bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Recruitment Methods for Vulnerable, Traumatized Adolescents
Authors: Campbell Rebecca , Greeson Megan R. , Fehler-Cabral Giannina
Published: October 2013

This article describes the process by which we created a recruitment protocol for engaging adolescent sexual assault victims in a qualitative evaluation study. Working in collaboration with forensic nurses, rape victim advocates, adolescent rape survivors, and our institutional review board (IRB), we created a prospective recruitment method whereby adolescent victims were given information about the evaluation project at the time of postassault treatment services, but data collection was deferred until the trauma of the assault had a chance to diminish. In-person qualitative interviews were conducted with 25 clients at the treatment programs approximately 10 weeks after the assault. Although we recruited only a small number of youth (21% of the eligible sample), the methods were sufficient to achieve saturation, and comparisons to the agencies’ quantitative records suggest that the interview sample was not different from program population norms. We examine why some teens chose not to participate and provide recommendations for recruiting hard-to-find, vulnerable, and/or traumatized adolescent populations.
The “Process” of Process Use
Authors: Shaw Jessica , Campbell Rebecca
Published: October 2013

Process use refers to the ways in which stakeholders and/or evaluands change as a function of participating in evaluation activities. Although the concept of process use has been well discussed in the literature, exploration of methodological strategies for the measurement and assessment of process use has been limited. Typically, empirical research on process use has been limited to cross-sectional studies in single-site evaluation projects. In this method note, we present a longitudinal study of process use in a multisite evaluation project. Stakeholders’ changes in learning, attitudes, and behavior/action were assessed at three time points: prior to the onset of evaluation consultation; near the conclusion of a 1-year participatory consultation project; and 6–8 weeks after the termination of the project. Results showed that different domains of process use had differential development over time. Implications for measuring process use are discussed.
Sleeping and resting respiratory rates in healthy adult cats and cats with subclinical heart disease
Authors: Ljungvall Ingrid , Rishniw Mark , Porciello Francesco , Häggström Jens , Ohad Dan
Published: October 2013

Sleeping and resting respiratory rates are commonly measured variables in patients with cardiac disease. However, little information is available on these variables in healthy client-owned cats or cats with subclinical heart disease (SHD). Therefore, we examined and characterized the sleeping respiratory rate (SRR) and resting respiratory rate (RRR) in 59 echocardiographically normal (EN) and 28 apparently healthy (AH) cats, and 54 SHD cats acquired by the cat owners in the home environment on eight to 10 separate occasions. The within-cat mean sleeping respiratory rate (SRRmean) in EN cats, AH cats and SHD cats with mild or moderate left atrial (LA) enlargement (as defined by quantiles of the ratio of the LA to the aorta [LA:AO]) was consistently <30 breaths/min; median SRRmean approximated 21 breaths/min. The SRRmean of SHD cats with severe LA enlargement sometimes exceeded 30 breaths/min, and was higher than SRRmean of other SHD cats ( P <0.05). The within-cat mean resting respiratory rate was consistently higher than SRRmean ( P <0.05). Age and geographic location, but not bodyweight, affected SRRmean in EN and AH cats. Within-cat SRR and within-cat RRR did not vary markedly from day-to-day, as evidenced by a low within-cat coefficient of variation. Data acquisition was considered easy or non-problematic by most participants. Our data provide useful guidelines for SRR and RRR, obtained in the home environment, in healthy cats and cats with SHD, and might prove useful in managing cats with clinical heart disease. Cats with SRRmean >30 breaths/min and cats with multiple SRR measurements >30 breaths/min likely warrant additional evaluation.
Treatment for stable HIV patients in England: can we increase efficiency and improve patient care?
Authors: Adams Elisabeth , Ogden David , Ehrlich Alice , Hay Phillip
Published: October 2013

Objectives

To estimate the costs and potential efficiency gains of changing the frequency of clinic appointments and drug dispensing arrangements for stable HIV patients compared to the costs of hospital pharmacy dispensing and home delivery.

Methods

We estimated the annual costs per patient (HIV clinic visits and either first-line treatment or a common second-line regimen, with some patients switching to a second-line regimen during the year). The cost of three-, four- and six-monthly clinic appointments and drug supply was estimated assuming hospital dispensing (incurring value-added tax) and home delivery. Three-monthly appointments and hospital drug dispensing (baseline) were compared to other strategies.

Results

The baseline was the most costly option (£10,587 if first-line treatment and no switch to second-line regimen). Moving to six-monthly appointments and home delivery yielded savings of £1883 per patient annually. Assuming patients start on different regimens and may switch to second-line therapies, six-monthly appointments and three-monthly home delivery of drugs is the least expensive option and could result in nearly £2000 savings per patient. This translates to annual cost reduction of about £8 million for the estimated 4000 eligible patients not currently on home delivery in London, England.

Conclusions

Different appointment schedules and drug supply options should be considered for stable HIV patients based on efficiency gains. However, this should be assessed for individual patients to meet their needs, especially around adherence and patient support.
Unreliable item or inconsistent person? A study of variation in health beliefs and belief-anchors to biomedical models
Authors: Ip Edward H , Saldana Santiago , Chen Shyh-Huei , Kirk Julienne K , Bell Ronny A , Nguyen Ha , Grzywacz Joseph G , Arcury Thomas A , Quandt Sara A
Published: October 2013

The reliability of an item designed to measure health belief is often confounded with response consistency at the person level. The study applied contemporary measurement methods to an inventory of common sense beliefs about diabetes and used a sample of N = 563 adults with diabetes to test the hypothesis that individuals whose beliefs are congruent with a biomedical model are more consistent in their responses. Item-level analysis revealed that the domains of Causes and Medical Management were the least reliable. Person-level analysis showed that respondents who held views congruent with the biomedical model were more consistent than people who did not.
Intersectionality of internalized HIV stigma and internalized substance use stigma: Implications for depressive symptoms
Authors: Earnshaw Valerie A , Smith Laramie R , Cunningham Chinazo O , Copenhaver Michael M
Published: October 2013

We adopted an intersectionality framework and examined whether the relationship between internalized HIV stigma and depressive symptoms is moderated by internalized substance use stigma. A total of 85 people living with HIV with a history of substance use in the Bronx, New York, completed a survey. Results revealed evidence of moderation: Participants who internalized HIV stigma experienced greater depressive symptoms only if they also internalized substance use stigma. Researchers should examine stigma associated with multiple socially devalued characteristics to best understand how stigma impacts mental health among people living with HIV. Healthcare providers should address stigma associated with the full range of socially devalued characteristics with which people living with HIV live.
Investigation of strength mis-match effect on elastic plastic fracture parameters in laser beam welded aluminium alloy joints using the finite element method
Authors: Özdemir Uğur , Yeni Çınar
Published: October 2013

In this study, elastic plastic fracture toughness parameters of laser-welded 6013 aluminium alloy are investigated. For this purpose, compact tension specimens used in the experimental study are modelled using the finite element software. In the analyses, crack tip opening displacement ( δ5) and J-integral values are determined and crack tip opening displacement, δ5 and J-integral resistance curves (R-curves) are generated. Crack tip opening displacement, δ5 resistance curves are compared with those obtained from the experimental work, and J-resistance curves are compared with those obtained from formulation. Effect of weld strength undermatching on crack tip opening displacement, δ5 and J-resistance curves is discussed. δph values obtained by the plastic hinge method are compared with the crack tip opening displacement, δ5 values. Fracture toughness parameters obtained from the finite element analysis showed a good agreement with those obtained from the experimental work and formulation. It is observed that the resistance curves obtained using the crack tip opening displacement, δ5 and J-integral characterize the resistance of the material against crack growth in a similar manner, and strength undermatching decreases the fracture resistance. The relationship between δph and crack tip opening displacement, δ5 is nonlinear, and as crack tip opening displacement increases, crack tip opening displacement, δ5 becomes larger than δph.
Identification of a class of nonlinear dynamic relationships: Application to the identification of engine emission models
Authors: Alamir Mazen , Alberer Daniel , Del Re Luigi
Published: October 2013

In this article, a novel identification framework is proposed to capture a class of nonlinear dynamic relationships that link several input signals (and their past values) to a single output. The class of relationships is the one in which the single output to be identified may be any monotonic nonlinear function of a linear regressor that may be built up with the input signals and their past values. This obviously recalls the known Wiener identification structure with differences that are underlined in the article. The whole framework is validated using the difficult problem of deriving real data–based dynamic model of emissions (including NOx and particulate matter) of a diesel engine. The compelling feature of the proposed approach lies in the fact that the underlying optimization problem to be solved is a constrained quadratic programming problem and this, despite the nonlinear character of the identified relationship.
Solving the Impediment Induced Variable Shape Covering Problem
Authors: Arbour B. , Massel P.
Published: October 2013

Given finite resources, organizations are in a constant struggle to satisfy conflicting demands for resource allocation. Finding the right number of response units needed to respond to an incident in a given area is one such problem. Different geographical areas have different characteristics that further complicate the problem. For example, Canada’s Arctic waters is a large area with many islands and where varying ice coverage conditions are the norm. These impediments complicate what would otherwise be a straightforward application of the Circle Packing or Circle Covering Problem. The authors propose to call such a problem the Impediment Induced Variable Shape Covering Problem and present the Incident Response Model that determines the minimum number of units needed to respond to an incident anywhere in a given Area of Interest within a predetermined response time while avoiding or accounting for impediments.
Performance effects of imperfect multi-modal sensory cueing in a target detection simulation
Authors: Mercado Joseph E. , White Timothy L. , Sanders Tracy , Wright Julia , Hancock PA
Published: October 2013

Past research has shown that multi-modal sensory cues can reduce the workload of the user while simultaneously increasing performance capacity. This study looks to examine how performance is impacted in a multi-modal sensory cueing target detection task in which the cueing automation is imperfect. Twenty-seven undergraduate participants volunteered to take part in the present multi-modal sensory automation target detection task. The independent variables were trial (i.e., three five-minute trial blocks) and the cueing method (i.e., tactile, auditory or a combination of tactile and auditory cueing) used to assist visual search for target detection across three screens. Dependent variables included each participant’s response time and rate of accuracy. Results illustrate a significant decrease in response in the final trial when compared with the first trial. Results also illustrated a decrease in response time in each successive trial compared with the previous, each reflective of learning effects. A one-trial block exposure (5 minutes) to imperfect automation resulted in a response time decrease of 24%, while a two-trial block exposure (10 minutes) resulted in a response time decrease of 38%. Errors of omission results showed significantly lower miss rates in the final trial block when compared with the first trial block. In addition, errors of omission were lower in each successive trial compared with the previous. A one-trial block exposure (5 minutes) to imperfect automation resulted in a decrease in misses of 45%, while a two-trial block exposure (10 minutes) to imperfect automation resulted in a decrease of 65% in such misses. Our results suggest that interchanging multi-modal cues create stronger learning trends in a human–automation system than uni-modal cues. Results also showed that in spite of the automation used, automation failure resulted in a significant performance decrement. Auditory automation cueing failure produced a sevenfold increase in response time, while tactile automation cueing failure and a combination of auditory and tactile automation cueing failure produced a fourfold increase in response time. A speed–accuracy trade-off is not the cause of these results, because auditory automation cueing failure produces a twofold decrease in accuracy, and a combination of auditory and tactile automation cueing failure produced a threefold decrease in accuracy.
Volitional Control of Heartbeat and Its Dependence on Pallium
Authors: Yu Xiaolin , Zhang Chong , Yang Yong , Zhang Jianbao
Published: October 2013

It is believed that we cannot change our heart rhythm by will because the heartbeat is mainly controlled by the autonomic nervous system (ANS), which cannot be affected directly by subjective will. An experiment was designed to determine whether the heartbeat and ANS could be controlled by volition, and, if it is true, how they were controlled. It was demonstrated that the ANS could be partly controlled by volition. The volition, which tended to slow down the heartbeat, initiated synchronized activity in the medial prefrontal cortex, inhibited the sympathetic system, and then decreased the heartbeat. On the other hand, another kind of volition, which sped up the heartbeat, initiated desynchronized activity at the precentral, central, parietal, and occipital regions, inhibited the parasympathetic system and excited the sympathetic system, and then increased the heartbeat. Moreover, information flow from posterior cortex to anterior cortex was observed during the experiment. The parietal area played an important role in triggering the sensorimotor cortex and integrating the information, and the information flow from the central and precentral cortex to heart was dominant. All that demonstrated that volition can partly control the heartbeat, but the behavior was different from the motor nervous system.
Considerations in the surgical use of the flexor sheath and pulley system
Authors: Lowrie A. G. , Lees V. C.
Published: October 2013

The use of the digital flexor sheath to reconstruct damaged structures in the fingers is an intriguing but under-investigated subject. The sheath is anchored firmly to the phalanges and palmar plates and has well-vascularized outer and synovial inner layers. The middle layer is strong and fibrous and not all of it is required for its main biomechanical function of maintaining the moment arm of the flexor tendons. These characteristics have led to several descriptions of different reconstructive uses. In sheath reconstruction, flaps can be used to repair damaged A2 and A4 pulleys. As an anchor, the sheath is useful for tenodeses and tendon transfers. It has been used in the correction of ulnar claw and swan neck deformities. In ligament reconstruction, the A1 pulley has been used to reconstruct the transverse intermetacarpal ligament in cleft hand and ray amputations. The sheath has also been used to cover tendon repairs and periosteal defects with the aim of decreasing adhesions. There is potential for further use of the flexor sheath in reconstructive surgery.

The digital flexor sheath can be used to restore various finger functions providing its physiological roles are recognized and preserved. This review considers the different techniques described and their potential uses.
A comparison of the functional difficulties in staged and simultaneous open carpal tunnel decompression
Authors: Dickson D. R. , Boddice T. , Collier A. M.
Published: October 2013

There is no agreement about whether patients with bilateral carpal tunnel syndrome should undergo staged or simultaneous open decompression. The purpose of this study was to quantify and compare the functional difficulties during the recovery from surgery for patients undergoing staged or simultaneous decompressions. Sixty-three patients had surgery; 33 had staged decompression (Group 1) and 30 simultaneous decompressions (Group 2). Functional difficulties were recorded using the Levine and Quick-DASH scores along with a visual analogue score for pain. There were no complications in either group. There was no significant difference in terms of pain or satisfaction. Functional difficulties were greater in the simultaneous group; however, there was no difference in completing simple tasks. Patients reported high satisfaction with either management approach. However, significantly fewer would consider undergoing simultaneous decompression again.
Adrenal cortical carcinoma mimicking early severe preeclampsia
Authors: Jarvis Elizabeth , Morton Adam
Published: October 2013

Preeclampsia is a common disorder in pregnancy and may affect multiple maternal and foetal organ systems. Less common disorders with similar features may imitate preeclampsia though require different management strategies and with different prognostic implications for mother and baby. We present a case of a pregnant woman who developed severe hypertension and proteinuria in pregnancy. The early onset of these changes prompted investigation for causes other than preeclampsia, leading to a diagnosis of Cushing’s syndrome due to stage III adrenocortical cancer. The changes in management strategy, the importance of a multidisciplinary approach to care, and the prognostic implications for the mother are discussed.
Exposure to Ideological News and Perceived Opinion Climate
Authors: Tsfati Yariv , Stroud Natalie Jomini , Chotiner Adi
Published: October 2013

Spiral-of-silence theory assumes that a monolithic stream of messages from mainstream media, leaving little ability for audiences to seek ideologically congruent news, affects people’s perceptions of the distribution of opinion in society. While these assumptions may have been valid when Noelle-Neumann developed her theory forty years ago, the new media landscape, characterized by the proliferation of ideological media outlets, makes them seem outdated. Do audiences of conservative-leaning media perceive a conservative opinion climate while audiences of liberal-leaning media perceive a more liberal distribution of opinion? And if so, what are the consequences? We examine these questions using two data sets collected in extremely different contexts (Study 1 in the context of the 2005 Israeli disengagement from Gaza, n = 519; Study 2, in the context of the 2004 U.S. presidential elections using the National Annenberg Election Survey, n = 9,058). In both studies, selective exposure to ideological media outlets was associated with opinion climate perceptions that were biased in the direction of the media outlets’ ideologies. In Study 2, we also demonstrated that partisan selective exposure indirectly contributes to political polarization, and that this effect is mediated by opinion climate perceptions.
Orbital phlebography in idiopathic intracranial hypertension and chronic tension-type headache
Authors: Hannerz Jan , Ericson Kaj , Greitz Dan , Skejo Pernille Hanne Bro , Edman Gunnar
Published: October 2013

Background

Pathologic signs in orbital phlebographies have been reported in various neurological diseases.

Purpose

To study if pathologic signs in orbital phlebography may be markers of inflammation primarily affecting intracranial capillaries, which would cause intracranial hypertension.

Material and Methods

Two groups with different intracranial cerebrospinal fluid pressures (Pcsf) were compared as to inflammatory markers in serum and pathologic signs in orbital phlebographies. Nine consecutive patients with idiopathic intracranial hypertension (IIH) with bilateral papilledema and eight consecutive patients with chronic tension-type headache (CTTH) were investigated prospectively with fibrinogen, orosomucoid, haptoglobin in serum, and invasive orbital phlebograms. The angiograms were evaluated by two skilled neuroradiologists, independent of each other and without knowledge of the diagnoses or aim of the study, as to the following pathologic signs: (i) narrowing of superior ophthalmic veins; (ii) caliber changes of intraorbital veins; (iii) collaterals of intraorbital veins; (iv) flow to cavernous sinus; and (v) asymmetric drainage of cavernous sinus.

Results

Mean body mass index was >30 kg/m2 in both groups. Pcsf was >200 < 250 mm H2O in 50% of the CTTH and >350 mm H2O in all IIH patients. No difference in inflammatory markers in blood was found. The phlebographies of the IIH patients had more pathologic signs and were considered pathologic significantly more often than the ones of the CTTH patients ( P < 0.001).

Conclusion

The difference as to phlebographic pathologic signs between the IIH and the CTTH patients with different Pcsf supports the hypothesis that such phlebographic signs are markers of inflammation primarily affecting intracranial capillaries, which would disturb cerebrospinal fluid regulation causing intracranial hypertension.
Need for Cognition and Electronic Health Literacy and Subsequent Information Seeking Behaviors Among University Undergraduate Students
Authors: Britt Rebecca K. , Hatten Kristen Nicole
Published: October 2013

eHealth literacy (eHEALS) has yet to be examined with regard to need for cognition (NFC), as well as whether NFC moderates the relationship between eHealth literacy and seeking out online health information. Past research that has examined NFC as an interaction between whether interactivity on health web sites affected comprehension and attitudes, but no research to date has examined whether cognitive need interacts with eHEALS and subsequent information seeking behaviors. The present study tests eHEALS and its connection to need for cognition (NFC) in the role of online health information seeking behaviors. Results showed that high eHEALS individuals were more likely to seek out online health information and were more likely to have higher NFC scores. NFC did not emerge as a moderator on the relationship between eHealth literacy and online health information seeking behaviors. Future directions are discussed, in particular, examining eHEALS as a construct of efficacy and further need to examine eHEALS with need for cognition in health communication research.
Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis
Authors: Cervantes Francisco , Vannucchi Alessandro M. , Kiladjian Jean-Jacques , Al-Ali Haifa Kathrin , Sirulnik Andres , Stalbovskaya Viktoriya , McQuitty Mari , Hunter Deborah S. , Levy Richard S. , Passamonti Francesco , Barbui Tiziano , Barosi Giovanni , Harrison Claire N. , Knoops Laurent , Gisslinger Heinz
Published: October 2013

Key Points

Long-term analysis of the COMFORT-II Trial shows that ruxolitinib treatment results in durable reductions in splenomegaly and is well tolerated. Patients randomized to ruxolitinib showed longer overall survival than those receiving the BAT.
Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis
Authors: Walusimbi Simon , Bwanga Freddie , De Costa Ayesha , Haile Melles , Joloba Moses , Hoffner Sven
Published: October 2013

Background

Smear-negative pulmonary tuberculosis (SN-PTB), which is common in HIV-infected patients, is difficult to diagnose using smear microscopy alone. In 2007, the WHO developed an algorithm to improve the diagnosis and management of smear-negative tuberculosis in HIV prevalent and resource constrained settings. Implementation of the algorithm required individuals with presumptive TB to be initially evaluated using two sputum microscopy examinations followed by clinical diagnosis that may include chest X-ray and antibiotic treatment in smear-negative individuals. Since that time, the WHO has endorsed several new tests for diagnosis of tuberculosis. However, it is unclear how the new tests perform when compared to the WHO 2007 algorithm in diagnosis of SN-PTB. Using meta-analysis study design, we summarized and compared the accuracy of Xpert® MTB/Rif assay (GeneXpert) and Microscopic Observation Drug Susceptibility assay (MODS), with the WHO 2007 algorithm in the diagnosis of SN-PTB.

Methods

A systematic review and meta-analysis of publications on GeneXpert, or MODS, or the WHO 2007 algorithm for diagnosis of SN-PTB, using culture as reference test was performed. Meta-Disc software was used to obtain pooled sensitivity and specificity of the diagnostic methods. Heterogeneity in the accuracy estimates was tested by reviewing the generated forest plots, sROC curves and the Spearman correlation coefficient of the logit of true positive rate versus the logit of false positive rate.

Results

Twenty-four publications on all three diagnostic methods were meta-analyzed. The pooled sensitivity and specificity for detection of smear-negative pulmonary tuberculosis were 67% and 98% for GeneXpert, 73% and 91% for MODS, and 61% and 69% for WHO 2007 algorithm, respectively. The sensitivity of GeneXpert reduced from 67% to 54% when sub-group analysis of studies with patient HIV prevalence ≥30% was performed.

Conclusion

The GeneXpert, MODS, and the WHO algorithm have moderate to high accuracy for the diagnosis of SN-PTB. However, the accuracy of the tests is extremely variable. The setting and context under which the tests are conducted in addition to several other factors could explain this variability. There is therefore need to investigate these factors further. The information from these studies would inform the adoption and placement of these new tests.
DNA extraction from long-term stored urine
Authors: Hilhorst Marc , Theunissen Ruud , van Rie Henk , van Paassen Pieter , Tervaert Jan Willem Cohen
Published: October 2013

Background

Traditionally, for DNA analyses, DNA is recovered from buffy coats. Since DNA in urine has been reported to deteriorate quickly, this option is often not considered. To complete our DNA database in patients with ANCA-associated vasculitis, we aimed to extract DNA from stored urine.

Methods

Urine was stored at the time of kidney biopsy from patients included in our regional kidney biopsy database, who had given informed consent for further study. Urine was subsequently filtered, dialyzed, concentrated and freeze dried and finallyresolubilized and centrifuged. DNA was extracted using the high pure PCR template preparation kit (Roche Diagnostics). Next, concentration and purity were determined by Nanodrop analysis and by Quant-iT analysis.

Results

One hundred and eighty-one patients with ANCA-associated vasculitis were included. Of 114 patients (63%), DNA was available. From 53 of the remaining 67 patients, stored urine was available. Of the 53 samples that were processed, 46 (86.8%) yielded DNA with a mean concentration of 258.7 ng/μL (range 33.2-529) with a mean purity ratio of 1.81 (λ 260/280).

Conclusion

DNA extraction from fresh urine has been described before, yielding DNA usable for PCR analysis in healthy subjects. Storage of fresh urine at 4°C or lower temperatures results in significant degradation of the DNA, making recovery of DNA more difficult with longer periods of storage. In the current study, we demonstrated that DNA could be retrieved from subsequently filtered, dialyzed, concentrated and freeze dried urine that was stored at room temperature. In addition, we demonstrated tthat this DNA could be used for PCR analysis. This method is useful when no other material from these patients is available.
Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma
Authors: Betsunoh Hironori , Fukuda Takehiko , Anzai Naohiko , Nishihara Daisaku , Mizuno Tomoya , Yuki Hideo , Masuda Akinori , Yamaguchi Yoshiyuki , Abe Hideyuki , Yashi Masahiro , Fukabori Yoshitatsu , Yoshida Ken-Ichiro , Kamai Takao
Published: October 2013

Background

The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer.

Methods

To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting.

Results

Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors.

Conclusions

These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.
EXCAVATOR: detecting copy number variants from whole-exome sequencing data
Authors: Magi Alberto , Tattini Lorenzo , Cifola Ingrid , D’Aurizio Romina , Benelli Matteo , Mangano Eleonora , Battaglia Cristina , Bonora Elena , Kurg Ants , Seri Marco , Magini Pamela , Giusti Betti , Romeo Giovanni , Pippucci Tommaso , Bellis Gianluca De , Abbate Rosanna , Gensini Gian Franco
Published: October 2013

We developed a novel software tool, EXCAVATOR, for the detection of copy number variants (CNVs) from whole-exome sequencing data. EXCAVATOR combines a three-step normalization procedure with a novel heterogeneous hidden Markov model algorithm and a calling method that classifies genomic regions into five copy number states. We validate EXCAVATOR on three datasets and compare the results with three other methods. These analyses show that EXCAVATOR outperforms the other methods and is therefore a valuable tool for the investigation of CNVs in largescale projects, as well as in clinical research and diagnostics. EXCAVATOR is freely available at http://sourceforge.net/projects/excavatortool/.
NKG2D- and CD28-mediated costimulation regulate CD8+ T cell chemotaxis through different mechanisms: the role of Cdc42/N-WASp
Authors: Serrano-Pertierra Esther , Cernuda-Morollón Eva , López-Larrea Carlos
Published: October 2013

The activating receptor NKG2D is mainly expressed in NK cells and CD8+ T cells. NKG2D and CD28 recruit the p85 subunit of PI3K to propagate their signals through the YXXM signaling motif. The function of CD28 as a costimulatory molecule is well-established in T cells. Ligation of NKG2D on T cells costimulates TCR signaling, although the intracellular signaling pathways triggered by the two receptors may not be identical. In this study, we analyzed the function of the NKG2D receptor in human CD8+ T cell chemotaxis toward a CXCL12 gradient. We found that costimulation of the TCR together with CD28 or NKG2D impairs cell migration, although the signaling pathways responsible for this effect differ. Whereas the Rho GTPase Rac1 is activated upon TCR and costimulation via CD28 and NKG2D, the activity of Cdc42 is increased only upon CD3/NKG2D activation. Moreover, knockdown of N-WASp expression with siRNA rescues migration rates after NKG2D-mediated costimulation but not after CD3/CD28 activation. CD28- and NKG2D-mediated costimulation induces cofilin activation by dephosphorylation. Inhibition of N-WASp by wiskostatin further decreases phosphorylation levels of cofilin, although this effect is especially severe upon CD3/NKG2D activation. Thus, our findings reveal new differences in the signaling pathways between CD28- and NKG2D-mediated costimulation in the regulation of cell chemotaxis in human CD8+ T cells.
Calcium-Sensing Receptor Mediates Ca2+ Homeostasis by Modulating Expression of PTH and Stanniocalcin
Authors: Lin Chia-Hao , Su Che-Hsien , Hwang Pung-Pung
Published: October 2013

Regulation of the synthesis and/or secretion of hypocalcemic and hypercalcemic hormones by the calcium-sensing receptor (CaSR) is believed to be a major pathway for maintaining Ca2+ homeostasis in vertebrates, based primarily on findings in mammals. However, understanding the evolution of this physiological process requires that it be described in nonmammalian species. Here, we describe the use of zebrafish as a model to investigate whether CaSR contributes to body fluid Ca2+ homeostasis by regulating synthesis of hypercalcemic (PTH1 and PTH2) and hypocalcemic (stanniocalcin [STC]) hormones. We report that PTH1, but not PTH2, increases Ca2+ uptake through stimulation of the expression of the gene encoding the epithelial Ca2+ channel (ecac). Furthermore, we demonstrate that CaSR, as a Ca2+ sensor, may affect stc-1 and pth1 expressions differently, thereby suppressing ecac expression and Ca2+ uptake. Finally, we show that CaSR knockdown has time-dependent effects on STC-1 and PTH1 expression, and these 2 hormones have mutual effects on the expression, thus forming a possible counterbalance. These findings enhance our understanding of CaSR-PTH-STC control of Ca2+ homeostasis in vertebrates.
Leonhard Euler’s Unfinished Theory of Rhythm
Authors: Grant Roger Mathew
Published: October 2013

The music-theoretical formulations of the early modern mathematician Leonhard Euler (1707-83) are customarily remembered—and often dismissed—for their unconventional rankings of the consonances. A closer examination of Euler’s writings, however, reveals that he intended his theory of consonance to assess and explain the interaction of rhythms as well as the interaction of pitches. At several points in his 1739 Tentamen novae theoriae musicae (Attempt at a New Theory of Music), Euler suggests that everything he has written about consonance should also apply to duration. Curiously, the transference of Euler’s consonance principles to the temporal elements of music renders a theory that has interesting and provocative connections to several contemporary theories of rhythm and meter, such as those of Harald Krebs, Richard Cohn, Daphne Leong, and Scott Murphy. This article sketches the theory of rhythm that Euler suggested but never finished. The analytical applications of this model are surprising and extend beyond the music of the eighteenth century. Elaborating Euler’s unfinished theory sheds light not only on his work as a music theorist but also—and perhaps more provocatively—on twenty-first-century music theory.
Action and Agency Revisited
Authors: Monahan Seth
Published: October 2013

For centuries, metaphors of agency have pervaded music-analytical writing. Today, as in generations past, critics routinely vivify their analytical narrations by ascribing sentience, emotion, and volition to musical works, their internal elements (pitch classes, contrapuntal voices, etc.), and fictionalized versions of their composers. This study investigates the use of such agential conceits and the conventions that seem to govern them, using the opening of Beethoven’s A-minor Quartet, op. 132, as a central test case. The descriptive model it constructs borrows key concepts from the seemingly incompatible agential theories of Edward T. Cone, who heard music’s agencies as obligatory and hierarchically nested, and Fred E. Maus, who clarified the poietic function of such agential ascriptions while stressing their provisional, ad hoc, and often ephemeral nature. After arriving at a fourfold hierarchy of fictional agent types—the individuated element, the work-persona, the fictional composer, and the analyst—the study then examines their relational logic, with special interest in (1) the ways that explicit agency claims at one level can spin off implicit claims at another and (2) the deeper consistencies that underlie seemingly contradictory accounts in which agency shifts from one locus to another. It also considers the various alternative guises (or avatars) that these agent classes take and the kinds of semantic ambiguities that often arise from their use.
Eukaryotic ribosome biogenesis at a glance
Authors: Thomson Emma , Ferreira-Cerca Sébastien , Hurt Ed
Published: October 2013

Ribosomes play a pivotal role in the molecular life of every cell. Moreover, synthesis of ribosomes is one of the most energetically demanding of all cellular processes. In eukaryotic cells, ribosome biogenesis requires the coordinated activity of all three RNA polymerases and the orchestrated work of many (>200) transiently associated ribosome assembly factors. The biogenesis of ribosomes is a tightly regulated activity and it is inextricably linked to other fundamental cellular processes, including growth and cell division. Furthermore, recent studies have demonstrated that defects in ribosome biogenesis are associated with several hereditary diseases. In this Cell Science at a Glance article and the accompanying poster, we summarise the current knowledge on eukaryotic ribosome biogenesis, with an emphasis on the yeast model system.
Boron Diffusion in Surface-Treated Framing Lumber
Authors: Lebow Patricia K. , Lebow Stan T. , Halverson Steven A.
Published: October 2013

The extent of boron penetration in framing lumber treated by spray applications during construction is not well quantified. This study evaluated the effect of formulation and concentration on diffusion of boron in lumber specimens that were equilibrated in conditions that produced wood moisture contents of 18 to 21 percent. One set of specimens was pressure treated with water before equilibration. Borate solutions were prepared from powdered disodium octaborate tetrahydrate (DOT) or from two commercial glycol-borate formulations and applied with a garden-type sprayer. The DOT solution was applied at a 15 percent concentration, while the glycol-borate formulations were applied at 15 and 23 percent concentrations. Boron penetration was evaluated after 6, 13, and 26 weeks and boron retention after 26 weeks of diffusion. Boron penetration was observed for all treatments and progressed for the duration of the study. There was no significant penetration difference between the powdered DOT and glycol-borate solutions when they were applied at the same (15%) DOT concentration. However, after 6 weeks, the glycol-borate solutions applied at the 23 percent DOT concentration produced significantly greater depth of penetration than the solutions applied at the 15 percent concentration. The exception was the 15 percent DOT solution applied to the specimens that had been wetted and then dried down to equilibrium conditions. These specimens had the greatest penetration, possibly as a result of their higher equilibrium moisture content. Retention analysis revealed that the glycol-borate solutions applied at the 23 percent DOT concentration yielded significantly greater boron retentions in the outer assay zone. This effect was less apparent for the inner assay zones. Although boron retentions in the outer assay zone were below those standardized for pressure-treated wood, in some cases they exceeded reported concentrations needed for protection against termites and decay fungi.
Circulating Fetuin-A and Risk of Ischemic Stroke in Women
Authors: Jiménez Monik C , Sun Qi , Schürks Markus , Hu Frank B , Manson JoAnn E , Rexrode Kathryn M
Published: October 2013

BACKGROUND

Fetuin-A, a protein secreted primarily by the liver, has been associated with nonalcoholic fatty liver disease and insulin resistance. In a recent study, higher circulating fetuin-A was associated with cardiovascular events, particularly ischemic stroke. However, these data have not been replicated.

METHODS

A nested case control design was used to examine the relationship between fetuin-A and ischemic stroke among female participants of the Nurses' Health Study. Fetuin-A was measured in blood samples collected and stored between 1989 and 1990. A total of 459 incident cases of ischemic stroke were identified and confirmed by medical records according to the National Survey of Stroke criteria between 1990 and 2006 and matched to 459 controls by age, race/ethnicity, date of sample collection, menopausal status, postmenopausal hormone use, and smoking status. The association between fetuin-A and ischemic stroke was modeled using conditional logistic regression.

RESULTS

Circulating fetuin-A was higher in women (P < 0.01) who reported increased body mass index (BMI) of ≥25 kg/m2, total cholesterol ≥200 mg/dL, high-sensitivity C-reactive protein ≥3 mg/L, and current hormone use at baseline. Significant partial Spearman correlations (P < 0.001), adjusted for matching factors, were found between measured concentrations of fetuin-A and triglycerides (r = 0.20), C-reactive protein (r = 0.14), and BMI (r = 0.15). Fetuin-A quartiles were not significantly associated with increased risk of incident ischemic stroke when adjusted for matching factors (relative risk, 1.03; 95% CI, 0.69–1.54, extreme quartiles); additional adjustment for lifestyle factors or cardiovascular disease risk factors and biomarkers did not alter results.

CONCLUSIONS

In this sample of women, fetuin-A was not significantly associated with risk of ischemic stroke. Further research is needed to explore this association.
Netrin-1 Promotes Excitatory Synaptogenesis between Cortical Neurons by Initiating Synapse Assembly
Authors: Goldman Jennifer S. , Ashour Mohammed A. , Magdesian Margaret H. , Tritsch Nicolas X. , Harris Stephanie N. , Christofi Nicolas , Chemali Raja , Stern Yaakov E. , Thompson-Steckel Greta , Gris Pavel , Glasgow Stephen D. , Grutter Peter , Bouchard Jean-Francois , Ruthazer Edward S. , Stellwagen David , Kennedy Timothy E.
Published: October 2013

Netrin-1 is a secreted protein that directs long-range axon guidance during early stages of neural circuit formation and continues to be expressed in the mammalian forebrain during the postnatal period of peak synapse formation. Here we demonstrate a synaptogenic function of netrin-1 in rat and mouse cortical neurons and investigate the underlying mechanism. We report that netrin-1 and its receptor DCC are widely expressed by neurons in the developing mammalian cortex during synapse formation and are enriched at synapsesin vivo. We detect DCC protein distributed along the axons and dendrites of cultured cortical neurons and provide evidence that newly translated netrin-1 is selectively transported to dendrites. Using gain and loss of function manipulations, we demonstrate that netrin-1 increases the number and strength of excitatory synapses made between developing cortical neurons. We show that netrin-1 increases the complexity of axon and dendrite arbors, thereby increasing the probability of contact. At sites of contact, netrin-1 promotes adhesion, while locally enriching and reorganizing the underlying actin cytoskeleton through Src family kinase signaling and m-Tor-dependent protein translation to locally cluster presynaptic and postsynaptic proteins. Finally, we demonstrate using whole-cell patch-clamp electrophysiology that netrin-1 increases the frequency and amplitude of mEPSCs recorded from cortical pyramidal neurons. These findings identify netrin-1 as a synapse-enriched protein that promotes synaptogenesis between mammalian cortical neurons.
Receptor Interacting Protein Kinase-Mediated Necrosis Contributes to Cone and Rod Photoreceptor Degeneration in the Retina Lacking Interphotoreceptor Retinoid-Binding Protein
Authors: Sato Kota , Li Songhua , Gordon William C. , He Jibao , Liou Gregory I. , Hill James M. , Travis Gabriel H. , Bazan Nicolas G. , Jin Minghao
Published: October 2013

Interphotoreceptor retinoid-binding protein (IRBP) secreted by photoreceptors plays a pivotal role in photoreceptor survival with an unknown mechanism. A mutation in the humanIRBPhas been linked to retinitis pigmentosa, a progressive retinal degenerative disease. Mice lacking IRBP display severe early and progressive photoreceptor degeneration. However, the signaling pathway(s) leading to photoreceptor death in IRBP-deficient mice remains poorly understood. Here, we show that amounts of tumor necrosis factor-α (TNF-α) in the interphotoreceptor matrix and retinas ofIrbp−/−mice were increased more than 10-fold and fivefold, respectively, compared with those in wild-type mice. Moreover, TNF-α receptor 1, an important membrane death receptor that mediates both programmed apoptosis and necrosis, was also significantly increased inIrbp−/−retina, and was colocalized with peanut agglutinin to theIrbp−/−cone outer segments. Although these death signaling proteins were increased, the caspase-dependent and independent apoptotic pathways were mildly activated in theIrbp−/−retinas, suggesting that other cell death mechanism(s) also contributes to the extensive photoreceptor degeneration inIrbp−/−retina. We found that receptor interacting protein 1 and 3 (RIP1 and RIP3) kinases, the intracellular key mediators of TNF-induced cellular necrosis, were elevated at least threefold in theIrbp−/−retinas. Moreover, pharmacological inhibition of RIP1 kinase significantly prevented cone and rod photoreceptor degeneration inIrbp−/−mice. These results reveal that RIP kinase-mediated necrosis strongly contributes to cone and rod degeneration inIrbp−/−mice, implicating the TNF-RIP pathway as a potential therapeutic target to prevent or delay photoreceptor degeneration in patients with retinitis pigmentosa caused by IRBP mutation.