bluuebunny/crossref_metadata_2025 huggingface dataset:
Atypical pupillary light reflex in 2–6‐year‐old children with autism spectrum disorders
Authors: Dinalankara Dinalankara M. R. , Miles Judith H. , Nicole Takahashi T. , Yao Gang
Published: February 2017

The purpose of this study was to investigate pupillary light reflex (PLR) in 2–6‐years‐old children with autism spectrum disorders (ASD). A total of 117 medication‐free 2–6‐year‐old boys participated in this study. Sixty participants were diagnosed with ASD (the “ASD group”) and the other 57 were in the control group of typical development (the “TD group”). A questionnaire was completed by the parent/guardian for assessing potential dysfunctions in the autonomic nervous system (ANS). The base pupil radius, PLR latency, and constriction time showed a significant age‐related trend in both the ASD and TD groups. The base pupil size increased with age in the typically developing children, but not in the ASD group. The ASD group showed more symptoms related to ANS dysfunctions. An association between abnormal sweating with base pupil radius and PLR constriction was observed in the TD group but not the ASD group. The different association of PLR parameters with ANS dysfunction may suggest disrupted autonomic controls in children with ASD. Autism Res 2017, 10: 829–838. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Undergraduate students who are required to withdraw from university: The role of ethnicity
Authors: Woodfield Ruth
Published: February 2017

A large body of international research focuses on identifying reasons why students do not ‘persist’ (Tinto, ) within higher education. Little research has focused on students whose leaving is non‐voluntary and where narratives of ‘persistence’ are therefore not as pertinent. This paper seeks to refocus some of the attention onto the distinct group of students who do not elect to leave their studies but who are, instead, required to withdraw; such students leave under ‘Academic fail’ and ‘Exclusion’ categories. More specifically, it explores the relationship between student leavers’ ethnicity and their likelihood of being required to withdraw. Utilising a large dataset comprising UK‐domiciled undergraduate students enrolled to take a degree within an English higher education institution in 2010/11, it finds that most groups of Black and Minority Ethnic students are more likely to be required to withdraw than White students. Ethnicity exerts an independent impact on a student's likelihood of being required to withdraw, when other background and on‐course characteristics are controlled for, but this impact varies by disciplinary area. It is suggested that these findings implicate factors within the higher education sector itself as key drivers in the process that leads to students being required to withdraw. Lessons are drawn out for those tasked with managing the student experience within higher education.
Design, construction, and optimization of a novel, modular, and scalable incubation chamber for continuous viral inactivation
Authors: Orozco Raquel , Godfrey Scott , Coffman Jon , Amarikwa Linus , Parker Stephanie , Hernandez Lindsay , Wachuku Chinenye , Mai Ben , Song Brian , Hoskatti Shashidhar , Asong Jinkeng , Shamlou Parviz , Bardliving Cameron , Fiadeiro Marcus
Published: February 2017

We designed, built or 3D printed, and screened tubular reactors that minimize axial dispersion to serve as incubation chambers for continuous virus inactivation of biological products. Empirical residence time distribution data were used to derive each tubular design's volume equivalent to a theoretical plate (VETP) values at a various process flow rates. One design, the Jig in a Box (JIB), yielded the lowest VETP, indicating optimal radial mixing and minimal axial dispersion. A minimum residence time (MRT) approach was employed, where the MRT is the minimum time the product spends in the tubular reactor. This incubation time is typically 60 minutes in a batch process. We provide recommendations for combinations of flow rates and device dimensions for operation of the JIB connected in series that will meet a 60‐min MRT. The results show that under a wide range of flow rates and corresponding volumes, it takes 75 ± 3 min for 99% of the product to exit the reactor while meeting the 60‐min MRT criterion and fulfilling the constraint of keeping a differential pressure drop under 5 psi. Under these conditions, the VETP increases slightly from 3 to 5 mL though the number of theoretical plates stays constant at about 1326 ± 88. We also demonstrated that the final design volume was only 6% ± 1% larger than the ideal plug flow volume. Using such a device would enable continuous viral inactivation in a truly continuous process or in the effluent of a batch chromatography column. Viral inactivation studies would be required to validate such a design. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:954–965, 2017
Evaluation of heavy chain C‐terminal deletions on productivity and product quality of monoclonal antibodies in Chinese hamster ovary (CHO) cells
Authors: Hu Zhilan , Tang Danming , Misaghi Shahram , Jiang Guoying , Yu Christopher , Yim Mandy , Shaw David , Snedecor Brad , Laird Michael W. , Shen Amy
Published: February 2017

Monoclonal antibodies (mAbs) have been well established as potent therapeutic agents and are used to treat many different diseases. During cell culture production, antibody charge variants can be generated by cleavage of heavy chain (HC) C‐terminal lysine and proline amidation. Differences in levels of charge variants during manufacturing process changes make it challenging to demonstrate process comparability. In order to reduce heterogeneity and achieve consistent product quality, we generated and expressed antibodies with deletion of either HC C‐terminal lysine (‐K) or lysine and glycine (‐GK). Interestingly, clones that express antibodies lacking HC C‐terminal lysine (‐K) had considerably lower specific productivities compared to clones that expressed either wild type antibodies (WT) or antibodies lacking HC glycine and lysine (‐GK). While no measurable differences in antibody HC and LC mRNA levels, glycosylation and secretion were observed, our analysis suggests that the lower specific productivity of clones expressing antibody lacking HC C‐terminal lysine was due to slower antibody HC synthesis and faster antibody degradation. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:786–794, 2017
Control of chitin nanofiber production by the lipid‐producing diatom Cyclotella Sp. through fed‐batch addition of dissolved silicon and nitrate in a bubble‐column photobioreactor
Authors: Chiriboga N. Omar G. , Rorrer Gregory L.
Published: February 2017

Diatoms are single‐celled algae that make cell walls of nanopatterned biogenic silica called frustules through metabolic uptake of dissolved silicon and its templated condensation into biosilica. The centric marine diatom Cyclotella sp. also produces intracellular lipids and the valued coproduct chitin, an N‐acetyl glucosamine biopolymer that is extruded from selected frustule pores as pure nanofibers. The goal of this study was to develop a nutrient feeding strategy to control the production of chitin nanofibers from Cyclotella with the coproduction of biofuel lipids. A two‐stage phototrophic cultivation process was developed where Stage I set the cell suspension to a silicon‐starved state under batch operation, and Stage II continuously added silicon and nitrate to the silicon‐starved cells to enable one more cell doubling to 4 × 106 cells mL−1. The silicon delivery rate was set to enable a silicon‐limited cell division rate under cumulative delivery of 0.8 mM Si and 1.2 mM nitrate (1.5:1 mol N/mol Si) over a 4‐ to 14‐day addition period. In Stage II, both cell number and chitin production were linear with time. Cell number and the specific chitin production rate increased linearly with increasing silicon delivery rate to achieve cumulative product yields of 13 ± 1 mg chitin/109 cells and 33 ± 3 mg lipid/109 cells. Therefore, chitin production is controlled through cell division, which is externally controlled through silicon delivery. Lipid production was not linearly correlated to silicon delivery and occurred primarily during Stage I, just after the complete co‐consumption of both dissolved silicon and nitrate. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:407–415, 2017
Applied in situ product recovery in ABE fermentation
Authors: Outram Victoria , Lalander Carl‐Axel , Lee Jonathan G. M. , Davies E. Timothy , Harvey Adam P.
Published: February 2017

The production of biobutanol is hindered by the product's toxicity to the bacteria, which limits the productivity of the process. In situ product recovery of butanol can improve the productivity by removing the source of inhibition. This paper reviews in situ product recovery techniques applied to the acetone butanol ethanol fermentation in a stirred tank reactor. Methods of in situ recovery include gas stripping, vacuum fermentation, pervaporation, liquid–liquid extraction, perstraction, and adsorption, all of which have been investigated for the acetone, butanol, and ethanol fermentation. All techniques have shown an improvement in substrate utilization, yield, productivity or both. Different fermentation modes favored different techniques. For batch processing gas stripping and pervaporation were most favorable, but in fed‐batch fermentations gas stripping and adsorption were most promising. During continuous processing perstraction appeared to offer the best improvement. The use of hybrid techniques can increase the final product concentration beyond that of single‐stage techniques. Therefore, the selection of an in situ product recovery technique would require comparable information on the energy demand and economics of the process. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:563–579, 2017
Bioreactor scale up and protein product quality characterization of piggyBac transposon derived CHO pools
Authors: Rajendra Yashas , Balasubramanian Sowmya , Peery Robert B. , Swartling James R. , McCracken Neil A. , Norris Dawn L. , Frye Christopher C. , Barnard Gavin C.
Published: February 2017

Chinese hamster ovary (CHO) cells remain the most popular host for the production of biopharmaceutical drugs, particularly monoclonal antibodies (mAbs), bispecific antibodies, and Fc‐fusion proteins. Creating and characterizing the stable CHO clonally‐derived cell lines (CDCLs) needed to manufacture these therapeutic proteins is a lengthy and laborious process. Therefore, CHO pools have increasingly been used to rapidly produce protein to support and enable preclinical drug development. We recently described the generation of CHO pools yielding mAb titers as high as 7.6 g/L in a 16 day bioprocess using piggyBac transposon‐mediated gene integration. In this study, we wanted to understand why the piggyBac pool titers were significantly higher (2–10 fold) than the control CHO pools. Higher titers were the result of a combination of increased average gene copy number, significantly higher messenger RNA levels and the homogeneity (i.e. less diverse population distribution) of the piggyBac pools, relative to the control pools. In order to validate the use of piggyBac pools to support preclinical drug development, we then performed an in‐depth product quality analysis of purified protein. The product quality of protein obtained from the piggyBac pools was very similar to the product quality profile of protein obtained from the control pools. Finally, we demonstrated the scalability of these pools from shake flasks to 36L bioreactors. Overall, these results suggest that gram quantities of therapeutic protein can be rapidly obtained from piggyBac CHO pools without significantly changing product quality attributes. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:534–540, 2017
The effect of radiation therapy in the treatment of adult soft tissue sarcomas of the extremities: a long‐term community‐based cancer center experience
Authors: Kneisl Jeffrey S. , Ferguson Chad , Robinson Myra , Crimaldi Anthony , Ahrens Will , Symanowski James , Bates Michael , Ersek Jennifer L. , Livingston Michael , Patt Joshua , Kim Edward S.
Published: February 2017

The aim of the study was to determine the effect of external beam radiotherapy (RT) in the treatment of extremity soft tissue sarcoma (STS) before or after limb‐sparing surgery (LSS) in a community‐based setting. Patients presenting to our institution from 1992 to 2010 and meeting eligibility criteria were stratified into low (G1) or high (G2, G3) pathologic grade and evaluated. Major complication events, including amputation, radiation‐induced sarcoma, and pathologic fracture, were assessed. Kaplan–Meier techniques and Cox proportional hazards regression models were used. One hundred and sixty‐two eligible patients underwent LSS for extremity STS (120 high grade, 42 low grade). Median time of follow‐up was 5.1 years (0.8–20.3 years). RT was administered to 111 patients. In unadjusted models, RT significantly decreased the risk of local recurrence (LR) in high‐grade STS patients (P = 0.005) and had a trend for improved recurrence‐free survival (RFS) (P = 0.069). In multivariable‐adjusted models, RT significantly improved time to LR (P = 0.001), RFS (P = 0.003), and overall survival (OS) (P = 0.003). Analysis of all patients showed those who underwent RT had a major complication rate (MCR) of 16.2%, compared to 3.9% in the no RT group (P = 0.037); however, the difference in MCR did not differ significantly when the analysis was restricted to high‐grade sarcomas. In our large experience of patients with extremity STS undergoing limb sparing surgery (LSS), RT significantly improved local recurrence (LR), RFS, and OS, in patients with high‐grade tumors. Efficacy benefits of RT should be weighed against potential complications. External beam RT should be considered in patients with resected high‐grade sarcomas.
Getting personal: A feminist argument for research aligned to therapeutic practice
Authors: Bondi Liz , Fewell Judith
Published: February 2017

Students and practitioners tend to assume that research requires them to set aside their embodied knowledge of practice and to produce radically different, objective and depersonalised forms of knowledge. Troubled by these assumptions, and coming from backgrounds within the humanities and social sciences shaped by critiques of this model of research, we offer personal stories through which to articulate and argue for a very different approach. Feminist critiques of science occupy a central place within our stories, which tell of the pull of the particular, the personal and the subjective, the importance of personally engaged, reflexive stories, and the influence of moving between disciplines. We understand the personal in research as inevitable, contextually located and deeply relational.
A Nonarchetypal 5,6‐Dihydro‐2H‐pyrano[3,2‐g]indolizine‐Based Solution‐Solid Dual Emissive AIEgen with Multicolor Tunability
Authors: Raghuvanshi Ashutosh , Jha Ajay Kumar , Sharma Ashutosh , Umar Shahida , Mishra Shachi , Kant Ruchir , Goel Atul
Published: February 2017

Screening of a chemical library of pyranones and their ring transformed fluorophores led to the discovery of a novel 5,6‐dihydro‐2H‐pyrano[3,2‐g]indolizine (DPI) class of the luminogen DPI 7, which exhibited unique solution–solid dual emission (SSDE) behavior with an emission color shift from bright‐green in solution to a strong red emission in the solid state. The AIE mechanism of these luminogens revealed a well‐defined set of noncovalent interactions (CH⋅⋅⋅O and CH⋅⋅⋅N) that block the motion of C2‐flexure leading to restriction of intramolecular vibrations (RIV) in the solid state. DPI‐7 is the first example of solution–solid dual emissive RIV‐based AIEgen, which has great potential both in biomedical imaging and optoelectronic fields.
Metal–Organic‐Framework‐Derived Carbons: Applications as Solid‐Base Catalyst and Support for Pd Nanoparticles in Tandem Catalysis
Authors: Li Xinle , Zhang Biying , Fang Yuhui , Sun Weijun , Qi Zhiyuan , Pei Yuchen , Qi Shuyan , Yuan Pengyu , Luan Xuechen , Goh Tian Wei , Huang Wenyu
Published: February 2017

The facile pyrolysis of a bipyridyl metal‐organic framework, MOF‐253, produces N‐doped porous carbons (Cz‐MOF‐253), which exhibit excellent catalytic activity in the Knoevenagel condensation reaction and outperform other nitrogen‐containing MOF‐derived carbons. More importantly, by virtue of their high Lewis basicity and porous nature, Cz‐MOF‐253‐supported Pd nanoparticles (Pd/Cz‐MOF‐253‐800) show excellent performance in a one‐pot sequential Knoevenagel condensation‐hydrogenation reaction.
Engineering of Ruthenium(II) Photosensitizers with Non‐Innocent Oxyquinolate and Carboxyamidoquinolate Ligands for Dye‐Sensitized Solar Cells
Authors: Ngo Ken T. , Lee Nicholas A. , Pinnace Sashari D. , Rochford Jonathan
Published: February 2017

An alternative approach to replacing the isothiocyantate ligands of the N3 photosensitizer with light‐harvesting bidentate ligands is investigated for application in dye‐sensitized solar cells (DSSCs). An in‐depth theoretical analysis has been applied to investigate the optical and redox properties of four non‐innocent ligand platforms, which is then corroborated with experiment. Taking advantage of the 5‐ and 7‐positions of 8‐oxyquinolate, or the carboxyaryl ring system of the N‐arylcarboxy‐8‐amidoquinolate ligand, fluorinated aryl substituents are demonstrated as an effective means of tuning complex redox potentials and light‐harvesting properties. The non‐innocent character, resulting from mixing of both the central metal‐dπ and ligand‐π manifolds, generates hybrid metal–ligand frontier orbitals. These play a major role by contributing to the redox properties and visible electronic transitions, and promoting an improved power conversion efficiency in a Ru DSSC device featuring non‐innocent ligands.
Effect of Ti (III) Surface Defects on the Process of Photocatalytic Reduction of Hexavalent Chromium
Authors: Qin Hongxia , Bian Yingying , Zhang Yaxi , Liu Longfei , Bian Zhenfeng
Published: February 2017

In this paper, the process of photocatalytic reduction of hexavalent chromium was investigated over Ti3+‐modified TiO2 photocatalysts. The Ti3+ surface defects were repaired by annealing as‐prepared sample at different temperatures to control the amount of Ti3+ sites. The samples were characterized by SEM, XRD, BET, UV–vis absorption, EPR and XPS. The results showed Ti3+ defects were successfully doped in TiO2. The surface selective adsorption of hexavalent chromium [Cr2O72− (Cr(VI))] and the desorption of trivalent chromium [Cr3+ (Cr(III))] were investigated during the process of photocatalytic reduction. Zeta potential results presented that the increased positive charges due to more Ti3+ defects on the surface show a significant improvement for adsorption of Cr(VI). Accordingly, the surface positive charges controlled by the Ti3+ defects play important roles in the photocatalytic reduction of Cr(VI).
Optic nerve, superior colliculus, visual thalamus, and primary visual cortex of the northern elephant seal (Mirounga angustirostris) and California sea lion (Zalophus californianus)
Authors: Turner Emily C. , Sawyer Eva K. , Kaas Jon H.
Published: February 2017

The northern elephant seal (Mirounga angustirostris) and California sea lion (Zalophus californianus) are members of a diverse clade of carnivorous mammals known as pinnipeds. Pinnipeds are notable for their large, ape‐sized brains, yet little is known about their central nervous system. Both the northern elephant seal and California sea lion spend most of their lives at sea, but each also spends time on land to breed and give birth. These unique coastal niches may be reflected in specific evolutionary adaptations to their sensory systems. Here, we report on components of the visual pathway in these two species. We found evidence for two classes of myelinated fibers within the pinniped optic nerve, those with thick myelin sheaths (elephant seal: 9%, sea lion: 7%) and thin myelin sheaths (elephant seal: 91%, sea lion: 93%). In order to investigate the architecture of the lateral geniculate nucleus, superior colliculus, and primary visual cortex, we processed brain sections from seal and sea lion pups for Nissl substance, cytochrome oxidase, and vesicular glutamate transporters. As in other carnivores, the dorsal lateral geniculate nucleus consisted of three main layers, A, A1, and C, while each superior colliculus similarly consisted of seven distinct layers. The sea lion visual cortex is located at the posterior side of cortex between the upper and lower banks of the postlateral sulcus, while the elephant seal visual cortex extends far more anteriorly along the dorsal surface and medial wall. These results are relevant to comparative studies related to the evolution of large brains.
Orthogonal topography in the parallel input architecture of songbird HVC
Authors: Elliott Kevin C. , Wu Wei , Bertram Richard , Hyson Richard L. , Johnson Frank
Published: February 2017

Neural activity within the cortical premotor nucleus HVC (acronym is name) encodes the learned songs of adult male zebra finches (Taeniopygia guttata). HVC activity is driven and/or modulated by a group of five afferent nuclei (the Medial Magnocellular nucleus of the Anterior Nidopallium, MMAN; Nucleus Interface, NIf; nucleus Avalanche, Av; the Robust nucleus of the Arcopallium, RA; the Uvaeform nucleus, Uva). While earlier evidence suggested that HVC receives a uniformly distributed and nontopographic pattern of afferent input, recent evidence suggests this view is incorrect (Basista et al., ). Here, we used a double‐labeling strategy (varying both the distance between and the axial orientation of dual tracer injections into HVC) to reveal a massively parallel and in some cases topographic pattern of afferent input. Afferent neurons target only one rostral or caudal location within medial or lateral HVC, and each HVC location receives convergent input from each afferent nucleus in parallel. Quantifying the distributions of single‐labeled cells revealed an orthogonal topography in the organization of afferent input from MMAN and NIf, two cortical nuclei necessary for song learning. MMAN input is organized across the lateral‐medial axis whereas NIf input is organized across the rostral‐caudal axis. To the extent that HVC activity is influenced by afferent input during the learning, perception, or production of song, functional models of HVC activity may need revision to account for the parallel input architecture of HVC, along with the orthogonal input topography of MMAN and NIf.
Pressure‐Induced Photoluminescence Adjustment and Lattice Disorder in Monolayer WSe2
Authors: Gong Yuanbo , Zhou Qiang , Huang Xiaoli , Han Bo , Fu Xinpeng , Gao Hanxue , Li Fangfei , Cui Tian
Published: February 2017

Pressure engineering is considered as a novel strategy to modulate the properties of transition metal dichalcogenide materials. Here, through photoluminescence (PL) and Raman measurements, we investigate the electronic band structure variation and lattice vibrational dynamics of monolayer tungsten diselenide (WSe2) under pressure. As the pressure increases, the energy of the direct Κ→Κ interband transition increases, whereas that of the indirect Λ→Κ interband transition decreases, leading to a significant transition from direct to indirect band gap at 3.8 GPa. With the increase of pressure, the intensity of the direct Κ→Κ interband transition constantly decreases and finally vanishes around 12.2 GPa. Moreover, a remarkable transition between A′ and LA(M) modes under pressure has been determined by virtue of Raman spectra variations, which indicate a pressure‐induced lattice disorder. This work provides a deep understanding of the intrinsic variation of WSe2 under pressure, which effectively facilitates the development of device applications.
A Simple and Mild Approach for the Synthesis of p‐Xylene from Bio‐Based 2,5‐Dimethyfuran by Using Metal Triflates
Authors: Ni Lingli , Xin Jiayu , Dong Huixian , Lu Xingmei , Liu Xiaomin , Zhang Suojiang
Published: February 2017

The production of aromatic platform chemicals from biomass‐derived feedstocks is of considerable importance in biomass conversion. However, the development of effective routes with simple steps and under mild conditions is still challenging. In this work, we report an original route for the direct synthesis of p‐xylene from 2,5‐dimethylfuran and acrylic acid catalyzed by scandium(III) triflate (Sc(OTf)3) in 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide ([Emim]NTf2) under mild conditions. An overall 63 % selectivity towards p‐xylene and 78 % selectivity towards aromatics were obtained at 90 % conversion of 2,5‐dimethylfuran by enhancing the dehydration and introducing an extra one‐pot decarboxylation step. Furthermore, various dienes and dienophiles were employed as reactants to extend the substrate scope. The aromatic compounds were obtained in moderate yields, which proved the potential of the method to be a generic approach for the conversion of bio‐based furanics into renewable aromatics.
Interconnected Network of Core–Shell CoP@CoBiPi for Efficient Water Oxidation Electrocatalysis under Near Neutral Conditions
Authors: Cui Liang , Qu Fengli , Liu Jingquan , Du Gu , Asiri Abdullah M. , Sun Xuping
Published: February 2017

Developing earth‐abundant electrocatalysts for efficient and stable water oxidation under near neutral conditions is of great importance but still remains a key challenge. Herein, we demonstrate the development of an interconnected network of core–shell CoP@CoBiPi through anodic polarization of a CoP nanoarray in potassium borate aqueous electrolyte (KBi). This 3 D CoP@CoBiPi exhibits high catalytic activity for water oxidation at pH 9.2 and needs an overpotential (η) of only 410 mV to drive a geometrical catalytic current density of 10 mA cm−2, with a high turnover frequency of 819 h−1 at an overpotential of 610 mV. Remarkably, this catalyst also demonstrates high long‐term electrochemical stability with its activity being maintained for at least 27 h in KBi. This study provides us an attractive earth‐abundant 3 D catalyst electrode for water‐splitting devices toward efficient and stable water oxidation under benign conditions.
Quantitative Flow Cytometry: Concerns and Recommendations in Clinic and Research
Authors: Mizrahi Olga , Ish Shalom Eliran , Baniyash Michal , Klieger Yair
Published: February 2017

Background

Quantitative flow cytometry (QFCM) can be an important element within the developing toolbox for clinical diagnostics which relies on precise and rapid tests that provide a conclusive answer for physicians. The FC technology combines all of these features. Until recently, this imperative discipline was based on qualitative assessments of cell populations. However, due to the enormous advancement in FC technology, which allows the quantification of a number of antigens on cell surface and within the cells by units of median fluorescence intensity (MFI), this method becomes meaningful and fits the clinical needs. Methods: On the basis of our experience in the field of quantitative FC, we wish to highlight some of the key concerns related to this methodology and suggest possible solutions for achieving uniform and standardized QFCM tests based on MFI. Results: Several parameters are responsible for inter and intra laboratory variations. The standardization of quantitative FC relies on three major components; Samples and reagents handling, FC maintenance and data analysis. The use of specialized beads as a part of the routine calibration process lowers inter‐test variability between different operators and different FC instruments. Similarly, the use of agreed biological controls contributes significantly to lowering test variability. Conclusions: The field of QFCM displays a significant part in the diagnostic clinical toolbox. We believe that the recommendations described herein can improve significantly the stability and accuracy of this method, thus assuring a more standardized cell analyses. © 2017 International Clinical Cytometry Society
How “suspicious” is that nodule? Review of “suspicious” Afirma gene expression classifier in high risk thyroid nodules
Authors: Roychoudhury Sudarshana , Klein Melissa , Souza Fabiola , Gimenez Cecilia , Laser Alice , Shaheen Cocker Rubina , Chau Karen , Das Kasturi
Published: February 2017

Background

The Afirma gene expression classifier (GEC) is being increasingly utilized to confirm the benign nature of indeterminate FNA cytology results thus avoiding unnecessary surgical procedures. However the “suspicious” result of the Afirma GEC does not classify these indeterminate nodules further in determining appropriate management. This study investigated the outcome of the thyroid nodules deemed to be “suspicious” by the Afirma GEC in a high risk population.

Methods

The pathology database was searched for all thyroid nodules with Afirma test results over a three year period, 2013–2015. All thyroid nodules with a “suspicious” Afirma GEC result were investigated. Patient medical records were retrospectively reviewed for clinical history, FNA results, radiologic findings, management and follow‐up.

Results

Afirma result was suspicious in 69 cases. On cytologic evaluation 3.0% of the cases were non diagnostic (ND), 9% benign, 62% AUS, and 26% suspicious for neoplasm (SN). There was no follow up in 13% of cases and 87% were resected (50% lobectomies and 50% total thyroidectomies). On surgical resection 82% were benign, with 45% follicular adenoma (FA), and 37% nodular goiter (NG). The remaining 18% were malignant.

Conclusion

The rate of malignancy in nodules suspicious by Afirma was 18.3% (11/60). The rate of malignancy in nodules suspicious for neoplasm (SN) on cytology interpretation was 31.2% (5/16). False positive rate of Afirma was 56% (32/57). We conclude that cytology interpretation has a higher rate of predicting malignancy, in nodules interpreted as SN, when compared with the Afirma test, by almost twofold Diagn. Cytopathol. 2017;45:308–311. © 2016 Wiley Periodicals, Inc.
Maturation‐dependent control of vocal temporal plasticity in a songbird
Authors: Tachibana Ryosuke O. , Takahasi Miki , Hessler Neal A. , Okanoya Kazuo
Published: February 2017

Birdsong is a unique model to address learning mechanisms of the timing control of sequential behaviors, with characteristic temporal structures consisting of serial sequences of brief vocal elements (syllables) and silent intervals (gaps). Understanding the neural mechanisms for plasticity of such sequential behavior should be aided by characterization of its developmental changes. Here, we assessed the level of acute vocal plasticity between young and adult Bengalese finches, and also quantified developmental change in variability of temporal structure. Acute plasticity was tested by delivering aversive noise bursts contingent on duration of a target gap, such that birds could avoid the noise by modifying their song. We found that temporal variability of song features decreased with birds' maturation. Noise‐avoidance experiments demonstrated that maximal changes of gap durations were larger in young that in adult birds. After these young birds matured, the maximal change decreased to a similar level as adults. The variability of these target gaps also decreased as the birds matured. Such parallel changes suggest that the level of acute temporal plasticity could be predicted from ongoing temporal variability. Further, we found that young birds gradually began to stop their song at the target gap and restart from the introductory part of song, whereas adults did not. According to a synaptic chain model for timing sequence generation in premotor nuclei, adult learning would be interpreted as adaptive changes in conduction delays between chain‐to‐chain connections, whereas the learning of young birds could mainly depend on changes of the connections. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 995–1006, 2017
Electrical transmission: Two structures, same functions?
Authors: Pereda Alberto E. , Macagno Eduardo
Published: February 2017

Electrical synapses are finding increasing representation and importance in our understanding of signaling in the nervous system. In contrast to chemical synapses, at which molecules are evolutionary conserved, vertebrate and invertebrate electrical synapses represent molecularly different structures that share a common communicating strategy that allows them to serve very similar functions. A better understanding of differences and commonalities regarding the structure, function and regulation of vertebrate and invertebrate electrical synapses will lead to a better understanding of the properties and functional diversity of this modality of synaptic communication. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 517–521, 2017
Zebrafish transgenic constructs label specific neurons in Xenopus laevis spinal cord and identify frog V0v spinal neurons
Authors: Juárez‐Morales José L. , Martinez‐De Luna Reyna I. , Zuber Michael E. , Roberts Alan , Lewis Katharine E.
Published: February 2017

A correctly functioning spinal cord is crucial for locomotion and communication between body and brain but there are fundamental gaps in our knowledge of how spinal neuronal circuitry is established and functions. To understand the genetic program that regulates specification and functions of this circuitry, we need to connect neuronal molecular phenotypes with physiological analyses. Studies using Xenopus laevis tadpoles have increased our understanding of spinal cord neuronal physiology and function, particularly in locomotor circuitry. However, the X. laevis tetraploid genome and long generation time make it difficult to investigate how neurons are specified. The opacity of X. laevis embryos also makes it hard to connect functional classes of neurons and the genes that they express. We demonstrate here that Tol2 transgenic constructs using zebrafish enhancers that drive expression in specific zebrafish spinal neurons label equivalent neurons in X. laevis and that the incorporation of a Gal4:UAS amplification cassette enables cells to be observed in live X. laevis tadpoles. This technique should enable the molecular phenotypes, morphologies and physiologies of distinct X. laevis spinal neurons to be examined together in vivo. We have used an islet1 enhancer to label Rohon‐Beard sensory neurons and evx enhancers to identify V0v neurons, for the first time, in X. laevis spinal cord. Our work demonstrates the homology of spinal cord circuitry in zebrafish and X. laevis, suggesting that future work could combine their relative strengths to elucidate a more complete picture of how vertebrate spinal cord neurons are specified, and function to generate behavior. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1007–1020, 2017
Assessing the importance of demographic parameters for population dynamics using Bayesian integrated population modeling
Authors: Eacker Daniel R. , Lukacs Paul M. , Proffitt Kelly M. , Hebblewhite Mark
Published: February 2017

To successfully respond to changing habitat, climate or harvest, managers need to identify the most effective strategies to reverse population trends of declining species and/or manage harvest of game species. A classic approach in conservation biology for the last two decades has been the use of matrix population models to determine the most important vital rates affecting population growth rate (λ), that is, sensitivity. Ecologists quickly realized the critical role of environmental variability in vital rates affecting λ by developing approaches such as life‐stage simulation analysis (LSA) that account for both sensitivity and variability of a vital rate. TheseLSAmethods used matrix‐population modeling and Monte Carlo simulation methods, but faced challenges in integrating data from different sources, disentangling process and sampling variation, and in their flexibility. Here, we developed a Bayesian integrated population model (IPM) for two populations of a large herbivore, elk (Cervus canadensis) in Montana,USA. We then extended theIPMto evaluate sensitivity in a Bayesian framework. We integrated known‐fate survival data from radio‐marked adults and juveniles, fecundity data, and population counts in a hierarchical population model that explicitly accounted for process and sampling variance. Next, we tested the prevailing paradigm in large herbivore population ecology that juvenile survival of neonates <90 d old drives λ using our BayesianLSAapproach. In contrast to the prevailing paradigm in large herbivore ecology, we found that adult female survival explained more of the variation in λ than elk calf survival, and that summer and winter elk calf survival periods were nearly equivalent in importance for λ. Our BayesianIPMimproved precision of our vital rate estimates and highlighted discrepancies between count and vital rate data that could refine population monitoring, demonstrating that combining sensitivity analysis with population modeling in a Bayesian framework can provide multiple advantages. Our BayesianLSAframework will provide a useful approach to addressing conservation challenges across a variety of species and data types.
Will I get fat? 22‐year weight trajectories of individuals with eating disorders
Authors: Murray Helen B. , Tabri Nassim , Thomas Jennifer J. , Herzog David B. , Franko Debra L. , Eddy Kamryn T.
Published: February 2017

Objective

For some, fat phobia or fear of uncontrollable weight gain is diagnostic of eating disorders, often inhibiting treatment engagement and predicting symptom relapse. Prior research has reported weight changes at infrequent or long intervals, but rate, shape, and magnitude of long‐term changes remain unknown. Our study examined 22‐year longitudinal trajectories of body mass index (BMI) in women with anorexia nervosa (AN) and bulimia nervosa (BN).

Method

Participants were followed over 10 years (N = 225) and at 22‐year follow‐up (N = 175). Using latent growth curves, we examined: (1) shape and rate of intra‐individual BMI change over 10 years; (2) predictors of BMI change over 10 years, (3) 22‐year BMI outcomes; and (4) BMI changes over 10 years as predictors of 22‐year BMI.

Results

The best‐fitting model captured overall intra‐individual rates of BMI change in three intervals, showing moderate rate of BMI increase from intake to year 2, modest increase from year 2 to 5, and plateau from year 5 to 10. At 22 years, 14% were underweight, 69% were normal weight, and only 17% were overweight or obese. Greater increases from intake to year 2 predicted higher BMI at 22 years (β = 0.43, p < 0.01) and were predicted by intake diagnosis of AN‐restricting (β = 0.31, p < 0.01) or AN‐binge eating/purging (β = 0.29, p < 0.01).

Discussion

BMI increased most rapidly during earlier years of the study for those with lower weight at study intake (i. e., AN) and plateaued over time, settling in the normal range for most. Psychoeducation about expected BMI trajectory may challenge patients' long‐term fat phobic predictions.
Subgrid modeling of salt marsh hydrodynamics with effects of vegetation and vegetation zonation
Authors: Wu Guoxiang , Li Huajun , Liang Bingchen , Shi Fengyan , Kirby James T. , Mieras Ryan
Published: February 2017

Vegetation plays a critical role in modifying inundation and flow patterns in salt marshes. In this study, the effects of vegetation are derived and implemented in a high‐resolution, subgrid model recently developed for simulating salt marsh hydrodynamics. Vegetation‐induced drag forces are taken into account as momentum sink terms. The model is then applied to simulate the flooding and draining processes in a meso‐tidal salt marsh, both with and without vegetation effects. Marsh inundation and flow patterns are significantly changed with the presence of vegetation. A smaller area of inundation occurs when vegetation is considered. Tides propagate both on the platform and through the channels when vegetation is absent, whereas flows concentrate mainly in channels when vegetation is present. Local inundation on vegetated platforms is caused mainly by water flux spilled from nearby channels, with a flow direction perpendicular to the channel edges, whereas inundation on bare platforms has contributions from both local spilled‐over water flux and remote advection from adjacent platforms. The flooding characteristics predicted by the model showed a significant difference between higher marsh and lower marsh, which is consistent with the wetlands classification by the National Wetlands Inventory (NWI). The flooding characteristics and spatial distribution of hydroperiod are also highly correlated with the vegetation zonation patterns observed in Google Earth imagery. Regarding the strong interaction between flow, vegetation and geomorphology, the conclusion highlights the importance of including vegetation in the modeling of salt marsh dynamics. Copyright © 2017 John Wiley & Sons, Ltd.
Predictors of distant metastasis in human papillomavirus–associated oropharyngeal cancer
Authors: Weller Michael A. , Ward Matthew C. , Berriochoa Camille , Reddy Chandana A. , Trosman Samuel , Greskovich John F. , Nwizu Tobenna I. , Burkey Brian B. , Adelstein David J. , Koyfman Shlomo A.
Published: February 2017

Background

Human papillomavirus (HPV)‐positive oropharyngeal cancer is associated with favorable outcomes, prompting investigations into treatment deintensification. The purpose of this study was for us to present the predictors of distant metastases in patients with HPV‐positive oropharyngeal cancer treated with cisplatin‐based chemoradiotherapy (CRT) or cetuximab‐based bioradiotherapy (bio‐RT).

Methods

In patients with stage III to IVb HPV‐positive oropharyngeal cancer, the Kaplan–Meier analysis was used to calculate distant metastases rates. Univariate analysis (UVA) and multivariate analysis (MVA) were used to identify factors associated with distant metastases.

Results

Increased distant metastases rates were noted in active smokers versus never/former smokers (22% vs 5%), T4 vs T1 to T3 (15% vs 6%), and cetuximab‐based bio‐RT versus CRT (23% vs 5%). All remained significant on MVA.

Conclusion

T4 tumors and active smokers have substantial rates of distant metastases, and trials investigating intensified systemic therapies may be considered. Higher rates of distant metastases observed with concurrent cetuximab are hypothesis generating, but further data are needed. © 2017 Wiley Periodicals, Inc. Head Neck 39: 940–946, 2017
Minimizing adjuvant treatment after transoral robotic surgery through surgical margin revision and exclusion of radiographic extracapsular extension: A Prospective observational cohort study
Authors: Morisod Benoit , Venara–Vulpe Ioana I. , Alzuphar Stephen , Monnier Yan , Bongiovanni Massimo , Hagmann Patric , Bouchaab Hanan , Bourhis Jean , Simon Christian
Published: February 2017

Background

We investigated in a prospective cohort of patients treated with trans‐oral robotic surgery (TORS) for oropharyngeal cancer (OPC), who were selected for the absence of radiographic extra‐capsular extension (ECS) and surgically revised for inadequate margins, the possibility of reducing adjuvant radiation (RT)/chemo‐radiation therapy (CRT) without jeopardizing tumor control and functional outcome.

Methods

We conducted a prospective observational cohort of patients treated with TORS for oropharyngeal cancer.

Results

Twenty‐nine patients with T1/2N0 to N2B stage cancers were treated with TORS. Forty‐five percent of them were treated for secondary primaries. Nine of 29 patients (31%) were revised for close/positive margins. Adjuvant RT was prescribed for 2 of 19 patients with early squamous cell carcinoma (SCCs) and CRT for 1 of 10 patients with advanced oropharyngeal SCCs. Overall survival (OS), disease‐specific survival (DSS), and locoregional control at 2 years were 85%, 96%, and 93%, respectively. Posttreatment Functional Outcome Swallowing Scale (FOSS) scores worsened with prior or adjuvant RT, local recurrence, site, and revision for margins.

Conclusion

Patients with early and moderately advanced oropharyngeal SCC selected for radiographic ECS and revised for inadequate margins have excellent tumor control and favorable functional recovery. © 2017 Wiley Periodicals, Inc. Head Neck 39: 965–973, 2017
Memory for relations in the short term and the long term after medial temporal lobe damage
Authors: Squire Larry R.
Published: February 2017

A central idea about the organization of declarative memory and the function of the hippocampus is that the hippocampus provides for the coding of relationships between items. A question arises whether this idea refers to the process of forming long‐term memory or whether, as some studies have suggested, memory for relations might depend on the hippocampus even at short retention intervals and even when the task falls within the province of short‐term (working) memory. The latter formulation appears to place the operation of relational memory into conflict with the idea that working memory is independent of medial temporal lobe (MTL) structures. In this report, the concepts of relational memory and working memory are discussed in the light of a simple demonstration experiment. Patients with MTL lesions successfully learned and recalled two word pairs when tested directly after learning but failed altogether when tested after a delay. The results do not contradict the idea that the hippocampus has a fundamental role in relational memory. However, there is a need for further elaboration and specification of the idea in order to explain why patients with MTL lesions can establish relational memory in the short term but not in long‐term memory. © 2017 Wiley Periodicals, Inc.
Toxic effects of TiO2 nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca2+/PKC/p38 MAPK/NF‐κB cascade
Authors: Ye Lingqun , Hong Fashui , Ze Xiao , Li Lingjuan , Zhou Yaoming , Ze Yuguan
Published: February 2017

Although numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) can be accumulated in various animal organs and can cause toxicity, there is currently only limited data regarding reproductive toxicity especially on the toxic mechanisms of TiO2 NPs in Sertoli cells. In order to investigate the mechanism of reproductive toxicity, primary cultured rat Sertoli cells were exposed to 5, 15, or 30 μg/mL TiO2 NPs for 24 h, and TiO2 NPs internalization, expression of PKC (p‐PKC) and p38 MAPK (p‐p38 MAPK) as well as calcium homeostasis were examined. Our findings demonstrated that TiO2 NPs crossed the membrane into the cytoplasm or nucleus, and significantly suppressed cell viability of primary cultured rat Sertoli cells in a concentration‐dependent manner. Furthermore, immunological dysfunction caused by TiO2 NPs was involved in the increased expression of NF‐κB, TNF‐α, and IL‐1β, and decreased IκB expression. TiO2 NPs significantly decreased Ca2+‐ATPase and Ca2+/Mg2+‐ATPase activity and enhanced intracellular Ca2+ levels, and up‐regulated the expression of p‐PKC and p‐p38 MAPK in a dose‐dependent manner in primary cultured rat Sertoli cells. Taken together, these findings indicate that TiO2 NPs may induce immunological dysfunction of primary cultured rat Sertoli cells by stimulating the Ca2+/PKC/p38 MAPK cascade, which triggers NF‐κB activation and ultimately induces the expression of inflammatory cytokines in primary cultured rat Sertoli cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1374–1382, 2017.