bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Differences and Growth-Related Adaptations in Bone Microarchitecture, Geometry, Density, and Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR-pQCT Study
Authors: Gabel Leigh , Macdonald Heather M , McKay Heather A
Published: August 2016

Sex differences in bone strength and fracture risk are well documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density, and geometry that accompany gains in bone strength. Thus, our objectives were to (1) describe growth related adaptations in bone microarchitecture, geometry, density, and strength at the distal tibia and radius in boys and girls; and (2) compare differences in adaptations in bone microarchitecture, geometry, density, and strength between boys and girls. We used HR-pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9 to 20 years old at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity [APHV]) and fit a mixed effects model to these longitudinal data. Importantly, boys showed 28% to 63% greater estimated bone strength across 12 years of longitudinal growth. Boys showed 28% to 80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post-APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post-APHV at the tibia when girls’ values were 2% greater than boys’. Boys showed 13% to 48% greater cortical and total bone area across growth. Load-to-strength ratio was 26% to 27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR-pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys’ superior bone size and strength compared with girls may confer them a protective advantage. However, boys’ consistently more porous cortices may contribute to their higher fracture incidence during adolescence. Large prospective studies using HR-pQCT that target boys and girls who have sustained a fracture are needed to verify this. © 2016 American Society for Bone and Mineral Research.
Reaction rates in a theory of mechanochemical pathways
Authors: Quapp Wolfgang , Bofill Josep Maria
Published: August 2016

If one applies mechanical stress to a molecule in a defined direction then one generates a new, effective potential energy surface (PES). Changes for minima and saddle points (SP) by the stress are described by Newton trajectories on the original PES (Quapp and Bofill, Theor. Chem. Acc. 2016, 135, 113). The barrier of a reaction fully breaks down for the maximal value of the norm of the gradient of the PES along a pulling Newton trajectory. This point is named barrier breakdown point (BBP). Depending on the pulling direction, different reaction pathways can be enforced. If the exit SP of the chosen pulling direction is not the lowest SP of the reactant valley, on the original PES, then the SPs must change their role anywhere: in this case the curve of the log(rate) over the pulling force of a forward reaction can show a deviation from the normal concave curvature. We discuss simple, two‐dimensional examples for this model to understand more deeply the mechanochemistry of molecular systems under a mechanical stress. © 2016 Wiley Periodicals, Inc.
Synthesis of Some New Azoloazines with Potent Anti‐inflammatory and Analgesic Activity
Authors: Dawood Dina H. , Jasass Rabab S. , Amin Mohamed M. , Farghaly Thoraya A. , Abbas Eman M. H.
Published: August 2016

Starting from pyrimidine‐2‐thiones, a set of new fused triazoles, thiazoles, and thiazines has been obtained. The mechanistic pathway and structures of all the novel products were ascertained on the foundation of spectral information and elemental analyses. The analgesic and anti‐inflammatory activities of all the prepared compounds were predestined. The outcomes disclosed that all of the examined samples revealed potent activity. Moreover, the relation between the structure and the activity has been researched.
6,7‐Dimethoxy‐Quinazolin‐4‐yl‐Amino‐Nicotinamide Derivatives as Potent Inhibitors of VEGF Receptor II
Authors: Ashok Abhishek , Thanukrishnan Kannan , Bhojya Naik Halehatty S. , Ghosh Soma
Published: August 2016

The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life‐threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor‐induced angiogenesis. Inhibition of the VEGF signaling pathway has emerged as one of the most promising new approaches for cancer therapy. A series of 6,7‐dimethoxy‐quinazolin‐4‐yl‐amino‐nicotinamides were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR‐2). Many compounds display VEGFR‐2 inhibitory activity, and compound 7a was found to be a potent inhibitor of VEGFR‐2 in an homogeneous time‐resolved fluorescence enzymatic assay with an IC50 as low as 48 nM (comparable activity to ZD‐6474).
Light and electron microscopic analyses of the high deformability of adhesive toe pads in White's tree frog, Litoria caerulea
Authors: Nakano Masato , Saino Tomoyuki
Published: August 2016

White's tree frog (Litoria caerulea) has large, adhesive toe pads that are among the softest of all known biological structures. To explore the morphological basis for the physical properties of the toe pads, the internal microstructure of the toe pads in L. caerulea was examined using both light and transmission electron microscopy. Three design elements that are distinct from other areas of skin were observed. First, the keratinocytes comprising the adhesive surface of the toe pad all contained keratin filament bundles (tonofibrils) exhibiting structural anisotropy. Specifically, the curved conformation of the hierarchical (branching) tonofibrils was characterized by the formation of anastomoses consisting of tonofibrils beneath the adhesive cell surface and stem keratin filament bundles concentrated in the lower‐middle part of the dorsal‐side of adhesive cells. Second, the cytoplasm of keratinocytes in the most superficial cell layer contained glycoproteins (stained by periodic acid/Schiff reagent) that are considered to confer high viscoelasticity. Third, the dermis contained large lymph spaces interspersed with elastic fibers and collagen fibers, which were relatively sparsely distributed compared to the dorsal skin of the toe pads. The profiles of these structures were easily deformed by the slight application of pressure. These findings reaffirmed that the unique internal architecture of the toe pads in L. caerulea contributed to their remarkable softness and high deformability, which in turn increased the contact area and provided improved adaptability to the local topography of natural surfaces. J. Morphol. 277:1509–1516, 2016. © 2016 Wiley Periodicals, Inc.
Quantification of metabolite concentrations in benign and malignant prostate tissues using 3D proton MR spectroscopic imaging
Authors: Weis Jan , von Below Catrin , Tolf Anna , Ortiz‐Nieto Francisco , Wassberg Cecilia , Häggman Michael , Ladjevardi Sam , Ahlström Håkan
Published: August 2016

Purpose

To estimate concentrations of choline (Cho), spermine (Spm), and citrate (Cit) in prostate tissue using 3D proton magnetic resonance spectroscopic imaging (MRSI) with water as an internal concentration reference as well as to assess the relationships between the measured metabolites and also between the metabolites and apparent diffusion coefficient (ADC).

Materials and Methods

Forty‐six prostate cancer patients were scanned at 3T. Spectra were acquired with the point‐resolved spectroscopy (PRESS) localization technique. Single‐voxel spectra of four healthy volunteers were used to estimate T1 relaxation time of Spm. Spm, Cho concentrations, and ADC values of benign prostate tissues were correlated with Cit content.

Results

The T1 value, 708 ± 132 msec, was estimated for Spm. Mean concentrations in the benign peripheral zone (PZ) were Cho, 4.5 ± 1 mM, Spm, 13.0 ± 4.4 mM, Cit, 64.4 ± 16.1 mM. Corresponding values in the benign central gland (CG) were Cho, 3.6 ± 1 mM, Spm, 13.3 ± 4.5 mM, Cit, 34.3 ± 12.9 mM. Concentrations of Cit and Spm were positively correlated in the benign PZ zone (r = 0.730) and CG (r = 0.664). Positive correlation was found between Cit and Cho in the benign CG (r = 0.705). Whereas Cit and ADC were positively correlated in the benign PZ (r = 0.673), only low correlation was found in CG (r = 0.265).

Conclusion

We have shown that it is possible to perform water‐referenced quantitative 3D MRSI of the prostate at the cost of a relatively short prolongation of the acquisition time. The individual metabolite concentrations provide additional information compared to the previously used metabolite‐to‐citrate ratios.

Level of Evidence: 1

J. Magn. Reson. Imaging 2017;45:1232–1240
Comparison study between multicontrast atherosclerosis characterization (MATCH) and conventional multicontrast MRI of carotid plaque with histology validation
Authors: Dai Yuanyuan , Lv Peng , Lin Jiang , Luo Rongkui , Liu Hao , Ji Aihua , Liu Hui , Fu Caixia
Published: August 2016

Purpose

To compare Multicontrast ATherosclerosis Characterization (MATCH) with conventional multicontrast magnetic resonance imaging (MRI) in the characterization and quantification of carotid plaque components.

Materials and Methods

Fifty‐three consecutive patients underwent carotid plaque 3.0T MRI including conventional multicontrast sequences and MATCH, with 13 of them having carotid endarterectomy for histology validation. The detection of major plaque components including lipid‐rich necrotic core (LRNC), loose matrix (LM), intraplaque hemorrhage (IPH), and calcification (CA) and measurement of lumen area, outer wall area, normalized wall index (NWI), and plaque components areas were compared between the two protocols.

Results

Plaque analysis and comparison were done on 298 matched cross‐sectional MRI. MATCH detected significantly more calcifications than conventional consequences (P < 0.01). The difference in detection of IPH (P = 0.07) and LRNC (P = 0.10) approached significance. There was no significant difference in demonstration of LM (P =0.52). A larger area of IPH and CA was measured on MATCH (P < 0.01). The difference nearly reached significance between the two protocols in measuring lumen area (P = 0.09) and outer wall area (P = 0.08). No significant difference was found when measuring the mean area of LRNC (P = 0.15) and LM (P = 0.14) and NWI (P = 0.38). By using receiver operating characteristic curve (ROC) analysis, the accuracy of MATCH and conventional protocols did not differ significantly in the detection of IPH (P = 0.15), LRNC (P = 0.61), LM (P = 0.48), and CA (P = 0.11) when histology served as a reference.

Conclusion

MATCH was comparable if not superior to conventional protocol in identification and quantification of major carotid plaque components.

Level of Evidence: 1

J. Magn. Reson. Imaging 2017;45:764–770.
Agricultural anaerobic digestion power plants in Ireland and Germany: policy and practice
Authors: Auer Agathe , Vande Burgt Nathan H , Abram Florence , Barry Gerald , Fenton Owen , Markey Bryan K , Nolan Stephen , Richards Karl , Bolton Declan , De Waal Theo , Gordon Stephen V , O'Flaherty Vincent , Whyte Paul , Zintl Annetta
Published: August 2016

The process of anaerobic digestion (AD) is valued as a carbon‐neutral energy source, while simultaneously treating organic waste, making it safer for disposal or use as a fertilizer on agricultural land. The AD process in many European nations, such as Germany, has grown from use of small, localized digesters to the operation of large‐scale treatment facilities, which contribute significantly to national renewable energy quotas. However, these large AD plants are costly to run and demand intensive farming of energy crops for feedstock. Current policy in Germany has transitioned to support funding for smaller digesters, while also limiting the use of energy crops. AD within Ireland, as a new technology, is affected by ambiguous governmental policies concerning waste and energy. A clear governmental strategy supporting on‐site AD processing of agricultural waste will significantly reduce Ireland's carbon footprint, improve the safety and bioavailability of agricultural waste, and provide an indigenous renewable energy source. © 2016 Society of Chemical Industry
Patterns of olfactory impairment reflect underlying disease etiology
Authors: Whitcroft Katherine L. , Cuevas Mandy , Haehner Antje , Hummel Thomas
Published: August 2016

Objective

We aimed to determine whether the pattern of olfactory impairment seen in psychophysical testing reflects underlying disease etiology.

Study Design

Retrospective cohort.

Methods

We performed a retrospective analysis of 1,226 patients from our tertiary referral center. Only hyposmic patients with the following conditions were included: postinfectious hyposmia, posttraumatic hyposmia, hyposmia secondary to sinonasal disease, and hyposmia secondary to Parkinson disease. Patients with anosmia were excluded.

Results

Using a repeated measures analysis of variance (within subject factor “test”: threshold [T], discrimination [D], identification [I]; between subject factor: “etiology”) with posthoc Bonferroni corrected t tests, we found significant interaction between the factors “test” and “etiology” (F6,2444 = 8.46, P < 0.001), indicating that different causes of hyposmia produce different patterns of olfactory loss with respect to the individual subtests T, D, and I . Specifically, patients with Parkinson disease performed relatively well in odor threshold testing, but poorly in odor identification and discrimination compared with the other etiology groups. Conversely, patients with sinonasal disease performed well in odor identification and discrimination but poorly in odor threshold. Patients with postinfectious and posttraumatic hyposmia performed relatively well in both thresholds and discrimination but poorly in identification. However, patients with posttraumatic hyposmia had globally reduced scores compared with the other groups.

Conclusion

This is the first study to comprehensively show that patterns of olfactory impairment reflect underlying disease etiology. We suggest that multicomponent olfactory testing should be performed, especially if there is diagnostic uncertainty. However, to clearly separate different patterns of olfactory loss to the various causes at an individual level, more work is needed.

Level of Evidence

4. Laryngoscope, 2016 127:291–295, 2017
Anti‐inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation
Authors: Goldaracena Nicolas , Echeverri Juan , Spetzler Vinzent N. , Kaths Johan M. , Barbas Andrew S. , Louis Kristine S. , Adeyi Oyedele A. , Grant David R. , Selzner Nazia , Selzner Markus
Published: August 2016

Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart‐beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti‐inflammatory strategies (alprostadil, n‐acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33°C]) were applied. This was compared with a perfused control group (group 2) where livers (n = 5) were perfused at 37°C without anti‐inflammatory agents, similar to the setup used in current European clinical trials, and to a control group preserved with static cold storage (group 3). During 3‐day follow‐up, markers of reperfusion injury, bile duct injury, and liver function were examined. Aspartate aminotransferase (AST) levels during perfusion were significantly lower in the study versus control group at 1 hour (52 ± 6 versus 162 ± 86 U/L; P = 0.01), 2 hours (43 ± 5 versus 191 ± 111 U/L; P = 0.008), and 3 hours (24 ± 16 versus 218 ± 121 U/L; P = 0.009). During perfusion, group 1 versus group 2 had reduced interleukin (IL) 6, tumor necrosis factor α, and galactosidase levels and increased IL10 levels. After transplantation, group 1 had lower AST peak levels compared with group 2 and group 3 (1400 ± 653 versus 2097 ± 1071 versus 1747 ± 842 U/L; P = 0.47) without reaching significance. Bilirubin levels were significantly lower in group 1 versus group 2 at day 1 (3.6 ± 1.5 versus 6.60 ± 1.5 μmol/L; P = 0.02) and 3 (2 ± 1.1 versus 9.7 ± 7.6 μmol/L; P = 0.01). A trend toward decreased hyaluronic acid, as a marker of improved endothelial cell function, was observed at 1, 3, and 5 hours after reperfusion in group 1 versus group 2. Only 1 early death occurred in each group (80% survival). In conclusion, addition of anti‐inflammatory strategies further improves warm perfused preservation. Liver Transplantation 22 1573–1583 2016 AASLD.
Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response
Authors: Inoue Taeko , Griffin Deric M. , Huq Redwan , Samuel Errol L. G. , Ruano Simone H. , Stinnett Gary , Majid Tabassum J. , Beeton Christine , Tour James M. , Pautler Robia G.
Published: August 2016

In many human diseases, the presence of inflammation is associated with an increase in the level of reactive oxygen species (ROS). The resulting state of oxidative stress is highly detrimental and can initiate a cascade of events that ultimately lead to cell death. Thus, many therapeutic attempts have been focused on either modulating the immune system to lower inflammation or reducing the damaging caused by ROS. Berlin et al. reported the development of a novel nanoantioxidant known as poly(ethylene glycol)‐functionalized‐hydrophilic carbon clusters (PEG‐HCCs). They showed that PEG‐HCCs could be targeted to cancer cells, utilized as a drug delivery vector, and can even be visualized ex vivo. Our work here furthers this work and characterizes Gd‐DTPA conjugated PEG‐HCCs and explores the potential for in vivo tracking of T cells in live mice. We utilized a mouse model of delayed‐type hypersensitivity (DTH) to assess the immunomodulatory effects of PEG‐HCCs. The T1‐agent Gd‐DTPA was then conjugated to the PEG‐HCCs and T1 measurements, and T1‐weighted MRI of the modified PEG‐HCCs was done to assess their relaxivity. We then assessed if PEG‐HCCs could be visualized both ex vivo and in vivo within the mouse lymph node and spleen. Mice treated with PEG‐HCCs showed significant improvements in the DTH assay as compared to the vehicle (saline)‐treated control. Flow cytometry demonstrated that splenic T cells are capable of internalizing PEG‐HCCs whereas fluorescent immunohistochemistry showed that PEG‐HCCs are detectable within the cortex of lymph nodes. Finally, our nanoantioxidants can be visualized in vivo within the lymph nodes and spleen of a mouse after addition of the Gd‐DTPA. PEG‐HCCs are internalized by T cells in the spleen and can reduce inflammation by suppression of a recall immune response. PEG‐HCCs can be modified to allow for both in vitro and in vivo visualization using MRI. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.
Simple, efficient location‐based routing for data center network using IP address hierarchy
Authors: Ashok Kumar A. R. , Rao S. V. , Goswami Diganta
Published: August 2016

Increasing demand and sophistication of applications deployed on data centers resulted in various designs for data center networks (DCNs). One of the major challenges in the design of DCNs is the design of routing protocol that scales to support millions of servers that a typical DCN hosts. Many alternative routing protocols are proposed to overcome the scalability problem of conventional routing protocols such as Open Shortest Path First and Routing Information Protocol. These alternative protocols that use topology characteristics of DCN are broadly classified as source routing and location‐based routing. In the process of fixing the scalability problem, these protocols introduced additional complexities such as large network control overhead and reprogramming of network elements. The extra control overhead in these protocols is the result of their effort to determine the relative location of the end hosts in a given topology. Further, existing location‐based routing is not entirely location based and covers only the latter half of a route. In our work, we present a new location‐based routing based on IP address hierarchy that (a) does not need any additional network control plane and management planes, (b) deployable on proven network technologies, and (c) covers entire path of the route. We establish the correlation between topology design and address assignments that helps determining the location of an end host directly from the address assigned to it. We demonstrate our proposed location‐based routing on an existing proven architecture for DCN, BCube‐IP and on our proposed architecture 4‐4, 1‐4. We give proper justification for proposing 4‐4, 1‐4, a better design for our proposed location‐based routing. Copyright © 2016 John Wiley & Sons, Ltd.
Flammability and thermal degradation behavior of ethylene‐vinyl acetate/layered double hydroxides/zinc borate composites
Authors: Qian Yi , Zhou Shaojie , Chen Xilei
Published: August 2016

Mg‐Al‐Fe ternary‐layered double hydroxides (LDHs) were synthesized by a calcination‐rehydration method using Bayer red mud. The products were characterized using X‐ray diffraction and thermogravimetric analysis. The flammability and thermal degradation of ethylene‐vinyl acetate/layered double hydroxides/zinc borate (EVA/LDHs/ZB) composites were studied with limiting oxygen index, UL 94, cone calorimeter test, smoke density test, and thermogravimetry‐Fourier transform infrared spectrometry. Although limiting oxygen index value of the composites decreased with increasing ZB amount, a suitable addition of ZB can apparently improve the UL 94 rating of the material. The heat release rate of the 5% ZB containing ternary composites decreased compared with the EVA/LDHs composites. It is obtained from smoke density test that ZB could help smoke suppression. The ternary composites possessed a higher thermal stability than the EVA/LDHs composites. Copyright © 2016 John Wiley & Sons, Ltd.
The CHEVI tethering complex: facilitating special deliveries
Authors: Rogerson Clare , Gissen Paul
Published: August 2016

VPS33B and VIPAR comprise the two known components of the recently christened class C Homologues in Endosome–Vesicle Interaction (CHEVI) complex, thought to act as a tethering complex in endosomal trafficking distinct from the HOPS and CORVET complexes in mammalian cells. A recent paper in The Journal of Pathology further explores the role of the CHEVI complex in the biogenesis of α‐granules in megakaryocytes, identifying two novel interactors of this complex: α‐tubulin and SEC22B, and demonstrating that VPS33B expression is required for the localization of SEC22B and the α‐granule cargo VWF to proplatelets in megakaryocytes. These findings advance the current knowledge of the function of the CHEVI complex in α‐granule biogenesis and together with studies in other systems, corroborate its role in the specialized delivery of cargo in different cell types. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Macrophage‐mediated psoriasis can be suppressed by regulatory T lymphocytes
Authors: Leite Dantas Rafael , Masemann Dörthe , Schied Tanja , Bergmeier Vera , Vogl Thomas , Loser Karin , Brachvogel Bent , Varga Georg , Ludwig Stephan , Wixler Viktor
Published: August 2016

We recently described an inducible human TNF transgenic mouse line (ihTNFtg) that develops psoriasis‐like arthritis after doxycycline stimulation and analysed the pathogenesis of arthritis in detail. Here, we show that the skin phenotype of these mice is characterized by hyperproliferation and aberrant activation of keratinocytes, induction of pro‐inflammatory cytokines, and infiltration with Th1 and Treg lymphocytes, particularly with macrophage infiltration into lesional skin, thus pointing to a psoriasis‐like phenotype. To reveal the contribution of T cells and macrophages to the development of TNF‐mediated psoriasis, ihTNFtg mice were crossbred into RAG1KO mice lacking mature T and B cells. Surprisingly, the psoriatic phenotype in the double mutants was not reduced; rather, it was enhanced. The skin showed significantly increased inflammation and in particular, increased infiltration by macrophages. Consequently, depletion of macrophages in RAG1KO or wild‐type mice led to decreased disease severity. On the contrary, depletion of Treg cells in wild‐type mice increased both psoriasis and the number of infiltrating macrophages, while adoptive transfer of Foxp3‐positive cells into RAG1KO or wild‐type mice decreased both the development of psoriasis and macrophage infiltration. Thus, we conclude that Treg lymphocytes inhibit the pro‐inflammatory activity of macrophages, which are the major immune effector cells in hTNF‐mediated psoriasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Measuring the efficacy of a project for adolescents and young adults with cancer: A study from the Milan Youth Project
Authors: Ferrari Andrea , Silva Matteo , Veneroni Laura , Magni Chiara , Clerici Carlo Alfredo , Meazza Cristina , Terenziani Monica , Spreafico Filippo , Chiaravalli Stefano , Casanova Michela , Luksch Roberto , Catania Serena , Schiavello Elisabetta , Biassoni Veronica , Podda Marta , Bergamaschi Luca , Puma Nadia , Indini Alice , Proserpio Tullio , Massimino Maura
Published: August 2016

Background

Various projects dedicated specifically to adolescents and young adults (AYA) with cancer have been developed in recent years. A critical aspect of such programs is the ability to demonstrate its value, and therefore how to measure desired outcomes.

Methods

A list of metrics to consider for demonstrating the advantages of an AYA program was identified and used to assess the activity of the Youth Project operating at the Pediatric Oncology Unit of the Istituto Nazionale Tumori in Milan.

Results

The number of newly diagnosed AYA patients seen at the Unit has increased since the formal launch of the Youth Project, from 65 to 81.2 cases/year. Concerning the 78 AYA patients presenting with malignant neoplasms in 2015, 82% were included in clinical trials (the other 18% in prospective observational studies). Fertility preservation measures were implemented for 59% of AYA patients considered at risk, and specific psychological support was provided in 70.6% of cases; 72.5% of patients actively participated in support activities. Other parameters considered were a preliminary satisfaction questionnaire administered to patients and the program's scientific recognition and acknowledgment by the community.

Conclusions

The study proposed a number of potentially reproducible, practical parameters to consider in assessing the value of a program dedicated to AYA. These metrics were examined in terms of the activities of our Youth Project, and confirmed its efficacy. To be sustainable over time, AYA projects have to be accepted as a standard of care at the community and government levels.
Role of neuroimaging in children with acute lymphoblastic leukemia and central nervous system involvement at diagnosis
Authors: Ranta Susanna , Palomäki Maarit , Levinsen Mette , Taskinen Mervi , Abrahamsson Jonas , Mellgren Karin , Niinimäki Riitta , Schmiegelow Kjeld , Heyman Mats , Harila‐Saari Arja ,   on behalf of the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
Published: August 2016

Background

Each year approximately 200 children and adolescents are diagnosed with acute lymphoblastic leukemia (ALL) in the five Nordic countries, and 3% of these have central nervous system (CNS) involvement confirmed by leukemic cells in the cerebrospinal fluid (CSF) or neurological symptoms. We sought to determine the significance of neuraxis imaging in such patients.

Procedure

Magnetic resonance images of children aged 1–17.9 with CNS leukemia at diagnosis of ALL were centrally reviewed and clinical data were retrieved from the medical records and the Nordic leukemia registry. Patients were diagnosed in the period 2000–2012 in Sweden, Finland, or Denmark.

Results

The cohort comprised 1,877 patients, and 66 (3.5%) had CNS involvement. Forty‐five percent (30/66) had CNS related symptoms. Symptoms included vomiting, facial palsy, headache, visual symptoms, and impaired hearing. CNS imaging was performed in 32 of 66 children (48%), and confirmed CNS involvement in 6 of 21 patients with symptoms (29%) and 5 of 11 (45%) without (P = 0.44). There was no difference in the overall survival between CNS‐positive patients with and without signs of leukemic involvement by imaging (P = 0.53).

Conclusions

Radiological imaging of asymptomatic children with CNS leukemia at diagnosis lacks clinical importance, but may be useful in patients with cranial nerve symptoms and negative CSF, as well as for follow‐up. Imaging of symptomatic patients is warranted in order to exclude other causes underlying the symptoms.
Excellent remission rates with limited toxicity in relapsed/refractory Langerhans cell histiocytosis with pulse dexamethasone and lenalidomide in children
Authors: Uppuluri Ramya , Ramachandrakurup Sreejith , Subburaj Divya , Bakane Atish , Raj Revathi
Published: August 2016

Refractory/relapsed Langerhans cell histiocytosis (LCH) has a difficult course with a guarded prognosis. We used a novel protocol including six cycles of pulse dexamethasone and lenalidomide in four children with LCH refractory to first‐line agents and courses of cladribine and cytarabine or single‐agent cladribine. All four children completed the protocol without any significant adverse effects and remain in complete and durable remission 15–18 months posttreatment. The novel protocol we propose for relapsed/refractory LCH is cost‐effective and outpatient‐based with durable remission and minimal toxicity. This is particularly suited for resource‐limited settings.
A researcher's guide to mass spectrometry‐based proteomics
Authors: Savaryn John P. , Toby Timothy K. , Kelleher Neil L.
Published: August 2016

Mass spectrometry (MS) is widely recognized as a powerful analytical tool for molecular research. MS is used by researchers around the globe to identify, quantify, and characterize biomolecules like proteins from any number of biological conditions or sample types. As instrumentation has advanced, and with the coupling of liquid chromatography (LC) for high‐throughput LC‐MS/MS, a proteomics experiment measuring hundreds to thousands of proteins/protein groups is now commonplace. While expert practitioners who best understand the operation of LC‐MS systems tend to have strong backgrounds in physics and engineering, consumers of proteomics data and technology are not exposed to the physio‐chemical principles underlying the information they seek. Since articles and reviews tend not to focus on bridging this divide, our goal here is to span this gap and translate MS ion physics into language intuitive to the general reader active in basic or applied biomedical research. Here, we visually describe what happens to ions as they enter and move around inside a mass spectrometer. We describe basic MS principles, including electric current, ion optics, ion traps, quadrupole mass filters, and Orbitrap FT‐analyzers.
Theoretical studies on nitrogen‐rich furoxan‐based heterocyclic derivatives
Authors: Li Xiao‐Hong , Ju Wei‐Wei , Zhang Rui‐Zhou
Published: August 2016

The density functional theory method was used to study the heats of formation (HOFs), energetic properties, electronic structure of a series of 4,4″‐dinitro(3,3′:4′,3′′)tris([1,2,5]oxadiazole)‐2′‐oxide (3,4‐bis[4′‐nitrofurazan‐3′‐yl]furoxan) derivatives. The results show that the substitution of the nitro group is very useful for improving their HOFs and detonation performances. The HOFs of the title compounds are all positive and larger than those of 1,3,5‐trinitro‐1,3,5‐triazinane and 1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane. The analysis of oxygen balance shows that the studied compounds need the oxygen in the explosive. Compound A1 has larger detonation velocity and detonation pressure than those of 1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane and can be regarded as a potential candidate for high‐energy compounds because of the moderate heat of detonation, high density, and high N. In addition, the energy gaps between the highest occupied molecular orbital and lowest unoccupied molecular orbital of the studied compounds are further investigated.
Effects of wind shear and radiative cooling on the stratocumulus‐topped boundary layer
Authors: Kopec Marta K. , Malinowski Szymon P. , Piotrowski Zbigniew P.
Published: August 2016

The effects of wind shear and radiative cooling on the stratocumulus‐topped boundary layer (STBL) were investigated via a set of large‐eddy simulations. The set‐up of the numerical experiments was based on Flight TO13 from the Physics of Stratocumulus Top (POST) field campaign, in which sensible and latent heat fluxes at the surface were small and thermodynamic conditions prevented cloud‐top entrainment instability.

The results demonstrate that the presence of radiative cooling invigorated convective circulations across the STBL and sharpened the inversion above the cloud, while wind shear at the top of the STBL was a source of turbulence in the capping inversion and caused dilution of the cloud top. The flux and gradient Richardson numbers in the capping inversion and in the topmost layer of the cloud were nearly critical.

Analysis of the turbulent kinetic energy (TKE) budget and its transport indicated that turbulence in the inversion capping the cloud was produced locally by wind shear and was dynamically decoupled from the turbulence driven by convective circulations across the STBL. Similar conclusions were derived for the topmost part of the cloud.
Investigation of active tracking for robotic arm assisted magnetic resonance guided focused ultrasound ablation
Authors: Xiao Xu , Huang Zhihong , Rube Martin A. , Melzer Andreas
Published: August 2016

Background

Focused ultrasound surgery (FUS) is a technique that does not need invasive access to the patient while allowing precise targeted therapy. Magnetic resonance (MR) guided FUS provides capabilities for monitoring treatments. Because the targeted tumours are distributed at different positions, focus repositioning becomes necessary.

Methods

An MR compatible robot was used to increase the operational range of FUS application. Active tracking was developed to detect the robotic arm with regard to the MR coordinate system. The purpose of this study was to construct active tracking to allow a wide spatial range of repositioning the FUS transducer that is fast and accurate. The technique was characterised and validated by a series of positioning tests to prove its efficiency for guiding the robot.

Results

In the calibration range, tracking achieved an RMS accuracy of 0.63 mm. Results of phantom ablation showed a focal scanning precision Δx = 0.4 ± 0.37 mm, Δy = 0.4 ± 0.28 mm and Δz = 0.7 ± 0.66 mm.

Conclusions

The active tracking localisation can be considered a feasible approach for the MR guided FUS system positioned by a robot. Copyright © 2016 John Wiley & Sons, Ltd.
Reliability and time‐to‐failure bounds for discrete‐time constrained Markov jump linear systems
Authors: Hernández‐Mejías Manuel A. , Sala Antonio
Published: August 2016

This paper presents a methodology to obtain a guaranteed‐reliability controller for constrained linear systems, which switch between different modes according to a Markov chain (Markov jump linear systems). Inside the classical maximal robust controllable set, there is 100% guarantee of never violating constraints at future time. However, outside such set, some sequences might make hitting constraints unavoidable for some disturbance realisations. A guaranteed‐reliability controller based on a greedy heuristic approach was proposed in an earlier work for disturbance‐free, robustly stabilisable Markov jump linear systems. Here, extensions are presented by, first, considering bounded disturbances and, second, presenting an iterative algorithm based on dynamic programming. In non‐stabilisable systems, reliability is zero; therefore, prior results cannot be applied; in this case, optimisation of a mean‐time‐to‐failure bound is proposed, via minor algorithm modifications. Optimality can be proved in the disturbance‐free, finitely generated case. Copyright © 2016 John Wiley & Sons, Ltd.
Modeling and quadratic stabilization of a class of linear uncertain time‐varying systems
Authors: Jetto L. , Orsini V. , Romagnoli R.
Published: August 2016

This paper considers the quadratic stabilization of a class of uncertain linear time‐varying (LTV) continuous‐time plants. The state‐space representation of each plant is based on the physically meaningful assumption of a dynamical matrix containing uncertain elements whose time trajectories are sufficiently smooth to be well described by interval polynomial functions with arbitrarily time varying coefficients. At some isolated time instants, the parameters trajectories can exhibit some first‐kind discontinuities due for example to sharply varying operating conditions. Using a parameter independent Lyapunov function, a quadratically stabilizing dynamic output controller is directly obtained by the solution of some LMIs. A salient feature of the paper is that, unlike all the other existing methods, quadratic stabilization can be achieved over possibly arbitrarily large uncertain domains of parameters. Copyright © 2016 John Wiley & Sons, Ltd.
Design of a new CP‐ABE with constant‐size secret keys for lightweight devices using elliptic curve cryptography
Authors: Odelu Vanga , Das Ashok Kumar
Published: August 2016

The energy cost of public‐key cryptography is a vital component of modern secure communications. It inhibits the widespread adoption within the ultra‐low energy regimes (for example, implantable medical devices and Radio Frequency Identification tags). In the ciphertext‐policy attribute‐based encryption (CP‐ABE), an encryptor can decide the access policy that who can decrypt the data. Thus, data will be protected from the unauthorized users. However, most of the existing CP‐ABE schemes require huge storage and computational overheads. Moreover, CP‐ABE schemes based on bilinear map loose high efficiency over the elliptic curve cryptography because of the requirement of the security parameters of larger size. These drawbacks prevent the use of ultra‐low energy devices in practice. In this paper, we aim to propose a novel expressive AND gate access structured CP‐ABE scheme with constant‐size secret keys (CSSK) with cost‐efficient solutions for encryption and decryption using elliptic curve cryptography, called the CP‐ABE‐CSSK scheme. In the proposed CP‐ABE‐CSSK, the size of the secret key is as small as 320 bits. In addition, elliptic curve cryptography is efficient and more suitable for lightweight devices as compared with bilinear pairing‐based cryptosystem. Thus, the proposed CP‐ABE‐CSSK scheme provides low computation and storage overheads with an expressive AND gate access structure as compared with related existing schemes. Consequently, our scheme becomes very practical for CP‐ABE key storage and computation cost for ultra‐low energy devices. Copyright © 2016 John Wiley & Sons, Ltd.
Development of electrostatic spherical aberration corrector using annular and circular electrodes
Authors: Kawasaki Tadahiro , Ishida Takafumi , Takai Yasuyuki , Ogawa Yuki , Tomita Masahiro , Matsutani Takaomi , Kodama Tetsuji , Ikuta Takashi
Published: August 2016

The spherical aberration corrector for high‐resolution electron microscopes has been newly designed and constructed. This aberration correction device is formed by an electrostatic lens consisted of only two electrodes having annular and circular holes and a constant‐voltage supply. We call it ‘annular and circular electrodes (ACE) corrector’. The ACE corrector has big advantages in easy alignment and very low‐cost over the conventional Cs‐correctors. In this study, we have constructed the corrector for the scanning transmission electron microsope (STEM) probe‐forming optical system. The developed device is very small (less than several tens millimeter) so that this can be assembled at the tip of the conventional aperture holder and installed in a 200kV‐STEM column. In experiments using specimens of nanocrystals, we have successfully controlled the spatial resolution of the dark‐field STEM images by changing the voltage applied to the corrector and also have imaged lattice fringes. These results clearly demonstrate that our developed device can correct effectively the inherent aberration of the objective lens of the STEM. Copyright © 2016 John Wiley & Sons, Ltd.
Cytotoxicity and Anti–inflammation Profiles of Synthesized Thiazoles‐Based N‐Bisphosphonates and Relevant Bisphosphonic acids
Authors: Abdou Wafaa M. , Barghash Reham F. , Bekheit Mohamed S. , Geronikaki Athina
Published: August 2016

A series of substituted thiazole‐bisphosphonates and relevant bisphosphonic acid counterparts was synthesized from the reaction of 2‐chloro‐N‐(substituted)thiazole acetamides with tetraethyl methylene‐1,1‐bisphosphonate reagent in the presence of a base. The reactions proceeded smoothly via nucleophilic substitution to give our targets in good to high yields. Among the products, 4 bisphosphonic acids exhibited excellent anticancer activity vs four tested carcinoma cell lines (MCF7, HELA, DU‐145, and HCT‐116) with GI50 values ranging from 1.8 to 4.8 μMmL−1. According to the prediction results (using PASS program), the same acids and their BP‐analogs were also evaluated for their anti‐inflammatory properties. The acute carrageenan induced paw edema in rats model was used and the tested compounds showed notable anti‐inflammatory potency without toxicity side effects.
Structural and Topological Study of Two Coordination Polymers Formed by 1,2,4,5 – Benzenetetracarboxylic Acid, Isonicotinylhydrazine and Metallic Ions Co2+ and Zn2+
Authors: de Almeida Filipe B. , Cunha Mariana S. , De Abreu Heitor A. , Diniz Renata
Published: August 2016

In this work it is highlighted the structural and topological study of two coordination polymers formed by 1,2,4,5–Benzenetetracarboxylic acid (H4BTC), Isonicotinylhydrazine (INH) and metallic ions Co2+ and Zn2+. Even formed by the same ligands, these coordination polymers are very different. The polymer formed by ligands and Co2+ (compound 1), forms as a 3D coordination polymer and it crystalline stability is due to its coordination bonds. On the other hand, the compound formed by ligands and Zn2+ (compound 2), forms a 1D coordination polymer and it is mainly stabilized by hydrogen bonds. Due to these facts, their structures present different and interesting topologies. Other interesting difference is related to coordination mode of H4BTC ligand. In compound 1, the H4BTC ligand is coordinated by carboxylate groups to cobalt ion by a monodentate way and by a bidentate bridge way. However, in compound 2 the H4BTC coordinates to zinc ion in a bidentate way by two different carboxylate groups. In both compounds the INH ligand coordinates in the same way to the metallic sites.
Solvent–free and Selective Autooxidation of Alkylbenzenes Catalyzed by Co/NHPI under Phase Transfer Conditions
Authors: Patil Rajendra D , Fuchs Batya , Taha Nimer , Sasson Yoel
Published: August 2016

Solvent‐free, selective and sustainable reaction protocol for an autoxidation of alkylbenzenes catalyzed by Co‐NHPI (Cobalt‐N‐hydroxyphthalimide) under PTC (Phase Transfer Conditions) is described. A multigram scale preparation of acetophenone from ethylbenzene oxidation is demonstrated. The effect of catalyst [Cobalt, DDAB (Di‐n‐decyl‐di‐methyl ammonium bromide) and NHPI] concentrations, different types of catalysts, effect of temperature and oxygen pressure as well as reaction kinetics related to present auto‐oxidation of alkylbezenes is studied in details. Light microscope image shows that DDAB has Multi Lamellar Vesicles (MLVs) structures through which it protects NHPI at high temperatures. Thus efficient recovery and reuse of present ternary catalytic system (Co‐NHPI/DDAB) is feasible.
The necessity, logic, and forms of replication
Authors: Bettis Richard A. , Helfat Constance E. , Shaver J. Myles
Published: August 2016

Research summary: A replication study assesses whether the results of a particular prior study can be reproduced, including in new contexts with different data. Replication studies are critical for building a cumulative body of research knowledge. This article discusses and provides a typology of different types of replications, compares replications with other approaches to cumulating knowledge, and provides guidelines toward producing high‐quality replication studies. The articles in this Special Issue provide examples of replication studies in strategic management.

Managerial summary: Research studies sometimes draw implications for managerial practice. A single empirical study, however, is specific to a particular context, relies on a particular set of data, and uses a particular research design. As a consequence, a single study cannot establish whether the findings generalize to a different context and whether the research design is robust to alternative approaches. Replication studies can help to establish the range of applicability of prior studies and better support what implications can be drawn for managerial practice. Copyright © 2016 John Wiley & Sons, Ltd.
An extended release local anaesthetic: potential for future use in veterinary surgical patients?
Authors: Lascelles B. Duncan X. , Kirkby Shaw Kristin
Published: August 2016

One of the most effective means of preventing the transduction and transmission of acute and perioperative pain is through the use of local anaesthetics. However, local anaesthetics currently available have a relatively short duration of action. Although there are several tools available to treat perioperative pain in companion animals, overall, there is an unmet need for products that can be administered in the clinic, and provide pain relief for the crucial first few days following surgery in the home environment. Specifically, in relation to local anaesthetics, there is a clear unmet need for a long‐acting local anaesthetic that can be added to the multimodal analgesic protocol to provide pain relief to patients in the home environment or during extended hospitalization. Bupivacaine liposomal injectable suspension recently became available for use in humans, and has proven efficacious and safe. This paper will review the use of local anaesthetics, particularly bupivacaine, in dogs and cats, and introduce a new formulation of prolonged release bupivacaine that is in development for dogs and cats.