bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of mid‐successional dominant species on the diversity and progress of succession in regenerating temperate grasslands
Authors: Bartha Sándor , Szentes Szilárd , Horváth András , Házi Judit , Zimmermann Zita , Molnár Csaba , Dancza István , Margóczi Katalin , Pál Róbert W. , Purger Dragica , Schmidt Dávid , Óvári Miklós , Komoly Cecília , Sutyinszki Zsuzsanna , Szabó Gábor , Csathó András István , Juhász Melinda , Penksza Károly , Molnár Zsolt
Published: October 2013

Questions

(i) Which species dominate mid‐successional old‐fields in Hungary? How does the identity of these species relate to local (patch‐scale) diversity and to the progress of succession? (ii) Which species have the strongest negative impact on diversity in spontaneous old‐field succession and what generalizations are possible about traits of these species? (iii) Are these species dominant or subordinate components in mature target communities? (iv) Do native or alien species have stronger effects on the diversity and progress of succession?

Location

Abandoned agricultural fields (abandoned croplands, orchards and vineyards) at various locations throughout Hungary.

Methods

Vegetation patterns on 112 old‐fields, in 25 sites varying in soil and climatic conditions, topography, landscape contexts and land‐use histories were sampled. Most old‐fields had appropriate seed sources in the immediate vicinity, i.e. natural or semi‐natural grasslands (meadows steppes, closed and open sand steppes) as source and target habitats. Age of abandoned fields ranged from 1 to 69 yr, but most sites were between 15 and 60 yr. The cover of vascular plant species (%) was estimated in 2 × 2‐m plots. Relationships between diversity, progress of succession (similarity to target communities) and identity of dominants were tested.

Results

A small portion of successional dominants (eight species) had strong negative impacts on diversity. These species belonged to Poaceae, Asteraceae and Fabaceae. Most of these species were wind‐pollinated, and capable of lateral vegetative spread. Dominant species varied in size and had, on average, a low requirement for N but a high requirement for light. With one exception, Solidago gigantea, they were native to the Hungarian flora. Significant differences were found among the impact of successional dominants when dominant species were grouped according to their original role (dominants or subordinates) in natural communities. The overall effect of species identity was also significant. Bothriochloa ischaemum was identified as the species with the strongest negative effect on species diversity.

Conclusions

Our results suggest that mid‐successional dominant species differ in their impact on diversity and progress of succession. Mid‐successional plots dominated by alien species, or by native species that were originally subordinate in natural communities, regenerate less successfully and may temporarily arrest succession. Therefore, early colonization of native dominants should be enhanced with restoration measures.
Role of Platelets in Inflammation and Cancer: Novel Therapeutic Strategies
Authors: Dovizio Melania , Alberti Sara , Guillem‐Llobat Paloma , Patrignani Paola
Published: October 2013

Platelets play a central role in inflammation through their direct interaction with other cell types, such as leucocytes and endothelial cells, and by the release of many factors, that is, lipids [such as thromboxane (TX)A2] and proteins (a wide number of angiogenic and growth factors) stored in α‐granules, and adenosine diphosphate (ADP), stored in dense granules. These platelet actions trigger autocrine and paracrine activation processes that lead to leucocyte recruitment into different tissues and phenotypic changes in stromal cells which contribute to the development of different disease states, such as atherosclerosis and atherothrombosis, intestinal inflammation and cancer. The signals induced by platelets may cause pro‐inflammatory and malignant phenotypes in other cells through the persistent induction of aberrant expression of cyclooxygenase (COX)‐2 and increased generation of prostanoids, mainly prostaglandin (PG)E2. In addition to cardiovascular disease, enhanced platelet activation has been detected in inflammatory disease and intestinal tumourigenesis. Moreover, the results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer. All these pieces of evidence support the notion that colorectal cancer and atherothrombosis may share a common mechanism of disease, that is, platelet activation in response to epithelial (in tumourigenesis) and endothelial (in tumourigenesis and atherothrombosis) injury. Extensive translational medicine research is necessary to obtain a definitive mechanistic demonstration of the platelet‐mediated hypothesis of colon tumourigenesis. The results of these studies will be fundamental to support the clinical decision to recommend the use of low‐dose aspirin, and possibly other antiplatelet agents, in primary prevention, that is, even for individuals at low cardiovascular risk.
Justification for Conscience Exemptions in Health Care
Authors: Kantymir Lori , McLeod Carolyn
Published: October 2013

Some bioethicists argue that conscientious objectors in health care should have to justify themselves, just as objectors in the military do. They should have to provide reasons that explain why they should be exempt from offering the services that they find offensive. There are two versions of this view in the literature, each giving different standards of justification. We show these views are each either too permissive (i.e. would result in problematic exemptions based on conscience) or too restrictive (i.e. would produce problematic denials of exemption). We then develop a middle ground position that we believe better combines respect for the conscience of healthcare professionals with concern for the duties that they owe to patients. Our claim, in short, is that insofar as objectors should have to justify themselves, they should have to do it according to the standard that we defend rather than according to the standards that others have developed.
Biomedical Enhancements as Justice
Authors: Nam Jeesoo
Published: October 2013

Biomedical enhancements, the applications of medical technology to make better those who are neither ill nor deficient, have made great strides in the past few decades. Using Amartya Sen's capability approach as my framework, I argue in this article that far from being simply permissible, we have a prima facie moral obligation to use these new developments for the end goal of promoting social justice. In terms of both range and magnitude, the use of biomedical enhancements will mark a radical advance in how we compensate the most disadvantaged members of society.
The roles of emotion regulation and ruminative thoughts in non‐suicidal self‐injury
Authors: Voon David , Hasking Penelope , Martin Graham
Published: October 2013

Objectives

This study explored how cognitive reappraisal, expressive suppression, and facets of ruminative thinking could be brought together in a model to explain non‐suicidal self‐injury (NSSI) in the context of experiencing stressful life events and psychological distress.

Methods

Data from 2,507 participants aged 12–18 years (68% female, mean age 13.93 years) recruited from 40 Australian secondary schools were analysed, including 254 participants with a history of NSSI (72% female, mean age 14.21 years). Participants completed a self‐report questionnaire assessing the constructs of interest.

Results

Although meeting minimum fit indices, our hypothesized model showed poorer fit compared to an empirically derived model. There was little evidence for the mediating role of psychological distress in NSSI, and we found adverse life events, psychological distress, emotion regulation, and two facets of ruminative thinking (counterfactual thinking and anticipatory thoughts) had direct, though weak, relationships with NSSI. Among the subsample of adolescents with a history of NSSI, anticipatory rumination moderated the relationship between psychological distress and NSSI, while cognitive reappraisal demonstrated a direct, although weak relationship with NSSI.

Conclusions

Our observations suggest that, among adolescents, contextual, social, and behavioural factors may have a strong influence on NSSI and this may suggest that prevention and treatment efforts for NSSI among adolescents need to focus on contextual, social, and behavioural factors.

Practitioner points

Emotion regulation and repetitively dwelling on current problems and concerns are implicated in non‐suicidal self‐injury (NSSI) only to the extent they increase or reduce the experience of psychological distress.

Prevention and treatment efforts for NSSI among adolescents would be better focused on contextual, social, and behavioural factors than cognitive factors.

The cross‐sectional nature of the research suggests interpretations regarding the influence of these psychological factors on NSSI can only be speculative and further research is warranted to establish causality.

Replication with a larger, more representative sample is warranted.
Twitter for teaching: Can social media be used to enhance the process of learning?
Authors: Evans Chris
Published: October 2013

Can social media be used to enhance the process of learning by students in higher education? Social media have become widely adopted by students in their personal lives. However, the application of social media to teaching and learning remains to be fully explored. In this study, the use of the social media tool Twitter for teaching was considered. Undergraduate students in Business and Management (n = 252) were encouraged to use Twitter for communicating with their tutor and each other during a 12‐week course. Their involvement was evaluated using a survey considering amount of Twitter usage and students' attitudes and experiences. The data were analysed using factor analyses, which revealed a single usage construct and three attitudinal factors. Three findings emerged. Firstly, a positive correlation was found between amount of Twitter usage and student engagement in university‐associated activities including organising their social lives and sharing information. Secondly, course‐related tweeting was not related to interpersonal relationships between students and their tutor. Thirdly, Twitter usage did not impact class attendance. The results are salient for educational practitioners wishing to introduce social media into their teaching.
Clinical applicability and prognostic significance of molecular response assessed by fluorescent‐PCRof immunoglobulin genes in multiple myeloma. Results from aGEM/PETHEMAstudy
Authors: Martinez‐Lopez Joaquin , Fernández‐Redondo Elena , García‐Sánz Ramón , Montalbán María Angeles , Martínez‐Sánchez Pilar , Pavia Bruno , Mateos María Victoria , Rosiñol Laura , Martín Marisa , Ayala Rosa , Martínez Rafael , Blanchard María Jesus , Alegre Adrian , Besalduch Joan , Bargay Joan , Hernandez Miguel T. , Sarasquete María Eugenia , Sanchez‐Godoy Pedro , Fernández Manuela , Blade Joan , San Miguel Jesús F. , Lahuerta Juan Jose ,   the GEM (Grupo Español Multidisciplinar de Melanoma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group
Published: October 2013

Minimal residual disease monitoring is becoming increasingly important in multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele‐specific oligonucleotide polymerase chain reaction (ASO‐PCR) techniques are not routinely available. This study investigated the prognostic influence of achieving molecular response assessed by fluorescent‐PCR(F‐PCR) in 130 newly diagnosedMMpatients fromGrupoEspañolMultidisciplinar deMelanoma (GEM)2000/GEM05 trials (NCT00560053,NCT00443235,NCT00464217) who achieved almost very good partial response after induction therapy. As a reference, we used the results observed with simultaneousMFC. F‐PCRat diagnosis was performed onDNAusing three different multiplexPCRs:IGHD‐J,IGKV‐J andKDErearrangements. The applicability of F‐PCRwas 91·5%. After induction therapy, 64 patients achieved molecular response and 66 non‐molecular response; median progression‐free survival (PFS) was 61versus36 months, respectively (P = 0·001). Median overall survival (OS) was not reached (NR) in molecular response patients (5‐year survival: 75%)versus66 months in the non‐molecular response group (P = 0·03). The correspondingPFSandOSvalues for patients with immunophenotypicversusnon‐immunophenotypic response were 67versus42 months (P = 0·005) andNR(5‐year survival: 95%)versus69 months (P = 0·004), respectively. F‐PCRanalysis is a rapid, affordable, and easily performable technique that, in some circumstances, may be a valid approach for minimal residual disease investigations inMM.
Pro‐apoptotic TP53 homolog TAp63 is repressed via epigenetic silencing and B‐cell receptor signalling in chronic lymphocytic leukaemia
Authors: Humphries Leigh A. , Godbersen J. Claire , Danilova Olga V. , Kaur Prabhjot , Christensen Brock C. , Danilov Alexey V.
Published: October 2013

Chronic lymphocytic leukaemia (CLL) is an accumulative disorder marked by deficient apoptosis. The TP53 homolog TAp63 promotes apoptosis and chemosensitivity in solid tumours and its deregulation may contribute to CLL cell survival. We found that TAp63α was the most prevalent TP63 isoform in CLL. Compared to healthy B cells, TAp63 mRNA was repressed in 55·7% of CLL samples. TP63 promoter methylation was high in CLL and inversely correlated with TP63 protein expression in B‐cell lymphoma cell lines. siRNA‐mediated knockdown of TP63 resulted in partial protection from spontaneous apoptosis accompanied by reductions in PMAIP1 (NOXA), BBC3 (PUMA), and BAX mRNA in CLL cells and increased proliferation of Raji lymphoma cells. TAp63 mRNA levels were higher in CLL with unmutated IGHV. B‐cell receptor (BCR) engagement led to repression of TP63 mRNA expression in malignant B cells, while pharmacological inhibition of BCR signalling prevented TP63 downregulation. MIR21, known to target TAp63, correlated inversely with TAp63 expression in CLL, and BCR‐mediated downregulation of TP63 was accompanied by MIR21 upregulation in most CLL samples. Our data illustrate the pro‐apoptotic function of TP63, provide insights into the mechanisms of BCR‐targeting agents, and establish a rationale for designing novel approaches to induce TP63 in CLL and B‐cell lymphoma.
Prospective phase II study of rituximab with alternating cycles of hyper‐CVAD and high‐dose methotrexate with cytarabine for young patients with high‐risk diffuse large B‐cell lymphoma
Authors: Oki Yasuhiro , Westin Jason R. , Vega Francisco , Chuang Hubert , Fowler Nathan , Neelapu Sattva , Hagemeister Fredrick B. , McLaughlin Peter , Kwak Larry W. , Romaguera Jorge E. , Fanale Michelle , Younes Anas , Rodriguez Maria Alma , Orlowski Robert Z. , Wang Michael , Ouzounian Souzanne T. , Samaniego Felipe , Fayad Luis
Published: October 2013

We conducted a prospective randomized phase II study to evaluate two chemotherapy regimens: (i) rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (R‐HCVAD) alternating with rituximab, high‐dose methotrexate, and cytarabine (R‐MA) and (ii) rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) in diffuse large B‐cell lymphoma (DLBCL). This study randomized patients aged ≤60 years with DLBCL and an age‐adjusted international prognostic index ≥2 to R‐HCVAD/R‐MA or R‐CHOP based on a Bayesian adaptive algorithm. Interim analysis of the first 26 eligible patients showed that the complete response rate (CRR) was higher with R‐HCVAD/R‐MA than R‐CHOP (P = 0·03); thus, R‐CHOP arm was closed. In the final analysis, 49 and 10 eligible patients were treated in R‐HCVAD/R‐MA and R‐CHOP arms respectively; CRR were 82% and 60% respectively (P = 0·13); 3‐year progression‐free survival (PFS) rates were 75·7% and 77·8% respectively (P = 0·53). In the R‐HCVAD/R‐MA arm, 3‐year PFS rates in patients aged 46–60 years and ≤45 years were 70·3% and 87·1% respectively (P = 0·13), and the treatment‐associated early mortality rate in patients >45 years was 12%. In conclusion, R‐HCVAD/R‐MA is associated with excellent outcome in patients ≤45 years old. However, in patients >45 years old, R‐HCVAD/R‐MA is associated with unacceptable mortality rates.
Assessing vividness of mental imagery: The Plymouth Sensory Imagery Questionnaire
Authors: Andrade Jackie , May Jon , Deeprose Catherine , Baugh Sarah‐Jane , Ganis Giorgio
Published: October 2013

Mental imagery may occur in any sensory modality, although visual imagery has been most studied. A sensitive measure of the vividness of imagery across a range of modalities is needed: the shorter version of Bett's Questionnaire upon Mental Imagery (Sheehan, , J. Clin. Psychology, 23, 386) uses outdated items and has an unreliable factor structure. We report the development and initial validation of the Plymouth Sensory Imagery Questionnaire (Psi‐Q) comprising items for each of the following modalities: Vision, Sound, Smell, Taste, Touch, Bodily Sensation, and Emotional Feeling. An exploratory factor analysis on a 35‐item form indicated that these modalities formed separate factors, rather than a single imagery factor, and this was replicated by confirmatory factor analysis. The Psi‐Q was validated against the Spontaneous Use of Imagery Scale (Reisberg et al., , Appl. Cogn. Psychology, 17, 147) and Marks' (, J. Mental Imagery, 19, 153) Vividness of Visual Imagery Questionnaire‐2 (VVIQ‐2). A short 21‐item form comprising the best three items from the seven factors correlated with the total score and subscales of the full form, and with the VVIQ‐2. Inspection of the data shows that while visual and sound imagery is most often rated as vivid, individuals who rate one modality as strong and the other as weak are not uncommon. Findings are interpreted within a working memory framework and point to the need for further research to identify the specific cognitive processes underlying the vividness of imagery across sensory modalities.
Maintaining shared knowledge of acquaintance: Methods people use to establish who knows whom
Authors: Ekberg Stuart
Published: October 2013

Acquaintance is a fundamental determinant of how people behave when interacting with one another. This article focuses on how this type of personal knowledge is an important consideration for people as social actors. Studying naturally occurring social encounters, I describe how speakers use particular references to convey whether a recipient should be able to recognize a non‐present third party. On some occasions, however, the presumption of recognizability or non‐recognizability that underpins the use of a particular reference proves questionable. By exploring how recipients can challenge reference forms, and thereby reject claims of either recognizability or non‐recognizability, I explain how people establish and maintain a shared understanding of who knows whom. I conclude by discussing motivations for this behaviour, and thereby contribute to understanding the commonsense reasoning that underpins orderly conduct in this aspect of social encounters.
MRI‐safe robot for targeted transrectal prostate biopsy: animal experiments
Authors: Srimathveeravalli Govindarajan , Kim Chunwoo , Petrisor Doru , Ezell Paula , Coleman Jonathan , Hricak Hedvig , Solomon Stephen B. , Stoianovici Dan
Published: October 2013

Objectives

To study the feasibility and safety of using a magnetic resonance imaging (MRI)‐safe robot for assistingMRI‐guided transrectal needle placement and biopsy in the prostate, using a canine model.

To determine the accuracy and precision afforded by the use of the robot while targeting a desired location in the organ.

Materials and Methods

In a study approved by theInstitutionalAnimalCare andUseCommittee, six healthy adult male beagles with prostates of at least 15 × 15 mm in size at the largest transverse section were chosen for the procedure.

The probe portion of the robot was placed into the rectum of the dog, images were acquired and image‐to‐robot registration was performed. Images acquired after placement of the robot were reviewed and a radiologist selected targets for needle placement in the gland.

Depending on the size of the prostate, up to a maximum of six needle placements were performed on each dog. After needle placement, robot‐assisted core biopsies were performed on four dogs that had larger prostate volumes and extracted cores were analysed for potential diagnostic value.

Results

Robot‐assistedMRI‐guided needle placements were performed to target a total of 30 locations in six dogs, achieving a targeting accuracy of 2.58 mm (mean) and precision of 1.31 mm (sd).

All needle placements were successfully completed on the first attempt. The mean time required to select a desired target location in the prostate, align the needle guide to that point, insert the needle and perform the biopsy was ∼ 3 min. For this targeting accuracy study, the inserted needle was also imaged after its placement in the prostate, which took an additional 6–8 min.

Signal‐to‐noise ratio analysis indicated that the presence of the robot within the scanner bore had minimal impact on the quality of the images acquired.

Analysis of intact biopsy core samples indicated that the samples contained prostatic tissues, appropriate for making a potential diagnosis.

Dogs used in the study did not experience device‐ or procedure‐related complications.

Conclusions

Results from this preclinical pilot animal study suggest thatMRI‐targeted transrectal biopsies are feasible to perform and this procedure may be safely assisted by anMRI‐safe robotic device.
Cryoablation for locally advanced clinical stage T3 prostate cancer: a report from the Cryo‐On‐Line Database (COLD) Registry
Authors: Ward John F. , DiBlasio Christopher J. , Williams Christopher , Given Robert , Jones J. Stephen
Published: October 2013

Objective

To assess the oncological and functional outcomes of primary prostate cryoablation for men with clinical stage T3 (cT3) prostate cancer, as although radical prostatectomy (RP) or external beam radiotherapy (EBRT) are the standard treatments for locally advanced cT3 prostate cancer some patients opt for nonextirpative prostate cryoablation instead.

Patients and Methods

The Cryo‐On‐Line Database (COLD) Registry was queried to identify patients with cT3 prostate cancer treated with whole‐gland cryoablation (366 patients).

We assessed biochemical disease‐free survival (bDFS) using the Phoenix definition and determined reported rates of urinary incontinence and retention, sexual activity, and rectourethral fistulisation after treatment.

Patients were subsequently assessed according to whether they were administered neoadjuvant androgen‐deprivation therapy or not (ADT; 115 patients, 31.4%).

Results

For the entire cohort, the 36‐ and 60‐month bDFS rates were 65.3% and 51.9%, respectively.

Patients who received neoadjuvant ADT had statistically nonsignificantly higher 36‐ and 60‐month bDFS rates (68.0% and 55.4%, respectively) than patients who did not receive neoadjuvant ADT (55.3% and 36.9%, respectively).

The after treatment urinary incontinence rate was 2.6%; urinary retention rate, 6.0%; sexual activity rate, 30.4%; and rectourethral fistulisation rate, 1.1%.

Conclusions

Cryoablation for patients with cT3 prostate cancer leads to less favourable bDFS than that after RP or RT for the same group of men.

The after treatment rectourethral fistulisation rates for patients with cT3 disease are higher than in those with organ‐confined prostate cancer treated with cryoablation; however, urinary dysfunction and sexual activity rates are similar for men with cT3 to those reported from this same registry in men with cT2 disease.

The addition of neoadjuvant ADT (though not studied prospectively here) should be strongly considered if a patient with cT3 prostate cancer is to be treated with cryoablation.
Urothelial carcinoma involving the prostate: the association of revised tumour stage and coexistent bladder cancer with survival after radical cystectomy
Authors: Knoedler John J. , Boorjian Stephen A. , Tollefson Matthew K. , Cheville John C. , Thapa Prabin , Tarrell Robert F. , Frank Igor
Published: October 2013

Objective

To evaluate survival among patients with urothelial carcinoma (UC) within the prostate in order to assess the impact of depth of tumour invasion as well as the importance of a concurrent bladder tumour.

Patients and Methods

We identified 201 patients who underwent radical cystectomy (RC) between 1980 and 2006 and were found to have UC involving the prostate.

All specimens were re‐reviewed by a genitourinary pathologist.

Survival was estimated using the Kaplan–Meier method and compared with the log‐rank test. Cox hazard regression models tested the association of clinicopathological variables with outcome.

Results

In all, 93 patients had pTis disease in the prostate, 43 had pT2 tumours, and 66 patients were pT4a. The median follow‐up was 10.5 years.

The 5‐year cancer‐specific survival for patients with pTis, pT2, and pT4a prostate UC was 73%, 57%, and 21% respectively (P < 0.001).

On multivariable analysis, higher prostate tumour stage (hazard ratio [HR] 2.09; P = 0.01), positive lymph node status (HR 2.09; P = 0.002), and concurrent ≥pT3 bladder cancer (HR 4.16; P < 0.001) were significantly associated with an increased risk of death from UC.

Conclusions

Among patients with prostatic UC involvement, depth of tumour invasion was significantly associated with cancer‐specific mortality, validating the staging reclassification.

Concurrent locally advanced bladder cancer also negatively impacted survival, suggesting the potential prognostic value of reporting a secondary tumour stage in such cases.
The Challenge of Inclusive Identities and Solidarities: Discourses on Gender and Sexuality in the Nicaraguan Women's Movement and the Legacy of Sandinismo
Authors: HEUMANN SILKE
Published: October 2013

This article addresses the ways in which Sandinismo has affected the Nicaraguan women's movement from ‘within’, analysing how its legacy is reflected in personal discourses on gender and sexuality within the women's movement. In‐depth interviews show that the women's movement inherited from the Sandinistas specific ideas about social justice and social change based on a primary identity, a corresponding hierarchy of rights and a notion of the state as the privileged site of power and social change. I argue that this legacy has hindered the development of feminism in Nicaragua and especially the mobilisation around sexual and reproductive rights.
Internationalisation as a Democratic Tool: Revisiting Mexico's Double Transition
Authors: CALDERON MARTINEZ PABLO
Published: October 2013

Mexico's double transition—democratisation and internationalisation—offers a good case study to analyse the interaction between internationalisation processes and domestic developments during transitions to democracy. This article explains how the specific way in which Mexico linked with North America worked as a causal mechanism during the country's democratisation. In the end, an inadequate project of internationalisation—spearheaded by the North American Free Trade Agreement (NAFTA)—failed to fulfil its democratising potential.
Jo's Story: the journey of one woman's experience of having cancer and a ‘learning disability’
Authors: Martean Melissa Hannah , Dallos Rudi , Stedmon Jacqui , Moss Duncan
Published: October 2013

Accessible summary

Tells story of a woman with learning disability and cancer.

Highlights importance of research with people with learning disabilities.

Promotes people with learning disabilities as reliable research participants.

With increasing longevity amongst people with learning disabilities, it is not surprising that prevalence and incidence rates of cancer are growing at a significant rate. Much of the research undertaken in the area of psycho‐oncology has focused on the ‘general population’, and over the last decade, there has been increasing interest in using a narrative approach to explore the lived experiences of people who have had cancer. Traditionally, research into cancer amongst people with learning disabilities has focused upon epidemiology or palliative care. However, the present article uses a narrative analysis to explore the lived and told experience of a person with a learning disability, who has been given a diagnosis of cancer. This article highlights the need and provides justification, for more qualitative research to be undertaken in this area.
‘My brother likes meeting new people, but don't ask him any direct questions’: involving adults with autism plus learning disability in a qualitative research project
Authors: Tozer Rosemary , Atkin Karl , Wenham Aniela
Published: October 2013

Accessible Summary

People who have difficulties in communication and understanding are often excluded from research which is about them

In our research, we wanted to find out how people with autism plus learning disability get on with their brothers and sisters once they are grown up

We met with twelve people with autism along with their brother or sister without disability in a way that we hoped would make them feel relaxed

Meeting the brothers and sisters with autism was important, and it helped us understand their relationships much better. It also helped us make suggestions about how they and their siblings could be better supported.

Adult siblings of people with autism and a learning disability have hitherto been largely overlooked by research, policy and practice in the UK. As part of a qualitative study focussing on adult siblings, we met twelve people with autism plus severe learning disability with their brother or sister. Individually tailored resources were used to make the meeting accessible and positive. Sibling involvement was essential to the participation, and inclusion of adults with autism plus learning disability strengthened the research findings, making them more valid and more relevant to policy and practice. This article describes our experiences of facilitating this involvement, the methods used and understandings gained, with the aim of encouraging practitioners and researchers to do likewise.
Engendering biased signalling from the calcium‐sensing receptor for the pharmacotherapy of diverse disorders
Authors: Leach K , Sexton P M , Christopoulos A , Conigrave A D
Published: October 2013

The human calcium‐sensing receptor (CaSR) is widely expressed in the body, where its activity is regulated by multiple orthosteric and endogenous allosteric ligands. Each ligand stabilizes a unique subset of conformational states, which enables the CaSR to couple to distinct intracellular signalling pathways depending on the extracellular milieu in which it is bathed. Differential signalling arising from distinct receptor conformations favoured by each ligand is referred to as biased signalling. The outcome of CaSR activation also depends on the cell type in which it is expressed. Thus, the same ligand may activate diverse pathways in distinct cell types. Given that the CaSR is implicated in numerous physiological and pathophysiological processes, it is an ideal target for biased ligands that could be rationally designed to selectively regulate desired signalling pathways in preferred cell types.

Linked Articles

This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐5
Methionine down‐regulates TLR4/MyD88/NF‐κB signalling in osteoclast precursors to reduce bone loss during osteoporosis
Authors: Vijayan V , Khandelwal M , Manglani K , Gupta S , Surolia A
Published: October 2013

Background and Purpose

Studies have demonstrated that a moderate intake of amino acids is associated with development of bone health. Methionine, a sulphur‐containing essential amino acid, has been largely implicated for improving cartilage formation, however its physiological significance on bone integrity and functionality have not been elucidated. We investigated whether methionine can prevent osteoporotic bone loss.

Experimental Approach

The anti‐resorptive effect of methionine, (250 mg kg−1 body wt administered in drinking water for 10 weeks), was evaluated in ovariectomized (OVX) rats by monitoring changes in bone turnover, formation of osteoclasts from blood‐derived mononuclear cells and changes in the synthesis of pro‐osteoclastogenic cytokines.

Key results

Methionine improved bone density and significantly decreased the degree of osteoclast development from blood mononuclear cells in OVX rats, as indicated by decreased production of osteoclast markers tartarate resistant acid phosphatase b (TRAP5b) and MIP‐1α. siRNA‐mediated knockdown of myeloid differentiation primary response 88 [MyD88], a signalling molecule in the toll‐like receptor (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP‐1α in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR‐4/MyD88/NF‐κB pathway.

Conclusions and Implications

TLR‐4/MyD88/NF‐κB signalling pathway is integral for osteoclast development and this is down‐regulated in osteoporotic system on methionine treatment. Methionine treatment could be beneficial for the treatment of postmenopausal osteoporosis.
Cannabidiol inhibits paclitaxel‐induced neuropathic pain through 5‐HT1A receptors without diminishing nervous system function or chemotherapy efficacy
Authors: Ward Sara Jane , McAllister Sean D , Kawamura Rumi , Murase Ryuchi , Neelakantan Harshini , Walker Ellen A
Published: October 2013

Background and Purpose

Paclitaxel (PAC) is associated with chemotherapy‐induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non‐psychoactive cannabinoid cannabidiol (CBD) prevents PAC‐induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy.

Experimental Approach

The ability of acute CBD pretreatment to prevent PAC‐induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant‐conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay.

Key Results

PAC‐induced mechanical sensitivity was prevented by administration of CBD (2.5 – 10 mg·kg−1) in female C57Bl/6 mice. This effect was reversed by co‐administration of the 5‐HT1A antagonist WAY 100635, but not the CB1 antagonist SR141716 or the CB2 antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability.

Conclusions and Implications

Our data suggest that CBD is protective against PAC‐induced neurotoxicity mediated in part by the 5‐HT1A receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC‐induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN.
G protein‐gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites
Authors: Nakamura Atsushi , Fujita Masahide , Ono Hiroko , Hongo Yoshie , Kanbara Tomoe , Ogawa Koichi , Morioka Yasuhide , Nishiyori Atsushi , Shibasaki Masahiro , Mori Tomohisa , Suzuki Tsutomu , Sakaguchi Gaku , Kato Akira , Hasegawa Minoru
Published: October 2013

Background and Purpose

Oxycodone and morphine are μ‐opioid receptor agonists prescribed to control moderate‐to‐severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opioids and investigated the role of G protein‐gated inwardly rectifying potassium (KIR3 also known as GIRK) channels in their antinociceptive effects.

Experimental Approach

Opioid‐induced antinociceptive effects were assessed in mice, using the tail‐flick test, by i.c.v. and intrathecal (i.t.) administration of morphine and oxycodone, alone and following inhibition of KIR3.1 channels with tertiapin‐Q (30 pmol per mouse, i.c.v. and i.t.) and KIR3.1‐specific siRNA. The antinociceptive effects of oxycodone and morphine were also examined after tertiapin‐Q administration in the mouse femur bone cancer and neuropathic pain models.

Key Results

The antinociceptive effects of oxycodone, after both i.c.v. and i.t. administrations, were markedly attenuated by KIR3.1 channel inhibition. In contrast, the antinociceptive effects of i.c.v. morphine were unaffected, whereas those induced by i.t. morphine were attenuated, by KIR3.1 channel inhibition. In the two chronic pain models, the antinociceptive effects of s.c. oxycodone, but not morphine, were inhibited by supraspinal administration of tertiapin‐Q.

Conclusion and Implications

These results demonstrate that KIR3.1 channels play a primary role in the antinociceptive effects of oxycodone, but not those of morphine, at supraspinal sites and suggest that supraspinal KIR3.1 channels are responsible for the unique analgesic profile of oxycodone.
Confronting inconsistencies in the amphibian‐chytridiomycosis system: implications for disease management
Authors: Venesky Matthew D. , Raffel Thomas R. , McMahon Taegan A. , Rohr Jason R.
Published: October 2013

Chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), is one of the largest threats to wildlife and is putatively linked to the extirpation of numerous amphibians. Despite over a decade of research on Bd, conflicting results from a number of studies make it difficult to forecast where future epizootics will occur and how to manage this pathogen effectively. Here, we emphasize how resolving these conflicts will advance Bd management and amphibian conservation efforts. We synthesize current knowledge on whether Bd is novel or endemic, whether amphibians exhibit acquired resistance to Bd, the importance of host resistance versus tolerance to Bd, and how biotic (e.g. species richness) and abiotic factors (e.g. climate change) affect Bd abundance. Advances in our knowledge of amphibian–chytrid interactions might inform the management of fungal pathogens in general, which are becoming more common and problematic globally.
Using Habitat Characteristics to Predict Faunal Diversity in Tropical Production Forests
Authors: Lam Tzeng Yih , Fletcher Christine , Ramage Benjamin S. , Doll Hannah M. , Joann C. Luruthusamy , Nur‐Zati A. Mustafa , Butod Elizabeth , Kassim Abdul R. , Harrison Rhett D. , Potts Matthew D.
Published: October 2013

Biodiversity conservation in managed tropical forests is becoming increasingly important as forest area continues to decline. Accordingly, there is growing interest in developing conservation‐driven silvicultural prescriptions and identifying indicator habitat metrics (similar to indicator taxa) that could be easily assessed via routine vegetation sampling. Successfully achieving these goals, however, requires an understanding of how habitat characteristics affect biodiversity. The purpose of this study was to determine the associations between the species diversity of three taxa (ants, insectivorous bats, and dung beetles) and the habitat characteristics of hill dipterocarp production forests. We sampled both within (three samples) and adjacent to (six samples) six Virgin Jungle Reserves distributed throughout Peninsular Malaysia, and related habitat predictors to univariate diversity metrics (species richness and Shannon diversity) as well as multivariate compositional metrics. We found that influential predictors and directional effects differed across taxa. Ant diversity was most affected by stand density and canopy cover, and positively associated with both. Bat diversity was most strongly linked to primary forest area, with smaller reserves harboring greater bat diversity. Dung beetles were most affected by canopy cover and elevation, with greater diversity at lower elevation and with less canopy cover. Our multivariate analyses did not reveal any strong relationships between species composition and habitat variables. Overall, our results provide evidence that tropical forest structure is associated with biodiversity, but also suggest that it will be difficult to identify a single silvicultural prescription or landscape management strategy to maximize the diversity of all three taxa simultaneously.
Does family drawing assess attachment representations of late‐adopted children? A preliminary report
Authors: Pace Cecilia Serena , Zavattini Giulio Cesare , Tambelli Renata
Published: October 2013

Background

Attachment representations of late‐adopted children have usually been measured by attachment narratives or observational procedures. Recently an attachment‐based coding system for family drawings was developed by attachment researchers and it was used both with clinical and nonclinical samples, but it has never been used with adoptees.

Method

This study examined the differences between attachment representations of 29 late‐adopted children aged 5–7 years (M = 6.35, 51.7% girls) and 12 non‐adopted peers as assessed by family drawings, controlling for demographic variables and children's cognitive status. The attachment‐based coding system of family drawings included three levels: (1) 24 individual markers, (2) eight global rating scales (1–7 points), and (3) four attachment categories (secure, avoidant, resistant, and disorganized).

Results

Late‐adopted children assessed with the family drawings were more insecure on the attachment categories and achieved lower scores on positive global ratings such as the Vitality/Creativity and Family Pride/Happiness scales, higher scores on the Role Reversal scale, and a tendency toward higher scores on the Bizarreness/Dissociation scale. No difference emerged between the two groups regarding the individual markers.

Conclusions

Family drawing seemed to be a useful tool for classifying attachment representations, and able to capture underlying mental states that it was hard for late‐adopted children to express in words.
Heregulin induces resistance to lapatinib‐mediated growth inhibition of HER2‐amplified cancer cells
Authors: Sato Yuji , Yashiro Masakazu , Takakura Nobuyuki
Published: October 2013

Human epidermal growth factor receptor 2 (HER2) amplification occurs in approximately 20% of gastric and gastroesophageal junction cancers in the United States and European Union. Lapatinib, a dual HER2 and epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated clinical efficacy in HER2‐amplified cancer cells. However, several studies have shown that some cytokines can mediate resistance to lapatinib using their receptor tyrosine kinase (RTK) pathways. One of these, Heregulin1 (HRG1), can confer resistance to lapatinib‐mediated growth inhibition in HER2‐amplified breast cancer cells, but the underlying mechanisms remain unknown. Here, we investigated whether and how HRG1 causes resistance to lapatinib in gastric and gastroesophageal junction cancers in vitro. HER2‐amplified gastric and gastroesophageal junction cancer cell lines were highly sensitive to lapatinib. Exposure to HRG1 together with lapatinib rescued cells from lapatinib‐induced cell cycle arrest and apoptosis. Downregulation of HER3 with siRNA in the presence of HRG1 re‐sensitized HER2‐amplified cancer cells to lapatinib. Immunoblotting analysis indicated that HRG1 re‐activated HER3 and AKT in the presence of lapatinib, which persisted for at least 72 h. Activation of HER3 and downstream AKT was mediated by residual activity of HER2. HRG1‐mediated resistance could be reduced by PI3K/mTOR inhibitors or by complete inhibition of HER2. Thus, we conclude that HRG1 mediates resistance to lapatinib through HER3 and AKT activation, and that this depends on residual HER2 activity. Lapatinib in combination with anti‐PI3K therapies or more potent HER2 inhibitors would improve the efficacy and avoid the emergence of resistant cells.
B3GNT3 expression suppresses cell migration and invasion and predicts favorable outcomes in neuroblastoma
Authors: Ho Wan‐Ling , Che Mei‐Ieng , Chou Chih‐Hsing , Chang Hsiu‐Hao , Jeng Yung‐Ming , Hsu Wen‐Ming , Lin Kai‐Hsin , Huang Min‐Chuan
Published: October 2013

Aberrant expression of the simple mucin‐type carbohydrate antigens such as T, Tn, sialyl‐T and sialyl‐Tn is associated with poor prognosis in several cancers. β1,3‐N‐acetylglucosaminyltransferase‐3 (B3GNT3), a member of the β3GlcNAcT family, is responsible for forming extended core 1 (T antigen) oligosaccharides. The role of B3GNT3, which is expressed in various tissues including human fetal brain, in regulating neuroblastoma (NB) formation and cell behaviors remains unclear. Here, we showed that increased B3GNT3 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as a favorable Shimada's subset of pathology. Univariate and multivariate analyses revealed that positive B3GNT3 expression in tumor tissues predicted a favorable prognosis in NB patients independent of other prognostic markers. B3GNT3 overexpression suppresses T antigen formation and malignant phenotypes including migration and invasion of SK‐N‐SH cells, whereas B3GNT3 knockdown enhances these phenotypes of SK‐N‐SH cells. Moreover, B3GNT3 expression decreased phosphorylation of focal adhesion kinase (FAK), Src, paxillin, Akt and ERK1/2. We conclude that B3GNT3 predicts a favorable cancer behavior of NB and suppresses malignant phenotypes by modulating mucin‐type O‐glycosylation and signaling in NB cells.
Small compound bigelovin exerts inhibitory effects and triggers proteolysis of E2F1 in multiple myeloma cells
Authors: Liu Jing‐Lei , Zeng Guang‐Zhi , Liu Xiao‐Li , Liu Yong‐Qiang , Hu Zhong‐Guo , Liu Ying , Tan Ning‐Hua , Zhou Guang‐Biao
Published: October 2013

Multiple myeloma (MM) is a currently incurable blood cancer. Here we tested the effects of a small compound bigelovin on MM cells, and reported that it caused cell cycle arrest and subsequently induced apoptosis. Bigelovin triggered proteolysis of E2F1, which could be inhibited by caspase inhibitor. To investigate the clinical relevance, the expression of E2F1 in MM specimens was tested, and the results showed that E2F1 was overexpressed in 25–57% of MM patients and was associated with higher International Staging System (ISS) stage. These results suggest that E2F1 may be important for MM pathogenesis, and bigelovin could serve as a lead compound for the development of E2F1 inhibitor.