bluuebunny/crossref_metadata_2025 huggingface dataset:
Bisphosphonate use and risk of colorectal cancer: a systematic review and meta‐analysis
Authors: Bonovas Stefanos , Nikolopoulos Georgios , Bagos Pantelis
Published: April 2013

Aim

A growing body of evidence suggests that bisphosphonates may have chemopreventive potential against colorectal cancer. Our aim was to examine this association through a meta‐analysis of observational studies.

Methods

A comprehensive search for relevant articles published up to October 2012 was performed, reviews of each study were conducted and data were abstracted. Prior to meta‐analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random effects and the fixed effects models. Subgroup and sensitivity analyses were also performed.

Results

Eight large population‐based epidemiological studies (one case‐control, two nested case‐control analyses within a cohort and five cohort studies), involving more than 630 000 participants, contributed to the analysis. We found no evidence of publication bias. However, significant heterogeneity was detected among the cohort studies. The analysis revealed a significant protective association between bisphosphonate use and colorectal cancer risk (fixed RR = 0.85, 95% CI 0.80, 0.90, random RR = 0.85, 95% CI 0.75, 0.96). When the analysis was stratified into subgroups according to study design, the association was inverse in both case‐control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis confirmed the stability of our results. Furthermore, we found evidence for a dose effect; Long term bisphosphonate use was associated with a 27% decrease in the risk of developing colorectal cancer as compared with non‐use (RR = 0.73, 95% CI 0.57, 0.93).

Conclusion

Our findings support a protective effect of bisphosphonates against colorectal cancer. However, further evidence is warranted.
D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma
Authors: Gerrie Alina S. , Mikhael Joseph R. , Cheng Lu , Jiang Haiyan , Kukreti Vishal , Panzarella Tony , Reece Donna , Stewart Keith A. , Trieu Young , Trudel Suzanne , Chen Christine I.
Published: April 2013

Dexamethasone ± thalidomide with infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide [D(T)PACE] is generally reserved as salvage therapy for aggressive multiple myeloma (MM) or plasma cell leukaemia (PCL) resistant to conventional therapies. The efficacy and durability of this potentially toxic regimen in this setting is unclear. We identified 75 patients who received D(T)PACE for relapsed/refractory MM at two tertiary care centres: Princess Margaret Hospital, Toronto and Mayo Clinic Arizona. At time of D(T)PACE, 16 patients had PCL and three patients had leptomeningeal disease. Patients were heavily pretreated (median three prior regimens, range 1–12; prior autologous stem cell transplant [ASCT] 33%). Overall response rate was 49% (very‐good partial response 16%, partial response 33%) with stable disease in an additional 36%. Median progression‐free survival (PFS) was 5·5 months (95% confidence interval [CI]:4·3–9·8); overall survival (OS) 14·0 months (95% CI:8·7–19·3). Thirty‐five patients proceeded to ASCT or clinical trial, with median PFS for this subset of 13·4 months (95% CI:7·7–20·1) and OS 20·5 months (95% CI:14·8–63·8). D(T)PACE is an effective salvage therapy for heavily pretreated MM patients. Although the overall response rate of 49% in this poor prognosis cohort is reasonable, the PFS is short, suggesting the best role for D(T)PACE is in bridging to definitive therapy, such as transplantation.
Immature dendritic cells in multiple myeloma are prone to osteoclast‐like differentiation through interleukin‐17A stimulation
Authors: Tucci Marco , Stucci Stefania , Savonarola Annalisa , Ciavarella Sabino , Cafforio Paola , Dammacco Franco , Silvestris Franco
Published: April 2013

Interleukin 17A (IL17A), a cytokine involved in allergy, inflammation and osteoclastogenesis, was investigated in multiple myeloma (MM) to assess its role in the osteoclast (OC)‐like activity of marrow immature dendritic cells (iDCs). Comparing nine MM patients with control subjects affected by monoclonal gammopathy of undetermined significance, we found high IL17A expression in the marrow plasma of MM patients in parallel with its deposits within the stromal matrix. Increased expression of the IL17A receptor (IL17RA) was also found in primary myeloma iDCs, which underwent OC‐like transdifferentiation after IL17A stimulation. To assess the role of IL17A, we measured the activity of the IL17/IL17RA pathway in IL17A‐transdifferentiated iDCs and the expression of functional OC genes by Western blotting and real‐time polymerase chain reaction. These cells showed increased RNA transcription of genes enrolled in the maturation of OCs, while NFATC1 and FOS were induced by IL17A, independently of NFKB1 phosphorylation. Moreover, the concurrent phosphorylation of the Lip isoform of CEBPB and the down‐regulation of MAFB supported the activation of IL17RA pathway in OC‐like transdifferentiated iDCs that was apparently unrelated to TNFRSF11A signalling. These data emphasize the involvement of iDCs in MM hyperactive osteoclastogenesis and suggest that their bone resorption activity is also regulated, at least in vitro, by IL17RA.
Malignancies and monoclonal gammopathy in Gaucher disease; a systematic review of the literature
Authors: Arends Maarten , van Dussen Laura , Biegstraaten Marieke , Hollak Carla E. M.
Published: April 2013

Gaucher disease is an autosomal, recessively inherited, lysosomal storage disease, which has been associated with gammopathies and malignancies. This report represents the results of a systematic review of the literature on the prevalence of monoclonal gammopathies and malignancies in Gaucher disease. A PubMed search identified 365 studies, of which 80 reported on concomitant Gaucher disease and malignancies and/or gammopathies (15 cohort/cross sectional studies, and 65 case reports/series). Based on these studies, we conclude that compared to the general population, Gaucher patients have an increased risk of cancer in general [pooled relative risk of 1·70 (95% confidence interval 1·27–2·31)], and multiple myeloma and haematological malignancies in particular (estimated risk between 25·0 and 51·1 and 3·5 and 12·7, respectively). In addition, an increased risk has been reported for hepatocellular carcinoma and renal cell carcinoma. Several factors have been hypothesized to play a role in the pathophysiology. These include: splenectomy, immune dysregulation, endoplasmic reticulum stress, genetic modifiers, altered iron metabolism and insulin resistance.
Interplay between coagulation and vascular inflammation in sickle cell disease
Authors: Sparkenbaugh Erica , Pawlinski Rafal
Published: April 2013

Sickle cell disease is the most common inherited haematological disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso‐occlusion are central to the pathophysiology of sickle cell disease, the importance of haemolytic anaemia and vasculopathy has been recently recognized. A hypercoagulable state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease.
B‐cell lymphoma, unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and burkitt lymphoma: study of 39 cases
Authors: Perry Anamarija M. , Crockett David , Dave Bhavana J. , Althof Pamela , Winkler Lisa , Smith Lynette M. , Aoun Patricia , Chan Wing C. , Fu Kai , Greiner Timothy C. , Bierman Phillip , Gregory Bociek Robert , Vose Julie M. , Armitage James O. , Weisenburger Dennis D.
Published: April 2013

B‐cell lymphoma, unclassifiable (B‐UCL), with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma, is a poorly characterized entity. Therefore, we investigated cases of B‐UCL treated by the Nebraska Lymphoma Study Group (NLSG). We searched the NLSG registry for years 1985–2010 for cases of B‐UCL. Immunohistochemical stains and fluorescence in situ hybridization studies for MYC, BCL2 and BCL6 gene rearrangements were performed. Among the 39 cases studied, 54% were male and 46% were female, with a median age of 69 years. The majority of patients presented with advanced‐stage disease (62%) and had high (3–5) International Prognostic Index (IPI) scores (54%). The median overall survival (OS) was only 9 months and the 5‐year OS was 30%. Patients with low IPI scores (0–2) had a better survival than those with high scores (3–5). The cases were genetically heterogeneous and included 11 ‘double‐hit’ lymphomas with rearrangements of both MYC and BCL2 or BCL6. None of the immunohistochemical or genetic features was predictive of survival. This B‐cell lymphoma is a morphologically‐recognizable entity with a spectrum of genetic abnormalities. New and better treatments are needed for this aggressive lymphoma.
Adult T‐cell leukemia cells are characterized by abnormalities of Helios expression that promote T cell growth
Authors: Asanuma Satomi , Yamagishi Makoto , Kawanami Katsuaki , Nakano Kazumi , Sato‐Otsubo Aiko , Muto Satsuki , Sanada Masashi , Yamochi Tadanori , Kobayashi Seiichiro , Utsunomiya Atae , Iwanaga Masako , Yamaguchi Kazunari , Uchimaru Kaoru , Ogawa Seishi , Watanabe Toshiki
Published: April 2013

Molecular abnormalities involved in the multistep leukemogenesis of adult T‐cell leukemia (ATL) remain to be clarified. Based on our integrated database, we focused on the expression patterns and levels of Ikaros family genes, Ikaros, Helios, and Aiolos, in ATL patients and HTLV‐1 carriers. The results revealed profound deregulation of Helios expression, a pivotal regulator in the control of T‐cell differentiation and activation. The majority of ATL samples (32/37 cases) showed abnormal splicing of Helios expression, and four cases did not express Helios. In addition, novel genomic loss in Helios locus was observed in 17/168 cases. We identified four ATL‐specific short Helios isoforms and revealed their dominant‐negative function. Ectopic expression of ATL‐type Helios isoform as well as knockdown of normal Helios or Ikaros promoted T‐cell growth. Global mRNA profiling and pathway analysis showed activation of several signaling pathways important for lymphocyte proliferation and survival. These data provide new insights into the molecular involvement of Helios function in the leukemogenesis and phenotype of ATL cells, indicating that Helios deregulation is one of the novel molecular hallmarks of ATL.
HY‐1 induces G2 / M cell cycle arrest in human colon cancer cells through the ATR‐Chk1‐Cdc25C and Weel pathways
Authors: Zhao Yu , Wu Zhonghua , Zhang Yuting , Zhu Li
Published: April 2013

The novel aroylthiourea analogue of podophyllotoxin HY‐1 (4β‐[benzoyl‐thioureido]‐4‐deoxypodophyllotoxin) was synthesized in our laboratory with the aim of developing multitargeted DNA topoisomerase II inhibitors. The compound showed significant antiproliferative effects on seven cancer cell lines and induced G2/M phase arrest in HCT116 cells. Moreover, HY‐1 showed a potent inhibitory effect on topoisomerase II‐mediated kinetoplast DNA decatenation in a dose‐dependent manner. Our results showed that cdc2 phosphorylation and decreased cdc2 kinase acitivity through the ATR‐Chk1‐Cdc25C and Weel pathways were the central mechanisms for G2/M phase arrest in human colon cancer cells.
Family ecology of young children with cerebral palsy
Authors: LaForme Fiss A. , Chiarello L. A. , Bartlett D. , Palisano R. J. , Jeffries L. , Almasri N. , Chang H‐J.
Published: April 2013

Background

Family ecology in early childhood may influence children's activity and participation in daily life. The aim of this study was to describe family functioning, family expectations of their children, family support to their children, and supports for families of young children with cerebral palsy (CP) based on children's gross motor function level.

Methods

Participants were 398 children withCP(mean age = 44.9 months) and their parents residing in theUSAandCanada. Parents completed four measures of family ecology, theFamilyEnvironmentScale (FES),FamilyExpectations ofChild (FEC),FamilySupport toChild (FSC) andFamilySupport Scale (FSS).

Results

The median scores on theFESindicated average to high family functioning and the median score on theFSSindicated that families had helpful family supports. On average, parents reported high expectations of their children on theFECand strong support to their children on theFSC. On theFES, higher levels of achievement orientation were reported by parents of children in Gross Motor Function Classification System (GMFCS) levelIIthan parents of children in level I, and higher levels of control were reported by parents of children in level I than parents of children in levelIV. On theFEC, parents of children with limited gross motor function (levelV) reported lower expectations than parents of children at all other levels.

Conclusions

Family ecology, including family strengths, expectations, interests, supports and resources, should be discussed when providing interventions and supports for young children withCPand their families.
Sleep‐related factors: associations with poor attention and depressive symptoms
Authors: Lehto J. E. , Uusitalo‐Malmivaara L.
Published: April 2013

Background

Sleep duration is known to be associated with depression and attention deficits in children, though the majority of studies have focused on adolescents. Attention problems and depressive symptoms related to sleep factors have not been studied simultaneously in the non‐clinical child population before.

Methods

Sleep quantity, adverse bedtime behaviour, daytime sleepiness, poor attention and symptoms of depression were assessed using self‐report measures. The participants were 11 years old (n = 439).

Results

Short sleep duration during the school week is related to poor attention and high depression. It is not a significant predictor of low attention and high depression symptoms in logistic regression analyses. Instead, adverse bedtime behaviour and daytime sleepiness predict them highly significantly.

Conclusions

Short sleep duration is related to poor attention and depressive symptoms as suggested by previous work. However, the significant role of other sleep‐related factors calls for further research.
Cross‐sectional survey of daily junk food consumption, irregular eating, mental and physical health and parenting style of British secondary school children
Authors: Zahra J. , Ford T. , Jodrell D.
Published: April 2013

Background

Previous research has established that poor diets and eating patterns are associated with numerous adverse health outcomes. This study explored the relationships between two specific eating behaviours (daily junk food consumption and irregular eating) and self‐reported physical and mental health of secondary school children, and their association with perceived parenting and child health.

Methods

10 645 participants aged between 12 and 16 completed measures of junk food consumption, irregular eating, parental style, and mental and physical health through the use of an online survey implemented within 30 schools in a large British city.

Results

2.9% of the sample reported never eating regularly and while 17.2% reported daily consumption of junk food. Young people who reported eating irregularly and consuming junk food daily were at a significantly greater risk of poorer mental (OR 5.41, 95% confidence interval 4.03–7.25 and 2.75, 95% confidence interval 1.99–3.78) and physical health (OR 4.56, 95% confidence interval 3.56–5.85 and 2.00, 95% confidence interval 1.63–2.47). Authoritative parenting was associated with healthier eating behaviours, and better mental and physical health in comparison to other parenting styles.

Discussion

A worrying proportion of secondary school children report unhealthy eating behaviours, particularly daily consumption of junk food, which may be associated with poorer mental and physical health. Parenting style may influence dietary habits. Interventions to improve diet may be more beneficial if also they address parenting strategies and issues related to mental and physical health.
Youth Participation in U.S. Contexts: Student Voice Without a National Mandate
Authors: Mitra Dana , Serriere Stephanie , Kirshner Ben
Published: April 2013

Unlike the United Kingdom and other nations that mandate youth participation to some degree, U.S. policies instead tend to inhibit child participation rather than encourage it. Given these policy contexts, it can be challenging to locate spaces where robust opportunities for democratic participation and student voice exist. We use this article as an opportunity to examine the disciplinary, philosophical and methodological approaches that have framed youth participation in youth contexts. We conclude by identifying critical issues of citizenship and belonging that must be considered in participatory research.
Children of Exception: Redefining Categories of Illegality and Citizenship in Canada
Authors: Meloni Francesca , Rousseau Cécile , Montgomery Catherine , Measham Toby
Published: April 2013

This article examines legal discourses on precarious status children in Canada over the last decade. Drawing on different theoretical frameworks and taking into account laws and court decisions, the paper will examine the way in which precarious status children are regarded as powerless subjects in need of protection and as threatening others. The article argues that these two apparently contrasting discourses are embedded within specific socio‐historical constructions of childhood and children's citizenship which deny and limit their agency and conceive of their claim to membership as illegitimate. In the case of precarious status children, illegality and citizenship need to be redefined in a developmental perspective, questioning the potential risks associated with prevalent moral and social assumptions on childhood.
Does It Matter What Mama Says: Evaluating the Role of Parental Mediation in European Adolescents’ Excessive Internet Use
Authors: Kalmus Veronika , Blinka Lukas , Ólafsson Kjartan
Published: April 2013

This study investigated the relationship between adolescents’ excessive Internet use (EIU) and parental mediation. A random stratified sample of 11‐ to 16‐year olds (N = 18 709) and their parents from 25 European countries (EU Kids Online II project) was analysed to explore to what extent different types of parental mediation and other factors predict EIU. Active parental involvement in the child's Internet use (when the child had experienced online harm) and restrictive mediation were associated with lower EIU. Harmful online experiences, time spent online, scope of online activities and adolescents’ age predicted higher EIU.
‘Orphans and Rich People’: A Discourse Analysis of the ‘Children's Lives’ Exhibition in Birmingham, UK
Authors: McDougall Julian , O'Connor Jane
Published: April 2013

In 2012, an art gallery in Birmingham, England presented an exhibition of ‘Children's Lives’. Through its curation of photography, fine art, objects, video and text, ‘Children's Lives’ claimed to ‘let childhood through the ages speak for itself’ and to contribute ‘to a debate over what it means to be a child’. In this article, we offer a critical analysis of the exhibition, examining the relationship between the exhibition as discourse and the ‘external’ discourses around childhood that are reinforced, negotiated and in some cases challenged by the assemblage of image, text and the spatial ‘narrative’ of the gallery.
A retrospective analysis of the resorption rate of deproteinized bovine bone as maxillary sinus graft material on cone beam computed tomography
Authors: Umanjec‐Korac S. , Wu G. , Hassan B. , Liu Y. , Wismeijer D.
Published: April 2013

Objectives

Graft resorption remains a major disadvantage of the various employed materials in maxillary sinus augmentation. Our aim was to assess the percentage of graft volume reduction in deproteinized bovine bone (DBB) using cone beam computed tomography (CBCT).

Materials and Methods

A retrospective analysis of 29 augmented sinuses in 19 patients was conducted. The graft material was eitherDBBalone orDBBmixed with autologous bone chips (80%DBB/20% bone chips).CBCTscans of the augmented sinuses were obtained pre‐ and post‐operatively up to 2‐year follow‐up.

Results

In total, 55 dental implants were placed in the posterior maxillary region following sinus augmentation. The mean height of the alveolar ridge pre‐operative was 2.7 ± 1.2 mm and post‐operative was 14.13 ± 4.6 mm. The mean percentages of alveolar ridge height reduction were 18.58% (SD14.23%) and 27.62% (SD12.70%), and the mean percentages of graft volume reduction were 19.30% (SD9.19%) and 19.85% (SD9.61%) forDBBandDBB + bone chips, respectively.

Conclusions

The results indicate thatDBBgraft volume resorption is approximately (20 ± 10%) following 2‐year follow‐up.CBCTis a useful radiographic tool to follow‐up changes in sinus graft volumes.
Assessing the Impact of the NIH CTSA Program on Institutionally Sponsored Clinical Trials
Authors: Liu Guodong , Chen Gang , Sinoway Lawrence I. , Berg Arthur
Published: April 2013

Objective

To assess the impact of the NIH CTSA program on patient enrollment in clinical trials sponsored/collaborated by CTSA consortium institutions.

Material and Methods

Using publicly available clinical trial data at ClinicalTrials.gov, we identify positive trend changes in the number of patients enrolled in clinical trials performed at CTSA consortium institutions over the years before and after their respective CTSA award dates. CTSA consortium institutions were matched with similar non‐CTSA institutions.

Results

As compared to matched non‐CTSA institutions CTSA consortium sites noted an increase in patient enrollment after the CTSA awards. In particular, we detected a change‐point, where a new enrollment trend emerged, 338 days after the CTSA award. No such trend was noted over the same period in the non‐CTSA institutions.

Conclusion

Our analysis provides evidence that the NIH CTSA funding program made a positive impact on patient enrollment.
Developing a Competency‐Based Educational Structure within Clinical and Translational Science
Authors: Dilmore Terri Collin , Moore Debra W. , Bjork Zuleikha
Published: April 2013

In the emerging field of clinical and translational science (CTS), where researchers use both basic and clinical science research methodologies to move discoveries to clinical practice, establishing standards of competence is essential for preparing physician–scientists for the profession and for defining the field. The diversity of skills needed to execute quality research within the field of CTS has heightened the importance of an educational process that requires learners to demonstrate competence. Particularly within the more applied clinical science disciplines where there is a multi‐ or interdisciplinary approach to conducting research, defining and articulating the unique role and associated competencies of a physician–scientist is necessary. This paper describes a systematic process for developing a competency‐based educational framework within a CTS graduate program at one institution.
Teaching Research Ethics Better: Focus on Excellent Science, Not Bad Scientists
Authors: Yarborough Mark , Hunter Lawrence
Published: April 2013

A recent report of the United States’ Presidential Commission for the Study of Bioethical Issues highlights how important it is for the research community to enjoy the “earned confidence” of the public and how creating a “culture of responsibility” can contribute to that confidence. It identifies a major role for “creative, flexible, and innovative” ethics education in creating such a culture. Other recent governmental reports from various nations similarly call for a renewed emphasis on ethics education in the sciences. We discuss why some common approaches to ethics education in the graduate sciences fail to meet the goals envisioned in the reports and we describe an approach, animated by primary attention on excellent science as opposed to bad scientists, that we have employed in our ethics teaching that we think is better suited for inspiring and sustaining responsible, trustworthy science.
Evaluation Guidelines for the Clinical and Translational Science Awards (CTSAs)
Authors: Trochim William M. , Rubio Doris M. , Thomas Veronica G. ,   Evaluation Key Function Committee of the CTSA Consortium
Published: April 2013

The National Center for Advancing Translational Sciences (NCATS), a part of the National Institutes of Health, currently funds the Clinical and Translational Science Awards (CTSAs), a national consortium of 61 medical research institutions in 30 states and the District of Columbia. The program seeks to transform the way biomedical research is conducted, speed the translation of laboratory discoveries into treatments for patients, engage communities in clinical research efforts, and train a new generation of clinical and translational researchers. An endeavor as ambitious and complex as the CTSA program requires high‐quality evaluations in order to show that the program is well implemented, efficiently managed, and demonstrably effective. In this paper, the Evaluation Key Function Committee of the CTSA Consortium presents an overall framework for evaluating the CTSA program and offers policies to guide the evaluation work. The guidelines set forth are designed to serve as a tool for education within the CTSA community by illuminating key issues and practices that should be considered during evaluation planning, implementation, and utilization. Additionally, these guidelines can provide a basis for ongoing discussions about how the principles articulated in this paper can most effectively be translated into operational reality.
Correlates of pain in an in‐treatment sample of opioid‐dependent people
Authors: Nielsen Suzanne , Larance Briony , Lintzeris Nicholas , Black Emma , Bruno Raimondo , Murnion Bridin , Dunlop Adrian , Degenhardt Louisa
Published: April 2013

Introduction and Aims

The limited literature on pain in opioid‐treatment samples indicates that it is highly prevalent. Understanding the implications of pain on treatment outcomes is important, particularly in light of ageing opioid‐treatment cohorts. This study explores correlates of pain, including aberrant behaviours related to prescribed opioids. Our hypothesis is that pain may increase aberrant opioid‐related behaviours, including illicit substance use, among opioid‐dependent people.

Design and Methods

We examined pain in methadone or buprenorphine patients (n = 141) from three treatment services. Measures included basic demographics, Brief Pain Inventory, general mental health, physical health and quality of life measures, pain history and treatments, and an aberrant opioid‐related behaviour scale. Univariate and multivariate analyses were used to examine correlates of pain.

Results

Forty percent reported current pain, measured with the first question of the Brief Pain Inventory. Correlates of pain were depression ratings [adjusted odds ratio (OR) 2.24, 95% confidence interval (CI) 1.04, 4.83], anxiety ratings (adjusted OR 4.29, 95% CI 1.88, 9.80) and self‐reported health ratings (adjusted OR 0.35, 95% CI 0.16, 0.76). Contrary to our hypothesis, pain was not associated with greater use of illicit opioids, nor any aberrant opioid‐related behaviours. Pain was comparable among methadone and buprenorphine patients.

Discussion and Conclusions

The lack of association with pain and aberrant behaviours suggest that it should not be assumed that those in opioid treatment misuse medications in response to pain. The high prevalence of depression/anxiety symptoms indicates a need for further work with larger samples to explore pain and co‐morbidity among opioid‐dependent people. [Nielsen S, Larance B, Lintzeris N, Black E, Bruno R, Murnion B, Dunlop A, Degenhardt L. Correlates of pain in an in‐treatment sample of opioid‐dependent people. Drug Alcohol Rev 2013;32:489–494]
Ethics of ARV Based Prevention: Treatment‐as‐Prevention and PrEP
Authors: Haire Bridget , Kaldor John M.
Published: April 2013

Published data show that new HIV prevention strategies including treatment‐as‐prevention and pre‐exposure prophylaxis (PrEP) using oral antiretroviral drugs (ARVs) are highly, but not completely, effective if regimens are taken as directed. Consequently, their implementation may challenge norms around HIV prevention. Specific concerns include the potential for ARV‐based prevention to reframe responsibility, erode beneficial sexual norms and waste resources. This paper explores what rights claims uninfected people can make for access to ARVs for prevention, and whether moral claims justify the provision of ARV therapy to those who do not yet clinically require treatment as a way of reducing HIV transmission risk. An ethical analysis was conducted of the two strategies, PrEP and treatment‐as‐prevention, using a public health stewardship model developed by the Nuffield Bioethics Council to consider and compare the application of PrEP and treatment‐as‐prevention strategies. We found that treating the person with HIV rather than the uninfected person offers advantages in settings where there are limited opportunities to access care. A treatment‐as‐prevention strategy that places all the emphasis upon the positive person's adherence however carries a disproportionate burden of responsibility. PrEP remains an important option for receptive partners who face increased biological vulnerability. We conclude that the use of ARV for prevention is ethically justified, despite imperfect global to drugs for those in clinical need. The determination of which ARV‐based HIV prevention strategy is ethically preferable is complex and must take into account both public health and interpersonal considerations.
A Love Letter
Authors: Porcini Mauro
Published: April 2013

Thoughts on a career.
Left Atrial Volume Index in Healthy Subjects: Clinical and Echocardiographic Correlates
Authors: D'Andrea Antonello , Riegler Lucia , Rucco Maria Antonietta , Cocchia Rosangela , Scarafile Raffaella , Salerno Gemma , Martone Francesca , Vriz Olga , Caso Pio , Calabrò Raffaele , Bossone Eduardo , Russo Maria Giovanna
Published: April 2013

Left atrial (LA) size is related to cardiovascular morbidity and mortality. The relative role of multiple determinants of LA morphology in healthy subjects remains incompletely defined. The aim of this study is to define normal ranges for LA diameters and volume index (LAVi), and to investigate clinical and echocardiographic correlates. A total of 1480 healthy individuals (mean age 36.1 ± 15.5 years, range 20–80; 61% males) underwent a comprehensive transthoracic echocardiography exam including assessment of LAVi calculated using the biplane area‐length method at the apical four‐chamber and two‐chamber views at ventricular end systole (maximum LA size) and indexed for body surface area (BSA). Mean LAVi in the overall population was 29.5 ± 10.8 mL/m2 (range: 26.1–41.8 mL/m2). Distinct higher values were found in subjects ≥50 years as compared with those <50 years of age (33.4 ± 12.5 vs. 29.1 ± 13.5; P < 0.001). On univariate analysis, LA volume was significantly associated with age (r = 0.48, P < 0.0001), male gender (r = 0.28, P < 0.05), BSA (r = 0.51, P < 0.0001), mitral E/E' (r = 0.47, P < 0.0001), LV end‐diastolic volume (r = 0.52, P < 0.0001), and LV mass index (r = 0.31, P < 0.05). Multivariable analysis identified age, BSA, LV end‐diastolic volume, and mitral E/E' ratio as the only independent determinants of LA volume (model R2 = 0.54, P < 0.0001). Gender was an independent predictor of most absolute LA volume, but following normalization to BSA, some associations became nonsignificant. In healthy individuals LAVi vary significantly by age, BSA, diastolic function, and LV dimensions, with lesser effects of gender.
Predation Risk and Opportunity Cost of Fleeing While Foraging on Plants Influence Escape Decisions of an Insular Lizard
Authors: Pérez‐Cembranos Ana , Pérez‐Mellado Valentín , Cooper William E.
Published: April 2013

Cost‐benefit models of escape behaviour predict how close a prey allows a predator to approach [flight initiation distance (FID)] based on cost of not fleeing (predation risk) and cost of fleeing (loss of opportunities). Models for FID have been used with some success to predict distance fled (DF). We studied effects of foraging opportunity cost of fleeing and examined differences between age‐sex groups in the omnivorous Balearic Lizard, Podarcis lilfordi. Balearic lizards forage on the ground for invertebrate prey and climb the thistle Carlina corymbosa to forage on its inflorescences. We studied escape behaviour in three experimental groups, with human beings as simulated predators: lizard foraging above ground on C. corymbosa, foraging on the ground away from thistles and on the ground with cut inflorescences. Flight initiation distance was shorter for lizards with cut inflorescences than for (1) lizards above ground due to the greater risk above ground due to conspicuousness of black lizards on yellow flowers; and (2) lizards on ground away from flowers due to the cost of leaving while feeding. The only age‐sex difference was slightly greater FID for adult males than subadults, presumably because larger adult males are more likely to be attacked by predators. Other potential factors affecting this difference are discussed. Experimental group and age‐sex group did not interact for FID or DF. Because lizards foraging on inflorescences above ground fled to the base of the plants to refuge provided by spiny thistle leaves, their DF was shorter than in the other groups, which fled across the ground, usually without entering refuge. DF did not differ between groups on the ground or among age‐sex groups. The predicted shorter DF for lizards with cut inflorescences than on ground without inflorescences did not occur. We hypothesize that the opportunity cost was small due to the abundance of blooming thistles and that DF may be less sensitive to opportunity cost than FID.
Temporal patterns of genetic variation in a salmon population undergoing rapid change in migration timing
Authors: Kovach Ryan P. , Gharrett Anthony J. , Tallmon David A.
Published: April 2013

Though genetic diversity is necessary for population persistence in rapidly changing environments, little is known about how climate‐warming influences patterns of intra‐population genetic variation. For a pink salmon population experiencing increasing temperatures, we used temporal genetic data (microsatellite = 1993, 2001, 2009; allozyme = 1979, 1981, 1983) to quantify the genetic effective population size (Ne) and genetic divergence due to differences in migration timing and to estimate whether these quantities have changed over time. We predicted that temporal trends toward earlier migration timing and a corresponding loss of phenotypic variation would decrease genetic divergence based on migration timing and Ne. We observed significant genetic divergence based on migration timing and genetic heterogeneity between early‐ and late‐migrating fish. There was also some evidence for divergent selection between early‐ and late‐migrating fish at circadian rhythm genes, but results varied over time. Estimates of Ne from multiple methods were large (>1200) and Ne/Nc generally exceeded 0.2. Despite shifts in migration timing and loss of phenotypic variation, there was no evidence for changes in within‐population genetic divergence or Ne over the course of this study. These results suggest that in instances of population stability, genetic diversity may be resistant to climate‐induced changes in migration timing.
Regulation of hypoxia‐inducible factor‐1α and related genes in equine digital lamellae and in cultured keratinocytes
Authors: Pawlak E. A. , Geor R. J. , Watts M. R. , Black S. J. , Johnson P. J. , Belknap J. K.
Published: April 2013

Reasons for performing study

Hypoxia‐inducible factor‐1α (HIF‐1A) is an important protein in the regulation/induction of many genes in the cellular and tissue response to hypoxia and a central mediator in inflammatory signalling. As both hypoxia and inflammatory events are purported to occur in the lamellar epidermis in sepsis‐related laminitis in the equid,HIF‐1Amay play a central role in this disease process.

Objectivess

To assess the regulation ofHIF‐1AandHIF‐1A‐related genes in the equine keratinocytein vitroand in the lamellar tissue of horses with sepsis‐related laminitis.

Study design

In vivoandin vitroexperiments.

Methods

Real‐time quantitativePCR(RT‐qPCR) and immunoblotting were performed to assess themRNAand protein concentrations ofHIF‐1Aand themRNAconcentrations ofHIF‐1A‐related genes in cultured equine keratinocytes and in lamellar samples from black walnut extract (BWE)‐ and carbohydrate overload (CHO)‐induced laminitis. Hypoxia‐inducible factor‐1α was further localised via indirect immunofluorescence in frozen lamellar tissue sections.

Results

Hypoxia‐inducible factor‐1α appears to be regulated primarily at the post transcriptional level in the cultured equine keratinocyte, resulting in increasedHIF‐1Ain response to hypoxia but not to lipopolysaccharide exposure. Hypoxia‐inducible factor‐1α is present at high concentrations in the normal equine lamina, and is increased inObel grade 1 (OG1) stage laminitis in theCHOmodel of laminitis. Equine lamellarmRNAconcentrations of cyclo‐oxygenase‐2 and inducible nitric oxide synthase, but not glucose transporter 1, are increased in theBWEandCHOmodels of laminitis.

Conclusions and potential relevance

These data indicate that the normal equine lamellae are profoundly hypoxic in comparison with other tissues. The increasedmRNAconcentrations of cyclo‐oxygenase‐2 and inducible nitric oxide synthase 2 in equine keratinocytes exposed to hypoxia and lipopolysaccharide, and in lamellar tissue fromBWEandCHOmodels of sepsis‐related laminitis, suggest that the marked lamellar inflammatory gene expression in sepsis‐related laminitis may be due to an interaction of constitutively high lamellar keratinocyteHIF‐1Asignalling with inflammatory signalling, possibly induced by circulating inflammatory mediators.

The Summary is available in Chinese – see Supporting information.
PABPN1: molecular function and muscle disease
Authors: Banerjee Ayan , Apponi Luciano H. , Pavlath Grace K. , Corbett Anita H.
Published: April 2013

The polyadenosine RNA binding protein polyadenylate‐binding nuclear protein 1 (PABPN1) plays key roles in post‐transcriptional processing of RNA. Although PABPN1 is ubiquitously expressed and presumably contributes to control of gene expression in all tissues, mutation of the PABPN1 gene causes the disease oculopharyngeal muscular dystrophy (OPMD), in which a limited set of skeletal muscles are affected. A major goal in the field of OPMD research is to understand why mutation of a ubiquitously expressed gene leads to a muscle‐specific disease. PABPN1 plays a well‐documented role in controlling the poly(A) tail length of RNA transcripts but new functions are emerging through studies that exploit a variety of unbiased screens as well as model organisms. This review addresses (a) the molecular function of PABPN1 incorporating recent findings that reveal novel cellular functions for PABPN1 and (b) the approaches that are being used to understand the molecular defects that stem from expression of mutant PABPN1. The long‐term goal in this field of research is to understand the key molecular functions of PABPN1 in muscle as well as the mechanisms that underlie the pathological consequences of mutant PABPN1. Armed with this information, researchers can seek to develop therapeutic approaches to enhance the quality of life for patients afflicted with OPMD.
Foreign Language Student Teaching: Do Supervisor Qualifications Really Matter?
Authors: Kissau Scott P. , Algozzine Bob
Published: April 2013

According to national standards for foreign language (L2) teacher education programs established by the ACTFL and the Council for the Accreditation of Educator Preparation (CAEP), L2 student teachers must be supervised by university faculty who are qualified L2 educators. An exploratory study was conducted to better understand the impact of content‐specific pedagogical knowledge, L2 experience, and qualifications on the effectiveness of the university supervisor. Its purpose was to compare the beliefs of L2 teacher candidates and supervisors with and without L2 teaching qualifications to explore the extent to which these three groups share similar beliefs about effective L2 teaching. Results indicated that all participants demonstrated general pedagogical knowledge associated with good teaching practices. However, supervisors without L2 teacher training and experience were less familiar with theories of L2 acquisition, standards, and best practices than were their counterparts with L2 teaching qualifications. Lacking pedagogical content knowledge related to L2 teaching, the generalist supervisors were unable to provide appropriate feedback to their L2 interns, had lower expectations for their interns, and relied more heavily on others to provide them with support.
Contrasting effects of natural and anthropogenic stressors on beta diversity in river organisms
Authors: Gutiérrez‐Cánovas Cayetano , Millán Andrés , Velasco Josefa , Vaughan Ian P. , Ormerod Steve J.
Published: April 2013

Aim

We hypothesized that mechanisms underlying beta diversity in rivers would differ between gradients where (1) natural stressors result in progressive species turnover with high specificity and (2) anthropogenic stressors result in the loss of specialist taxa thus giving rise to nestedness.

Location

Great Britain, the Iberian Peninsula and the Himalayan Mountains.

Methods

We analysed five datasets describing benthic macroinvertebrates sampled along natural (elevation, salinity) and anthropogenic (acidity, metals, land use) stress gradients. Predictions were tested by fitting models relating species richness and beta‐diversity components (total, turnover and nestedness dissimilarities) to putative stress intensity (i.e. the degree to which a particular environmental constraint filters species occurrence).

Results

Stress intensity accounted for most of the variability in species richness (r2 = 0.64–0.93), which declined with increasing stress. Dissimilarity in community composition between locations increased with the difference in stress intensity for all datasets. For natural stressors, beta‐diversity patterns mainly reflected species turnover, whilst for anthropogenic stressors beta diversity mainly reflected nesting of subsets of species as stress intensity increased.

Main conclusions

Our results support the hypothesis that natural and anthropogenic stressors generate contrasting patterns in beta diversity that arise through different mechanisms.
Olive trees as bio‐indicators of climate evolution in the Mediterranean Basin
Authors: Moriondo Marco , Trombi Giacomo , Ferrise Roberto , Brandani Giada , Dibari Camilla , Ammann Caspar M. , Lippi Marta Mariotti , Bindi Marco
Published: April 2013

Aim

This paper aims to project areas of olive cultivation into future scenarios. Accordingly, we first asked the question whether global circulation models (GCMs) are able to reproduce past climatic conditions and we used historical ranges of olive cultivation as a palaeoclimate proxy.

Location

The Mediterranean basin.

Methods

We used an ecological model, calibrated and validated for modern times, to test the reliability of a general circulation model (NCAR‐CSM GCM) in reproducing past ranges of olive tree cultivation inferred from the literature, archaeo‐botanical investigations and fossil pollen analyses.

Results

The re‐constructions of olive growing areas, obtained for the Medieval Climate Anomaly (MCA, 1200‐1300 AD) and the Little Ice Age (LIA, 1600‐1700 AD) by coupling the outputs of NCAR‐CSM to the ecological model, were in agreement to those observed. Simulations of olive growing areas for future time‐windows showed that a northwards expansion of the species is expected to occur by 2100.

Main conclusions

These results demonstrate that the NCAR‐CSM can provide an accurate reconstruction of past climate with results sensitive to climate forcing factors and thus, it is more likely to give reliable projections for the future. Additionally, the warming and drying conditions expected in the coming decades may determine changes across the Mediterranean basin that is unprecedented.
Altered root traits due to elevated CO2: a meta‐analysis
Authors: Nie Ming , Lu Meng , Bell Jennifer , Raut Swastika , Pendall Elise
Published: April 2013

Aim

Plant root traits regulate belowground C inputs, soil nutrient and water uptake, and play critical roles in determining sustainable plant production and consequences for ecosystem C storage. However, the effects of elevated CO2 on root morphology and function have not been well quantified. We reveal general patterns of root trait responses to elevated CO2 from field manipulative experiments.

Location

North America, Europe, Oceania, Asia.

Methods

The meta‐analysis approach was used to examine the effects of CO2 elevation on 17 variables associated with root morphology, biomass size and distribution, C and N concentrations and pools, turnover and fungal colonization from 110 published studies.

Results

Elevated CO2 increased root length (+26.0%) and diameter (+8.4%). Elevated CO2 also stimulated total root (+28.8%), fine root (+27.7%) and coarse root biomass (+25.3%), demonstrating strong responses of root morphology and biomass. Elevated CO2 increased the root:shoot ratio (+8.5%) and decreased the proportion of roots in the topsoil (–8.4%), suggesting that plants expand rooting systems. In addition, elevated CO2 decreased N concentration (–7.1%), but did not affect C concentration, and thus increased the C:N ratio (+7.8%). Root C (+29.3%) increased disproportionately relative to root N pools (+9.4%) under elevated CO2. Functional traits were also strongly affected by elevated CO2, which increased respiration (+58.9%), rhizodeposition (+37.9%) and fungal colonization (+3.3%).

Main conclusions

These results suggest that elevated CO2 promoted root morphological development, root system expansion and C input to soils, implying that the sensitive responses of root morphology and function to elevated CO2 would increase long‐term belowground C sequestration.