bluuebunny/crossref_metadata_2025 huggingface dataset:
Complications of Central Venous Catheters in Children Undergoing Hematopoietic Stem Cell Transplantation in Turkey
Authors: Yilmaz Medine C. , Aksoylar Serap , Erdogan Durdane , Demirag Bengu
Published: July 2012

Although central venous catheters (CVCs) have become an integral element of the care of patients undergoing hematopoietic stem cell transplantation (HSCT), the associated complications can lead to treatment delays and negatively affect the child and family’s quality of life. The aim of this study was to identify the types, rate of, and risk factors for the complications relating to CVCs used in children undergoing HSCT in Turkey. One hundred children were followed prospectively to track catheter-related complications in the transplantation unit. Overall, 186 complications were documented. The most frequent complications were catheter-related infections and malfunctions. Children who had nonhematological disease had a higher rate of complications than those with hematological disease. HSCT nurses should follow and apply evidence-based clinical practice guidelines to support the management of catheters. Nurse staffing ratios and workload may be an issue in developing countries. The authors believe that proper maintenance of CVCs contributes to the reduction of catheter-related complications despite these issues and that problems can be overcome by hiring experienced staff, appropriate nursing education, and by organizing and improving home care programs for HSCT patients.
Predisposing Factors to the Quality of Life of Childhood Cancer Survivors
Authors: Chung Oi Kwan Joyce , Li Ho Cheung William , Chiu Sau Ying , Lopez Violeta
Published: July 2012

The aim of this study was to examine the predisposing factors to the quality of life of Hong Kong Chinese childhood cancer survivors. A cross-sectional study was conducted with 153 survivors (9-16 years of age) during follow-up at the oncology outpatient clinic. The study found that depressive symptoms are a strong predictor of quality of life in childhood cancer survivors and that systematic screening of this population is important. It is essential for health care professionals to develop, plan, and evaluate interventions with the aim of alleviating depressive symptoms for childhood cancer survivors so as to enhance their quality of life.
Dying is a Transition
Authors: Renz Monika , Mao Miriam Schuett , Bueche Daniel , Cerny Thomas , Strasser Florian
Published: July 2012

Purpose:

End-of-life care is designed as response to patients' verbally communicated needs. The concept of dying as a process would allow us to improve care. This concept may combine the needs of the dying, their outburst of emotions, gradual maturation, family processes, acute problems such as decreasing independence, with their inner experience and transformation of perception. In this study we explored dying patients' mode of perception, and deeper reasons for anxiety and existential suffering.

Methods:

Dying inpatients of a major cancer centre treated by an interdisciplinary team were eligible. Psychotherapy records of cancer patients (course, reactions, discussions with nurses and physicians) provided the data. Participant observation and Interpretative Phenomenological Analysis (IPA) was applied.

Results:

Our data (pilot study N=80/follow-up-study N=600) suggest that patients undergo transition into another state of consciousness beyond anxiety, ego, and pain. Transition appears to have three stages. Anxiety, struggle, denial/acceptance, family processes, and maturation (ie, finding meaning and dignity, coping with trauma) may depend on the transitional process and also hinder or facilitate this transitional process.

Conclusions:

Understanding dying as transition may induce a radical reinterpretation of what patients need.
A Filial Therapy Model Through a Family Therapy Lens
Authors: Cornett Nick
Published: July 2012

The call for family-centered therapeutic services, especially for families of young children, has come from governmental organizations, professional associations, practitioners, and families. Play therapists and family therapists are prime candidates to provide such services, but professional research and literature suggest that practitioners within these fields tend to exclude members of the family system. This had led some to propose filial therapy, an outgrowth of child-centered play therapy, as a means of meaningfully integrating parents and children in treatment. However, play therapists may have difficultly conceptualizing from a family systems lens, while family therapists may struggle to see the theoretical compatibility of filial therapy with their systemic views. This article demonstrates the conceptual overlap between filial therapy and the major family therapy models with the goal of encouraging play therapists and family therapists to answer the call to provide family-centered services.
A Test of Two Typologies of Sexual Homicide
Authors: Sewall Lindsay A. , Krupp Daniel Brian , Lalumière Martin L.
Published: July 2012

Published typologies of sexual homicide lack theoretical grounding and empirical support. They also conceptualize the phenomenon of sexual homicide as somewhat discrete, though offenders are not typically specialists. Here, we propose a model that situates the phenomenon of sexual killing into broader categories of antisocial behavior, positing three types of perpetrators of serial sexual homicides: competitively disadvantaged, psychopathic, and sadistic offenders. Using biographical data of 82 serial sexual homicide offenders, we tested our model as well as the influential organized/disorganized model. Principal components analysis produced five components consisting of offender and offense characteristics, and cluster analysis revealed three distinct groups of perpetrators (sadistic offenders, competitively disadvantaged offenders, and slashers), as well as a fourth, heterogeneous group; this cluster solution, however, may be unstable. In summary, there is only mixed support for either model.
How to Integrate the Good Lives Model Into Treatment Programs for Sexual Offending
Authors: Willis Gwenda M. , Yates Pamela M. , Gannon Theresa A. , Ward Tony
Published: July 2012

The good lives model (GLM) represents a new theoretical framework informing sex offender treatment programs; however, substantial variation has been observed in terms of how GLM-related ideas and practices have been applied. Integrated appropriately, the GLM offers potential for improving outcomes of programs following a cognitive-behavioral therapy (CBT) approach and operating according to a narrow operationalization of risk, need, responsivity (RNR) principles. Conversely, misguided or otherwise poor integration could increase the very risk practitioners work to prevent and manage. The purpose of this article is to provide an introduction and overview on how to integrate the GLM into treatment using CBT and RNR. The authors describe clinical implications of the GLM as they relate to program aims and orientation, assessment and intervention planning, content, and delivery.
Pro
Authors: Singh Karen E. , Baum Victor C.
Published: July 2012

There is growing evidence that the general current approach in many centers of continued mechanical ventilation following cardiac surgery has evolved through historical experience rather than having a strong physiological basis in current practice. There is evidence going back several decades supporting very early (in the operating room [OR]) extubation in pediatric cardiac anesthesia. The authors provide evidence from numerous sources showing that extubation in the OR or shortly after arrival in the ICU is safe and cost-effective and is not prevented by the type of cardiac surgery or the use of cardiopulmonary bypass. They query if the paradigm should not be reversed and very early extubation be the routine unless contraindicated. Like any anesthetic technique, appropriate patient selection is called for, but this technique is widely appropriate.
Understanding Knowledge Sharing in Online Travel Communities
Authors: Lee Haeyoung , Reid Earl , Kim Woo Gon
Published: July 2012

This study explores the nature of knowledge sharing in online travel communities by proposing three types of antecedents: individual, community, and affiliation. These antecedents generate the formation of community identification and its influence on ongoing knowledge contribution. In addition, this study examines the moderating role of a traveler’s interaction mode on the proposed sharing paradigm. The findings reveal the following: (a) community identification is positively influenced by a member’s travel involvement and community benefits, (b) strong identification strengthens a member’s sharing intentions, and (c) the postulated relationships differ based on a member’s interaction mode. In short, community identification for travelers’ intent on seeking information is almost solely influenced by community benefits, whereas travelers inclined to relationship building are primarily influenced by travel involvement. In terms of knowledge sharing, relationship builders shared more frequently and to a greater extent than information seekers.
Selection Criteria of an Overseas Travel Intermediary for Group Package Tours
Authors: Tsaur Sheng-Hshiung , Lin Wei-Rong
Published: July 2012

This research applied a fuzzy analytic hierarchy process (AHP) to explore the criteria required for the selection of an overseas travel intermediary (OTI) for group package tours (GPTs). Selecting an OTI is a complex decision for host travel agencies, especially the choice of evaluation criteria for GPTs. Therefore, this study adopts an AHP method and further integrates a fuzzy set theory into the assessment of the selection criteria. This work collected 20 selection criteria from literature reviews, focus group, and the Delphi technique. Criteria were categorized into four dimensions, namely service capabilities, payment conditions and cost, reputation, and interactive relationships. Twenty-two general managers from different travel agencies were asked to weigh up and rank the overall criteria by applying a fuzzy AHP. The results could provide travel agencies with objective and suitable criteria for the selection of OTIs for GPTs.
The Impact of Top Management’s Environmental Attitudes on Hotel Companies’ Environmental Management
Authors: Park Jeongdoo , Jeong Kim Hyun , McCleary Ken W.
Published: July 2012

This study integrates the environmental attitude–behavior theory and the upper echelons theory to examine hotel companies’ environmental behavior. This study hypothesizes that top managers’ environmental attitudes have a positive effect on perceived advantages of the environmental program, which in turn leads to hotel companies’ involvement in environmental management. An online survey brought responses from 206 top managers (e.g., general managers, owners, CEOs, presidents, etc.) in U.S. hotels. The contact information of the participating hotels was taken from the websites of 11 state lodging associations in the United States. The results of structural equation modeling indicate that top managers’ perceived advantages, derived from environmental management, mediate the proposed relationship. In other words, top managers’ environmental attitudes influence hotels’ environmental management activities through perceived benefits of the environmental program. Managerial implications are discussed based on the study results.
The economic and cultural aspects of the social web
Authors: Amersdorffer Daniel , Bauhuber Florian , Oellrich Jens
Published: July 2012

The social web is more than a technological innovation: it is a social innovation – it changes the way people and companies interact and communicate. New business models, new structures and new hierarchies in tourism enterprises and tourism organisations are the reason for this transformation. Because of this circumstance, tourism organisations and companies not only meet tough challenges, but also hold a multiplicity of potential. The environment of tourism is going to change permanently by the influence of the social web on media landscapes, media consumption and the construction of tourism imaginations. This article visualises the challenges in tourism associated with the developments of the social web out of a scientific and practical point of view.
Credibility of online reviews and initial trust
Authors: Kusumasondjaja Sony , Shanka Tekle , Marchegiani Christopher
Published: July 2012

This article investigates the main and interactional effects of review valence and the presence of source identity on consumer perception of credibility of an online review and initial trust of travel services being reviewed. An experimental design is developed involving 639 travel consumers. Results indicate that a negative online review is deemed more credible than a positive online review, while a positive online review leads to a greater initial trust than a negative review. These findings apply when the identity of the reviewer is disclosed. However, when the reviewer’s identity is not disclosed, there is no significant difference between positive and negative reviews either in terms of perceived credibility or impact on consumer trust. Theoretical and managerial implications, limitations and future directions are also discussed.
Computer-assisted Webnography
Authors: Horster Eric , Gottschalk Carsten
Published: July 2012

Through social media applications, consumers are increasingly participating in information processes. When booking a journey, consumer opinions exchanged via modern media shape the reputation of enterprises like travel agencies and thus have a major impact on the decision to book a journey. Online market research is regarded as a crucial tool to steer these online discourses, with the emphasis on quantitative analyses. However, looking at the Web as a social forum can provide additional insights. Taking user-generated data has the advantage that it is collected within a natural setting. Webnography is an attempt to capture this information in a systematic way. Therefore, in this article, Computer-Assisted Webnography is presented as an innovative control method. It is based on the practical modification of ethnographic methods. Computer-Assisted Webnography is meant to combine quantitative and qualitative methods and merges both the approaches on a virtual working platform, so that the semiotic codes of any given target group can be extracted efficiently and precisely. The results shall be used to create individual reputation management strategies.
Effects of a physical activity governmental health programme on the quality of life of elderly people
Authors: Figueira Helena A. , Figueira Alan A. , Cader Samária A. , Guimarães Andrea C. , De Oliveira Ricardo J. , Figueira Joana A. , Figueira Olivia A. , Dantas Estélio H.M.
Published: July 2012

Background:

The population ageing occurring worldwide resulted in multiple researches on sedentary ageing and quality of life.

Purpose:

To verify the effects of a physical activity programme on the quality of life (QOL) of elderly individuals served by a governmental health programme.

Design:

Descriptive inquiry research.

Methods:

Randomly distributing 70 elderly individuals in a control group ( n=35; mean±SD 69.80±8.05 years) and an experimental group ( n=35; 68.66±5.93 years) plus QOL evaluation via WHOQOL-Old.

Results:

The experimental group showed significant best results on the post-test by repeated-measures ANOVA on sensorial functioning (Δ%=0.022%, p=0. 0001), social participation (Δ%=0.012%, p=0.013), perceptions of death and dying (Δ%=0.04%, p=0.009), intimacy (Δ%=0.059%, p=0.05), and total score (Δ%=0.001, p=0.000).

Conclusions:

Sensorial functioning, social participation, perceptions of death and dying, and intimacy play an important role in the positive relationship between physical activity and QOL.
Social participation, interpersonal trust, and health: A study of 65- and 75-year-olds in western Finland
Authors: Nyqvist Fredrica , Nygård Mikael , Jakobsson Gunborg
Published: July 2012

Aim: To study the association between social participation, interpersonal trust, and self-rated health among 65- and 75-year-olds. Methods: The data originates from a cross-sectional postal questionnaire survey conducted among 1577 persons aged 65 and 75 years in western Finland (response rate 67%). Logistic regression analyses were performed in order to investigate the association between social capital – in terms social participation and interpersonal trust – and health while controlling for sociodemographic variables. Results: The results showed that the social participation indicator (“active membership in organisations”) was positively associated with health among 75-year-olds, but not among 65-year-olds. By contrast, interpersonal trust was positively associated with health in both age groups. Conclusions: The results imply that social participation and its association with health is moderated by age, whereas interpersonal trust is not.
Fabrication and characterization of carbonized and activated cotton nonwovens
Authors: Chen Jonathan Yan , Jiang Nan
Published: July 2012

A needle-punched cotton nonwoven was produced as a precursor for making activated carbon material. Carbonization and activation of the cotton nonwoven was carried out in a high temperature clean room oven. Microporous properties of the nonwoven in terms of surface area, micropore volume, micropore size, and adsorption isotherms were characterized using a micropore physisorption analyzer. Influence of carbonization temperature and difference between the N2 and CO2 adsorptions was analyzed. Tensile strength of the cotton nonwoven before and after the carbonization and activation was evaluated. Microporous structure of the carbonized and activated cotton nonwoven was examined using an scanning electron microscopy technique. The study exhibited that the carbonized and activated cotton nonwoven was a special type of renewable and biodegradable material featuring lightweight, high microporosity, and high performance of chemical adsorption and separation.
Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps
Authors: Zaheer Fariha , Berger Joseph R.
Published: July 2012

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the brain caused by a ubiquitous polyomavirus, JC virus. PML is almost always associated with some underlying immunosuppression and acquired immune deficiency syndrome has been the most common predisposing disorder. Recently, different pharmacological agents have been demonstrated to increase the risk of PML. Therapies that predispose people to PML can be classified into three categories: therapies that uniquely increase the risk for the disorder, such as the monoclonal antibodies natalizumab and efalizumab; therapies that appear to increase the risk in individuals already at risk of PML due to pre-existing conditions, such as rituximab and mycophenolate mofetil; and therapies with a mechanism of action that might suggest a potential for increased PML risk and/or with which rare cases of PML have been observed. Unlike the latter two classes, therapeutic agents uniquely increasing the risk of PML are associated with a much greater prevalence of the disorder and a latent interval from the time of drug initiation to the development of PML. PML development with pharmacological agents has provided new insight into the pathogenesis of this devastating disorder. This review focuses on the risks of PML with multiple pharmacological agents, the proposed pathogenesis with these agents, and potential risk mitigation strategies.
The Proximity of Common Unhappiness and Misery
Authors: Schnittker Jason
Published: July 2012

The author explores whether the effects of established social risk factors are consistent across the entire range of depression symptoms, guided by the intuition that more severe depression is endogenous in origin and therefore less subject to social influence. Using the National Comorbidity Survey Replication, the author specifically explores transitions between progressive quintiles on the K10 scale of psychological distress using a continuation ratio model. The results reveal that the risk factors sociologists have explored almost exclusively using dimensional measures (e.g., schooling, income, subjective status, life events, social support, marriage) have effects that are generally consistent across the range of symptom severities, whether in terms of transitioning from no symptoms to average unhappiness or from average unhappiness to major depression. Indeed, for a few distal causes, including schooling and income, the association grows stronger with more severe symptoms, whereas for some proximate causes, including traumatic life events and headache, the association grows weaker. Although the results encourage sociologists to remain confident in the power of social risk factors, they complicate debates regarding what a “normal” response to stress is. Normal has no natural benchmark that can be identified using the range of effects associated with social risk factors.
Outcome of hematopoietic stem cell transplantation for adenosine deaminase–deficient severe combined immunodeficiency
Authors: Hassan Amel , Booth Claire , Brightwell Alex , Allwood Zoe , Veys Paul , Rao Kanchan , Hönig Manfred , Friedrich Wilhelm , Gennery Andrew , Slatter Mary , Bredius Robbert , Finocchi Andrea , Cancrini Caterina , Aiuti Alessandro , Porta Fulvio , Lanfranchi Arnalda , Ridella Michela , Steward Colin , Filipovich Alexandra , Marsh Rebecca , Bordon Victoria , Al-Muhsen Saleh , Al-Mousa Hamoud , Alsum Zobaida , Al-Dhekri Hasan , Al Ghonaium Abdulaziz , Speckmann Carsten , Fischer Alain , Mahlaoui Nizar , Nichols Kim E. , Grunebaum Eyal , Al Zahrani Daifulah , Roifman Chaim M. , Boelens Jaap , Davies E. Graham , Cavazzana-Calvo Marina , Notarangelo Luigi , Gaspar H. Bobby
Published: July 2012

Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.
Fbw7γ-mediated degradation of KLF13 prevents RANTES expression in resting human but not murine T lymphocytes
Authors: Kim Dong Seok , Zhang Wei , Millman Scott E. , Hwang Byung Joon , Kwon Seok Joo , Clayberger Carol , Pagano Michele , Krensky Alan M.
Published: July 2012

RANTES (CCL5) is a chemokine implicated in many human diseases. We previously showed that the transcription factor Kruppel-like factor 13 (KLF13) controls the late (3-5 days after activation) expression of RANTES in T lymphocytes and that KLF13 itself is translationally regulated through the 5′-untranslated region of its mRNA. Here, we show that KLF13 levels are further regulated by ubiquitination and degradation. KLF13 protein is undetectable in resting human T lymphocytes, but treatment with either proteosomal or lysosomal inhibitors increases KLF13 protein levels. Glycogen synthase kinase 3β (GSK3β)–mediated phosphorylation of KLF13 triggers the ubiquitination of KLF13 by the E3 ligase Fbw7γ, resulting in KLF13 protein degradation. Knockdown of either Fbw7γ or GSK3β by small interfering RNA increases KLF13 expression in resting human T lymphocytes. In contrast, in murine T lymphocytes, KLF13 protein is abundant because of the absence of Fbw7γ. Treatment of unactivated human lymphocytes with lysosomal inhibitors stabilizes KLF13 protein, resulting in an increase of RANTES mRNA and protein. Taken together, these studies found that tightly regulated control of both synthesis and degradation allows rapid changes in the level of KLF13 in human T lymphocytes.
Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice
Authors: So Alex Yick-Lun , Garcia-Flores Yvette , Minisandram Aarathi , Martin Ayana , Taganov Konstantin , Boldin Mark , Baltimore David
Published: July 2012

APCs are essential for innate and adaptive immunity as well as self-immune tolerance. Here, we show that the Cap'n'collar member Bach1 regulates the generation of APCs, specifically macrophages and dendritic cells, in mice. The impaired APC development in Bach1−/− mice was accompanied by defects in downstream T-cell responses and partial protection from experimental autoimmune encephalomyelitis. Genomewide analyses identified a panel of Bach1 target genes and ablation of the direct Bach1 target gene HO-1 exacerbated the impaired APC development observed in Bach1−/− mice. This was attributed to the impaired ability of HO-1−/−Bach1−/− double mutants to produce upstream APC progenitor cells, including common myeloid progenitor (CMP)–Flk2+. By contrast, we observed an increase in hematopoietic stem-progenitor cells (HSPCs) in these mice, suggesting a developmental block in the progression of HSPCs to CMP-Flk2+ and subsequently APCs.
Munc18b/STXBP2 is required for platelet secretion
Authors: Al Hawas Rania , Ren Qiansheng , Ye Shaojing , Karim Zubair A. , Filipovich Alexandra H. , Whiteheart Sidney W.
Published: July 2012

Platelets are vital for hemostasis because they release their granule contents in response to vascular damage. Platelet exocytosis is mediated by soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs), whose interactions are governed by regulators, eg, Sec/Munc18 proteins. These proteins chaperone syntaxin t-SNAREs and are required for exocytosis. Platelets contain 3 Munc18 isoforms: Munc18a, Munc18b, and Munc18c. We report that Munc18b is the major isoform and is required for platelet secretion. Familial hemophagocytic lymphohistiocytosis type 5 (FHL5) is caused by defects in the Munc18b/STXBP2 gene. We confirm a previous report showing that platelets from FHL5 patients have defective secretion. Serotonin, ADP/ATP, and platelet factor 4 release was profoundly affected in the 2 biallelic patients and partially in a heterozygous patient. Release of lysosomal contents was only affected in the biallelic platelets. Platelets from the FHL5 biallelic patients showed decreased Munc18b and syntaxin-11 levels were significantly reduced; other syntaxins were unaffected. Munc18b formed complexes with syntaxin-11, SNAP-23, and vesicle-associated membrane protein-8 in human platelets. Other potential secretion regulators, Munc13-4 and Rab27, were also found associated. These data demonstrate a key role for Munc18b, perhaps as a limiting factor, in platelet exocytosis and suggest that it regulates syntaxin-11.
Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia
Authors: Jaako Pekka , Debnath Shubhranshu , Olsson Karin , Bryder David , Flygare Johan , Karlsson Stefan
Published: July 2012

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Recently, a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for RPS19-deficient DBA. Administration of L-leucine significantly improved the anemia in Rps19-deficient mice (19% improvement in hemoglobin concentration; 18% increase in the number of erythrocytes), increased the bone marrow cellularity, and alleviated stress hematopoiesis. Furthermore, the therapeutic response to L-leucine appeared specific for Rps19-deficient hematopoiesis and was associated with down-regulation of p53 activity. Our study supports the rationale for clinical trials of L-leucine as a therapeutic agent for DBA.
Is there a role for consolidative radiotherapy in the treatment of aggressive and localized Non-Hodgkin Lymphoma? A systematic review with meta-analysis
Authors: dos Santos Lucas Vieira , Lima JoãoPaulodaSilveiraNogueira , Lima Carmens Sílvia Passos , Sasse Emma Chen , Sasse André Deeke
Published: July 2012

Background

Chemotherapy is the mainstay of non-Hodgkin lymphoma (NHL) treatment. Based on expert opinion, the use of radiotherapy (RT) is currently preferred in some institutions as consolidative treatment for patients with localized disease. The lack of conclusive data coming from conflicting studies about the impact of treatment demands a systematic review, which could provide the most reliable assessment for clinical decision-making. We evaluate the addition of RT post-CT, for aggressive and localized NHL (ALNHL).

Methods

Randomized controlled trials (RCT) that evaluated chemotherapy alone versus chemotherapy plus RT were searched in databases. The outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity. Risk ratio (RR) and hazard ratio (HR) with their respective 95% confidence intervals (CI) were calculated using a fized-effect model.

Results

Four trials (1,796 patients) met the inclusion criteria. All trials tested the use of RT after systemic therapy comprising anthracycline-based chemotherapy. This systematic review showed that RT enhances PFS after chemotherapy (hazard ratio [HR] 0.81; 95% CI 0.67-0.98; p = 0.03), with no impact on ORR and OS. Some heterogeneity between trials could limit the conclusions about OS. Toxicity data could not be pooled due to differences in reporting adverse events.

Conclusions

This systematic review with meta-analysis shows no improvement in survival when adding RT to systemic therapy for ALNHL. Our conclusions are limited by the available data. Further evaluations of new RT technologies and its association with biologic agents are needed.
Prospective in-patient cohort study of moves between levels of therapeutic security: the DUNDRUM-1 triage security, DUNDRUM-3 programme completion and DUNDRUM-4 recovery scales and the HCR-20
Authors: Davoren Mary , O'Dwyer Sarah , Abidin Zareena , Naughton Leena , Gibbons Olivia , Doyle Elaine , McDonnell Kim , Monks Stephen , Kennedy Harry G
Published: July 2012

Background

We examined whether new structured professional judgment instruments for assessing need for therapeutic security, treatment completion and recovery in forensic settings were related to moves from higher to lower levels of therapeutic security and added anything to assessment of risk.

Methods

This was a prospective naturalistic twelve month observational study of a cohort of patients in a forensic hospital placed according to their need for therapeutic security along a pathway of moves from high to progressively less secure units in preparation for discharge. Patients were assessed using the DUNDRUM-1 triage security scale, the DUNDRUM-3 programme completion scale and the DUNDRUM-4 recovery scale and assessments of risk of violence, self harm and suicide, symptom severity and global function. Patients were subsequently observed for positive moves to less secure units and negative moves to more secure units.

Results

There were 86 male patients at baseline with mean follow-up 0.9 years, 11 positive and 9 negative moves. For positive moves, logistic regression indicated that along with location at baseline, the DUNDRUM-1, HCR-20 dynamic and PANSS general symptom scores were associated with subsequent positive moves. The receiver operating characteristic was significant for the DUNDRUM-1 while ANOVA co-varying for both location at baseline and HCR-20 dynamic score was significant for DUNDRUM-1. For negative moves, logistic regression showed DUNDRUM-1 and HCR-20 dynamic scores were associated with subsequent negative moves, along with DUNDRUM-3 and PANSS negative symptoms in some models. The receiver operating characteristic was significant for the DUNDRUM-4 recovery and HCR-20 dynamic scores with DUNDRUM-1, DUNDRUM-3, PANSS general and GAF marginal. ANOVA co-varying for both location at baseline and HCR-20 dynamic scores showed only DUNDRUM-1 and PANSS negative symptoms associated with subsequent negative moves.

Conclusions

Clinicians appear to decide moves based on combinations of current and imminent (dynamic) risk measured by HCR-20 dynamic score and historical seriousness of risk as measured by need for therapeutic security (DUNDRUM-1) in keeping with Scott's formulation of risk and seriousness. The DUNDRUM-3 programme completion and DUNDRUM-4 recovery scales have utility as dynamic measures that can off-set perceived 'dangerousness'.
Investigation of phase composition and nanoscale microstructure of high-energy ball-milled MgCu sample
Authors: Ma Zongqing , Liu Yongchang , Yu Liming , Cai Qi
Published: July 2012

The ball milling technique has been successfully applied to the synthesis of various materials such as equilibrium intermetallic phases, amorphous compounds, nanocrystalline materials, or metastable crystalline phases. However, how the phase composition and nanoscale microstructure evolute during ball milling in various materials is still controversial due to the complex mechanism of ball milling, especially in the field of solid-state amorphization caused by ball milling. In the present work, the phase evolution during the high-energy ball milling process of the Mg and Cu (atomic ratio is 1:1) mixed powder was investigated. It was found that Mg firstly reacts with Cu, forming the Mg2Cu alloy in the primary stage of ball milling. As the milling time increases, the diffracted peaks of Mg2Cu and Cu gradually disappear, and only a broad halo peak can be observed in the X-ray diffraction pattern of the final 18-h milled sample. As for this halo peak, lots of previous studies suggested that it originated from the amorphous phase formed during the ball milling. Here, a different opinion that this halo peak results from the very small size of crystals is proposed: As the ball milling time increases, the sizes of Mg2Cu and Cu crystals become smaller and smaller, so the diffracted peaks of Mg2Cu and Cu become broader and broader and result in their overlap between 39° and 45°, at last forming the amorphous-like halo peak. In order to determine the origin of this halo peak, microstructure observation and annealing experiment on the milled sample were carried out. In the transmission electron microscopy dark-field image of the milled sample, lots of very small nanocrystals (below 20 nm) identified as Mg2Cu and Cu were found. Moreover, in the differential scanning calorimetry curve of the milled sample during the annealing process, no obvious exothermic peak corresponding to the crystallization of amorphous phase is observed. All the above results confirm that the broad halo diffracted peak in the milled MgCu sample is attributed to the overlap of the broadened peaks of the very small Mg2Cu and Cu nanocrystalline phase, not the MgCu amorphous phase. The whole milling process of MgCu can be described as follows:Mg+Cu→Mg2Cu+Cu→Mg2Cunanocrystal+Cunanocrystal.
Study of the omnidirectional photonic bandgap for dielectric mirrors based on porous silicon: effect of optical and physical thickness
Authors: Ariza-Flores Augusto David , Gaggero-Sager Luis Manuel , Agarwal Vivechana
Published: July 2012

We report the theoretical comparison of the omnidirectional photonic bandgap (OPBG) of one-dimensional dielectric photonic structures, using three different refractive index profiles: sinusoidal, Gaussian, and Bragg. For different values of physical thickness (PT) and optical thickness (OT), the tunability of the OPBG of each profile is shown to depend on the maximum/minimum refractive indices. With an increase in the value of the maximum refractive index, the structures with the same PT showed a linear increment of the OPBG, in contrast to the structures with the same OT, showing an optimal combination of refractive indices for each structure to generate the maximum OPBG. An experimental verification was carried out with a multilayered dielectric porous silicon structure for all the three profiles.
Exploring the interaction between SNP genotype and postmenopausal hormone therapy effects on stroke risk
Authors: Huang Ying , Ballinger Dennis G , Stokowski Renee , Beilharz Erica , Robinson Jennifer G , Liu Simin , Robinson Randal D , Henderson Victor W , Rossouw Jacques E , Prentice Ross L
Published: July 2012

Background

Genome-wide association studies have identified several genomic regions that are associated with stroke risk, but these provide an explanation for only a small fraction of familial stroke aggregation. Genotype by environment interactions may contribute further to such an explanation. The Women's Health Initiative (WHI) clinical trial found increased stroke risk with postmenopausal hormone therapy (HT) and provides an efficient setting for evaluating genotype-HT interaction on stroke risk.

Methods

We examined HT by genotype interactions for 392 SNPs selected from candidate gene studies, and 2,371 SNPs associated with changes in blood protein concentrations after hormone therapy, in analyses that included 2,045 postmenopausal women who developed stroke during WHI clinical trial and observational study follow-up and one-to-one matched controls. A two-stage procedure was implemented where SNPs passing the first stage screening based on marginal association with stroke risk were tested in the second stage for interaction with HT using case-only analysis.

Results

The two-stage procedure identified two SNPs, rs2154299 and rs12194855, in the coagulation factor XIII subunit A (F13A1) region and two SNPs, rs630431 and rs560892, in the proprotein convertase subtilisin kexin 9 (PCSK9) region, with an estimated false discovery rate <0.05 based on interaction tests. Further analyses showed significant stroke risk interaction between these F13A1 SNPs and estrogen plus progestin (E+P) treatment for ischemic stroke and for ischemic and hemorrhagic stroke combined, and suggested interactions between PCSK9 SNPs with either E+P or estrogen-alone treatment.

Conclusions

Genotype by environment interaction information may help to define genomic regions relevant to stroke risk. Two-stage analysis among postmenopausal women generates novel hypotheses concerning the F13A1 and PCSK9 genomic regions and the effects of hormonal exposures on postmenopausal stroke risk for subsequent independent validation.
Type II NKT cells facilitate Alum-sensing and humoral immunity
Authors: Shah Hemangi B , Devera T Scott , Rampuria Pragya , Lang Gillian A , Lang Mark L
Published: July 2012

Type II NKT cells contribute to Alum-enhanced T helper-2 type responses.

Alum-based adjuvants facilitate vaccine-driven humoral immunity, but their mechanism of action remains poorly understood. Herein, we report that lack of type II NKT cells is associated with intact, mature B cells but dampened humoral immunity following immunization with Alum-adsorbed T-dependent antigen. Type II NKT cells facilitated production of IL-4, IL-5, IL-10, IL-13, and antibody by LN and splenocyte cultures following Alum/antigen administration in vivo and antigen restimulation in vitro. Addition of IL-4 and IL-5 to type II NKT-deficient cultures restored in vitro antibody production. Intracellular staining revealed that Alum-primed type II NKT cells coordinated IL-4 secretion by T cells. Alum did not significantly affect CD1d expression in vivo, but addition of CD1d-blocking mAb diminished cytokine production and in vitro antibody production. Type II NKT cells therefore function as part of the Alum-sensing apparatus and in a CD1d-dependent manner, facilitate TH2-driven humoral immunity. This may have important consequences for understanding the mechanism of action of Alum-containing vaccines.
A hybrid regularization scheme for the inversion of magnetotelluric data from natural and controlled sources to layer and distortion parameters
Authors: Kalscheuer Thomas , Hübert Juliane , Kuvshinov Alexey , Lochbühler Tobias , Pedersen Laust B.
Published: July 2012

Magnetotelluric (MT), radiomagnetotelluric (RMT), and, in particular, controlled-source audiomagnetotelluric (CSAMT) data are often heavily distorted by near-surface inhomogeneities. We developed a novel scheme to invert MT, RMT, and CSAMT data in the form of scalar or tensorial impedances and vertical magnetic transfer functions simultaneously for layer resistivities and electric and magnetic galvanic distortion parameters. The inversion scheme uses smoothness constraints to regularize layer resistivities and either Marquardt-Levenberg damping or the minimum-solution length criterion to regularize distortion parameters. A depth of investigation range is estimated by comparing layered model sections derived from first- and second-order smoothness constraints. Synthetic examples demonstrate that earth models are reconstructed properly for distorted and undistorted tensorial CSAMT data. In the inversion of scalar CSAMT data, such as the determinant impedance or individual tensor elements, the reduced number of transfer functions inevitably leads to increased ambiguity for distortion parameters. As a consequence of this ambiguity for scalar data, distortion parameters often grow over the iterations to unrealistic absolute values when regularized with the Marquardt-Levenberg scheme. Essentially, compensating relationships between terms containing electric and/or magnetic distortion are used in this growth. In a regularization with the minimum solution length criterion, the distortion parameters converge into a stable configuration after several iterations and attain reasonable values. The inversion algorithm was applied to a CSAMT field data set collected along a profile over a tunnel construction site at Hallandsåsen, Sweden. To avoid erroneous inverse models from strong anthropogenic effects on the data, two scalar transfer functions (one scalar impedance and one scalar vertical magnetic transfer function) were selected for inversion. Compared with a regularization of distortion parameters with the Marquardt-Levenberg method, the minimum-solution length criterion yielded smaller absolute values of distortion parameters and a horizontally more homogeneous distribution of electrical conductivity.
Long-Acting FGF21 Has Enhanced Efficacy in Diet-Induced Obese Mice and in Obese Rhesus Monkeys
Authors: Véniant Murielle M. , Komorowski Renee , Chen Ping , Stanislaus Shanaka , Winters Katherine , Hager Todd , Zhou Lei , Wada Russell , Hecht Randy , Xu Jing
Published: July 2012

Fibroblast growth factor 21 (FGF21), a hormone with short half-life, has consistently shown strong pharmacological efficacy. We first assessed the efficacy of murine recombinant FGF21 in C57BL6 lean mice for 5 wk. We then generated a long-acting FGF21 molecule by fusing a Fc to a variant of human recombinant FGF21 (hrFGF21) that contained two engineered mutations [L98R, P171G; Fc-FGF21(RG)] and tested it in C57BL6 diet-induced obese mice and obese rhesus monkeys. We compared its metabolic properties with those of the hrFGF21. Groups of diet-induced obese mice were treated for 36 d with different doses of hrFGF21 (01, 0.3, and 1 mg/kg twice daily) and with Fc-FGF21(RG) (2.3 mg/kg, every 5 d). Body weight, glucose, insulin, cholesterol, and triglyceride levels were decreased after treatment with either compound. A glucose tolerance test (GTT) was also improved. Obese rhesus monkeys were treated with hrFGF21 (once a day) and Fc-FGF21(RG) (once a week) in a dose-escalation fashion. Doses started at 0.1 and 0.3 mg/kg and ended at 3 and 5 mg/kg for hrFGF21 and Fc-FGF21(RG), respectively. Doses were escalated every 2 wk, and animals were followed up for a washout period of 3 wk. Body weight, glucose, insulin, cholesterol, and triglyceride levels and the GTT profile were decreased to a greater extent with Fc-FGF21(RG) than with hrFGF21. The PK-PD relationship of Fc-FGF21(RG) exposure and triglyceride reduction was also conducted with a maximum response model. In conclusion, in more than one species, Fc-FGF21(RG) chronically administered once a week showed similar or greater efficacy than hrFGF21 administered daily.
The Potassium Channel, Kir3.4 Participates in Angiotensin II-Stimulated Aldosterone Production by a Human Adrenocortical Cell Line
Authors: Oki Kenji , Plonczynski Maria W. , Lam Milay Luis , Gomez-Sanchez Elise P. , Gomez-Sanchez Celso E.
Published: July 2012

Angiotensin II (A-II) regulation of aldosterone secretion is initiated by inducing cell membrane depolarization, thereby increasing intracellular calcium and activating the calcium calmodulin/calmodulin kinase cascade. Mutations in the selectivity filter of the KCNJ5 gene coding for inward rectifying potassium channel (Kir)3.4 has been found in about one third of aldosterone-producing adenomas. These mutations result in loss of selectivity of the inward rectifying current for potassium, which causes membrane depolarization and opening of calcium channels and activation of the calcium calmodulin/calmodulin kinase cascade and results in an increase in aldosterone secretion. In this study we show that A-II and a calcium ionophore down-regulate the expression of KCNJ5 mRNA and protein. Activation of Kir3.4 by naringin inhibits A-II-stimulated membrane voltage and aldosterone secretion. Overexpression of KCNJ5 in the HAC15 cells using a lentivirus resulted in a decrease in membrane voltage, intracellular calcium, expression of steroidogenic acute regulatory protein, 3-β-hydroxysteroid dehydrogenase 3B2, cytochrome P450 11B1 and cytochrome P450 11B2 mRNA, and aldosterone synthesis. In conclusion, A-II appears to stimulate aldosterone secretion by depolarizing the membrane acting in part through the regulation of the expression and activity of Kir3.4.
Identification of Molecular Phenotypes and Biased Signaling Induced by Naturally Occurring Mutations of the Human Calcium-Sensing Receptor
Authors: Leach Katie , Wen Adriel , Davey Anna E. , Sexton Patrick M. , Conigrave Arthur D , Christopoulos Arthur
Published: July 2012

More than 200 naturally occurring mutations have been identified in the human CaSR, which have been linked to diseases involving dysregulation of extracellular Ca2+ homeostasis. These mutations have classically been termed “loss-” or “gain-of-function” mutations, which is an oversimplification given that amino acid changes can alter numerous molecular properties of a receptor. We thus sought to characterize the effects of 21 clinically relevant mutations, the majority located in the heptahelical domains and extracellular loop regions of the CaSR, using flow cytometry to measure cell surface receptor expression levels, and measurements of intracellular Ca2+ mobilization and ERK1/2 phosphorylation to monitor receptor signaling. We identified distinct molecular phenotypes caused by these naturally occurring amino acid substitutions, which included combinations of loss- and gain-of-expression and changes in intrinsic signaling capacity. Importantly, we also identified biased signaling in the response of the CaSR to different mutations across the two pathways, indicating that some mutations resulted in receptor conformations that differentially altered receptor-coupling preferences. These findings have important implications for understanding the causes of diseases linked to the CaSR. A full appreciation of the molecular effects of these amino acid changes may enable the development of therapeutics that specifically target the molecular determinant of impairment in the receptor.