Pivotal Approach Research Articles

CT-guided nephrostomy–An expedient tool for complex clinical scenarios

Introduction & objectivesPercutaneous nephrostomy [1] has emerged as a pivotal approach in the therapeutic management of the obstructed urinary tract. A consecutive incorporation of ultrasonic and radiographic guidance, the approach experienced an almost ubiquitious distribution while most centers currently applying either one or both of these tools jointly. However, success of ultrasound-guidance is limited in obese patients and non-dilated uropathy. In turn, fluoroscopy usually requires an opacification of the urinary collecting system by intravenous or antegrade contrast media injection, which might be harmful for already impaired renal function, raise intrapelvic pressure and augment the risk of sepsis and hemorrhage. CT-guided PCN aids in overcoming these limitations. In the current study, we present the experience of a tertiary referral center with this technique. Materials & methodsEpidemiological and clinical data of all patients treated with a CT-guided PCN of native kidneys at the University Hospital Frankfurt between October 2003 and October 2013 were retrospectively collected from the patient charts. Procedural parameters including radiological aspects, technical and therapeutic success, complication and mortality rate have been analyzed statistically. ResultsIn total, 140 PCN procedures have been performed in 77 patients with a median age of 69 (± 13). The median body mass index was 27 with 66.6% of patients being overweight or obese. Charlson comorbidity index was 7 ranging 0-16. Indications for PCNs were obstructive uropathy (62.9), urine extravasation (22.9%), urinary tract fistulas (11.4%) and technical reasons (2.8%). In 68.8% of patients, initial diagnosis was malignancy. 56.4% of kidneys were non-dilated before puncture. In 78.4% prone position, otherwise supine oblique position (17.3%) or supine position (4.3%) was used. 71.4% of PCNs were carried out solely under local anesthesia. Technical success has been achieved in 90% with a complication rate of 3.6% (all grade minor B) and was not significantly different between dilated and non-dilated kidneys. 42.9% of fistulas and 64.3% of urinary tract leakages, healed after PCN placement. 30 days mortality rate was 5.2% without being directly associated with the PCN procedure itself. ConclusionCT-guided PCN is a feasible approach associated with low morbidity. It is particularly useful in complex clinical scenarios e.g. critically ill, newly operated or obese patients as well as non-dilated kidneys. Moreover, it represents a minimally-invasive option for treating leakages and fistulas of the urinary tract.

Opportunities and Challenges of Whole-Cell and -Tissue Simulations of the Outer Retina in Health and Disease

Visual processing starts in the outer retina, where photoreceptor cells sense photons that trigger electrical responses. Retinal pigment epithelial cells are located external to the photoreceptor layer and have critical functions in supporting cell and tissue homeostasis and thus sustaining a healthy retina. The high level of specialization makes the retina vulnerable to alterations that promote retinal degeneration. In this review, we discuss opportunities and challenges in proposing whole-cell and -tissue simulations of the human outer retina. An implicit position taken throughout this review is that mapping diverse data sets onto integrative computational models is likely to be a pivotal approach to understanding complex disease and developing novel interventions.

The Policy of Whistleblowing in Nigeria

One of the most direct methods of exposing corruption in corporate or public institutions is whistleblowing. Quite a number of countries, including Nigeria, have introduced a whistleblowing policy. Among its provisions is to deter corrupt behaviours and guide formal investigations into them. However, Nigeria still lags far behind in this respect, perhaps out of structural inertia in dealing with corruption cases. In this article, the author argues that Nigeria can benefit from the institutional, educational and spiritual framework embedded in whistleblowing in Islam through ‘amr bi-l-ma'rūf wa-naḥy ‘an al-munkar i.e., enjoining good and forbidding wrong. The article, through historical and descriptive approaches, explains the policy of whistleblowing from the Islamic perspective, hence, clarifying some Muslims misconceptions. This study, therefore, presents Islamic principles on the whistleblowing policy and explains some pivotal approaches to addressing whistleblowing policy in Nigeria.

Формирование навыков научной коммуникации в процессе подготовки иностранных граждан к поступлению в магистратуру российского вуза

The study reviews the pivotal approaches to mastering the scientific language by foreign citizens, future philologists, applying for a Master’s degree in a Russian university. The author focuses on the problem of obtaining new knowledge in a foreign language environment against the background of dynamic sociocultural and communicative processes in modern scientific writing. By a case study of Preparatory School at Pushkin State Russian Language Institute, the research demonstrates the features of international students enrolled in the course in Training Non-Citizens to Join the Master’s Degree Programs (in Humanities) in the Russian language. Based on the research findings, the author developed recommendations for amending and complementing the course syllabus for the in-depth study of the professional language.

Targeting phosphodiesterase 4 as a potential therapeutic strategy for enhancing neuroplasticity following ischemic stroke.

Sensorimotor recovery following ischemic stroke is highly related with structural modification and functional reorganization of residual brain tissues. Manipulations, such as treatment with small molecules, have been shown to enhance the synaptic plasticity and contribute to the recovery. Activation of the cAMP/CREB pathway is one of the pivotal approaches stimulating neuroplasticity. Phosphodiesterase 4 (PDE4) is a major enzyme controlling the hydrolysis of cAMP in the brain. Accumulating evidences have shown that inhibition of PDE4 is beneficial for the functional recovery after cerebral ischemia; i. subtype D of PDE4 (PDE4D) is viewed as a risk factor for ischemic stroke; ii. inhibition of PDE4 enhances neurological behaviors, such as learning and memory, after stroke in rodents; iii.PDE4 inhibition increases dendritic density, synaptic plasticity and neurogenesis; iv. activation of cAMP/CREB signaling by PDE4 inhibition causes an endogenous increase of BDNF, which is a potent modulator of neuroplasticity; v. PDE4 inhibition is believed to restrict neuroinflammation during ischemic stroke. Cumulatively, these findings provide a link between PDE4 inhibition and neuroplasticity after cerebral ischemia. Here, we summarized the possible roles of PDE4 inhibition in the recovery of cerebral stroke with an emphasis on neuroplasticity. We also made some recommendations for future research.

Test Path Prioritization from UML Activity Diagram Using a Hybridized Approach

Software testing is regarded as a pivotal approach to realize a high reliable product. To check for the correctness of results, we require appropriate test cases. UML models are largely used to depict the specifications for software development. Test cases are created independently and based on the sequence of occurrence in the diagrams; they lead to corresponding test paths in the program. In this paper, we have analyzed an activity diagram, consisting of concurrent activities, for generating test paths. The obtained test paths are therefore required to be ranked. We have demonstrated that it is conceivable to apply Genetic Algorithm procedures alongside Ant Colony Optimization technique for not only finding the most critical path but also prioritizing the other paths too for enhancing the effectiveness of software testing.

Diet enrichment with a specific essential free amino acid mixture improves healing of undressed wounds in aged rats

Chronic wounds are a major, often underestimated, health problem for the elderly. Standard wound care products are not usually manufactured to meet the increased demand of nutrients by skin cells in order to regenerate new tissue and accelerate healing. This work was therefore undertaken to establish whether wound healing could be accelerated by nutritional supplementation with a specific mixture tailored to human need of essential amino acids (EAAs) without topical medication. To this end, using a skin full-thickness excisional model in aged rats, we compared the closure dynamics of undressing wounds in animals fed an EAAs-enriched diet or standard diet. We assessed the degree of fibrosis and inflammation, as well as relevant signaling molecules such as COL1A1, iNOS and TGFβ1. The results showed wound healing was accelerated in EAAs-fed rats, which was accompanied by reduced inflammation and changes in TGFβ1 and COL1A1 expression. Collectively, our findings indicate that dietary supplementation with balanced EAAs diet could serve as a strategy to accelerate wound healing without inducing fibrosis and could therefore be a simple but pivotal therapeutic approach in human also.

A structure-preserving pivotal method for affine variational inequalities

Affine variational inequalities (AVI) are an important problem class that subsumes systems of linear equations, linear complementarity problems and optimality conditions for quadratic programs. This paper describes PathAVI, a structure-preserving pivotal approach, that can efficiently process (solve or determine infeasible) large-scale sparse instances of the problem with theoretical guarantees and at high accuracy. PathAVI implements a strategy known to process models with good theoretical properties without reducing the problem to specialized forms, since such reductions may destroy sparsity in the models and can lead to very long computational times. We demonstrate formally that PathAVI implicitly follows the theoretically sound iteration paths, and can be implemented in a large scale setting using existing sparse linear algebra and linear programming techniques without employing a reduction. We also extend the class of problems that PathAVI can process. The paper illustrates the effectiveness of our approach by comparison to the Path solver used on a complementarity reformulation of the AVI in the context of applications in friction contact and Nash Equilibria. PathAVI is a general purpose solver, and freely available under the same conditions as Path.

A generalized pivotal quantity approach to portfolio selection

ABSTRACTThe major problem of mean–variance portfolio optimization is parameter uncertainty. Many methods have been proposed to tackle this problem, including shrinkage methods, resampling techniques, and imposing constraints on the portfolio weights, etc. This paper suggests a new estimation method for mean–variance portfolio weights based on the concept of generalized pivotal quantity (GPQ) in the case when asset returns are multivariate normally distributed and serially independent. Both point and interval estimations of the portfolio weights are considered. Comparing with Markowitz's mean–variance model, resampling and shrinkage methods, we find that the proposed GPQ method typically yields the smallest mean-squared error for the point estimate of the portfolio weights and obtains a satisfactory coverage rate for their simultaneous confidence intervals. Finally, we apply the proposed methodology to address a portfolio rebalancing problem.

Radiation Synthesis of Poly(Starch/Acrylic acid) pH Sensitive Hydrogel for Rutin Controlled Release

The copolymerization of starch with acrylic acid AAc using direct gamma radiation technique was performed. The effect of AAc concentrations on the gel (%) and swelling behavior were investigated. It is found that as AAc concentrations increase both gel(%) and swelling behavior increase. The Poly(starch/acrylic acid) (1:10wt%) hydrogel were selected due to its high swelling properties. From the in-vitro release study of the rutin-loaded hydrogel it is observed that it is strong pH-dependent release behavior, thus offering a maximum release as pH increased. The dextran sulphate sodium (DSS)-induced rat colitis model was treated with rutin-loaded Poly(starch/acrylic acid) (1:10wt%) hydrogel and free rutin solution by oral administration. Colitic control group showed a significant elevation in colon/body weight ratio, myeloperoxgidase activity, tumor necrosis factor, nitric oxide and malondialdehyde levels. However, glutathione level was reduced. It was found that the rutin-loaded hydrogel was more efficient than free rutin as evidenced by improvement of all measured parameters. These effects were confirmed histopathologically and may be attributed to its ability to control delivery of rutin to colon with minor early release of rutin before colon. The Poly(starch/acrylic acid) (1:10wt%) can represent a pivotal anti-inflammatory approach for patients with inflammatory bowel disease in order to increase efficacy and reduce toxicity.

Abstract 4677: Tumor suppressor p53 reactivation by oncolytic adenovirus reverses chemoresistance in human osteosarcomas

Abstract Background: Osteosarcoma is a primary malignant bone tumor. Despite recent advances in multi-agent chemotherapy and aggressive surgical resection, the poor response to chemotherapy often contributes to poor prognosis in osteosarcoma patients. Therefore, the development of novel strategies for reversing the chemoresistance is a pivotal approach to improve the clinical outcome for osteosarcoma patients. We recently developed a tumor suppressor p53-expressing oncolytic adenovirus, OBP-702, which drives the adenoviral E1 gene under the control of the human telomerase reverse transcriptase promoter for tumor-specific virus replication and induces profound p53 expression for tumor-specific cell death. We recently found that OBP-702 effectively kills human osteosarcoma cells. In this study, we investigated the therapeutic potential of OBP-702 as a chemosensitizing reagent in human osteosarcoma cells with different p53 status. Methods: We used 4 human osteosarcoma cell lines with different p53 status, including U2OS (p53 wild-type), MNNG/HOS (p53 mutant), 143B (p53 mutant), SaOS2 (p53 null). We also used the doxorubicin (DOX)-resistant U2OS cells, which were established by sequential exposure to DOX over 3 months. We performed the XTT assay to examine the antitumor effects of DOX and OBP-702. Combination efficacy between DOX and OBP-702 was assessed by calculating the combination index using CalcuSyn software (BioSoft, Inc.). We further investigated the DOX- and OBP-702-mediated apoptosis in parental and DOX-resistant U2OS cells using Western blot analysis. Results: OBP-702 improved the sensitivity to DOX in a dose-dependent manner in all 4 osteosarcoma cell lines. The calculation of combination index revealed the synergistic effect in all 4 osteosarcoma cell lines. Combination with DOX and OBP-702 induced more profound apoptosis than monotherapy in all 4 osteosarcoma cell lines. Moreover, in DOX-resistant U2OS cells, OBP-702 induced the cytopathic effect as well as parental U2OS cells. Synergistic effect was also observed in DOX-resistant U2OS cells when we treated with DOX and OBP-702. Although DOX-resistant U2OS cells was more resistant to the DOX-mediated apoptosis than parental cells, OBP-702 enhanced the DOX-mediated apoptosis in DOX-resistant U2OS cells as well as parental cells. Conclusions: These results suggest that OBP-702-mediated p53 reactivation reverses the chemoresistance in human osteosarcomas. Citation Format: Kazuhisa Sugiu, Hiroshi Tazawa, Joe Hasei, Shuhei Osaki, Yasuaki Yamakawa, Toshinori Omori, Tadashi Komatsubara, Kouji Uotani, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara. Tumor suppressor p53 reactivation by oncolytic adenovirus reverses chemoresistance in human osteosarcomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4677.

Probabilistic measures of cost-effectiveness.

Several probability-based measures are introduced in order to assess the cost-effectiveness of a treatment. The basic measure consists of the probability that one treatment is less costly and more effective compared with another. Several variants of this measure are suggested as flexible options for cost-effectiveness analysis. The proposed measures are invariant under monotone transformations of the cost and effectiveness measures. Interval estimation of the proposed measures are investigated under a parametric model, assuming bivariate normality, and also non-parametrically. The delta method and a generalized pivotal quantity approach are both investigated under the bivariate normal model. A non-parametric U-statistics-based approach is also investigated for computing confidence intervals. Numerical results show that under bivariate normality, the solution based on generalized pivotal quantities exhibits accurate performance in terms of maintaining the coverage probability of the confidence interval. The non-parametric U-statistics-based solution is accurate for sample sizes that are at least moderately large. The results are illustrated using data from a clinical trial for prostate cancer therapy. Copyright © 2016 John Wiley & Sons, Ltd.

Improved prediction intervals in heteroscedastic mixed-effects models

Prediction intervals are developed for the best linear unbiased predictor under heteroscedastic mixed models using the generalized pivotal quantity approach. The superiority of the proposed intervals, over widely used REML based intervals, is established via a simulation study.

Uncovering the exercise‐related proteome signature in skeletal muscle

Exercise training has been recommended as a nonpharmacological strategy for the prevention and attenuation of skeletal muscle atrophy in distinct pathophysiological conditions. Despite the well-established phenotypic alterations, the molecular mechanisms underlying exercise-induced skeletal muscle remodeling are poorly characterized. Proteomics based on mass spectrometry have been successfully applied for the characterization of skeletal muscle proteome, representing a pivotal approach for the wide characterization of the molecular networks that lead to skeletal muscle remodeling. Nevertheless, few studies were performed to characterize the exercise-induced proteome remodeling of skeletal muscle, with only six research papers focused on the cross-talk between exercise and pathophysiological conditions. In order to add new insights on the impact of distinct exercise programs on skeletal muscle proteome, molecular network analysis was performed with bioinformatics tools. This analysis highlighted an exercise-related proteome signature characterized by the up-regulation of the capacity for ATP generation, oxygen delivery, antioxidant capacity and regulation of mitochondrial protein synthesis. Chronic endurance training up-regulates the tricarboxylic acid cycle and oxidative phosphorylation system, whereas the release of calcium ion into cytosol and amino acid metabolism are the biological processes up-regulated by a single bout of exercise. Other issues as exercise intensity, load, mode and regimen as well as muscle type also influence the exercise-induced proteome signature. The comprehensive analysis of the molecular networks modulated by exercise training in health and disease, taking in consideration all these variables, might not only support the therapeutic effect of exercise but also highlight novel targets for the development of enhanced pharmacological strategies.

The PIVOTAL Leadership Model: Improving School Leaders’ Professional Capacity and Personal Vitality through Innovative Postgraduate Course Design

The PIVOTAL Model, developed at two Australian universities based on research with practicing school leaders and current students, has impacted school leaders’ capacity to lead and to retain personal vitality. The Commonwealth Government of Australia-funded research underpinning the development of the “PIVOTAL” (Partnerships, Innovation, and Vitality—Opportunities for Thriving Academic Learning) Model, addresses the gap identified in recent research in the preparation and on-going development of school leaders. The PIVOTAL approach to postgraduate leadership course design was implemented in education and business courses at two universities in Queensland, Australia. Data from school principal reference groups and student focus groups informed innovations to leadership courses. Subsequent research confirmed the impact these innovations had for school leaders at the beginning of 2015. Success has resulted from the introduction of peer mentoring and activities which promote an understanding of factors contributing to personal vitality in complex leadership roles. The introduction of a simulated leadership project option for international students has also been well-received. The accommodation of diverse learning needs of students with varying levels of prior leadership experience remains to be addressed fully. The PIVOTAL Model is planned to be developed further by working with other Australian and international tertiary partners in 2016.

Neue Konzepte der Energieversorgung landtechnischer Systeme

The design of future agricultural production systems requires innovative approaches. For creating a more productive, resource-efficient and low-emission agriculture the systemic development of the agricultural processes, the operating conditions and the organizational processes is necessary. Fundamentally new approaches can be found by defining scenarios. Such a hypothetic concept does field operation without using internal combustion engines. Instead of this the power supply of performant machines can be done by electric direct supply systems or for small machines by battery systems with charging points. However, all this requires the electrical energy supply of agricultural fields. A direct electric energy supply utilizing the Center Pivot approach via rotating structures enables new production systems. Using innovative technologies new solutions with great potential for automation and a productive precision agriculture can be designed. This paper highlights an unconventional approach stimulating the discussion about future developments in agricultural engineering.

Angiotensin type 1a receptor deficiency decreases amyloid β-protein generation and ameliorates brain amyloid pathology.

Alzheimer’s disease is characterized by neuronal loss and cerebral accumulation of amyloid-β protein (Aβ) and lowering the generation of Aβ is a pivotal approach in the strategy of Alzheimer’s disease treatment. Midlife hypertension is a major risk factor for the future onset of sporadic Alzheimer’s disease and the use of some antihypertensive drugs may decrease the incidence of Alzheimer’s disease. However, it is largely unknown how the blood pressure regulation system is associated with the pathogenesis of Alzheimer’s disease. Here we found that the deficiency of angiotensin type 1a receptor (AT1a), a key receptor for regulating blood pressure, significantly decreased Aβ generation and amyloid plaque formation in a mouse model of Alzheimer’s disease. The lack of AT1a inhibited the endocleavage of presenilin-1 (PS1), which is essential for γ-secretase complex formation and Aβ generation. Notably, the ligand of AT1a, angiotensin II, enhanced Aβ generation, PS1 endocleavage and γ-secretase complex formation. Our results suggest that AT1a activation is closely associated with Aβ generation and brain amyloid accumulation by regulating γ-secretase complex formation. Thus, removal of life style factors or stresses that stimulate AT1a to elevate blood pressure may decrease Aβ generation and brain amyloid accumulation, thereby preventing the pathogenesis of Alzheimer’s disease.

Reusability-based quality framework for software components

Component based software engineering (CBSE) is a pivotal approach to software development since it helps to give much aspired benefits like reusability, on-time delivery, high quality at low cost to software companies. Therefore, individual software components must be selected with care as these are crucial to the success of the CBSE approach. The selection of a highly reusable and high-quality component is still a herculean task since stakeholders with varying expectations are involved in the software engineering process. This paper presents a reusability based quality model, which is suited to the identification and evaluation of software components. Three major stakeholders are recognized, which are important in the selection of a software component as well as to the development of software. In the proposed model, only those quality properties are incorporated that are preferred by stakeholders and necessary to increase the reuse of software components.

Comments to: ?Type 2 diabetes mellitus ? time to change the concept?

Authors of the paper ?Diabetes mellitus ? time to change the concept? (Diabetes Mellitus, 2013; №1: 91) address weight-reduction treatment modalities (including bariatric surgery) as the pivotal approach to type 2 diabetes management. While acknowledging the importance of weight loss in patients with type 2 diabetes mellitus (T2DM), this short letter aims to advise the endocrinology community against viewing bariatric surgery as the ultimate solution of all challenges of T2DM.

Lost in Post-Translation, Found by Mass Spectrometry: Identification of Novel Biomarkers and Biologic Insights in Lymphoma Pathogenesis

Malignant lymphomas are neoplastic clonal expansions of B, T, or NK cells and are the seventh most common cause of cancer deaths. The majority (70-80%) of lymphomas that occur in the United States and Europe are non-Hodgkin lymphomas (NHL) while approximately 20 to 30 percent are classical Hodgkin lymphomas (CHL). Multi-parameter evaluation of protein expression is an important component of laboratory-based diagnosis and sub-classification of malignant lymphoma. The protein expression repertoires of lymphoma subtypes have not been well characterized and compendia of proteins expressed by lymphoma cells would constitute a valuable resource for tumor biomarkers for diagnosis and therapy. Liquid chromatography (LC) combined with high mass resolution tandem mass spectrometry (MS/MS) has emerged as a pivotal approach for large-scale analysis of proteins from complex mixtures. Importantly, the detection of proteins with low-stoichiometry, post-translational modifications requires enrichment strategies to isolate the proteins of interest. Strategies that exploit the unique biochemical characteristics of critical post-translational modifications such as phosphorylation and glycosylation can be used to specifically enrich for proteins containing those modifications. Tandem mass spectrometry is then used in an unbiased manner to identify and quantify the modified proteins as well as localize the specific amino acid residues bearing the modifications. Protein glycosylation is the most common post-translational modification that typically occurs by covalent modification of serine, threonine (O-glycosylation), or asparagine residues (N-glycosylation). In particular, N-glycosylation is prevalent in proteins that are destined for localization to membrane or intended for secretion into the extracellular environment. Thus these N-glycosylated proteins constitute an untapped reservoir of potential cellular biomarkers in extracellular fluids such as blood and urine. Indeed, many diagnostic protein biomarkers currently in clinical use are N-glycoproteins. These include many cluster of differentiation (CD) proteins that define hematopoietic sub-populations as well as hematologic neoplasms. Furthermore, many of these proteins represent important targets for therapeutic antibodies and immunotoxins. Enrichment techniques based on glycoprotein affinity for lectins, or linkage by specific chemistry of the sugar moiety to solid surfaces followed by their release using peptide N-glycosidase F (PNGase F) have been successfully employed for subsequent LC-MS/MS identification of N-glycosylated proteins. Using N-glycosylation enrichment strategies followed by LC-MS/MS, we catalogued the N-linked glycoproteins expressed in several human malignant lymphoma categories. We identified many known and several previously unidentified proteins with restricted expression in different lymphoma subtypes. Unsupervised hierarchical clustering based on N-glycoproteomic data classified primary tumors and cell lines into their appropriate disease classes. Orthogonal immunophenotypic studies of selected proteins in primary lymphoma tissue biopsies and lymphoma-derived cell lines corroborated the MS-based glycoproteomic data. Functional studies validated therapeutic targeting of a biomarker using a toxin-conjugated ligand. Overall, our studies indicate that mass spectrometry-driven proteomics provides a general strategy for discovery of cancer biomarkers and targets for precision therapeutics. Disclosures:No relevant conflicts of interest to declare.