bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial Acute Animal Experiment Using a New Miniature Axial Flow Pump in Series With the Natural Heart
Authors: Okamoto Eiji , Yano Tetsuya , Shiraishi Yasuyuki , Miura Hidekazu , Yambe Tomoyuki , Mitamura Yoshinori
Published: August 2015

We have advocated an axial flow blood pump called “valvo pump” that is implanted at the aortic valve position, and we have developed axial flow blood pumps to realize the concept of the valvo pump. The latest model of the axial flow blood pump mainly consists of a stator, a directly driven impeller, and a hydrodynamic bearing. The axial flow blood pump has a diameter of 33 mm and length of 74 mm, and the length of anatomical occupation is 33 mm. The axial flow blood pump is anastomosed to the aorta with polytetrafluoroethylene (PTFE) cuffs worn on the inflow and outflow ports. Dp‐Q curves of the axial flow blood pump are flatter than those of ordinary axial flow pumps, and pump outflow of 5 L/min was obtained against a pressure difference of 50 mm Hg at a rotational speed of 9000 rpm in vitro. The axial flow blood pump was installed in a goat by anastomosing with the thoracic descending aorta using PTFE cuffs, and it was rotated at a rotational speed of 8000 rpm. Unlike in case of the ventricular assistance in parallel with the natural heart, pulsatilities of aortic pressure and aortic flow were preserved even when the pump was on, and mean aortic flow was increased by 1.5 L/min with increase in mean aortic pressure of 30 mm Hg. In conclusion, circulatory assistance in series with the natural heart using the axial flow blood pump was able to improve hemodynamic pulsatility, and it would contribute to improvement of end‐organ circulation.
S100A6 expression in cutaneous smooth muscle neoplasms
Authors: Idriss Munir H. , Elston Dirk M.
Published: August 2015

The S100A6 protein is expressed in a variety of tissues and distinct staining patterns in S100A6 immunohistochemistry may be useful in the differential diagnosis of difficult lesions. We evaluated the staining pattern of the S100A6 antibody in 22 cases each of pilar leiomyoma (LM), angioleiomyoma (ALM), and cutaneous leiomyosarcoma (LMS). S100A6 labeled both the nucleus and cytoplasm of myocytes in positive cases. About 64% of LM and 86% ALM had positive staining to the S100A6 antibody but predominantly in a weak staining pattern. In contrast, 95% of the LMS exhibited moderate to strong staining with the S100A6 antibody. The difference in the frequency of positive cases was statistically significant in the LM vs LMS comparison (p = 0.025), but we found intensity of staining to be of greatest practical utility. Analysis between the groups taking in to consideration differences in intensity of staining using the nonparametric rank sum (Mann–Whitney U test) demonstrated that there was a statistically significant difference between LM and LMS and between ALM and LMS. Weak or absent S100A6 staining supports a diagnosis of LM, whereas strong positive staining supports a diagnosis of LMS.
Liver injury is associated with mortality in sickle cell disease
Authors: Feld J. J. , Kato G. J. , Koh C. , Shields T. , Hildesheim M. , Kleiner D. E. , Taylor J. G. , Sandler N. G. , Douek D. , Haynes‐Williams V. , Nichols J. S. , Hoofnagle J. H. , Jake Liang T. , Gladwin M. T. , Heller T.
Published: August 2015

Background

Increased life expectancy in sickle cell disease (SCD) has resulted in greater recognition of the consequences of repeated intravascular vaso‐occlusion and chronic haemolysis to multiple organ systems.

Aim

To report the long‐term consequences of liver dysfunction in SCD.

Methods

A cohort of SCD patients was prospectively evaluated at the National Institutes of Health (NIH) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression.

Results

Exactly, 247 SCD patients were followed up for 30 months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (DB), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high DB and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (HVPG) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. DB correlated with bile acid levels suggesting liver pathology. Platelet count and soluble CD14 correlated with HVPG indicating portal hypertension.

Conclusions

Ferritin and direct bilirubin are independently associated with mortality in sickle cell disease. Ferritin likely relates to transfusional iron overload, while direct bilirubin suggests impairment of hepatic function, possibly impairing patients’ ability to tolerate systemic insults.
A Permutation Approach for Selecting the Penalty Parameter in Penalized Model Selection
Authors: Sabourin Jeremy A. , Valdar William , Nobel Andrew B.
Published: August 2015

We describe a simple, computationally efficient, permutation-based procedure for selecting the penalty parameter in LASSO-penalized regression. The procedure, permutation selection, is intended for applications where variable selection is the primary focus, and can be applied in a variety of structural settings, including that of generalized linear models. We briefly discuss connections between permutation selection and existing theory for the LASSO. In addition, we present a simulation study and an analysis of real biomedical data sets in which permutation selection is compared with selection based on the following: cross-validation (CV), the Bayesian information criterion (BIC), scaled sparse linear regression, and a selection method based on recently developed testing procedures for the LASSO.
Deductive Derivation and Turing-Computerization of Semiparametric Efficient Estimation
Authors: Frangakis Constantine E. , Qian Tianchen , Wu Zhenke , Diaz Ivan
Published: August 2015

Researchers often seek robust inference for a parameter through semiparametric estimation. Efficient semiparametric estimation currently requires theoretical derivation of the efficient influence function (EIF), which can be a challenging and time-consuming task. If this task can be computerized, it can save dramatic human effort, which can be transferred, for example, to the design of new studies. Although the EIF is, in principle, a derivative, simple numerical differentiation to calculate the EIF by a computer masks the EIF's functional dependence on the parameter of interest. For this reason, the standard approach to obtaining the EIF relies on the theoretical construction of the space of scores under all possible parametric submodels. This process currently depends on the correctness of conjectures about these spaces, and the correct verification of such conjectures. The correct guessing of such conjectures, though successful in some problems, is a nondeductive process, i.e., is not guaranteed to succeed (e.g., is not computerizable), and the verification of conjectures is generally susceptible to mistakes. We propose a method that can deductively produce semiparametric locally efficient estimators. The proposed method is computerizable, meaning that it does not need either conjecturing, or otherwise theoretically deriving the functional form of the EIF, and is guaranteed to produce the desired estimates even for complex parameters. The method is demonstrated through an example.
Quantile Regression Analysis of Censored Longitudinal Data with Irregular Outcome-Dependent Follow-Up
Authors: Sun Xiaoyan , Peng Limin , Manatunga Amita , Marcus Michele
Published: August 2015

In many observational longitudinal studies, the outcome of interest presents a skewed distribution, is subject to censoring due to detection limit or other reasons, and is observed at irregular times that may follow a outcome-dependent pattern. In this work, we consider quantile regression modeling of such longitudinal data, because quantile regression is generally robust in handling skewed and censored outcomes and is flexible to accommodate dynamic covariate-outcome relationships. Specifically, we study a longitudinal quantile regression model that specifies covariate effects on the marginal quantiles of the longitudinal outcome. Such a model is easy to interpret and can accommodate dynamic outcome profile changes over time. We propose estimation and inference procedures that can appropriately account for censoring and irregular outcome-dependent follow-up. Our proposals can be readily implemented based on existing software for quantile regression. We establish the asymptotic properties of the proposed estimator, including uniform consistency and weak convergence. Extensive simulations suggest good finite-sample performance of the new method. We also present an analysis of data from a long-term study of a population exposed to polybrominated biphenyls (PBB), which uncovers an inhomogeneous PBB elimination pattern that would not be detected by traditional longitudinal data analysis.
The novel atypical retinoid ST5589 down‐regulates Aurora Kinase A and has anti‐tumour activity in lymphoma pre‐clinical models
Authors: Bernasconi Elena , Gaudio Eugenio , Kwee Ivo , Rinaldi Andrea , Cascione Luciano , Tarantelli Chiara , Mensah Afua Adjeiwaa , Stathis Anastasios , Zucca Emanuele , Vesci Loredana , Giannini Giuseppe , Bertoni Francesco
Published: August 2015

Despite the marked improvements in the treatment of lymphomas, there is still a need for new therapeutic agents. Synthetic retinoids represent a class of compounds with anti‐cancer activity. Here, we report the preclinical activity of a new member of this class, the ST1926‐derivative ST5589, in lymphomas. ST5589 presented a dose‐dependent anti‐proliferative activity in almost all of the 25 lymphoma cell lines analysed, with a median 50% inhibitory concentration of 433 nM. Apoptosis was observed in 8/11 cell lines. ST5589 induced changes in the gene expression profiles of the cell lines, including the down‐regulation of Aurora Kinase A (AURKA). Specific gene expression signatures were associated with a higher sensitivity to the compound and combination of ST5589 with carfilzomib revealed the importance of proteasome activity in mediating the anti‐tumour activity of ST5589. In conclusion, we have identified a new mechanism of action of atypical retinoids as anti‐cancer compounds, and the encouraging results obtained with the new ST1926‐derivative ST5589 provide the basis for further developments of the compound.
The value of magnetic resonance imaging and ultrasonography (MRI/US)‐fusion biopsy platforms in prostate cancer detection: a systematic review
Authors: Gayet Maudy , van der Aa Anouk , Beerlage Harrie P. , Schrier Bart Ph. , Mulders Peter F.A. , Wijkstra Hessel
Published: August 2015

Despite limitations considering the presence, staging and aggressiveness of prostate cancer, ultrasonography (US)‐guided systematic biopsies (SBs) are still the ‘gold standard’ for the diagnosis of prostate cancer. Recently, promising results have been published for targeted prostate biopsies (TBs) using magnetic resonance imaging (MRI) and ultrasonography (MRI/US)‐fusion platforms. Different platforms are USA Food and Drug Administration registered and have, mostly subjective, strengths and weaknesses. To our knowledge, no systematic review exists that objectively compares prostate cancer detection rates between the different platforms available. To assess the value of the different MRI/US‐fusion platforms in prostate cancer detection, we compared platform‐guided TB with SB, and other ways of MRI TB (cognitive fusion or in‐bore MR fusion). We performed a systematic review of well‐designed prospective randomised and non‐randomised trials in the English language published between 1 January 2004 and 17 February 2015, using PubMed, Embase and Cochrane Library databases. Search terms included: ‘prostate cancer’, ‘MR/ultrasound(US) fusion’ and ‘targeted biopsies’. Extraction of articles was performed by two authors (M.G. and A.A.) and were evaluated by the other authors. Randomised and non‐randomised prospective clinical trials comparing TB using MRI/US‐fusion platforms and SB, or other ways of TB (cognitive fusion or MR in‐bore fusion) were included. In all, 11 of 1865 studies met the inclusion criteria, involving seven different fusion platforms and 2626 patients: 1119 biopsy naïve, 1433 with prior negative biopsy, 50 not mentioned (either biopsy naïve or with prior negative biopsy) and 24 on active surveillance (who were disregarded). The Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool was used to assess the quality of included articles. No clear advantage of MRI/US fusion‐guided TBs was seen for cancer detection rates (CDRs) of all prostate cancers. However, MRI/US fusion‐guided TBs tended to give higher CDRs for clinically significant prostate cancers in our analysis. Important limitations of the present systematic review include: the limited number of included studies, lack of a general definition of ‘clinically significant’ prostate cancer, the heterogeneous study population, and a reference test with low sensitivity and specificity. Today, a limited number of prospective studies have reported the CDRs of fusion platforms. Although MRI/US‐fusion TB has proved its value in men with prior negative biopsies, general use of this technique in diagnosing prostate cancer should only be performed after critical consideration. Before bringing MRI/US fusion‐guided TB in to general practice, there is a need for more prospective studies on prostate cancer diagnosis.
Epithelioid Glioblastomas and Anaplastic Epithelioid Pleomorphic Xanthoastrocytomas—Same Entity or First Cousins?
Authors: Alexandrescu Sanda , Korshunov Andrey , Lai Siang Hui , Dabiri Salma , Patil Sushama , Li Rong , Shih Chie‐Schin , Bonnin Jose M. , Baker Jonathan A. , Du Emma , Scharnhorst David W. , Samuel David , Ellison David W. , Perry Arie
Published: August 2015

Epithelioid glioblastoma (eGBM) and pleomorphic xanthoastrocytoma (PXA) with anaplastically transformed foci (ePXA) show overlapping features. Eleven eGBMs and 5 ePXAs were reviewed and studied immunohistochemically. Fluorescence in situ hybridization for EGFR amplification, PTEN deletion and ODZ3 deletion was also performed, with Ilumina 450 methylome analysis obtained in five cases. The average age for eGBM was 30.9 (range 2–79) years, including five pediatric cases and a M : F ratio of 4.5. The ePXA patients had a M : F ratio of 4 and averaged 21.2 (range 10–38) years in age, including two pediatric cases. Six eGBMs and two ePXAs recurred (median recurrence interval of 12 and 3.3 months, respectively). All tumors were composed of solid sheets of loosely cohesive, “melanoma‐like” cells with only limited infiltration. ePXAs showed lower grade foci with classic features of PXA. Both tumor types showed focal expression of epithelial and glial markers, retained INI1 and BRG1 expression, occasional CD34 positivity, and lack of mutant IDH1 (R132H) immunoreactivity. BRAF V600E mutation was present in four eGBMs and four ePXAs. ODZ3 deletion was detected in seven eGBMs and two ePXAs. EGFR amplification was absent. Methylome analysis showed that one ePXA and one eGBM clustered with PXAs, one eGBM clustered with low‐grade gliomas, and two eGBMs clustered with pediatric‐type glioblastomas. Common histologic, immunohistochemical, molecular and clinical features found in eGBM and ePXA suggest that they are closely related or the same entity. If the latter is true, the nomenclature and WHO grading remains to be resolved.
Deformation of a young salt giant: regional topography of the Red Sea Miocene evaporites
Authors: Mitchell Neil C. , Ligi Marco , Feldens Peter , Hübscher Christian
Published: August 2015

The deformational behaviour of ‘salt giants’ during and shortly after their deposition is difficult to decipher in ocean margin settings where the original evaporites have been deeply buried and strongly mobilized. Here, we examine seismic reflection data from the Red Sea, where evaporites deposited until the end of the Miocene (~5.3 Ma), are generally covered by only 200–300 m of low‐density sediments and where the presence of an axial spreading centre allows us to observe how they have responded to a varied configuration of underlying basement. The regional morphology of the S‐reflection, representing the evaporite surface, is mapped out from seismic data from 13 cruises. The S‐reflection is locally rugged and commonly angular. It is either underlain by layered reflectivity, suggestive of layered evaporite beds, or by more transparent seismic character, suggestive of massive halite. On average, the depth of the reflection on the flanks of the axial rift systematically declines from 700 to 1100 m below sea level (mbsl) going northwards from 16 to 23°N. In the central Red Sea, the S‐reflection has 100‐ to 200‐m‐deep depressions, extending towards the coasts in places. In the southern Red Sea, the S‐reflection forms a surface at 300–800 mbsl that appears less disrupted. We suggest that the evaporites originally had a flat, horizontal surface at the end of the Miocene and have subsequently been distorted by isostatic effects and axial rifting, which in turn promoted evaporite flowage. Off‐axis evaporite depressions correspond with flows identified with multibeam sonar. Furthermore, across‐rift lows in Bouguer gravity anomalies represent valleys in the underlying basement. The off‐axis evaporite depressions overlie those valleys, as would be expected if halokinetic movements were greatest where the evaporites are locally thick, leading to deflation of the evaporite surface. The thickness of post‐Miocene sediment, also mapped out as part of this procedure, confirms the generally pelagic nature of this interval and increases on average from ~250 to 300 m from the central to the southern Red Sea, mimicking the variation in pelagic productivity observed in the present water column.
Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?
Authors: Matsumoto Koji , Maeda Hiroo , Oki Akinori , Takatsuka Naoyoshi , Yasugi Toshiharu , Furuta Reiko , Hirata Ranko , Mitsuhashi Akira , Kawana Kei , Fujii Takuma , Iwata Takashi , Hirai Yasuo , Yokoyama Masatoshi , Yaegashi Nobuo , Watanabe Yoh , Nagai Yutaka , Yoshikawa Hiroyuki ,   the Japan HPV and Cervical Cancer (JHACC) Study Group
Published: August 2015

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross‐sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ2‐test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low‐grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3–4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low‐grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302‐positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.
Early sustained unresponsiveness after short‐course egg oral immunotherapy: a randomized controlled study in egg‐allergic children
Authors: Escudero C. , Rodríguez del Río P. , Sánchez‐García S. , Pérez‐Rangel I. , Pérez‐Farinós N. , García‐Fernández C. , Ibáñez M. D.
Published: August 2015

Background

No studies have evaluated the potential of egg oral immunotherapy (egg‐OIT) to induce sustained unresponsiveness after discontinuing therapy following short‐term treatments.

Objective

We assessed the efficacy of short‐course egg‐OIT to induce sustained unresponsiveness.

Methods

Sixty‐one egg‐allergic children, 5 to 17 years old, with positive double‐blind placebo‐controlled food challenge (DBPCFC) to dehydrated egg white (EW) were randomized to receive egg‐OIT (OITG) for 3 months (maintenance dose one undercooked egg every 48 hours) or to continue egg avoidance diet (control group, CG) for 4 months. Children who completed egg‐OIT avoided egg for 1 month. At 4 months, both groups underwent a DBPCFC. OITG participants who passed this challenge were instructed to add egg to their diet ad libitum. Immune markers were studied at different time points.

Results

Ninety‐three percent (28/30) of OITG children were desensitized in a median of 32.5 days (IQR, 14 days). At 4 months, 1/31 (3%) in CG passed DBPCFC and 11/30(37%) of OITG (95% CI, 14 to 51%; P = 0.003), all of them were consuming egg at 36 months. A decrease in EW, OVA and OVM skin test results and OVA‐specific IgE (sIgE) levels was observed on OITG at 4 months (P = 0.001). EW‐, OVA‐ and OVM‐sIgE levels prior to the start of egg avoidance diet were lower in OITG children who passed DBPCFC at 4 months than in those who did not pass it. EW‐ and OVM‐sIgE showed the best diagnostic performance in predicting DBPCFC result at 4 months. Levels above optimal EW‐sIgE cut‐off of 7.1 kU/L indicated 90% probability of failing DBPCFC.

Conclusion

This is the first demonstration of sustained unresponsiveness with a three‐month egg‐OIT protocol. Almost all treated subjects were desensitized and 37% achieved sustained unresponsiveness. EW‐sIgE levels at the end of treatment predicted sustained unresponsiveness. This protocol shows a new approach to OIT for egg‐allergic children.
Implication of circulating memory B cells in late‐onset myasthenia gravis
Authors: Murai Hiroyuki
Published: August 2015

Myasthenia gravis is a heterogeneous disease, and it presents various clinical differences according to the age of onset. Immunological backgrounds that cause these differences are not well understood. Kubota et al. investigated subsets of circulating T and B lymphocytes using various markers. They argued that a reduced percentage of memory B cells seems to be a characteristic of late‐onset myasthenia gravis.
Intravenous immunoglobulin and suppression of the production of matrix metalloproteinase‐9
Authors: Matsuo Hidenori
Published: August 2015

Matrix metalloproteinase‐9 is a biomarker and therapeutic target in multiple sclerosis. Okada and Adachi reported the matrix metalloproteinase‐9/tissue inhibitor of metalloproteinase‐1 imbalance was a predisposition in patients with multiple sclerosis, and human immunoglobulin G restored it in vitro, supporting the potential of intravenous immunoglobulin therapy in multiple sclerosis.
Debate on the pathogenesis of paraneoplastic cerebellar degeneration with anti‐Yo antibody: T‐cell mediated or antibody mediated?
Authors: Tanaka Keiko
Published: August 2015

It is widely believed that paraneoplastic neurological syndromes with antibodies against intracellular antigens are a cytotoxic T‐cell‐mediated disease triggered in the process of cancer immunity. During this process, coactivation of a humoral immune mechanism is elicited, and autoantibodies against onconeural antigens are produced. These onconeural proteins are usually located in the neuronal cytoplasm or nucleus, and are not targets of antibody‐mediated neuronal damage. Greenlee et al. asserted that the anti‐Yo antibody had a direct effect on Purkinje cell apoptosis, which conflicts with the commonly believed view.
NAPB – a novel SNARE‐associated protein for early‐onset epileptic encephalopathy
Authors: Conroy J. , Allen N.M. , Gorman K. M. , Shahwan A. , Ennis S. , Lynch S.A. , King M.D.
Published: August 2015

Next‐generation sequencing has accelerated the identification of disease genes in many rare genetic disorders including early‐onset epileptic encephalopathies (EOEEs). While many of these disorders are caused by neuronal channelopathies, the role of synaptic and related neuronal proteins are increasingly being described. Here, we report a 6‐year‐old girl with unexplained EOEE characterized by multifocal seizures and profound global developmental delay. Recessive inheritance was considered due to parental consanguinity and Irish Traveller descent. Exome sequencing was performed. Variant prioritization identified a homozygous nonsense variant in the N‐ethylmaleimide‐sensitive factor attachment protein, beta (NAPB) gene resulting in a premature stop codon and 46% loss of the protein. NAPB plays a role in soluble N‐ethylmaleimide‐sensitive fusion attachment protein receptor (SNARE)‐complex dissociation and recycling (synaptic vesicle docking). Knockout mouse models of the murine ortholog Napb have been previously reported. These mice develop recurrent post‐natal epileptic seizures in the absence of structural brain changes. The identification of a disease‐causing variant in NAPB further recognizes the importance of the SNARE complex in the development of epilepsy and suggests that this gene should be considered in patients with unexplained EOEE.
Improving Performance of Image Retrieval Based on Fuzzy Colour Histograms by Using Hybrid Colour Model and Genetic Algorithm
Authors: Ljubovic V. , Supic H.
Published: August 2015

A hybrid colour model is a colour descriptor formed by combining channels from several different colour models. Although rarely used in computer graphics applications due to redundancy, hybrid colour models may be of interest for the Content‐Based Image Retrieval (CBIR). Best features of each colour model can be combined to obtain optimal retrieval performance. This paper evaluates several approaches to the construction of a hybrid colour model that is used to construct a fuzzy colour histogram of image as a compact feature for retrieval. By evaluating each channel separately, a colour model named HSY is proposed. Various parameters of fuzzy histogram are further improved using Genetic algorithm (GA). Using standard data sets and the Average Normalized Modified Retrieval Rank (ANMRR) as a metric for retrieval performance, it is shown that this novel approach can give an improved retrieval performance.
Global Illumination Using Well‐Separated Pair Decomposition
Authors: Bus N. , Mustafa N. H. , Biri V.
Published: August 2015

Instant radiosity methods rely on using a large number of virtual point lights (VPLs) to approximate global illumination. Efficiency considerations require grouping the VPLs into a small number of clusters that are treated as individual lights with respect to each point to be shaded. Two examples of clustering algorithms are Lightcuts [WFA*05] and LightSlice [OP11]. In this work, we use the notion of geometric separatedness of point sets as a basis for a data structure for pre‐computing and compactly storing a set of candidate VPL clusterings. Our data structure is created prior to rendering, is view‐independent and relies only on geometric and radiometric information. For any point to be shaded, we show that a suitable clustering of the VPLs can be efficiently extracted from this data structure. We develop the above framework into an accurate and efficient clustering algorithm based on well‐separated pair decompositions which outperforms earlier work in speed and/or quality for diffuse scenes.
Graph‐Based Wavelet Representation of Multi‐Variate Terrain Data
Authors: Cioaca Teodor , Dumitrescu Bogdan , Stupariu Mihai‐Sorin
Published: August 2015

Terrain data can be processed from the double perspective of computer graphics and graph theory. We propose a hybrid method that uses geometrical and vertex attribute information to construct a weighted graph reflecting the variability of the vertex data. As a planar graph, a generic terrain data set is subjected to a geometry‐sensitive vertex partitioning procedure. Through the use of a combined, thin‐plate energy and multi‐dimensional quadric metric error, feature estimation heuristic, we construct ‘even’ and ‘odd’ node subsets. Using an invertible lifting scheme, adapted from generic weighted graphs, detail vectors are extracted and used to recover or filter the node information. The design of the prediction and update filters improves the root mean squared error of the signal over general graph‐based approaches. As a key property of this design, preserving the mean of the graph signal becomes essential for decreasing the error measure and conserving the salient shape features.
Non‐invasive Assessment and Symptomatic Improvement of the Obstructed Nose (NASION): a physiology‐based patient‐centred approach to treatment selection and outcomes assessment in nasal obstruction
Authors: Nouraei S.A.R. , Virk J.S. , Kanona H. , Zatonski M. , Koury E.F. , Chatrath P.
Published: August 2015

Objectives

To evaluate the impact of selecting treatment for nasal obstruction on the basis of a structured physiology‐based assessment protocol on patient outcomes.

Design

Prospective longitudinal study.

Setting

District general hospital.

Participants

A population of 71 patients with a mean age of 33 years, containing 36 males, presented with nasal obstruction for consideration of nasal surgery. All patients underwent a structured clinical assessment, skin prick allergy testing and oral–nasal flow‐volume loop examination. Fifty‐one patients completed the follow‐up, and mean follow‐up was 11 months.

Main outcome measures

NOSE, SNOT‐22 and NASION scales.

Results

Of the 51 patients who completed follow‐up, six had conservative treatment, 28 had septal/turbinate surgery, and 17 underwent nasal valve surgery. Mean NOSE score fell from 68 ± 18 to 39 ± 31 following the treatment. Mean SNOT‐22 score fell from 47 ± 20 to 29 ± 26 following the treatment. The difference between pre‐treatment and post‐treatment NOSE and SNOT‐22 scores were statistically significant. Success rate of septal/turbinate surgery in patients without nasal allergy was 88%, and this fell to 42% in patients undergoing septal/turbinate surgery who also had nasal allergy. Presence of nasal allergy was the only independent predictor of treatment failure. Patients with nasal valve surgery reported significantly greater symptomatic improvement following surgery. The newly formed NASION scale demonstrated internal consistency with a Cronbach α of 0.9 and excellent change‐responsiveness and convergent validity with correlation coefficients of 0.64 and 0.77 against treatment‐related changes in SNOT‐22 and NOSE scales, respectively.

Conclusions

Successful surgical outcomes can be achieved with the use of a structured history, clinical evaluation and physiological testing. Flow‐volume loops can help elucidate the cause of nasal obstruction. The newly formed NASION scale is a validated retrospective single time‐point patient outcome measure.
Dissemination, Implementation, and Improvement Science Research in Population Health: Opportunities for Public Health and CTSAs
Authors: Kuo Tony , Gase Lauren N. , Inkelas Moira ,   The Population Health and Policy Workgroup
Published: August 2015

Importance

The complex, dynamic nature of health systems requires dissemination, implementation, and improvement (DII) sciences to effectively translate emerging knowledge into practice. Although they hold great promise for informing multisector policies and system‐level changes, these methods are often not strategically used by public health.

Objectives and Methods

More than 120 stakeholders from Southern California, including the community, federal and local government, university, and health services were convened to identify key priorities and opportunities for public health departments and Clinical and Translational Science Awards programs (CTSAs) to advance DII sciences in population health.

Main Outcomes

Participants identified challenges (mismatch of practice realities with narrowly focused research questions; lack of iterative learning) and solutions (using methods that fit the dynamic nature of the real world; aligning theories of change across sectors) for applying DII science research to public health problems. Pragmatic steps that public health and CTSAs can take to facilitate DII science research include: employing appropriate study designs; training scientists and practicing professionals in these methods; securing resources to advance this work; and supporting team science to solve complex‐systems issues.

Conclusions

Public health and CTSAs represent a unique model of practice for advancing DII research in population health. The partnership can inform policy and program development in local communities.
Convergent adaptive evolution – how insects master the challenge of cardiac glycoside‐containing host plants
Authors: Dobler Susanne , Petschenka Georg , Wagschal Vera , Flacht Lara
Published: August 2015

Cardiac glycosides are a prime example of highly toxic plant secondary compounds, which block an essential transmembrane carrier in animals, the Na,K‐ATPase. Nevertheless, over 100 insect species from diverse orders are known to feed on plants containing these compounds and in many cases these toxins are additionally sequestered without ill effect. We investigated whether the insects’ adaptations for handling cardiac glycosides are based on a single physiological mechanism or whether various strategies have evolved across groups. We analyzed gene sequences of the Na,K‐ATPase α‐subunit from cardiac glycoside‐adapted insects and screened for amino‐acid substitutions which could alter the affinity of the enzyme toward cardiac glycosides. In representatives from five insect orders, separated by over 300 million years of evolutionary divergence, we uncovered amino‐acid substitutions at identical positions. Especially striking is the convergent substitution of a histidine for the conserved asparagine at position 122, which we report here for the first time in a sawfly, Monophadnus latus Costa (Hymenoptera: Tenthredinidae), and which was previously observed in the orders Lepidoptera, Coleoptera, Hemiptera, and Diptera. Prior in vitro expression and enzyme assays indicated that this substitution as well as combined substitutions with other residues result in a strongly increased cardenolide resistance of the Na,K‐ATPase. The substitutions to threonine111 and histidine122 observed in M. latus are highly effective and were previously known only in lygaeid bugs. However, not all insects dealing with dietary cardenolides rely on target‐site insensitivity as a mechanism of resistance. An impermeable gut or the exclusion of cardenolides from the nervous tissue with the greatest expression of Na,K‐ATPase by the perineurium, the insect blood brain barrier, apparently represent alternative strategies. Immuno‐histochemical data presented here support the existence of P‐glycoprotein‐like efflux transporters in insect gut membranes that might prevent the uptake of allelochemicals like cardenolides.
Costs of epilepsy and cost‐driving factors in children, adolescents, and their caregivers inGermany
Authors: Riechmann Janna , Strzelczyk Adam , Reese Jens P. , Boor Rainer , Stephani Ulrich , Langner Cornelia , Neubauer Bernd A. , Oberman Bettina , Philippi Heike , Rochel Michael , Seeger Jürgen , Seipelt Peter , Oertel Wolfgang H. , Dodel Richard , Rosenow Felix , Hamer Hajo M. ,   the EpiPaed Study Group
Published: August 2015

Objective

To provide first data on the cost of epilepsy and cost‐driving factors in children, adolescents, and their caregivers in Germany.

Methods

A population‐based, cross‐sectional sample of consecutive children and adolescents with epilepsy was evaluated in the states of Hessen and Schleswig‐Holstein (total of 8.796 million inhabitants) in all health care sectors in 2011. Data on socioeconomic status, course of epilepsy, and direct and indirect costs were recorded using patient questionnaires.

Results

We collected data from 489 children and adolescents (mean age ± SD 10.4 ± 4.2 years, range 0.5–17.8 years; 264 [54.0%] male) who were treated by neuropediatricians (n = 253; 51.7%), at centers for social pediatrics (“Sozialpaediatrische Zentren,” n = 110, 22.5%) and epilepsy centers (n = 126; 25.8%). Total direct costs summed up to €1,619 ± €4,375 per participant and 3‐month period. Direct medical costs were due mainly to hospitalization (47.8%, €774 ± €3,595 per 3 months), anticonvulsants (13.2%, €213 ± €363), and ancillary treatment (9.1%, €147 ± €344). The total indirect costs amounted to €1,231 ± €2,830 in mothers and to €83 ± €593 in fathers; 17.4% (n = 85) of mothers and 0.6% (n = 3) of fathers reduced their working hours or quit work because of their child's epilepsy. Independent cost‐driving factors were younger age, symptomatic cause, and polytherapy with anticonvulsants. Older age, active epilepsy, symptomatic cause, and polytherapy were independent predictors of higher antiepileptic drug (AED) costs, whereas younger age, longer epilepsy duration, symptomatic cause, disability, and parental depression were independent predictors for higher indirect costs.

Significance

Treatment of children and adolescents with epilepsy is associated with high direct costs due to frequent inpatient admissions and high indirect costs due to productivity losses in mothers. Direct costs are age‐dependent and higher in patients with symptomatic epilepsy and polytherapy. Indirect costs are higher in the presence of a child's disability and parental depression.
Population‐level consequences for wild fish exposed to sublethal concentrations of chemicals – a critical review
Authors: Hamilton Patrick B , Cowx Ian G , Oleksiak Marjorie F , Griffiths Andrew M , Grahn Mats , Stevens Jamie R , Carvalho Gary R , Nicol Elizabeth , Tyler Charles R
Published: August 2015

Concentrated chemical spills have been shown to impact adversely on fish populations and even cause localized population extinctions. Evaluating population‐level impacts of sublethal exposure concentrations is, however, complex and confounded by other environmental pressures. Applying effect measures derived from laboratory‐based chemical exposures to impacts in wild fish populations is constrained by uncertainty on how biochemical response measures (biomarkers) translate into health outcomes, lack of available data for chronic exposures and the many uncertainties in available fish population models. Furthermore, wild fish show phenotypic plasticity and local adaptations can occur that adds geographic and temporal variance on responses. Such population‐level factors are rarely considered in the chemical risk assessment process and can probably be derived only from studies on wild fish. Molecular technologies, including microsatellite and SNP genotyping, and RNASeq for gene expression studies, are advancing our understanding of mechanisms of eco‐toxicological response, tolerance, adaptation and selection in wild populations. We examine critically the application of such approaches with examples including using microsatellites that has identified roach (Rutilus rutilus) populations living in rivers contaminated with sewage effluents that are self‐sustaining, and studies of stickleback (Gasterosteus aculeatus) and killifish (Fundulus heteroclitus) that have identified genomic regions under selection putatively related to pollution tolerance. Integrating data on biological effects between laboratory‐based studies and wild populations, and building understanding on adaptive responses to sublethal exposure are some of the priority research areas for more effective evaluation of population risks and resilience to contaminant exposure.
Males on demand: the environmental–neuro‐endocrine control of male sex determination in daphnids
Authors: LeBlanc Gerald A. , Medlock Elizabeth K.
Published: August 2015

Branchiopod crustaceans (e.g., Daphnia sp.) and some other taxa utilize both asexual and sexual reproduction to maximize population sustainability. The decision to switch from asexual to sexual reproduction is triggered by environmental cues that foretell a potentially detrimental change in environmental conditions. This review describes the cascade of events beginning with environmental cues and ending with changes in gene expression that dictate male sex determination in daphnids, the initial event in the switch to sexual reproduction. Several environmental cues have been identified which, either in isolation or in combination, stimulate male sex determination. These cues are typically associated with change of season, exhaustion of resources or loss of habitat. Maternal daphnids receive and respond to these cues, we propose, through the secretion of neuropeptides, which suppress (hyperglycemic hormone‐like neuropeptides, allatostatin) or stimulate (allatotropin) the male sex differentiation program. In response, maternal daphnids produce the male sex‐determining hormone, methyl farnesoate. Methyl farnesoate binds to a protein MET that dimerizes with the protein SRC forming an active transcription factor. This complex then regulates the expression of genes, primarily doublesex (dsx), involved in programming the single‐celled embryo to develop into a male. In the absence of methyl farnesoate programming, the embryo develops into a female. Epigenetic modifications of the genome as a possible mode of methyl farnesoate action and the utility of this model to decipher the role of epigenetics in sex differentiation in other species are discussed.
NF‐κB signaling regulates the generation of intermediate progenitors in the developing neocortex
Authors: Yamanishi Emiko , Yoon Keejung , Alberi Lavinia , Gaiano Nicholas , Mizutani Ken‐ichi
Published: August 2015

In addition to its well‐established role during immune system function, NF‐κB regulates cell survival and synaptic plasticity in the mature nervous system. Here, we show that during mouse brain development, NF‐κB activity is present in the neocortical ventricular and subventricular zones (VZ and SVZ), where it regulates proliferative pool maintenance. Activation of NF‐κB signaling, by expression of p65 or an activated form of the IκB kinase complex subunit IKK2, inhibited neuronal differentiation and promoted retention of progenitors in the VZ and SVZ. In contrast, blockade of the pathway with dominant negative forms of IKK2 and IκBα promoted neuronal differentiation both in vivo and in vitro. Furthermore, by modulating both the NF‐κB and Notch pathways, we show that in the absence of canonical Notch activity, after knockdown of the pathway effector CBF1, NF‐κB signaling promoted Tbr2 expression and intermediate neural progenitor fate. Interestingly, however, activation of NF‐κB in vivo, with canonical Notch signaling intact, promoted expression of the radial glial marker Pax6. This work identifies NF‐κB signaling as a regulator of neocortical neurogenesis and suggests that the pathway plays roles in both the VZ and SVZ.
Recurrent Spontaneous Paresthesia in the Upper Limb Could Be Due to Migraine: A Case Series
Authors: Prakash Sanjay , Rathore Chaturbhuj , Makwana Prayag , Rathod Mitali
Published: August 2015

Transient neurologic dysfunction is a characteristic feature of migraine. About 20% of migraineurs may experience various symptoms in the absence of any headache at one time or another. Visual auras are the most common auras of migraine, and migraine is considered as the most common cause of transient vision loss in young patients. Sensory auras are the second most common migrainous auras. However, the literature is silent for isolated sensory aura as a migraine equivalent. Herein we report 14 patients with recurrent episodic paresthesia in the limbs and other body parts. All patients fulfilled the diagnostic criteria of “typical aura without headache” of ICHD‐3β. All patients were subjected to various investigations to rule out secondary causes. Ten patients received antimigraine drugs and all showed a positive response to therapy.

Recurrent spontaneous paresthesia is quite common in the general population and many patients remain undiagnosed. We speculate that a subset of patients might be related to migrainous sensory auras.
External Nasal Neuralgia: A Neuropathic Pain Within the Territory of the External Nasal Nerve
Authors: García‐Moreno Héctor , Aledo‐Serrano Ángel , Gimeno‐Hernández Jesús , Cuadrado María‐Luz
Published: August 2015

Background

Nasal pain is a challenging diagnosis and very little has been reported in the neurological literature. The nose is a sophisticated structure regarding its innervation, which is supplied by the first and second divisions of the trigeminal nerve. Painful cranial neuropathies are an important group in the differential diagnosis, although they have been described only scarcely. Here, we report a case that can conform a non‐traumatic external nasal nerve neuralgia.

Case

A 76‐year‐old woman was referred to our office due to pain in her left nose. She was suffering from daily excruciating attacks, which were strictly limited to the territory supplied by her left external nasal nerve (left ala nasi and apex nasi). She denied previous traumatisms and the ancillary tests did not yield any underlying pathology. An anesthetic blockade of her left external nasal nerve achieved a marked reduction of the number of episodes as well as their intensity.

Conclusion

External nasal neuralgia seems a specific neuralgia causing nasal pain. Anesthetic blockades of the external nasal nerve may be a valid treatment for this condition.
People with insomnia: experiences with sedative hypnotics and risk perception
Authors: Cheung Janet M. Y. , Bartlett Delwyn J. , Armour Carol L. , Ellis Jason G. , Saini Bandana
Published: August 2015

Background

Sedative hypnotics form an important part of managing insomnia and are recommended for short‐term use. It is standard practice for clinicians to inform the patient to use medications only ‘when required’, but the use of these medications is often chronic. Little is known about the impact of standard labelling/instructions on promoting appropriate medication use for managing insomnia.

Objective

To explore patient medication‐taking beliefs, experiences and behavioural practices relating to the use of pharmacological/complementary sleep aids for insomnia.

Setting and Participants

Specialist sleep/psychology clinics and the general community in Sydney, Australia.

Method

Semi‐structured interviews were conducted with 51 people with insomnia using a schedule of questions to gauge their experiences, beliefs and current practices relating to insomnia medication use. Interviews were audio‐recorded, transcribed verbatim and subjected to Framework Analysis to identify emergent themes.

Results

Participants held distinctive views about the safety and efficacy of complementary and pharmacological agents but do not intuitively turn to medications to resolve their sleep complaint. Medication use was affirmed through tangible medication‐taking cues due to the ambivalence in current instructions and labelling. Practices such as dosage modification, medication substitution and delaying medication use might be important drivers for psychological dependence.

Conclusion

Current labelling and instructions do not necessarily promote the quality use of sedative hypnotics due to the variability in patient interpretations. Clarifying the timing, quantity and frequency of medication administration as well as insomnia symptom recognition would play a significant role in optimizing the role of pharmacotherapy in the management of insomnia.