bluuebunny/crossref_metadata_2025 huggingface dataset:
Ulnar Collateral Ligament Reconstruction Using Bisuspensory Fixation
Authors: Jackson Timothy J. , Adamson Gregory J. , Peterson Alexander , Patton John , McGarry Michelle H. , Lee Thay Q.
Published: April 2013

Background:

Many ulnar collateral ligament (UCL) reconstruction techniques have been created and biomechanically tested. Single-bundle reconstructions aim to re-create the important anterior bundle of the UCL. To date, no technique has utilized suspensory fixation on the ulnar and humeral sides to create a single-bundle reconstruction.

Hypothesis:

The bisuspensory technique will restore valgus laxity to its native state, with comparable load-to-failure characteristics to the docking technique.

Study Design:

Controlled laboratory study.

Methods:

Six matched pairs of fresh-frozen cadaveric elbows were randomized to undergo UCL reconstruction using either the docking technique or a novel single-bundle bisuspensory technique. Valgus laxity and rotation measurements were quantified using a MicroScribe 3DLX digitizer at various flexion angles for the native ligament, transected ligament, and 1 of the 2 tested reconstructed ligaments. Laxity testing was performed from maximum extension to 120° of flexion. Each reconstruction was then tested to failure, and the method of failure was recorded.

Results:

Valgus laxity was restored to the intact state at all degrees of elbow flexion for both the docking and bisuspensory techniques. In load-to-failure testing, there was no significant difference with regard to stiffness, ultimate torque, ultimate torque angle, energy absorbed, and applied moment to reach 10° of valgus. Yield torques for the bisuspensory and docking reconstructions were 18.7 ± 7.8 N·m and 18.6 ± 4.4 N·m, respectively ( P = .95). The ultimate torque for the bisuspensory technique measured 26.5 ± 9.2 N·m and for the docking technique measured 25.1 ± 7.1 N·m ( P = .78).

Conclusion:

The bisuspensory fixation technique, a reproducible single-bundle reconstruction, was able to restore valgus laxity to the native state, with similar load-to-failure characteristics as the docking technique.

Clinical Relevance:

This reconstruction technique could be considered in a clinical setting as a primary method of UCL reconstruction or as a backup fixation method should intraoperative complications occur.
Patrick de Maré’s Median Group and Its Application to Prison and the Community
Authors: Parsons David
Published: April 2013

This presentation to the Bolzano Congress in 2010 describes the value of Median Group Dialogue in work with offenders in prison and the community, and the success achieved.

Pat de Maré’s Median Group is the missing link between the disaffected individual and the depersonalized institution, which can bring about a transformation of humanizing the institution and socializing the individual. Institutional failure has resulted in a chasm between an increasingly sophisticated/divided society fuelled by the rapid advance of the technological revolution and the outmoded feudal controlling institution. When free to operate effectively the Median Group creates an atmosphere where the institution can become flexible and sensitive towards the needs and demands of individual members.

Having illustrated the application of Median Group Dialogue to the prison situation, this article proceeds to the difficulties encountered through the tendency of ossified institutions to reject change, and imagines another way forward starting in the community at large.
Experimental study of large-scale fire behavior under low pressure at high altitude
Authors: Yao Wei , Hu Xiaokang , Rong Jianzhong , Wang Jian , Zhang Hui
Published: April 2013

To investigate the fire behavior under low pressure, four configurations of cardboard box fires were comparatively tested in a sea-level city, Hefei, and a high-altitude city, Lhasa. During each test, mass burning rate, total heat release rate, multipoint flame temperature, and radiative heat flux were measured. From the experimental data, some specific fire behavior was observed that (1) the mass burning rate divided by fire base dimension can be correlated against the production of pressure-squared times length-cubed ( P2 L3) to the power of 0.31, (2) the heat of combustion is lower in Lhasa probably due to the incomplete solid pyrolysis limited by oxygen, (3) the dimensionless plume temperature is correlated against the dimensionless flame height with a pressure term to the power of −2.0, and (4) the relative flame temperature estimated from the radiative heat flux indicated that the overall flame temperature is higher in Lhasa.
“It Helps Me Transform in My Life From the Past to the New”
Authors: Vindevogel Sofie , Broekaert Eric , Derluyn Ilse
Published: April 2013

Although former child soldiers face considerable challenges after their return from the warring faction to the war-affected society, the presence of resources enables many to maintain well-being in the wake of child soldiering. Academic research has recently engaged with identifying these salient resources, but has left the question why they are helpful to former child soldiers largely unaddressed.

This study therefore focuses on the meaning underlying certain phenomena that causes them to become resources. Semistructured in-depth interviews and a free-listing task on resources were conducted with 48 northern Ugandan former child soldiers. The phenomenological hermeneutical method is applied to analyze their lived experiences and the meaning they assign to resources.

Four essential themes emerge from this study, representing the fourfold meaning of resources for former child soldiers in helping them (a) to break with their former existence as child soldiers, (b) to be able to overcome the challenges in their current life, (c) to belong to others and the environment to which they have returned, and (d) to become the person they aspire to be.

Considering these research themes in the context of former child soldiers’ return process, parallels with theories on transition are recognized and further explored so as to contextualize this emerging meaning. As such, this research delivers empirical evidence illustrating how resources help to pilot former child soldiers through transition in the wake of child soldiering.
B cell biology: implications for treatment of systemic lupus erythematosus
Authors: Anolik JH
Published: April 2013

B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody-independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B cell activation thresholds, B cell longevity, and apoptotic cell processing. Once tolerance is broken, autoantibodies contribute to autoimmunity by multiple mechanisms including immune-complex mediated Type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread utilization of B cell depletion therapy in autoimmune diseases and the need for new therapeutic approaches in SLE, a better understanding of human B cell subsets and the balance of pathogenic and regulatory functions is of the essence.
Minimising steroids in lupus nephritis – will B cell depletion pave the way?
Authors: Lightstone L
Published: April 2013

The aim of this review is to briefly explore how steroids came to be a presumed adjunct to all treatment regimens for lupus nephritis, despite being the main cause of long term damage among patients with lupus and despite increasingly effective alternative agents. I then go on to compare and contrast how differently immunosuppression regimens have developed in the world of solid organ transplantation. Almost from the start of transplantation a clear goal was to develop steroid sparing regimens – and now units such as our own routinely use induction with a biological, a single week of steroids and then monotherapy with tacrolimus. There has been a clear trend of using biologicals as induction agents and less immunosuppression in the long run but with improved outcomes. The drive has not been the same in lupus nephritis despite there being almost no evidence to support the use of steroids and certainly nothing to suggest correct dosage and timing. Rituximab, a B cell depleting antibody, offers great promise as a treatment agent despite the negative randomised control LUNAR trial. I briefly review our own data, demonstrating that early use of rituximab in lupus nephritis allows omission of oral steroids with excellent rates of remission (complete and partial). I review why the LUNAR trial should not discourage the use of rituximab. Finally, I introduce the RITUXILUP trial, a multicentre randomised controlled trial we are developing to formally evaluate our oral steroid avoiding regimen against a standard treatment regimen of mycophenolate mofetil and steroids. We have to follow the lead of our transplant colleagues and challenge the assumption that the future for lupus nephritis cannot be steroid free.
Spanish LupusPRO: cross-cultural validation study for lupus
Authors: Jolly M , Toloza S , Block J , Mikolaitis R , Kosinski M , Wallace D , Durran-Barragan S , Bertoli A , Blazevic I , Vilá L , Cooray D , Moldovan I , Katsaros E , Weisman M , Torralba KM , Alarcón G
Published: April 2013

Purpose

LupusPRO is a disease-targeted, patient-reported, outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). To expand the availability and use of the tool, we undertook a cross-cultural adaptation and validation study of the Spanish-translated version of the LupusPRO.

Method

Forward and back translations of the 43-item English LupusPRO were undertaken and pretested in five individuals. The finalized Spanish version was administered to 211 SLE patients of Hispanic ancestry from the US and Latin America. Short Form-36 (Spanish) and Spanish LupusPRO were also administered. Disease activity was ascertained using the systemic lupus erythematosus disease activity index. A Spanish LupusPRO questionnaire that could be completed within 2–3 days was mailed to SLE patients of Hispanic ancestry and they mailed it back. Internal consistency reliability, test-retest reliability, criterion validity (against disease activity or health status) and convergent validity were tested. All reported p values are two-tailed.

Results

A total of 211 Spanish-speaking SLE patients (90% women) participated. Test-retest reliability of LupusPRO domains ranged from 0.80–0.95, while internal consistency reliability of the domains ranged from 0.71–0.96. Convergent validity with corresponding domains of the SF-36 was present. All health-related quality of life domains of the LupusPRO (except procreation) performed well against disease activity measures, establishing its criterion validity. Confirmatory factor analysis showed a good fit.

Conclusion

The Spanish LupusPRO has fair psychometric properties and is now available to be included in clinical trials and in longitudinal studies for testing of responsiveness to change.
Kidney-limited thrombotic microangiopathy in patients with SLE treated with romiplostim
Authors: Tomov S , Lazarchick J , Self SE , Bruner ET , Budisavljevic MN
Published: April 2013

We present the case of a 19 year-old Caucasian female with history of systemic lupus erythematosus (SLE) and normal baseline kidney function who developed severe acute renal failure following treatment of thrombocytopenia with the thrombopoietic agent romiplostim. Percutaneous kidney biopsy revealed thrombotic microangiopathy (TMA) without immune complex lupus glomerulonephritis. We discuss pathogenesis and differential diagnosis of TMA in patients with SLE and raise concerns regarding the use of thrombopoietic agents in such patients. Based on favorable long-term outcome in our case aggressive treatment and in particular prolonged use of plasma exchange in these patients are advocated.
Steps Towards a Conceptualisation of Digital Institutions of Knowledge
Authors: Madsen Anders Koed
Published: April 2013

Digital traces are increasingly used as data with which to generate insights into social dynamics around complex issues such as the controversies surrounding biotechnology. Hyperlinks can, for example, be used to locate a network of relevant stakeholders around an emerging technology and a popular way to makes sense of this kind of data is to rely on software that can synthesise it and present it in ‘Web-based visualisations’. This short article presents a discussion of ways in which such visualisations can be made an object of social scientific study and it provides tentative steps towards a theoretical framework that allows us to conceptualise such visualisations as emerging ‘Digital Institutions of Knowledge’. This framework is rooted in discursive and process oriented institutionalisms and in the concept of ‘market devices’ which has been powerful within economic sociology. The ordinally ranked results of Google are presented as the simplest examples of a Web-based visualisation and its relevant theoretical characteristics are emphasised by juxtaposing it to FICO-scores which serve as an example of a market device. Similarities and differences between the two devices are used as a basis from which to ponder the institutional aspects of Web-based visualisations.
A Retrospective Survey of Childhood ADHD Symptomatology Among Adult Narcoleptics
Authors: Modestino Edward J. , Winchester Jeanna
Published: April 2013

Objective: This study examined the retrospective history of childhood ADHD symptomatology in an adult narcoleptic population (Narcolepsy Group [NG]: n = 161) compared with a control group (CG: n = 117). Method: Both groups completed the Wender Utah Rating Scale (WURS), a retrospective self-report questionnaire indicating the presence of childhood ADHD symptomatology in adults. Results: Childhood ADHD symptoms were significantly greater in NG than CG ( p < .001). Joint prevalence calculations of childhood ADHD symptomatology in NG were more than 8 to 15 times greater than expected. Among NG, those individuals with a greater score on the WURS, indicative of childhood ADHD symptomatology, also had shorter sleep onsets on the Multiple Sleep Latency Test, a common objective measure of sleepiness, t(97) = −7.11, p < .05. Conclusion: It appears that self-reported childhood ADHD symptomatology history among adult narcoleptics is common. Future research is warranted with adult narcoleptics to elucidate the true nature of this.
Neuromyelitis optica in patients with coexisting human immunodeficiency virus infections
Authors: Feyissa Anteneh M , Singh Parbhdeep , Smith Robert G
Published: April 2013

Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic’s disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge.
Impaired brachial artery flow-mediated vasodilation in response to handgrip exercise-induced increases in shear stress in young smokers
Authors: Findlay Briar B , Gupta Parnika , Szijgyarto Ingrid C , Pyke Kyra E
Published: April 2013

Smoking is an established risk factor for cardiovascular disease. It has also been shown to result in endothelial dysfunction as assessed by flow-mediated dilation (FMD) in response to reactive hyperemia (RH)-induced increases in shear stress. Handgrip exercise (HGEX) is an emerging alternative method to increase shear stress for FMD assessment (HGEX-FMD) and the purpose of this study was to identify the impact of smoking on HGEX-FMD in young healthy subjects. Brachial artery RH-FMD and HGEX-FMD (10-minute bout of HGEX) was assessed in eight smokers (S) and 14 non-smokers (NS) (age 21 ± 2 years). Brachial artery diameter and mean blood velocity were assessed with echo and Doppler ultrasound, respectively. Shear stress was estimated by shear rate (SR = brachial artery blood velocity/diameter). The SR stimulus did not differ between groups for either test (RH-FMD (SR area under the curve until peak diameter measurement), p = 0.897; HGEX-FMD (average SR over 10-minute exercise bout), p = 0.599). The RH-FMD magnitude was not significantly different between groups (S: 7.7 ± 2.2% vs NS: 7.9 ± 2.4%, p = 0.838); however, the HGEX-FMD magnitude was significantly impaired in smokers (S: 6.1 ± 3.4% vs NS: 9.6 ± 3.6%, p = 0.037). In conclusion, HGEX-FMD assessment detected vascular dysfunction in young healthy smokers while RH-FMD did not. This suggests that HGEX-FMD may be useful in the early detection of smoking-induced impairments in endothelial function. Further research is required to explore this phenomenon in other populations and to isolate underlying mechanisms.
Popularizing ethnography: reflections on writing for popular audiences in magazines and blogs
Authors: Vannini Phillip
Published: April 2013

Ethnography has witnessed a staggering proliferation of genres over the last three decades. Modes of communication have similarly expanded. In spite of this, most ethnographers still rely on the prototypical media of their trade: the book and the journal article. The objective of this article is to examine the process of communicating ethnography through more widely accessible media such as popular print magazines, web-based magazines, and blogs. Drawing examples from my own public ethnography, I reflect on practical considerations that ethnographers might want to entertain whenever they attempt to popularize their work through these channels. I also provide reflections on the risks and limitations typical of these media.
Equality-tempered prioritarianism
Authors: Dorsey Dale
Published: April 2013

In this paper, I present and explore an alternative to a standard prioritarian axiology. Equality-tempered prioritarianism holds that the value of welfare increases should be balanced against the value of equality. However, given that, under prioritarianism, the value of marginal welfare benefits decreases as the welfare of beneficiaries increases, equality-tempered prioritarianism holds that the intrinsic value of equality will be sufficient to alter a prioritarian verdict only in cases in which welfare benefits are granted to the very well-off. I argue that this view, suitably refined, solves a persistent problem for prioritarianism, and is superior to alternatives.
The Impact of Political Skill on Employees’ Perceptions of Ethical Leadership
Authors: Harvey Paul , Harris Kenneth J. , Kacmar K. Michele , Buckless Anne , Pescosolido Anthony T.
Published: April 2013

We investigate whether leader political skill (LPS) increases employees’ perceptions of ethical leadership, even among leaders who acknowledge engaging in deviant behaviors. Study 1 indicated a positive relationship between LPS and ethical leadership perceptions, resulting in improved commitment and reduced stress levels among employees. Study 2 indicated that politically skilled leaders who engaged in deviant behaviors were perceived to be more ethical than deviant leaders with low political skill. Study 2 also suggested that LPS was negatively associated with employee deviance. These results suggest that political skill promotes ethical employee behaviors and other beneficial outcomes but might also help leaders disguise deviant intentions.
Al Jazeera’s Palestine Papers: Middle East media politics in the post-WikiLeaks era
Authors: Zayani Mohamed
Published: April 2013

Shortly after WikiLeaks published thousands of confidential US diplomatic cables, Al Jazeera released hundreds of classified documents pertaining to the Palestinian–Israeli negotiations. Known as the ‘Palestine Papers’, these documents are noteworthy not only because they provide insights into the stalled negotiations and rekindle the debate over the Middle East conflict, but also because they offer a glimpse into the complex interpenetration between media, geo-politics, and state interests in a conflict-ridden region in the post-WikiLeaks era.
Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis
Authors: Williams Patrick A. , Bhaijee Feriyl , Rezeanu Luminita , Hamilton Robert D. , Vijayakumar Srinivasan
Published: April 2013

Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.
Spontaneous Atraumatic Mediastinal Hemorrhage
Authors: Iskander Morkos , Siddique Khurram , Kaul Anil
Published: April 2013

Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.
Circulating microRNAs in hematological diseases: principles, challenges, and perspectives
Authors: Grasedieck Sarah , Sorrentino Antonio , Langer Christian , Buske Christian , Döhner Hartmut , Mertens Daniel , Kuchenbauer Florian
Published: April 2013

The complex microRNA (miRNA) network plays an important role in the regulation of cellular processes such as development, differentiation, and apoptosis. Recently, the presence of cell-free miRNAs that circulate in body fluids was discovered. The ability of these circulating miRNAs to mirror physiological and pathophysiological conditions as well as their high stability in stored patient samples underlines the potential of these molecules to serve as biomarkers for various diseases. In this review, we describe recent findings in miRNA-mediated cell-to-cell communication and the functions of circulating miRNAs in the field of hematology. Furthermore, we discuss current approaches to design biomarker studies with circulating miRNAs. This article critically reviews the novel field of circulating miRNAs and highlights their suitability for clinical and basic research in addition to their potential as a novel class of biomarkers.
Burden of disease due to dementia in the elderly population of Korea: present and future
Authors: Park Jae-Hyun , Eum Jin-Hee , Bold Bolor , Cheong Hae-Kwan
Published: April 2013

Background

With the rapid aging of populations around the world, dementia has become one of the most important public health problems in Eastern Asian countries. The purpose of the present study was to provide an estimate of the burden of dementia and forecast its future burden, as generalized to the Korean population, and to provide detailed gender- and age-specific information regarding the burden of dementia in the elderly population of Korea.

Methods

‘Disability-adjusted life years’ (DALYs) were used to estimate the burden of dementia. Epidemiologic data from national statistics and nationwide epidemiologic studies in the year 2008 were used to obtain representative outcomes for the Korean population. We estimated the DALYs due to dementia from the years 2010 to 2050 by applying demographic structure projections in terms of 5-year age groups in Korea.

Results

The burden of disease due to dementia in Korea is 528 per 100,000 population (males: 435, females: 622) and 5,117 per 100,000 in those over the age of 65 years (males: 5,228; females: 5,041); this accounts for 4.5% of the total burden of disease in the year 2008. In the year 2050, DALYs due to dementia (814,629) are expected to be 3.0 times higher than those in the year 2010 (274,849).

Conclusion

Dementia has the highest burden of disease in the elderly Korean population, and this burden will increase sharply with the aging of the population. More comprehensive and multi-dimensional approaches, including clinical, psychological, social, and political means will be needed for the management of the dramatically increasing burden of dementia.
Helium beam shadowing for high spatial resolution patterning of antibodies on microstructured diagnostic surfaces
Authors: Cacao Eliedonna , Sherlock Tim , Nasrullah Azeem , Kemper Steven , Knoop Jennifer , Kourentzi Katerina , Ruchhoeft Paul , Stein Gila E , Atmar Robert L , Willson Richard C
Published: April 2013

We have developed a technique for the high-resolution, self-aligning, and high-throughput patterning of antibody binding functionality on surfaces by selectively changing the reactivity of protein-coated surfaces in specific regions of a workpiece with a beam of energetic helium particles. The exposed areas are passivated with bovine serum albumin (BSA) and no longer bind the antigen. We demonstrate that patterns can be formed (1) by using a stencil mask with etched openings that forms a patterned exposure, or (2) by using angled exposure to cast shadows of existing raised microstructures on the surface to form self-aligned patterns. We demonstrate the efficacy of this process through the patterning of anti-lysozyme, anti-Norwalk virus, and anti-Escherichia coli antibodies and the subsequent detection of each of their targets by the enzyme-mediated formation of colored or silver deposits, and also by binding of gold nanoparticles. The process allows for the patterning of three-dimensional structures by inclining the sample relative to the beam so that the shadowed regions remain unaltered. We demonstrate that the resolution of the patterning process is of the order of hundreds of nanometers, and that the approach is well-suited for high throughput patterning.
Emission spectra profiling of fluorescent proteins in living plant cells
Authors: Mylle Evelien , Codreanu Mirela-Corina , Boruc Joanna , Russinova Eugenia
Published: April 2013

Background

Fluorescence imaging at high spectral resolution allows the simultaneous recording of multiple fluorophores without switching optical filters, which is especially useful for time-lapse analysis of living cells. The collected emission spectra can be used to distinguish fluorophores by a computation analysis called linear unmixing. The availability of accurate reference spectra for different fluorophores is crucial for this type of analysis. The reference spectra used by plant cell biologists are in most cases derived from the analysis of fluorescent proteins in solution or produced in animal cells, although these spectra are influenced by both the cellular environment and the components of the optical system. For instance, plant cells contain various autofluorescent compounds, such as cell wall polymers and chlorophyll, that affect the spectral detection of some fluorophores. Therefore, it is important to acquire both reference and experimental spectra under the same biological conditions and through the same imaging systems.

Results

Entry clones (pENTR) of fluorescent proteins (FPs) were constructed in order to create C- or N-terminal protein fusions with the MultiSite Gateway recombination technology. The emission spectra for eight FPs, fused C-terminally to the A- or B-type cyclin dependent kinases (CDKA;1 and CDKB1;1) and transiently expressed in epidermal cells of tobacco (Nicotiana benthamiana), were determined by using the Olympus FluoView™ FV1000 Confocal Laser Scanning Microscope. These experimental spectra were then used in unmixing experiments in order to separate the emission of fluorophores with overlapping spectral properties in living plant cells.

Conclusions

Spectral imaging and linear unmixing have a great potential for efficient multicolor detection in living plant cells. The emission spectra for eight of the most commonly used FPs were obtained in epidermal cells of tobacco leaves and used in unmixing experiments. The generated set of FP Gateway entry vectors represents a valuable resource for plant cell biologists.
Lipid production of Chlorella vulgaris and Pseudokirchneriella subcapitata
Authors: Gonçalves Ana L , Pires José CM , Simões Manuel
Published: April 2013

Background

The depletion of fossil fuel reserves has stimulated the search for sustainable sources of energy that are carbon-neutral or renewable. In this context, microalgae are a promising energetic resource. They are photosynthetic microorganisms that use CO2 as carbon source, with high specific growth rates. Furthermore, some species present high lipid content that can be easily converted into biodiesel. Accordingly, this study aims to analyze the effect of light supply (one of the most important culture parameters) on lipid production of selected microalgae, Chlorella vulgaris and Pseudokirchneriella subcapitata.

Methods

Both microalgal species were cultured under different light irradiance values (36, 72, 96, and 126 μE m−2 s−1) and for each light irradiance value, three light/dark ratios (10:14, 14:10, and 24:0) were tested. Lipid contents of both microalgae were then determined using a recently developed colorimetric method.

Results/Conclusions

P. subcapitata presented higher lipid productivity than C. vulgaris. High lipid concentration was achieved in microalgal cultures with higher light irradiance values. However, for 96 and 126 μE m−2 s−1, lipid productions of both microalgae were not significantly higher than with 72 μE m−2 s−1, which means that microalgal light saturation point may be achieved.
Time to change, time to evaluate. Invited commentary on … Evaluation of England's Time to Change programme
Authors: Sartorius Norman
Published: April 2013

Time to Change is the largest national programme to counter stigma ever undertaken. It demonstrates that stigmatisation and its consequences are gradually becoming recognised as the most important obstacle to the development of mental health programmes. It also demonstrates that they can be prevented or reduced. The programme's evaluation answered many questions but others remain - concerning the indicators of success and ways of assessing them and relevance of the programme's achievements. The programme and its evaluation are important steps in the development of anti-stigma programmes worldwide.
Time to Change campaign through the of a service user. Invited commentary on … Evaluation of England's Time to Change programme
Authors: Nettle Mary
Published: April 2013

The Time to Change campaign and its evaluation in this supplement are looked at from a service user's perspective. A number of achievements are applauded, but pertinent questions about the campaign analysis are raised and a qualitative evaluation is called for.
ERK2 but not ERK1 mediates HGF-induced motility in non small cell lung carcinoma cell lines
Authors: Radtke Simone , Milanovic Mina , Rossé Carine , de Rycker Manu , Lachmann Sylvie , Hibbert Andrew , Kermorgant Stéphanie , Parker Peter J.
Published: April 2013

Aberrant signalling of receptor tyrosine kinases (RTKs), such as c-Met, the receptor for hepatocyte growth factor (HGF), has been implicated in the oncogenesis of various tumours including non-small cell lung carcinoma (NSCLC). Through its pro-migratory properties, c-Met has been implicated specifically in the process of tumour metastasis demanding a better understanding of the underlying signalling pathways. Various players downstream of c-Met have been well characterised, including the extracellular-signal-regulated kinases (ERKs) 1/2. In a small interfering (si) RNA based high throughput wound healing screen performed in A549 lung carcinoma cells, we identified ERK2 but not ERK1 as a strong mediator of HGF-induced motility. This finding was confirmed in several NSCLC cell lines as well as HeLa cells. One known substrate for ERK kinases in cell migration, the focal adhesion protein paxillin, was also one of the hits identified in the screen. We demonstrate that HGF stimulation results in a time dependent phosphorylation of paxillin on serine 126, a process which can be blocked by inhibition of the ERK1/2 upstream kinase Mitogen-Activated Protein Kinase/ERK Kinase 1 (MEK1) or inhibition of glycogen synthase kinase (GSK) 3. Further we show that paxillin turnover at focal adhesions is increased upon HGF-stimulation, an effect that is dependent on serines 126 (GSK3 site) and 130 (ERK site) within paxillin. In line with the isoform specific requirement of ERK2 for HGF-mediated migration in lung tumour cell models, ERK2 but not ERK1 is shown to be responsible for paxillin S126 phosphorylation and its increased turnover at focal adhesions.
Netrin-1 induced activation of Notch signaling mediates glioblastoma cell invasion
Authors: Ylivinkka Irene , Hu Yizhou , Chen Ping , Rantanen Ville , Hautaniemi Sampsa , Nyman Tuula A. , Keski-Oja Jorma , Hyytiäinen Marko
Published: April 2013

Glioblastoma multiforme is an aggressively invading human brain cancer, which lacks effective treatment. Axonal guidance protein, netrin-1, is overexpressed in glioblastoma tumor biopsies. By experimental overexpression we observed that netrin-1 increased and downregulation of it decreased cell invasiveness in Matrigel invasion assays. Using tandem affinity purification and mass spectrometry protein identification we observed that netrin-1 forms a complex with both Notch2 and Jagged1. Recombinant Netrin-1 colocalized with Jagged1 and Notch2 at the cell surface and was further found in the intracellular vesicles with Jagged1, but not with Notch2. Netrin-1 activated Notch signaling and subsequent glioblastoma cell invasion. Interestingly, the recombinant central domain of netrin-1 counteracted the effects of the full-length netrin-1: it inhibited glioblastoma cell invasion and Notch activation by retaining the Notch signaling complex at the cell surface. This finding may have therapeutic implications. Current results reveal a new mechanism leading to glioblastoma cell invasion, where netrin-1 activates Notch signaling.
Microtubule motors mediate endosomal sorting by maintaining functional domain organization.
Authors: Hunt Sylvie D. , Townley Anna K. , Danson Chris M. , Cullen Peter J. , Stephens David J.
Published: April 2013

Many microtubule motors have been shown to couple to endosomal membranes. These motors include dynein as well as many different kinesin family members. Sorting nexins (SNXs) are central to the organization and function of endosomes. These proteins can actively shape endosomal membranes and couple directly or indirectly to the minus-end microtubule motor dynein. Motor proteins acting on endosomes drive their motility, dictate their morphology and impact on cargo segregation. We have used well-characterized members of the sorting nexin family to elucidate motor coupling using high resolution light microscopy coupled with depletion of specific microtubule motors. Endosomal domains labelled with sorting nexins 1, 4, and 8 (SNX1, SNX4, SNX8) couple to discrete combinations of dynein and kinesin motors. These specific combinations govern the structure and motility of each SNX-coated membrane as well as the segregation of distinct functional endosomal subdomains. Together our data show that these key features of endosome dynamics are governed by the same set of opposing microtubule motors. Thus, microtubule motors help to define the mosaic layout of endosomes that underpins cargo sorting.
Systematic Review and Quality Assessment of Cost-Effectiveness Analysis of Pharmaceutical Therapies for Advanced Colorectal Cancer
Authors: Leung Henry WC , Chan Agnes LF , Leung Matthew SH , Lu Chin-Li
Published: April 2013

OBJECTIVE

To systematically review and assess the quality of cost-effectiveness analyses (CEAs) of pharmaceutical therapies for metastatic colorectal cancer (mCRC).

DATA SOURCES

The MEDLINE, EMBASE, Cochrane, and EconLit databases were searched for the Medical Subject Headings or text key words quality-adjusted, QALY, life-year gained (LYG), and cost-effectiveness (January 1, 1999–December 31, 2009).

STUDY SELECTION

Original CEAs of mCRC pharmacotherapy published in English were included. CEAs that measured health effects in units other than quality-adjusted life years or LYG and letters to the editor, case reports, posters, and editorials were excluded.

DATA EXTRACTION

Each article was independently assessed by 2 trained reviewers according to a quality checklist created by the Panel on Cost-Effectiveness in Health and Medicine.

RESULTS

Twenty-four CEA studies pertaining to pharmaceutical therapies for mCRC were identified. All studies showed a wide variation in methodologic approaches, which resulted in a different range of incremental cost-effectiveness ratios reported for each regimen. We found common methodologic flaws in a significant number of CEA studies, including lack of clear description for critique of data quality; lack of method for adjusting costs for inflation and methods for obtaining expert judgment; no results of model validation; wide differences in the types of perspective, time horizon, study design, cost categories, and effect outcomes; and no quality assess ment of data (cost and effectiveness) for the interventions evaluation.

CONCLUSIONS

This study has shown a wide variation in the methodology and quality of cost-effectiveness analysis for mCRC. Improving quality and harmonization of CEA for cancer treatment is needed. Further study is suggested to assess the quality of CEA methodology outside the mCRC disease state.
Safety of New Oral Anticoagulants with Dual Antiplatelet Therapy in Patients with Acute Coronary Syndromes
Authors: Tsu Laura V , Dager William E
Published: April 2013

OBJECTIVE

To determine the safety of dabigatran, rivaroxaban, or apixaban with dual antiplatelet therapy in patients with acute coronary syndromes.

DATA SOURCES

A literature search of MEDLINE (1946–January 2013) was conducted, using the search terms dabigatran, rivaroxaban, or apixaban in combination with dual antiplatelet therapy. A search of literature citations was conducted to identify additional references.

STUDY SELECTION AND DATA EXTRACTION

Randomized controlled trials involving the use of one of the new anticoagulants with concomitant dual antiplatelet therapy were included in the review.

DATA SYNTHESIS

Five randomized controlled trials were reviewed, including 1 trial of dabigatran, 2 trials of rivaroxaban, and 2 trials of apixaban. These studies were conducted in patients with a recent acute coronary syndrome, so most patients were receiving aspirin and clopidogrel as dual antiplatelet therapy in addition to a therapeutic dose of one of the anticoagulants. The 3 Phase 2 dose-ranging trials (1 each of dabigatran, rivaroxaban, and apixaban) found an increasing risk of major and clinically relevant nonmajor bleeding with increasing doses of the anticoagulants. The Phase 3 trial of apixaban was terminated early due to an excess of bleeding events, and the trial of rivaroxaban also found an increased risk of bleeding.

CONCLUSIONS

The emerging use of dabigatran, rivaroxaban, and apixaban into clinical practice has introduced additional management options, but also safety concerns when combined with antiplatelet agents. Due to the increased risk of bleeding when combining an anticoagulant with 2 antiplatelet agents, clinicians should monitor and educate patients on avoiding potential complications. The need for continued triple regimens should be periodically reviewed.
Current Approaches to Punitive Action for Medication Errors by Boards of Pharmacy
Authors: Holdsworth Mark , Wittstrom Kristina , Yeitrakis Tiffany
Published: April 2013

BACKGROUND

To increase disclosure of errors and lead to system improvements, publications recommend a nonpunitive approach to medication errors. To our knowledge there is no published information regarding the extent or bases on which boards of pharmacy invoke punitive action against pharmacists involved in medication errors.

OBJECTIVE

To determine how often and on what bases boards of pharmacy determine punitive action to be taken against pharmacists involved in medication error events.

METHODS

The policies, procedures, and practices regarding medication errors by pharmacists for 49 of the 50 US boards of pharmacy were reviewed by pharmacy students at the University of New Mexico as a Safe Medication Practices class assignment.

RESULTS

Most boards of pharmacy invoke punitive action against pharmacists involved in medication errors. Most states do not have specific rules or regulations that stipulate errors as actual violations and most determinations are made on a case-by-case basis. The major determinants of punitive action were error severity, actual patient injury, patient complaints, and factors related to the pharmacist. The most common types of punitive action include license suspension, probation, or revocation, and fines. In at least 17 states, incarceration was also a possible punitive action. The most common bases for punitive action were to address public safety/health and public complaints.

CONCLUSIONS

Despite the fact that punitive action is not recommended as best practice for addressing medication errors made by health care practitioners, most state boards of pharmacy use punitive measures against pharmacists involved in medication errors. Based on current recommendations, such actions would not be expected to lead to improvements in the health care system.
Disruption of Arp2/3 Results in Asymmetric Structural Plasticity of Dendritic Spines and Progressive Synaptic and Behavioral Abnormalities
Authors: Kim Il Hwan , Racz Bence , Wang Hong , Burianek Lauren , Weinberg Richard , Yasuda Ryohei , Wetsel William C. , Soderling Scott H.
Published: April 2013

Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involved. Several known genetic risk factors for psychiatric disease are related to the regulation of actin polymerization, which plays a key role in synaptic plasticity. To gain insight into and test the possible pathogenetic role of this pathway, we designed a conditional knock-out of the Arp2/3 complex, a conserved final output for actin signaling pathways that orchestratesde novoactin polymerization. Here we report that postnatal loss of the Arp2/3 subunit ArpC3 in forebrain excitatory neurons leads to an asymmetric structural plasticity of dendritic spines, followed by a progressive loss of spine synapses. This progression of synaptic deficits corresponds with an evolution of distinct cognitive, psychomotor, and social disturbances as the mice age. Together, these results point to the dysfunction of actin signaling, specifically that which converges to regulate Arp2/3, as an important cellular pathway that may contribute to the etiology of complex psychiatric disorders.
Abstract Representations of Location and Facing Direction in the Human Brain
Authors: Vass Lindsay K. , Epstein Russell A.
Published: April 2013

Humans, like other mobile organisms, rely on spatial representations to guide navigation from place to place. Although previous work has identified neural systems involved in wayfinding, the specific spatial codes supported by these systems are not well understood. We use functional magnetic resonance imaging to identify regions within the human medial temporal and medial parietal lobes that encode two fundamental spatial quantities—location and facing direction—in a manner that abstracts away from sensory inputs. University students were scanned while viewing photographs taken at several familiar campus locations. Multivoxel pattern analyses indicated that the left presubiculum, retrosplenial complex, and parietal-occipital sulcus coded location identity even across non-overlapping views, whereas the right presubiculum coded facing direction even across noncontiguous locations. The location and direction codes supported by these regions may be critical to our ability to navigate within the extended environment and to understand its large-scale spatial structure.