bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Sensitivity of a Media-Fill Challenge Test Under Various Situations as a Reliable Method for Recommended Aseptic Technique Competency Assessment
Authors: Moody Colleen A. , Eckel Stephen F. , Amerine Lindsey B.
Published: October 2015

Background: Microbial contamination of compounded medications is a serious concern within hospital pharmacies as it can lead to severe patient injury. The United States Pharmacopeia <797> mandates that pharmacy personnel responsible for preparing compounded sterile preparations must annually demonstrate competency in aseptic technique by performing a media-fill challenge test. Objective: The purpose of this study is to evaluate the sensitivity of a commonly used media-fill test through proper and improper compounding techniques. Methods: Two aseptically trained pharmacy technicians performed media-fill challenge testing by carrying out 5 separate manipulations 5 times each for a total of 25 trials. Sterile vials, syringes, and intravenous bags were prepared. The first manipulation followed best-practice aseptic technique and sterile compounding procedures. Each of the following 4 manipulations removed one aspect of best-practice aseptic technique. The prepared products were incubated at 20°C to 25°C. A positive result for microbial contamination is indicated by visible turbidity within the vials, syringes, and intravenous bags at the following check points: 24 hours, 72 hours, 7 days, 14 days, 21 days, and >30 days. Results: Twenty-five trials, each containing 10 distinct admixtures, resulted in a total of 250 compounded preparations. No single preparation showed signs of turbidity, sedimentation, or visible microbial growth at any of the 6 checkpoints yielding a 0% contamination rate. However, the positive controls inoculated with bacteria did have positive microbial growth results. Conclusion: A more sensitive test needs to be developed to provide assurances that all poor aseptic practices are detected in compounding personnel.
Intraparenchymal Hemorrhage and Fungemia in a Preterm Neonate
Authors: Kozlowski Emily A.
Published: October 2015

Intraparenchymal hemorrhage, also known as grade IV hemorrhage, is a severe and uncommon type of intracranial hemorrhage. Intraparenchymal hemorrhage is associated with poor clinical outcomes; therefore, recognition and differentiation of the correct type of intracranial hemorrhage is important for the treatment of the patient. This case report demonstrates the use of real-time sonographic imaging in a preterm neonate as an effective method of diagnosing intraparenchymal hemorrhage and demonstrates a possible presence of fungemia.
NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating the IL-1α/G-CSF axis
Authors: Bagaitkar Juhi , Pech Nancy K. , Ivanov Stoyan , Austin Anthony , Zeng Melody Yue , Pallat Sabine , Huang Guangming , Randolph Gwendalyn J. , Dinauer Mary C.
Published: October 2015

Key Points

Dysregulated IL-1α in NADPH oxidase null (Cybb KO) mice initiated increased G-CSF–induced neutrophilia, exacerbating sterile inflammation. Reduction of early neutrophilic response promoted resolution in Cybb KO mice.
Mesenchymal stromal cells loaded with paclitaxel induce cytotoxic damage in glioblastoma brain xenografts
Authors: Pacioni Simone , D’Alessandris Quintino Giorgio , Giannetti Stefano , Morgante Liliana , De Pascalis Ivana , Coccè Valentina , Bonomi Arianna , Pascucci Luisa , Alessandri Giulio , Pessina Augusto , Falchetti Maria Laura , Pallini Roberto
Published: October 2015

Introduction

The goal of cancer chemotherapy is targeting tumor cells and/or tumor-associated microvessels with the lowest systemic toxicity. Mesenchymal stromal cells (MSCs) are promising vehicles for selective drug delivery due to their peculiar ability to home to pathological tissues. We previously showed that MSCs are able to uptake and subsequently to release the chemotherapeutic compound Paclitaxel (PTX) and to impair the growth of subcutaneous glioblastoma multiforme (GBM) xenografts. Here we used an orthotopic GBM model 1) to assess whether PTX-loaded MSCs (PTX-MSCs) retain a tropism towards the tumor cells in the brain context, and 2) to characterize the cytotoxic damage induced by MSCs-driven PTX release in the tumor microenvironment.

Methods

U87MG GBM cells were fluorescently labeled with the mCherry protein and grafted onto the brain of immunosuppressed rats. In adjacent brain regions, we injected green fluorescent protein-expressing murine MSCs, either loaded with PTX or unloaded. After 1 week survival, the xenografted brain was assessed by confocal microscopy for PTX-induced cell damage.

Results

Overall, MSCs showed remarkable tropism towards the tumor. In rats grafted with PTX-MSCs, the nuclei of U87MG cells showed changes that are typically induced by PTX, including multi-spindle mitoses, centrosome number alterations, and nuclear fragmentation. Multi-spindle mitoses resulted in multinucleated cells that were significantly higher in tumors co-grafted with PTX-MSCs than in controls. Nuclear changes did not occur in astrocytes and neurons surrounding the tumor.

Conclusions

MSCs appear particularly suited for anti-neoplastic drug delivery in the brain since PTX-specific damage of GBM cells can be achieved avoiding side effects to the normal tissue.
On fixed point theory in topological posets, extended quasi-metric spaces and an application to asymptotic complexity of algorithms
Authors: Shahzad Naseer , Valero Oscar , Alghamdi Mohammed A , Alghamdi Maryam A
Published: October 2015

In this paper we present a few fixed point results in the framework of topological posets. To this end, we introduce an appropriate notion of completeness and order-continuity. Special attention is paid to the case that the topology of the topological poset is induced by an extended quasi-metric. Finally, the applicability of the exposed results is illustrated providing a methodology to determine the asymptotic upper bound of the complexity of those algorithms whose running time of computing is the solution to a special type of recurrence equation.
Projective contractions, generalized metrics, and fixed points
Authors: Alghamdi Maryam A , Shahzad Naseer , Valero Oscar
Published: October 2015

In 1981, Borsík and Doboš studied the aggregation problem for metric spaces. Thus, they characterized those functions that allow one to merge a collection of metrics providing a single metric as a result (Borsík and Doboš in Math. Slovaca 31:193-205, 1981).

Later on, in 1994, the notion of partial metric space was introduced by Matthews with the aim of providing an appropriate mathematical tool for program verification (Matthews in Ann. N.Y. Acad. Sci. 728:183-197, 1994). In the aforesaid reference, an extension of the well-known Banach fixed point theorem to the partial metric framework was given and, in addition, an application of such a result to denotational semantics and program verification was provided.

Inspired by the applicability of partial metric spaces to computer science and by the fact that there are partial metrics useful in such a field which can be induced through aggregation, in 2012 Massanet and Valero analyzed the aggregation problem in the partial metric framework (Massanet and Valero in Proc. of the 17th Spanish Conference on Fuzzy Technology and Fuzzy Logic (Estylf 2012), pp.558-563, 2012).

In this paper, motivated by the fact that fixed point techniques are essential in order to apply partial metric spaces to computer science and that, as we have pointed out above, some of such partial metrics can be induced by aggregation, we introduce a new notion of contraction between partial metric spaces which involves aggregation functions. Besides, since fixed point theory in partial metric spaces from an aggregation viewpoint still is without exploring, we provide a fixed point theorem in the spirit of Matthews for the new type of contractions and, in addition, we give examples which illustrate that the assumptions in such a result cannot be weakened. Furthermore, we provide conditions that vouch the existence and uniqueness of fixed point for this new class of contractions. Finally, we discuss the well-posedness for this kind of fixed point problem and the limit shadowing property for the new sort of contractions.
Hybrid iterative algorithms for two families of finite maximal monotone mappings
Authors: Qiu Yang-Qing , Ceng Lu-Chuan , Chen Jin-Zuo , Hu Hui-Ying
Published: October 2015

In this paper, we introduce and analyze a new general hybrid iterative algorithm for finding a common element of the set of common zeros of two families of finite maximal monotone mappings, the set of fixed points of a nonexpansive mapping and the set of solutions of the variational inequality problem for a monotone, Lipschitz-continuous mapping in a real Hilbert space. Our algorithm is based on four well-known methods: Mann’s iteration method, composite method, outer-approximation method and extragradient method. We prove the strong convergence theorem for the proposed algorithm. The results presented in this paper extend and improve the corresponding results of Wei and Tan (Fixed Point Theory Appl. 2014:77, 2014). Some special cases are also discussed.
A fixed point iterative approach to integer programming and its distributed computation
Authors: Dang Chuangyin , Ye Yinyu
Published: October 2015

Integer programming is concerned with the determination of an integer or mixed-integer point in a polytope. It is an NP-hard problem and has many applications in economics and management. Although several popular methods have been developed for integer programming in the literature and extensively utilized in practices, it remains a challenging problem and appeals for more endeavors. By constructing an increasing mapping satisfying certain properties, we develop in this paper an alternative method for integer programming, which is called a fixed point iterative method. Given a polytope, the method, within a finite number of iterations, either yields an integer or mixed-integer point in the polytope or proves no such point exists. As a very appealing feature, the method can easily be implemented in a distributed way. Furthermore, the construction implies that determining the uniqueness of Tarski’s fixed point is an NP-hard problem, and the method can be applied to compute all integer or mixed-integer points in a polytope and directly extended to convex nonlinear integer programming. Preliminary numerical results show that the method seems promising.
Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review
Authors: Panelli Danielle M. , Phillips Catherine H. , Brady Paula C.
Published: October 2015

Background

Ectopic pregnancy is a potentially life-threatening condition occurring in 1-2 % of all pregnancies. The most common ectopic implantation site is the fallopian tube, though 10 % of ectopic pregnancies implant in the cervix, ovary, myometrium, interstitial portion of the fallopian tube, abdominal cavity or within a cesarean section scar.

Findings

Diagnosis involves a combination of clinical symptoms, serology, and ultrasound. Medical management is a safe and effective option in most clinically stable patients. Patients who have failed medical management, are ineligible, or present with ruptured ectopic pregnancy or heterotopic pregnancy are most often managed with excision by laparoscopy or, less commonly, laparotomy. Management of nontubal ectopic pregnancies may involve medical or surgical treatment, or a combination, as dictated by ectopic pregnancy location and the patient's clinical stability. Following tubal ectopic pregnancy, the rate of subsequent intrauterine pregnancy is high and independent of treatment modality.

Conclusion

This review describes the incidence, risk factors, diagnosis, and management of tubal and non-tubal ectopic and heterotopic pregnancies, and reviews the existing data regarding recurrence and future fertility.
Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer
Authors: Enzinger Andrea C. , Zhang Baohui , Schrag Deborah , Prigerson Holly G.
Published: October 2015

Purpose

To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer.

Patients and Methods

This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences.

Results

Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses.

Conclusion

Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to their emotional well-being or the patient-physician relationship.
Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis
Authors: Johung Kimberly L. , Yeh Norman , Desai Neil B. , Williams Terence M. , Lautenschlaeger Tim , Arvold Nils D. , Ning Matthew S. , Attia Albert , Lovly Christine M. , Goldberg Sarah , Beal Kathryn , Yu James B. , Kavanagh Brian D. , Chiang Veronica L. , Camidge D. Ross , Contessa Joseph N.
Published: October 2015

Purpose

We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and brain metastasis.

Patients and Methods

A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling.

Results

Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001).

Conclusion

Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.
Routine Imaging for Diffuse Large B-Cell Lymphoma in First Complete Remission Does Not Improve Post-Treatment Survival: A Danish–Swedish Population-Based Study
Authors: El-Galaly Tarec Christoffer , Jakobsen Lasse Hjort , Hutchings Martin , de Nully Brown Peter , Nilsson-Ehle Herman , Székely Elisabeth , Mylam Karen Juul , Hjalmar Viktoria , Johnsen Hans Erik , Bøgsted Martin , Jerkeman Mats
Published: October 2015

Purpose

Routine imaging for diffuse large B-cell lymphoma (DLBCL) in first complete remission (CR) is controversial and plays a limited role in detecting relapse. This population-based study compared the survival of Danish and Swedish patients with DLBCL for whom traditions for routine imaging have been different.

Patients and Methods

Patients from the Danish and Swedish lymphoma registries were included according to the following criteria: newly diagnosed DLBCL from 2007 to 2012, age 18 to 65 years, and CR after R-CHOP/CHOEP. Follow-up for Swedish patients included symptom assessment, clinical examinations, and blood tests at 3- to 4-month intervals for 2 years, with longer intervals later in follow-up. Imaging was only recommended when relapse was clinically suspected. Follow-up for Danish patients was similar but included routine imaging (usually computed tomography every 6 months for 2 years).

Results

Danish (n = 525) and Swedish (n = 696) patients with DLBCL had comparable baseline characteristics. Cumulative 2-year progression rate after CR was 6% (95% CI, 4 to 9) for International Prognostic Index (IPI) ≤ 2 versus 21% (95% CI, 13 to 28) for IPI > 2. Age > 60 years (hazard ratio [HR], 2.3; 95% CI, 1.6 to 3.4), elevated lactate dehydrogenase (HR, 2.3; 95% CI, 1.4 to 3.8), B symptoms (HR, 1.7; 95% CI, 1.1 to 2.5), and Eastern Cooperative Oncology Group performance status ≥ 2 (HR, 1.8; 95% CI, 1.0 to 3.0) were associated with worse post-CR survival. Imaging-based follow-up strategy had no impact on survival, neither for all patients nor for IPI-specific subgroups.

Conclusion

DLBCL relapse after first CR is infrequent, and the widespread use of routine imaging in Denmark did not translate into better survival. This favors follow-up without routine imaging and, more generally, a shift of focus from relapse detection to improved survivorship.
Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015
Authors: Allegra Carmen J. , Rumble R. Bryan , Hamilton Stanley R. , Mangu Pamela B. , Roach Nancy , Hantel Alexander , Schilsky Richard L.
Published: October 2015

Purpose

An American Society of Clinical Oncology Provisional Clinical Opinion (PCO) offers timely clinical direction after publication or presentation of potentially practice-changing data from major studies. This PCO update addresses the utility of extended RAS gene mutation testing in patients with metastatic colorectal cancer (mCRC) to detect resistance to anti–epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy.

Clinical Context

Recent results from phase II and III clinical trials in mCRC demonstrate that patients whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs directed against EGFR, when used as monotherapy or combined with chemotherapy.

Recent Data

In addition to the evidence reviewed in the original PCO, 11 systematic reviews with meta-analyses, two retrospective analyses, and two health technology assessments based on a systematic review were obtained. These evaluated the outcomes for patients with mCRC with no mutation detected or presence of mutation in additional exons in KRAS and NRAS.

PCO

All patients with mCRC who are candidates for anti-EGFR antibody therapy should have their tumor tested in a Clinical Laboratory Improvement Amendments–certified laboratory for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). The weight of current evidence indicates that anti-EGFR MoAb therapy should only be considered for treatment of patients whose tumor is determined to not have mutations detected after such extended RAS testing.
A High-Calcium and Phosphate Rescue Diet and VDR-Expressing Transgenes Normalize Serum Vitamin D Metabolite Profiles and Renal Cyp27b1 and Cyp24a1 Expression in VDR Null Mice
Authors: Kaufmann Martin , Lee Seong Min , Pike J. Wesley , Jones Glenville
Published: October 2015

Vitamin D receptor (VDR)-mediated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-dependent gene expression is compromised in the VDR null mouse. The biological consequences include: hypocalcemia, hypophosphatemia, elevated parathyroid hormone (PTH) and 1,25(OH)2D3, and consequential skeletal abnormalities. CYP24A1 is a cytochrome P450 enzyme that is involved in the side chain oxidation and destruction of both 1,25(OH)2D3 and 25-hydroxyvitamin D3 (25-OH-D3). In the current studies, we used liquid chromatography-tandem mass spectrometry technology to compare the metabolic profiles of VDR null mice fed either a normal or a calcium and phosphate-enriched rescue diet and to assess the consequence of transgenic expression of either mouse or human VDR genes in the same background. Serum 1,25(OH)2D3 levels in VDR null mice on normal chow were highly elevated (>3000 pg/mL) coincident with undetectable levels of catabolites such as 24,25-(OH)2D3 and 25-OH-D3-26,23-lactone normally observed in wild-type mice. The rescue diet corrected serum Ca++, PTH, and 1,25(OH)2D3 values and restored basal expression of Cyp24a1 as evidenced by both renal expression of Cyp24a1 and detection of 24,25-(OH)2D3 and the 25-OH-D3-26,23-lactone. Unexpectedly, this diet also resulted in supranormal levels of 3-epi-24,25-(OH)2D3 and 3-epi-25-OH-D3-26,23-lactone. The reappearance of serum 24,25-(OH)2D3 and renal Cyp24a1 expression after rescue suggests that basal levels of Cyp24a1 may be repressed by high PTH. Introduction of transgenes for either mouse or human VDR also normalized vitamin D metabolism in VDR null mice, whereas this metabolic pattern was unaffected by a transgene encoding a ligand binding-deficient mutant (L233S) human VDR. We conclude that liquid chromatography-tandem mass spectrometry-based metabolic profiling is an ideal analytical method to study mouse models with alterations in calcium/phosphate homeostasis.
Structural and Functional Evidence for Testosterone Activation of GPRC6A in Peripheral Tissues
Authors: Pi Min , Kapoor Karan , Wu Yunpeng , Ye Ruisong , Senogles Susan E. , Nishimoto Satoru K. , Hwang Dong-Jin , Miller Duane D. , Narayanan Ramesh , Smith Jeremy C. , Baudry Jerome , Quarles L. Darryl
Published: October 2015

G protein-coupled receptor (GPCR) family C group 6 member A (GPRC6A) is a multiligand GPCR that is activated by cations, L-amino acids, and osteocalcin. GPRC6A plays an important role in the regulation of testosterone (T) production and energy metabolism in mice. T has rapid, transcription-independent (nongenomic) effects that are mediated by a putative GPCR. We previously found that T can activate GPRC6A in vitro, but the possibility that T is a ligand for GPRC6A remains controversial. Here, we demonstrate direct T binding to GPRC6A and construct computational structural models of GPRC6A that are used to identify potential binding poses of T. Mutations of the predicted binding site residues were experimentally found to block T activation of GPRC6A, in agreement with the modeling. Using Gpr6ca−/− mice, we confirmed that loss of GPRC6A resulted in loss of T rapid signaling responses and elucidated several biological functions regulated by GPRC6A-dependent T rapid signaling, including T stimulation of insulin secretion in pancreatic islets and enzyme expression involved in the biosynthesis of T in Leydig cells. Finally, we identified a stereo-specific effect of an R-isomer of a selective androgen receptor modulator that is predicted to bind to and shown to activate GPRC6A but not androgen receptor. Together, our data show that GPRC6A directly mediates the rapid signaling response to T and uncovers previously unrecognized endocrine networks.
Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus
Authors: Thélie Aurore , Desiderio Simon , Hanotel Julie , Quigley Ian , Van Driessche Benoit , Rodari Anthony , Borromeo Mark D. , Kricha Sadia , Lahaye François , Croce Jenifer , Cerda-Moya Gustavo , Ordoño Fernandez Jesús , Bolle Barbara , Lewis Katharine E. , Sander Maike , Pierani Alessandra , Schubert Michael , Johnson Jane E. , Kintner Christopher R. , Pieler Tomas , Van Lint Carine , Henningfeld Kristine A. , Bellefroid Eric J. , Van Campenhout Claude
Published: October 2015

V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show that the transcription factor Prdm12 is selectively expressed in p1 progenitors of the hindbrain and spinal cord in the frog embryo, and that a similar restricted expression profile is observed in the nerve cord of other vertebrates as well as of the cephalochordate amphioxus. Using frog, chick and mice, we analyzed the regulation of Prdm12 and found that its expression in the caudal neural tube is dependent on retinoic acid and Pax6, and that it is restricted to p1 progenitors, due to the repressive action of Dbx1 and Nkx6-1/2 expressed in the adjacent p0 and p2 domains. Functional studies in the frog, including genome-wide identification of its targets by RNA-seq and ChIP-Seq, reveal that vertebrate Prdm12 proteins act as a general determinant of V1 cell fate, at least in part, by directly repressing Dbx1 and Nkx6 genes. This probably occurs by recruiting the methyltransferase G9a, an activity that is not displayed by the amphioxus Prdm12 protein. Together, these findings indicate that Prdm12 promotes V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes, and suggest that this function might have only been acquired after the split of the vertebrate and cephalochordate lineages.
Regulation ofNematostellaneural progenitors by SoxB, Notch and bHLH genes
Authors: Richards Gemma Sian , Rentzsch Fabian
Published: October 2015

Notch signalling, SoxB and Group A bHLH ‘proneural’ genes are conserved regulators of the neurogenic program in many bilaterians. However, the ancestry of their functions and interactions is not well understood. We address this question in the sea anemone Nematostella vectensis, a representative of the Cnidaria, the sister clade to the Bilateria. It has previously been found that the SoxB orthologue NvSoxB(2) is expressed in neural progenitor cells (NPCs) in Nematostella and promotes the development of both neurons and nematocytes, whereas Notch signalling has been implicated in the negative regulation of neurons and the positive regulation of nematocytes. Here, we clarify the role of Notch by reporting that inhibition of Notch signalling increases the numbers of both neurons and nematocytes, as well as increasing the number of NvSoxB(2)-expressing cells. This suggests that Notch restricts neurogenesis by limiting the generation of NPCs. We then characterise NvAth-like (Atonal/Neurogenin family) as a positive regulator of neurogenesis that is co-expressed with NvSoxB(2) in a subset of dividing NPCs, while we find that NvAshA (Achaete-scute family) and NvSoxB(2) are co-expressed in non-dividing cells only. Reciprocal knockdown experiments reveal a mutual requirement for NvSoxB(2) and NvAth-like in neural differentiation; however, the primary expression of each gene is independent of the other. Together, these data demonstrate that Notch signalling and NvSoxB(2) regulate Nematostella neural progenitors via parallel yet interacting mechanisms; with different aspects of these interactions being shared with Drosophila and/or vertebrate neurogenesis.
Spreading the word: non-autonomous effects of apoptosis during development, regeneration and disease
Authors: Pérez-Garijo Ainhoa , Steller Hermann
Published: October 2015

Apoptosis, in contrast to other forms of cell death such as necrosis, was originally regarded as a ‘silent’ mechanism of cell elimination designed to degrade the contents of doomed cells. However, during the past decade it has become clear that apoptotic cells can produce diverse signals that have a profound impact on neighboring cells and tissues. For example, apoptotic cells can release factors that influence the proliferation and survival of adjacent tissues. Apoptosis can also affect tissue movement and morphogenesis by modifying tissue tension in surrounding cells. As we review here, these findings reveal unexpected roles for apoptosis in tissue remodeling during development, as well as in regeneration and cancer.
Relationship between the Bowl-Shaped Geometry of Phosphangulene and an Axial Group on the Phosphorus Atom
Authors: Yamamura Masaki , Nabeshima Tatsuya
Published: October 2015

Phosphangulene derivatives having various substituents on the phosphorus atom, which featured a bowl geometry and restrained bond angle, were synthesized in order to shed light on the relationship between the bowl geometry and the substituent. X-ray analysis revealed that the bowl geometry is significantly dependent on the axial group. An NBO analysis suggested that the bowl geometries become deep as the s-orbital character of the phosphorus orbital in the P–X bonds increases. The NMR, IR, CV, and DFT showed the large s-character in the P–X bonds of the phosphangulene lone pair.
Project Office Selection in Retail Companies
Authors: ��������  , Artemev Dmitry , ��������  , Panacheva O.
Published: October 2015

This article deals with a Project office formation based on classical models, taking into account the specifics of the projects implemented in retail trade companies. Based on the definition of Project Office�s role and place in company structure and its core functions, the authors propose an algorithm to select the most suitable model of project management office for retail companies.
Funding a second specialist nurse post: the business of development and approval
Authors: Eftekhari Helen , Paul Geeta , Osman Faizel
Published: October 2015

With the current strapped financial climate, specialist nursing posts are often difficult to secure funding for. Improvements in the quality of patient care and reductions in financial costs, either directly or indirectly, are often missed. This article draws on one centre's experience of achieving a second specialist nursing post, explaining how the case was developed and culminated in the successful approval of a permanent post. The aim of this article is to encourage nurses to become involved with business managers in actively demonstrating their value and developing business cases to support their services.
Treatment protocols for male facial contouring with cosmetic injectables
Authors: Tonks Sarah
Published: October 2015

Male facial contouring can be undertaken effectively in the medical aesthetic clinic using dermal fillers and botulinum toxin. Communication is essential as male patients can be more demanding and less accepting of any complications, such as bruising. Male attractiveness is linked to perceived masculinity and facial symmetry. Treatment can be broken down into the correction of asymmetry, followed by rejuvenation and enhancement. The facial aesthetic subunits can be divided into thirds as they would be with a female face; however, more emphasis is placed on the middle and lower thirds of the face to achieve best treatment outcomes. This article provides a practical framework for the treatment of several areas of the male face, with reference to specific injection points.
Optimising appearance-related psychosocial care in European settings
Authors: Gaskin Emma , Persson Martin , Williamson Heidi
Published: October 2015

Appearance-related concerns are prevalent among patients and are associated with a range of negative physical and psychosocial outcomes, yet many health professionals across Europe report that they are often ill-equipped to provide adequate support. Researchers from the Centre for Appearance Research examine the impact of two projects aiming to identify training needs to optimise psychosocial care for patients
Developing proficient aesthetic practitioners using a workforce development approach
Authors: Mcnall Anne , Senior Emma , Mather Linda
Published: October 2015

In a move towards protecting the public, Health Education England has developed and consulted on qualification requirements for practitioners providing non-surgical cosmetic procedures. While some feel the resulting standards have not gone far enough to regulate the industry through ensuring that only professionally registered practitioners, accountable for their practice, undertake invasive treatments, it is likely that the proposed qualification requirements will be published in the near future. This article explores the limitations of the proposed qualification requirements based on an educational approach and contends that a workforce development strategy is more appropriate, by explaining how this approach is being used to create the necessary infrastructure to develop and assure proficient aesthetic practitioners.
Making your clinic attractive to consumers and responding to online reviews
Authors: Von Garnier Maximilian
Published: October 2015

Consumers are becoming reliant on the internet to make decisions on everything from choosing which coffee shop to get their latte from, to where they should have a clinical procedure done. It is therefore only natural that review websites have become people's go-to place to make this choice. Maximilian von Garnier explains how clinics can make their online shop window attractive to potential new customers
Reducing lateness to lessons
Authors: Davies Rhian
Published: October 2015

When Marple Hall School reviewed lateness levels, they found 883 hours of teaching had been missed in one year due to students not arriving in class on time. Rhian Davies explains how they tackled this
Transferring learning into new contexts
Authors: Bromley Matt
Published: October 2015

The ability to transfer and apply learning and skills between different contexts is a key part of an effective education, says Matt Bromley. In the first of two articles, he offers advice on how to teach this ability
Spectral Bounds for Matrix Polynomials with Unitary Coefficients
Authors: Cameron Thomas
Published: October 2015

It is well known that the eigenvalues of any unitary matrix lie on the unit circle. The purpose of this paper is to prove that the eigenvalues of any matrix polynomial, with unitary coefficients, lie inside the annulus A_{1/2,2) := {z â C | 1/2 < |z| < 2}. The foundations of this result rely on an operator version of Roucheâs theorem and the intermediate value theorem.
A Note on Eigenvalues Location for Trace Zero Doubly Stochastic Matrices
Authors: Benvenuti Luca
Published: October 2015

Some results on the location of the eigenvalues of trace zero doubly stochastic matrices are provided. A result similar to that provided in [H. Perfect and L. Mirsky. Spectral properties of doublyâstochastic matrices. Monatshefte fur Mathematik, 69(1):35â57, 1965.] for doubly stochastic matrices is given.
Unmanned aerial system imagery and photogrammetric canopy height data in area-based estimation of forest variables
Authors: Tuominen Sakari , Balazs Andras , Saari Heikki , Pölönen Ilkka , Sarkeala Janne , Viitala Risto
Published: October 2015

In this paper we examine the feasibility of data from unmanned aerial vehicle (UAV)-borne aerial imagery in stand-level forest inventory. As airborne sensor platforms, UAVs offer advantages cost and flexibility over traditional manned aircraft in forest remote sensing applications in small areas, but they lack range and endurance in larger areas. On the other hand, advances in the processing of digital stereo photography make it possible to produce three-dimensional (3D) forest canopy data on the basis of images acquired using simple lightweight digital camera sensors. In this study, an aerial image orthomosaic and 3D photogrammetric canopy height data were derived from the images acquired by a UAV-borne camera sensor. Laser-based digital terrain model was applied for estimating ground elevation. Features extracted from orthoimages and 3D canopy height data were used to estimate forest variables of sample plots. -nearest neighbor method was used in the estimation, and a genetic algorithm was applied for selecting an appropriate set of features for the estimation task. Among the selected features, 3D canopy features were given the greatest weight in the estimation supplemented by textural image features. Spectral aerial photograph features were given very low weight in the selected feature set. The accuracy of the forest estimates based on a combination of photogrammetric 3D data and orthoimagery from UAV-borne aerial imaging was at a similar level to those based on airborne laser scanning data and aerial imagery acquired using purpose-built aerial camera from the same study area.K
Lipids contribute to epigenetic control via chromatin structure and functions
Authors: Zhdanov Renad , Schirmer Eric C. , Venkatasubramani Anuroop V. , Kerr Alastair R. W. , Mandrou Elena , Rodriguez-Blanco Giovanny , Kagansky Alexander
Published: October 2015

Isolated cases of experimental evidence over the last few decades have shown that, where specifically tested, both prokaryotes and eukaryotes have specific lipid molecules bound to nucleoproteins of the genome. In vitro, some of these lipids exhibit stoichiometric association with DNA polynucleotides with differential affinities toward certain secondary and tertiary structures. Hydrophobic interactions with inner nuclear membrane could provide attractive anchor points for lipid-modified nucleoproteins in organizing the dynamic genome and accordingly there are precedents for covalent bonds between lipids and core histones and, under certain conditions, even DNA. Advances in biophysics, functional genomics, and proteomics in recent years brought about the first sparks of light that promises to uncover some coherent new level of the epigenetic code governed by certain types of lipid–lipid, DNA–lipid, and protein–lipid interactions among other biochemical lipid transactions in the nucleus. Here, we review some of the older and more recent findings and speculate on how critical nuclear lipid transactions are for individual cells, tissues, and organisms.
Time-dependent Dirichlet conditions in finite element discretizations
Authors: Benner Peter , Heiland Jan
Published: October 2015

For the modeling and numerical approximation of problems with time-dependent Dirichlet boundary conditions, one can call on several consistent and inconsistent approaches. We show that spatially discretized boundary control problems can be brought into a standard state space form accessible for standard optimization and model reduction techniques. We discuss several methods that base on standard finite element discretizations, propose a newly developed problem formulation, and investigate their performance in numerical examples. We illustrate that penalty schemes require a wise choice of the penalization parameters in particular for iterative solves of the algebraic equations. Incidentally, we confirm that standard finite element discretizations of higher order may not achieve the optimal order of convergence in the treatment of boundary forcing problems and that convergence estimates by the common method of manufactured solutions can be misleading.
Elementos terras raras e urânio em águas subterrâneas sob influência de aquíferos distintos em Campinas (SP)
Authors: Bulia Isabella Longhi , Enzweiler Jacinta
Published: October 2015

A composição química de águas subterrâneas resulta, em parte, de reações água-rocha nos respectivos aquíferos. Dentre os vários constituintes das águas, os elementos terras raras (ETR) e urânio podem ser traçadores de processos geoquímicos e de fluxos hidrológicos. O principal objetivo deste trabalho foi procurar associações entre as assinaturas químicas de águas subterrâneas extraídas de três sistemas aquíferos distintos (cristalino, sedimentar e diabásio) e suas respectivas rochas hospedeiras. As amostras foram coletadas a partir de quatro poços tubulares do campus da Universidade Estadual de Campinas (Campinas, SP), nas quais foram determinados parâmetros físico-químicos, íons principais e elementos-traço, incluindo os ETR. Os resultados indicam que a água de dois poços (IMECC e IB) é predominantemente influenciada pelos aquíferos cristalino e diabásio, enquanto a dos outros dois (GM e FEF) pelo aquífero sedimentar. Os valores individuais e normalizados dos ETR nos quatro poços são distintos entre si, evidenciando a heterogeneidade da geologia local. A água de um poço (GM) apresentou concentrações de urânio superiores ao valor máximo permitido vigente para água potável. O U na água provavelmente resulta da dissolução oxidativa de fase(s) com U presente(s) no aquífero sedimentar. Entretanto, a modelagem hidroquímica indicou Ca2UO2(CO3)3 e CaUO2(CO3)22- como as principais espécies de U dissolvidas, as quais são consideradas não tóxicas e não biodisponíveis, conforme dados da literatura. 
Estrategias de suplementacion y función gastrointestinal en atletas de resistencia
Authors: Duarte Vivian Ximeno , Giménez-Sánchez Jaume
Published: October 2015

La prevalencia de síntomas gastrointestinales en el atleta de resistencia oscila entre el 25% y el 70%. Aunque se reconoce que la etiología del dolor abdominal durante el ejercicio es multifactorial, la redistribución del flujo sanguíneo y por lo tanto la isquemia gastrointestinal (GI) son frecuentemente reconocidos como los principales mecanismos fisiopatológicos mediante los cuales se altera la función de la barrera intestinal y en consecuencia se presentan los síntomas. Esta revisión evalúa los mecanismos fisiopatológicos que afectan la función de la barrera intestinal en consecuencia al ejercicio intenso y prolongado, y analiza diferentes nutrientes y/o fitoquímicos que pueden mejorar o mantener la función de la barrera intestinal en atletas de resistencia y ultrarresistencia en pedestrismo. Se analizan diferentes nutrientes que podrían mejorar la perfusión esplácnica durante el ejercicio, reducir o mejorar la disfunción de la pared gastrointestinal, encontrando que a pesar de que existen algunos estudios en el área, la evidencia científica no respalda su uso en población deportista.
Protocol development for a scale to assess self-efficacy in adherence to a gluten free diet: Self-Efficacy and Celiac Disease Scale
Authors: Fueyo-Díaz Ricardo , Magallón-Botaya Rosa , Sánchez-Calavera María Antonia , Asensio-Martínez Angela , Gascón-Santos Santiago
Published: October 2015

Background: Celiac disease is a chronic autoimmune disorder consisting of a permanent intolerance for gluten, with a prevalence of 1%, for which the only treatment to date is to follow a strict gluten free diet for life. Lack of adherence to this treatment is related to severe health problems while compliance leads to normalization. Recently, self-efficacy has been associated with self-management behaviors in chronic disease and health status in many fields.Aims: To construct and validate a self-administered scale to measure self-efficacy in adherence to gluten free diet in the different areas a patient with celiac disease must face everyday.Material and Methods: For the validation phase, the research team aims to recruit 500 celiac individuals over 12 years of age from primary care services and patient associations. The scale will be designed to explore specific self efficacy to adhere to a gluten free diet in the following areas: purchases, eating out, eating at home with others, travelling and at work or school. An expert panel will be conducted to assure quality of the items and utility of the scale. The preliminary form will be tested in as many pilot studies as necessary. An exploratory factor analysis will be applied to study construct validity while concurrent validity will be measured with the correlation coefficient between the new instrument and the Baessler and Schwarzer General Self Efficacy Scale. The reliability of the instrument as well as that of each of the factors extracted from the prior analysis will be analyzed using Cronbach’s alpha internal consistency coefficient. Two weeks later, the scale will be administered to, at least, one third of the sample as a retest in the validation process and to allow for confirmatory factor analysis.Results: This research will design, develop and validate a questionnaire for two types of measures: A score for Self-Efficacy for the management of celiac disease, and a score of self-efficacy for each of the identified key areas. This research will result in the first scale to assess specific self efficacy while following a strict gluten free diet and will allow further research in the role that this expectation may play in patient´s adherence to the unique treatment developed to date and it may be useful in both clinical and research settings. The new scale will be easy to apply and it is expected to have a higher predictive value than instruments assessing general self-efficacy.Conclusions: This questionnaire will be the first of its kind to determine levels of self-efficacy for adherence to gluten free diet and will help to the design of self-management interventions for celiac patients.
Mitochondrial Metabolism – Neglected Link of Cancer Transformation and Treatment
Authors: Pokorný Jiří , Jandová A. , Nedbalová M. , Jelínek F. , Cifra M. , Kučera O. , Havelka D. , Vrba J. , Vrba J. , Čoček A. , Kobilková J.
Published: October 2015

Physical processes in living cells were not taken into consideration among the essentials of biological activity, regardless of the fact that they establish a state far from thermodynamic equilibrium. In biological system chemical energy is transformed into the work of physical forces for various biological functions. The energy transformation pathway is very likely connected with generation of the endogenous electrodynamic field as suggested by experimentally proved electrodynamic activity of biological systems connected with mitochondrial and microtubule functions. Besides production of ATP and GTP (adenosine and guanosine triphosphate) mitochondria form a proton space charge layer, strong static electric field, and water ordering around them in cytosol – that are necessary conditions for generation of coherent electrodynamic field by microtubules. Electrodynamic forces are of a long-range nature in comparison with bond and cohesive forces. Mitochondrial dysfunction leads to disturbances of the electromagnetic field; its power and coherence may be diminished, and frequency spectrum altered. Consequently, defective electrodynamic interaction forces between cancer and healthy cells may result in local invasion of cancer cells. Further deformation of interaction forces connected with experimentally disclosed spatial disarrangement of the cytoskeleton and disordered electrodynamic field condition metastatic process. Cancer therapeutic strategy targeting mitochondria may restore normal physiological functions of mitochondria and open the apoptotic pathway. Apoptosis of too much damaged cancer cells was observed. Considerable experience with DCA (dichloroacetate) cancer treatment in humans was accumulated. Clinical trials should assess DCA therapeutic potential and collect data for development of novel more effective drugs for mitochondrial restoration of various cancers.