bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion-weighted MRI of metastatic liver lesions: is there a difference between hypervascular and hypovascular metastases?
Authors: Schmid-Tannwald Christine , Thomas Stephen , Ivancevic Marko K , Dahi Farid , Rist Carsten , Sethi Ila , Oto Aytekin
Published: August 2013

Background

Different perfusion characteristics and histopathologic features of liver metastasis may potentially lead to different diffusion-weighted magnetic resonance imaging (DW-MRI) characteristics which can affect the performance of DW-MRI in their diagnosis.

Purpose

To compare ADC values of hypervascular and hypovascular metastases and the added value of DW-MRI to T2-weighted (T2-w) images in their detection.

Material and Methods

In this retrospective study, 46 patients (21 with hypervascular, 25 with hypovascular liver metastases) who had undergone abdominal MRI were included. Two independent observers first reviewed T2-w images only and then T2-w + DW-MR images and recorded number of metastases in each session. Lesion detection rate was compared using McNemar test. ADC of metastases in each patient was measured and compared between hypo- and hypervascular lesions using t-test.

Results

A total of 153 hypervascular and 187 hypovascular metastases were detected at consensus review. Two observers detected significantly more hypervascular metastases on T2-w + DW-MR image review session compared to T2-w image only review session (reader 1: 148 [96.7%] vs. 129 [84.3%], P = 0.002; reader 2: 125 [81.9%] vs. 113 [73.8%], P = 0.004). Detection rate of hypovascular metastases was similar between two sessions for both observers (reader 1: 180 [96.2%] vs. 184 [98.4%]; reader 2: 176 [94.1%] vs. 180 [96.2%], P > 0.05). The mean ADC value of hypervascular metastases was significantly lower than mean ADC value of hypovascular metastases (1.23+/−0.31 × 10−3 mm2/s vs. 1.49+/−0.19 × 10−3 mm2/s) ( P = 0.001).

Conclusion

Liver metastases are not a homogenous group of lesions with uniform DW-MRI features. Hypervascular metastases demonstrate significantly lower ADC values compared to hypovascular metastases. DW-MRI improved detection of hypervascular metastases compared to T2-w images alone and is a useful adjunct to T2-w images for their detection.
The effects of background music on the evaluation of crying faces
Authors: Hanser Waldie E. , Mark Ruth E. , Zijlstra Wobbe P. , Vingerhoets Ad J. J. M.
Published: August 2013

This exploratory study was designed to determine the effects of background music of different valence on the perception of tearful faces and other emotional expressions. Participants (154 men, age range 9–64 years, and 208 women, age range 9–77 years) rated photographs of crying, smiling, anger expressing and yawning unique men and women ( N = 12 each) on the following three dimensions: kindness, attractiveness and pleasantness, while concurrently being exposed to happy, angry, sad and calm music, or a no-music condition. Mixed models analysis revealed that observers made more favourable judgments about a crier when listening to sad and calm background music. This particularly concerned the ratings on the dimensions kindness and pleasantness, while calm music additionally increased ratings of attractiveness. Opposite effects were found for angry faces, for which lower ratings were obtained on all three dimensions with calm music. We speculate that calm background music may be helpful to boost social bonding and empathy, when people are in tears.
Gelatin-apatite bone mimetic co-precipitates incorporated within biopolymer matrix to improve mechanical and biological properties useful for hard tissue repair
Authors: Won Jong-Eun , El-Fiqi Ahmed , Jegal Seung-Hwan , Han Cheol-Min , Lee Eun-Jung , Knowles Jonathan C , Kim Hae-Won
Published: August 2013

Synthetic biopolymers are commonly used for the repair and regeneration of damaged tissues. Specifically targeting bone, the composite approach of utilizing inorganic components is considered promising in terms of improving mechanical and biological properties. We developed gelatin-apatite co-precipitates which mimic the native bone matrix composition within poly(lactide- co-caprolactone) (PLCL). Ionic reaction of calcium and phosphate with gelatin molecules enabled the co-precipitate formation of gelatin-apatite nanocrystals at varying ratios. The gelatin-apatite precipitates formed were carbonated apatite in nature, and were homogeneously distributed within the gelatin matrix. The incorporation of gelatin-apatite significantly improved the mechanical properties, including tensile strength, elastic modulus and elongation at break, and the improvement was more pronounced as the apatite content increased. Of note, the tensile strength increased to as high as 45 MPa (a four-fold increase vs. PLCL), the elastic modulus was increased up to 1500 MPa (a five-fold increase vs. PLCL), and the elongation rate was ∼240% (twice vs. PLCL). These results support the strengthening role of the gelatin-apatite precipitates within PLCL. The gelatin-apatite addition considerably enhanced the water affinity and the acellular mineral-forming ability in vitro in simulated body fluid; moreover, it stimulated cell proliferation and osteogenic differentiation. Taken together, the GAp-PLCL nanocomposite composition is considered to have excellent mechanical and biological properties, which hold great potential for use as bone regenerative matrices.
Acts of Charity as Acts of Remembrance in the Book of Tobit
Authors: Macatangay Francis M.
Published: August 2013

This article argues that charitable acts in the book of Tobit are religious acts of remembrance. On the one hand, the narrative emphasizes the practice of righteousness, the doing of what is true, and the performance of charitable deeds. On the other hand, the remembrance of God is an equally prominent motif in the story. This gives rise to the question of how remembering is linked to acts of charity. The close connection between remembering and almsgiving argues against the commonly held view that the story endorses acts of charity because such acts facilitate social cohesion and mutual support in the Diaspora. Given the theological value the narrative places on almsgiving, the book of Tobit witnesses to the emergence of a horizontal expression of service to God as part of the religious piety in Second Temple Judaism.
Twin-tube- and bypass-containing magneto-rheological damper for use in railway vehicles
Authors: Guo Chaoyang , Gong Xinglong , Zong Luhang , Peng Chao , Xuan Shouhu
Published: August 2013

A 9-kN magneto-rheological (MR) damper for lateral suspension control of a railway vehicle is created in this paper. The twin-tube style is adopted in order to obtain a long damper stroke and guarantee the symmetry of the output damping force. A bypass MR valve with a radial flow path is utilised to control the generated damping force. Three-dimensional finite element analysis studies are performed to determine the magnetic field strength inside the MR valve region. The MR damper is mathematically modelled for the situation of a unidirectional fluid flow in the chamber and valve. The test results indicate that the MR damper can produce a considerable range of dynamic force and can operate as a fail-safe device. Sedimentation is detected in the damper; however, the response time is acceptable for real-world deployment.
Reducing the risk of suicide or trespass on railways: developing better interventions through understanding behaviours of people
Authors: Ryan Brendan
Published: August 2013

Suicide and trespass are major problems for railway operators in Great Britain, leading to around 250–300 fatalities per year, as well as associated major disruption to the rail network. The European Union project RESTRAIL, composed of a broad consortium of experts and rail operators from across Europe, is attempting to tackle these important issues. This paper presents an overview of two parts of the project that are being led by research in the UK; understanding observable behaviours prior to suicide and trespass incidents and the development of a methodology for the evaluation of preventative measures against suicide and trespass. Solving the problems of railway suicide and trespass is difficult. Opportunities for interventions, based on a better understanding of the behaviours displayed by people leading up to these incidents, are discussed.
Prevalence of HIV, human papillomavirus type 16 and herpes simplex virus type 2 among female sex workers in Guinea and associated factors
Authors: Aho Joséphine , Koushik Anita , Coutlée François , Diakité Soumaïla Laye , Rashed Sélim
Published: August 2013

Female sex workers are at high risk for HIV infection. Sexually transmitted infections are known to be co-factors for HIV infection. Our aims were (1) to assess the prevalence of HIV and other sexually transmitted infections in this population; (2) to determine the association between sociodemographic characteristics, behavioural variables, and variables related to HIV prevention and HIV infection. A cross-sectional study was conducted in Conakry, Guinea, among a convenience sample of 223 female sex workers. A questionnaire on sociodemographic characteristics, risk factors, and exposure to prevention was administered. Screening for HIV, herpes simplex virus type 2, human papillomavirus type 16, Neisseria gonorrhoeae, and Chlamydia trachomatis was performed. Prevalences of HIV, herpes simplex virus type 2, human papillomavirus type 16, N. gonorrhoeae, and C. trachomatis were 35.3%, 84.1%, 12.2%, 9.0%, and 13.6%, respectively. Having a child, lubricant use, and human papillomavirus type 16 infection were associated with HIV infection. Interventions that promote screening and treatment of sexually transmitted infections are needed in order to achieve successful interventions to prevent HIV among female sex workers in resource-limited settings.
Flow separation impacts on the hydrodynamic performance analysis of a marine current turbine using CFD
Authors: Shi Weichao , Wang D , Atlar M , Seo K-C
Published: August 2013

Although there are different strategies to control the operation of marine turbines, the so-called ‘stall-regulated strategy’ is one of the most widely used and mature control strategies. Since the stall phenomenon is closely related to flow separation around the turbine blades the treatment of this separation requires great care during the design and performance analysis of turbines when using computational fluid dynamics (CFD). This study investigates appropriate methodologies and approaches to simulate the hydrodynamic performance of horizontal marine turbines with a specific emphasis on the flow separation phenomena. The well-known viscous flow solver ANSYS-CFX was employed as the main CFD code to predict the power extraction coefficient of these turbines. The investigations were carried out by using both numerical and experimental methods applied on tidal stream turbine models tested in the Emerson Cavitation Tunnel of Newcastle University, UK and the circulating water channel of Harbin Institute of Technology, China. The measured power extraction coefficients generally agreed well with the numerically predicted ones except for one of the models with the lower pitch angle which displayed large discrepancies over the entire operating range. The detailed flow analyses from the CFD studies with this turbine and other model at higher pitch angles revealed that large-scale detached vortices developed downstream of the model with the lower pitch angle may have contributed to this large discrepancy. The study therefore draws attention to the importance of the combined use of the CFD and model test-based approaches in the design and performance analysis of marine turbines.
Rescaling and urban-regional restructuring in Finland and in the Helsinki region
Authors: Pelkonen Antti
Published: August 2013

While Finland has traditionally been a country where major political forces have put important emphasis on balancing the regional structure and supporting the peripheral regions, development since the 1990s has been characterised by growing regional differences and increasing dominance of centralising tendencies. In the first decade of the new millennium, these tendencies have further intensified. This article analyses the processes, dynamics and underlying rationalities of this state restructuring and state spatial transformation in Finland and in the Helsinki region, the capital area of the country. The developments in Finland are placed in broader international context as they are analysed in relation to recent debates on state rescaling. The validity of some of the core arguments presented in these debates is examined in the Finnish context. The case of the Helsinki region and Finland is also set into a Nordic perspective by presenting a comparison of rescaling tendencies in the Nordic countries (Sweden, Denmark and Norway). The findings are mixed, as there are both elements supporting the rescaling thesis and clear deviations from the core arguments.
Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients
Authors: Elsone Liene , Panicker Jay , Mutch Kerry , Boggild Mike , Appleton Richard , Jacob Anu
Published: August 2013

Prompt treatment of neuromyelitis optica (NMO) relapses with steroids or plasma exchange (PLEX) often prevents irreversible disability. The objective of this study is to report the use of intravenous immunoglobulins (IVIG) as treatment for acute relapses in NMO. A retrospective review of 10 patients treated with IVIG for acute relapses was conducted. IVIG was used in the majority of cases because of lack of response to steroids with/without PLEX. Improvement was noted in five of 11 (45.5%) events; the remaining had no further worsening. One patient, a 79-year-old woman, had a myocardial infarction seven days after IVIG. IVIG may have a role in treating acute NMO relapses.
Strategies to identify future shortages due to interruptions in the health care procurement supply chain and their impact on health services: a method from the English National Health Service
Authors: Grose Jane , Richardson Janet
Published: August 2013

Objectives

The uninterrupted supply of essential items for patient care is crucial for organizations that deliver health care. Many products central to health care are derived from natural resources such as oil and cotton, supplies of which are vulnerable to climate change and increasing global demand. The purpose of this study was to identify which items would have the greatest effect on service delivery and patient outcomes should they no longer be available.

Methods

Using a consensus development approach, all items bought by one hospital, over one year, were subjected to a filtering process. Criteria were developed to identify at-risk products and assess them against specific risks and opportunities. Seventy-two items were identified for assessment against a range of potential impacts on service delivery and patient outcomes, from no impact to significant impact. Clinical and non-clinical participants rated the items.

Results

In the category of significant impact, consensus was achieved for 20 items out of 72. There were differences of opinion between clinical and non-clinical participants in terms of significant impact in relation to 18 items, suggesting that priority over purchasing decisions may create areas of conflict. Reducing reliance on critically scarce resources and reducing demand were seen as the most important criteria in developing sustainable procurement.

Conclusion

The method was successful in identifying items vulnerable to supply chain interruption and should be repeated in other areas to test its ability to adapt to local priorities, and to assess how it functions in a variety of public and private settings.
Applying neural networks to solve the inverse problem of indoor environment
Authors: Zhang Tian-hu , You Xue-yi
Published: August 2013

The computational fluid dynamics (CFD) analysis and back propagation neural network (BPNN) were employed to solve the inverse problem of indoor environment (IPIE). The approaches to identify the contaminant source locations and inlet boundary conditions by the measurement data at specified observation locations were put forward separately. The inverse design of the indoor boundary conditions by the desired distribution of predicted mean vote (PMV) in the control domain was also presented. The result demonstrated the utility of our proposed method in solving the IPIE.
Evaluation of air cleaning technologies existing in the Danish market: Experiments in a duct and in a test room
Authors: Ardkapan Siamak Rahimi , Afshari Alireza , Bergsøe Niels C. , Nielsen Peter V.
Published: August 2013

Five portable air cleaning technologies including one new technology were evaluated to find their effectiveness in removing ultrafine particles. Measurements were carried out both in a duct and in a test room. The results showed that the technologies that use/create ozone to clean air can increase the ozone level significantly in the room. Moreover, they can cause generation of ultrafine particles and consequently increase ultrafine particle concentration in the room. The study suggests using a mechanical filter with low pressure drop as a recommended air cleaning technology in order to remove ultrafine particles efficiently from the indoor environment.
A Good Living Versus A Good Life
Authors: Chalofsky Neal , Cavallaro Liz
Published: August 2013

The Problem

The expectation for meaningful work and work–life integration is firmly entrenched in the minds of the GenerationY/Millennial generations in the workplace. Yet, in updating the literature and rethinking the impact on Chalofsky’s (2003) construct for meaningful work, the question arose as to whether meaningful work can and should exist in a vacuum or should it be viewed as part of a meaningful life. If so, what are the implications for the construct and for human resource development (HRD). How far can and should HRD go to help ensure a meaningful and purposeful life for present and future generations in the workplace?

The Solution

This article provides a sketch of the current research and thinking about meaningful work and a basis for the rest of the articles in this issue. The tightness of the “fit” between self and work can determine how meaningful one’s work is perceived. How work fits within a meaningful life, and how one’s life fits within the context of the organization, the community, the society, and the planet can shape a meaningful existence.

The Stakeholders

The intended audience for this article includes HRD scholars, scholar-practitioners, consultants, and students interested in the construct of meaningful work, and the implications of reframing HRD around meaning and purpose.
Cellular mechanisms underlying failed beta cell regeneration in offspring of protein-restricted pregnant mice
Authors: Cox Aaron R , Beamish Christine A , Carter David E , Arany Edith J , Hill David J
Published: August 2013

Low birth weight and poor foetal growth following low protein (LP) exposure are associated with altered islet development and glucose intolerance in adulthood. Additionally, LP-fed offspring fail to regenerate their β-cells following depletion with streptozotocin (STZ) in contrast to control-fed offspring that restore β-cell mass. Our objective was to identify signalling pathways and cellular functions that may be critically altered in LP offspring rendering them susceptible to developing long-term glucose intolerance and decreased β-cell plasticity. Pregnant Balb/c mice were fed a control (C; 20% protein) or an isocaloric LP (8% protein) diet throughout gestation and C diet thereafter. Female offspring were injected intraperitoneally with 35 mg/kg STZ or vehicle on days 1 to 5 for each dietary treatment. At 30 days of age, total RNA was extracted from pancreatic tissue for microarray analysis using the Affymetrix GeneChip Mouse Genome 430 2.0. Gene and protein expression were quantified from isolated islets. Finally, β-cell proliferation was determined in vitro following REG1α treatment. The microarray data and GO enrichment analysis indicated that foetal protein restriction alters the early expression of genes necessary for many cell functions, such as oxidative phosphorylation and free radical scavenging. Expression of Reg1 was upregulated following STZ, whereas protein content was decreased in LP + STZ islets. Furthermore, REG1α failed to stimulate β-cell proliferation in vitro in LP + STZ islets. Therefore, early nutritional insults may programme the Reg1 pathway resulting in a limited ability to increase β-cell mass during metabolic stress. In conclusion, this study implicates the Reg1 pathway in β-cell regeneration and describes altered programming of gene expression in LP offspring, which underlies later development of cell dysfunction and glucose intolerance in adulthood.
Non-Hodgkin’s B-cell lymphoma: Advances in molecular strategies targeting drug resistance
Authors: Maxwell Steve A , Mousavi-Fard Seyed
Published: August 2013

Non-Hodgkin’s lymphoma (NHL) is a heterogeneous class of cancers displaying a diverse range of biological phenotypes, clinical behaviours and prognoses. Standard treatments for B-cell NHL are anthracycline-based combinatorial chemotherapy regimens composed of cyclophosphamide, doxorubicin, vincristine and prednisolone. Even though complete response rates of 40–50% with chemotherapy can be attained, a substantial proportion of patients relapse, resulting in 3-year overall survival rates of about 30%. Relapsed lymphomas are refractory to subsequent treatments with the initial chemotherapy regimen and can exhibit cross-resistance to a wide variety of anticancer drugs. The emergence of acquired chemoresistance thus poses a challenge in the clinic preventing the successful treatment and cure of disseminated B-cell lymphomas. Gene-expression analyses have increased our understanding of the molecular basis of chemotherapy resistance and identified rational targets for drug interventions to prevent and treat relapsed/refractory diffuse large B-cell lymphoma. Acquisition of drug resistance in lymphoma is in part driven by the inherent genetic heterogeneity and instability of the tumour cells. Due to the genetic heterogeneity of B-cell NHL, many different pathways leading to drug resistance have been identified. Successful treatment of chemoresistant NHL will thus require the rational design of combinatorial drugs targeting multiple pathways specific to different subtypes of B-cell NHL as well as the development of personalized approaches to address patient-to-patient genetic heterogeneity. This review highlights the new insights into the molecular basis of chemorefractory B-cell NHL that are facilitating the rational design of novel strategies to overcome drug resistance.
Topical treatment with the opioid antagonist naltrexone accelerates the remodeling phase of full-thickness wound healing in type 1 diabetic rats
Authors: Immonen Jessica A , Zagon Ian S , Lewis Gregory S , McLaughlin Patricia J
Published: August 2013

Wound repair involves a series of overlapping phases that include inflammation, proliferation, and tissue remodeling, with the latter phase requiring months for proper healing. Delays in any of these processes can result in infection, chronic ulceration, and possible amputation. Diabetes is a major risk factor for improper wound repair, and impaired wound healing is a major complication for more than 26 million people in the US diagnosed with diabetes. Previous studies have demonstrated that the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in streptozotocin-induced type 1 diabetic (T1D) rats. NTX accelerated DNA synthesis and increased the number of epithelial and mast cells, as well as new blood vessel formation. In this study, remodeling was evaluated in T1D rats up to eight weeks after initial wounding. Twenty days following wounding, diabetic rats treated with vehicle had elevated numbers of MMP-2+ fibroblasts, suggesting delayed healing processes; birefringence of granulation tissue stained with Sirius red revealed diminished collagen formation and maturation. Wound tissue from NTX-treated T1D rats had comparable numbers of MMP-2+ fibroblasts to control specimens, as well as accelerated maturation of granulation tissue. The integrity of wounded skin was evaluated by tensile strength measurements. T1D resulted in delayed wound healing, and wounded skin that displayed reduced tensile strength relative to normal rats. Topical NTX applied to wounds in T1D rats resulted in enhanced collagen formation and maturation over a 60-day period of time. Moreover, the force required to tear skin of NTX-treated T1D rats was elevated relative to the force necessary to tear the skin of vehicle-treated T1D rats, and comparable to that for normal rats. These data reveal that complications in wound healing associated with T1D involve the novel OGF-OGFr pathway, and that topical NTX is an effective treatment to enhance wound healing.
School Consolidation and the Politics of School Closure Across Communities
Authors: Karanxha Zorka , Agosto Vonzell , Black William R. , Effiom Claudius B.
Published: August 2013

This case involves dilemmas for educational leaders who may face the process of school consolidation brought on by decreased funding and demands for accountability. We highlight the challenges and opportunities to collaborate within and across diverse communities and schools with varying expressions of cultural, political, ethical, and organizational power and interests. The teaching notes coincide with aspects of the case that involve principal responsibilities, equity concerns, and negotiations amid the demands of multiple constituencies. Theoretical frameworks highlighting asset-based approaches, leadership for social justice, and micropolitics are emphasized.
The Case of Rivera Elementary School
Authors: Maxcy Brendan D. , Nguyen Thu Suong T.
Published: August 2013

This case involves a struggle for control among differently situated leaders—district- and building-level administrators, teachers, parents and community members, and university partners—seeking to influence the reform agenda of a high-poverty urban elementary school serving Latina/Latino students. The various stakeholders encounter a variety of means–ends dilemmas as they respond to pressures to improve school performance, enhance students achievement, promote democratic participation, and pursue professional goals. The discussion and teaching notes draw on theories of micropolitics, distributed leadership and organizational behavior to help students surface and consider dilemmas facing the actors.
Is Lunch Still Gross? A Qualitative Evaluation of a New School Lunch Program
Authors: Cohn Daniel J. , Pickering Rachel , Chin Nancy P.
Published: August 2013

The childhood obesity epidemic has raised national awareness about the need to improve school meals. Our research study partnered University of Rochester researchers with the Healthi Kids Coalition, a local health planning organization, to evaluate a newly instituted food service program in a metropolitan school district of western New York. Using the Centers for Disease Control and Prevention’s Program Evaluation stepwise framework, we focused on stakeholder accountability and student satisfaction. The first author collected data through informal, conversational group interviews with students, key informant interviews (with school board members, food service employees, and the food services management company), and participant-observations at 2 schools. Then, we sorted data across the categories of “accountability” and “satisfaction.” Analysis of stakeholder accountability data revealed 3 themes: (a) unsustainable program costs, (b) strained working relationships among stakeholders, and (c) student–staff interactions that could potentially encourage consumption, but often resulted in rushed, unfinished meals. Analysis of student satisfaction data also revealed 3 themes: (a) dissatisfaction with food quality, including taste, texture, and food preparation; (b) unappealing food presentation; and (c) tremendous food waste with large amounts of uneaten food thrown away. Our study identified a complex system of relationships between the school board, food services management company, and unionized food service workers, which ultimately affected the food quality and (non)consumption at the point of delivery. We recommend improving stakeholder relationships, training staff to reduce waste, reevaluating labor contracts pertaining to food services, continued program evaluation, and using an evaluation process that represents all relevant perspectives.
Core Stabilization Exercise Prescription, Part I
Authors: Brumitt Jason , Matheson J. W. , Meira Erik P.
Published: August 2013

Context:

Injury to the low back can cause significant pain and dysfunction, which can affect an athlete’s performance and result in time lost from sport. A common conservative treatment is therapeutic core stabilization exercises, which can address pain and musculoskeletal dysfunction in patients with low back pathology.

Evidence Acquisition:

MEDLINE and CINAHL were searched (from 1966 to March 2013) to identify relevant research. Keywords and keyword combinations searched included motor control exercise, segmental stabilization, core stabilization, transversus abdominis, multifidi, and low back pain.

Results:

There are 2 popular rehabilitation strategies to assess core function and promote core stabilization. Each has been developed based on biomechanical models of lumbar segmental stability and observed motor control dysfunction in patients with low back pain.

Conclusion:

Controversy exists among clinical and research groups as to the optimal strategy for an athlete with low back pain.
Feasibility of the Nintendo WiiFit™ for improving walking in individuals with a lower limb amputation
Authors: Imam Bita , Miller William C , McLaren Linda , Chapman Paul , Finlayson Heather
Published: August 2013

Objectives:

To evaluate the feasibility of the Nintendo WiiFit™ as an adjunct to usual therapy in individuals with a lower limb amputation.

Methods:

The study was a Multiple Baseline (AB) Single Subject Research Design. Subjects were ≥19 years old, had their first unilateral transtibial or transfemoral amputation  ≤12 months ago, and were participating in prosthetic training. WiiFit training was provided for 30 min, 5 times a week, for a minimum of 2 and a maximum of 6 weeks in addition to usual therapy. Feasibility indicators were safety, post-intervention fatigue and pain levels, adherence, and subject’s acceptability of the program as measured by the Short Feedback Questionnaire–modified (SFQ-M). The primary clinical outcome was walking capacity assessed by the 2 Minute Walk Test (2MWT). The secondary clinical outcomes were the Short Physical Performance Battery, L-test, and Activities-Specific Balance Confidence.

Results:

Subjects (4 transtibial; 2 transfemoral) had a median age of 48.5 years (range = 45–59 years). No adverse events associated with the intervention occurred. Median pain and fatigue levels were 1.3 (range = 0.5–3.5) and 3.1 (range = 1.4–4.1), respectively. Median adherence was 80%. Subjects found the WiiFit enjoyable and acceptable (median SFQ-M = 35). Five subjects showed statistical improvement on the 2MWT and four on the secondary outcomes ( p < 0.05).

Conclusion:

The WiiFit intervention was found to be feasible in individuals with unilateral lower limb amputation. This research provides the foundation for future clinical research investigating the use of the WiiFit as a viable adjunctive therapy to improve outcomes in individuals with unilateral lower limb amputation who are participating in prosthetic training.
Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma
Authors: Ben-Batalla Isabel , Schultze Alexander , Wroblewski Mark , Erdmann Robert , Heuser Michael , Waizenegger Jonas S. , Riecken Kristoffer , Binder Mascha , Schewe Denis , Sawall Stefanie , Witzke Victoria , Cubas-Cordova Miguel , Janning Melanie , Wellbrock Jasmin , Fehse Boris , Hagel Christian , Krauter Jürgen , Ganser Arnold , Lorens James B. , Fiedler Walter , Carmeliet Peter , Pantel Klaus , Bokemeyer Carsten , Loges Sonja
Published: August 2013

Key Points

Axl inhibition by BGB324 is active in FLT3-mutated and FLT3 wild-type AML, and presence of Axl and Gas6 are required for therapeutic efficacy. AML cells educate BMDSCs to secrete Gas6, which mediates leukemia cell proliferation and therapy resistance.
Composite schemes for variational inequalities over equilibrium problems and variational inclusions
Authors: Yao Yonghong , Kang Jung Im , Cho Yeol Je , Liou Yeong-Cheng
Published: August 2013

Let C be a nonempty closed convex subset of a Hilbert space H, and let

T
:
H
→
H

be a nonlinear mapping. It is well known that the following classical variational inequality has been applied in many areas of applied mathematics, modern physical sciences, computerized tomography and many others. Find a point

x
∗

∈
C

such that

〈
T

x
∗

,
x
−

x
∗

〉

≥
0
,

∀
x
∈
C
.

In this paper, we consider the following variational inequality. Find a point

x
∗

∈
C

such that

〈
(
F
−
γ
f
)

x
∗

,
x
−

x
∗

〉

≥
0
,

∀
x
∈
C
,

and, for solutions of the variational inequality (B) with the feasibility set C, which is the intersection of the set of solutions of an equilibrium problem and the set of a solutions of a variational inclusion, construct the two composite schemes, that is, the implicit and explicit schemes to converge strongly to the unique solution of the variational inequality (B).

Recently, many authors introduced some kinds of algorithms for solving the variational inequality problems, but, in fact, our two schemes are more simple for finding solutions of the variational inequality (B) than others.

MSC:49J30, 47H10, 47H17, 49M05.
Geological and climatic changes in quaternary shaped the evolutionary history of Calibrachoa heterophylla, an endemic South-Atlantic species of petunia
Authors: Mäder Geraldo , Fregonezi Jéferson N , Lorenz-Lemke Aline P , Bonatto Sandro L , Freitas Loreta B
Published: August 2013

Background

The glacial and interglacial cycles that characterized the Quaternary greatly affected the distribution and genetic diversity of plants. In the Neotropics, few phylogeographic studies have focused on coastal species outside of the Atlantic Rainforest. Climatic and sea level changes during the Quaternary played an important role in the evolutionary history of many organisms found in coastal regions. To contribute to a better understanding of plant evolution in this environment in Southern South America, we focused onCalibrachoa heterophylla(Solanaceae), an endemic and vulnerable wild petunia species from the South Atlantic Coastal Plain (SACP).

Results

We assessed DNA sequences from two cpDNA intergenic spacers and analyzed them using a phylogeographic approach. The present phylogeographic study reveals the influence of complex geologic and climatic events on patterns of genetic diversification. The results indicate thatC. heterophyllaoriginated inland and subsequently colonized the SACP; the data show that the inland haplogroup is more ancient than the coastal one and that the inland was not affected by sea level changes in the Quaternary. The major diversification ofC.heterophyllathat occurred after 0.4 Myr was linked to sea level oscillations in the Quaternary, and any diversification that occurred before this time was obscured by marine transgressions that occurred before the coastal sand barrier’s formation. Results of the Bayesian skyline plot showed a recent population expansion detected inC. heterophyllaseems to be related to an increase in temperature and humidity that occurred at the beginning of the Holocene.

Conclusions

The geographic clades have been formed when the coastal plain was deeply dissected by paleochannels and these correlate very well with the distributional limits of the clades. The four major sea transgressions formed a series of four sand barriers parallel to the coast that progressively increased the availability of coastal areas after the regressions and that may have promoted the geographic structuring of genetic diversity observed today. The recent population expansion for the entire species may be linked with the event of marine regression after the most recent sea transgression at ~5 kya.
Identification of differential expression genes associated with host selection and adaptation between two sibling insect species by transcriptional profile analysis
Authors: Li Haichao , Zhang Hao , Guan Ruobing , Miao Xuexia
Published: August 2013

Background

Cotton bollworm (Helicoverpa armigera) and oriental tobacco budworm (Helicoverpa assulta) are noctuid sibling species. Under artificial manipulation, they can mate and produce fertile offspring. As serious agricultural insect pests, cotton bollworms are euryphagous insects, but oriental tobacco budworms are oligophagous insects. To identify the differentially expressed genes that affect host recognition and host adaptation between the two species, we constructed digital gene expression tag profiles for four developmental stages of the two species. High-throughput sequencing results indicated that we have got more than 23 million 17nt clean tags from both species, respectively. The number of unique clean tags was nearly same in both species (approximately 357,000).

Results

According to the gene annotation results, we identified 83 and 68 olfaction related transcripts from H. armigera and H. assulta, respectively. At the same time, 1137 and 1138 transcripts of digestion enzymes were identified from the two species. Among the olfaction related transcripts, more odorant binding protein and G protein-coupled receptor were identified in H. armigera than in H. assulta. Among the digestion enzymes, there are more detoxification enzyme, e.g. P450, carboxypeptidase and ATPase in H. assulta than in H. armigera. These differences partially explain that because of the narrow host plant range of H. assulta, more detoxification enzymes would help them increase the food detoxification and utilization efficiency.

Conclusions

This study supplied some differentially expressed genes affecting host selection and adaptation between the two sibling species. These genes will be useful information for studying on the evolution of host plant selection. It also provides some important target genes for insect species-specific control by RNAi technology.
Comprehensive characterization of erythroid-specific enhancers in the genomic regions of human Krüppel-like factors
Authors: Xiong Qian , Zhang Zhaojun , Chang Kai-Hsin , Qu Hongzhu , Wang Hai , Qi Heyuan , Li Yajuan , Ruan Xiuyan , Yang Yaran , Yang Yadong , Li Yanming , Sandstrom Richard , Sabo Peter J , Li Qiliang , Stamatoyannopoulos George , Stamatoyannopoulos John A , Fang Xiangdong
Published: August 2013

Background

Mapping of DNase I hypersensitive sites (DHSs) is a powerful tool to experimentally identify cis-regulatory elements (CREs). Among CREs, enhancers are abundant and predominantly act in driving cell-specific gene expression. Krüppel-like factors (KLFs) are a family of eukaryotic transcription factors. Several KLFs have been demonstrated to play important roles in hematopoiesis. However, transcriptional regulation of KLFs via CREs, particularly enhancers, in erythroid cells has been poorly understood.

Results

In this study, 23 erythroid-specific or putative erythroid-specific DHSs were identified by DNase-seq in the genomic regions of 17 human KLFs, and their enhancer activities were evaluated using dual-luciferase reporter (DLR) assay. Of the 23 erythroid-specific DHSs, the enhancer activities of 15 DHSs were comparable to that of the classical enhancer HS2 in driving minimal promoter (minP). Fifteen DHSs, some overlapping those that increased minP activities, acted as enhancers when driving the corresponding KLF promoters (KLF-Ps) in erythroid cells; of these, 10 DHSs were finally characterized as erythroid-specific KLF enhancers. These 10 erythroid-specific KLF enhancers were further confirmed using chromatin immunoprecipitation coupled to sequencing (ChIP-seq) data-based bioinformatic and biochemical analyses.

Conclusion

Our present findings provide a feasible strategy to extensively identify gene- and cell-specific enhancers from DHSs obtained by high-throughput sequencing, which will help reveal the transcriptional regulation and biological functions of genes in some specific cells.
Identification of a novel infection-enhancing epitope on dengue prM using a dengue cross-reacting monoclonal antibody
Authors: Luo Ya-Yan , Feng Jun-Jie , Zhou Jun-Mei , Yu Zhi-Zhun , Fang Dan-Yun , Yan Hui-Jun , Zeng Gu-Cheng , Jiang Li-Fang
Published: August 2013

Background

Dengue virus (DENV) infection is the most important arthropod- borne viral disease in human, but antiviral therapy and approved vaccines remain unavailable due to antibody-dependent enhancement (ADE) phenomenon. Many studies showed that pre-membrane (prM)-specific antibodies do not efficiently neutralize DENV infection but potently promote ADE infection. However, most of the binding epitopes of these antibodies remain unknown.

Results

In the present study, we characterized a DENV cross-reactive monoclonal antibody (mAb), 4D10, that neutralized poorly but potently enhanced infection of four standard DENV serotypes and immature DENV (imDENV) over a broad range of concentration. In addition, the epitope of 4D10 was successfully mapped to amino acid residues 14 to18 of DENV1-4 prM protein using a phage-displayed peptide library and comprehensive bioinformatics analysis. We found that the epitope was DENV serocomplex cross-reactive and showed to be highly immunogenic in Balb/c mice. Furthermore, antibody against epitope peptide PL10, like 4D10, showed broad cross-reactivity and weak neutralizing activtity with four standard DENV serotypes and imDENV but significantly promoted ADE infection. These results suggested 4D10 and anti-PL10 sera were infection-enhancing antibodies and PL10 was infection-enhancing epitope.

Conclusions

We mapped the epitope of 4D10 to amino acid residues 14 to18 of DENV1-4 prM and found that this epitope was infection-enhancing. These findings may provide significant implications for future vaccine design and facilitate understanding the pathogenesis of DENV infection.
The duration of sleep promoting efficacy by dual orexin receptor antagonists is dependent upon receptor occupancy threshold
Authors: Gotter Anthony L , Winrow Christopher J , Brunner Joseph , Garson Susan L , Fox Steven V , Binns Jacquelyn , Harrell Charles M , Cui Donghui , Yee Ka Lai , Stiteler Mark , Stevens Joanne , Savitz Alan , Tannenbaum Pamela L , Tye Spencer J , McDonald Terrence , Yao Leon , Kuduk Scott D , Uslaner Jason , Coleman Paul J , Renger John J
Published: August 2013

Background

Drugs targeting insomnia ideally promote sleep throughout the night, maintain normal sleep architecture, and are devoid of residual effects associated with morning sedation. These features of an ideal compound are not only dependent upon pharmacokinetics, receptor binding kinetics, potency and pharmacodynamic activity, but also upon a compound’s mechanism of action.

Results

Dual orexin receptor antagonists (DORAs) block the arousal-promoting activity of orexin peptides and, as demonstrated in the current work, exhibit an efficacy signal window dependent upon oscillating levels of endogenous orexin neuropeptide. Sleep efficacy of structurally diverse DORAs in rat and dog was achieved at plasma exposures corresponding to orexin 2 receptor (OX2R) occupancies in the range of 65 to 80%. In rats, the time course of OX2R occupancy was dependent upon receptor binding kinetics and was tightly correlated with the timing of active wake reduction. In rhesus monkeys, direct comparison of DORA-22 with GABA-A modulators at similar sleep-inducing doses revealed that diazepam produced next-day residual sleep and both diazepam and eszopiclone induced next-day cognitive deficits. In stark contrast, DORA-22 did not produce residual effects. Furthermore, DORA-22 evoked only minimal changes in quantitative electroencephalogram (qEEG) activity during the normal resting phase in contrast to GABA-A modulators which induced substantial qEEG changes.

Conclusion

The higher levels of receptor occupancy necessary for DORA efficacy require a plasma concentration profile sufficient to maintain sleep for the duration of the resting period. DORAs, with a half-life exceeding 8 h in humans, are expected to fulfill this requirement as exposures drop to sub-threshold receptor occupancy levels prior to the wake period, potentially avoiding next-day residual effects at therapeutic doses.
Human immunodeficiency virus, hepatitis C, and inflammatory biomarkers in individuals with alcohol problems: a cross-sectional study
Authors: Armah Kaku A , Quinn Emily K , Cheng Debbie M , Tracy Russell P , Baker Jason V , Samet Jeffrey H , Freiberg Matthew S
Published: August 2013

Background

Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers.

Methods

We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use.

Results

Detectable HIV and HCV RNA (OR = 2.49; 95% CI = 1.05–5.89) and detectable HCV RNA alone (2.95; 1.08–8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90–31.97) and TNF-α (7.70; 1.42–41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84).

Conclusions

Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities.