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Variety management is a cross-domain issue in product family design. In the real field, the relationships across the domains are so complex for most of the existing product families that they cannot be easily identified without proper reference architecture. This reference architecture should provide the cross- domain mapping mechanisms in an explicit manner and be able to identify the proper units for management. From this perspective of cross-domain framework, this paper introduces development architecture (DA) to describe the relationships between elements in market, design, and production domains and to give insights for the cross-domain variety management in the product development stage. DA has three parts: (1) the arrangement of elements in each domain, (2) the mapping between elements, and (3) the identification of management sets and key interfaces which are the proper units for variety management. The proposed development architecture framework is applied to the case of front chassis family of modules of an automobile.
Background: It is well understood that gliomas require vast supply of energy to proliferate, invade and spread. We wished to identify novel biomarkers by comparing normal brain and plasma to high and low grade gliomas using newer techniques in laser ionization mass spectroscopy - precision metabolomics and lipidomics. Methods: Single center IRB approved tissue bank of “normal” brain and plasma (n=6) and IDH wild-type GBM tissue and plamsa (n=29), IDH mutant GBM tissue and plamsa (n=6), Low grade glioma (n=4) tissue and plamsa were analyzed for over 2000 endogenous metbolites and complex lipids. Unbiased clustering and Random Forest plots and pathway analysis were performed with appropriate statsitical analysis (significance p < 0.05). Results: IDH mutant GBM had higher levels of 2-HG, however, plasma 2-HG did not reflect IDH genotype. Changes in glucose and fatty acid utilization were observed in IDH WT and mutant gliomas compared to normal brain tissue. Lipidomics of plasma and tissue of normal and gliomas did not reveal a biomarker reaching statistical significance. Conclusions: We will continue to investigate if plasma and tissue biomarkers including hypotaurine, methionine, branched chain amino acid catabolites and pregnonolone can be used to predict tumor progression, response to treatment and clinical outcomes.
We study the effect of corporate cultural similarity on merger decisions and outcomes. Using the similarity in firms’ corporate social responsibility characteristics to proxy for cultural similarity, we find that culturally similar firms are more likely to merge. Moreover, these mergers are associated with greater synergies, superior long-run operating performance, and fewer write-offs of goodwill. Our evidence is consistent with the notion that cultural similarity eases post-deal integration. Our results contribute to the literature on the determinants of merger success, provide new evidence on the impact of corporate culture, and offer a new approach to defining firms’ cultural similarity.
Background: Lactate, a by-product of glycolysis, has been well established as a marker of poor tissue perfusion. Elevated lactate production is observed in tumor glycolysis known as the Warburg effect. We have previously shown that serum lactate correlated with brain tumor grade. In this prospective study we aimed to determine if the preoperative serum lactate correlated with preoperative MR spectroscopy and in lactate levels in the fresh frozen tissue samples. Methods: Twenty-one glioma patients (13 male, 8 female) ages 34 – 86 underwent craniotomy at a single institution by lead author. Tumor pathology revealed a Glioblastoma (n=16), grade II (oligodendroglioma n=1) and Grade III Glioma (anaplastic astrocytoma n=4). Preoperative spectroscopy was performed on 18 patients. A fellowship trained neuro-radiologist (JPC) was blinded to the serum and tissue lactate levels and graded the spectroscopy lactate levels as low or elevated. Results: There was direct correlation of spectroscopy tissue lactate levels with serum lactate levels. Pre-operative serum lactate (range 6.6- 29.9 mg/dl) was directly correlated with the fresh frozen tissue lactate levels (range 0.1 – 0.39 ug/mg; Pearson r=0.6 p = 0.0021). Conclusions: This study supports that serum lactate correlates with spectroscopy and tissue lactate levels.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
The objective of this study was to develop a shared-care model to enable primary-care physicians to participate more fully in meeting the complex, multidisciplinary healthcare needs of patients with multiple sclerosis (MS). Design: The design consisted of development of consensus recommendations and a shared-care algorithm. Participants: A working group of 11 Canadian neurologists involved in the management of patients with MS were included in this study. Main message: The clinical management of patients with multiple sclerosis is increasing in complexity as new disease-modifying therapies (DMTs) become available, and ongoing safety monitoring is required. A shared-care model that includes primary care physicians is needed. Primary care physicians can assist in the early detection of MS of individuals presenting with neurological symptoms. Additional key roles for family physicians are health promotion, symptom management, and safety and relapse monitoring of DMT-treated patients. General principles of health promotion include counseling MS patients on maintaining a healthy lifestyle; performing standard screening measures; and identifying and treating comorbidities. Of particular importance are depression and anxiety, which occur in >20% of MS patients. Standard work-ups and treatments are needed for common MS-related symptoms, such as fatigue, pain, bladder dysfunction, sexual dysfunction, spasticity, and sleep disorders. Ongoing safety monitoring is required for patients receiving specific DMTs. Multiple sclerosis medications are generally contraindicated during pregnancy, and patients should be counseled to practice effective contraception. Conclusions: Multiple sclerosis is a complex, disabling illness, which, similar to other chronic diseases, requires ongoing multidisciplinary care to meet the evolving needs of patients throughout the clinical course. Family physicians can play an invaluable role in maintaining general health, managing MS-related symptoms and comorbidities, monitoring for treatment-related adverse effects and MS relapses, and coordinating allied health services to ensure continuity of care to meet the complex and evolving needs of MS patients through the disease course. RÉSUMÉ:Élaborer un modèle de soins partagés dans les cas de sclérose en plaques récurrente-rémittente.Objectif: Élaborer un modèle de soins partagés afin de permettre aux médecins de première ligne de mieux répondre aux besoins complexes et multidisciplinaires de patients atteints de la sclérose en plaques (SP). Conception : Recommandations résultant d’un consensus et élaboration d’un algorithme en matière de soins partagés. Participants : Un groupe de travail formé de onze neurologues canadiens impliqués dans la prise en charge de patients atteints de la SP. Message-clé : La prise en charge clinique de patients atteints de la SP est de plus en plus complexe dans la mesure où des médicaments modificateurs de l’évolution de la maladie (MMSP) deviennent accessibles et où un suivi permanent en matière de sécurité est nécessaire. Soulignons aussi qu’un modèle de soins partagés incluant les médecins de première ligne est nécessaire. Ces professionnels peuvent permettre un dépistage plus rapide de la SP chez des individus présentant des symptômes neurologiques. Ils peuvent aussi jouer un rôle de premier plan en matière de promotion de la santé, de soulagement des symptômes et de suivi de patients traités avec des MMSP en ce qui a trait à leur sécurité et à de possibles rechutes. Parmi les principes généraux de promotion de la santé, on peut inclure les suivants : offrir aux patients atteints de la SP des conseils leur permettant de maintenir de saines habitudes de vie ; adopter des mesures de dépistage standards ; identifier et traiter les comorbidités. À cet égard, l’anxiété et la dépression sont d’une importance particulière et sont fréquemment signalées (> 20 %) chez les patients atteints de SP. Des démarches d’investigation et des traitements standards sont nécessaires dans le cas des symptômes courants reliés à la SP, par exemple de la fatigue, des douleurs, une dysfonction vésicale, des dysfonctions sexuelles, de la spasticité et des troubles du sommeil. On l’a dit, un suivi permanent s’impose dans le cas de patients bénéficiant d’un traitement spécifique avec des MMSP. Les médicaments associés à la SP sont généralement contre-indiqués durant la grossesse de sorte qu’on devrait conseiller aux patients d’adopter des méthodes de contraception efficaces. Conclusions : La SP est une maladie complexe et invalidante qui, à l’instar d’autres maladies chroniques, exige des soins multidisciplinaires continus afin de répondre, en lien avec un tableau clinique précis, aux besoins en constante évolution des patients. Les médecins de première ligne peuvent jouer un rôle irremplaçable à plusieurs égards : dans le maintien d’une bonne santé ; le suivi et le soulagement des symptômes et des comorbidités reliés à la SP ; le suivi des rechutes et des effets indésirables associés aux traitements. N’oublions pas non plus la coordination des services paramédicaux afin d’assurer, durant l’évolution de la SP, une continuité des soins répondant aux besoins complexes et en constante évolution des patients atteints de cette maladie.
An estimated 293,300 healthcare-associated cases of Clostridium difficile infection (CDI) occur annually in the United States. To date, research has focused on developing risk prediction models for CDI that work well across institutions. However, this one-size-fits-all approach ignores important hospital-specific factors. We focus on a generalizable method for building facility-specific models. We demonstrate the applicability of the approach using electronic health records (EHR) from the University of Michigan Hospitals (UM) and the Massachusetts General Hospital (MGH).
We utilized EHR data from 191,014 adult admissions to UM and 65,718 adult admissions to MGH. We extracted patient demographics, admission details, patient history, and daily hospitalization details, resulting in 4,836 features from patients at UM and 1,837 from patients at MGH. We used L2 regularized logistic regression to learn the models, and we measured the discriminative performance of the models on held-out data from each hospital.
Using the UM and MGH test data, the models achieved area under the receiver operating characteristic curve (AUROC) values of 0.82 (95% confidence interval [CI], 0.80–0.84) and 0.75 ( 95% CI, 0.73–0.78), respectively. Some predictive factors were shared between the 2 models, but many of the top predictive factors differed between facilities.
A data-driven approach to building models for estimating daily patient risk for CDI was used to build institution-specific models at 2 large hospitals with different patient populations and EHR systems. In contrast to traditional approaches that focus on developing models that apply across hospitals, our generalizable approach yields risk-stratification models tailored to an institution. These hospital-specific models allow for earlier and more accurate identification of high-risk patients and better targeting of infection prevention strategies.
With the increase in regulations regarding the use of antibiotic growth promoters and the rise in consumer demand for poultry products from ‘Raised Without Antibiotics’ or ‘No Antibiotics Ever’ flocks, the quest for alternative products or approaches has intensified in recent years. A great deal of research has focused on the development of antibiotic alternatives to maintain or improve poultry health and performance. This review describes the potential for the various alternatives available to increase animal productivity and help poultry perform to their genetic potential under existing commercial conditions. The classes of alternatives described include probiotics, prebiotics, synbiotics, organic acids, enzymes, phytogenics, antimicrobial peptides, hyperimmune egg antibodies, bacteriophages, clay, and metals. A brief description of the mechanism of action, efficacy, and advantages and disadvantages of their uses are also presented. Though the beneficial effects of many of the alternatives developed have been well demonstrated, the general consensus is that these products lack consistency and the results vary greatly from farm to farm. Furthermore, their mode of action needs to be better defined. Optimal combinations of various alternatives coupled with good management and husbandry practices will be the key to maximize performance and maintain animal productivity, while we move forward with the ultimate goal of reducing antibiotic use in the animal industry.
Hearing loss can impair effective communication between caregivers and individuals with cognitive impairment. However, hearing loss is not often measured or addressed in care plans for these individuals. The aim of this study is to measure the prevalence of hearing loss and the utilization of hearing aids in a sample of individuals with cognitive impairment in a tertiary care memory clinic.
A retrospective review of 133 charts of individuals >50 years who underwent hearing assessment at a tertiary care memory clinic over a 12-month period (June 2014–June 2015) was undertaken. Using descriptive statistics, the prevalence of hearing loss was determined and associations with demographic variables, relevant medical history, cognitive status, and hearing aid utilization were investigated.
Results indicate that hearing loss is highly prevalent among this sample of cognitively impaired older adults. Sixty percent of the sample had at least a mild hearing loss in the better hearing ear. Among variables examined, age, MMSE, and medical history of diabetes were strongly associated with hearing impairment. Hearing aid utilization increased in concordance with severity of hearing loss, from 9% to 54% of individuals with a mild or moderate/severe hearing loss, respectively.
Hearing loss is highly prevalent among older adults with cognitive impairment. Despite high prevalence of hearing loss, hearing aid utilization remains low. Our study highlights the importance of hearing evaluation and rehabilitation as part of the cognitive assessment and care management plan in this vulnerable population.
We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.
7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.
Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.
We show how estimates of parameters characterizing inflation-based theories of structure formation localized over the past year when large scale structure (LSS) information from galaxy and cluster surveys was combined with the rapidly developing cosmic microwave background (CMB) data, especially from the recent Boomerang and Maxima balloon experiments. All current CMB data plus a relatively weak prior probability on the Hubble constant, age and LSS points to little mean curvature (Ωtot = 1.08±0.06) and nearly scale invariant initial fluctuations (ns = 1.03±0.08), both predictions of (non-baroque) inflation theory. We emphasize the role that degeneracy among parameters in the Lpk = 212 ± 7 position of the (first acoustic) peak plays in defining the Ωtot range upon marginalization over other variables. Though the CDM density is in the expected range (Ωcdmh2 = 0.17 ± 0.02), the baryon density Ωbh2 = 0.030 ± 0.005 is somewhat above the independent 0.019 ± 0.002 nucleosynthesis estimates. CMB+LSS gives independent evidence for dark energy (ΩΛ = 0.66 ± 0.06) at the same level as from supernova (SN1) observations, with a phenomenological quintessence equation of state limited by SN1+CMB+LSS to wQ < −0.7 cf. the wQ=−1 cosmological constant case.
In light of the growing burden of dementia, continued research into risk factors and potential contributors to disease development is essential. Clearly established risk factors can not only inform our understanding of disease pathophysiology and treatments but also identify potential preventive strategies. While age and the ApoE4 allele have consistently been shown to increase risk of developing dementia (Kukull et al., 2002), other risk factors have been less studied or have had inconsistent findings. The study by Booker and colleagues (Booker et al., 2016) re-examines proposed late-life medical risk factors for incident dementia in a large population-based case-control study. This important contribution is best interpreted in the context of existing research.
Objectives: Developing a search strategy for use in a systematic review is a time-consuming process requiring construction of detailed search strings using complicated syntax, followed by iterative fine-tuning and trial-and-error testing of these strings in online biomedical search engines.
Methods: Building upon limitations of existing online-only search builders, a user-friendly computer-based tool was created to expedite search strategy development as part of production of a systematic review.
Results: Search Builder 1.0 is a Microsoft Excel®-based tool that automatically assembles search strategy text strings for PubMed (www.pubmed.com) and Embase (www.embase.com), based on a list of user-defined search terms and preferences. With the click of a button, Search Builder 1.0 automatically populates the syntax needed for functional search strings, and copies the string to the clipboard for pasting into Pubmed or Embase. The offline file-based interface of Search Builder 1.0 also allows for searches to be easily shared and saved for future reference.
Conclusions: This novel, user-friendly tool can save considerable time and streamline a cumbersome step in the systematic review process.
Background: A definitive diagnosis of multiple sclerosis (MS), as distinct from a clinically isolated syndrome, requires one of two conditions: a second clinical attack or particular magnetic resonance imaging (MRI) findings as defined by the McDonald criteria. MRI is also important after a diagnosis is made as a means of monitoring subclinical disease activity. While a standardized protocol for diagnostic and follow-up MRI has been developed by the Consortium of Multiple Sclerosis Centres, acceptance and implementation in Canada have been suboptimal. Methods: To improve diagnosis, monitoring, and management of a clinically isolated syndrome and MS, a Canadian expert panel created consensus recommendations about the appropriate application of the 2010 McDonald criteria in routine practice, strategies to improve adherence to the standardized Consortium of Multiple Sclerosis Centres MRI protocol, and methods for ensuring effective communication among health care practitioners, in particular referring physicians, neurologists, and radiologists. Results: This article presents eight consensus statements developed by the expert panel, along with the rationale underlying the recommendations and commentaries on how to prioritize resource use within the Canadian healthcare system. Conclusions: The expert panel calls on neurologists and radiologists in Canada to incorporate the McDonald criteria, the Consortium of Multiple Sclerosis Centres MRI protocol, and other guidance given in this consensus presentation into their practices. By improving communication and general awareness of best practices for MRI use in MS diagnosis and monitoring, we can improve patient care across Canada by providing timely diagnosis, informed management decisions, and better continuity of care.
A novel nano-scale manipulator capable of handling low-dimensional materials with three-dimensional linear motion, gripping action, and push–pull action of the gripper was developed for an in situ experiment in transmission electron microscopy. X-Y-Z positioning and push–pull action were accomplished by a piezotubing system, combined with a specially designed assembly stage that consisted of a lever-action gripping tip backed by a push–pull piezostack. The gripper tip consisted of tungsten wire fabricated by electrochemical etching followed by a focused ion beam process. Performance of the nano-scale manipulator was demonstrated in a grab-and-pick test of a single silver nanowire and in an in situ tensile test of a pearlitic steel sample with a specific orientation.
Considerable interest in understanding interfacial phenomena occurring across nanostructured solid oxide fuel cell (SOFC) membrane electrode assemblies has increased demand for in situ characterization techniques with higher resolution. We briefly outline recent advancements in atomic force microscopy (AFM) instrumentation and subsystems in realizing real time imaging at high temperatures and ambient pressures, and the use of these in situ, multi-stimuli probes in collecting local information related to physical and fundamental processes. Here we demonstrate direct probing of local surface potential gradients related to the ionic conductivity of yttria-stabilized zirconia (YSZ) within symmetric SOFCs under intermediate operating temperatures (500–600 °C) via variable temperature scanning surface potential microscopy (VT-SSPM). The conductivity values obtained at different temperatures are then used to estimate the activation energy. These locally collected conductivity and activation energy values are subsequently compared to macroscopic electrochemical impedance results and bulk literature values, thus supporting the validity of the approach.