bluuebunny/crossref_metadata_2025 huggingface dataset:
VFR traveller demographics
Authors: Backer Elisa , King Brian
Published: August 2016

The global phenomenon of visiting friends and relatives (VFR) travel is substantial, including in developed countries. In profiling its dimensions, researchers have examined various VFR characteristics including length of stay, origins and travel mode, though no thorough exploration has been undertaken of VFR demographics. Surprisingly this is the first large-scale study to examine VFR demographics and to consider all destination-related VFR data, not only those that are confined to purpose of visit. The researchers drew upon official Australian domestic travel data ( n = 81,579) to undertake a profile of the respective demographics of VFRs and non-VFRs. This assessment revealed that many people who would be classified as socio-economically disadvantaged engage in VFR travel. Previous literature has documented the lower participation of socio-economically disadvantaged groups in tourism and this article shows that they participate actively as VFRs. It is concluded that stimulating VFR travel provision may provide a mechanism for extending leisure experiences to those excluded from other forms of tourism.
Have you found what you’re looking for? Analysing tourist experiences of Wagner’s Bayreuth, ABBA’s Stockholm and U2’s Dublin
Authors: Bolderman Leonieke , Reijnders Stijn
Published: August 2016

Music tourism, the act of travelling to places associated with music, has become part of the tourism itinerary of many European cities. Although academic interest in this phenomenon is growing, little empirical research explores the experiences of music tourists – what are music tourists looking for? This study is based on participant observation and 15 in-depth interviews with tourists to Wagner’s Bayreuth, ABBA’s Stockholm and U2’s Dublin. It is argued that music tourism experiences involve a process of identity-work on a personal, cultural and embodied level. For most of the respondents, music plays an important role in their story of self, which is one of the main motives for travel and a source of performing self through music tourism practices. Once there, tourists relate personal music memories to music histories encountered in situ. Thus, music tourism effectively connects personal memories with shared identities and social spaces created by embodied practices.
Why the host community just isn’t enough: Processes and impacts of backpacker social interactions
Authors: Reichenberger Ina
Published: August 2016

This research employs an extended social situation analysis to examine how social interactions of backpackers in New Zealand are manifested, how they can contribute to the visitor experience, to common travel motivations such as self-development and cultural exploration, and how they compare to and influence contacts with the host community. Results from 37 in-depth interviews indicate that backpacker interactions underlie strict rules and are based on a shared understanding of how they are to proceed in terms of conversation topics and personal elements. Certain settings and a positive relationship between interaction participants contribute to longer and more personal social interactions. These in turn are required for emotional well-being, which is why fellow backpackers often replace friends and family as a social support system. Due to the national diversity of backpacker travellers, these interactions also provide exposure to different cultures as well as opportunity for self-development. Contacts with the host community, however, have been reported to be more difficult to establish and were found to be less beneficial for backpackers who have to rely heavily on interaction partners who are social, desire to spend longer amounts of time and are willing to proceed to a more familiar level faster than non-travellers.
Tourism, gender and consumer culture in late- and post-authoritarian Portugal
Authors: Sampaio Sofia
Published: August 2016

Tourism was a major player in the introduction of mass consumerism in post-war European societies. In Portugal, during the Estado Novo, it remained limited in scale and kind, being mostly targeted at a foreign and up-market consumer niche. In 1964, the number of international tourists finally reached the million mark, a figure that would rise threefold in the next 6 years. Bodily centred leisure practices were on the rise, taking tourism beyond the confines of state propaganda and tourists beyond sightseeing. Drawing on archival research conducted at the Portuguese Film Museum, this article analyses how the late 1950s, 1960s and 1970s saw the appearance of a renewed idea of tourism that owed as much to an expanding consumer culture as to the period’s experimental filmmaking practices. The contours of this renewal can be appreciated in short tourism documentaries around the figure of the foreign woman tourist.
The Youth Guarantee Education Initiative and Its Impact on Criminality: Māori Youth Perceptions
Authors: Poa Daniel , Wright Monod Sarah
Published: August 2016

Māori youth are over-represented within the New Zealand criminal justice system. Māori youth comprise 60 per cent of the total youth apprehensions and represent only 20 per cent of New Zealand’s youth population. This qualitative study focuses on the narratives of six young Māori men and women about their criminal histories, and how their engagement in a re-education initiative – the Youth Guarantee policy – impacted upon their criminal activity. Although the study provided evidence that is congruent with assumptions about the education–crime relationship, the participants’ narratives implied that the impact the Youth Guarantee had on Māori youth offending could be attributed to a number of proxy impacts that they received as a result of their re-engagement in the open-door practices of one provider’s Youth Guarantee–funded programme.
Locating material defects via wavefield demixing with morphologically germane dictionaries
Authors: Druce Jeff , Gonella Stefano , Kadkhodaie Mojtaba , Jain Swayambhoo , Haupt Jarvis D
Published: August 2016

This article introduces a methodology for the detection and localization of structural defects in solid media using morphological demixing algorithms. The demixing algorithms are designed to separate spatiotemporal response data into two morphologically antithetical components: one contribution captures the spatially sparse and temporally persistent features of the medium’s response, while the other provides a representation of the dominant, globally smooth component as it would be observed in a defect-free medium. Within the demixing paradigm, we explore two methods: in the first, we cast the demixing task in terms of a group Lasso regularization problem with simply structured orthonormal dictionaries; the second method makes use of a more morphologically germane dictionary whose additional structure allows for the localization of defects whose signature may be highly elusive, for example, buried in noise or masked by competing features. After the demixing is complete, an automatic visualization tool highlights the regions associated with potential anomalies and outputs their local coordinates. Since the method does not invoke any knowledge of the material properties of the medium, or of its behavior in its pristine conditions, and is solely based on data processing of current wavefield information, it is endowed with significant model agnostic and baseline-free attributes. These properties are desirable in systems where there exists limited or unreliable a priori knowledge of the constitutive model, when the physical domain is highly heterogeneous or compromised by large damage zones, or when accurate baseline simulations are unavailable. The efficacy of the proposed method is evaluated against synthetically generated data and experimental data obtained using a scanning laser Doppler vibrometer.
Operative and Midterm Outcomes of the Fenestrated Anaconda Stent-Graft in the Endovascular Treatment of Juxtarenal, Suprarenal, and Type IV Thoracoabdominal Aortic Aneurysms
Authors: Kotelis Drosos , Schleimer Karina , Foldenauer Christina , Jalaie Houman , Grommes Jochen , Jacobs Michael J. , Kalder Johannes
Published: August 2016

Purpose: To report operative and midterm outcomes of fenestrated endovascular aneurysm repair (FEVAR) with the Anaconda device. Methods: A retrospective analysis was conducted of 39 consecutive patients (median age 74 years; 36 men) treated with the fenestrated Anaconda stent-graft between July 2011 and December 2015 at a single center. Indications for FEVAR were abdominal aortic aneurysms (AAAs) with neck anatomy unsuitable for a standard stent-graft. Median infrarenal neck length was 4 mm (range 0–9). Four (10%) patients presented with type IV thoracoabdominal aortic aneurysm (TAAA), 12 (31%) with suprarenal aneurysms, and 23 (59%) with juxtarenal aneurysms. Four (10%) patients had previous infrarenal aortic repair. Five (13%) patients had an infrarenal neck angulation >60°. A total of 106 fenestrations were incorporated into the stent-grafts (73 renal arteries, 25 superior mesenteric arteries, and 8 celiac trunks). Technical success, perioperative and midterm mortality and morbidity, target vessel patency, endoleaks, and reinterventions were documented. Results: Technical success was 95% (37/39). Three (8%) patients died in-hospital from mesenteric embolism in 2 and renal artery rupture with consequent multiorgan failure in 1. Two (5%) patients suffered an intraoperative embolic stroke. During a median follow-up of 33 months (range 4–55), adjunctive maneuvers were performed in 9 (23%) patients, including reintervention for type II endoleak with enlarged aneurysm sac in 2 (5%). Four additional patients died of causes unrelated to the aortic pathology (overall mortality 18%). In 34 (94%) of the 36 patients seen in follow-up, aneurysm sac size was stable or decreased. Target vessel stent patency was 99% (95/96). Conclusion: FEVAR with the Anaconda device delivers satisfactory short-term technical and clinical success rates in patients with juxtarenal, suprarenal, and type IV TAAA. Midterm efficacy and durability with respect to aneurysm sac regression and target vessel patency appear very good. Overall mortality and the need for reintervention were significant in this patient cohort.
The Short-Term Impact of Dietary Counseling on Sodium Intake and Blood Pressure in Renal Allograft Recipients
Authors: Asai Kanae , Kobayashi Takashi , Miyata Hitomi , Tanaka Yukari , Okada Yoshiyuki , Sakai Kaoru , Negoro Hiromitsu , Kamba Tomomi , Tsuji Hidemi , Shide Kenichiro , Yanagita Motoko , Inagaki Nobuya , Ogawa Osamu
Published: August 2016

Background:

Sodium retention causes posttransplant hypertension, and sodium restriction is recommended in kidney allograft recipients. However, there have been few studies on the impact of dietary counseling on sodium intake and blood pressure (BP) in this population.

Objective:

To determine the effect of dietary counseling on sodium intake and consequent BP control in kidney allograft recipients.

Design, Setting, and Participants:

A prospective single-arm study to determine the effect of dietary counseling on sodium intake. Enrolled were renal allograft recipients with sodium intake >100 mEq/d, BP >130/80, antihypertensive use, or body mass index >25 kg/m2. Of 53 renal transplant recipients who met the criteria, 48 participated in the present study. Sodium intake was estimated based on 24-hour urinary sodium excretion before and after 3 sessions of dietary counseling by a board-certified dietitian.

Results:

Sodium intake was significantly decreased after dietary counseling (158.7 vs 129.6 mEq/d; P = .005). Systolic BP was significantly decreased from 124 mm Hg (interquartile range: 122-134) before counseling to 121 mm Hg (interquartile range: 117-128) after counseling ( P < .001). The number of patients with systolic BP >130 mm Hg was decreased by 30% (n = 19-13; P = .07). Among 34 patients on antihypertensive medications, 8 (23.5%) ceased or reduced their drugs due to improvement in BP, whereas 2 increased or changed the drugs due to poor control of BP.

Conclusion:

Dietary counseling showed a short-term efficacy of reducing sodium intake and clinically relevant BP improvement in renal allograft recipients.
Knockdown of Hypoxia-Inducible Factor 1α Improved the Efficacy of Low-Dose Metronomic Chemotherapy of Paclitaxel in Human Colon Cancer Xenografts
Authors: Zhang Mu , Chen Chen , Su Feng , Huang Zhiguo , Li Xiangmin , Li Xiaogang
Published: August 2016

Low-dose metronomic chemotherapy represents a new strategy for solid tumor treatments with a strong antiangiogenic activity and few side effects. However, low-dose metronomic therapy alone is not always as effective as traditional chemotherapy on eradication of tumor. On the contrary, low-dose metronomic in some cases could stimulate tumor growth due to hypoxia of tumor cells induced during therapy. Our study aimed to investigate whether knockdown of hypoxia-inducible factor-1α expression in tumor cell could facilitate low-dose metronomic therapy with paclitaxel for human colon cancer. Human colon cancer cell line (HT-29) stably transfected with specific short hairpin RNAs silencing hypoxia-inducible factor-1α exhibited marked attenuation of hypoxia-induced expression of the target genes such as vascular endothelial growth factor, glucose transporter 1, and P-glycoprotein. Compared with HT-29-c xenograft tumor model established by subcutaneous injection of HT-29 cells stably transfected with scrambled control short hairpin RNA, HT-29-ih xenograft tumor model showed more significant and long-lasting antitumor responses of empirical metronomic paclitaxel regimens, accompanied by drastic angiogenesis decrease and neglectable toxicity. All these data indicated that the combination of paclitaxel low-dose metronomic therapy with hypoxia-inducible factor-1α knockdown might provide a potent battle against colon cancer.
Changes in synaptic transmission of substantia gelatinosa neurons after spinal cord hemisection revealed by analysis using in vivo patch-clamp recording
Authors: Kozuka Yuji , Kawamata Mikito , Furue Hidemasa , Ishida Takashi , Tanaka Satoshi , Namiki Akiyoshi , Yamakage Michiaki
Published: August 2016

Background

After spinal cord injury, central neuropathic pain develops in the majority of spinal cord injury patients. Spinal hemisection in rats, which has been developed as an animal model of spinal cord injury in humans, results in hyperexcitation of spinal dorsal horn neurons soon after the hemisection and thereafter. The hyperexcitation is likely caused by permanent elimination of the descending pain systems. We examined the change in synaptic transmission of substantia gelatinosa neurons following acute spinal hemisection by using an in vivo whole-cell patch-clamp technique.

Results

An increased spontaneous action potential firings of substantia gelatinosa neurons was detected in hemisected rats compared with that in control animals. The frequencies and amplitudes of spontaneous excitatory postsynaptic currents and of evoked excitatory postsynaptic currentss in response to non-noxious and noxious stimuli were not different between hemisected and control animals. On the contrary, the amplitude and frequency of spontaneous inhibitory postsynaptic currents of substantia gelatinosa neurons in hemisected animals were significantly smaller and lower, respectively, than those in control animals ( P < 0.01). Large amplitude and high-frequency spontaneous inhibitory postsynaptic currents, which could not be elicited by mechanical stimuli, were seen in 44% of substantia gelatinosa neurons in control animals but only in 17% of substantia gelatinosa neurons in hemisected animals. In control animals, such large amplitude spontaneous inhibitory postsynaptic currents were suppressed by spinal application of tetrodotoxin (1 µM). Cervical application of lidocaine (2%, 10 µl) also inhibited such large amplitude of inhibitory postsynaptic currents. The proportion of multi-receptive substantia gelatinosa neurons, which exhibit action potential firing in response to non-noxious and noxious stimuli, was much larger in hemisected animals than in control animals.

Conclusions

These suggest that substantia gelatinosa neurons receive tonic inhibition by spinal inhibitory interneurons which generate persistent action potentials. Spinal hemisection results in hyperexcitation of substantia gelatinosa neurons at least in part by eliminating the tonic descending control of spinal inhibitory interneurons from supraspinal levels.
Current and emergent pharmacologic treatments for irritable bowel syndrome with diarrhea: evidence-based treatment in practice
Authors: Lucak Susan , Chang Lin , Halpert Albena , Harris Lucinda A.
Published: August 2016

Irritable bowel syndrome with diarrhea (IBS-D) is a common, chronic functional gastrointestinal disorder with symptoms that can be distressing for patients and often result in substantially impaired quality of life. This review focuses on providing clinicians with information on practical, evidence-based treatment for IBS-D. Current therapies commonly used for the treatment of IBS-D, including pharmacologic and nonpharmacologic interventions, are briefly reviewed, followed by discussion of the emergent pharmacologic treatments (rifaximin and eluxadoline) and medical foods (IBgard® and EnteraGam®). Given the lack of a standard treatment algorithm for IBS-D and the emergence of new pharmacologic therapies, treatment needs to be tailored to the individual patient and take into account the severity of disease. In this context, the latter part of this manuscript examines how treatments for IBS-D can be used in clinical practice by presenting three patient case scenarios with varying degrees of IBS-D severity. For each case, the patient’s medical history and clinical presentation are related to the Rome Foundation multidimensional clinical profile (MDCP) and potential treatment options with current and emergent therapies are reviewed. The interplay of gastrointestinal symptoms and their psychosocial impact, as well as the importance of a patient-centered approach to therapy, are discussed. Consideration is given to the potential need for combination therapies and how emergent treatments could fit into the treatment pathway for mild, moderate, and severe cases of IBS-D in clinical practice.
Multiple sclerosis in First Nations Canadians: A pilot comparison study
Authors: Marrie Ruth Ann , Hall Nicholas , Sadovnick A Dessa
Published: August 2016

Background

Genetic and clinical characteristics associated with multiple sclerosis (MS) may differ by ethnicity but few studies have evaluated whether characteristics of MS differ between individuals according to First Nations (FN) ethnicity.

Objective

Using a cross-sectional observational design, we compared clinical and genetic characteristics between people with MS of FN and non-FN ethnicity.

Methods

We recruited participants of FN ethnicity with MS. We conducted a medical records review for each participant followed by a standardized interview and drawing of blood samples. The blood underwent genetic analyses for several HLA alleles. We compared the study sample with 127 non-FN MS participants from another study conducted in the same region using the same data collection procedures.

Results

We included 144 participants with MS, of whom 17 (11.8%) self-identified as FN. The age of symptom onset was earlier and the diagnostic delay shorter among FN participants although these differences did not reach statistical significance. As compared to non-FN participants, FN participants with MS had increased odds of comorbid psychiatric disease (OR 5.38; 95% CI: 1.84–15.8), and were less likely to be HLA-DRB1*1501 positive (OR 0.32; 95% CI: 0.11–0.96).

Conclusion

Genetic and clinical characteristics of MS differ among Canadians of FN and non-FN ethnicity.
Self-Employment Success and Challenges
Authors: Yamamoto Scott H. , Olson Deborah L.
Published: August 2016

There have been indications that self-employment could be a viable option for individuals with disabilities. Unfortunately, the sparse empirical literature limits our understanding of the phenomenon. Thus, the present study sought to contribute new knowledge. An empirical study was conducted of individuals with disabilities who were self-employed through vocational rehabilitation (VR) services. Individual and in-depth, in-person qualitative interviews were conducted with VR counselors and clients. From our analyses emerged three predominant themes: relationship dynamics, system mechanics, and social identities. Relationship dynamics described facets of counselor–client interactions; system mechanics described facets of procedures in a self-employment case; and social identities described facets of self-employment case development. These themes highlighted and explained differences between counselors’ and clients’ perspectives on self-employment success and challenges. While tentative, the findings in the present study inform the conceptual framework in new ways while also circumscribing implications for researchers, VR counselors and administrators, and government policymakers.
Narratives of Ambivalent Meanings of Acquired Physical Disability in Japan
Authors: Tagaki Masakuni
Published: August 2016

Experiences of people with disabilities cannot be simply examined from positive aspects or negative ones; both aspects are required. This study examines the ambivalent meanings of acquired disability through a qualitative analysis of the life stories of Japanese men with spinal cord injuries. Semi-structured interviews were conducted with 10 men who had sustained the injury over 10 years ago, at around the age of 20. The participants valued job and welfare or social activities, by managing their impairments. They regarded their personal disability issues as social ones and actively promoted social awareness. However, some of them recounted ambivalent experiences; they maintained the vision that they would become able-bodied people again, or were reluctant to participate in social activities, because they felt inferior to more socially active peers. Examination of ambivalent meanings of acquired disability is necessary for an understanding of the actual situation of people with disabilities.
Emerging Adults’ Self-Identified Peer Crowd Affiliations, Risk Behavior, and Social–Emotional Adjustment in College
Authors: Hopmeyer Andrea , Medovoy Tal
Published: August 2016

Although peer crowd affiliations have been studied extensively in adolescence, less is known about the crowd structure of emerging adults. The current study tested whether college students’ self-reported crowd affiliations were uniquely associated with a broad range of adjustment indices. Participants were 588 emerging adults at a small liberal arts college in the Western United States ( Mage = 20.07, SD = 1.34; range = 18–26; 411 women). Exploratory factor analysis revealed that the peer crowds examined were best described by four underlying crowd dimensions (i.e., social, athletic, scholastic, and counterculture). Regression analyses showed that scholastic and athletic affiliations predicted social–emotional adjustment and low-risk-related behaviors. Social and counterculture identification predicted risk-related behaviors. However, while social affiliation predicted social–emotional adjustment, affiliation with the counterculture crowd predicted high levels of loneliness and low belongingness. The results highlight the importance of crowd affiliations in emerging adulthood and their implications for college students’ adjustment.
Canagliflozin-Induced Diabetic Ketoacidosis
Authors: Turner Jessica , Begum Tahmina , Smalligan Roger D.
Published: August 2016

Introduction: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are relatively new antihyperglycemic agents that lower renal glucose reabsorption. They are used as adjunctive therapy to standard diabetes treatment. Case Report: We present the case of a 62-year-old woman with a past medical history of type 2 diabetes mellitus and sudden-onset diabetic ketoacidosis (DKA). Use of canagliflozin, a SGLT-2 inhibitor, was determined to be the cause of the DKA. The patient ultimately recovered after 5 days in the intensive care unit. She was changed to long- and short-acting insulins and instructed to avoid canagliflozin. Conclusion: Although SGLT-2 inhibitors are effective at lowering a patient’s hemoglobin A1C, physicians must be aware of the rare but dangerous potential adverse effect of inducing DKA. This article reports an illustrative case and presents a review of the literature.
Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy
Authors: Cheson Bruce D. , Ansell Stephen , Schwartz Larry , Gordon Leo I. , Advani Ranjana , Jacene Heather A. , Hoos Axel , Barrington Sally F. , Armand Philippe
Published: August 2016

Uniformly adopted response criteria are essential for assessment of therapies incorporating conventional chemotherapy and chemoimmunotherapy regimens. Recently, immunomodulatory agents, such as immune checkpoint inhibitors, have demonstrated impressive activity in a broad range of lymphoma histologies. However, these agents may be associated with clinical and imaging findings during treatment suggestive of progressive disease (PD) despite evidence of clinical benefit (eg, tumor flare or pseudo-progression). Considering this finding as PD could lead to patients being prematurely removed from a treatment from which they actually stand to benefit. This phenomenon has been well described with checkpoint blockade therapy in solid tumors and anecdotally seen in lymphoma as well. To address this issue in the context of lymphoma immunomodulatory therapy, a workshop was convened to provide provisional recommendations to modify current response criteria in patients receiving these and future agents in clinical trials. The term “indeterminate response” was introduced to identify such lesions until confirmed as flare/pseudo-progression or true PD by either biopsy or subsequent imaging.
Integrating multiple molecular sources into a clinical risk prediction signature by extracting complementary information
Authors: Hieke Stefanie , Benner Axel , Schlenl Richard F. , Schumacher Martin , Bullinger Lars , Binder Harald
Published: August 2016

Background

High-throughput technology allows for genome-wide measurements at different molecular levels for the same patient, e.g. single nucleotide polymorphisms (SNPs) and gene expression. Correspondingly, it might be beneficial to also integrate complementary information from different molecular levels when building multivariable risk prediction models for a clinical endpoint, such as treatment response or survival. Unfortunately, such a high-dimensional modeling task will often be complicated by a limited overlap of molecular measurements at different levels between patients, i.e. measurements from all molecular levels are available only for a smaller proportion of patients.

Results

We propose a sequential strategy for building clinical risk prediction models that integrate genome-wide measurements from two molecular levels in a complementary way. To deal with partial overlap, we develop an imputation approach that allows us to use all available data. This approach is investigated in two acute myeloid leukemia applications combining gene expression with either SNP or DNA methylation data. After obtaining a sparse risk prediction signature e.g. from SNP data, an automatically selected set of prognostic SNPs, by componentwise likelihood-based boosting, imputation is performed for the corresponding linear predictor by a linking model that incorporates e.g. gene expression measurements. The imputed linear predictor is then used for adjustment when building a prognostic signature from the gene expression data. For evaluation, we consider stability, as quantified by inclusion frequencies across resampling data sets. Despite an extremely small overlap in the application example with gene expression and SNPs, several genes are seen to be more stably identified when taking the (imputed) linear predictor from the SNP data into account. In the application with gene expression and DNA methylation, prediction performance with respect to survival also indicates that the proposed approach might work well.

Conclusions

We consider imputation of linear predictor values to be a feasible and sensible approach for dealing with partial overlap in complementary integrative analysis of molecular measurements at different levels. More generally, these results indicate that a complementary strategy for integrating different molecular levels can result in more stable risk prediction signatures, potentially providing a more reliable insight into the underlying biology.
Fold-specific sequence scoring improves protein sequence matching
Authors: Leelananda Sumudu P. , Kloczkowski Andrzej , Jernigan Robert L.
Published: August 2016

Background

Sequence matching is extremely important for applications throughout biology, particularly for discovering information such as functional and evolutionary relationships, and also for discriminating between unimportant and disease mutants. At present the functions of a large fraction of genes are unknown; improvements in sequence matching will improve gene annotations. Universal amino acid substitution matrices such as Blosum62 are used to measure sequence similarities and to identify distant homologues, regardless of the structure class. However, such single matrices do not take into account important structural information evident within the different topologies of proteins and treats substitutions within all protein folds identically. Others have suggested that the use of structural information can lead to significant improvements in sequence matching but this has not yet been very effective. Here we develop novel substitution matrices that include not only general sequence information but also have a topology specific component that is unique for each CATH topology. This novel feature of using a combination of sequence and structure information for each protein topology significantly improves the sequence matching scores for the sequence pairs tested. We have used a novel multi-structure alignment method for each homology level of CATH in order to extract topological information.

Results

We obtain statistically significant improved sequence matching scores for 73 % of the alpha helical test cases. On average, 61 % of the test cases showed improvements in homology detection when structure information was incorporated into the substitution matrices. On average z-scores for homology detection are improved by more than 54 % for all cases, and some individual cases have z-scores more than twice those obtained using generic matrices. Our topology specific similarity matrices also outperform other traditional similarity matrices and single matrix based structure methods. When default amino acid substitution matrix in the Psi-blast algorithm is replaced by our structure-based matrices, the structure matching is significantly improved over conventional Psi-blast. It also outperforms results obtained for the corresponding HMM profiles generated for each topology.

Conclusions

We show that by incorporating topology-specific structure information in addition to sequence information into specific amino acid substitution matrices, the sequence matching scores and homology detection are significantly improved. Our topology specific similarity matrices outperform other traditional similarity matrices, single matrix based structure methods, also show improvement over conventional Psi-blast and HMM profile based methods in sequence matching. The results support the discriminatory ability of the new amino acid similarity matrices to distinguish between distant homologs and structurally dissimilar pairs.
A genetic algorithm-based weighted ensemble method for predicting transposon-derived piRNAs
Authors: Li Dingfang , Luo Longqiang , Zhang Wen , Liu Feng , Luo Fei
Published: August 2016

Background

Predicting piwi-interacting RNA (piRNA) is an important topic in the small non-coding RNAs, which provides clues for understanding the generation mechanism of gamete. To the best of our knowledge, several machine learning approaches have been proposed for the piRNA prediction, but there is still room for improvements.

Results

In this paper, we develop a genetic algorithm-based weighted ensemble method for predicting transposon-derived piRNAs. We construct datasets for three species: Human, Mouse and Drosophila. For each species, we compile the balanced dataset and imbalanced dataset, and thus obtain six datasets to build and evaluate prediction models. In the computational experiments, the genetic algorithm-based weighted ensemble method achieves 10-fold cross validation AUC of 0.932, 0.937 and 0.995 on the balanced Human dataset, Mouse dataset and Drosophila dataset, respectively, and achieves AUC of 0.935, 0.939 and 0.996 on the imbalanced datasets of three species. Further, we use the prediction models trained on the Mouse dataset to identify piRNAs of other species, and the models demonstrate the good performances in the cross-species prediction.

Conclusions

Compared with other state-of-the-art methods, our method can lead to better performances. In conclusion, the proposed method is promising for the transposon-derived piRNA prediction. The source codes and datasets are available in https://github.com/zw9977129/piRNAPredictor.
Solid organ fabrication: comparison of decellularization to 3D bioprinting
Authors: Jung Jangwook P. , Bhuiyan Didarul B. , Ogle Brenda M.
Published: August 2016

Solid organ fabrication is an ultimate goal of Regenerative Medicine. Since the introduction of Tissue Engineering in 1993, functional biomaterials, stem cells, tunable microenvironments, and high-resolution imaging technologies have significantly advanced efforts to regenerate in vitro culture or tissue platforms. Relatively simple flat or tubular organs are already in (pre)clinical trials and a few commercial products are in market. The road to more complex, high demand, solid organs including heart, kidney and lung will require substantive technical advancement. Here, we consider two emerging technologies for solid organ fabrication. One is decellularization of cadaveric organs followed by repopulation with terminally differentiated or progenitor cells. The other is 3D bioprinting to deposit cell-laden bio-inks to attain complex tissue architecture. We reviewed the development and evolution of the two technologies and evaluated relative strengths needed to produce solid organs, with special emphasis on the heart and other tissues of the cardiovascular system.
A branched TAT cell-penetrating peptide as a novel delivery carrier for the efficient gene transfection
Authors: Jeong Chanuk , Yoo Jisang , Lee DaeYong , Kim Yeu-Chun
Published: August 2016

Background

Cell penetrating peptides (CPPs) as one class of non-viral vectors, have been widely explored as a delivery tool due to their cell-penetrating capability with low cytotoxicity. However, CPPs have reported to have low gene transfection efficiency mainly due to the fact that DNA is larger than other biomolecules. On the other hand, the conventional linear CPPs are unstable for constructing the DNA complexes with it. Thus, here we designed a branched CPP using disulfide bridges based on the linear TAT peptide, to enhance the gene delivery efficiency in a better way.

Results

The branched TAT (BTAT) was synthesized by the DMSO oxidation method and showed high-molecular-weight about 294 kDa. The resulting BTAT was complexed with plasmid green fluorescence protein (pGFP) gene at various N/P ratios. The gene transfection efficiency was assessed on HeLa cells after treating with BTAT/pGFP complexes, showed high gene transfection efficiency as conformed by flowcytometry followed by confocal laser scanning microscopy (CLSM) visualization.

Conclusion

The novel BTAT/pGFP complex exhibited significantly higher stability and redox cleavability by reducing agent. In addition, BTAT showed higher transfection efficiency approximately 40-fold than those of the TAT and mTAT complexes. Our primary experiments demonstrated the potential of BTAT as a suitable candidate for gene delivery and it could be applied for various types of gene delivery platforms.
HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials
Authors: Press Michael F. , Sauter Guido , Buyse Marc , Fourmanoir Hélène , Quinaux Emmanuel , Tsao-Wei Denice D. , Eiermann Wolfgang , Robert Nicholas , Pienkowski Tadeusz , Crown John , Martin Miguel , Valero Vicente , Mackey John R. , Bee Valerie , Ma Yanling , Villalobos Ivonne , Campeau Anaamika , Mirlacher Martina , Lindsay Mary-Ann , Slamon Dennis J.
Published: August 2016

Purpose

ASCO and the College of American Pathologists (ASCO-CAP) recently recommended further changes to the evaluation of human epidermal growth factor receptor 2 gene (HER2) amplification by fluorescent in situ hybridization (FISH). We retrospectively assessed the impact of these new guidelines by using annotated Breast Cancer International Research Group (BCIRG) -005, BCIRG-006, and BCIRG-007 clinical trials data for which we have detailed outcomes.

Patients and Methods

The HER2 FISH status of BCIRG-005/006/007 patients with breast cancers was re-evaluated according to current ASCO-CAP guidelines, which designates five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell: group 1 (in situ hybridization [ISH]–positive): HER2-to-chromosome 17 centromere ratio ≥ 2.0, average HER2 copies ≥ 4.0; group 2 (ISH-positive): ratio ≥ 2.0, copies < 4.0; group 3 (ISH-positive): ratio < 2.0, copies ≥ 6.0; group 4 (ISH-equivocal): ratio < 2.0, copies ≥ 4.0 and < 6.0; and group 5 (ISH-negative): ratio < 2.0, copies < 4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free survival (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio [HR]).

Results

Among 10,468 patients with breast cancers who were successfully screened for trial entry, 40.8% were in ASCO-CAP ISH group 1, 0.7% in group 2; 0.5% in group 3, 4.1% in group 4, and 53.9% in group 5. Distributions were similar in screened compared with accrued subpopulations. Among accrued patients, FISH group 1 breast cancers were strongly correlated with immunohistochemistry 3+ status (P < .0001), whereas groups 2, 3, 4, and 5 were not; however, groups 2, 4 and, 5 were strongly correlated with immunohistochemistry 0/1+ status (all P < .0001), whereas group 3 was not. Among patients accrued to BCIRG-005, group 4 was not associated with significantly worse DFS or OS compared with group 5. Among patients accrued to BCIRG-006, only group 1 showed a significant benefit from trastuzumab therapy (DFS HR, 0.71; 95% CI, 0.60 to 0.83; P < .0001; OS HR, 0.69; 95% CI, 0.55 to 0.85; P = .0006), whereas group 2 did not.

Conclusion

Our findings support the original categorizations of HER2 by FISH status in BCIRG/Translational Research in Oncology trials.
How Does Caregiver Well-Being Relate to Perceived Quality of Care in Patients With Cancer? Exploring Associations and Pathways
Authors: Litzelman Kristin , Kent Erin E. , Mollica Michelle , Rowland Julia H.
Published: August 2016

Purpose

Perceived quality of care (QOC) is an increasingly important metric of care quality and can be affected by such factors among patients with cancer as quality of life and physician trust. This study sought to evaluate whether informal caregiver well-being was also associated with perceived QOC among patients with cancer and assessed potential pathways that link these factors.

Methods

This study used data from the Cancer Care Outcomes Research and Surveillance (CanCORS) consortium. Patients with lung and colorectal cancer enrolled in CanCORS (N = 689) nominated an informal caregiver to participate in a caregiving survey. Both groups self-reported sociodemographic, psychosocial, and caregiving characteristics; cancer characteristics were obtained from the CanCORS core data set. Multivariable logistic regression was used to assess the association between caregiver psychosocial factors and subsequent patient-perceived QOC, controlling for earlier patient-perceived QOC and covariates. Secondary analysis examined potential pathways that link these factors.

Results

Patients whose informal caregiver had higher levels of depressive symptoms were significantly more likely to report fair or poor QOC (odds ratio, 1.06; 95% CI, 1.01 to 1.13). When caregivers reported fair or poor self-rated health, patients were more than three times more likely to report fair or poor perceived QOC (odds ratio, 3.76; 95% CI, 1.76 to 9.55). Controlling for patient psychosocial factors and physician communication and coordination of medical care reduced the effect size and/or statistical significance of these relationships.

Conclusion

Informal caregivers are an important part of the care team and their well-being is associated with patient-perceived QOC. Engaging informal cancer caregivers as part of the care team and conducting ongoing risk stratification screening and intervention to optimize their health may improve patient-reported outcomes and QOC.
Phase II Weekly Vinblastine for Chemotherapy-Naïve Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study
Authors: Lassaletta Alvaro , Scheinemann Katrin , Zelcer Shayna M. , Hukin Juliette , Wilson Beverley A. , Jabado Nada , Carret Anne Sophie , Lafay-Cousin Lucie , Larouche Valerie , Hawkins Cynthia E. , Pond Gregory Russell , Poskitt Ken , Keene Daniel , Johnston Donna L. , Eisenstat David D. , Krishnatry Rahul , Mistry Matthew , Arnoldo Anthony , Ramaswamy Vijay , Huang Annie , Bartels Ute , Tabori Uri , Bouffet Eric
Published: August 2016

Purpose

Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children.

Patients and Methods

Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible. Vinblastine was administered once per week at a dose of 6 mg/m2 intravenously over a period of 70 weeks. Vision, quality of life, neurofibromatosis type 1 (NF1) status, and BRAF mutation/fusion status were also determined and correlated with outcome.

Results

Fifty-four patients were enrolled onto the study, with a median age of 8 years (range, 0.7 to 17.2 years). Most patients had chiasmatic/hypothalamic tumors (55.5%), and 13 patients (24.1%) had NF1. The most common histology was pilocytic astrocytoma (46.3%). Seventeen patients were diagnosed using radiologic criteria alone. Best response to chemotherapy was centrally reviewed with a response rate (complete, partial, or minor response) of 25.9%. Disease stabilization (complete, partial, or minor response or stable disease) was achieved in 47 patients (87.0%). Visual improvement was observed in 20% of patients with optic pathway glioma. Five-year overall survival and progression-free survival (PFS) rates were 94.4% (95% CI, 88.5% to 100%) and 53.2% (95% CI, 41.3% to 68.5%), respectively, for the entire cohort. Patients with NF1 had a significantly better PFS (85.1%; 95% CI, 68.0% to 100%) when compared with patients without NF1 (42.0%; 95% CI, 29.1% to 60.7%; P = .012). Age< 3 years or > 10 years was not associated with poor outcome. Treatment was well tolerated, and quality of life was not affected during treatment. In this trial, there was no correlation between BRAF alterations and outcome.

Conclusion

Vinblastine administered once per week is well tolerated in children with treatment naïve PLGG. Overall survival and PFS are comparable to current therapies, with a favorable toxicity profile and a maintained quality of life.
A Novel Way to Secure the Laryngeal Mask Airway During Oral Surgery Procedures
Authors: Mireles Ramiro , Devgun Ravinder , Tucker Blake , Votta Timothy , Chahal Prabhdeep , Ramsdell Robert , Heard Christopher
Published: August 2016

The laryngeal mask airway (LMA) has been used successfully for an ever-increasing number of applications. Utilization in oral maxillofacial surgery has been hampered by surgical difficulties working around the device. In this case series, a novel device, the LMA-PROP, was used to determine whether it was possible to alleviate device-positioning concerns with third molar extraction cases. LMA-PROP was used with both anesthesia and surgical satisfaction in this small pilot study. LMA-PROP appears to be a helpful new tool allowing the surgeon to maintain current surgical techniques for third molar extraction while securing LMA adequately for anesthesia maintenance.
The Future-as-Past in Dystopian Fiction
Authors: Stock Adam
Published: August 2016

Most twentieth-century dystopian fictions such as Aldous Huxley's Brave New World (1932), Katharine Burdekin's Swastika Night (1937), George Orwell's Nineteen Eighty-Four (1949), and John Wyndham's The Chrysalids (1955) adhere to a generic convention by which they project forward into a narrated future to look back critically toward the present. In this focus on the past, such dystopias include slivers of contested and incomplete accounts of how the dystopian state came to exist, here termed future histories. Such accounts exist in a time frame that runs from the authorial present to the point in the future at which the main narrative is set. In Orwell's Nineteen Eighty-Four, for example, this time frame runs from 1949 (the publication date) to 1984, when the main story occurs. The time frame between the authorial present and the future temporal setting of the main story world is here termed the future-as-past. This article explores the development of the complex temporality of dystopian fiction from the early to the mid-twentieth century. Discussion focuses on the manner in which the fragmented future-as-past is employed critically in relation to the story world and to historical reality. By providing scattered hints from which further information can be deduced or inferred, often but not always with the help of contextual knowledge, this temporal narrative strategy invites the reader to actively participate and politically engage in the reconstruction of future histories. Such future histories can never be completed or fully mapped as dystopian fictions and are usually less specifically predictive than they at first appear.