bluuebunny/crossref_metadata_2025 huggingface dataset:
The Challenge for a European Network of Biobanks for Rare Diseases Taken up by RD-Connect
Authors: Monaco Lucia , Crimi Marco , Wang Chiuhui Mary
Published: March 2015

Access to biological materials is a key prerequisite for scientific research in any medical field and in particular for research into rare diseases (RDs), for which obtaining high-quality samples and the related clinical data remains a major hurdle. RD biobanks play a pivotal role in making such materials and data available to the scientific community. In order to increase the effectiveness of RD biobanks, three major challenges need to be met: maximise access to rare biological samples stored in RD biobanks spread globally by the international scientific community, promote networking among such biobanks to share quality standards and procedures and allow collaboration with RD registries and databases, and finally adopt an efficient management model compliant with legal and ethical issues and ensuring biobank sustainability. The European program RD-Connect, funded under the FP7 program, addresses all of these issues through an articulated action plan aimed at building a network of European RD biobanks. Ultimately, RD-Connect will offer access to precious, quality-controlled biological samples from RD patients through an online, searchable, dynamic catalogue in the context of an integrated platform that links RD patient registries to biobanks and to clinical bioinformatics data for RD research.
Infrastructure and Facilities for Human Biobanking in Low- and Middle-Income Countries: A Situation Analysis
Authors: Mendy Maimuna , Caboux Elodie , Sylla Bakary S. , Dillner Joakim , Chinquee Joseph , Wild Christopher ,   BCNet survey participants
Published: March 2015

Objective: To collect information on biobanking facilities in low- and middle-income countries (LMICs) as a first step towards establishing an LMIC biobank and cohort building network (BCNet) to support research, with a focus on cancer control. Method: Sixty centres were identified from sources including cancer centres, universities, hospitals, and public health facilities and invited to participate in a survey between December 2012 and March 2013. Results: Of the 27 centres (45%) that responded, most have existed for <10 years. They store between 1,000 and 1,000,000 research samples as well as samples remaining after clinical diagnosis. Sample storage is mostly in freezers, although 45% (9/20) of the centres do not have regular access to electricity. Biobank managers, sample management systems, and mechanisms for follow-up using linkages are uncommon. Many (80%; 21/26) of the centres have regulations to govern research, but regulations for the use of biobank resources (samples and data) are not well developed. Conclusions: Biobanking facilities are being developed in LMICs. Shortcomings in international visibility, sample sharing regulations, standardization, quality assurance, and sample management systems could be alleviated by international networking. Stakeholders need to work together to increase access to high-quality biological resources for scientific research.
The Role of Diagnostic Tissue in Research
Authors: Cheung Carol C. , Torlakovic Emina E. , Porwit Anna
Published: March 2015

There are two broad classes (or categories) of excised human tissue: diagnostic tissue (DT) and research tissue (RT). Classification of excised human tissue does not define its ultimate use and ultimate use of excised human tissue does not define its classification. While both DT and RT can be used for research, DT has specific requirements with respect to how it must be handled if and when being accessed for research. We highlight distinguishing features of DT: (1) it is a clinical record, (2) it must be identifiable to a specific individual, (3) it is stewarded by pathology departments/clinical laboratories and (4) it has a mandatory retention period. We discuss how the further sub-classification of DT into archived DT (aDT) and excess DT (eDT) impacts the nature of its role in research. We examine the concept of DT as a clinical record and emphasize the impact of mandatory retention as it applies to how DT may be accessed for research purposes. We explain the role of post-retention eDT as a source of RT as well as procedures for access to in-retention aDT for research. Clarity of such issues will facilitate responsible access to DT for research.
Implementation of a Cost-Accounting Model in a Biobank: Practical Implications
Authors: Gonzalez-Sanchez Maria Beatriz , Lopez-Valeiras Ernesto , García-Montero Andres C.
Published: March 2015

Given the state of global economy, cost measurement and control have become increasingly relevant over the past years. The scarcity of resources and the need to use these resources more efficiently is making cost information essential in management, even in non-profit public institutions. Biobanks are no exception. However, no empirical experiences on the implementation of cost accounting in biobanks have been published to date. The aim of this paper is to present a step-by-step implementation of a cost-accounting tool for the main production and distribution activities of a real/active biobank, including a comprehensive explanation on how to perform the calculations carried out in this model. Two mathematical models for the analysis of (1) production costs and (2) request costs (order management and sample distribution) have stemmed from the analysis of the results of this implementation, and different theoretical scenarios have been prepared. Global analysis and discussion provides valuable information for internal biobank management and even for strategic decisions at the research and development governmental policies level.
A Pilot Study to Investigate the Efficacy of Fibrin Sealant (Tisseel®) in the Loop Electrosurgical Excision Procedure
Authors: Kim Jin Hwi , Park Tae Chul , Park Geum Ae , Song Jae Yeon , Kim Yeon Hee , Lee Hee Joong , Lee Sung Jong , Lee Keun Ho , Hur Soo Young , Park Jong Sup
Published: March 2015

Aims: The objective of the current study was to evaluate the efficacy and feasibility of fibrin sealant (Tisseel®) in the loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN 2 or 3). Methods: We designed a single-blind, prospective, randomized study in 40 consecutive women undergoing LEEP for CIN 2 or 3 at our institute. Two milliliters of fibrin sealant (Tisseel) was applied to the uterine cervix of 20 women immediately after LEEP surgery (treatment group). We evaluated abdominal pain, vaginal bleeding, vaginal discharge and impairment in daily living after 1 week using visual analogue scale questionnaires and compared the results with those of 20 women who did not receive fibrin sealant (control group). Results: Among 40 women who returned for a follow-up 1 week after LEEP, 25 women (62.5%) reported at least one moderate to severe postprocedural symptom. The mean duration of moderate to severe vaginal bleeding and impairment in daily living during postoperative week 1 for the treatment group and the control group was 0.3 ± 0.80 versus 1.7 ± 2.36 days (p = 0.015) and 0.9 ± 1.37 versus 3.00 ± 2.62 days (p = 0.060), respectively. Conclusion: Intraoperative application of fibrin sealant (Tisseel) in LEEP can decrease postoperative vaginal bleeding and impairment in daily living.
Association of MDM2 Polymorphism with Risk and Prognosis of Leukemia: A Meta-Analysis
Authors: He Xuepeng , Chen Peng , Yang Kai , Liu Bing , Zhang Yuan , Wang Fang , Guo Zhi , Liu Xiaodong , Lou Jinxing , Chen Huiren
Published: March 2015

Objective: In this study, we performed an updated meta-analysis by summarizing all available relevant association studies to evaluate whether the murine double minute-2 (MDM2) T309G polymorphism is associated with risk of leukemia and to determine its prognostic effect. Material and Methods: Studies published in PubMed, Embase and the Cochrane Controlled Trial Register were searched till June 2014 using the search terms ‘MDM2', ‘polymorphism' and ‘leukemia'. Results: Eleven studies were included in this meta-analysis, with a total of 2,478 patients accrued. There were 8 studies providing data on single nucleotide polymorphism at position 309 (SNP309) and risk of leukemia and 7 studies providing data on SNP309 and overall survival. Our analysis showed that patients having G/G mutations had a significantly higher risk of developing leukemia (HR 1.90, 95% CI 1.56-2.31, p < 0.00001), while the association between G/T and leukemia was not significant (HR 1.18, 95% CI 0.96-1.45, p = 0.11). In addition, SNP309 was not significantly associated with patient survival (HR 1.29, 95% CI 0.79-2.13, p = 0.31). Conclusions: Our meta-analysis showed that the MDM2 T309G variation, especially homozygous G/G, might be associated with an increased risk of leukemia. Additional studies are needed to confirm the findings as well as to understand the underlying mechanisms.
Normal Development of Human Brain White Matter from Infancy to Early Adulthood: A Diffusion Tensor Imaging Study
Authors: Uda Satoshi , Matsui Mie , Tanaka Chiaki , Uematsu Akiko , Miura Kayoko , Kawana Izumi , Noguchi Kyo
Published: March 2015

Diffusion tensor imaging (DTI), which measures the magnitude of anisotropy of water diffusion in white matter, has recently been used to visualize and quantify parameters of neural tracts connecting brain regions. In order to investigate the developmental changes and sex and hemispheric differences of neural fibers in normal white matter, we used DTI to examine 52 healthy humans ranging in age from 2 months to 25 years. We extracted the following tracts of interest (TOIs) using the region of interest method: the corpus callosum (CC), cingulum hippocampus (CGH), inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF). We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). Approximate values and changes in growth rates of all DTI parameters at each age were calculated and analyzed using LOESS (locally weighted scatterplot smoothing). We found that for all TOIs, FA increased with age, whereas ADC, AD and RD values decreased with age. The turning point of growth rates was at approximately 6 years. FA in the CC was greater than that in the SLF, ILF and CGH. Moreover, FA, ADC and AD of the splenium of the CC (sCC) were greater than in the genu of the CC (gCC), whereas the RD of the sCC was lower than the RD of the gCC. The FA of right-hemisphere TOIs was significantly greater than that of left-hemisphere TOIs. In infants, growth rates of both FA and RD were larger than those of AD. Our data show that developmental patterns differ by TOIs and myelination along with the development of white matter, which can be mainly expressed as an increase in FA together with a decrease in RD. These findings clarify the long-term normal developmental characteristics of white matter microstructure from infancy to early adulthood.
Human Umbilical Cord Blood Cells Ameliorate Motor Deficits in Rabbits in a Cerebral Palsy Model
Authors: Drobyshevsky Alexander , Cotten C. Michael , Shi Zhongjie , Luo Kehuan , Jiang Rugang , Derrick Matthew , Tracy Elizabeth T. , Gentry Tracy , Goldberg Ronald N. , Kurtzberg Joanne , Tan Sidhartha
Published: March 2015

Cerebral palsy (CP) has a significant impact on both patients and society, but therapy is limited. Human umbilical cord blood cells (HUCBC), containing various stem and progenitor cells, have been used to treat various brain genetic conditions. In small animal experiments, HUCBC have improved outcomes after hypoxic-ischemic (HI) injury. Clinical trials using HUCBC are underway, testing feasibility, safety and efficacy for neonatal injury as well as CP. We tested HUCBC therapy in a validated rabbit model of CP after acute changes secondary to HI injury had subsided. Following uterine ischemia at 70% gestation, we infused HUCBC into newborn rabbit kits with either mild or severe neurobehavioral changes. Infusion of high-dose HUCBC (5 × 106 cells) dramatically altered the natural history of the injury, alleviating the abnormal phenotype including posture, righting reflex, locomotion, tone, and dystonia. Half the high dose showed lesser but still significant improvement. The swimming test, however, showed that joint function did not restore to naïve control function in either group. Tracing HUCBC with either MRI biomarkers or PCR for human DNA found little penetration of HUCBC in the newborn brain in the immediate newborn period, suggesting that the beneficial effects were not due to cellular integration or direct proliferative effects but rather to paracrine signaling. This is the first study to show that HUCBC improve motor performance in a dose-dependent manner, perhaps by improving compensatory repair processes.
Schwannoma of the Sinonasal Tract and the Pterygopalatine Fossa with or without Intracranial Extension
Authors: Zhou Han , Xing Guangqian , Gao Xia , Wang Junguo , Chen Feng , Lu Lin , Zhang Yifen , Chen Zhibin , Qian Xiaoyun
Published: March 2015

Aims: Compared with those in other head and neck regions, schwannomas in the nasal cavity or paranasal sinuses are rare. The aim of this study was to present the experience of the authors in 11 schwannoma cases of the sinonasal tract and pterygopalatine fossa over a decade. Methods: A retrospective study from 2003 to 2014. Results: Three female and 8 male patients from 22 to 61 years of age (mean age 42 years) were admitted. The most common complaints were unilateral nasal congestion. A total of 10 of the patients received surgery, including 6 functional endoscopic sinus surgeries (FESS). The postoperative course was generally uneventful. Among the patients, 10 remained regionally asymptomatic, and there has been no clinical or radiological evidence of recurrence or residual tumor. Conclusion: Surgical treatment is effective for schwannomas of the sinonasal tract and the pterygopalatine fossa with a low recurrence rate. Conducting CT and MRI (particularly fluid-attenuated inversion recovery) before surgery is mandatory. FESS could become the primary treatment of choice.
Relationship between Treatment Effects on Progression-Free Survival and Overall Survival in Multiple Myeloma: A Systematic Review and Meta-Analysis of Published Clinical Trial Data
Authors: Cartier Shannon , Zhang Bin , Rosen Virginia M. , Zarotsky Victoria , Bartlett J. Blake , Mukhopadhyay Pralay , Wagner Samuel , Davis Catherine
Published: March 2015

Background: Demonstrating improved overall survival (OS) with new multiple myeloma (MM) treatments is becoming difficult because of extended survival, so progression-free survival (PFS) is commonly used as a surrogate endpoint for OS. We evaluated PFS as a potential surrogate for OS by examining whether observed treatment effects on PFS are positively associated with treatment effects on OS in MM. Methods: A systematic literature review identified 21 randomized control trials reporting hazard ratios (HRs) for treatment effects on PFS and OS. Pearson's r estimated the relationship between HRs (HRPFS and HROS), and between log-transformed HRs (log(HRPFS) and log(HROS)). R2 values were estimated from linear regression models of the HR and the log(HR) relationships. Sensitivity and subgroup analyses examined the robustness of the HR findings. Results: Positive correlations were found between HRPFS and HROS (r = 0.82; p < 0.0001) and between log(HRPFS) and log(HROS) (r = 0.80; p < 0.0001). Linear regression models produced R2 values of 0.67 and 0.63 when regressing HROS on HRPFS, and log(HROS) on log(HRPFS), respectively. Sensitivity analyses supported the HR findings. Conclusion: This analysis provides evidence for a positive association between treatment effects on PFS and OS. Studies involving patient level data are necessary to confirm whether PFS is a valid surrogate for OS in MM.
Ustekinumab as an Alternative Treatment Option for Chronic Pityriasis Rubra Pilaris
Authors: Chowdhary Mudit , Davila Ulysses , Cohen David J.
Published: March 2015

Pityriasis rubra pilaris (PRP) is an exceptionally rare, chronic inflammatory dermatosis of unknown etiology. Patients classically present with small, follicular keratosis and salmon-colored plaques that begin at the head and neck and slowly progress to widespread erythroderma including the palms and soles. It is difficult to distinguish PRP from other inflammatory dermatoses; however, features that help aid in the diagnosis include ‘islands' of spared skin, orangish hue and typical findings on biopsy. There are no specific guidelines on therapy and treatment options include corticosteroids, vitamin D analogs, retinoids, methotrexate, cyclosporine, azathioprine and tumor necrosis factor alpha antagonists. Unfortunately options are limited for patients when these drugs do not work. We report a case of chronic PRP, refractory to conventional treatment, successfully treated with ustekinumab monotherapy. The patient was treated with 90 mg subcutaneous ustekinumab injections and began to show improvement within only 8 weeks. Long-term control of the disease has been attained without any significant side effects. We report this case to show that ustekinumab can be used as an alternative treatment method for patients with chronic, unremitting PRP. Treatment response is remarkably rapid and the infrequent dosing leads to patient compliance and a significantly improved quality of life.
Identification of MicroRNAs Differentially Expressed in Lung Carcinoid Subtypes and Progression
Authors: Rapa Ida , Votta Arianna , Felice Barbara , Righi Luisella , Giorcelli Jessica , Scarpa Aldo , Speel Ernst-Jan M. , Scagliotti Giorgio V. , Papotti Mauro , Volante Marco
Published: March 2015

Aim: To extensively explore microRNA expression profiles in lung carcinoids in correlation with clinical and pathological features. Methods: A PCR-based array was employed in the screening phase to analyze 752 microRNAs in a discovery set of 12 lung carcinoids, including 6 typical (3 with lymph node metastasis) and 6 atypical (3 with lymph node metastasis). The results were validated by means of real-time PCR in 37 carcinoids, including 22 typical (4 with lymph node metastasis) and 15 atypical (7 with lymph node metastasis), and 19 high-grade neuroendocrine carcinomas. Results: Unsupervised cluster analysis segregated the pilot cases into 3 distinct groups. Twenty-four microRNAs were differentially regulated in atypical versus typical carcinoids, and 29 in metastatic versus nonmetastatic cases. Eleven microRNAs were selected for validation. All but 1 were significantly different among lung neuroendocrine tumor histotypes. Moreover, 5 (miR-129-5p, miR-409-3p, miR-409-5p, miR-185 and miR-497) were significantly upregulated in typical compared to atypical carcinoids. MiR-409-3p, miR-409-5p and miR-431-5p were also significantly downregulated in carcinoids metastatic to the lymph nodes. Predictive in silico analysis of specific target genes showed that these 3 latter microRNAs linked to metastatic potential are implicated in several cellular functions and highlighted several novel genes which may be worth exploring. Conclusions: Our findings demonstrate that lung carcinoids have distinct microRNA expression profiles as compared to high-grade neuroendocrine carcinomas and that specific microRNAs might have potential implications as diagnostic tools or clinical biomarkers.
Status of Cardiovascular Health in US Children Up to 11 Years of Age
Authors: Ning Hongyan , Labarthe Darwin R. , Shay Christina M. , Daniels Stephen R. , Hou Lifang , Van Horn Linda , Lloyd-Jones Donald M.
Published: March 2015

Background—

The American Heart Association recently defined cardiovascular health (CVH) to monitor it over time for all Americans. Nationally representative prevalence estimates for children under 12 years according to sex and race/ethnicity have not been reported.

Methods and Results—

The study sample comprised 8961 children aged 2 to 11 years from 2003 to 2010 National Health and Nutrition Examination Surveys. National prevalence of ideal, intermediate, and poor CVH as defined by American Heart Association was estimated for each of 4 available metrics (body mass index [BMI], healthy diet score, total cholesterol, and blood pressure). No children had ideal levels for either zero or all 4 metrics. Ideal healthy diet score was least prevalent, ranging from 0 to 0.1%, whereas ideal blood pressure was most prevalent ranging from 88% to 93% across sex, race/ethnicity groups. Ideal BMI was less frequent at ages 6 to 11 years than at ages 2 to 5 years (67% versus 77%). Approximately 40% of children had intermediate or poor total cholesterol levels. The dietary intake of diet score components was associated with BMI, which was associated with blood pressure and total cholesterol.

Conclusions—

Ideal CVH status for BMI, total cholesterol, and blood pressure was prevalent in young children, whereas ideal diet was rare. Diet and BMI were important components to achieve ideal CVH metrics in children. Limited availability of data for all CVH metrics is a major obstacle for CVH assessment in the youngest age groups and represents an important missed opportunity for surveillance and secular trends analyses with aging.
Measurement of Peripheral Plasma 18-Oxocortisol Can Discriminate Unilateral Adenoma From Bilateral Diseases in Patients With Primary Aldosteronism
Authors: Satoh Fumitoshi , Morimoto Ryo , Ono Yoshikiyo , Iwakura Yoshitsugu , Omata Kei , Kudo Masataka , Takase Kei , Seiji Kazumasa , Sasamoto Hidehiko , Honma Seijiro , Okuyama Mitsunobu , Yamashita Kouwa , Gomez-Sanchez Celso E. , Rainey William E. , Arai Yoichi , Sasano Hironobu , Nakamura Yasuhiro , Ito Sadayoshi
Published: March 2015

Adrenal venous sampling is currently the only reliable method to distinguish unilateral from bilateral diseases in primary aldosteronism. In this study, we attempted to determine whether peripheral plasma levels of 18-oxocortisol (18oxoF) and 18-hydroxycortisol could contribute to the clinical differentiation between aldosteronoma and bilateral hyperaldosteronism in 234 patients with primary aldosteronism, including computed tomography (CT)–detectable aldosteronoma (n=113) and bilateral hyperaldosteronism (n=121), all of whom underwent CT and adrenal venous sampling. All aldosteronomas were surgically resected and the accuracy of diagnosis was clinically and histopathologically confirmed. 18oxoF and 18-hydroxycortisol were measured using liquid chromatography tandem mass spectrometry. Receiver operating characteristic analysis of 18oxoF discrimination of adenoma from hyperplasia demonstrated sensitivity/specificity of 0.83/0.99 at a cut-off value of 4.7 ng/dL, compared with that based on 18-hydroxycortisol (sensitivity/specificity: 0.62/0.96). 18oxoF levels above 6.1 ng/dL or of aldosterone >32.7 ng/dL were found in 95 of 113 patients with aldosteronoma (84%) but in none of 121 bilateral hyperaldosteronism, 30 of whom harbored CT-detectable unilateral nonfunctioning nodules in their adrenals. In addition, 18oxoF levels below 1.2 ng/dL, the lowest in aldosteronoma, were found 52 of the 121 (43%) patients with bilateral hyperaldosteronism. Further analysis of 27 patients with CT-undetectable micro aldosteronomas revealed that 8 of these 27 patients had CT-detectable contralateral adrenal nodules, the highest values of 18oxoF and aldosterone were 4.8 and 24.5 ng/dL, respectively, both below their cut-off levels indicated above. The peripheral plasma 18oxoF concentrations served not only to differentiate aldosteronoma but also could serve to avoid unnecessary surgery for nonfunctioning adrenocortical nodules concurrent with hyperplasia or microadenoma.
Mutation of
SH2B3
(
LNK
), a Genome-Wide Association Study Candidate for Hypertension, Attenuates Dahl Salt-Sensitive Hypertension via Inflammatory Modulation
Authors: Rudemiller Nathan P. , Lund Hayley , Priestley Jessica R.C. , Endres Bradley T. , Prokop Jeremy W. , Jacob Howard J. , Geurts Aron M. , Cohen Eric P. , Mattson David L.
Published: March 2015

Human genome-wide association studies have linked SH2B adaptor protein 3 (
SH2B3
,
LNK
) to hypertension and renal disease, although little experimental investigation has been performed to verify a role for
SH2B3
in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between
SH2B3
and hypertension, we targeted the
SH2B3
gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases. The resulting mutation was a 6-bp, in-frame deletion within a highly conserved region of the Src homology 2 (SH2) domain of
SH2B3
. This mutation significantly attenuated Dahl SS hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3
em1Mcwi
mutant rats. To determine whether this was because of differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3
em1Mcwi
mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3
em1Mcwi
mutant bone marrow. Rats that received Sh2b3
em1Mcwi
mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease.
Discordant Orthostatic Reflex Renin–Angiotensin and Sympathoneural Responses in Premenopausal Exercising-Hypoestrogenic Women
Authors: O’Donnell Emma , Goodman Jack M. , Mak Susanna , Murai Hisayoshi , Morris Beverley L. , Floras John S. , Harvey Paula J.
Published: March 2015

Our prior observations in normotensive postmenopausal women stimulated the hypotheses that compared with eumenorrheic women, active hypoestrogenic premenopausal women with functional hypothalamic amenorrhea would demonstrate attenuated reflex renin–angiotensin–aldosterone system responses to an orthostatic challenge, whereas to defend blood pressure reflex increases in muscle, sympathetic nerve activity would be augmented. To test these hypotheses, we assessed, in recreationally active women, 12 with amenorrhea (ExFHA; aged 25±1 years; body mass index 20.7±0.7 kg/m
2
; mean±SEM) and 17 with eumenorrhea (ExOv; 24±1 years; 20.9±0.5 kg/m
2
), blood pressure, heart rate, plasma renin, angiotensin II, aldosterone, and muscle sympathetic nerve activity at supine rest and during graded lower body negative pressure (−10, −20, and −40 mm Hg). At baseline, heart rate and systolic blood pressure were lower (
P
<0.05) in ExFHA (47±2 beats/min and 94±2 mm Hg) compared with ExOv (56±2 beats/min and 105±2 mm Hg), but muscle sympathetic nerve activity and renin–angiotensin–aldosterone system constituents were similar (
P
>0.05). In response to graded lower body negative pressure, heart rate increased (
P
<0.05) and systolic blood pressure decreased (
P
<0.05) in both groups, but these remained consistently lower in ExFHA (
P
<0.05). Lower body negative pressure elicited increases (
P
<0.05) in renin, angiotensin II, and aldosterone in ExOv, but not in ExFHA (
P
>0.05). Muscle sympathetic nerve activity burst incidence increased reflexively in both groups, but more so in ExFHA (
P
<0.05). Otherwise, healthy hypoestrogenic ExFHA women demonstrate low blood pressure and disruption of the normal circulatory response to an orthostatic challenge: plasma renin, angiotensin II, and aldosterone fail to increase and blood pressure is defended by an augmented sympathetic vasoconstrictor response.
Differential Effect of Baseline Computed Tomographic Angiography Collaterals on Clinical Outcome in Patients Enrolled in the Interventional Management of Stroke III Trial
Authors: Menon Bijoy K. , Qazi Emmad , Nambiar Vivek , Foster Lydia D. , Yeatts Sharon D. , Liebeskind David , Jovin Tudor G. , Goyal Mayank , Hill Michael D. , Tomsick Thomas A. , Broderick Joseph P. , Demchuk Andrew M.
Published: March 2015

Background and Purpose—

In the Interventional Management of Stroke (IMS) III trial, we sought to demonstrate evidence of a differential treatment effect of endovascular treatment of acute ischemic stroke compared with intravenous tissue-type plasminogen activator, according to baseline collateral status measured using computed tomographic angiography.

Methods—

Of 656 patients enrolled in Interventional Management of Stroke III trial, 306 had baseline computed tomographic angiography. Of these, 185 patients had M1 middle cerebral artery ± intracranial internal carotid artery occlusion, where baseline collateral status could be measured. Collateral status was assessed by consensus using 3 different ordinal scales and categorized as good, intermediate, and poor. Multivariable modeling was used to assess the effect of collateral status and treatment type on clinical outcome by modified Rankin Scale (mRS 0–2, mRS 0–1, and the ordinal mRS).

Results—

Of 185 patients, 126 randomized to endovascular therapy (87.6% recanalized, 41.3% 90-day mRS 0–2) and 59 to intravenous tissue-type plasminogen activator only (60.5% recanalized, 30.5% 90-day mRS 0–2). In multivariable modeling, collateral status was a significant predictor of all clinical outcomes (
P
<0.05). Maximal benefit with endovascular treatment across all clinical outcomes was seen in patients with intermediate collaterals, some benefit in patients with good collaterals, and none in patients with poor collaterals, although small sample size limited the power of the analysis to show a statistically significant interaction between collateral status and treatment type (
P
>0.05).

Conclusion—

Using data from a large randomized controlled trial (IMS III), we show that baseline computed tomographic angiography collaterals are a robust determinant of final clinical outcome and could be used to select patients for endovascular therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov/ct2/show/
. Unique identifier: 0020NCT00359424.
Fast and Efficient Black Box Optimization Using the Parameter-less Population Pyramid
Authors: Goldman B. W. , Punch W. F.
Published: March 2015

The parameter-less population pyramid (P3) is a recently introduced method for performing evolutionary optimization without requiring any user-specified parameters. P3’s primary innovation is to replace the generational model with a pyramid of multiple populations that are iteratively created and expanded. In combination with local search and advanced crossover, P3 scales to problem difficulty, exploiting previously learned information before adding more diversity. Across seven problems, each tested using on average 18 problem sizes, P3 outperformed all five advanced comparison algorithms. This improvement includes requiring fewer evaluations to find the global optimum and better fitness when using the same number of evaluations. Using both algorithm analysis and comparison, we find P3’s effectiveness is due to its ability to properly maintain, add, and exploit diversity. Unlike the best comparison algorithms, P3 was able to achieve this quality without any problem-specific tuning. Thus, unlike previous parameter-less methods, P3 does not sacrifice quality for applicability. Therefore we conclude that P3 is an efficient, general, parameter-less approach to black box optimization which is more effective than existing state-of-the-art techniques.
The Best Interests of the Child in the Expulsion and First-entry Jurisprudence of the European Court of Human Rights: How Principled is the Court’s Use of the Principle?
Authors: Smyth Ciara
Published: March 2015

The principle of the best interests of the child is regularly referred to by the European Court of Human Rights in its jurisprudence involving children. However, the principle is notoriously problematic, and nowhere more so than in the immigration context where the state’s sovereign interests are keenly at stake. This article critically examines the expulsion and first-entry jurisprudence of the European Court of Human Rights under Article 8 of the European Convention on Human Rights, interrogating whether a ‘principled’ approach is adopted to the best interests principle. It is argued that a principled approach is one which sees the best interests principle interpreted in the light of its parent document, the un Convention on the Rights of the Child, as interpreted by the un Committee on the Rights of the Child. It is demonstrated that despite widespread recourse to the best interests principle, the European Court of Human Rights fails to adopt a rights-based approach when identifying the best interests of the child and does not always give sufficient weight to the best interests of the child when balancing the interests of the state against those of the individual. The analysis also reveals a way for the Court to develop a more principled approach to the best interests principle.
An Analysis of the Ben Alaya Case (C-491/13): When Conditions of the Students Directive are met, that Directive Confers Entitlement to a Student Visa, without Leaving the National Authorities any Discretion in that Regard
Authors: Fernhout Roel
Published: March 2015

Article 12 of Council Directive 2004/114/ec of 13 December 2004 on the conditions of admission of third-country nationals for the purposes of studies, pupil exchange, unremunerated training or voluntary service must be interpreted as meaning that the Member State concerned is obliged to admit to its territory a third-country national who wishes to stay for more than three months in that territory for study purposes, where that national meets the conditions for admission exhaustively listed in Articles 6 and 7 of that directive and provided that that Member State does not invoke against that person one of the grounds expressly listed by the directive as justification for refusing a residence permit. This case report is an elaborated version of my annotation under cjeu 10 September 2014, C-491/13 (Ben Alaya) in Jurisprudentie Vreemdelingenrecht 2014/345 (a Dutch case law journal on aliens law).
Be Careful When Assuming the Obvious
Authors: Alday Phillip M.
Published: March 2015

Ferrer-i-Cancho (this volume) presents a mathematical model of both the synchronic and diachronic nature of word order based on the assumption that memory costs are a never decreasing function of distance and a few very general linguistic assumptions. However, even these minimal and seemingly obvious assumptions are not as safe as they appear in light of recent typological and psycholinguistic evidence. The interaction of word order and memory has further depths to be explored.
Elite Management in Electoral Authoritarian Regimes: A View From Bashkortostan and Tatarstan
Authors: Sharafutdinova Gulnaz
Published: March 2015

Contributing to the literature on authoritarian elite management, this study explores a puzzle concerned with the elite evolution in Russia’s two ethnic republics, Tatarstan and Bashkortostan. The variation of political legacies left by these two republics’ first presidents cannot be addressed using mainstream explanations that are usually considered principal for the Kremlin’s decisionmaking on gubernatorial cadres in Russia. Both Rakhimov and Shaimiev were very successful as political bosses who could effectively deliver electoral votes to the Kremlin and maintain relative social and economic stability within their republics. Yet, toward the end of their political careers, they faced different degrees of freedom in their negotiations with federal elites and had varying degrees of success in ensuring political and economic continuity within their republics. The study instead focuses on the legacies of republican privatization and the institutional dynamics of patronal presidentialism as two alternative explanations for their divergent political outcomes.
Reliability and validity of the attitude towards research scale for a sample of industrial psychology students
Authors: van der Westhuizen Sanet
Published: March 2015

The study investigated the reliability and validity of the Attitudes towards Research Scale for a South African sample. A cross-sectional survey design was used and a convenience sample of postgraduate students in industrial psychology ( N = 185) participated in the study. A biographical scale and the Attitudes towards Research Scale were administered. Confirmatory factor analysis, exploratory factor analysis, correlations and descriptive statistics were used to analyse the data. The results indicated that none of the previously suggested one-factor, five-factor or three-factor structures of the Attitudes towards Research fitted the data well. A revised three-factor structure consisting of positive outlook on research, anxiety and difficulty, and the usefulness of research fitted the data acceptably. Students in this sample displayed positive attitudes towards research, regarded it as beneficial to them in their profession, but deemed it to be somewhat difficult and displayed moderate levels of anxiety about it.
Attitudes toward Human Papilloma Virus Vaccination and Head and Neck Cancer Prevention in a Diverse, Urban Population
Authors: Kram Yoseph A. , Schmidt Timothy H. , Saghezchi Sohail , Russell Marika D.
Published: March 2015

Objective

(1) To understand if awareness of the human papilloma virus (HPV) vaccination’s potential to prevent head and neck cancer improves acceptability of the vaccine in a large urban population and (2) to identify characteristics of those in whom such discussions would have the greatest impact.

Study Design

In‐person, anonymous survey.

Setting

Academic public hospital between March 2014 and June 2014.

Subjects

Patients aged 12 to 24 years and their parents or guardians awaiting scheduled outpatient pediatric appointments.

Methods

Demographics and modified Carolina HPV Immunization Attitudes and Beliefs Scales data were cross‐analyzed, followed by univariate binomial logistic regression to identify predictors for major outcomes of interest.

Results

More than 78% of those surveyed indicated they would be more receptive to the HPV vaccine if given strong evidence that it prevented head and neck cancer. Respondents were more likely to increase receptivity to HPV vaccination if they held the belief that they did not have enough information about the vaccine or indicated they preferred to wait because the vaccine was too new.

Conclusion

Increasing public awareness of head and neck cancer prevention with HPV vaccination could increase HPV vaccination acceptance.
An assistive decision-and-control architecture for force-sensitive hand–arm systems driven by human–machine interfaces
Authors: Vogel J. , Haddadin S. , Jarosiewicz B. , Simeral J.D. , Bacher D. , Hochberg L.R. , Donoghue J.P. , van der Smagt P.
Published: March 2015

Fully autonomous applications of modern robotic systems are still constrained by limitations in sensory data processing, scene interpretation, and automated reasoning. However, their use as assistive devices for people with upper-limb disabilities has become possible with recent advances in “soft robotics”, that is, interaction control, physical human–robot interaction, and reflex planning. In this context, impedance and reflex-based control has generally been understood to be a promising approach to safe interaction robotics.

To create semi-autonomous assistive devices, we propose a decision-and-control architecture for hand–arm systems with “soft robotics” capabilities, which can then be used via human–machine interfaces (HMIs). We validated the functionality of our approach within the BrainGate2 clinical trial, in which an individual with tetraplegia used our architecture to control a robotic hand–arm system under neural control via a multi-electrode array implanted in the motor cortex. The neuroscience results of this research have previously been published by Hochberg et al.

In this paper we present our assistive decision-and-control architecture and demonstrate how the semi-autonomous assistive behavior can help the user. In our framework the robot is controlled through a multi-priority Cartesian impedance controller and its behavior is extended with collision detection and reflex reaction. Furthermore, virtual workspaces are added to ensure safety. On top of this we employ a decision-and-control architecture that uses sensory information available from the robotic system to evaluate the current state of task execution. Based on a set of available assistive skills, our architecture provides support in object interaction and manipulation and thereby enhances the usability of the robotic system for use with HMIs. The goal of our development is to provide an easy-to-use robotic system for people with physical disabilities and thereby enable them to perform simple tasks of daily living. In an exemplary real-world task, the participant was able to serve herself a beverage autonomously for the first time since her brainstem stroke, which she suffered approximately 14 years prior to this research.
Relational Validity and the “Where” of Inquiry
Authors: Tuck Eve , McKenzie Marcia
Published: March 2015

This article reviews discussions of place in qualitative research that have appeared in Qualitative Inquiry over the past 20 years to foreground a conceptualization of critical place inquiry. The article describes relational validity and emphasizes possibilities for engaging place more meaningfully in qualitative inquiry.
Impact of perceptions of bus service performance on mode choice preference
Authors: Hu Xiaojian , Zhao Linna , Wang Wei
Published: March 2015

As transit service performance should be considered from the transit passengers’ perspectives, it is essential to determine passengers’ perceptions of service performance and to understand the role of these perceptions in travel decisions. As the bus market share has steadily declined, the aim of this study is to explore the impact of perceptions of bus service performance on mode choice preference to increase bus ridership. To achieve this research objective, an intention survey is conducted to obtain bus passengers’ attitudes. Exploratory factor analysis and confirmatory factor analysis are used to measure passengers’ perceptions and to extract the main factors from the bus service attributes. Next, structural equation modeling is used to reveal how passengers’ perceptions vary by demographics and trip characteristics. Finally, multinomial logit modeling is used to explore the impact of perception factors on mode choice preference. The results of this study show that perceptions of the reliability and comfort of bus services have a more significant impact on passengers’ mode choice preference than perceptions of availability and safety do. The implications in terms of improving bus service reliability and comfort can increase bus ridership.
American and Chinese leadership during the global financial crisis: Testing Kindleberger’s stabilization functions
Authors: Norrlof Carla , Reich Simon
Published: March 2015

Heavily reliant on the work of Charles P Kindleberger, theories of hegemony and power transition have been built on the largely unchallenged assumption that the United States acts as a global economic stabilizer in time of crisis. However, there has been no attempt systematically to delineate, operationalize and test whether the United States performs this role utilizing Kindleberger’s five functions. Proponents of these theories have, in contrast, characterized China as either a free-rider or a predator waiting to challenge American leadership in times of crisis. In evaluating these characterizations, we test two hypotheses that examine the extent to which the United States and China have performed these stabilizing functions with regard to three major economic crises (the 1997 Asian economic crisis, the 2001 “DotCom” crisis and the Great Recession of 2007–2009). Our findings suggest that Kindleberger’s functions are more evenly shared than conventional scholarship would predict and that China has played a supportive, stabilizing role. Without evidence of explicit collaboration between the two countries, these functions were shared. Furthermore, China played an increasingly important role in supporting the global economic system over time and the trend line suggests they will continue to do so in the future. If Kindleberger’s criteria are correct, the assumption of a single country, the United States, acting as a stabilizer is therefore empirically mistaken. If his criteria are flawed, major IR theories that have assumed the criteria to be true and/or have assumed that the United States plays this unique role in the global economy are in need of critical reassessment.
BET bromodomain inhibition suppresses graft-versus-host disease after allogeneic bone marrow transplantation in mice
Authors: Sun Yaping , Wang Ying , Toubai Tomomi , Oravecz-Wilson Katherine , Liu Chen , Mathewson Nathan , Wu Julia , Rossi Corinne , Cummings Emily , Wu Depei , Wang Shaomeng , Reddy Pavan
Published: March 2015

Key Points

Demonstrates that targeting BET bromodomain is a novel strategy to mitigate acute GVHD. BET bromodomain inhibition regulates DCs and T cells and causes disruption of interaction between BRD4 and acetyl-310 RelA of nuclear factor kappa B.
Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma
Authors: Moreau Philippe , Kolb Brigitte , Attal Michel , Caillot Denis , Benboubker Lotfi , Tiab Mourad , Touzeau Cyrille , Leleu Xavier , Roussel Murielle , Chaleteix Carine , Planche Lucie , Chiffoleau Anne , Fortin June , Avet-Loiseau Hervé , Mary Jean-Yves , Hulin Cyrille , Facon Thierry
Published: March 2015

Key Points

CMP is an effective induction regimen for transplant-ineligible MM patients. The CMP regimen is safe and well tolerated with a notable lack of peripheral neuropathy.