers within London to map current neuropsychiatric service provision and explore perceived barriers.

Results

All the specialist mental health service providers responded. There was huge variability in neuropsychiatric service provision within different parts of London. There was evidence of significant unmet need and variability in service pathways. Lack of earmarked funds for neuropsychiatry and disjointed funding stream for such services were identified by providers as a barrier.

Clinical implications

This study provides further evidence of an ongoing lack of adequate neuropsychiatric service provision. Reasons for variability and unmet need are discussed. Adoption of a previously proposed hub-and-spoke model of service provision and the removal of commissioning barriers through uniform national commissioning may help deal with this problem.