bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of β-cyclodextrin-mediated single bimolecular inclusion complex: characterization, molecular docking, in-vitro release and bioavailability studies for gefitinib and simvastatin conjugate
Authors: Basak Souvik , Mondal Sandip , Dey Suddhasattya , Bhattacharya Plaban , Saha Achintya , Deep Punetha Vinay , Abbas Ali , Gopal Sahoo Nanda
Published: June 2017

Objectives

Introduction of multiple molecules in a single inclusion complex, albeit cheaper, lacks conclusive attempts in earlier drug delivery reports. This manuscript emphasizes simultaneous incorporation of two anticancer drugs, gefitinib (G) and simvastatin (S), in a single molecule of β-cyclodextrin for the first time to achieve effective drug delivery.

Methods

The inclusion complex (GSBCD) was prepared by cosolvent evaporation technique using β-cyclodextrin (BCD) as carrier. Characterization of GSBDC was performed by Fourier transform infrared spectroscopy, COSY, differential scanning calorimetry, X-ray diffraction and dynamic light scattering analyses, which were ascribed to the complex formation inside BCD cavity, micronization of drugs and conversion to amorphous state.

Key findings

The complex revealed entrapment of G and S in 3 ± 0.48: 2 ± 0.19 molar ratio and showed more than 3.5 and 10 fold increase in drug release in in vitro and in vivo, respectively. Docking and COSY studies revealed molecular alignment into BCD central cavity that been achieved via hydrogen bonding between certain groups of the ligands (G and S) and the polar heads of BCD. Partial incorporation of the molecular backbone inside inclusion complex suggests superficial contact with the solvent indicating slow steady release kinetics.

Conclusions

This approach of forming inclusion complex with multiple molecules within a single cavity can be a landmark for further studies in drug delivery.
Distinct post‐translational features of type I collagen are conserved in mouse and human periodontal ligament
Authors: Hudson D. M. , Garibov M. , Dixon D. R. , Popowics T. , Eyre D. R.
Published: June 2017

Background and Objective

Specifics of the biochemical pathways that modulate collagen cross‐links in the periodontal ligament (PDL) are not fully defined. Better knowledge of the collagen post‐translational modifications that give PDL its distinct tissue properties is needed to understand the pathogenic mechanisms of human PDL destruction in periodontal disease. In this study, the post‐translational phenotypes of human and mouse PDL type I collagen were surveyed using mass spectrometry.

PDL is a highly specialized connective tissue that joins tooth cementum to alveolar bone. The main function of the PDL is to support the tooth within the alveolar bone while under occlusal load after tooth eruption. Almost half of the adult population in the USA has periodontal disease resulting from inflammatory destruction of the PDL, leading to tooth loss. Interestingly, PDL is unique from other ligamentous connective tissues as it has a high rate of turnover. Rapid turnover is believed to be an important characteristic for this specialized ligament to function within the oral‐microbial environment. Like other ligaments, PDL is composed predominantly of type I collagen. Collagen synthesis is a complex process with multiple steps and numerous post‐translational modifications including hydroxylation, glycosylation and cross‐linking. The chemistry, placement and quantity of intermolecular cross‐links are believed to be important regulators of tissue‐specific structural and mechanical properties of collagens.

Material and Methods

Type I collagen was isolated from several mouse and human tissues, including PDL, and analyzed by mass spectrometry for post‐translational variances.

Results

The collagen telopeptide cross‐linking lysines of PDL were found to be partially hydroxylated in human and mouse, as well as in other types of ligament. However, the degree of hydroxylation and glycosylation at the helical Lys87 cross‐linking residue varied across species and between ligaments. These data suggest that different types of ligament collagen, notably PDL, appear to have evolved distinctive lysine/hydroxylysine cross‐linking variations. Another distinguishing feature of PDL collagen is that, unlike other ligaments, it lacks any of the known prolyl 3‐hydroxylase 2‐catalyzed 3‐hydroxyproline site modifications that characterize tendon and ligament collagens. This gives PDL a novel modification profile, with hybrid features of both ligament and skin collagens.

Conclusion

This distinctive post‐translational phenotype may be relevant for understanding why some individuals are at risk of rapid PDL destruction in periodontal disease and warrants further investigation. In addition, developing a murine model for studying PDL collagen may be useful for exploring potential clinical strategies for promoting PDL regeneration.
Comparing the risk of hepatitis B virus reactivation between direct‐acting antiviral therapies and interferon‐based therapies for hepatitis C
Authors: Kawagishi N. , Suda G. , Onozawa M. , Kimura M. , Maehara O. , Ohara M. , Izumi T. , Umemura M. , Ito J. , Nakai M. , Sho T. , Natsuizaka M. , Morikawa K. , Ogawa K. , Sakamoto N.
Published: June 2017

Hepatitis B virus (HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus (HCV) and HBV co‐infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti‐HCV therapy and compared those between interferon (IFN)‐free direct‐acting antiviral (DAA) therapies and IFN‐based therapies. Three hundred and twenty‐two patients with HCV infection receiving anti‐HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV‐DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti‐HBs positivity, changes in anti‐HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN‐free DAA therapies and 72 were treated with IFN‐based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN‐free DAA therapies, while no patient developed HBV reactivation after IFN‐based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti‐HBs titre to <12 mIU mL−1 by the end of treatment. The decline changes of anti‐HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN‐free DAA therapies. Low levels of anti‐HBs and their decrease to <12 mIU mL−1 after treatment are significant risk factors for HBV reactivation or reappearance.
HBsAg loss after peginterferon‐nucleotide combination treatment in chronic hepatitis B patients: 5 years of follow‐up
Authors: Stelma F. , van der Ree M. H. , Jansen L. , Peters M. W. , Janssen H. L. A. , Zaaijer H. L. , Takkenberg R. Bart , Reesink H. W.
Published: June 2017

Combining peginterferon‐alfa‐2a (pegIFN) with a nucleotide analogue can result in higher rates of HBsAg loss than either therapy given alone. Here, we investigated the durability of the response to combination therapy in chronic hepatitis B (CHB) patients after 5 years of follow‐up. In the initial study, 92 CHB patients (44 HBeAg‐positive, 48 HBeAg‐negative) with HBV DNA >100 000 c/mL (~20 000 IU/mL) and active hepatitis were treated for 48 weeks with pegIFN 180 μg/week and 10 mg adefovir dipivoxil daily. For the long‐term follow‐up (LTFU) study, patients were followed up for 5 years after the end of treatment. At year 5, 70 (32 HBeAg‐positive, 38 HBeAg‐negative) patients remained in the study. At year 5, 19% (6/32) of HBeAg‐positive patients and 16% (6/38) of HBeAg‐negative patients lost HBsAg, and no HBsAg seroreversion was observed. The 5‐year cumulative Kaplan‐Meier estimate for HBsAg loss was 17.2% for HBeAg‐positive patients and 19.3% for HBeAg‐negative patients. Fourteen of sixteen patients who lost HBsAg at any time point during follow‐up developed anti‐HBs antibodies (>10 IU/L). At year 5, in total 63% (20/32) of HBeAg‐positive and 71% (27/38) of HBeAg‐negative patients were retreated with nucleos(t)ide analogues during follow‐up. The cumulative Kaplan‐Meier estimate for retreatment was 60% of patients at year 5. At year 5 of follow‐up, 18% of CHB patients treated with pegIFN/nucleotide analogue combination therapy had durable HBsAg loss and 88% of these had developed anti‐HBs antibodies.
Decreased portal vein velocity is predictive of the development of portal vein thrombosis: A matched case‐control study
Authors: Stine Jonathan G. , Wang Jennifer , Shah Puja M. , Argo Curtis K. , Intagliata Nicolas , Uflacker Andre , Caldwell Stephen H. , Northup Patrick G.
Published: June 2017

Background & Aims

Portal vein thrombosis (PVT) in cirrhosis may lead to hepatic decompensation and increased mortality. We aimed to investigate if decreased portal vein (PV) velocity is associated with future PVT.

Methods

Data on adult patients with cirrhosis and PVT between January 1, 2005 and July 30, 2015 were obtained. Cases with PVT were matched by age, gender and Model for End‐stage Liver Disease (MELD) score to corresponding controls without PVT. Cox proportional hazards models, receiver operator curves and Kaplan Meier curves were constructed.

Results

One hundred subjects (50 matched pairs) with mean age 53.8±13.1 y and MELD score 14.9±5.5 were included in our analysis. Sixty‐four percent were male and 76% were Child‐Turcotte‐Pugh Class A or B. Baseline characteristics (prior to development of PVT) were similar, except for baseline PV velocity (16.9 cm/s, 95% CI 13.9‐20.0 PVT vs 25.0, 95% CI 21.8‐28.8 no PVT, P<.001). 30 PVT subjects had PV velocity <15 cm/s compared to five without PVT (P<.001). On adjusted multivariable analysis, PV velocity was the strongest independent risk factor predicting PVT development (HR 0.86, 95% CI 0.80‐0.93). The predictive value for PVT development was greatest for flow <15 cm/s (c‐statistic 0.77). PV velocity <15 cm/s had a highly significant association with future PVT (HR 6.00, 95% CI 2.20‐16.40, P=<.001).

Conclusions

Decreased PV velocity is associated with increased risk of future PVT. Patients with cirrhosis and decreased PV velocity are a high‐risk subgroup that warrants further investigation with prospective study.
Children's Enactment of Characters' Movements: A Novel Measure of Spatial Situation Model Representations and Indicator of Comprehension
Authors: Nyhout Angela , O'Neill Daniela K.
Published: June 2017

A story's space or setting often determines and constrains the actions of its characters. We report on an experiment with 106 children of 7–8 years old in which, using a novel enactment task, we measured children's representation of a story character's movement during story listening. We found that children were more likely to enact movements that were explicitly stated in the passage than those they had to infer based on their situation model representation of the house and the character's location within it. We found that this ability to infer movements was significantly predictive of children's narrative comprehension after controlling for oral comprehension, vocabulary, working memory, and enactment of explicitly stated movements. We discuss the role of spatial situation models in comprehension and potential future uses for this enactment task in research and classrooms.
Novel intracytoplasmic inclusions immunoreactive for phosphorylated‐TDP43 and cystatin C in anterior horn cells in a case of sporadic amyotrophic lateral sclerosis
Authors: Shintaku Masayuki , Kaneda Daita , Oyanagi Kiyomitsu
Published: June 2017

Novel intracytoplasmic inclusions immunoreactive for phosphorylated transactivation response DNA‐binding protein 43 (p‐TDP43), cystatin C, and transferrin were found in anterior horn cells in a case of sporadic amyotrophic lateral sclerosis (ALS). The patient was a 59‐year‐old woman, who died of ALS after a clinical course of 8 years. She had been receiving mechanical support for respiration for 6 years and in a “totally locked‐in” state for 4 years prior to death. The spinal cord showed severe degeneration involving the anterior and lateral funiculi, whereas the posterior funiculus was preserved. Neurons in the anterior horn and Clarke's column were markedly lost, and many Bunina bodies and a few skein‐like inclusions were found. Some remaining anterior horn cells had round and densely eosinophilic or amphophilic intracytoplasmic inclusions. They were immunoreactive for ubiquitin, p‐TDP43, cystatin C and transferrin. On confocal laser microscopy, cystatin C was found to consistently surround p‐TDP43 within the inclusions. The inclusions ultrastructurally consisted of granule‐associated fibrils and, in the central portion, dense aggregates of fibrils were associated with masses of electron‐dense, coarsely granular or amorphous material. Although their pathogenesis remains unknown, these unique inclusions may have been formed under a specific condition whereby p‐TDP43 and cystatin C interacted with each other.
Spindle cell oncocytoma of adenohypophysis: Review of literature and report of another recurrent case
Authors: Sali Akash , Epari Sridhar , Tampi Chandralekha , Goel Atul
Published: June 2017

Spindle cell oncocytoma (SCO) of adenohypophysis was first described in 2002 by Roncaroli et al. as a new entity in the tumors originating from adenohypophysis. It was subsequently recognized as a distinct entity in the 2007 WHO classification of CNS tumors and retained in the current updated classification. In contrast to that suggested by the original authors, this tumor does have a potential for recurrence as first described by Kloub et al. and later with many such case reports. This tumor can be confused with other sellar tumors like pituicytomas and pituitary adenoma, both radiologically and histopathologically. However, it is imperative to differentiate these tumors from the above‐mentioned differential diagnoses as it certainly has a recurrent potential. To date only 34 cases of SCO have been published in the English literature. Herein we present a rare SCO case with unusually aggressive course in a 64‐year‐old man, which recurred 4 years after the initial diagnosis.
Exploration of difficult conversations among Australian paramedics
Authors: Williams Brett , Beovich Bronwyn , Flemming Geoff , Donovan Grant , Patrick Ian
Published: June 2017

Previous studies indicate that healthcare professionals find it challenging to engage in difficult conversations regarding concerning behavior of colleagues. As a result, these conversations are often avoided. The inability to have these difficult conversations is associated with poorer patient outcomes, staff commitment, discretionary effort, and employee satisfaction. This descriptive study used an online questionnaire to examine responses of paramedics employed by Ambulance Victoria (Australia) regarding difficult conversations between colleagues about concerning behavior of co‐workers. The results suggest that, like other healthcare professions, many paramedics find it challenging to raise these concerns. To the best knowledge of the authors, this is the first study of its type to be undertaken within the paramedic profession and provides a platform for further research within this and other health professions.
Expansion of sesquiterpene biosynthetic gene clusters in pepper confers nonhost resistance to the Irish potato famine pathogen
Authors: Lee Hyun‐Ah , Kim Sejun , Kim Seungill , Choi Doil
Published: June 2017

Chemical barriers contribute to nonhost resistance, which is defined as the resistance of an entire plant species to nonadapted pathogen species. However, the molecular basis of metabolic defense in nonhost resistance remains elusive.

Here, we report genetic evidence for the essential role of phytoalexin capsidiol in nonhost resistance of pepper (Capsicumspp.) to potato late blightPhytophthora infestansusing transcriptome and genome analyses.

Two different genes for capsidiol biosynthesis, 5‐epi‐aristolochene synthase (EAS) and 5‐epi‐aristolochene‐1,3‐dihydroxylase (EAH), belong to multigene families. However, only a subset ofEAS/EAHgene family members were highly induced uponP. infestansinfection, which was associated with parallel accumulation of capsidiol inP. infestans‐infected pepper. Silencing ofEAShomologs in pepper resulted in a significant decrease in capsidiol accumulation and allowed the growth of nonadaptedP. infestansthat is highly sensitive to capsidiol. Phylogenetic and genomic analyses ofEAS/EAHmultigene families revealed that the emergence of pathogen‐inducibleEAS/EAHgenes inCapsicum‐specific genomic regions rendered pepper a nonhost ofP. infestans.

This study provides insights into evolutionary aspects of nonhost resistance based on the combination of a species‐specific phytoalexin and sensitivity of nonadapted pathogens.
Flavonoids as modulators of metabolic enzymes and drug transporters
Authors: Miron Anca , Aprotosoaie Ana Clara , Trifan Adriana , Xiao Jianbo
Published: June 2017

Flavonoids, natural compounds found in plants and in plant‐derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug‐metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP‐glucuronosyltransferases, glutathione S‐transferases (GSTs)). Flavonoids have been reported to inhibit ATP‐binding cassette (ABC) transporters (multidrug resistance (MDR)–associated proteins, breast cancer–resistance protein) that contribute to the development of MDR. P‐glycoprotein, an ABC transporter that limits drug bioavailability and also induces MDR, was differently modulated by flavonoids. Flavonoids and their phase II metabolites (sulfates, glucuronides) inhibit organic anion transporters involved in the tubular uptake of nephrotoxic compounds. In vivo studies have partially confirmed in vitro findings, suggesting that the mechanisms underlying the modulatory effects of flavonoids are complex and difficult to predict in vivo. Data summarized in this review strongly support the view that flavonoids are promising candidates for the enhancement of oral drug bioavailability, chemoprevention, and reversal of MDR.
Intraoperative acidosis and hypercapnia during thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia/tracheoesophageal fistula
Authors: Zani Augusto , Lamas‐Pinheiro Ruben , Paraboschi Irene , King Sebastian K. , Wolinska Justyna , Zani‐Ruttenstock Elke , Eaton Simon , Pierro Agostino
Published: June 2017

Background

Intraoperative hypercapnia and acidosis have been associated with thoracoscopic repair of both congenital diaphragmatic hernia and esophageal atresia/tracheoesophageal fistula.

Aim

The aim of the present study was to investigate whether thoracoscopic repair of congenital diaphragmatic hernia or esophageal atresia/tracheoesophageal fistula was associated with acidosis and hypercapnia in a large group of neonates, and to analyze the effects of acidosis and hypercapnia on early postoperative outcomes.

Methods

We reviewed the charts of neonates who underwent open or thoracoscopic congenital diaphragmatic hernia or esophageal atresia/tracheoesophageal fistula repair (2004‐2014). Patients with available intraoperative arterial gas values were included. Data (PaCO2: mm Hg) were compared using paired/unpaired tests and are reported as difference [95% confidence interval].

Results

Congenital diaphragmatic hernia: 187 neonates underwent open (n=153) or thoracoscopic (n=34) repair. Intraoperative arterial gas values were recorded in 96 open and in 23 thoracoscopic operations. Both groups had similar preoperative pH and PaCO2, and developed intraoperative acidosis (open −0.08 [−0.11, −0.05] P<.001, thoracoscopic −0.14 [−0.24, −0.04] P=.01) and hypercapnia (open: 7.8 [3.2, 12.4], P=.002; thoracoscopic: 20.2 [−2.5, 43, P=.07). Intraoperatively, neonates undergoing thoracoscopic repair developed lower pH than those having open surgery (−0.06 [−0.01, −0.10] P=.018), but maintained similar levels of PaCO2 (−4.0 [−9.0, 4.4] P=.39). Esophageal atresia/tracheoesophageal fistula: 205 neonates underwent open (n=180) or thoracoscopic (n=25) repair. Intraoperative arterial gas values were recorded in 62 open and in 14 thoracoscopic operations. Both groups had similar preoperative pH and PaCO2, and developed intraoperative acidosis (open: −0.09 [−0.14, −0.04], P<.001; thoracoscopic: 0.21 [−0.28, −0.14], P<.001) and hypercapnia (open: 9.2 [2.6, 15.7] P=.008; thoracoscopic: 15.2 [1.6, 28.7], P=.03). Intraoperatively, neonates undergoing thoracoscopic repair developed lower pH than those having open surgery (difference 0.08 [0.01, 0.15], P=.02) but maintained similar levels of PaCO2 (difference −1 [−9, 3], P=.35).

Conclusion

Neonates undergoing operative repair of congenital diaphragmatic hernia and esophageal atresia/tracheoesophageal fistula develop intraoperative acidosis and hypercapnia, regardless of the approach used. However, this phenomenon is more severe during thoracoscopic repair. Novel modalities to reduce intraoperative gas derangements, particularly during thoracoscopic repair, need to be established.
A Novel Minimally Invasive Wireless Technology for Neuromodulation via Percutaneous Intercostal Nerve Stimulation for Post‐Herpetic Neuralgia: A Case Report with Short‐Term Follow‐up
Authors: Billet Bart , Wynendaele Roel , Vanquathem Niek E.
Published: June 2017

Background

Peripheral nerve stimulation of primary afferent neurons provides control of localized chronic pain. This technique applies permanent electrical stimulation at the target area via a minimally invasive, subcutaneous placement of an electrode.

Objective

To assess the analgesic effects of minimally invasive wireless neuromodulation in the treatment of chronic intractable pain secondary to post‐herpetic neuralgia.

Case Summary

A 78‐year‐old man presented with severe intractable post‐herpetic neuralgic pain. He was known to have non‐Hodgkin's lymphoma under remission following treatment with chemotherapy and stem cell transplantation, twice. He also developed steroid‐induced diabetes mellitus during this treatment. In view of his compromised immune status, he was deemed a suitable candidate for our minimally invasive neuromodulation technology. Two subcutaneous electrodes were placed on the right‐hand side of the trunk, 10 cm medial and parallel to the spinous process at the level of T7–T8 under fluoroscopic guidance along the T7 intercostal nerve. The external transmitter was worn with a belt over a single layer of clothing and used to transmit power to the stimulator. The entire procedure required only a small incision for the introduction of the electrode placement.

Results

After an uneventful procedure, the pain score decreased from 8 to 3, with a reduction in pain medication. The EuroQol Five Dimensions Questionnaire scores were 0.102 before the trial, 0.630 at 1 month, and 0.576 at 3 months.

Conclusions

Subcutaneous placement of electrodes with our minimally invasive technique and wireless neuromodulation technology was safe and effective. Significant improvements in pain relief ensued, and no further adverse events had been reported at the end of 3 months' follow‐up.
Genetic analysis of yield and fruit traits in cantaloupe cultivars
Authors: Pouyesh Alireza , Lotfi Mahmoud , Ramshini Hossein , Karami Ezzat , Shamsitabar Aliasghar , Armiyoun Elahe
Published: June 2017

The purpose of this research was to evaluate the combining ability of six local Iranian and one imported cantaloupe cultivar. Heritability of traits was estimated using a half‐diallel mating design. Seven parents and their crosses were evaluated in 2013 and 2014. The greatest general combining ability (GCA) for yield and fruit number was for “Rish‐baba” (0.53 kg/plant and 0.3, respectively). The cultivar “Ananasi” had the highest GCA for fruit weight and soluble solids content (SSC) (0.088 kg and 1.4, respectively). “Ananasi” presented the highest GCA values for fruit firmness, chlorophyll a and b and carotenoid content, as well as the highest total chlorophyll content. The cross Garmak × Rish‐baba showed the highest specific combining ability (SCA) for yield with heterosis value of 99%. High heritability estimates for SSC (0.52), flesh thickness (0.61) and concentration of chlorophyll a (0.7) were obtained. Although there were significant SCAs for yield, the parents are suggested to be improved prior to hybrid development. The parent “Ananasi” appears to be a suitable donor in breeding programmes.
Comparing the resistance of mid‐maturing maize varieties to European corn borer (Ostrinia nubilalis Hbn.)—results from the Polish VCU registration field trials
Authors: Przystalski Marcin , Lenartowicz Tomasz
Published: June 2017

European corn borer is a major pest in the United States and Europe. This pest causes grain yield losses worth billions of Dollars. One of the best methods to control this pest making damages is cultivation of resistant varieties. In the present work, using the generalized linear mixed model methodology, we identified maize varieties with improved resistance to European corn borer from a Polish VCU series of field trials performed in the two consecutive years 2014 and 2015.
Lateralized hippocampal volume increase following high‐frequency left prefrontal repetitive transcranial magnetic stimulation in patients with major depression
Authors: Hayasaka Shunsuke , Nakamura Motoaki , Noda Yoshihiro , Izuno Takuji , Saeki Takashi , Iwanari Hideo , Hirayasu Yoshio
Published: June 2017

Aim

Repetitive transcranial magnetic stimulation (rTMS) has been applied as a treatment for patients with treatment‐resistant depression in recent years, and a large body of evidence has demonstrated its therapeutic efficacy through stimulating neuronal plasticity. The aim of this study was to investigate structural alterations in the hippocampus (HIPP) and amygdala (AM) following conventional rTMS in patients with depression.

Methods

Twenty‐eight patients with depression underwent 10 daily 20‐Hz left prefrontal rTMS over 2 weeks. The left dorsolateral prefrontal cortex (DLPFC) was identified using magnetic resonance imaging‐guided neuronavigation prior to stimulation. Magnetic resonance imaging scans were obtained at baseline and after the completion of rTMS sessions. The therapeutic effects of rTMS were evaluated with the 17‐item Hamilton Depression Rating Scale (HAM‐D17), and the volumes of the HIPP and AM were measured by a manual tracing method.

Results

Statistical analyses revealed a significant volume increase in the left HIPP (+3.4%) after rTMS but no significant volume change in the AM. No correlation was found between the left HIPP volume increase and clinical improvement, as measured by the HAM‐D17.

Conclusion

The present study demonstrated that conventional left prefrontal rTMS increases the HIPP volume in the stimulated side, indicating a remote neuroplastic effect through the cingulum bundle.
Endobronchial ultrasound‐guided transbronchial needle aspiration: Safe as it sounds
Authors: Vaidya Preyas J. , Munavvar Mohammed , Leuppi Joerg D. , Mehta Atul C. , Chhajed Prashant N.
Published: June 2017

ABSTRACT

Real‐time endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) has earned its place as a standard of care in the evaluation of mediastinal and hilar lymphadenopathy. It is a minimally invasive and a safe procedure with high diagnostic accuracy and efficacy. The increased usage of EBUS‐TBNA worldwide has thrown light on its possible complications including death. The complications range from minor to life threatening in few and may occur either early or later in the course after the procedure. The present review summarizes the reported complications from EBUS‐TBNA, their outcome and the modalities used for their management.
EBUS‐TBNA risks and repairs
Authors: Bellinger Christina , Dotson Travis
Published: June 2017

See DOI: 10.1111/resp.13094
Product and process innovation and total factor productivity: Evidence for manufacturing in four Latin American countries
Authors: Demmel M. Constanza , Máñez Juan A. , Rochina‐Barrachina María E. , Sanchis‐Llopis Juan A.
Published: June 2017

The literature on firm productivity recognizes the important role played by firm innovation activities on firm productivity in developed countries. However, the literature for developing and emerging economies is scarce and far from conclusive. The aim of this paper is to study the innovation–productivity link (distinguishing between process and product innovations) for manufacturing at the firm level for four Latin American countries (two classified as upper‐middle income countries by the World Bank—Argentina and Mexico—and two as lower‐middle income—Colombia and Peru). We aim testing whether the level of development is a mediating factor in the innovation–productivity link. The data used have been drawn from the World Bank panel enterprise surveys, for 2006 and 2010. First, we estimate total factor productivity (TFP) and, second, we use the estimated TFP as a regressor or as dependent variable, in two models for testing self‐selection of the most productive firms into innovation or the existence of returns to innovation in terms of productivity. Our results confirm the mediating role of the level of development in the innovation–productivity link: both the self‐selection and the returns‐to‐innovation hypotheses work only for the upper‐middle income countries.
Skewed Invariant Natural Killer T (iNKT) Cells, Impaired iNKT:B Cell Help and Decreased SAP Expression in Blood Lymphocytes from Patients with Common Variable Immunodeficiency
Authors: Erazo‐Borrás L. V. , Álvarez‐Álvarez J. A. , Perez‐Romero C. A. , Orrego‐Arango J. C. , Franco‐Restrepo J. L. , Trujillo‐Vargas C. M.
Published: June 2017

Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4‐/CD8‐ and CCR5+/CXCR3+. These findings were associated with an enrichment of memory‐like and a tendency towards a reduction in TNF‐α‐expressing effector iNKT cells in the peripheral blood mononuclear cells (PBMC) of CVID patients. Moreover, an accumulation of follicular helper iNKT cells in the PB of CVID patients was demonstrated. CVID αGalCer‐pulsed iNKT cells are not able to induce autologous B cell proliferation although they do induce proliferation to healthy donor B cells. Interestingly, autologous and heterologous co‐cultures did not differ in the amount of immunoglobulin secreted by B cells in vitro. Finally, reduced intracellular SAP expression in iNKT cells and other lymphocytes in the blood from CVID patients was observed. These results provide further insights into the immunological mechanisms underlying the iNKT cell defects and the potential targets to improve B cell help in CVID.
Maximum Likelihood Estimators in Regression Models for Error‐prone Group Testing Data
Authors: Huang Xianzheng , Sarker Warasi Md Shamim
Published: June 2017

Since Dorfman's seminal work on the subject, group testing has been widely adopted in epidemiological studies. In Dorfman's context of detecting syphilis, group testing entails pooling blood samples and testing the pools, as opposed to testing individual samples. A negative pool indicates all individuals in the pool free of syphilis antigen, whereas a positive pool suggests one or more individuals carry the antigen. With covariate information collected, researchers have considered regression models that allow one to estimate covariate‐adjusted disease probability. We study maximum likelihood estimators of covariate effects in these regression models when the group testing response is prone to error. We show that, when compared with inference drawn from individual testing data, inference based on group testing data can be more resilient to response misclassification in terms of bias and efficiency. We provide valuable guidance on designing the group composition to alleviate adverse effects of misclassification on statistical inference.
Endemic time-spaces of Finland: from wilderness lands to ‘vacant production spaces’
Authors: Mustonen Tero
Published: June 2017

Traditional land use and occupancy of the wilderness lands of Finnish pre- and early- historic communities has not received much discussion in contemporary geographical debates. This article explores such occupancies and analyses transformations to present land use through two case studies: the Lake Kuivasjärvi basin in Western Finland and the Linnunsuo marsh-mire in Eastern Finland. Environmental justice provides the analytical framing through which the processes of change are analysed within each case by using historical geographical data and reviewing literature. Both locations were communally used by occupying villages prior to the advent of the industrial era. Yet the forestry and peat production industries that were pursued in the twentieth century ignored this historical use and saw them as ‘vacant spaces’ to be developed. In Linnunsuo, a post-production space has developed since the end of the peat production.
Extreme geographies: a response from a dependent semi-periphery of the post-neoliberal Europe
Authors: Riding James
Published: June 2017

We live in a time of paranoid borderism, a time of intense paranoia of the Other, and a time where the privileging of the nation state as the symbolic container of space, our territory, seems to have made a lurid return to the European continent. The consequences of this socio-spatial ordering and othering, the legacy of Euclidian thinking, and Cartesian models of knowing the world, can become an extreme geography: a form of cartographic cleansing that seriously needs to be addressed. In this short response to the Fennia Lecture given by Professor Henk van Houtum on Extreme Geographies, I offer a report from a region that has become a dependent semi-periphery of the new largely neoliberal Europe that emerged post-1989: a new Europe that is now entering a post-neoliberal era and is becoming increasingly neofascist. I draw from this region as a warning from history, and argue that the hopeful politics of the New Left in the former Yugoslavia provide an answer. The New Left, as it has been termed, in the Post-Yugoslav space, articulates the need for a new radically democratic European project: a project that is no longer neoliberal, but equally a project that does not turn to a nostalgic nationalism, a neofascism, or indeed any other form of authoritarian capitalism.
Towards a cultural geopolitics: on the making of a documentary-poetry film about a post-conflict place
Authors: Riding James , Wake-Walker Jack
Published: June 2017

Made in collaboration with an independent filmmaker and two poets, the documentary-poetry film Bridges  presents life in post-conflict Bosnia-Herzegovina, and delivers a clear message: the war in Bosnia is not yet firmly located in the past. Shot through a computer screen, Bridges  forces the viewer to witness the war in Bosnia and its aftermath via-the-gaze of an unknown spectator, sitting on an Apple Mac laptop. Through this modern technological distancing, we re-present here images of war in a digital age, question how war is usually packaged and represented on television, and in turn interrogate, through poetry, how war is traditionally remembered and memorialised. In so doing, Bridges  leads us to a conclusion, in Srebrenica, in 2015: in order to invest in the possibility of a just future after conflict, it is necessary to acknowledge the unthinkable realities to which traumatic experience bears witness.
Watch the film Bridges  here and visit the Bridges  website for more information
Bordering the “other”: the case of the Finnish-Russian border
Authors: Hannonen Olga
Published: June 2017

This short reflection on the keynote speech given by Henk van Houtum at the Annual Meeting of Finnish Geographers enhances discussion on bordering and border construction, both within the European Union (EU) and via the external border of the EU in the northeast, specifically the Finnish-Russian border. And it focuses attention upon the problem of Eurocentric geographies, and a dominant Western perspective of the rest of the world.
Multifeature-Fitting and Shape-Adaption Algorithm for Component Repair
Authors: Liu Renwei , Wang Zhiyuan , Liou Frank
Published: June 2017

In recent years, the usage of additive manufacturing (AM) provides new capabilities for component repair, which includes low heat input, small heat-affected zone, and freeform near-net-shape fabrication. Because the geometry of each worn component is unique, the automated repair process is a challenging and important task. The focus of this paper is to investigate and develop a general best-fit and shape-adaption algorithm for automating alignment and defect reconstruction for component repair. The basic principle of using features for rigid-body best-fitting is analyzed and a multifeature-fitting method is proposed to best fit the 3D mesh model of a worn component and its nominal component. The multifeature-fitting algorithm in this paper couples the least-squares method and a density-based outlier detection method. These two methods run alternately to approach the best-fit result gradually and eliminate the disturbance caused from the defect geometry. The shape-adaption algorithm is used to do cross section comparison and defect reconstruction based on the best-fitted 3D model. A “point-line-surface” fracture surface detection method is proposed to construct fracture surface and the fracture surface boundary is dilated to trim the nominal 3D model to obtain defect geometry. Illustrative examples with typical components and different kinds of defects are used to demonstrate the flexibility and capability of using multifeature-fitting and shape-adaption algorithm developed in this paper.
Displacement Analysis of Foldable V-Polyhedra Based on Dual Quaternions
Authors: Lin Song , Liu Jingshuai , Zhang Yu , Wang Hanchao
Published: June 2017

V-polyhedra is a Kokotsakis-type flat foldable rigid origami with increasing application in the engineering field. Currently, researches on origami mainly focused on foldability and mobility. In order to apply V-polyhedra in practical engineering, the analysis of kinematic characteristics is in need. This paper presents a displacement analysis methodology for the generic point belonging to any surfaces of foldable V-polyhedra. The rigid foldability of four-faced V-polyhedra and that of nine-faced V-polyhedra were discussed first. Then, the corresponding mathematical models are established with the rotating vector model constructed by dual quaternions. Finally, the correctness of the proposed method is verified through application of a symmetric pair of nine-faced V-polyhedra.
Reconfiguration Analysis of Multimode Single-Loop Spatial Mechanisms Using Dual Quaternions
Authors: Kong Xianwen
Published: June 2017

Although kinematic analysis of conventional mechanisms is a well-documented fundamental issue in mechanisms and robotics, the emerging reconfigurable mechanisms and robots pose new challenges in kinematics. One of the challenges is the reconfiguration analysis of multimode mechanisms, which refers to finding all the motion modes and the transition configurations of the multimode mechanisms. Recent advances in mathematics, especially algebraic geometry and numerical algebraic geometry, make it possible to develop an efficient method for the reconfiguration analysis of reconfigurable mechanisms and robots. This paper first presents a method for formulating a set of kinematic loop equations for mechanisms using dual quaternions. Using this approach, a set of kinematic loop equations of spatial mechanisms is composed of six polynomial equations. Then the reconfiguration analysis of a novel multimode single-degree-of-freedom (1DOF) 7R spatial mechanism is dealt with by solving the set of loop equations using tools from algebraic geometry. It is found that the 7R multimode mechanism has three motion modes, including a planar 4R mode, an orthogonal Bricard 6R mode, and a plane symmetric 6R mode. Three (or one) R (revolute) joints of the 7R multimode mechanism lose their DOF in its 4R (or 6R) motion modes. Unlike the 7R multimode mechanisms in the literature, the 7R multimode mechanism presented in this paper does not have a 7R mode in which all the seven R joints can move simultaneously.
A Novel Three-Loop Parallel Robot With Full Mobility: Kinematics, Singularity, Workspace, and Dexterity Analysis
Authors: Li Wei , Angeles Jorge
Published: June 2017

A novel parallel robot, dubbed the SDelta, is the subject of this paper. SDelta is a simpler alternative to both the well-known Stewart–Gough platform (SGP) and current three-limb, full-mobility parallel robots, as it contains fewer components and all its motors are located on the base. This reduces the inertial load on the system, making it a good candidate for high-speed operations. SDelta features a symmetric structure; its forward-displacement analysis leads to a system of three quadratic equations in three unknowns, which admits up to eight solutions, or half the number of those admitted by the SGP. The kinematic analysis, undertaken with a geometrical method based on screw theory, leads to two Jacobian matrices, whose singularity conditions are investigated. Instead of using the determinant of a 6 × 6 matrix, we derive one simple expression that characterizes the singularity condition. This approach is also applicable to a large number of parallel robots whose six actuation wrench axes intersect pairwise, such as all three-limb parallel robots whose limbs include, each, a passive spherical joint. The workspace is analyzed via a geometric method, while the dexterity analysis is conducted via discretization. Both show that the given robot has the potential to offer both large workspace and good dexterity with a proper choice of design variables.
Enhanced atomic layer etching of native aluminum oxide for ultraviolet optical applications
Authors: Hennessy John , Moore Christopher S. , Balasubramanian Kunjithapatham , Jewell April D. , France Kevin , Nikzad Shouleh
Published: June 2017

The authors report on the development and application of an atomic layer etching (ALE) procedure based on alternating exposures of trimethylaluminum and anhydrous hydrogen fluoride (HF) implemented to controllably etch aluminum oxide. The ALE process utilizes the same chemistry previously demonstrated in the atomic layer deposition of aluminum fluoride thin films, and can therefore be exploited to remove the surface oxide from metallic aluminum and replace it with thin fluoride layers in order to improve the performance of ultraviolet aluminum mirrors. This ALE process is modified relative to existing methods through the use of a chamber conditioning film of lithium fluoride, which is shown to enhance the loss of fluorine surface species and results in conformal layer-by-layer etching of aluminum oxide films. Etch properties were explored over a temperature range of 225–300 °C with the Al2O3 etch rate increasing from 0.8 to 1.2 Å per ALE cycle at a fixed HF exposure of 60 ms per cycle. The effective etch rate has a dependence on the total HF exposure, but the process is shown to be scalable to large area substrates with a postetch uniformity of better than 2% demonstrated on 125 mm diameter wafers. The efficacy of the ALE process in reducing interfacial native aluminum oxide on evaporated aluminum mirrors is demonstrated using characterization by x-ray photoelectron spectroscopy and measurements of ultraviolet reflectance at wavelengths down to 120 nm.
Modal active control of Chinese gongs
Authors: Jossic Marguerite , Mamou-Mani Adrien , Chomette Baptiste , Roze David , Ollivier François , Josserand Christophe
Published: June 2017

Instruments that belong to the gong family exhibit nonlinear dynamics at large amplitudes of vibration. In the specific case of the xiaoluo gong, this nonlinear behavior results in a pitch glide of several modes of the instrument in addition to harmonic distortion and internal resonances. This study applies a linear modal active control to a xiaoluo gong in an attempt to change its sound properties. First, a modal damping control of the fundamental mode based on a linear identification and a state space controller is applied in the small amplitude regime (no pitch glide). Results indicate that modal control influences not only the controlled mode but also the frequency components involved in distortion or internal resonance phenomena. Second, a modal damping control is performed in the large amplitude regime (in the presence of pitch glide). Results show that modal control does not affect the pitch glide. However, the controller becomes effective at a time trigger which is related to the instantaneous frequency.
In Vivo
Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice
Authors: Kimura Genki , Nakaoki Takahiro , Colley Thomas , Rapeport Garth , Strong Pete , Ito Kazuhiro , Kizawa Yasuo
Published: June 2017

PC945 is a novel triazole optimized for lung delivery, and the objective of this study is to determine the effects of intranasally dosed PC945 on
Aspergillus fumigatus
infection and associated biomarkers in immunocompromised mice. PC945, posaconazole, or voriconazole was administered intranasally once daily on days 0 to 3 (early intervention) or days 1 to 3 (late intervention) postinfection in temporarily neutropenic A/J mice infected intranasally with
A. fumigatus
, and bronchoalveolar lavage fluid (BALF) and serum were collected on day 3. The effects of extended prophylaxis treatment (daily from days −7 to +3 or days −7 to 0) were also compared with those of the shorter treatment regimens (days −1 to +3 or days −1 and 0). Early and late interventions with PC945 (2.8 to 350 μg/mouse; approximately 0.11 to ∼14 mg/kg of body weight) were found to inhibit lung fungal loads and to decrease the concentrations of galactomannan (GM) in both BALF and serum as well as several biomarkers in BALF (interferon gamma [IFN-γ], interleukin-17 [IL-17], and malondialdehyde) and serum (tumor necrosis factor alpha [TNF-α] and IL-6) in a dose-dependent manner and were >3- and >47-fold more potent than intranasally dosed posaconazole and voriconazole, respectively. Furthermore, extended prophylaxis with low-dose PC945 (0.56 μg/mouse; 0.022 mg/kg) was found to inhibit fungal loads and to decrease the concentrations biomarkers more potently than did the shorter treatment regimens. Thus, PC945 dosed intranasally once daily showed potent antifungal effects, and the effects of PC945 accumulated upon repeat dosing and were persistent. Therefore, PC945 has the potential to be a novel inhaled therapy for the treatment of
A. fumigatus
infection in humans.