bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross‐space‐time clustering of childhood cancer in Great Britain: Evidence for a common aetiology
Authors: McNally Richard J.Q. , Stiller Charles , Vincent Tim J. , Murphy Michael F.G.
Published: June 2013

Previously, we identified space‐time clustering in certain childhood cancers. This study aimed to determine whether there was cross‐space‐time clustering between different diagnostic groups. A total of 32,295 cases were diagnosed during 1969–1993. Cross‐space‐time clustering was analyzed by a second‐order procedure based on Diggle's method. Locations were birth and diagnosis addresses. The following space‐time combinations were examined: address and date of birth; address at birth and date of diagnosis; address and date of diagnosis. Cross‐space‐time clustering analyses considered clustering pairs of cases from two different diagnostic groups. Formal statistical significance was taken as p < 0.00067 and marginal significance 0.01 > p ≥ 0.00067. Based on address at birth and date of diagnosis, there was statistically significant cross‐clustering between cases of HL and intracranial and intraspinal embryonal tumors (IIET), both aged 0–14 years (p < 0.0001). Based on address and date of birth, there was marginally significant cross‐clustering between cases of lymphoid leukemia (LL) aged 5‐14 years and Hodgkin lymphoma (HL) aged 0–14 years (p = 0.0019). Based on address and date of diagnosis there was marginally significant cross‐clustering between cases of LL aged 1–4 years and soft tissue sarcoma (STS) aged 0–14 years (p = 0.0041). Findings from this study are consistent with possible common aetiological factors between different diagnostic groups. They suggest a common aetiology for the following pairs of diagnostic groups: HL and IIET; older cases of LL and HL; younger cases of LL and STS. The possibility of common infectious mechanisms should be explored.
Behaviour Exchange Systems Training: The ‘BEST’ Approach for Parents Stressed by Adolescent Drug Problems
Authors: Toumbourou John W. , Bowes Glenn , Blyth Anne
Published: June 2013

Parents are challenged in the adolescent years by attempts to increase adolescent responsibility while also managing separation issues. Adolescent drug use can exacerbate parental concerns. Parental fears and anxieties surrounding adolescent drug use can undermine opportunities to respond effectively. This paper describes the theoretical rationale for, and early experience of delivering, a brief intervention program designed to assist parents coping with adolescent drug problems. The program emerges out of a hybrid of systems and behaviour therapy principles and has been designed to address issues associated with parenting characterised by a high level of emotional involvement and/or ineffective parental control. Group work encouraging more adolescent responsibility‐taking can assist parents disabled by feelings of guilt and failure. As parents develop emotional independence from adolescent behaviour, an appropriate expectation for adolescent control is established.
Problematic Gambling Patterns: Approaching a Systemic View
Authors: Hammond Greg
Published: June 2013

In this paper Family Therapy concepts are explored as a conceptual base from which to extend our understanding of problematic gambling patterns. Definitions of problematic gambling patterns vary considerably and are as often based on personal and cultural viewpoints as they are on clinical criteria. The two dominant descriptions of ‘problem gambling’ emphasise the individual. The older description is that ‘problem gambling’ results from personal immorality, weakness and self indulgence. The more contemporary and less vilifying description is that problem gamblers are in the grip of an ‘illness’. This paper proposes a systemic model using universal themes noted more generally in Family Therapy, that seem to have relevance in this specific field. Bateson's theory of relationships and particularly his description of ‘symmetrical systems’ are pivotal to one of three formulations of problem gambling phenomena proposed in this paper.
Why Postmodern Theory may be a Problematic Basis for Therapeutic Practice: A Feminist Perspective
Authors: Sanders Belinda
Published: June 2013

Both poststructural and social constructionist thinking are imbued with a masculine bias. First, I demonstrate that Foucault's theory of power and knowledge fails to take into account the female experience of power and the gendered nature of knowledge production. With the support of psychoanalytic theory I also claim that Foucault's theory of the ‘social’, ‘discursive’ production of ‘selves’ omits the contribution of the prelinguistic but no less ‘social’ mother–infant relationship, and in so doing obscures the prelinguistic foundations of emotionality. This poststructural reduction of ‘selves’ to, and subsequent subsuming of emotionality within, the instance of ‘language’, ‘discourse’ or ‘narrative’, is, I claim, replicated in the social constructionist thinking of Gergen and Bruner. Finally, I consider some of the consequences of a therapeutic practice which has its foundations in these two interrelated bodies of thought, suggesting, from a feminist perspective, that a major shortcoming of this narrative practice is its failure to attend to emotionality.
How Can You Tell when a Goldfish Cries? Finding the Words in Therapeutic Stories with Children
Authors: Wilson Jim
Published: June 2013

Stories provide one way to say the unspeakable. Drawing on systemic, constructionist and narrative ideas, this paper offers a commentary upon the development of a therapeutic story for a seven year old child and her mother.
Counselling and Psychotherapy: Is There a Difference? Does It Matter?
Authors: Crago Hugh
Published: June 2013

The terms ‘counselling’ and ‘psychotherapy’ are often employed in a loosely interchangeable way, especially in Australia. Where distinctions are made, there has been little agreement on what each term should cover. This article examines several axes on which ‘counselling’ might potentially be distinguished from ‘psychotherapy’; the most promising basis for such a distinction seems to be whether or not the mode of work attempts to access the unconscious. On this basis, several modalities currently termed ‘therapy’ would in fact be classed as types of ‘counselling’, including those modalities of family therapy which aim to engage clients at the level of conscious behaviour change and restructuring. Consideration of how new professionals are trained lends support to a continuum, with short‐term, problem‐focused conscious‐oriented approaches at one end, and longer‐term, transference‐focused, unconscious‐oriented approaches at the other, the dividing line coming at the point where trainees learn the skill of ‘immediacy’.
Towards an Integrated Approach to a Family Intervention for Co‐occurring Substance Abuse and Schizophrenia
Authors: Sheils Rebecca , Rolfe Timothy
Published: June 2013

Comorbid substance abuse and schizophrenia is a major cause for concern from clinical, economic and health care systems perspectives. Existing treatment strategies are frequently inadequate, partly due to a lack of research into the unique problems facing this dually diagnosed population. These individuals commonly place a disproportionate burden on the mental health delivery system. In addition, their families are left with the onerous task of caring for them. This paper reviews the literature on family interventions for both substance abuse and schizophrenia and postulates that a composite model of family therapy might be appropriate.
Associations between autonomic dysfunction and pain in chemotherapy‐induced polyneuropathy
Authors: Nahman‐Averbuch H. , Granovsky Y. , Sprecher E. , Steiner M. , Tzuk‐Shina T. , Pud D. , Yarnitsky D.
Published: June 2013

Background

Autonomic neuropathy, a relatively common complication of several chemotherapy agents, can affect the vagus nerve and its pain inhibitory capacity, thus increasing sensitivity to pain. This study aimed to evaluate the relationships between autonomic parasympathetic function and the perception of (1) spontaneous pain; (2) experimental non‐painful sensations; and (3) experimental painful sensations in chemotherapy‐induced neuropathy patients.

Methods

Twenty‐seven cancer patients with chemotherapy‐induced polyneuropathy were enrolled (20 women, age 56.6 ± 7.9). Autonomic parameters of heart rate variability, deep‐breathing and Valsalva ratios, experimental non‐painful parameters of warm, cold and mechanical detection thresholds, and painful parameters of heat pain thresholds, pain rating of suprathreshold stimulus, mechanical temporal summation and conditioned pain modulation response were examined.

Results

Autonomic parameters and spontaneous pain levels were not associated, yet autonomic parameters were positively correlated with non‐painful sensations – milder autonomic neuropathy was accompanied by milder sensory neuropathy as indicated by several parameters, e.g., lower Valsalva ratio was correlated with higher warmth detection threshold (r = −0.465; p = 0.033). Autonomic parameters were, however, negatively correlated with painful sensations – lower parasympathetic‐vagal activity was associated with higher pain sensitivity as indicated by several parameters, e.g., lower Valsalva ratio was correlated with higher pain rating of suprathreshold stimulus (r = −0.559; p = 0.008).

Conclusions

Diminished vagal function due to neuropathy is associated with, and may possibly underlie, pain disinhibition expressed as greater levels of experimental pain.
Role of surface charge and oxidative stress in cytotoxicity and genotoxicity of graphene oxide towards human lung fibroblast cells
Authors: Wang Anxin , Pu Kefeng , Dong Bing , Liu Yang , Zhang Liming , Zhang Zhijun , Duan Wei , Zhu Yimin
Published: June 2013

Recently, attempts have been made to apply graphene oxide (GO) in the field of biology and medicine, such as DNA sensing and drug delivery with some necessary modifications. Therefore, the toxicity of GO must be evaluated before it is applied further in biomedicine. In this paper, the cytotoxicity and genotoxicity of GO to human lung fibroblast (HLF) cells have been assessed with methyl thiazolyl tetrazolium (MTT), sub‐G1 measurement and comet assays, and the mechanism of its toxicity has been explored. Various modifications of GO have been made to help us determine the factors which could affect the toxicity of GO. The results indicated that cytotoxicity and genotoxicity of GO to HLF cells were concentration dependent, and the genotoxicity induced by GO was more severe than the cytotoxicity to HLF cells. Oxidative stress mediated by GO might explain the reason of its toxic effect. Furthermore, the electronic charge on the surface of GO would play a very important role in the toxicity of GO to HLF cells. Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis and Crystal Structure of Binuclear Copper(II) Complex Bridged by N‐(2‐Hydroxyphenyl)‐N′‐[3‐(diethylamino)propyl]oxamide: In Vitro Anticancer Activity and Reactivity Toward DNA and Protein
Authors: Gao Yang , Li Yan‐Tuan , Wu Zhi‐Yong , Yan Cui‐Wei
Published: June 2013

A new oxamido‐bridged bicopper(II) complex, [Cu2(pdpox)(bpy)(CH3OH)](ClO4), where H3pdpox and bpy stand for N‐(2‐hydroxyphenyl)‐N′‐[3‐(diethylamino)propyl]oxamide and 2,2′‐bipyridine, respectively, has been synthesized and characterized by elemental analyses, molar conductivity measurements, infrared and electronic spectra studies, and X‐ray single crystal diffraction. In the crystal structure, the pdpox3− ligand bridges two copper(II) ions as cisoid conformation. The inner copper(II) ion has a {N3O} square‐planar coordination geometry, while the exo‐ one is in a {N2O3} square‐pyramidal environment. There are two sets of interpenetrating two‐dimensional hydrogen bonding networks parallel to the planes (2 1 0) and (), respectively, to form a three‐dimensional supramolecular structure. The bicopper(II) complex exhibits cytotoxic activity against the SMMC7721 and A549 cell lines. The reactivity toward herring sperm DNA and bovine serum albumin revealed that the bicopper(II) complex can interact with the DNA by intercalation mode, and the complex binds to protein BSA responsible for quenching of tryptophan fluorescence by static quenching mechanism. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:412‐424, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21504
Freshwater Acclimation Induces Stress Responses and Expression of Branchial Na+/K+‐ATPase and Proliferating Cell Nuclear Antigen in Takifugu niphobles
Authors: TANG CHENG‐HAO , LEE TSUNG‐HAN
Published: June 2013

Almost the whole life cycle of the grass puffer (Takifugu niphobles) occurs in seawater (SW), but it is also sometimes found in fresh water (FW) rivers. This study aims to evaluate the effects of FW exposure on the stress, osmoregulatory, and physiological responses of the grass puffer. The grass puffers were captured from a local wetland and acclimated to SW (35‰) or FW in the laboratory. In the stress responses, plasma glucose concentrations and the abundances of hepatic and branchial heat shock proteins were higher in the FW group than in the SW group. FW acclimation led to a significant increase in the protein abundance and the specific activity of branchial Na+/K+‐ATPase (NKA). Immunochemical staining showed that the NKA immunoreactive (NKIR) cells of the FW and SW puffer were distributed mainly in gill filaments. Although the number of NKIR cells was similar in the two groups, the protein levels of proliferating cell nuclear antigen (PCNA) of nuclear fractions were elevated in the gills of the FW puffer. The induction of gill PCNA might contribute to cell proliferation which would maintain the amount of NKIR cells or repair DNA when exposed to FW, an osmotically stressful environment. Hence, activation of stress responses would provide the osmoprotection associated with FW adaptation of the grass puffer. Changes of branchial NKA expression and activity for osmoregulatory adjustment were required for stable blood osmolality and muscle water content. Based on our findings, the grass puffer was suggested to be a euryhaline teleost with SW preference. J. Exp. Zool. 319A: 409–421, 2013. © 2013 Wiley Periodicals, Inc.
An intraslab seismic sequence activated by the 2011 Tohoku‐oki earthquake: Evidence for fluid‐related embrittlement
Authors: Nakajima Junichi , Yoshida Keisuke , Hasegawa Akira
Published: June 2013

Using quantitative analysis of waveforms, we investigate a seismic cluster that occurred at a depth of 67 km in the Philippine Sea slab 8 months after the 11 March 2011 megathrust Tohoku‐oki earthquake (Mw 9.0). The sequence started with an M 4.1 normal‐fault event on 14 November in the deepest part of the cluster, and subsequent earthquakes migrated upward by 6 km along a narrow conduit‐like zone. The earthquakes have stress drops of 0.5–40 MPa, and groups of earthquakes with coherent waveforms are observed. We explain these observations in terms of fluid‐related embrittlement and the migration of overpressured fluids. The low‐permeability plate interface of the Pacific plate may have been broken by the coseismic or postseismic slips of the Tohoku‐oki earthquake, with the fluids subsequently being liberated from the underlying crust of the Pacific slab and migrating into the Philippine Sea slab due to the pore pressure gradient. The tensional stresses generated by the coseismic slip promoted the efficient upward migration of fluids and also acted to enhance the deviatoric stress around the source area. The heightened pore pressures and the resulting reduced effective normal stress lowered the strength of the faults sufficiently to bring the system into the brittle regime under the enhanced deviatoric stress. The lag of 8 months may represent the time needed for the unsealing of the plate interface, the upward migration of fluids, and the increase in pore pressure to become sufficient to overcome the lithostatic pressure.
The influence of vegetation on turbulence and bed load transport
Authors: Yager E. M. , Schmeeckle M. W.
Published: June 2013

Vegetation is ubiquitous in river channels and floodplains and alters mean flow conditions and turbulence. However, the effects of vegetation patches on near‐bed turbulence, bed load transport rates, and sedimentation are not well understood. To elucidate the influence of emergent vegetation on local and patch‐averaged bed load transport, we conducted a set of experiments in which we varied the mean flow velocity (U), total boundary shear stress (τ), or vegetation density between runs. We measured 2D velocity fields using Particle Imaging Velocimetry and bed load fluxes using high‐speed video. Simulated rigid vegetation caused bed load fluxes to vary spatially by an order of magnitude, causing distinct scour zones adjacent to, and depositional bed forms between stems. These local patterns of sedimentation could impact recruitment and survival of other plants. Large bed load fluxes were collocated with high near‐bed turbulence intensities that were three to four times larger than spatially averaged values. Higher vegetation densities increased the importance of inward and outward interactions, particularly downstream of vegetation. At the patch scale, greater stem densities caused either an increase or decrease in run‐averaged bed load fluxes, depending on whether U or τ was held constant between runs. This implies that sedimentation in vegetation patches is not only a function of bed grain size, sediment supply, and vegetation density and species, but whether vegetation significantly impacts mean and local flow properties, which could depend on vegetation location. Commonly used bed load transport equations did not accurately predict average sediment fluxes in our experiments unless they accounted for the spatial variability in the near‐bed Reynolds stress.
Promoting professionalism via a video‐based educational workshop for academic hospitalists and housestaff
Authors: Farnan Jeanne M. , O'Leary Kevin J. , Didwania Aashish , Icayan Liza , Saathoff Mark , Bellam Shashi , Anderson Andy , Reddy Shalini , Humphrey Holly J. , Wayne Diane B. , Arora Vineet M.
Published: June 2013

BACKGROUND

Unprofessional behavior can compromise care and detract from the hospital learning environment. Discrepancy between professional behaviors formally taught and what is witnessed has become increasingly evident.

METHODS

With funding from the American Board of Internal Medicine Foundation, a workshop was developed to address unprofessional behaviors related to inpatient care previously identified in a multi‐institution survey. The aims were to utilize video‐based education to illustrate unprofessional behaviors, how faculty play a role in promoting such behaviors, and facilitate reflection regarding motivation for and prevention of these behaviors. Hospitalists and housestaff at 3 Chicago‐area academic hospitals and 1 community teaching affiliate participated. Videos were debriefed, identifying barriers to professional behavior and improvement strategies. A postworkshop survey assessed beliefs on behaviors and intent to change practice.

RESULTS

Forty‐four (53%) faculty and 244 (68%) residents (postgraduate year 1 and greater) participated. The workshop was well received, with 89% reporting it “useful and effective.” Two‐thirds expressed intent to change behavior. Most (86%) believed videos were realistic and effective. Those who perceived videos as “very realistic” were more likely to report intent to change behavior (93% vs 53%, P = 0.01).

CONCLUSIONS

Video‐based education is a feasible way to promote reflection and address unprofessional behaviors among providers and may positively impact the learning environment. Journal of Hospital Medicine 2013;8:386–389. © 2013 Society of Hospital Medicine
Rotavirus shedding in symptomatic and asymptomatic children using reverse transcription‐quantitative PCR
Authors: Mukhopadhya Indrani , Sarkar Rajiv , Menon Vipin Kumar , Babji Sudhir , Paul Anu , Rajendran Priya , Sowmyanarayanan Thuppal V. , Moses Prabhakar D. , Iturriza‐Gomara Miren , Gray James J. , Kang Gagandeep
Published: June 2013

Reverse transcription‐real‐time polymerase chain reaction (RT‐qPCR) for the VP6 gene was used to study group A rotavirus shedding in children with symptomatic and asymptomatic rotavirus infection. Sequential stool samples (n = 345) from 10 children with rotavirus associated diarrhea and from five children (n = 161) with asymptomatic rotavirus infection were collected over a period of 2 months. A RT‐qPCR assay on the samples using a rotavirus VP6 plasmid standard demonstrated high reproducibility, with an inter‐assay coefficient of variation (CV) of 1.40–2.97% and an intra‐assay CV of 0.03–3.03%. The median duration of shedding was longer in children with diarrhea compared to asymptomatic children (24 days vs. 18 days; P = 0.066). The median quantitation cycle (Cq) at presentation in symptomatic children was 17.21 compared to 30.98 in asymptomatic children (P = 0.086). The temporal pattern in symptomatic children consisted of a high initial viral shedding coinciding with the duration of diarrhea, followed by a rapid fall, and then a small increase in secondary shedding 21 days later. Compared to children with rotavirus diarrhea, those with asymptomatic infection shed lower quantities of virus throughout the observation period. No difference was noted between the G and P genotypes of samples collected at onset of infection and during the shedding period. Shedding was intermittent in a subset of children in both groups. RT‐qPCR is a useful method to characterize shedding patterns. J. Med. Virol. 85:1661–1668, 2013. © 2013 Wiley Periodicals, Inc.
Purification and characterization of the extracellular laccase produced by Trametes polyzona WR710–1 under solid‐state fermentation
Authors: Chairin Thanunchanok , Nitheranont Thitinard , Watanabe Akira , Asada Yasuhiko , Khanongnuch Chartchai , Lumyong Saisamorn
Published: June 2013

Laccase from Trametes polyzona WR710–1 was produced under solid‐state fermentation using the peel from the Tangerine orange (Citrus reticulata Blanco) as substrate, and purified to homogeneity. This laccase was found to be a monomeric protein with a molecular mass of about 71 kDa estimated by SDS–PAGE. The optimum pH was 2.0 for ABTS, 4.0 for L‐DOPA, guaiacol, and catechol, and 5.0 for 2,6‐DMP. The Km value of the enzyme for the substrate ABTS was 0.15 mM, its corresponding Vmax value was 1.84 mM min−1, and the kcat/Km value was about 3960 s−1 mM−1. The enzyme activity was stable between pH 6.0 and 8.0, at temperatures of up to 40 °C. The laccase was inhibited by more than 50% in the presence of 20 mM NaCl, by 95% at 5 mM of Fe2+, and it was completely inhibited by 0.1 mM NaN3. The N‐terminal amino acid sequence of this laccase is AVTPVADLQISNAGISPDTF, which is highly similar to those of laccases from other white‐rot basidiomycetes.
Caribbean low‐level jets and accompanying moisture fluxes in a global warming climate projected with CMIP3 multi‐model ensemble and fine‐mesh atmospheric general circulation models
Authors: Nakaegawa T. , Kitoh A. , Ishizaki Y. , Kusunoki S. , Murakami H.
Published: June 2013

This study used the third phase of the Coupled Model Intercomparison Project (CMIP3) multi‐model ensemble (MME) and atmospheric general circulation models (AGCMs) with three horizontal resolutions, 20, 60, and 180 km, to investigate climate projections of the Caribbean low‐level jet (CLLJ) and accompanying moisture fluxes. Future climate simulations were also performed with 60‐ and 180‐km mesh AGCMs forced by four lower boundary conditions both to quantify uncertainty in the CLLJ projections and to determine the physical mechanism of change in the CLLJ. Changes among the CMIP3 MME models in projected CLLJ in the future climate were inconsistent in sign and statistically insignificant, whereas consistently among the models the easterly moisture flux accompanying the CLLJ significantly intensified. The AGCM simulations with three different horizontal resolutions demonstrated that the merits of dynamical downscaling for the CLLJ and moisture flux were limited for climate projections, although the high‐horizontal resolution models improved reproducibility of the CLLJ and moisture flux in the present‐day climate and can provide spatially detailed projections. Different projected sea surface temperatures (SSTs) as lower boundary conditions of the 60‐ and 180‐km mesh single‐AGCM simulations clearly affected changes in the CLLJ. Both the CMIP3 MME analysis and the 60‐ and 180‐km mesh AGCM ensembles showed that large‐scale SST patterns between the eastern tropical Pacific and the region from the Caribbean Sea to the western tropical Atlantic influenced changes in the CLLJ in the future climate, as seen in the present‐day climate.
Endoscopic hydroxyapatite augmentation for patulous eustachian tube
Authors: Vaezeafshar Reza , Turner Justin H. , Li Gang , Hwang Peter H.
Published: June 2013

Objectives/Hypothesis

To evaluate the safety and efficacy of endoscopic calcium hydroxyapatite injection in patients with patulous Eustachian tube.

Study Design

Retrospective case series.

Methods

Fourteen patients diagnosed with patulous Eustachian tube (PET) underwent endoscopic hydroxyapatite injection under general anesthesia. All patients had at least two of three major PET symptoms including voice autophony, breathing autophony, or aural fullness/pressure. Patients were evaluated postoperatively with nasal endoscopy and a symptom questionnaire.

Results

Endoscopic Eustachian tube injection was performed in a total of 23 sides in 14 patients with an average volume of 2.1 cc injected per side. Mean follow‐up was 17.5 months. The most common symptoms reported preoperatively were voice autophony (96%), breathing autophony (91%), and ear fullness (83%). A complete or significant response to treatment was noted in 13/22 sides with voice autophony (59%), 12/21 sides with breathing autophony (57%), and 12/19 sides with ear fullness (63%). All complete or significant symptom improvements remained durable through the entirety of the follow‐up period. Four sides that had temporary or no improvement with treatment underwent repeat injection but did not achieve additional improvement. No intraoperative or postoperative complications were observed.

Conclusion

Endoscopic hydroxyapatite injection of the Eustachian tube is a minimally invasive procedure that provided significant or complete relief of autophony and ear fullness in 57% to 63% of sides treated. The procedure is well tolerated and can be performed safely under endoscopic visualization. Hydroxyapatite injection may be a satisfactory alternative to more invasive treatments for PET.

Level of Evidence

4. Laryngoscope, 124:62–66, 2014
Radical Copolymerization Reactivity of N‐Substituted Maleimides with α‐Substituted Styrenes with Various N‐ and α‐Substituents and the Thermal and Optical Properties of the Resulting Copolymers
Authors: Hisano Miki , Takashima Tsutomu , Jin Zhengzhe , Shiibashi Akira , Matsumoto Akikazu
Published: June 2013

The radical alternating copolymerization of N‐substituted maleimides (RMIs) with N‐methyl, n‐butyl, and 2‐ethylhexyl groups and styrene derivatives with various α‐substituents (RSs) is carried out. The yield and the molecular weight of the obtained copolymers significantly decrease with an increase in the size of the α‐substituent of RSs, but are independent of the N‐substituents. The glass‐transition temperature of the copolymers increases on the introduction of the large substituents into the RS repeating units. The high‐molecular‐weight poly(RMI‐alt‐RS)s are soluble in organic solvents and provide flexible and transparent films with excellent transparency by casting the solutions.

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The −1195G allele increases the transcriptional activity of cyclooxygenase‐2 gene (COX‐2) in colon cancer cell lines
Authors: Pereira Carina , Sousa Hugo , Silva Joana , Brandão Carla , Elgueta‐Karstegl Claudio , Farrell Paul J. , Medeiros Rui , Dinis‐Ribeiro Mário
Published: June 2013

Up‐regulation of cyclooxygenase‐2 (COX‐2) is an early and key event in human colorectal carcinogenesis (CRC). Nevertheless, the molecular mechanisms leading to this over‐expression are largely unknown. We previously reported an association between the −1195G allele and higher predisposition for CRC in a Caucasian population. The biological explanation for the involvement of this polymorphism in CRC remains elusive. We aimed to functionally characterize the influence of the −1195A>G promoter region polymorphism on COX‐2 transcription activity in colon cancer cell lines. Luciferase reporter assays were performed to assess whether the −1195A/G alleles influenced COX‐2 transcription. The COX‐2 promoter's region containing either the −1195A or −1195G alleles was cloned into pGL3‐basic reporter vector. The reporter vectors were transiently co‐transfected with the pGL4.73 control plasmid to HCT‐116 and HCA‐7 colon cancer cell lines. The levels of reporter gene expression driven by the −1195G allele‐containing COX‐2 promoter were significantly higher in both colon cancer cell lines. A 2.2‐fold increase in promoter activity was observed in the HCT‐116 cell line (P < 0.001), and this over‐expression was even more noticeable in the HCA‐7 COX‐2 expressing cell line with a threefold higher transcriptional activity (P = 0.001). The −1195G allele appeared to enhance COX‐2 transcription, providing a molecular basis underlying the increased susceptibility for CRC and potentially a new mechanism for COX‐2 overexpression. © 2013 Wiley Periodicals, Inc.
Retinal nerve fiber layer thickness and visual hallucinations in Parkinson's Disease
Authors: Lee Jee‐Young , Kim Jae Min , Ahn Jeeyun , Kim Han‐Joon , Jeon Beom S. , Kim Tae Wan
Published: June 2013

Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case‐control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted. © 2013 International Parkinson and Movement Disorder Society
Early Diagnosis of Complex Diseases by Molecular Biomarkers, Network Biomarkers, and Dynamical Network Biomarkers
Authors: Liu Rui , Wang Xiangdong , Aihara Kazuyuki , Chen Luonan
Published: June 2013

Many studies have been carried out for early diagnosis of complex diseases by finding accurate and robust biomarkers specific to respective diseases. In particular, recent rapid advance of high‐throughput technologies provides unprecedented rich information to characterize various disease genotypes and phenotypes in a global and also dynamical manner, which significantly accelerates the study of biomarkers from both theoretical and clinical perspectives. Traditionally, molecular biomarkers that distinguish disease samples from normal samples are widely adopted in clinical practices due to their ease of data measurement. However, many of them suffer from low coverage and high false‐positive rates or high false‐negative rates, which seriously limit their further clinical applications. To overcome those difficulties, network biomarkers (or module biomarkers) attract much attention and also achieve better performance because a network (or subnetwork) is considered to be a more robust form to characterize diseases than individual molecules. But, both molecular biomarkers and network biomarkers mainly distinguish disease samples from normal samples, and they generally cannot ensure to identify predisease samples due to their static nature, thereby lacking ability to early diagnosis. Based on nonlinear dynamical theory and complex network theory, a new concept of dynamical network biomarkers (DNBs, or a dynamical network of biomarkers) has been developed, which is different from traditional static approaches, and the DNB is able to distinguish a predisease state from normal and disease states by even a small number of samples, and therefore has great potential to achieve “real” early diagnosis of complex diseases. In this paper, we comprehensively review the recent advances and developments on molecular biomarkers, network biomarkers, and DNBs in particular, focusing on the biomarkers for early diagnosis of complex diseases considering a small number of samples and high‐throughput data (or big data). Detailed comparisons of various types of biomarkers as well as their applications are also discussed.
The relationship between BMI and urinary incontinence subgroups: Results from EpiLUTS
Authors: Khullar Vik , Sexton Chris C. , Thompson Christine L. , Milsom Ian , Bitoun Caty Ebel , Coyne Karin S.
Published: June 2013

Aims

To evaluate the relationship between body mass index (BMI) and urinary incontinence (UI) in adults ≥40 from the United States, United Kingdom, and Sweden.

Methods

This was a secondary analysis of EpiLUTS—a population‐representative, cross‐sectional, Internet‐based survey conducted to assess the prevalence and HRQL impact of urinary symptoms. UI was evaluated by the LUTS Tool and categorized by subgroups: no UI, urgency urinary incontinence (UUI), stress urinary incontinence (SUI), mixed urinary incontinence (MUI) (UUI + SUI), UUI + other UI (OI), SUI + OI, and OI. Descriptive statistics were used. Logistic regressions examined the relationship of BMI to UI controlling for demographics and comorbid conditions.

Results

Response rate was 59%; 10,070 men and 13,178 women were included. Significant differences in BMI were found across UI subgroups. Obesity rates were highest among those with MUI (men and women), SUI + OI (women), UUI and UUI + OI (men). Logistic regressions of each UI subgroup showed that BMI ≥ 30 (obese) was associated with UI in general and MUI (women) and UUI + OI (men). Among women, being obese increased the odds of having SUI and SUI + OI. Women with BMI 25–29.9 (overweight) were more likely to have UI in general and SUI with and without other incontinence (SUI, MUI, and SUI + OI). Being overweight was unrelated to any form of UI in men.

Conclusions

Results were consistent with prior research showing BMI is associated with higher risk of UI. These findings indicate substantial differences in obesity by gender and UI subtype, suggesting different mechanisms for UI other than purely mechanical stress on the bladder. Neurourol. Urodynam. 33:392–399, 2014. © 2013 Wiley Periodicals, Inc.
Rapid Quantitation of Furanocoumarins and Flavonoids in Grapefruit Juice using Ultra‐Performance Liquid Chromatography
Authors: VanderMolen Karen M. , Cech Nadja B. , Paine Mary F. , Oberlies Nicholas H.
Published: June 2013

Introduction

Grapefruit juice can increase or decrease the systemic exposure of myriad oral medications, leading to untoward effects or reduced efficacy. Furanocoumarins in grapefruit juice have been established as inhibitors of cytochrome P450 3A (CYP3A)‐mediated metabolism and P‐glycoprotein (P‐gp)‐mediated efflux, while flavonoids have been implicated as inhibitors of organic anion transporting polypeptide (OATP)‐mediated absorptive uptake in the intestine. The potential for drug interactions with a food product necessitates an understanding of the expected concentrations of a suite of structurally diverse and potentially bioactive compounds.

Objective

Develop methods for the rapid quantitation of two furanocoumarins (bergamottin and 6′,7′‐dihydroxybergamottin) and four flavonoids (naringin, naringenin, narirutin and hesperidin) in five grapefruit juice products using ultra‐performance liquid chromatography (UPLC).

Methods

Grapefruit juice products were extracted with ethyl acetate; the concentrated extract was analysed by UPLC using acetonitrile:water gradients and a C18‐column. Analytes were detected using a photodiode array detector, set at 250 nm (furanocoumarins) and 310 nm (flavonoids). Intraday and interday precision and accuracy and limits of detection and quantitation were determined.

Results

Rapid (< 5.0 min) UPLC methods were developed to measure the aforementioned furanocoumarins and flavonoids. R2 values for the calibration curves of all analytes were >0.999. Considerable between‐juice variation in the concentrations of these compounds was observed, and the quantities measured were in agreement with the concentrations published in HPLC studies.

Conclusion

These analytical methods provide an expedient means to quantitate key furanocoumarins and flavonoids in grapefruit juice and other foods used in dietary substance–drug interaction studies. Copyright © 2013 John Wiley & Sons, Ltd.
Association of Antidepressant and Atypical Antipsychotic Use with Cardiovascular Events and Mortality in a Veteran Population
Authors: Acharya Tushar , Acharya Sabeena , Tringali Steven , Huang Jian
Published: June 2013

Study Objectives

To determine the patterns of antidepressant and atypical antipsychotic use in a veteran population with depression, and to determine if an association exists between specific antidepressant classes and atypical antipsychotics and the occurrence of cardiovascular events and all‐cause mortality.

Design

Retrospective, cross‐sectional study.

Setting

Primary care clinic at a Veterans Affairs hospital.

Patients

A total of 1136 patients diagnosed with depression who were receiving antidepressant monotherapy (664 patients) or no antidepressant therapy (472 patients [controls]) between June 2009 and December 2010.

Measurements and Main Results

Data on patient demographics, disease diagnoses, laboratory data, and drug therapy profiles were collected through medical record review. Of the 1136 patients, the mean patient age was 61 years, 90% were men, and 77% were smokers. Mean body mass index was 30.4 kg/m2, blood pressure 126/73 mm Hg, hemoglobin A1c 6%, low‐density lipoprotein cholesterol level 106.7 mg/dl, and Framingham score 17. Patients receiving antidepressant monotherapy were grouped according to antidepressant class; selective serotonin reuptake inhibitors (SSRIs) were most common. Concomitant use of atypical antipsychotics was more common with the serotonin‐norepinephrine reuptake inhibitor (venlafaxine), SSRI, and serotonin receptor antagonist (trazodone) classes (p=0.0067). After adjusting for demographics, concomitant drugs, and comorbidities, SSRI use was significantly associated with lower all‐cause mortality (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.19–0.71, p=0.0028). Notably, noradrenergic and specific serotonergic antidepressant (mirtazapine) use was significantly associated with higher prevalence of heart failure (OR 3.26, 95% CI 1.029–10.38, p=0.0445). Use of atypical antipsychotics was significantly associated with a higher prevalence of cerebrovascular events (OR 2.23, 95% CI 1.29–3.83, p=0.0036) and all‐cause mortality (OR 2.05, 95% CI 1.03–4.1, p=0.04).

Conclusion

Our results favor treatment of depression with SSRIs among patients at increased cardiovascular risk due to the potential mortality benefit of this class of drugs. Atypical antipsychotics should be used with caution in the elderly population. Mirtazapine use in patients with heart failure and depression deserves further investigation.
Increased bisecting N‐acetylglucosamine and decreased branched chain glycans of N‐linked glycoproteins in expressed prostatic secretions associated with prostate cancer progression
Authors: Nyalwidhe Julius O. , Betesh Lucy R. , Powers Thomas W. , Jones E. Ellen , White Krista Y. , Burch Tanya C. , Brooks Jasmin , Watson Megan T. , Lance Raymond S. , Troyer Dean A. , Semmes O. John , Mehta Anand , Drake Richard R.
Published: June 2013

Purpose

Using prostatic fluids rich in glycoproteins like prostate‐specific antigen and prostatic acid phosphatase (PAP), the goal of this study was to identify the structural types and relative abundance of glycans associated with prostate cancer status for subsequent use in emerging MS‐based glycopeptide analysis platforms.

Experimental design

A series of pooled samples of expressed prostatic secretions (EPS) and exosomes reflecting different stages of prostate cancer disease were used for N‐linked glycan profiling by three complementary methods, MALDI‐TOF profiling, normal‐phase HPLC separation, and triple quadropole MS analysis of PAP glycopeptides.

Results

Glycan profiling of N‐linked glycans from different EPS fluids indicated a global decrease in larger branched tri‐ and tetra‐antennary glycans. Differential exoglycosidase treatments indicated a substantial increase in bisecting N‐acetylglucosamines correlated with disease severity. A triple quadrupole MS analysis of the N‐linked glycopeptides sites from PAP in aggressive prostate cancer pools was done to cross‐reference with the glycan profiling data.

Conclusion and clinical relevance

Changes in glycosylation as detected in EPS fluids reflect the clinical status of prostate cancer. Defining these molecular signatures at the glycopeptide level in individual samples could improve current approaches of diagnosis and prognosis.
Development of a fluorescent monoclonal antibody‐based assay to measure the allosteric effects of synthetic peptides on self‐oligomerization of AGR2 protein
Authors: Gray Terry A. , Murray Euan , Nowicki Matthew W. , Remnant Lucy , Scherl Alexander , Muller Petr , Vojtesek Borek , Hupp Ted R.
Published: June 2013

Many regulatory proteins are homo‐oligomeric and designing assays that measure self‐assembly will provide novel approaches to study protein allostery and screen for novel small molecule modulators of protein interactions. We present an assay to begin to define the biochemical determinants that regulate dimerization of the cancer‐associated oncoprotein AGR2. A two site‐sandwich microtiter assay (2SMTA) was designed using a DyLight800‐labeled monoclonal antibody that binds to an epitope in AGR2 to screen for synthetic self‐peptides that might regulate dimer stability. Peptides derived from the intrinsically disordered N‐terminal region of AGR2 increase in trans oligomer stability as defined using the 2SMTA assay. A DSS‐crosslinking assay that traps the AGR2 dimer through K95‐K95 adducts confirmed that Δ45‐AGR2 was a more stable dimer using denaturing gel electrophoresis. A titration of wt‐AGR2, Δ45‐AGR2 (more stable dimer), and monomeric AGR2E60A revealed that Δ45‐AGR2 was more active in binding to Reptin than either wt‐AGR2 or the AGR2E60A mutant. Our data have defined a functional role for the AGR2 dimer in the binding to its most well characterized interacting protein, Reptin. The ability to regulate AGR2 oligomerization in trans opens the possibility for developing small molecules that regulate its' biochemical activity as potential cancer therapeutics. The data also highlight the utility of this oligomerization assay to screen chemical libraries for ligands that could regulate AGR2 dimer stability and its' oncogenic potential.
Practical marginalized multilevel models
Authors: Griswold Michael E. , Swihart Bruce J. , Caffo Brian S. , Zeger Scott L.
Published: June 2013

Clustered data analysis is characterized by the need to describe both systematic variation in a mean model and cluster‐dependent random variation in an association model. Marginalized multilevel models embrace the robustness and interpretations of a marginal mean model, while retaining the likelihood inference capabilities and flexible dependence structures of a conditional association model. Although there has been increasing recognition of the attractiveness of marginalized multilevel models, there has been a gap in their practical application arising from a lack of readily available estimation procedures. We extend the marginalized multilevel model to allow for nonlinear functions in both the mean and association aspects. We then formulate marginal models through conditional specifications to facilitate estimation with mixed model computational solutions already in place. We illustrate the MMM and approximate MMM approaches on a cerebrovascular deficiency crossover trial using SAS and an epidemiological study on race and visual impairment using R. Datasets, SAS and R code are included as supplemental materials. Copyright © 2013 John Wiley & Sons Ltd
Testing the functionality and contact error of a GPS‐based wildlife tracking network
Authors: Davis Melanie J. , Thokala Sravan , Xing Xinyu , Hobbs N. Thompson , Miller Michael W. , Han Richard , Mishra Shivakant
Published: June 2013

Telemetry is a fundamentally important tool for studying animal movements. Traditional telemetry systems have provided time‐specific information on locations of individuals; however, recent developments in instruments allow for the tracking of networks of interactions among individuals. Currently, these devices rely on very high frequency (VHF) radio technology, and cannot precisely gauge where interactions occurred without on‐site triangulation. Furthermore, although commercially available devices can log successful communication attempts between collars as little as 1 m apart, researchers cannot accurately determine distances within the pre‐set detection (contact) threshold of these units. Data loss from proximity‐logging devices, and even traditional telemetry devices that are lost or damaged in the field, poses another obstacle to monitoring wildlife social networks. We have developed a prototype proximity‐logging Global Positioning System (GPS) collar that offers greater spatial resolution of social interactions, and reduces probability of data loss. In this study, we used captive bighorn sheep (Ovis canadensis) to test the GPS capabilities, contact rates, and contact distance error of our prototype collars. The GPS fix success rate of our collars was >97.93% (n = 95,041; 95% CI = 97.84–98.02%). The collars were communicating with each other about 98% (n = 22,253; 95% CI = 98.50–98.81%) of the time and reciprocal communication occurred 9% of the time. Contact distance error was 9.5 m, which is what would be expected taking into account a baseline GPS spatial error of ±5 m in open environments. The high GPS fix success, low GPS error, and ability to log accurate social interactions with low contact distance error by our prototype collars suggest that the implementation of GPS with proximity‐logging technology has the potential to improve currently available social network data. © 2013 The Wildlife Society.