bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the efficiency of automotive manual gearboxes by experiment and simulation
Authors: Schaffner T , Allmaier H , Girstmair J , Reich FM , Tangasawi O
Published: June 2014

Energy losses in the drivetrain are a steady topic within the automotive industry, be it to lower emissions and fulfill demands by legislation or to stay longer on the track with a single filling of the fuel tank as in motor sport applications. All of these reasons fuel the motivation to reduce these parasitic losses. In this paper, the major sources of the energy losses in a gearbox are discussed. After the discussion of the sources, the losses in a longitudinally installed manual gearbox are investigated by using both experimental measurements as well as simulation. For the simulation, convenient empirical formulas from literature are used to describe the individual loss processes and combined together to describe the friction power losses of the entire gearbox. The comparison between simulation and the extensive experimental data show good agreement.
Identification of the dominant combustion characteristics on homogeneous charge compression ignition engine noise
Authors: Massey Jeffery A , Drallmeier James A
Published: June 2014

The upper load range of homogeneous charge compression ignition engines is limited by extreme noise levels. Previous studies have investigated the sources of this noise by investigating high-frequency (>4 kHz) acoustic energy typically associated with cylinder cavity resonances excited during high in-cylinder pressure rise rate combustion events. In this work, a broader frequency band (0.5–15 kHz) is investigated experimentally for a single-cylinder homogeneous charge compression ignition engine inside an acoustic sub-enclosure. It has been found that the 0.5–4-kHz frequency band being excited by the rapid in-cylinder pressure rise rate of the homogeneous charge compression ignition combustion event is dominating the acoustic signature of the engine. This indicates that the noise is generated from the structural response of the engine structure to the impulse-like load from the rapid cylinder pressure rise rather than ringing associated with the cavity resonances. A band-level analysis is used to explore the contribution of mechanical and combustion noise on the acoustic signature for various load conditions and combustion phasings. Based on this analysis, a method is proposed where a cylinder pressure rise rate threshold is established for determining the point at which the homogeneous charge compression ignition combustion noise will significantly exceed the mechanical noise level. This threshold, based on the theoretical band-level analysis, agrees with thresholds found from previous literature.
Model-order reduction for wave propagation dynamics in internal combustion engine air path systems
Authors: Stockar Stephanie , Canova Marcello , Guezennec Yann , Della Torre Augusto , Montenegro Gianluca , Onorati Angelo
Published: June 2014

With the advancements in engine design, the air path systems have become so complex that advanced optimization and control design methods are nowadays needed to fully exploit the potential of technologies such as flexible valve actuation. While the automotive industry is employing model-based methodologies for the engine air path system control design process, control-oriented engine air path models are currently limited in their accuracy and predictive ability and rely significantly on calibration. As the engine system complexity increases, there is considerable interest for accurate yet computationally efficient control-oriented engine system models that are able to predict the cylinder charge composition and the thermodynamic conditions with limited calibration effort. This article presents a novel model-order reduction approach for lumped-parameter modeling of pressure wave propagation dynamics in fluids, with application to full-engine simulation. Instead of approximating the geometry of the system to a simple control volume (as typically done in control-oriented engine air path models), this modeling methodology reduces the governing equations for compressible fluid flows and allows for systematically handling both complex geometries, such as sudden area changes and pipe elbows, as well as complex boundary conditions. The model-order reduction procedure projects the partial differential equations governing the air and gas flows onto a set of eigenfunctions, resulting in a set of ordinary differential equations that can be easily implemented in forward-looking simulation software. The modeling approach presented in this article is applied to characterize the wave propagation dynamics in the air path system of a single-cylinder engine, specifically predicting the crank-angle-resolved intake and outlet pressure, as well as the cylinder air charge and volumetric efficiency. The results are benchmarked against both experimental data and simulation results from a well-established one-dimensional gas dynamic model.
Coping with cognitive impairment and dementia: Rural caregivers’ perspectives
Authors: Branger Camille , Burton Rachel , O’Connell Megan E , Stewart Norma , Morgan Debra
Published: June 2014

Caregiving in a rural context is unique, but the experience of rural caregivers is understudied. This paper describes how rural caregivers cope with caring for a loved one diagnosed with mild cognitive impairment or dementia using qualitative description to generate a low-inference summary of a response to an open-ended question. This approach allowed these rural caregivers to describe their positive experiences in addition to the more commonly explored caregiver experiences related to stress. Analyses of coping revealed use of social support, engaging in relaxing and physical activity, and cognitive reframing. In addition, caregivers reported strong faith and religiosity, and to a lesser frequency behavioral changes, checking in with the person with dementia via telephone, and joint activity. Predominantly, these methods reflect approach-based strategies. The current data suggest that these caregivers manage well and adopt adaptive coping strategies to meet the demands of the caregiving role.
Object-love at the Science Museum: cultural geographies of museum storerooms
Authors: Geoghegan Hilary , Hess Alison
Published: June 2014

The field of museum geography is taking on new significance as geographers and museum-studies scholars make sense of the spatial relations between the people, things, practices and buildings that make and remake museums. In order to strengthen this spatial interest in museums, this paper makes important connections between recent work in cultural geography and museum studies on love, materiality and the museum effect. This paper marks a departure from the preoccupation with the public spaces of museums to go behind the scenes of the Science Museum in London to explore its rarely visited, but nonetheless lively, small-to-medium-sized object storerooms at Blythe House. Incorporating field diary entries and interview extracts from two research projects based upon the museum storerooms at Blythe House, this paper brings to life the social interactions that take place between museum curators and conservators and the objects they care for. This focus on object-love enables scholars to consider anew what museums are and what they are for, the life of the museum object in the storeroom, and the emotional practices of professional curatorship and conservation. This journey into the storeroom at Blythe House makes explicit how object-love shapes museum space.
Paying attention, digital media, and community-based critical GIS
Authors: Wilson Matthew W.
Published: June 2014

New web-based architectures and capacities for digital storage have made online social interactions more significant, discursively and materially. Increasingly, these media-centric shifts toward the online and the interactive have enabled for-profit and nonprofit organizations to capture the attention of potential customers and constituents through social and spatial media. In research on the everyday information- and data-practices of community-based organizations, websites and their mobile applications such as Facebook, Twitter, Foursquare, and Pinterest are examined as the emerging media toolset to build sustained connections to funders, constituents, and other members. These technologies and these new pressures around their utilization have made the daily work of nonprofits more complex. As the landscapes of digital media continually shift their interfaces, protocols, and membership settings (including privacy configurations), I suggest that this new normal – persistent change – presents challenges for collective memory and the attention-work of community-based organizations. Taking up and responding to concerns around the implications of digital information technologies on memory and culture, this paper highlights struggles over externalization as significant to the everyday work of collective action.
Controlling darkness: self, dark and the domestic night
Authors: Shaw Robert
Published: June 2014

Social science research into darkness (and light) has largely focused on public spaces. In particular it has been interested in night-time cityscapes, but also spaces of leisure and rural landscapes. This paper instead turns its eye towards the more private experiences of darkness in the home. In this paper I look to explore the active role that darkness plays in constituting our relation to the home, arguing that it takes on a central role. Drawing on phenomenological arguments about experience of dark, I argue that in darkness the self is rendered more open to the other. The ability to choose the conditions in which this openness to the other is experienced becomes important: where power over this choice exists, openness can be experienced as conviviality or intimacy; where power is absent, this openness is more likely to be experienced as vulnerability. As such, controlling darkness in the home is an act of power. This argument is then explored through a study of various trends in geography and social science research into the home, focusing on how the home can slide between poles of security and protection, and insecurity and danger. Though speculative, this paper seeks to set out new ground for research, and new understandings for existing knowledge about darkness and the home.
An Ecology of Values: critically interpreting John Newling’s art
Authors: Crouch David
Published: June 2014

In this article I articulate the cultural geographies of performing potential spaces of a gallery exhibition. I offer my participative, affective relations with the artwork, exploring the fluidity and openness of the spaces in which I found objects that were mutual, commingling and dissonant. In doing so, it is necessary to let the work speak, but not to leave it there. Nor is it to appraise, close-up the arrangement or individual elements of the show in an objective aesthetic. Rather it is to acknowledge circling atmospheres emerging in my cultural geography of practice. New spaces emerge in the practice, through my play with the spaces of the objects as set out, and through my own responses in an affective and productive relational engagement with them, singly and severally.
The simultaneous occurrence and relationship of sunlight and skylight under ISO/CIE standard sky types
Authors: Kittler R , Darula S
Published: June 2014

In daylight science the availability of sunlight and skylight at different times has been studied because of the desire to use daylight in both exterior and interior spaces. Exterior skylight illuminances under overcast skies were adopted as a standard for window design in the past. Current ISO/CIE sky types are standardised as relative luminance patterns normalised to the zenith. In this paper, the zenith luminance in candela/square metre and the resulting diffuse illuminance in lux are determined for all sky types. Furthermore, the proportions of sunlight and skylight under different levels of turbidity are found and documented. Efforts to harmonise electric lighting and daylighting standards need to analyse the data on available daylight in physical units in order to ensure energy savings that respect human requirements as well as providing information suitable for computer-aided design.
Effect of APOE and CHRNA7 Genotypes on the Cognitive Response to Cholinesterase Inhibitor Treatment at Different Stages of Alzheimer’s Disease
Authors: Braga Ianna Lacerda Sampaio , Silva Patricia Natalia , Furuya Tatiane Katsue , Santos Leonardo Caires , Pires Belisa Caldana , Mazzotti Diego Robles , Bertolucci Paulo Henrique , Cendoroglo Maysa Seabra , Smith Marília Cardoso
Published: June 2014

The loss of cholinergic transmission is considered to be an important cause of Alzheimer’s disease (AD). Treatment with acetyl cholinesterase inhibitors (ChEIs) shows benefits; however, great heterogeneity has been observed in patient responses. We evaluated apolipoprotein E ( APOE) and α7 nicotinic receptor ( CHRNA7) single-nucleotide polymorphisms (SNPs) and associated these SNPs with pharmacological responses to ChEIs in a Brazilian population with AD. We studied 177 outpatients using ChEIs, and they were classified as responders and nonresponders according to variation in Mini-Mental State Examination (MMSE) status. The analysis of APOE genotypes showed that patients with the ∊4 allele had a worse response than those without the ∊4 allele. We observed an association between the CHRNA7 T allele and a better response to treatment with ChEIs in patients with mild AD (MMSE ≥ 20). The SNP rs6494223 of CHRNA7 as well as APOE∊4 could be useful for understanding the response to ChEI treatment in patients with AD.
An Ambient Assisted Living Approach in Designing Domiciliary Services Combined With Innovative Technologies for Patients With Alzheimer’s Disease
Authors: Cavallo Filippo , Aquilano Michela , Arvati Marco
Published: June 2014

Background:

Alzheimer’s disease (AD) is one of the most disabling diseases to affect large numbers of elderly people worldwide. Because of the characteristics of this disease, patients with AD require daily assistance from service providers both in nursing homes and at home. Domiciliary assistance has been demonstrated to be cost effective and efficient in the first phase of the disease, helping to slow down the course of the illness, improve the quality of life and care, and extend independence for patients and caregivers. In this context, the aim of this work is to demonstrate the technical effectiveness and acceptability of an innovative domiciliary smart sensor system for providing domiciliary assistance to patients with AD which has been developed with an Ambient Assisted Living (AAL) approach.

Methods:

The design, development, testing, and evaluation of the innovative technological solution were performed by a multidisciplinary team. In all, 15 sociomedical operators and 14 patients with AD were directly involved in defining the end-users’ needs and requirements, identifying design principles with acceptability and usability features and evaluating the technological solutions before and after the real experimentation.

Results:

A modular technological system was produced to help caregivers continuously monitor the health status, safety, and daily activities of patients with AD. During the experimentation, the acceptability, utility, usability, and efficacy of this system were evaluated as quite positive.

Conclusion:

The experience described in this article demonstrated that AAL technologies are feasible and effective nowadays and can be actively used in assisting patients with AD in their homes. The extensive involvement of caregivers in the experimentation allowed to assess that there is, through the use of the technological system, a proven improvement in care performance and efficiency of care provision by both formal and informal caregivers and consequently an increase in the quality of life of patients, their relatives, and their caregivers.
Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure
Authors: Sung Jong Hwan , Srinivasan Balaji , Esch Mandy Brigitte , McLamb William T , Bernabini Catia , Shuler Michael L , Hickman James J
Published: June 2014

The continued development of in vitro systems that accurately emulate human response to drugs or chemical agents will impact drug development, our understanding of chemical toxicity, and enhance our ability to respond to threats from chemical or biological agents. A promising technology is to build microscale replicas of humans that capture essential elements of physiology, pharmacology, and/or toxicology (microphysiological systems). Here, we review progress on systems for microscale models of mammalian systems that include two or more integrated cellular components. These systems are described as a “body-on-a-chip”, and utilize the concept of physiologically-based pharmacokinetic (PBPK) modeling in the design. These microscale systems can also be used as model systems to predict whole-body responses to drugs as well as study the mechanism of action of drugs using PBPK analysis. In this review, we provide examples of various approaches to construct such systems with a focus on their physiological usefulness and various approaches to measure responses (e.g. chemical, electrical, or mechanical force and cellular viability and morphology). While the goal is to predict human response, other mammalian cell types can be utilized with the same principle to predict animal response. These systems will be evaluated on their potential to be physiologically accurate, to provide effective and efficient platform for analytics with accessibility to a wide range of users, for ease of incorporation of analytics, functional for weeks to months, and the ability to replicate previously observed human responses.
Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer
Authors: Tsuei Jessica , Chau Thinh , Mills David , Wan Yu-Jui Yvonne
Published: June 2014

Because of increasingly widespread sedentary lifestyles and diets high in fat and sugar, the global diabetes and obesity epidemic continues to grow unabated. A substantial body of evidence has been accumulated which associates diabetes and obesity to dramatically higher risk of cancer development, particularly in the liver and gastrointestinal tract. Additionally, diabetic and obese individuals have been shown to suffer from dysregulation of bile acid (BA) homeostasis and dysbiosis of the intestinal microbiome. Abnormally elevated levels of cytotoxic secondary BAs and a pro-inflammatory shift in gut microbial profile have individually been linked to numerous enterohepatic diseases including cancer. However, recent findings have implicated a detrimental interplay between BA dysregulation and intestinal dysbiosis that promotes carcinogenesis along the gut–liver axis. This review seeks to examine the currently investigated interactions between the regulation of BA metabolism and activity of the intestinal microbiota and how these interactions can drive cancer formation in the context of diabesity. The precarcinogenic effects of BA dysregulation and gut dysbiosis including excessive inflammation, heightened oxidative DNA damage, and increased cell proliferation are discussed. Furthermore, by focusing on the mediatory roles of BA nuclear receptor farnesoid x receptor, ileal transporter apical sodium dependent BA transporter, and G-coupled protein receptor TGR5, this review attempts to connect BA dysregulation, gut dysbiosis, and enterohepatic carcinogenesis at a mechanistic level. A better understanding of the intricate interplay between BA homeostasis and gut microbiome can yield novel avenues to combat the impending rise in diabesity-related cancers.
Distinct adipogenic differentiation phenotypes of human umbilical cord mesenchymal cells dependent on adipogenic conditions
Authors: Saben Jessica , Thakali Keshari M , Lindsey Forrest E , Zhong Ying , Badger Thomas M , Andres Aline , Shankar Kartik
Published: June 2014

The umbilical cord (UC) matrix is a source of multipotent mesenchymal stem cells (MSCs) that have adipogenic potential and thus can be a model to study adipogenesis. However, existing variability in adipocytic differentiation outcomes may be due to discrepancies in methods utilized for adipogenic differentiation. Additionally, functional characterization of UCMSCs as adipocytes has not been described. We tested the potential of three well-established adipogenic cocktails containing IBMX, dexamethasone, and insulin (MDI) plus indomethacin (MDI-I) or rosiglitazone (MDI-R) to stimulate adipocyte differentiation in UCMSCs. MDI, MDI-I, and MDI-R treatment significantly increased peroxisome proliferator-activated receptor gamma ( PPARγ) and CCAAT-enhancer binding protein alpha ( C/EBPα) mRNA and induced lipid droplet formation. However, MDI-I had the greatest impact on mRNA expression of PPARγ, C/EBPα, FABP4, GPD1, PLIN1, PLIN2, and ADIPOQ and lipid accumulation, whereas MDI showed the least. Interestingly, there were no treatment group differences in the amount of PPAR γ protein. However, MDI-I treated cells had significantly more C/EBP α protein compared to MDI or MDI-R, suggesting that indomethacin-dependent increased C/EBP α may contribute to the adipogenesis-inducing potency of MDI-I. Additionally, bone morphogenetic protein 4 (BMP4) treatment of UCMSCs did not enhance responsiveness to MDI-induced differentiation. Finally to characterize adipocyte function, differentiated UCMSCs were stimulated with insulin and downstream signaling was assessed. Differentiated UCMSCs were responsive to insulin at two weeks but showed decreased sensitivity by five weeks following differentiation, suggesting that long-term differentiation may induce insulin resistance. Together, these data indicate that UCMSCs undergo adipogenesis when differentiated in MDI, MDI-I, and MDI-R, however the presence of indomethacin greatly enhances their adipogenic potential beyond that of rosiglitazone. Furthermore, our results suggest that insulin signaling pathways of differentiated UCMSCs are functionally similar to adipocytes.
Clinical Effectiveness of Gene Therapy on Critical Limb Ischemia
Authors: Miao Yu-Liang , Wu Wei , Li Bao-Wei , Fang Wei-Wu , Liu Yan , Li Lu , Mi Wei-Dong
Published: June 2014

Therapeutic angiogenesis using gene therapy is a novel strategy for the treatment of critical limb ischemia (CLI). We conducted a meta-analysis to evaluate the efficacy and safety of gene therapy for the treatment of CLI with no option of revascularization. Randomized placebo controlled trials of gene therapy on CLI were identified by searching PubMed (from 1990 to October 2013) and EMBASE (from 1990 to October 2013). Five eligible studies were selected for the meta-analysis. Among these studies, a total of 425 patients received gene therapy of either fibroblast growth factor 1 or hepatocyte growth factor, and 365 patients were given placebo. No statistical differences were observed between the 2 groups in major amputation or death at 1 year (risk ratio [RR], 0.83; 95% confidence interval [CI], 0.51-1.39; P = .48) and wound healing at 6 months (RR, 1.55; 95% CI, 0.73-3.28; P = .25). Gene therapy had similar occurrence of serious adverse events as control (RR, 1.05; 95% CI, 0.97-1.14; P = .23).
Information Gathering and Technology Use Among Low-Income Minority Men at Risk for Prostate Cancer
Authors: Song Hayeon , Cramer Emily M. , McRoy Susan
Published: June 2014

Health communication researchers, public health workers, and health professionals must learn more about the health information-gathering behavior of low-income minority men at risk for prostate cancer in order to share information effectively with the population. In collaboration with the Milwaukee Health Department Men’s Health Referral Network, a total of 90 low-income adult men were recruited to complete a survey gauging information sources, seeking behavior, use of technology, as well as prostate cancer awareness and screening behavior. Results indicated participants primarily relied on health professionals, family, and friends for information about general issues of health as well as prostate cancer. The Internet was the least relied on source of information. A hierarchical regression indicated interpersonal information sources such as family or friends to be the only significant predictor enhancing prostate cancer awareness, controlling for other sources of information. Prostate screening behaviors were predicted by reliance on not only medical professionals but also the Internet. Practical implications of the study are discussed.
Translating Guidelines for the Diagnosis and Management of Sports-Related Concussion Into Practice
Authors: Donaldson Alex , Newton Joshua , McCrory Paul , White Peta , Davis Gavin , Makdissi Michael , Finch Caroline F.
Published: June 2014

Sports injuries are a significant clinical and public health concern. There is a growing call to improve the translation of available evidence-based and expert-informed sports injury prevention interventions into sustained use in practice by physicians and others (eg, athletic trainers, coaches, and parents) who care for injured athletes. This article provides a brief overview of the current sport injury prevention implementation literature before focusing specifically on the translation of guidelines (including consensus and position statements) developed to assist physicians and others diagnose and manage athletes with sport-related concussion and the associated return-to-play decisions. The outcomes of more than 20 published studies indicate that physician, athletic trainer, coach, parent, and athlete knowledge, use of, and compliance with sport-related concussion guidelines are limited. More concerted, coordinated, and theory-informed efforts are required to facilitate the widespread dissemination, translation, and implementation of such guidelines. An example is provided of how implementation drivers could be used to inform the development of a comprehensive, multilevel implementation strategy targeting the individual, organizational, and system-level changes necessary to support the translation of available sport-related concussion guidelines in both the clinical and sports settings.
Optimization of matching layer structure for piezoelectric fiber composite ultrasonic actuator and performance testing
Authors: Wang Ziping , Luo Ying , Yu Bo
Published: June 2014

Orthotropic piezoelectric fiber composite is used as a functional material for new phased array transducer, which can be applied in a wide range of fields such as natural gas, power industry, aerospace and other nondestructive evaluation fields. The backing layer of the transducer affects the pulse width and axial resolution directly. In order to find transducers with good sensitivity and short pulses, the pulse shape and frequency response for orthotropic piezoelectric fiber composite elements have been studied both theoretically and experimentally. The acoustic impedance of velocity testing criterion has been provided, and the relative theory and experiment have also been researched. The results show that orthotropic piezoelectric fiber composite has lower acoustic impedance and higher mechanical coupling factor. Also, the sensitivity and bandwidth of orthotropic piezoelectric fiber composite ultrasonic actuator have been improved.
Locating the qualitative interview: reflecting on space and place in nursing research
Authors: Gagnon Marilou , Jacob Jean Daniel , McCabe Janet
Published: June 2014

Interview location has been widely overlooked in the nursing literature. This paper presents a discussion of interview location in the context of nursing research with particular emphasis on the concepts of space and place. It draws on six research projects that were conducted between 2008 and 2013 in Canada, and is informed by key texts on the concepts of space and place. We argue that thinking about space and place in the context of interviewing is one way to engage in reflexivity. The reflexive accounts featured in this paper support the need for nursing researchers to engage in explicit analysis of their own interview locations and to discuss the significance of space and place in their own work. These accounts suggest that location is a fundamental aspect of the interview process.
Rare infection of implantable cardioverter-defibrillator lead with Candida albicans: case report and literature review
Authors: Rivera Nina Thakkar , Bray Natasha , Wang Hong , Zelnick Kenneth , Osman Ahmed , Vicuña Ricardo
Published: June 2014

Infection of implanted cardiac devices has a low rate of occurrence. Fungal infections of such devices represent an atypical phenomenon, associated with high mortality. Both medical and surgical therapies are recommended for a successful outcome.

A 60-year-old woman with past medical history of heart failure with reduced ejection fraction, implantable cardioverter-defibrillator (ICD) placement, sarcoidosis and diabetes presented with fevers and atypical pleuritic chest pain. Transthoracic echocardiogram revealed a highly mobile 2.09 cm by 4.49 cm mass associated with the ICD wire. Blood cultures were positive for Candida albicans. The patient underwent sternotomy for removal. The vegetation was 4 cm by 2 cm by 2 cm in size, attached to the right ventricle without interference with the tricuspid valve. The patient was treated with micafungin for 2 weeks and then fluconazole for 6 weeks.

In this case report, we describe the rare infection of an ICD lead with C. albicans, in the form of a fungal ball. This is the 18th reported case of Candida device-related endocarditis and the first reported in a woman. Prior case reports have occurred primarily in pacemaker rather than ICD leads. The vegetation size is also one of the largest that has been reported, measuring 4 cm at its greatest length.

As Candida device-related endocarditis is so rare, and as fatality occurs in half of cases, clinical management can only be derived from sporadic case reports. Therefore, the course of this patient’s disease care will be a useful adjunct to the current literature for determining treatment and prognosis in similar cases.
Assessing bowel preparation quality using the mean number of adenomas per colonoscopy
Authors: Hillyer Grace Clarke , Lebwohl Benjamin , Rosenberg Richard M. , Neugut Alfred I. , Wolf Randi , Basch Corey H. , Mata Jennie , Hernandez Edwin , Corley Douglas A. , Shea Steven , Basch Charles E.
Published: June 2014

Introduction:

The quality of the bowel preparation directly influences colonoscopy effectiveness. Quality indicators are widely employed to monitor operator performance and to gauge colonoscopy effectiveness. Some have suggested that the enumeration of the mean number of adenomas per colonoscopy (MNA) may be a more useful measure of bowel preparation quality, but evidence of the utility of this metric is limited. The relationship between bowel preparation quality and MNA was assessed.

Methods:

Records of adult patients, aged 50–74 years, who had undergone a screening colonoscopy in a 6 month period at a hospital-based endoscopy suite in New York City were examined. Excluded were those who were symptomatic or having a colonoscopy for surveillance. Patient and procedural characteristics and clinical findings were abstracted from the endoscopy database. Bowel preparation quality was recorded as excellent, good, fair and poor. Histology and size of polyps removed were gathered from pathology reports. MNA was calculated and incident rate ratios assessing the relationship between bowel preparation quality, MNA, and covariates was calculated using Poisson regression.

Results:

A total of 2422 colonoscopies were identified; 815 (33.6%) were screening colonoscopies among average risk individuals, 50–74 years; 203 (24.9%) had ≥1 adenomas; and 666 (81.7%) had excellent/good preparation quality. Overall MNA was 0.34 [standard deviation (SD) 0.68] and MNA was greater among those >60 years [incident rate ratio (IRR) 1.89, 95% confidence interval (CI) 1.48–2.42), males (IRR 1.60, 95%CI 1.26–2.04) and those with good bowel preparation (IRR 2.54, 95%CI 1.04–6.16). Among those with ≥1 adenomas, MNA was 1.48 (SD 1.05) for excellent and 1.00 (SD 0.00) for poor quality preparation ( p = 0.55).

Conclusions:

We found that MNA is sensitive to changes in bowel preparation with higher MNA among those with good bowel preparation compared with those with poor preparation. Our evidence suggests MNA was particularly sensitive when restricted to only those in whom adenomas were seen.
Peripheral Nervous System Manifestations of Infectious Diseases
Authors: Brizzi Kate T. , Lyons Jennifer L.
Published: June 2014

Infectious causes of peripheral nervous system (PNS) disease are underrecognized but potentially treatable. Heightened awareness educed by advanced understanding of the presentations and management of these infections can aid diagnosis and facilitate treatment. In this review, we discuss the clinical manifestations, diagnosis, and treatment of common bacterial, viral, and parasitic infections that affect the PNS. We additionally detail PNS side effects of some frequently used antimicrobial agents.
Tumefactive demyelinating disease with isolated spinal cord involvement
Authors: Makary Mina S , Kirsch Claudia F
Published: June 2014

Tumefactive multiple sclerosis (TMS) is an unusual variant of demyelinating disease. TMS has a variable and unknown progression and presents with features similar to a neoplasm making the determination a diagnostic challenge to clinicians. This report presents one of the very few reported cases of isolated spinal cord TMS, and the second case to describe TMS of the lower spinal cord, given that the lesions are typically cervical. This case study presents a diagnostic approach based on clinical, laboratory, and imaging characteristics, as well as sheds some light on the response to therapy and disease evolution.
Therapeutic vaccines as a promising treatment modality against prostate cancer: rationale and recent advances
Authors: Singh B. Harpreet , Gulley James L.
Published: June 2014

Cancer immunotherapy was deemed the medical breakthrough of 2013, in part because it can induce a rapid, durable, self-propagating and adaptable immune response. Specifically in prostate cancer, immunotherapy has emerged as a viable and attractive treatment strategy. To date, therapeutic cancer vaccines and immune checkpoint inhibitors are the two classes of immunotherapy that have demonstrated improvements in overall survival in patients with advanced tumors. The 2010 Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A class effect of these approved immune-based therapies is a benefit in overall survival without short-term changes in disease progression, apparently due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. A growing body of evidence suggests that the ideal population for clinical trials of cancer vaccines as monotherapy is patients with lower tumor volume and less aggressive disease. Combination strategies include immunotherapy with standard therapies or with other immunotherapies. Here we review emerging data on immunotherapy for patients with prostate cancer.
Hemostatic disorders in a JAK2V617F-driven mouse model of myeloproliferative neoplasm
Authors: Lamrani Lamia , Lacout Catherine , Ollivier Véronique , Denis Cécile V. , Gardiner Elizabeth , Ho Tin Noe Benoit , Vainchenker William , Villeval Jean-Luc , Jandrot-Perrus Martine
Published: June 2014

Key Points

Mice constitutively developing a JAK2V617F-induced PV exhibit a bleeding tendency combined with the accelerated formation of unstable clots. Hemostatic defects are not concomitant with JAK2V617F expression, suggesting they are not directly caused by the mutation.
The polycomb repressive complex 2 governs life and death of peripheral T cells
Authors: Zhang Yuxia , Kinkel Sarah , Maksimovic Jovana , Bandala-Sanchez Esther , Tanzer Maria C. , Naselli Gaetano , Zhang Jian-Guo , Zhan Yifan , Lew Andrew M. , Silke John , Oshlack Alicia , Blewitt Marnie E. , Harrison Leonard C.
Published: June 2014

Key Points

Ezh2 represses Ifng, Gata3, and Il10 loci in naïve CD4+T cells, and its deficiency leads to Th1 skewing and IL-10 overproduction in Th2 cells. Ezh2 deficiency activates multiple death pathways in differentiated effector Th cells.
Role of phenotypic and genetic testing in managing clopidogrel therapy
Authors: Chan Noel C. , Eikelboom John W. , Ginsberg Jeffrey S. , Lauw Mandy N. , Vanassche Thomas , Weitz Jeffrey I. , Hirsh Jack
Published: June 2014

The P2Y12 inhibitors, clopidogrel, prasugrel, and ticagrelor, are administered in fixed doses without laboratory monitoring. Randomized trials in acute coronary syndrome have shown that prasugrel and ticagrelor are more effective than standard-dose clopidogrel. Nonetheless, standard-dose clopidogrel remains widely used because it causes less bleeding and is less expensive. Patients treated with standard-dose clopidogrel have substantial variability in platelet inhibition, which is partly explained by genetic polymorphisms encoding CYP2C19, the hepatic enzyme involved in biotransformation of clopidogrel to its active metabolite. Some advocate tailoring P2Y12 inhibitor therapy according to the results of routine laboratory testing. Although there is good evidence for analytic, biological, and clinical validity of several phenotypic and genotypic biomarkers, the benefit of a management strategy that incorporates routine biomarker testing over standard of care without such testing remains unproven. Appropriately designed, adequately powered trials are needed but face the challenges of feasibility, cost, and the progressive switch from clopidogrel to prasugrel or ticagrelor.
A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity
Authors: Stalker Timothy J. , Welsh John D. , Tomaiuolo Maurizio , Wu Jie , Colace Thomas V. , Diamond Scott L. , Brass Lawrence F.
Published: June 2014

Key Points

β3 integrin tyrosine phosphorylation regulates thrombus consolidation in vivo. Intrathrombus solute transport regulates local thrombin activity and platelet activation during hemostatic thrombus formation in vivo.
A systems approach to hemostasis: 1. The interdependence of thrombus architecture and agonist movements in the gaps between platelets
Authors: Welsh John D. , Stalker Timothy J. , Voronov Roman , Muthard Ryan W. , Tomaiuolo Maurizio , Diamond Scott L. , Brass Lawrence F.
Published: June 2014

Key Points

Thrombus formation and contraction alters local molecular transport, which regulates agonist distribution and platelet activation. Semaphorin 4D contact-dependent signaling increases platelet activation, but does not affect platelet packing or agonist transport.
A systems approach to hemostasis: 2. Computational analysis of molecular transport in the thrombus microenvironment
Authors: Tomaiuolo Maurizio , Stalker Timothy J. , Welsh John D. , Diamond Scott L. , Sinno Talid , Brass Lawrence F.
Published: June 2014

Key Points

Hindered diffusion becomes the dominant force of molecular movement in a thrombus. The thrombus core acts as a selective molecular prison.
Fibrinogen γ′ increases the sensitivity to activated protein C in normal and factor V Leiden plasma
Authors: Omarova Farida , Uitte de Willige Shirley , Simioni Paolo , Ariëns Robert A. S. , Bertina Rogier M. , Rosing Jan , Castoldi Elisabetta
Published: June 2014

Key Points

Fibrinogen, and particularly fibrinogen γ′, counteracts plasma APC resistance, the most common risk factor for venous thrombosis. The C-terminal peptide of the fibrinogen γ′ chain inhibits protein C activation, but still improves the response of plasma to APC.
Acquired von Willebrand syndrome: von Willebrand factor propeptide to von Willebrand factor antigen ratio predicts remission status
Authors: Lee Adrienne , Sinclair Gary , Valentine Karen , James Paula , Poon Man-Chiu
Published: June 2014

Key Points

Remission status in relapsing-remitting AVWS depends on the balance of VWF clearance by anti-VWF antibody and VWF secretion. VWFpp:Ag ratio is a simple assay that provides information on this balance and predicts remission status in this case of AVWS.
Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
Authors: Girard-Gagnepain Anais , Amirache Fouzia , Costa Caroline , Lévy Camille , Frecha Cecilia , Fusil Floriane , Nègre Didier , Lavillette Dimitri , Cosset François-Loïc , Verhoeyen Els
Published: June 2014

Key Points

New LVs allow transduction of unstimulated hematopoietic stem cells.
Adhesion of Staphylococcus aureus to the vessel wall under flow is mediated by von Willebrand factor–binding protein
Authors: Claes Jorien , Vanassche Thomas , Peetermans Marijke , Liesenborghs Laurens , Vandenbriele Christophe , Vanhoorelbeke Karen , Missiakas Dominique , Schneewind Olaf , Hoylaerts Marc F. , Heying Ruth , Verhamme Peter
Published: June 2014

Key Points

vWbp mediates adhesion of S aureus under flow to activated endothelial cells and the subendothelium via VWF. vWbp activates prothrombin and triggers the formation of bacteria–fibrin–platelet aggregates, which enhance adhesion to vessels under flow.
Metabolic syndrome among psychiatric outpatients with mood and anxiety disorders
Authors: Hung Ching-I , Liu Chia-Yih , Hsiao Mei-Chun , Yu Nan-Wen , Chu Chun-Lin
Published: June 2014

Background

Few studies have simultaneously compared the impacts of pharmacotherapy and mental diagnoses on metabolic syndrome (MetS) among psychiatric outpatients with mood and anxiety disorders. This study aimed to investigate the impacts of pharmacotherapy and mental diagnoses on MetS and the prevalence of MetS among these patients.

Methods

Two-hundred and twenty-nine outpatients (men/women = 85/144) were enrolled from 1147 outpatients with mood and anxiety disorders by systematic sampling. Psychiatric disorders and MetS were diagnosed using the Structured Clinical Interview for DSM-IV-TR and the new International Diabetics Federation definition, respectively. The numbers of antipsychotics, mood stabilizers, and antidepressants being taken were recorded. Logistic regression was used to investigate the impacts of pharmacotherapy and psychiatric diagnoses on MetS.

Results

Among 229 subjects, 51 (22.3%) fulfilled the criteria for MetS. The prevalence of MetS was highest in the bipolar I disorder (46.7%) patients, followed by bipolar II disorder (25.0%), major depressive disorder (22.0%), anxiety-only disorders (16.7%), and no mood and/or anxiety disorders (14.3%). The percentages of MetS among the five categories were correlated with those of the patients being treated with antipsychotics and mood stabilizers. Use of antipsychotics and/or mood stabilizers independently predicted a higher risk of MetS after controlling for demographic variables and psychiatric diagnoses. When adding body mass index (BMI) as an independent variable in the regression model, BMI became the most significant factor to predict MetS.

Conclusion

BMI was found to be an important factor related to MetS. Pharmacotherapy might be one of underlying causes of elevated BMI. The interactions among MetS, BMI, pharmacotherapy, and psychiatric diagnoses might need further research.
Rapamycin up-regulation of autophagy reduces infarct size and improves outcomes in both permanent MCAL, and embolic MCAO, murine models of stroke
Authors: Buckley Kathleen M , Hess Daniel L , Sazonova Irina Y , Periyasamy-Thandavan Sudharsan , Barrett John R , Kirks Russell , Grace Harrison , Kondrikova Galina , Johnson Maribeth H , Hess David C , Schoenlein Patricia V , Hoda Md Nasrul , Hill William D
Published: June 2014

Background and purpose

The role of autophagy in response to ischemic stroke has been confusing with reports that both enhancement and inhibition of autophagy decrease infarct size and improve post-stroke outcomes. We sought to clarify this by comparing pharmacologic modulation of autophagy in two clinically relevant murine models of stroke.

Methods

We used rapamycin to induce autophagy, and chloroquine to block completion of autophagy, by treating mice immediately after stroke and at 24 hours post-stroke in two different models; permanent Middle Cerebral Artery Ligation (MCAL), which does not allow for reperfusion of distal trunk of middle cerebral artery, and Embolic Clot Middle Cerebral Artery Occlusion (eMCAO) which allows for a slow reperfusion similar to that seen in most human stroke patients. Outcome measures at 48 hours post-stroke included infarct size analysis, behavioral assessment using Bederson neurological scoring, and survival.

Results

Chloroquine treatment reduced the lesion size by approximately 30% and was significant only in the eMCAO model, where it also improved the neurological score, but did not increase survival. Rapamycin reduced lesion size by 44% and 50% in the MCAL and eMCAO models, respectively. Rapamycin also improved the neurological score to a greater degree than chloroquine and improved survival.

Conclusions

While both inhibition and enhancement of autophagy by pharmacological intervention decreased lesion size and improved neurological scores, the enhancement with rapamycin showed a greater degree of improvement in outcomes as well as in survival. The protective action seen with chloroquine may be in part due to off-target effects on apoptosis separate from blocking lysosomal activity in autophagy. We conclude pharmacologic induction of autophagy is more advantageous than its blockade in physiologically-relevant permanent and slow reperfusion stroke models.
A comparison of three 67/68Ga-labelled exendin-4 derivatives for β-cell imaging on the GLP-1 receptor: the influence of the conjugation site of NODAGA as chelator
Authors: Jodal Andreas , Lankat-Buttgereit Brigitte , Brom Maarten , Schibli Roger , Béhé Martin
Published: June 2014

Background

Various diseases derive from pathologically altered β-cells. Their function can be increased, leading to hyperinsulinism, or decreased, resulting in diabetes. Non-invasive imaging of the β-cell-specific glucagon-like peptide receptor-1 (GLP-1R) would allow the assessment of both β-cell mass and derived tumours, potentially improving the diagnosis of various conditions. We tested three new 67/68Ga-labelled derivatives of exendin-4, an agonist of GLP-1R, in vitro and in vivo. We determined the influence of the chelator NODAGA conjugated to resident lysines either at positions 12 and 27 or the C-terminally attached lysine at position 40 on the binding and kinetics of the peptide.

Methods

Binding and internalisation of 67Ga-labelled Ex4NOD12, Ex4NOD27 and Ex4NOD40 were tested on Chinese hamster lung (CHL) cells stably transfected to express the GLP-1 receptor (GLP-1R). In vivo biodistribution of 68Ga-labelled peptides was investigated in CD1 nu/nu mice with subcutaneous CHL-GLP-1R positive tumours; the specificity of the binding to GLP-1R was determined by pre-injecting excess peptide.

Results

All peptides showed good in vitro binding affinities to GLP-1R in the range of 29 to 54 nM. 67/68Ga-Ex4NOD40 and 67/68Ga-Ex4NOD12 show excellent internalisation (>30%) and high specific uptake in GLP-1R positive tissue, but high activity was also found in the kidneys.

Conclusions

We show that of the three peptides, Ga-Ex4NOD40 and Ga-Ex4NOD12 demonstrate the most favourable in vitro properties and in vivo binding to GLP-1R positive tissue. Therefore, we conclude that the lysines at positions 12 and 40 might preferentially be utilised for modifying exendin-4.