bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of valacyclovir on HIV and HSV-2 in HIV-infected persons on antiretroviral therapy with previously unrecognised HSV-2
Authors: Van Wagoner Nicholas , Geisler William M , Bachmann Laura H , Hook Edward W
Published: August 2014

In the absence of antiretroviral therapy, valacyclovir may reduce HIV viral load and increase CD4+ T-lymphocyte count. We sought to evaluate the impact of valacyclovir on HIV and HSV-2 in co-infected patients receiving antiretroviral therapy with previously unrecognised HSV-2 infection. A prospective, randomised-controlled, 24-week trial of valacyclovir 1000 mg was performed. Mean CD4+ T-lymphocyte count at 24 weeks compared to baseline CD4+ T-lymphocyte count was the primary outcome. HIV viral load suppression, HSV-2 outbreaks and asymptomatic HSV-2 shedding were secondary outcomes. Participants were randomised to valacyclovir (N = 66) or placebo (N = 35). Study completion was 64%. There was no change in 24 weeks compared to baseline CD4+ T-lymphocyte count in either group (valacyclovir p = 0.91, placebo p = 0.59) or the proportion with HIV viral load suppression (valacyclovir p = 0.75, placebo p = 1.0). Genital HSV and asymptomatic HSV-2 shedding were rare. Valacyclovir had no effect on CD4+ T-lymphocyte count or HIV viral load in this population. Valacyclovir may reduce clinical outbreaks and asymptomatic HSV-2 shedding, but the rarity of these events, along with its lack of benefit on HIV, does not support its use in this clinical setting.
Accelerated longitudinal designs: An overview of modelling, power, costs and handling missing data
Authors: Galbraith Sally , Bowden Jack , Mander Adrian
Published: August 2014

Longitudinal studies are often used to investigate age-related developmental change. Whereas a single cohort design takes a group of individuals at the same initial age and follows them over time, an accelerated longitudinal design takes multiple single cohorts, each one starting at a different age. The main advantage of an accelerated longitudinal design is its ability to span the age range of interest in a shorter period of time than would be possible with a single cohort longitudinal design. This paper considers design issues for accelerated longitudinal studies. A linear mixed effect model is considered to describe the responses over age with random effects for intercept and slope parameters. Random and fixed cohort effects are used to cope with the potential bias accelerated longitudinal designs have due to multiple cohorts. The impact of other factors such as costs and the impact of dropouts on the power of testing or the precision of estimating parameters are examined. As duration-related costs increase relative to recruitment costs the best designs shift towards shorter duration and eventually cross-sectional design being best. For designs with the same duration but differing interval between measurements, we found there was a cutoff point for measurement costs relative to recruitment costs relating to frequency of measurements. Under our model of 30% dropout there was a maximum power loss of 7%.
Promoting recovery via an integrated model of care to deliver a bed-based, mental health prevention and recovery centre
Authors: Lee Stuart J , Collister Laura , Stafrace Simon , Crowther Elizabeth , Kroschel Jon , Kulkarni Jayashri
Published: August 2014

Objective:

This research was conducted in order to explore the experience of care and outcomes for people entering a bed-based step-up/step-down Prevention and Recovery Centre (PARC).

Methods:

An audit of files for PARC participants in 2010 collected demographic (age, gender, and marital, housing, employment and education/training status) and clinical measures (length of stay, entry and exit outcome measures, psychiatric hospital use). Participants were also invited to a feedback group to discuss their PARC experience.

Results:

In 2010, 118 people entered PARC. Most were single and unemployed and 35% were in temporary housing or homeless. In the six months following PARC exit, participants spent significantly less time in psychiatric hospital than in the six months prior to entry ( p<0.001). Significant reductions in clinician-rated difficulties were documented at exit ( p<0.001). For 40 episodes of care with self-report measures at entry and exit, significant reductions in difficulties with relating to self/others ( p=0.004), daily living/role functioning ( p=0.006), and depression/anxiety ( p=0.019) were seen. Twelve participants attended a feedback group. Positive aspects of PARC included: supportive and caring staff; help with practical issues or community access; therapeutic activities and learning about health; and socialization opportunities.

Conclusions:

A step-up/step-down PARC can facilitate recovery for people with mental illness through promoting independence and illness self-management.
Evaluating the introduction of joint crisis plans into routine clinical practice in four community mental health services
Authors: Williams Theresa M , Smith Geoffrey P , Lumbus Anita M
Published: August 2014

Objective:

Our aim was to evaluate the implementation of joint crisis planning into routine clinical practice in community mental health services in Western Australia.

Method:

Four community mental health services, two metropolitan and two country based, were invited to participate in a 1-year pilot program to field test a crisis planning tool and the implementation process with a view to then rolling it out across Western Australia. Training and extensive support was offered to staff at the four sites.

Results:

Consumers experienced the process as both empowering and therapeutic. Despite acknowledgement of the value of interagency collaboration in the planning process, almost all plans were completed by consumers with their case managers. The most conspicuous finding was the marked difference in the number of completed plans at each site.

Conclusions:

This study supports previous research findings that joint crisis planning enhances the therapeutic relationship and empowers consumers. Organisational readiness was a major factor in the differential uptake of crisis plans between sites. Our study highlights the critical importance of addressing the context and culture of each individual service in which a new intervention is being introduced as part of the implementation process.
What has happened to the practice of short term dynamic psychotherapy in Australia’s mental health services? A multidisciplinary training programme in Western Sydney
Authors: Haliburn Joan , Baker Ashley
Published: August 2014

Objective:

Short term psychodynamic psychotherapies have been markedly phased out of Australia’s mental health services. This paper aims to describe the successful introduction of a Conversational Model of Short Term Intensive Psychodynamic Psychotherapy into a public health service in an attempt to revive its practice.

Method:

A brief review of relevant papers in the Royal Australian & New Zealand College of Psychiatrists journals since 1980 gives a background to the decline of dynamic psychotherapy in Australia. The development of a Conversational Model of Short Term Intensive Psychodynamic Psychotherapy in the author’s private practice over 20 years, and its introduction into a hospital-based training programme are described.

Results:

A structured programme by scholarship has been offered yearly since 2011 to 10 multidisciplinary mental health clinicians of the Western Sydney Health District. Trainees see two patients from their own service. Over three years, 29 trainees have treated 57 patients with weekly supervision provided.

Conclusions:

The model has been easily learned. Trainees report a sense of re-invigoration, refinement of existing skills and acquisition of new skills. Resolution of problems in a significant number of patients is noted and improvement and satisfaction reported by others. A valuable service is provided and research is underway.
“Being Heard”
Authors: Wilkenfeld Bonnie Fader
Published: August 2014

This article examines qualitative research dilemmas encountered with participants who have communication, physical and cognitive impairments. A review of the extant literature indicates the importance of identifying and resolving these research conundrums. The author will describe a qualitative study on identity formation in individuals with developmental disabilities (IWDD) as a medium to identify and explore the various dilemmas encountered while utilizing in depth interviews. Issues which arose during the research process include concerns about the potential of participants to be vulnerable to coercion, upholding privacy/confidentiality, role confusion and expressive language barriers in participating in narrative discourse; access to participants was an additional concern. Findings from this study indicated that IWDD benefit from participation in qualitative research. Three overarching themes were manifested: being heard, helping others, and enjoying the process. Suggestions for addressing the various dilemmas which might inhibit IWDD from participating in qualitative research are discussed and implications for social work practice and social justice initiatives are delineated.
Barriers to Living Donation Among Low-Resource Hispanics
Authors: Siegel Jason T. , O’Brien Erin Keely , Alvaro Eusebio M. , Poulsen Julie A.
Published: August 2014

Hispanics are disproportionately affected by renal failure. Although living donation has been heralded as a potential means for alleviating the need for transplantable kidneys, a nuanced understanding of the obstacles faced by Hispanics is necessary. In our study, we conducted focus groups with 28 first-generation Spanish-dominant Hispanic renal patients. Although some of the barriers that emerged were akin to those reported in previous research (e.g., a lack of knowledge about the process), others were unique. Rarely chronicled barriers include the disqualification of family members because of medical issues, potential donors being unable to miss work, disqualification of family members who are undocumented, concern that potential donors cannot support their family if they donate, and declining social support because of illness. The interaction among this constellation of barriers makes living donation particularly difficult among this population. Investigations focused on the unique barriers faced by these low-resource individuals are warranted.
Meanings of Being Received and Met by Others as Experienced by Women With Fibromyalgia
Authors: Juuso Päivi , Skär Lisa , Olsson Malin , Söderberg Siv
Published: August 2014

Fibromyalgia (FM) is a common chronic pain syndrome that mostly affects middle-aged women. Our aim with this study was to elucidate meanings of being received and met by others as experienced by women with FM. Interviews with a narrative approach were conducted with 9 women. We analyzed the transcribed interviews with a phenomenological hermeneutical interpretation. The findings revealed two themes: being seen as a malingerer and being acknowledged. Meanings of being received and met by others, as experienced by women with FM, can be understood as a movement between the two perspectives. When they were acknowledged, their feelings of security and trust increased, but the women could not rely on this because others received and met them in such an unpredictable manner.
Diffusion of chemically reacting fluids through nonlinear elastic solids: mixture model and stabilized methods
Authors: Hall R , Gajendran H , Masud A
Published: August 2014

This paper presents a stabilized mixed finite element method for advection-diffusion-reaction phenomena that involve an anisotropic viscous fluid diffusing and chemically reacting with an anisotropic elastic solid. The reactive fluid–solid mixture theory of Hall and Rajagopal (Diffusion of a fluid through an anisotropically chemically reacting thermoelastic body within the context of mixture theory. Math Mech Solid 2012; 17: 131–164) is employed wherein energy and entropy production relations are captured via an equation describing the Lagrange multiplier that results from imposing the constraint of maximum rate of entropy production. The primary partial differential equations are thus reduced to the balance of mass and balance of linear momentum equations for the fluid and the solid, together with an equation for the Lagrange multiplier. Present implementation considers a simplification of the full system of governing equations in the context of isothermal problems, although anisothermal studies are being investigated. The method is applied to problems involving Fickian diffusion, oxidation of PMR-15 polyimide resin, and slurry infiltration, within a one-dimensional finite element context. Results of the oxidation modeling of Tandon et al. (Modeling of oxidative development in PMR-15 resin. Polym Degrad Stab 2006; 91: 1861–1869) are recovered by employing the reaction kinetics model and properties assumed there; the only additional assumed properties are two constants describing coupled chemomechanical and purely chemical dissipation, and standard values for viscosity of air and PMR-15 stiffness properties. The present model provides the individual constituent kinematic and kinetic behaviors, thus adding rich detail to the interpretation of the process in comparison to the original treatment. The last problem considered is slurry infiltration that demonstrates the applicability of the model to account for the imposed mass deposition process and consequent effects on the kinematic and kinetic behaviors of the constituents.
ASPA’s Section on Transportation Policy and Administration
Authors: Plant Jeremy F. , Stich Bethany
Published: August 2014

The Section on Transportation Policy and Administration (STPA) of the American Society for Public Administration was chartered in 1992 as an organization dedicated to bringing together scholars, practitioners, and students interested in the role played by transportation in society. Although transportation policy and administration is somewhat specialized as a subject matter area in public administration, STPA grew rapidly in the 1990s due in large part to a stable group of founding members who provided both intellectual and organizational leadership. This article reviews the growth and development of STPA from its early years to the present. Attention is given to section activities, including publications, newsletters, awards, and conference presentations. Two themes are prevalent throughout the review: the importance of committed, diverse, and stable leadership and the high level of intellectual and professional discourse that has characterized the work of the section.
Under construction: Undergraduates’ perceptions of their music teacher role-identities
Authors: Draves Tami J.
Published: August 2014

The purpose of this research was to explore how participants perceived themselves as preservice music teachers. Bouij’s (1998) salient role-identities in music education served as an a priori theoretical framework. By investigating participants’ perceptions of role-identity, some of the socialization processes that contributed to identity development were also revealed. Multiple forms of data were collected including interviews, both individual and focus group, and field notes from peer teaching sessions. Analysis resulted in three themes: (a) Role-Identities, (b) Peers, and (c) Authentic Teaching Experiences. Participants believed they embodied a primary and secondary role-identity and perceived subtle expansions of their role-identities as they progressed through their undergraduate degree program. Participants discussed the importance of their peers and authentic teaching experiences in their development as music teachers. Suggestions for practice and further research are provided.
Effect of cylindricity on the tribological performance of heavily loaded slow-speed journal bearing
Authors: Muzakkir SM , Lijesh KP , Hirani Harish , Thakre GD
Published: August 2014

Theoretical and experimental studies have been conducted to analyze the effect of cylindricity on performance of a heavily loaded slow-speed journal bearing. The design of experiments has been employed to quantify the effect of bearing clearance and cylindricity on the wear. Since the initial experimental results did not establish any definitive trend, the effect of running-in was considered and the sliding distance required for reaching steady wear was estimated by conducting tests on lubricity tester employing conformal block and disc configuration. Further experiments incorporating the running-in were then conducted on journal bearing test rig. The wear coefficient was determined using the steady wear data obtained experimentally on the lubricity tester. A mathematical model was formulated to estimate wear of the bearing incorporating the actual cylindricity. The theoretical and experimental results corresponded well indicating a strong dependence of wear on the bearing cylindricity at the contact zone.
Serum anti-Müllerian hormone levels in reproductive-age women with relapsing–remitting multiple sclerosis
Authors: Thöne Jan , Kollar Susanne , Nousome Darryl , Ellrichmann Gisa , Kleiter Ingo , Gold Ralf , Hellwig Kerstin
Published: August 2014

Background:

Fertility might be reduced in women with multiple sclerosis (MS), although only few studies exist and the underlying reasons are not well understood. Similar to other autoimmune diseases, a decreased ovarian reserve may contribute to impaired fertility in women with MS. Anti-Müllerian hormone (AMH) is an established marker of the ovarian reserve and an objective indicator of ovarian function, which is independent of the hypothalamus-pituitary-gonadal axis function.

Objective:

The purpose of this study was to determine AMH levels in females with relapsing–remitting MS (RRMS) in combination with other reproduction and lifestyle factors.

Methods:

A total of 76 reproductive-age females with RRMS and 58 healthy controls were included in this case control study. An enzymatically amplified two-site immunoassay was used to measure serum AMH level.

Results:

Mean AMH level was significantly decreased in females with RRMS ( p<0.04), and a higher proportion of females with RRMS showed very low AMH values (<0.4 ng/ml) compared to healthy controls ( p<0.05). The majority of these women were currently without any disease modifying treatment.

Conclusions:

Our data contribute to our understanding of impaired fertility in women with MS. The unexpected finding that the majority of MS subjects with very low AMH levels were currently without medication requires further evaluation.
Similar biological effect of high-dose oral versus intravenous methylprednisolone in multiple sclerosis relapses
Authors: Grau-López L , Teniente-Serra A , Tintoré M , Rovira A , Ramió-Torrenta L , Brieva L , Saiz A , Cano A , Carmona O , Hervás JV , Martínez-Cáceres EM , Ramo-Tello C
Published: August 2014

Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 ( p = 0.05 / p = 0.03) and at week 4 ( p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP.

Trial registration: clinicaltrials.gov identifier: NCT00753792
The role of assessment packages for diagnostic consultations: A conversation analytic perspective
Authors: Rossen Camilla B , Buus Niels , Stenager Egon , Stenager Elsebeth
Published: August 2014

This article reports a conversation analysis of assessment package consultations. Healthcare delivery packages belong to a highly structured mode of healthcare delivery, in which specific courses of healthcare interventions related to assessment and treatment are predefined, both as to timing and content. Assessment packages are widely used in an increasing number of medical specialities; however, there is a lack of knowledge about how packaged assessment influences the interaction between doctor and patient. In this study, we investigate the final consultation in assessment packages, which is when the final clarification of the patient’s symptoms takes place. The primary data of the study were eight audio recordings of consultations, and the secondary data were ethnographic field descriptions. In most consultations, packaged assessment was a resource as it provided fast and efficient clarification. In most cases, clarification was treated as good news since it either confirmed the absence of a serious disease or resulted in a diagnosis leading to relevant treatment offers. However, in some cases, clarification was not perceived as good news. This was the case in consultations with patients whose goal was to leave the consultation with clarification in the form of a definite diagnosis, but who were not offered such clarification. These patients negotiated the outcome of the consultation by applying implicit and explicit pressure, which induced the doctors to disregard the boundaries of the package and offer the patient more tests. The study highlights some of the problems related to introducing narrow, specialized package assessment.
Towards using relevant collegial contexts for academic development
Authors: Heinrich Eva
Published: August 2014

Many academic development initiatives build on community-based approaches, such as communities of practice or learning communities. While these initiatives are largely successful for the individual academics involved, low participation rates prevent wide-reaching impact on learning about teaching. The research discussed in this article aims at reaching larger numbers of academics. It proposes to investigate ‘teaching groups’, which are defined as the already existing collegial contexts around academics based on shared teaching responsibilities. The teaching groups of focus group participants from a New Zealand university are identified; structure, interactions and atmosphere within these groups are explored. The research derives a scale of desirability for teaching groups, reaching from functioning to tight-knit groups. This scale is applied to the groups of study participants and reveals wide scope for improvement towards the development of stronger community characteristics. Future research into understanding why teaching groups show certain characteristics is recommended.
Communicating beyond Information? Mobile Phones and Mobilization to Offline Protests in China
Authors: Liu Jun
Published: August 2014

The past decade has seen an increase in the use of the mobile phone as a facilitator for political protests. Yet, to date, how the use of mobile phones affects participation in protests remains unclear. This study employs the distinction between communication and metacommunication to investigate the informational and relational dimensions of the mobile phone in protest mobilization in four cases in China. By drawing upon fifty-three in-depth interviews, the results reveal that, in addition to communicating mobilizing information, participants metacommunicate their mutual relationships via mobile phones in the mobilization process, and this shapes the practice of information exchange and the interpretation of information. As the pivotal driving force for protest participation, this metacommunication involves an engagement of reciprocal relationships, generates a sense of mutual engagement, and enhances a feeling of solidarity. The dynamic of the mobile phone as a facilitator in protest lies in its embedding of metacommunication beyond information dissemination.
Foodies Remaking Cities
Authors: Hanser Amy , Hyde Zachary
Published: August 2014

Drawing examples from the North American food cart movement and restaurant scenes in gentrifying neighborhoods, sociologists Amy Hanser and Zachary Hyde explore the role of food in transforming urban spaces.
Mapping the Flavors of New York City
Authors: Kang-Brown Hanna , Kang-Brown Jacob
Published: August 2014

Artist Hanna Kang-Brown and Sociologist Jacob Kang-Brown explores food as a medium for understanding the U.S. census, representing neighborhood data with spices and using the tasting experience to create a new conversational space in which to talk about the ways in which we identify ourselves and others and how that is shaped by census design.
Rhetorics of judge-penitence: Claiming moral superiority through admissions of past wrongdoing
Authors: Forchtner Bernhard
Published: August 2014

Over recent decades, public admissions of our past wrongdoing have become increasingly widespread. Usually, these practices are viewed as facilitating more inclusive modes of assimilating collective memories into collective identities. However, this article argues that such admissions can enable claims for having learnt the lessons which ultimately justify discrediting an external other as morally inferior vis-a-vis us. I do so by drawing on Albert Camus’ novel The Fall and its leitmotif ‘[t]he more I accuse myself, the more I have a right to judge you’. I demarcate such rhetorics of judge-penitence from claims for having learnt the lessons which are not based on narrating past wrongdoing as our wrongdoing ( rhetorics of judging) and self-critical admissions ( rhetorics of penitence). By differentiating and conceptualising these three utilisations of the claim for having learnt the lessons, and by drawing on a wide range of examples, I illustrate that even penitent sinners might turn into complacent judges.
A proposed field test method and an assessment of the rotational drag of contemporary front bicycle wheels
Authors: Dyer Bryce TJ , Noroozi Siamak
Published: August 2014

A proposed field test method was investigated to ascertain the differences in aerodynamic rotational drag between nine contemporary bicycle wheels and its robustness as an assessment method. The investigated test method achieved a very high level of intra-test repeatability of both power and speed data. However, the method did not obtain satisfactory levels of test–retest repeatability when the experiment was performed for the second time. However, the wheels that were tested at both events maintained their same ranking respective to each other at speeds above 8 m/s. The test method is recommended for the relative assessment of rotational aerodynamic drag. Five of the contemporary design wheels produced similar levels of rotational drag to each other, but additionally these were also close to that of a full disc wheel design. As a result, it is proposed that there is limited scope for further reductions in the rotational aerodynamic drag of contemporary bicycle front wheels. Future developments in bicycle front wheel research should therefore be directed towards investigating the translational aerodynamic drag.
Meniscus Injuries Alter the Kinematics of Knees With Anterior Cruciate Ligament Deficiency
Authors: Hosseini Ali , Li Jing-Sheng , Gill Thomas J. , Li Guoan
Published: August 2014

Background:

Most knee joint biomechanics studies have involved knees with an isolated anterior cruciate ligament (ACL) injury. However, a large portion of patients with injured ACLs have accompanied meniscus tearing. In this study, the in vivo alteration of knee biomechanics after tearing the ACL with or without combined medial or lateral meniscus tear was investigated during stair-ascending activity.

Hypothesis:

The kinematic behavior of ACL-deficient knees changes with a combined medial or lateral meniscus tear.

Study Design:

Controlled laboratory study.

Methods:

Twenty-one patients with injured ACLs (contralateral side intact) were recruited before undergoing ACL reconstruction. Among these patients, 5 had isolated ACL injuries (group I), 8 had combined ACL and medial meniscus injuries (group II), and 8 had combined ACL and lateral meniscus injuries (group III). Bilateral magnetic resonance scans were obtained on each patient to construct 3-dimensional anatomic knee models. Both knees were then scanned during stair-climbing activity using a dual fluoroscopic imaging system. The knee kinematics during stair climbing were reproduced using a bone model image matching method. Anteroposterior and mediolateral translations and axial tibial rotation of the knee during stair ascent were then compared between the injured and intact contralateral knees of the patients.

Results:

On average, injured knees in groups I and III showed more than 2 mm increased anterior tibial translation close to full knee extension. In group II, no statistically significant difference was observed between the injured and contralateral side in anteroposterior translation. Near full extension, in groups I and III, injured knees had less than 1 mm of increased medial tibial translation compared with the contralateral side, whereas in group II, a 1.0-mm increase in lateral tibial shift was observed in the injured knees. With regard to axial tibial rotation, group I showed an increased external tibial rotation (approximately 5°), group II had little variation, whereas group III had increased internal tibial rotation (approximately 3°).

Conclusion:

The results of this study demonstrate that a combined ACL/meniscus injury could alter the kinematics of ACL-injured knees in a different way compared with knees with isolated ACL tears, depending on the pattern of the meniscus tear. Considering the varying effect of meniscus injuries on knee joint kinematics, future studies might focus on specific treatment of patients with combined ACL and meniscus injuries to protect the joint from abnormal kinematics and subsequent postoperative cartilage degeneration.
NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report
Authors: Ostronoff Fabiana , Othus Megan , Gerbing Robert B. , Loken Michael R. , Raimondi Susana C. , Hirsch Betsy A. , Lange Beverly J. , Petersdorf Stephen , Radich Jerald , Appelbaum Frederick R. , Gamis Alan S. , Alonzo Todd A. , Meshinchi Soheil
Published: August 2014

Key Points

Coexpression of NUP98/NSD1 and FLT3/ITD in AML is associated with very low complete remission rates and poor survival. It is the interaction between NUP98/NSD1 and FLT3/ITD that determines poor outcome in NUP98/NSD1-associated AML.
Clinical and genetic characterization of basal cell carcinoma and breast cancer in a single patient
Authors: Morelle Alessandra , Cericatto Rodrigo , Krepischi Ana Cristina Victorino , Ruiz Itamar Romano Garcia
Published: August 2014

Introduction

Multiple environmental and genetic factors are involved with the development of basal cell carcinomas (BCC), as well as with breast cancers. Tumor initiation and progression are often associated with genomic instability such as aneuploidies, and gains or losses of large chromosomal segments, known as copy number alterations (CNAs). CNAs have been successfully detected using the microarray comparative genomic hybridization technique (array-CGH) at high resolution. Data thus obtained are useful to identify specific genomic aberrations, to classify tumor stages, and to stratify subgroups of patients with different prognosis and clinical behaviors.

Case description

Clinical study of a 66-year-old white female identified two primary tumors, a ductal invasive grade-II carcinoma of the breast, and one nodular BCC. Germline and tumor genomic survey utilized the 180 K array-CGH analysis to investigate chromosomal alterations.

Discussion and evaluation

Several chromosomal anomalies were detected in the breast tumor genome, including focal ~422 Kb 13q13.3 microdeletion. In the BCC, amplification of a chromosome 6 spanning the centromere region between the cytobands 6p23 and 6q12 was identified. Several 6p amplified genes correspond to families of histone and human leukocyte antigen genes, whereas some of the CNAs found in the breast tumor are uncommon. No germline CNA was detected in the normal skin of the patient at this technical resolution.

Conclusion

CNAs found in the two different tumors of the patient constitute independent events arisen in the somatic lineage. Relevant genes to both carcinogenesis and progression are to be affected by these CNAs.
Determining delayed admission to the intensive care unit for mechanically ventilated patients in the emergency department
Authors: Hung Shih-Chiang , Kung Chia-Te , Hung Chih-Wei , Liu Ber-Ming , Liu Jien-Wei , Chew Ghee , Chuang Hung-Yi , Lee Wen-Huei , Lee Tzu-Chi
Published: August 2014

Introduction

The adverse effects of delayed admission to the intensive care unit (ICU) have been recognized in previous studies. However, the definitions of delayed admission vary across studies. This study proposed a model to define `delayed admission’, and explored the effect of ICU waiting time on patients’ outcome.

Methods

This retrospective cohort study included nontraumatic adult patients on mechanical ventilation in the emergency department (ED), from July 2009 to June 2010. The primary outcomes measures were 21-ventilator-day mortality and prolonged hospital stays (over 30 days). Models of Cox regression and logistic regression were used for multivariate analysis. The non-delayed ICU waiting was defined as a period in which the time effect on mortality was not statistically significant in a Cox regression model. To identify a suitable cutoff point between `delayed’ and `non-delayed’ subsets from the overall data were made based on ICU waiting time and the hazard ratio of ICU waiting hour in each subset was iteratively calculated. The cutoff time was then used to evaluate the impact of delayed ICU admission on mortality and prolonged length of hospital stay.

Results

The final analysis included 1,242 patients. The time effect on mortality emerged after 4 hours, thus we deduced ICU waiting time in the ED of >4 hours as delayed. By logistic regression analysis, delayed ICU admission affected the outcomes of 21-ventilator-day mortality and prolonged hospital stay, with an odds ratio of 1.41 (95% confidence interval, 1.05 to 1.89) and 1.56 (95% confidence interval, 1.07 to 2.27) respectively.

Conclusions

For patients on mechanical ventilation in the ED, delayed ICU admission is associated with higher probability of mortality and additional resource expenditure. A benchmark waiting time of no more than 4 hours for ICU admission is recommended.
A Humanized Mouse Model of Hereditary 1,25-Dihydroxyvitamin D–Resistant Rickets Without Alopecia
Authors: Lee Seong Min , Goellner Joseph J. , O'Brien Charles A. , Pike J. Wesley
Published: August 2014

The syndrome of hereditary 1,25-dihydroxyvitamin D–resistant rickets (HVDRR) is a genetic disease of altered mineral homeostasis due to mutations in the vitamin D receptor (VDR) gene. It is frequently, but not always, accompanied by the presence of alopecia. Mouse models that recapitulate this syndrome have been prepared through genetic deletion of the Vdr gene and are characterized by the presence of rickets and alopecia. Subsequent studies have revealed that VDR expression in hair follicle keratinocytes protects against alopecia and that this activity is independent of the protein's ability to bind 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In the present study, we introduced into VDR-null mice a human VDR (hVDR) bacterial artificial chromosome minigene containing a mutation that converts leucine to serine at amino acid 233 in the hVDR protein, which prevents 1,25(OH)2D3 binding. We then assessed whether this transgene recreated features of the HVDRR syndrome without alopecia. RT-PCR and Western blot analysis in one strain showed an appropriate level of mutant hVDR expression in all tissues examined including skin. The hVDR-L233S mutant failed to rescue the aberrant systemic and skeletal phenotype characteristic of the VDR null mouse due to the inability of the mutant receptor to activate transcription after treatment with 1,25(OH)2D3. Importantly, however, neither alopecia nor the dermal cysts characteristic of VDR-null mice were observed in the skin of these hVDR-L233S mutant mice. This study confirms that we have created a humanized mouse model of HVDRR without alopecia that will be useful in defining additional features of this syndrome and in identifying potential novel functions of the unoccupied VDR.
No Evidence of Ectopic Lipid Accumulation in the Pathophysiology of the Acromegalic Cardiomyopathy
Authors: Winhofer Yvonne , Wolf Peter , Krššák Martin , Wolfsberger Stefan , Tura Andrea , Pacini Giovanni , Gessl Alois , Raber Wolfgang , Kukurova Ivica Just , Kautzky-Willer Alexandra , Knosp Engelbert , Trattnig Siegfried , Krebs Michael , Luger Anton
Published: August 2014

Context:

Patients with acromegaly frequently display disturbances of glucose and lipid metabolism, which might contribute to their increased cardiovascular risk. Because insulin resistance and increased lipolysis have been linked to ectopic lipid deposition, altered lipid accumulation in the liver and the myocardium might contribute to metabolic and cardiac complications in these patients.

Objective:

The aim of this study was to investigate myocardial (MYCL) and hepatic lipid content (HCL), insulin sensitivity, and cardiac function in active acromegaly and after control of GH excess through transsphenoidal surgery.

Patients:

Ten patients with newly diagnosed acromegaly (ACRO_active) were compared with 12 healthy controls (CON), matched for age, body mass index, and gender. In seven patients GH excess was controlled, and they were compared with their active state.

Methods:

MYCL and HCL were assessed by 1H-magnetic resonance spectroscopy, pericardial fat and cardiac function by 1H-magnetic resonance imaging, and insulin sensitivity and secretion by an oral glucose tolerance test.

Results:

Although MYCL tended to be lower, HCL was significantly lower in ACRO_active compared with CON (HCL: 1.2% ± 1.2% vs 4.3% ± 3.5% of 1H-magnetic resonance spectroscopy signal, P < .02). Parameters of systolic function and hypertrophy were significantly increased in ACRO_active compared with CON, as were insulin secretion and resistance. After the control of GH excess, HCL and MYCL remained unchanged, but pericardial fat was increased in the patients in whom GH excess was controlled (from 11.6 ± 5.5 to 14.7 ± 6.2 cm2, P = .02).

Conclusion:

Acromegaly represents a unique condition characterized by low myocardial and hepatic lipid content despite decreased insulin sensitivity, hyperinsulinemia, and hyperglycemia. Hence, ectopic lipid accumulation does not appear to contribute to cardiac morbidity, and increased lipid oxidation might counteract ectopic lipid accumulation in GH excess.
Minireview: Challenges and Opportunities in Development of PPAR Agonists
Authors: Wright Matthew B. , Bortolini Michele , Tadayyon Moh , Bopst Martin
Published: August 2014

The clinical impact of the fibrate and thiazolidinedione drugs on dyslipidemia and diabetes is driven mainly through activation of two transcription factors, peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ. However, substantial differences exist in the therapeutic and side-effect profiles of specific drugs. This has been attributed primarily to the complexity of drug-target complexes that involve many coregulatory proteins in the context of specific target gene promoters. Recent data have revealed that some PPAR ligands interact with other non-PPAR targets. Here we review concepts used to develop new agents that preferentially modulate transcriptional complex assembly, target more than one PPAR receptor simultaneously, or act as partial agonists. We highlight newly described on-target mechanisms of PPAR regulation including phosphorylation and nongenomic regulation. We briefly describe the recently discovered non-PPAR protein targets of thiazolidinediones, mitoNEET, and mTOT. Finally, we summarize the contributions of on- and off-target actions to select therapeutic and side effects of PPAR ligands including insulin sensitivity, cardiovascular actions, inflammation, and carcinogenicity.
“Drink Better, but Less”: The Rise of France’s Appellation System in the European Community, 1946-1976
Authors: Bohling Joseph
Published: August 2014

Two centerpieces of French identity, wine and statism, survived Europeanization and globalization in the postwar era. In charting the rise of France’s modern wine system, the Controlled Appellation of Origin (Appellation d’Origine Contrôlée; AOC), this article explains how the wine industry and the state adjusted to economic integration. The AOC system has been commonly viewed as a protector of local traditions when, more important, it developed as an economic strategy to promote the interests of French winegrowers and the state in an increasingly globalized world. The system’s success depended on the efforts of luxury wine producers, public health advocates, and state technocrats, who all invoked the “general interest” of consumers. This article inverts our understanding of the relationship between states and market integration to show how the Common Market and the world market actually reinforced state control over French vineyards, ultimately rebranding European wine production. Terroir gained widespread currency in the context of globalization.

Deux piliers de l’identité française—le dirigisme et le vin—ont réussi à faire face à l’Européanisation et la mondialisation après la Seconde Guerre mondiale. En montrant la montée en puissance du système de l’Appellation d’origine contrôlée (AOC)—cet article explique comment la filière viticole et l’Etat s’adaptent à l’intégration des marchés. L’opinion généralement répandue est que l’AOC a été une protection des traditions locales alors que, de manière plus importante encore, elle se développe comme une stratégie pour promouvoir les intérêts de la filière et l’Etat dans une économie de plus en plus mondialisée. Cet article intervertit notre compréhension du rapport entre l’Etat et l’intégration des marchés pour démontrer comment le Marché commun européen renforce l’autorité de l’Etat sur les vignobles français, changeant finalement l’image du vin français et européen. La notion du terroir se répand dans le contexte de la mondialisation.
The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis
Authors: Meyer Hemmo , Weihl Conrad C.
Published: August 2014

The ATPase valosin-containing protein (VCP)/p97 has emerged as a central and important element of the ubiquitin system. Together with a network of cofactors, it regulates an ever-expanding range of processes that stretch into almost every aspect of cellular physiology. Its main role in proteostasis and key functions in signaling pathways are of relevance to degenerative diseases and genomic stability. In this Cell Science at a Glance and the accompanying poster, we give a brief overview of this complex system. In addition, we discuss the pathogenic basis for VCP/p97-associated diseases and then highlight in more detail new exciting links to the translational stress response and RNA biology that further underscore the significance of the VCP/p97 system.
The relationship between cardiopulmonary size and aerobic performance in adult deer mice at high altitude
Authors: Shirkey Nicholas J. , Hammond Kimberly A.
Published: August 2014

Deer mice (Peromyscus maniculatus sonoriensis) populations in the White Mountains of Eastern California are found across a substantial range of partial pressures of oxygen (pO2). Reduction in pO2 at high altitude can have a negative impact on aerobic performance. We studied plastic changes in organ mass and volume involved in aerobic respiration in response to acclimation to high altitude, and how those changes are matched with aerobic performance measured by VO2 max. Adult deer mice born and raised at 340 m were acclimated at either 340 m or 3800 m for a period of nine weeks. Lung volume increased by 9% in mice acclimated to high altitude. VO2 max was also significantly higher under hypoxic conditions after high altitude acclimation compared to controls. Body mass corrected residuals of VO2 max were significantly correlated with an index of cardiopulmonary size (summed standardized residuals of lung volume and heart mass) under both hypoxic and normoxic conditions. These data show that phenotypic plasticity in lung volume and heart mass plays an important role in maintaining aerobic performance under hypoxic conditions, and account for up to 55% of the variance in aerobic performance.
Electromyographic analysis of goal-directed grasping behavior in American lobster
Authors: Tomina Yusuke , Takahata Masakazu
Published: August 2014

Animals spontaneously initiate goal-directed behavior including foraging action based on their appetitive motivation. American lobster Homarus americanus exhibits grasping behavior with its crusher claw as feeding behavior that can be initiated after appropriate operant conditioning. In order to quantitatively characterize the goal-directed grasping behavior with a time resolution fine enough for neurophysiological analysis of its initiation and control mechanisms, we made simultaneous electromyographic (EMG) recording from grasping- and reaching- related muscles of the crusher claw while animals initiated grasping behavior. We developed an in vivo extracellular recording chamber that allowed the animal under a semi-restrained condition to perform operant reward learning of claw grasping. Three muscles in the crusher claw (propodite-dactyl closer/ opener and coxal protractor) were found to be closely associated with spontaneous grasping behavior. In spontaneous grasping, the activation of those muscles consistently preceded the grasping onset time and exhibited different activity patterns from the grasp induced by a mechanical stimulus. Furthermore, we found that the timing of coxal protractor activation was closer to the grasp onset and its activity was briefer for goal-directed grasping behavior in trained and hungry animals than for non goal-directed spontaneous grasping behavior in naive or satiated animals. It is suggested that the goal-directed grasping behavior of lobster is characterized, at least partly, by experience-dependent briefer activity of specific muscles involved in reaching action.
Development of a Miniaturized Multi-Turn Time-of-Flight Mass Spectrometer with a Pulsed Fast Atom Bombardment Ion Source
Authors: Nagao Hirofumi , Miki Shinichi , Toyoda Michisato
Published: August 2014

A miniaturized multi-turn time-of-flight (TOF) mass spectrometer with a pulsed fast atom bombardment (FAB) ion source (FAB-MULTUM) has been designed and constructed in order to overcome the drawbacks associated with magnetic sector type instruments utilizing a FAB ion source such as size and weight. This instrument consists of a pulsed FAB ion source, a multi-turn TOF mass spectrometer, a detector, a vacuum system and electronic circuits. The size and weight of the system are less than H520 mm × L580 mm × W230 mm and 45 kg (including vacuum pumps and electronic circuits). The achieved resolving power and mass accuracy of this instrument were >25,000 and about 1 ppm, respectively, which are equivalent to those of magnetic sector type instruments, although the size and weight are much smaller than those of magnetic sector type instruments. The experimental results led us to the conclusion that this instrument enables accurate mass measurements and is a powerful tool for the confirmation of synthesized compounds.