bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of tyrosine kinase inhibitors in patients with metastatic kidney cancer receiving haemodialysis: a retrospective Italian survey
Authors: Masini Cristina , Sabbatini Roberto , Porta Camillo , Procopio Giuseppe , Di Lorenzo Giuseppe , Onofri Azzurra , Buti Sebastiano , Iacovelli Roberto , Invernizzi Roberta , Moscetti Luca , Aste Maria Giuseppina , Pagano Maria , Grosso Federica , Lucia Manenti Anna , Ortega Cinzia , Cosmai Laura , Del Giovane Cinzia , Conte Pier Franco
Published: February 2012

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

Sunitinib and sorafenib are orally administered multikinase inhibitors approved for the treatment of advanced RCC. The limited pharmacokinetics data on sunitinib and sorafenib suggest that haemodialysis does not significantly alter plasma concentrations.

In this retrospective study we define the safety and efficacy of tyrosine kinase inhibitors in patients with metastatic RCC (mRCC) and end‐stage renal disease requiring haemodialysis. Even though the retrospective nature of this survey and the relatively small sample size represent major limitations, these data indicate that treatment with sunitinib and sorafenib in this cohort of patients is feasible with no unexpected toxicity and good efficacy, results similar to those in the general population of patients with mRCC.

OBJECTIVE

To investigate the safety and efficacy of tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) and end‐stage renal disease requiring haemodialysis (HD).

PATIENTS AND METHODS

Between July 2006 and December 2010, 24 patients undergoing HD were treated with sunitinib and/or sorafenib for mRCC in 14 Italian institutions.

We retrospectively reviewed the medical records of these patients to evaluate the administered doses of TKIs, treatment‐related toxicities and the clinical response to therapy.

RESULTS

Sunitinib was administered at 50 mg daily for 4–6 weeks in six patients, 37.5 mg daily for 4–6 weeks in seven patients (one patient subsequently increased the dose to 50 mg daily), 25 mg daily for 4–6 weeks in two patients and 12.5 mg daily for 4–6 weeks in one patient. Among the eight patients treated with sorafenib, four patients received 800 mg daily (400 mg every 12 h), three patients 400 mg daily and one patient 200 mg daily with a continuous schedule.

The estimated median progression‐free and overall survival periods of this cohort of patients were 10.3 months and 22.6 months, respectively.

With regard to tolerability and safety, no unexpected adverse events were registered and no grade 4 haematological or non‐haematological toxicities were reported.

CONCLUSIONS

Sunitinib and sorafenib treatment is not contraindicated in patients with mRCC undergoing HD.

The outcome of this patient population is similar to that observed in patients with normal renal function treated with TKIs.

These results merit further confirmation by a larger prospective trial.
Higher Education and the Post‐Soviet Transition in Russia
Authors: Morgan W. John , Kliucharev Grigori A.
Published: February 2012

A video abstract of this article can be viewed at http://www.youtube.com/watch?v=LNMIwfWCmiI
Social Inequality and Access to Higher Education in Russia
Authors: Konstantinovskiy David L.
Published: February 2012

This article analyses research on social inequality and access to higher education in Russia. It argues that the myth about equality of life chances, as with certain other myths, was an important part of the Soviet ideology. However, children from privileged groups traditionally received the education and professional training which were most advantageous for their subsequent lives and careers. Recent research indicates that conditions in post‐Soviet Russia are not eliminating social differentiation. This is clearly seen in access to higher education. It is shown that the inequality is noticeable in secondary education and is aggravated during the transition to higher education and vocational training (universities, colleges, vocational schools). In order to explain the genesis of such inequality, the article considers research focusing on the situation at secondary school. The dynamics must be analysed over a long period, since the problems that post‐Soviet youth face today have roots in the Soviet past. Hence, the article considers the results of studies conducted between the 1960s and today.
Private Higher Education in Russia: capacity for innovation and investment
Authors: Geroimenko Vladimir A. , Kliucharev Grigori A. , Morgan W. John
Published: February 2012

This article considers the potential role of private institutions in the development of Russian higher education. After decades of a government centralised higher education system, there is a clear trend towards the privatisation of education institutions and the diversification of education practices. Some commentators consider this to indicate that the Russian State is losing control of education; others welcome private initiatives, both in formal and informal education. Russian higher education has also been greatly challenged by the current demographic gap: the total number of secondary school graduates expected in 2012 is half that of 2006. This strengthens the competition for the enrolment of students in private and public (federal and municipal) institutions. Based on recent interviews with senior management at a number of provincial private universities, this article suggests possible avenues for private universities to extend into the education market and considers the implications.
The Role of Religious Higher Education in the Training of Teachers of Russian ‘Orthodox Culture’1
Authors: Ładykowska Agata
Published: February 2012

This article provides an ethnographic account of the tensions arising from the different ways of building authority as teachers and the role of higher education in establishing teachers' legitimacy in Russia through the specific example of religious education. After state atheism was abandoned in 1991, an unprecedented demand for religious knowledge appeared in Russia, in particular in relation to Russian Orthodoxy. Since the Russian context of Orthodox education lacks shared standards, there is considerable latitude in the criteria determining norms and rules. Seeking to increase its influence, the Russian Orthodox Church aspires to have Orthodox catechism taught in a systematic way both in parishes and in secular schools. In practice, the Church is encouraging professional pedagogues to submit their curriculum proposals that would be suffused with Orthodoxy and at the same time be eligible for adoption in all settings and institutions. Thus, in order to educate teachers of religion, the Church has made available multiple, diverse sources of religious knowledge (self‐learning, various courses offered by the eparchies, Spiritual Academies, and other institutions of higher education). But the legitimacy of these sources is often questioned, for instance by asking whether the institution that delivers diplomas of religious higher education has been granted formal state recognition. The teachers' quest for being acknowledged as competent technicians of religious education leads to competing claims for the authenticity of the sources of their training.
How Europe Shapes Academic Research: insights from participation in European Union Framework Programmes
Authors: Primeri Emilia , Reale Emanuela
Published: February 2012

This article describes the effects of participating in European Union Framework Programmes (EUFPs) at the level of research units and researchers. We consider EUFPs as policy instruments that contribute to the Europeanisation of academic research and study the changes they produce with respect to: 1) the organisation and activities of Departments, 2) the type of knowledge produced, and 3) the ways of doing research. The analysis is based on a case study of the Sapienza University in Rome. We also discuss the extent to which EUFPs produce different effects at the level of scientific fields.

This pilot study analyses changes driven by EUFPs from an institutional perspective and uses the concept of institutionalisation to explain how these changes are translated into rules and practices by research units and researchers. Our preliminary investigation supports the idea that EUFPs do not trigger a process of Europeanisation and lead, within academic institutions, to highly diversified institutional responses by scientific fields rather than to undifferentiated ones. They strengthen leading research groups and Departments, already competitive at the EU level, by enhancing existing international behaviours and practices. However, they do not support and, at times, even decrease competition opportunities for less experienced participants and they do not promote the participation of new groups. Moreover, the absence of relevant organisational changes at the University level and the lack of incentives for EUFP participation seem to strengthen these trends. What emerges is the need for decisions at the University level, taking into account differences across scientific groups.
Research and Teaching Revisited: a pre‐Humboldtian or post‐Humboldtian phenomenon? The cases of France and the UK
Authors: Chiang Kuang‐Hsu
Published: February 2012

The evidence about the relationship between research and teaching at the level of doctoral education is far from conclusive. The focus of this study is to examine how teaching and research are related at doctoral level, especially when students' voices are heard, in two contrasting higher education systems — France and the UK.

Models from Schimank and Winnes, and Clark were used to analyse the contrasting research and teaching configurations at institutional level in France and the UK. France has a Pre‐Humboltian system of research and teaching, whilst the UK has a Post‐Humboltian one.

Two empirical studies were then drawn on: to measure teaching, a questionnaire composed of two major dimensions of research training experiences, supervision and research environment, was distributed to full‐time doctoral students in Economics & Management and Chemistry in France and was compared to a survey carried out earlier in Education and Chemistry in the UK. To measure research, the result of the CNRS (National Centre of Scientific Research) research classification in France was used. In the UK, the corresponding measurement, RAE score (Research Assessment Exercise) was adopted.

Strikingly similar findings were found in the two countries. First, there is little relationship between the departmental research performance and the quality of doctoral education as experienced by PhD students in either country. Next, this lack of significant relationship is found across all three disciplines. Thirdly, more consistent results were observed in France than in the UK. There is in‐depth discussion with regard to these findings.
Professional Doctorates and Careers: the Spanish case1
Authors: Canal Domínguez Juan Francisco , Muñiz Pérez Manuel Antonio
Published: February 2012

This article analyses the determining factors weighted by doctoral graduates when choosing their professional careers. In Spain, the analysis of such a group has been traditionally excluded from the empiric studies. On the one hand, the lack of databases made it difficult to see their professional situation, and on the other, a university career was understood as this group's innate purpose. The growing demand for qualified professionals in general and for those with a scientific training in particular has prompted the developed countries to carry out research on how to match the third‐level training cycle and labour market needs. The analysis of this group's labour conditions allows one to assess whether the current doctoral education programmes satisfy labour market needs. The estimation of a multinomial logit model reveals the different factors when choosing a professional career depending on the area of knowledge. Personal characteristics, such as age, training, area of knowledge or job, as well as the expected wages become fundamental when determining doctors' professional future. Moreover, the results prove that a job outside the university is becoming a preferred option for doctors in certain fields.
How Girls and Boys Expect Disclosure About Problems Will Make Them Feel: Implications for Friendships
Authors: Rose Amanda J. , Schwartz‐Mette Rebecca A. , Smith Rhiannon L. , Asher Steven R. , Swenson Lance P. , Carlson Wendy , Waller Erika M.
Published: February 2012

Although girls disclose to friends about problems more than boys, little is known about processes underlying this sex difference. Four studies (Ns = 526, 567, 769, 154) tested whether middle childhood to mid‐adolescent girls and boys (ranging from 8 to 17 years old) differ in how they expect that talking about problems would make them feel. Girls endorsed positive expectations (e.g., expecting to feel cared for, understood) more strongly than boys. Despite common perceptions, boys did not endorse negative expectations such as feeling embarrassed or worried about being made fun of more than girls. Instead, boys were more likely than girls to expect to feel “weird” and like they were wasting time. Sex differences in outcome expectations did help to account for girls’ greater disclosure to friends.
Find Your Manners: How Do Infants Detect the Invariant Manner of Motion in Dynamic Events?
Authors: Pruden Shannon M. , Göksun Tilbe , Roseberry Sarah , Hirsh‐Pasek Kathy , Golinkoff Roberta M.
Published: February 2012

To learn motion verbs, infants must be sensitive to the specific event features lexicalized in their language. One event feature important for the acquisition of English motion verbs is the manner of motion. This article examines when and how infants detect manners of motion across variations in the figure’s path. Experiment 1 shows that 13‐ to 15‐month‐olds (N = 30) can detect an invariant manner of motion when the figure’s path changes. Experiment 2 reveals that reducing the complexity of the events, by dampening the figure’s path, helps 10‐ to 12‐month‐olds (N = 19) detect the invariant manner. These findings suggest that: (a) infants notice event features lexicalized in English motion verbs, and (b) attention to manner can be promoted by reducing event complexity.
The Effects of Auditory Information on 4‐Month‐Old Infants’ Perception of Trajectory Continuity
Authors: Bremner J. Gavin , Slater Alan M. , Johnson Scott P. , Mason Uschi C. , Spring Jo
Published: February 2012

Young infants perceive an object’s trajectory as continuous across occlusion provided the temporal or spatial gap in perception is small. In 3 experiments involving 72 participants the authors investigated the effects of different forms of auditory information on 4‐month‐olds’ perception of trajectory continuity. Provision of dynamic auditory information about the object’s trajectory enhanced perception of trajectory continuity. However, a smaller positive effect was also obtained when the sound was continuous but provided no information about the object’s location. Finally, providing discontinuous auditory information or auditory information that was dislocated relative to vision had negative effects on trajectory perception. These results are discussed relative to the intersensory redundancy hypothesis and emphasize the need to take an intersensory approach to infant perception.
Surfactant Influence on Water Wave Packets
Authors: Akers B. F.
Published: February 2012

The influence of surfactant on water wave packets is investigated. An envelope equation for a slowly varying wave packet in the potential flow equations with variable Bond number is derived. The properties of this equation depend on the relative phases of the wave packet and the distribution of surface tension. We observe that small variations in the Bond number may change the focusing nature of the envelope equation from that of the constant Bond number problem. Variations in Bond number can thus suppress, or incite, the Benjamin‐Feir instability. The existence of envelope solitary waves depends in a similar way on the Bond number variation. The envelope equation is also derived in a larger class of models.
Over‐Education in Multilingual Economies: Evidence from Catalonia
Authors: Blázquez Maite , Rendón Silvio
Published: February 2012

Catalonia’s economy is characterized by linguistic diversity and provides a unique opportunity to measure the incidence of language proficiency on over‐education, that is, whether individuals with deficient language skills, as non‐natives, tend to accept jobs for which they have excessive formal skills. Descriptive evidence suggests the contrary, that individuals with better language knowledge are more likely to be over‐educated. However, estimating a model that controls for individuals’ socio‐demographic characteristics reveals the opposite: better language knowledge decreases over‐education. This effect, although robust to accounting for endogeneity of language knowledge and significant at the individual level, is mostly non‐significant on average.
Contextualizing Vocabularies of Motive in International Migration: The Case of Taiwanese in the United States
Authors: Gu Chien‐Juh
Published: February 2012

Immigrants’ motives are central to understanding immigration, yet they remain an under‐researched subject in immigration studies. To fill this gap, this article examines Taiwanese immigrants’ motives for relocating to the United States. Following Mills’ concept of vocabularies of motive, this article treats immigration as situated actions and explores how cumulative causation and structural positions shape immigrants’ interpretations of their immigration decisions. Based on 75 in‐depth interviews, this study discovers important differences in motive during two migration phases, initial migration and permanent settlement, as well as differences according to gender, ethnicity, and social class. Migration through education comprises the major pattern of Taiwanese immigration, as most Taiwanese move to the United States to study and then settle there for job opportunities. While men settle for careers, women stay for family wellbeing. One ethnic group, benshengren, tends to settle for job opportunities, while the other, waishengren, migrates to unite their families. Moreover, professionals always consider return as an option, while labourers are determined to stay permanently. Findings of the study suggest the importance of examining the influences of immigration contexts and individual structural positions in shaping personal motives.
The need for future alternatives: an investigation of the experiences and future of older parents caring for offspring with learning disabilities over a prolonged period of time
Authors: Cairns Deborah , Tolson Debbie , Brown Jayne , Darbyshire Chris
Published: February 2012

Accessible Summary

This article reports on interviews with eight older parent carers who cared for their children with learning disabilities.

The aim of this study was to understand parent carers’ experiences of caregiving and their views on the future.

The findings revealed the following:

Parents lacked support

Parents did not receive enough information and practical resources

Some parents continued caring despite poor mental and/or physical health

All parents were concerned about their child's future

Most parents said that they were unable to think about their future and their needs

This article reports on the results of a qualitative study (in‐depth interviews) carried out in the United Kingdom as part of a larger (two‐phased) study investigating the experiences, health and future perspectives of older parent carers (six mothers and two fathers) of offspring with learning disabilities over a prolonged period of time. The objectives of this article are twofold: (i) to present a conceptual framework, grounded in the experiences of older parent carers who participated in this research and; (ii) to come to a more in‐depth understanding of older parent carers’ experiences of caregiving, and views on their own future. A detailed analysis of the data revealed important issues with regard to prolonged caregiving. Overall, older parent carers felt that they lacked support, information and practical resources throughout their caregiving career. Some parents continued in their caregiving role despite their deteriorating mental and/or physical health as there appeared to be no alternative, and most parent carers expressed that they were unable to think ahead to their own future and needs owing to the absence of suitable care alternatives. The findings suggest that there is an urgent need to review how individuals with learning disabilities and parent carers are supported throughout their lifespan.
Study of the three‐dimensional orientation of the labrum: its relations with the osseous acetabular rim
Authors: Bonneau Noémie , Bouhallier July , Baylac Michel , Tardieu Christine , Gagey Olivier
Published: February 2012

Understanding the three‐dimensional orientation of the coxo‐femoral joint remains a challenge as an accurate three‐dimensional orientation ensure an efficient bipedal gait and posture. The quantification of the orientation of the acetabulum can be performed using the three‐dimensional axis perpendicular to the plane that passes along the edge of the acetabular rim. However, the acetabular rim is not regular as an important indentation in the anterior rim was observed. An innovative cadaver study of the labrum was developed to shed light on the proper quantification of the three‐dimensional orientation of the acetabulum. Dissections on 17 non‐embalmed corpses were performed. Our results suggest that the acetabular rim is better represented by an anterior plane and a posterior plane rather than a single plane along the entire rim as it is currently assumed. The development of the socket from the Y‐shaped cartilage was suggested to explain the different orientations in these anterior and posterior planes. The labrum forms a plane that takes an orientation in between the anterior and posterior parts of the acetabular rim, filling up inequalities of the bony rim. The vectors VL, VA2 and VP, representing the three‐dimensional orientation of the labrum, the anterior rim and the posterior rim, are situated in a unique plane that appears biomechanically dependent. The three‐dimensional orientation of the acetabulum is a fundamental parameter to understand the hip joint mechanism. Important applications for hip surgery and rehabilitation, as well as for physical anthropology, were discussed.
Advances in the use of botulinum neurotoxins in facial esthetics
Authors: Flynn Timothy Corcoran
Published: February 2012

Aim  To present the latest findings and future developments in the cosmetic use of botulinum neurotoxin.

Methods  Review of recent literature and new scientific developments.

Results  Botulinum neurotoxin type A preparations onabotulinumtoxinA (BOTOX® Cosmetic/Vistabel®, Allergan Inc.) and abobotulinumtoxinA (Dysport®/Azzalure®/Reloxin®, Ipsen Pharma,) have been used for many years and are effective and well tolerated for facial esthetic procedures. However, advances are continually made in the esthetics field. New formulations that may exhibit reduced antigenicity are becoming available, such as incobotulinumtoxinA (Xeomin®/Xeomeen®/Bocouture®; formerly known as NT 201, Merz Pharma), which is a botulinum neurotoxin type A free from complexing proteins. In addition, lower facial procedures using botulinum toxin combined with fillers are becoming increasingly popular. Injection techniques and patterns are also evolving, with the aim of creating a more natural result and avoiding a “frozen” appearance. Moreover, the diversity of individuals requesting esthetic procedures is increasing, with growing interest from men and patients with a variety of skin types and colors.

Conclusions  The uses of botulinum toxins for facial esthetics procedures continue to expand, with new techniques and formulations. The availability of products such as incobotulinumtoxinA may reduce the risk of neutralizing antibody development while maintaining the good efficacy and safety of existing formulations.
Effect of cosmetic ingredients as anticellulite agents: synergistic action of actives with in vitro and in vivo efficacy
Authors: Al‐Bader Tamara , Byrne Adam , Gillbro Johanna , Mitarotonda Andrea , Metois Adeline , Vial Francis , Rawlings Anthony V. , Laloeuf Aurelie
Published: February 2012

Background  The pathophysiology of cellulite involves changes in the subcutaneous adipose layer and the extracellular matrix (ECM) that supports it together with overlying dermal layer. Cellular mechanisms governing cellulite are not fully understood. However, it is accepted that changes include enhanced lipogenesis, decreased lipolysis, and increased lipid storage within the adipocytes as well as changes in the dermal architecture.

Aim  In our studies the ability of cosmetic agents Furcellaria lumbricalis, Fucus vesiculosus, retinoid, conjugated linoleic acid (CLA), and a glaucine mixture to stimulate in vitro1) lipolysis in human adipocytes and 2) production of pro‐collagen I by fibroblasts was investigated in vitro. The ability of these ingredients to improve cellulite condition in vivo was also determined.

Patients/Methods  Mature adipocytes and 'aged' fibroblasts were used for in vitro studies. The assessment of cellulite in vivo was performed by dermatological grading and ultrasound measurements.

Results  Mature adipocytes treated with combined actives resulted in a significant synergistic increase in free glycerol release. On “aged” fibroblasts, combined treatment of F. vesiculosus and F. lumbricalis stimulated pro‐collagen I production. CLA increased pro‐collagen I production, but the glaucine mixture had no effect. The clinical study demonstrated a significant improvement in cellulite grading by a dermatologist after 8 and 12 weeks vs. vehicle, and ultrasound imaging showed a significant decrease in fat thickness compared with placebo after 12 weeks.

Conclusions  Our studies revealed a potent cocktail of ingredients that when combined together can act in vitro to markedly improve lipolysis mechanisms and by way of stimulating pro‐collagen I can also have an effect on the surrounding extracellular matrix. The in vitro actions of the ingredients were translated in vivo, where a clinical improvement of cellulite condition was observed.
Carotenoids and polyphenols in nutricosmetics, nutraceuticals, and cosmeceuticals
Authors: Anunciato Talita Pizza , da Rocha Filho Pedro Alves
Published: February 2012

The market for cosmeceuticals continues with significant annual growth, but today consumers are more aware of nutritional products that contribute to both skin health and disease prevention. In the last 10 years, pharmacists, chemists, nutritionists, and physicians have been working together to develop new nutritional applications to satisfy people’s needs and demands. As a recent result of convergence phenomenon between cosmetics and food industries, nutricosmetics is a blurry area unfamiliar to many consumers and sometimes even to foods and cosmetics experts. Characterized by oral supplementation of nutrients, nutricosmetics are also known as “beauty pills,”“beauty from within,” and even “oral cosmetics.” The major claim is the antiaging effect, reducing wrinkles by fighting free radicals generated by solar radiation. Among the ingredients used in nutricosmetics, antioxidants represent the most crucial. The best‐known antioxidants are carotenoids (beta‐carotene, lycopene, lutein, zeaxanthin, and astaxanthin) and polyphenols (anthocyanidins, catechins, flavonoids, tannins, and procyanidins). This study presents an overview about the concept of nutricosmetics and gives us information about the difference between nutricosmetics, nutraceuticals, and cosmeceuticals. The article also discusses about carotenoids and polyphenols, two classes of ingredients often employed in such products.
In the shadow of the wrinkle: experimental models
Authors: Humbert Philippe , Viennet Céline , Legagneux Kévin , Grandmottet François , Robin Sophie , Muret Patrice
Published: February 2012

Research on aging has run for decades, and knowledge on the biologic process of skin chronological and photoaging is still increasing thanks to read across results generated between human, animal, and in vitro studies. However, wrinkles should not be considered to result only from the aging process. There are few reports on specific wrinkle histological features compared to the surrounding skin, and there is thus a need in really wrinkling skin animal and in vitro models. UV‐irradiated Hr mouse is a good model because it develops wrinkles. Nevertheless, as mouse skin is somehow different from human skin, the innovative model of wrinkling human skin xenograft on SCID mice seems to be really promising. Concerning in vitro and ex vivo models, although there have been considerable advances in reconstructing realistic aged skins, there is still a lack of in vitro wrinkling skin model, and unfortunately, this gap will probably be difficult to fill.
Baseline sebum IL‐1α is higher than expected in afro‐textured hair: a risk factor for hair loss?*
Authors: Beach Renée A , Wilkinson Katalin A , Gumedze Freedom , Khumalo Nonhlanhla P
Published: February 2012

Objective  To investigate changes in sebum cytokines in response to hair cosmetics.

Design and setting  A prospective study at a University hospital.

Methods  We used a novel method for scalp surface sebum collection (Sebutape®) on three visits, sequentially a week apart, to investigate changes in six cytokines in 36 healthy women before and after shampoo and compared various chemical treatments (ammonium thioglycolate, “lye” sodium hydroxide and “no‐lye” guanidine hydroxide relaxers) performed by a professional hairdresser.

Results  Significant levels detected were IL‐1 alpha (IL‐1α) and IL‐1 receptor antagonist (IL‐1ra), which were higher in untreated scalp vs. forehead: P < 0.001. Baseline levels of scalp sebum IL‐1α were 18 times higher than IL‐1ra. The levels of IL‐1α decreased uniformly after shampoo (visit 1) and various chemical treatments (both crown and vertex all P < 0.001 – visit 2) but increased on follow‐up at visit 3. Decreases in IL‐1ra mimicked IL‐1α at the vertex [after shampoo (P = 0.018) and visit 3 (P = 0.014)], but not on the crown, a finding which may suggest site‐specific scalp predisposition to inflammation. The ratio of IL‐1ra/IL‐1α increased in all groups after all chemical treatments and on follow‐up (all P < 0.001) but was surprisingly not significantly different from natural hair that underwent shampoo.

Limitations  A wider cytokine panel may reveal response differences in treatment groups.

Conclusions  Baseline inflammatory scalp cytokines are higher than expected and reduce with shampooing. Scrutiny of the influence of hair moisturizer formulations and shampoo intervals and studies investigating pro‐fibrotic cytokines are required. This may elucidate the predilection of afro‐textured hair to scarring alopecia.
Neoliberalising violence: of the exceptional and the exemplary in coalescing moments
Authors: Springer Simon
Published: February 2012

This paper sets out to develop two related ideas. First, it seeks to identify how both violence and neoliberalism can be considered as moments. From this shared conceptualisation of process and fluidity, I argue that it becomes easier to recognise how these two phenomena actually converge. Building upon this conceived coalescence of neoliberalism and violence, the second aim is to recognise how the hegemony of neoliberalism positions it as an abuser, which facilitates the abandonment of those ‘Others’ who fall outside of neoliberal normativity. I argue that the widespread banishment of ‘Others’ under neoliberalism produces a ‘state of exception’, wherein because of its inherently dialectic nature, exceptional violence is transformed into exemplary violence. This metamorphosis occurs as aversion for alterity intensifies under neoliberalism and its associated violence against ‘Others’ comes to form the rule.
Assessment of platelet function
Authors: Jandrey Karl E.
Published: February 2012

Objective

To review the current in vivo and in vitro tests of platelet function (PF) currently available and applicable to companion animals.

Data Sources

Scientific reviews, case reports, original clinical and laboratory research publications, and recent veterinary research conference proceedings.

Human Data Synthesis

Disorders of primary hemostasis are very common in human medicine. These include inborn errors of PF and granule storage contents, primary disease mechanisms that alter PF, disorders secondary to surgical interventions, and the effects of anticoagulant medications. Knowledge of PF disorders and the optimal method for assessment must be known to understand the mechanism and to monitor the process or drug therapy.

Veterinary Data Synthesis

Interest in the study and treatment of primary coagulopathies in clinical veterinary patients has resulted in a surge of recent publications and scientific research presentations. A translational approach that uses laboratory and point‐of‐care tools to uncover the pathophysiologic mechanisms in the patient with defects in primary hemostasis allows the clinician to plan the diagnosis and treatment more effectively.

Primary hemostatic disorders are being more commonly recognized in clinical veterinary practice. The diagnosis of platelet dysfunction may be obtained via point‐of‐care analyzers that use relatively small blood samples and have a quick turnaround time. Recent investigations may lead to a better understanding of the pathophysiology of PF disorders and potentially the optimization, or discovery, of novel treatments.

Conclusions

The assessment of PF can be completed through in vivo and in vitro point‐of‐care techniques as well as by submission of blood samples to more specialized platelet biology laboratories. The information obtained including the physical examination and clinical manifestations of a hemostatic disorder, as well as the benefits of each testing modality, must be known prior to the diagnostic investigation of a patient with a coagulopathy.
Evaluation of platelet aggregometry in dogs using the Multiplate platelet analyzer: impact of anticoagulant choice and assay duration
Authors: Marschner Clara B. , Kristensen Annemarie T. , Spodsberg Eva H. , Wiinberg Bo
Published: February 2012

Objective

To investigate the performance of the Multiplate platelet function analyzer with regards to: (1) the use of 3 different anticoagulants (ie, citrate, hirudin, and heparin) and (2) the evaluation of optimal assay time.

Design

Prospective observational in vitro study.

Setting

University veterinary teaching hospital.

Animals

Twenty clinically healthy dogs and 3 ill dogs.

Interventions

None.

Measurements and Main Results

A total of 184 analyses were performed with duplicate measurements in each test cell and results are reported as mean of the 2 measurements. Analyses were performed on blood samples from 20 dogs collected in citrate, hirudin, or heparin. A total of 4 analyses were performed on every blood sample using adenosine diphosphate, collagen, and arachidonic acid as agonists as well as a control with 0.9% sodium chloride (buffer). Aggregation in hirudin samples was significantly increased compared with heparin at all analysis times except at 6 minutes when using ADP as agonist; however, hirudin samples also demonstrated significant aggregation in the buffer control, compared to both citrate and heparin. Citrated samples yielded significantly lower aggregation compared with both hirudin‐ and heparin‐stabilized samples at 6 and 12 minutes when ADP and collagen were used as agonists, and at most analysis times with arachidonic acid. The assay performed best at shorter analyses times, whereas longer analyses times yielded larger variation in data.

Conclusions

There was a good aggregation response and acceptable analytical variation in both heparin‐ and hirudin‐anticoagulated samples with all tested agonist at the concentrations recommended by the manufacturer. The results suggest that heparin may be superior as anticoagulant for Multiplate analyses in dogs and that short analyses times are preferable. Spontaneous platelet autoaggregation in hirudin samples warrants careful evaluation of results using this anticoagulant, especially at longer test times. The use of citrate is discouraged for Multiplate analyses in dogs due to a weak aggregation response.
Use of fresh platelet concentrate or lyophilized platelets in thrombocytopenic dogs with clinical signs of hemorrhage: a preliminary trial in 37 dogs
Authors: Davidow Elizabeth B. , Brainard Benjamin , Martin Linda G. , Beal Matthew W. , Bode Arthur , Ford Michael J. , Ramsey Noel , Fagella Alicia , Jutkowitz Ari
Published: February 2012

Objective

To examine the safety and feasibility of using lyophilized platelets (LYO) and fresh platelet concentrate (FRESH) in bleeding thrombocytopenic dogs.

Design

Preliminary prospective randomized clinical trial.

Setting

Two private referral centers and 3 university teaching hospitals.

Animals

Thirty‐seven dogs with a complaint of hemorrhage associated with thrombocytopenia (platelet count <70 × 109/L [70,000/μL], a hematocrit >15%, and that had received neither vincristine nor platelet‐containing transfusions within 72 h of enrollment were studied.

Interventions

Animals were randomized to receiveLYOorFRESH, dosed according to weight. Physical examination, complete blood counts, and coagulation testing (prothrombin time and activated partial thromboplastin time) were performed at enrollment. Physical examinations were also performed immediately post transfusion, and at 1 and 24 h after transfusion. Complete blood counts were repeated immediately post transfusion and at 24 h. Collected data included bleeding score (BLS), response to transfusion, adverse reactions, hospitalization time, need for additional transfusions, survival to discharge, and 28‐d survival.

Measurements and Main Results

Twenty‐two dogs receivedLYOand 15 receivedFRESH. There was no difference between groups in age, weight,BLS, platelet count, white blood cell count, hematocrit, or presence of melena. There was no difference between groups in transfusion reaction rates, the need for additional transfusions, 24‐hBLS, hospitalization time, survival to discharge, or 28‐d survival.

Conclusions

Transfusion ofLYOwas feasible and associated with a low transfusion reaction rate in this limited study of thrombocytopenic canine patients presenting with mild‐to‐severe hemorrhage.LYOwere easy to use and provided storage advantages overFRESH. Further study of this product, including examination of efficacy and platelet life span, is warranted.
The successes and limitations of preclinical studies in predicting the pharmacodynamics and safety of cell‐surface‐targeted biological agents in patients
Authors: Polson Andrew G , Fuji Reina N
Published: February 2012

To improve drug development outcomes, it is important to review when preclinical pharmacodynamic and safety models have successfully predicted human responses and when they have not. In a recent issue of the BJP, Bugelski and Martin examined the concordance between preclinical and human data for biopharmaceuticals targeted to cell‐surface proteins. The cases are interesting and several trends emerge. The pharmacodynamics of biopharmaceuticals in non‐human primates is largely predictive; the use of surrogates in rodents may be similarly predictive, allowing for more conservative use of non‐human primates. While overall concordance of preclinical toxicology data and clinical safety was poor, this is largely a reflection of the immunomodulatory biology of the majority of the biopharmaceuticals evaluated. The examples show that adverse effects in animals that were the result of direct and/or exaggerated pharmacology were modelled well, but that specific infections or other indirect outcomes of immunomodulation, along with cytokine‐related events, were not modelled well in preclinical studies.

LINKED ARTICLES

To view Bugelski and Martin visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01811.x and to view Martin and Bugelski visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01812.x
Glucocorticoid receptors participate in the opiate withdrawal‐induced stimulation of rats NTS noradrenergic activity and in the somatic signs of morphine withdrawal
Authors: Navarro‐Zaragoza Javier , Hidalgo Juana M , Laorden M Luisa , Milanés M Victoria
Published: February 2012

BACKGROUND AND PURPOSE Recent evidence suggests that glucocorticoid receptor (GR) is a major molecular substrate of addictive properties of drugs of abuse. Hence, we performed a series of experiments to further characterize the role of GR signalling in opiate withdrawal‐induced physical signs of dependence, enhanced noradrenaline (NA) turnover in the hypothalamic paraventricular nucleus (PVN) and tyrosine hydroxylase (TH) phosphorylation (activation) as well as GR expression in the nucleus of the solitary tract noradrenergic cell group (NTS‐A2).

EXPERIMENTAL APPROACH The role of GR signalling was assessed by i.p. pretreatment of the selective GR antagonist, mifepristone. Rats were implanted with two morphine (or placebo) pellets. Six days later, rats were pretreated with mifepristone or vehicle 30 min before naloxone and physical signs of abstinence, NA turnover, TH activation, GR expression and the hypothalamus–pituitary–adrenocortical axis activity were measured using HPLC, immunoblotting and RIA.

KEY RESULTS Mifepristone alleviated the somatic signs of naloxone‐induced opiate withdrawal. Mifepristone attenuated the increase in the NA metabolite, 3‐methoxy‐4‐hydroxyphenylethylen glycol (MHPG), in the PVN, and the enhanced NA turnover observed in morphine‐withdrawn rats. Mifepristone antagonized the TH phosphorylation at Ser31 and the expression of c‐Fos expression induced by morphine withdrawal. Finally, naloxone‐precipitated morphine withdrawal induced up‐regulation of GR in the NTS.

CONCLUSIONS AND IMPLICATIONS These results suggest that the physical signs of opiate withdrawal, TH activation and stimulation of noradrenergic pathways innervating the PVN are modulated by GR signalling. Overall, the present data suggest that drugs targeting the GR may ameliorate stress and aversive effects associated with opiate withdrawal.
Inhibition of adrenergic human prostate smooth muscle contraction by the inhibitors of c‐Jun N‐terminal kinase, SP600125 and BI‐78D3
Authors: Strittmatter F , Walther S , Gratzke C , Göttinger J , Beckmann C , Roosen A , Schlenker B , Hedlund P , Andersson KE , Stief CG , Hennenberg M
Published: February 2012

BACKGROUND AND PURPOSE α1‐Adrenoceptor‐induced contraction of prostate smooth muscle is mediated by calcium‐ and Rho kinase‐dependent mechanisms. In addition, other mechanisms, such as activation of c‐jun N‐terminal kinase (JNK) may be involved. Here, we investigated whether JNK participates in α1‐adrenoceptor‐induced contraction of human prostate smooth muscle.

EXPERIMENTAL APPROACH Prostate tissue was obtained from patients undergoing radical prostatectomy. Effects of the JNK inhibitors SP600125 (50 µM) and BI‐78D3 (30 µM) on contractions induced by phenylephrine, noradrenaline and electric field stimulation (EFS) were studied in myographic measurements. JNK activation by noradrenaline (30 µM) and phenylephrine (10 µM), and the effects of JNK inhibitors of c‐Jun phosphorylation were assessed by Western blot analyses with phospho‐specific antibodies. Expression of JNK was studied by immunohistochemistry and fluorescence double staining.

KEY RESULTS The JNK inhibitors SP600125 and BI‐78D3 reduced phenylephrine‐ and noradrenaline‐induced contractions of human prostate strips. In addition, SP600125 reduced EFS‐induced contraction of prostate strips. Stimulation of prostate tissue with noradrenaline or phenylephrine in vitro resulted in activation of JNK. Incubation of prostate tissue with SP600125 or BI‐78D3 reduced the phosphorylation state of c‐Jun. Immunohistochemical staining demonstrated the expression of JNK in smooth muscle cells of human prostate tissue. Fluorescence staining showed that α1A‐adrenoceptors and JNK are expressed in the same cells.

CONCLUSIONS AND IMPLICATIONS Activation of JNK is involved in α1‐adrenoceptor‐induced prostate smooth muscle contraction. Models of α1‐adrenoceptor‐mediated prostate smooth muscle contraction should include this JNK‐dependent mechanism.
Similar Outcomes of Catheters Implanted by Nephrologists and Surgeons: Analysis of the Brazilian Peritoneal Dialysis Multicentric Study
Authors: de Moraes Thyago P. , Campos Rodrigo P. , de Alcântara Márcia Tokunaga , Chula Domingos , Vieira Marcos A. , Riella Miguel C. , Olandowski Márcia , Divino‐Filho José Carolino , Pecoits‐Filho Roberto ,   on behalf of the investigators of the BRAZPD
Published: February 2012

A good catheter implantation technique is important to allow for effective peritoneal access function and long‐term technique survival. Studies regarding results obtained by nephrologists in comparison with surgeons have been limited to small single‐center experiences. Thus, the objective of this study was to explore the impact of the peritoneal dialysis (PD) catheter insertion operator on early catheter complications and on technique survival in a large national multicentric cohort study (Brazilian Peritoneal Dialysis Multicentric Study, BRAZPD). Adult incident patients recruited in the BRAZPD from December 2004 to October 2007 having undergone first PD catheter implantation were included in the analysis. Mechanical and infectious early complication rates were defined as time to the first event occurring up to 3 months after catheter insertion and adjusted for comorbidities. Valid data of 736 patients (mean age of 59 ± 16 years old, 52% women, 61% white) were analyzed. Mechanical (HR 0.99 [CI 0.56–1.76]; p = 0.98) and infectious (HR 0.63 [CI 0.32–1.23]; p = 0.17) early complication rates were similar between groups. Long‐term catheter survival was also similar between groups. Early complications rates and catheter survival were similar between groups defined by operator profile (nephrologist or surgeon), supporting the role of interventional nephrology in the placement of PD catheters.
Comparison of the Palindrome vs. Step‐Tip Tunneled Hemodialysis Catheter: A Prospective Randomized Trial
Authors: Hwang Hyeon Seok , Kang Seok Hui , Choi Sun Ryoung , Sun In O , Park Hoon Suk , Kim Yongsoo
Published: February 2012

Numerous designs for tunneled hemodialysis catheter have been developed in an effort to improve catheter function and survival. In this prospective randomized controlled study, 97 patients were randomized into the palindrome catheter group (PC, n = 47) and step‐tip catheter group (SC, n = 50). Demographic characteristics were not different between the two groups. The effective blood flow rates at different pump speeds were comparable between the two groups. The recirculation was low within acceptable range in both types of catheter, and hemodialysis adequacy was not different between the two groups. However, when arterial and venous blood lines were reversed, while the recirculation was significantly increased in SC, it was not increased at all in PC. The catheter dysfunction‐free survival rate was significantly higher in PC than in SC (78.9% vs. 54.4% at 2 months, p = 0.008). The overall catheter survival rate was also higher in PC than in SC (90.6% vs. 68.8% at 2 months, p = 0.015). We conclude that both catheters are equally effective on the adequate hemodialysis and low recirculation. However, the PCs have advantages over the SCs in terms of lower catheter dysfunction rate, lower recirculation with reversed blood lines, higher short‐term catheter survival rate.