bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial
Authors: Menkarios Cathy , Vigneault Éric , Brochet Nicolas , Nguyen David HA , Bahary Jean-Paul , Jolicoeur Marjory , Beauchemin Marie-Claude , Villeneuve Hugo , Van Nguyen Thu , Fortin Bernard , Lambert Carole
Published: September 2011

Background

Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment.

Materials and Methods

We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival.

Results

Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%.

Conclusions

Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.
Adenovirus-mediated delivery of bFGF small interfering RNA reduces STAT3 phosphorylation and induces the depolarization of mitochondria and apoptosis in glioma cells U251
Authors: Liu Jun , Xu Xinnv , Feng Xuequan , Zhang Biao , Wang Jinhuan
Published: September 2011

Glioblastoma multiforme (GBM) carries a dismal prognosis primarily due to its aggressive proliferation in the brain regulated by complex molecular mechanisms. One promising molecular target in GBM is over-expressed basic fibroblast growth factor (bFGF), which has been correlated with growth, progression, and vascularity of human malignant gliomas. Previously, we reported significant antitumor effects of an adenovirus-vector carrying bFGF small interfering RNA (Ad-bFGF-siRNA) in glioma in vivo and in vitro. However, its mechanisms are unknown. Signal transducer and activator of transcription 3 (STAT3) is constitutively active in GBM and correlates positively with the glioma grades. In addition, as a specific transcription factor, STAT3 serves as the convergent point of various signaling pathways activated by multiple growth factors and/or cytokines. Therefore, we hypothesized that the proliferation inhibition and apoptosis induction by Ad-bFGF-siRNA may result from the interruption of STAT3 phosphorylation. In the current study, we found that in glioma cells U251, Ad-bFGF-siRNA impedes the activation of ERK1/2 and JAK2, but not Src, decreases IL-6 secretion, reduces STAT3 phosphorylation, decreases the levels of downstream molecules CyclinD1 and Bcl-xl, and ultimately results in the collapse of mitochondrial membrane potentials as well as the induction of mitochondrial-related apoptosis. Our results offer a potential mechanism for using Ad-bFGF-siRNA as a gene therapy for glioma. To our knowledge, it is the first time that the bFGF knockdown using adenovirus-mediated delivery of bFGF siRNA and its potential underlying mechanisms are reported. Therefore, this finding may open new avenues for developing novel treatments against GBM.
Long-term sickness absence among patients with chronic fatigue syndrome
Authors: Knudsen Ann Kristin , Henderson Max , Harvey Samuel B. , Chalder Trudie
Published: September 2011

Chronic fatigue syndrome is associated with high levels of occupational disability. Consecutive out-patients at a chronic fatigue syndrome treatment service were studied for associations between occupational status, symptom severity and cognitive and behavioural responses to symptoms. All patients had high symptom levels; however, those on long-term sickness absence had significantly more physical fatigue (β = 0.098, P<0.05) and worse sleep (β = 0.075, P<0.05). Patients with long-term sickness absence also demonstrated more embarrassment avoidance cognitions (β = 0.086, P<0.05) and avoidance resting behavioural responses (β = 0.078, P<0.05). Identifying and addressing avoidance behaviours and cognitions regarding embarrassment in interventions may enhance the chances of individuals returning to work.
Relationship of orthostatic blood pressure to white matter hyperintensities and subcortical volumes in late-life depression
Authors: Colloby Sean J. , Vasudev Akshya , O'Brien John T. , Firbank Michael J. , Parry Steve W. , Thomas Alan J.
Published: September 2011

Background

Structural brain abnormalities are associated with late-life major depression, with numerous studies reporting increased white matter hyperintensities (WMH) and reduced cortical/subcortical grey matter volumes. There is strong evidence linking vascular disease to WMH, but limited evidence on its association with subcortical volumes.

Aims

To investigate the relationship of orthostatic blood pressure changes to WMH and subcortical grey matter volumes in late-life depression.

Method

Thirty-eight people with depression and a similarly aged comparison group (n = 30) underwent fluid attenuated inversion recovery (FLAIR) and T1-weighted magnetic resonance imaging as well as systematic orthostatic blood pressure assessments. Volumetric estimates of WMH and subcortical grey matter were obtained for each participant and the relationship to blood pressure drop on active stand was examined.

Results

An association between orthostatic systolic blood pressure drop and WMH volumes in temporal and parietal regions was found in the depression group (age-corrected partial correlation r’ = 0.31–0.35, P<0.05). Subcortical volumes were not related to blood pressure changes or WMH volumes in either group.

Conclusions

We found evidence for an association between the degree of orthostatic systolic blood pressure drop and WMH volume in the depression group. Since blood pressure drops lead to WMH in animals our findings suggest systolic blood pressure drops may be a factor contributing to these lesions in late-life depression.
Renal collecting system growth and function depend upon embryonic γ1 laminin expression
Authors: Yang Dong-Hua , McKee Karen K. , Chen Zu-Lin , Mernaugh Glenda , Strickland Sidney , Zent Roy , Yurchenco Peter D.
Published: September 2011

In order to understand the functions of laminins in the renal collecting system, the Lamc1 gene was inactivated in the developing mouse ureteric bud (UB). Embryos bearing null alleles exhibited laminin deficiency prior to mesenchymal tubular induction and either failed to develop a UB with involution of the mesenchyme, or developed small kidneys with decreased proliferation and branching, delayed renal vesicle formation and postnatal emergence of a water transport deficit. Embryonic day 12.5 kidneys revealed an almost complete absence of basement membrane proteins and reduced levels of α6 integrin and FGF2. mRNA levels for fibroblast growth factor 2 (FGF2) and mediators of the GDNF/RET and WNT11 signaling pathway were also decreased. Furthermore, collecting duct cells derived from laminin-deficient kidneys and grown in collagen gels were found to proliferate and branch slowly. The laminin-deficient cells exhibited decreased activation of growth factor- and integrin-dependent pathways, whereas heparin lyase-treated and β1 integrin-null cells exhibited more selective decreases. Collectively, these data support a requirement of γ1 laminins for assembly of the collecting duct system basement membrane, in which immobilized ligands act as solid-phase agonists to promote branching morphogenesis, growth and water transport functions.
Control of final organ size by Mediator complex subunit 25 in Arabidopsis thaliana
Authors: Xu Ran , Li Yunhai
Published: September 2011

Control of organ size by cell proliferation and cell expansion is a fundamental developmental process, but the mechanisms that establish the final size of organs and whole organisms remain elusive in plants and animals. We have previously demonstrated that DA1, which encodes a predicted ubiquitin receptor, controls the final size of seeds and organs by restricting cell proliferation in Arabidopsis. Through a genetic screen for mutations that enhance the floral organ size of da1-1, we have identified an enhancer of da1-1 (eod8-1). The eod8-1 mutation was identified, using a map-based cloning approach, in Mediator complex subunit 25 (MED25; also known as PFT1), which is involved in the transcriptional regulation of gene expression. Loss-of-function mutants in MED25 form large organs, with larger and slightly increased numbers of cells as a result of an increased period of cell proliferation and cell expansion, whereas plants overexpressing MED25 have small organs owing to decreases in both cell number and cell size. Our genetic and physiological data suggest that MED25 acts to limit cell and organ growth independently of MED25-mediated phytochrome signaling and the jasmonate pathway. Genetic analyses show that MED25 functions redundantly with DA1 to control organ growth by restricting cell proliferation. Collectively, our findings show that MED25 plays a crucial role in setting final organ size, suggesting that it constitutes an important point of regulation in plant organ size control within the transcriptional machinery.
Hypothyroidism in preterm infants following normal screening
Authors: Hallett Andrew , Evans Carol , Moat Stuart , Barton John , Warner Justin , Gregory John W
Published: September 2011

Congenital hypothyroidism is screened for in the UK using blood spot thyroid-stimulating hormone (TSH) screening at 5–8 d of age. Although standards are set by the UK Newborn Screening Programme Centre, there are variations in TSH cut-offs used. The introduction of repeat screening of preterm babies at 36 weeks' gestational age in 2005 was controversial in its utility and timing. Two cases of preterm babies are presented, who had normal blood spot TSH values on the first test and who became screen positive when re-tested at term. The first with Trisomy 21 was born at 29 + 6 weeks with an initial blood spot TSH of 3.3 mU/L rising to 263 mU/L at term-corrected gestational age (plasma TSH 476.5 mU/L). The second was born at 24 + 6 weeks’ gestational age and on day 7, the heel prick blood spot TSH was <2 mU/L, rising to 6.4 mU/L at 36 weeks corrected gestational age. After a barium enema, the plasma TSH increased to 66.6 mU/L with a free thyroxine of 7.6 pmol/L at day 101. Both cases were treated with thyroxine until death due to complications of prematurity. These cases illustrate the difficulties in screening for congenital hypothyroidism in preterm infants, due to the immaturity of the hypothalamo–pituitary–thyroid axis, and the effect of intercurrent illness and drugs on thyroid function. Despite a reassuring published review of 2200 preterm infants, these cases suggest that it may be unwise not to re-screen ex-preterm infants for congenital hypothyroidism at term.
Ischaemic stroke following tranexamic acid in young patients carrying heterozygosity of MTHFR C677T
Authors: Nardi Katiuscia , Pelone Giordana , Bartolo Michelangelo , Di Ruzza Maria Rita , Storto Marianna , Notte Antonella , Grillea Giovanni , Colonnese Claudio , Lembo Giuseppe , Vecchione Carmine
Published: September 2011

The objective of this study is to report a new manifestation of acute stroke following antifibrinolytic agent administration in young women carrying heterozygosity for methylene-tetrahydrofolate reductase (MTHFR) C677T. The study included two young women who developed an acute ischaemic stroke following three days of tranexamic acid administration for bleeding gynaecological disorders. Case 1, a 44-year-old woman, presented left hemiplegia, mild dysarthria and anosognosia. Brain magnetic resonance imaging showed right ischaemic fronto-temporal lesion due to subocclusion of the right middle cerebral artery. Case 2, a 49-year-old woman, developed aphasia and right hemiplegia. Neuroimaging showed left capsular and periventricular infarcts due to near occlusion of the left internal carotid artery. Thrombophilia screening, coagulation parameters, homocysteine testing, 12-lead electrocardiography, and transthoracic and transoesophageal echocardiography were unremarkable. Genetic assay showed that both patients carried heterozygosity for MTHFR C677T, in which cytosine (C) is replaced by thymidine (T) at base position 677. To our knowledge, this is the first report describing the association between genetic factors and the onset of stroke following antifibrinolytic drugs intake. These data suggest a synergic effect of plasminogen activator inhibitor and heterozygosity for MTHFR C677T on the pathogenetic mechanisms leading to ischaemic stroke in young people.
Preliminary study of whole-body diffusion-weighted imaging in detecting pulmonary metastatic lesions from clear cell renal cell carcinoma: comparison with CT
Authors: Liu Jing , Yang Xuedong , Li Feiyu , Wang Xiaoying , Jiang Xuexiang
Published: September 2011

Background

Whole-body diffusion-weighted imaging (DWI) has been widely used in detecting malignant metastases, including pulmonary metastases.

Purpose

To evaluate the possible utility of whole-body DWI in detecting pulmonary metastases of patients with clear cell renal cell carcinoma (ccRCC) and compare the exact differences between MR and CT in detecting pulmonary lesions.

Material and Methods

Whole-body DWI and chest CT examinations were performed on nine consecutive patients (8 men and 1 woman) with histologically confirmed ccRCC and possible metastatic lesions before chemotherapy.

Results

CT and MR demonstrated pulmonary metastases in seven patients and no metastatic lesions in two patients. The numbers of pulmonary metastases detected on CT, DWI-only, T1WI-only and DWI in combination with T1WI were 83, 35, 34 and 39, respectively. Metastases with a diameter above 1.0 cm could all be detected by DWI and a diameter above 0.7 cm could all be detected by DWI in combination with T1WI. Significant differences were obtained both for correlationship between diameter and detection rates of DWI and T1WI by using Spearman rank correlation analysis.

Conclusion

Although MR cannot be considered a replacement for CT in pulmonary metastases from ccRCC, whole-body DWI, with the combination of T1 dual echo, might be helpful for the evaluation of tumor response to chemotherapy in the follow-up of patients when the diameter of the pulmonary metastases is over 1.0 cm.
Transplant research and deceased donors: laws, licences and fear of liability
Authors: Douglas J F , Rose M L , Dark J H , Cronin A J
Published: September 2011

Transplantation research on samples and organs from deceased donors in England, Wales and Northern Ireland is under threat. The key problems relate to difficulties encountered in gaining consent for research projects, as distinct from consent to donation for clinical transplantation. They are due partly to the terms of the Human Tissue Act 2004 (the 2004 Act), and partly to its interpretation by the Human Tissue Authority (HTA). They include excessive interaction with donor representatives regarding ‘informed consent’ to research projects, uncertainty as to the scope and duration of a donor's ‘authority’ over an organ, and restrictions caused by the apparent need for licensing of transplantation research under the 2004 Act, combined with lack of certainty, or guidance, as to the distinction between ‘research’, which requires a licence, and ‘service development’, which does not. In our view this confusion hinders and deters Specialist Nurses for Organ Donation in approaching donor representatives and discussing possible research projects with them. It has also, as we have reported elsewhere, led to abandonment of research projects for fear of liability, despite both Research Ethics Committee (REC) approval and donor consent. Such problems do not seem to occur under the transplant laws of most other comparable jurisdictions. The Transplantation Ethics Symposium, ‘The ethics of organ retrieval: goals, rights and responsibilities’, hosted by the MRC Centre for Transplantation at King's College London in December 2010, revealed that many senior clinicians and researchers, administrators, and lawyers are both unclear and in disagreement concerning the effects of the 2004 Act and the extent to which it is adhered to or ignored in practice. In this paper we examine the difficulties encountered and suggest solutions based on a less restrictive interpretation of the 2004 Act, or, more probably, a regulatory change under its authority. We propose that, in the long term, a law which includes consent for REC-approved research within the general consent for organ donation and transplantation seems preferable to the present system, both ethically and in practical terms.
Liver transplantation using ‘donation after circulatory death’ donors: the ethics of managing the end-of-life care of potential donors to achieve organs suitable for transplantation
Authors: Moorlock Greg , Draper Heather , Bramhall Simon R
Published: September 2011

The decline in organs donated after brain death has been countered by an increase in organs donated after circulatory death. Organs donated after circulatory death present an increased risk of complications for their eventual recipients when compared with organs donated after brain death, so the likelihood of successful transplantation is decreased. If organ donation is considered to be in the best interests of the patient, interventions that facilitate successful donation and transplantation might be permissible. This paper seeks to establish whether it is ethically permissible to manage the end-of-life care of a dying patient to maximize the chances of successful transplantation, and if so, whether it is permissible to further maximize these chances by managing the potential donor to enable donation after brain death rather than donation after circulatory death.
Optimizing donor potential in the UK
Authors: Murphy Paul G
Published: September 2011

Rates of deceased organ donation in the UK fall well short of those reported from other parts of the world, and result in unnecessary deaths and avoidable morbidity. A particular feature of the UK problem is that its total potential for donation is lower than the actual number of donors reported in the highest-donating countries. This implies that while the identification, referral and conversion of recognized potential deceased donors is an important component of any strategic effort to increase donation, more fundamental is an understanding of why some countries have a greater potential for donation, particularly donation after brain death. While it is possible that these differences reflect a difference in the incidence catastrophic brain injury or the outcomes from it, it is also possible that it reflects different approaches to the care that such patients receive when they are dying.
Supporting organ donation through end-of-life care: implications for heart-beating donation
Authors: Price D
Published: September 2011

New protocols have been developed for donors after circulatory death involving early assessment of donor status and premortem supporting treatment in appropriate cases where there is evidence that the patient wished to be an organ donor. These donors are now making an increasingly marked impact on overall deceased donor numbers in the UK. Donors after brainstem death, on the other hand, are much less buoyant yet require the same flexibility in approach in order to improve rates of donation and to realize the wishes of potential deceased organ donors to the proper requisite extent.
Progression of reflux patterns in saphenous veins of women with chronic venous valvular insufficiency
Authors: Engelhorn C A , Manetti R , Baviera M M , Bombonato G M , Lonardoni M , Cassou M F , Engelhorn A L , Salles-Cunha S X
Published: September 2011

Background

Venous ultrasonography identifies reflux patterns of the great and small saphenous veins (GSV, SSV), allowing evaluation of lower extremities for treatment planning and patient follow-up.

Objective

To determine progression of saphenous vein reflux patterns in women with primary venous valvular insufficiency.

Methods

Venous ultrasonography was performed in the extremities of 92 women, 43 ± 12 (23–77) years old, CEAP (clinical, aetiological, anatomical and pathological elements) clinical classes C1–C2. Two examinations were performed 33 ± 19 (8–89) months apart in patients without saphenous vein treatment. GSV and SSV reflux patterns were classified as segmental, multisegmental, distal, proximal, diffuse and normal. Prevalence was determined for each examination, separately for right and left extremities, and jointly. Prevalence was compared using χ2 statistics.

Results

Reflux prevalence was higher for the GSV, 89% (164/184) and 88% ( n = 162), than for the SSV, 24% ( n = 45) and 30% ( n = 56), respectively for first and second examinations ( P < 0.001). Reflux pattern prevalence was not significantly different in the right and left extremities (1.0 > P > 0.14). Most prevalent patterns were (a) GSV segmental reflux initially, 41% (76/184), decreasing to 28% (52/184) ( P = 0.009), and (b) GSV multisegmental reflux at the second examination, increasing from 26% (48/184) to 40% (73/184) ( P = 0.006). Prevalence of other GSV or SSV reflux patterns did not change significantly (0.88 > P > 0.19).

Conclusions

We documented early findings and venous reflux progression in a specific population of women with varicose veins, reticular veins and telangiectasias. GSV segmental reflux was most prevalent initially, progressing to GSV multisegmental reflux.
Morphological and haemodynamic abnormalities in the jugular veins of patients with multiple sclerosis
Authors: Radak D , Kolar J , Tanaskovic S , Sagic D , Antonic Z , Mitrasinovic A , Babic S , Nenezic D , Ilijevski N
Published: September 2011

Objectives

Multiple areas of stenosis and different levels of obstruction of internal jugular and azygous veins (a condition known as cronic cerebrospinal venous insufficiency) recently emerged as an additional theory to the well-known autoimmune concept, explaining etiology of multiple sclerosis (MS). The aim of our study was to evaluate internal jugular vein (IJV) morphology and haemodynamic characteristics in patients with MS and compare it with well-matched healthy individuals and to evaluate the prevalence of venous flow abnormalities in both groups.

Methods

Sixty-four patients with clinically proven MS and 37 healthy individuals were included in our study. In all patients, IJV morphology and haemodynamic characteristics were evaluated by colour Doppler sonography as well as venous flow disorder. The patients were classified into four groups according to MS clinical form presentation. The prevalence of morphological and haemodynamic abnormalities in the IJV were assessed.

Results

The presence of stenosing lesion, mostly intraluminal defects like abnormal IJV valves, were observed in 28 patients (43%) in the MS group, and in 17 patients (45.9%) in the control group ( P = NS). By adding haemodynamic Doppler information in the IJV venous outflow was significantly different in 42% of MS patients showing flow abnormalities (27/64), as compared with 8.1% of the controls (3/37), P < 0.001.

Conclusion

In our group of patients, patients suffering from MS had significantly more IJV morphological changes and haemodynamic abnormalities when compared with healthy individuals not suffering from MS. These findings can be well demonstrated by non-invasive and cost-effective Doppler ultrasound.
Heartsink encounters: a qualitative study of end-of-life care in out-of-hours general practice
Authors: Taubert Mark , Nelson Annmarie
Published: September 2011

Objectives

We aimed to establish how prepared GPs who work regular out-of-hours shifts feel when dealing with end-of-life issues in palliative care patients, what they thought about seeing such patients and whether they considered themselves emotionally equipped to do so.

Design

Semi-structured interviews were conducted with GPs who worked regular out-of-hours shifts. A detailed analysis of transcripts using Interpretative Phenomenological Analysis was undertaken.

Setting

South Wales.

Participants

GPs employed by the local health board's out-of-hours service were contacted.

Main outcome measures

All interview data were analysed systematically and statements that reflected emotional impact and strain were highlighted, coded and interpreted within their context.

Results

GPs expressed unease and used terms such as ‘heartsink’, when having to deal with palliative care issues out-of-hours. Heartsink in this context referred to the subjective experience of the clinician. Emotional ‘housekeeping’, i.e. looking after oneself after emotionally-charged encounters, was felt to be a very important process and GPs used a range of coping mechanisms, including reflective time, sharing with peers, compartmentalisation and personal empathy to deal with stress.

Conclusion

The emotional effects of palliative care encounters on out-of-hours GPs should not be underestimated. Our interpretation distinguished the term ‘heartsink’ from its usual context, the ‘heartsink patient’, to a different meaning, that of the imminent palliative care encounter triggering a sensation of heartsink for some out-of-hours doctors. Therefore, the term ‘heartsink encounter’, rather than heartsink patient, seemed more fitting. Pressed services may encourage a culture where discussion or debrief with a colleague after a palliative care encounter is not perceived as a practical option. This may contribute to work-related burnout in this group of doctors and out-of-hours collaboratives need to be aware of this issue, when planning their services.
Cultural services and social policy: exploring policy makers’ perceptions of culture and social inclusion
Authors: McCall Vikki
Published: September 2011

In post-devolution Scotland, New Labour added to the role of ‘culture’ by introducing ideas of social inclusion to policies concerning cultural services. Ten years later, with the Scottish National Party (SNP) minority government in the Scottish Parliament, do policy makers think social inclusion still has a role within cultural services? This article shows that policy makers’ understandings of ‘culture’ and social inclusion are vague, general and complex. This has encouraged policy makers to think of cultural services as resources to fulfil wider economic and social objectives. At the same time, cultural services are placed at an individual level, with cultural services seen as ‘generators of wellbeing’, rather than agents of social change. Social inclusion and cultural meanings are linked to individualistic causes of poverty and related to the SNP’s economic focus in Scotland. This complexity impacts on the interpretation and implementation of policy and has resulted in the cultural agenda being seen as less of a priority within the new SNP administration.
Progressive social justice and responding to the crisis
Authors: Atkinson A.B.
Published: September 2011

We may not be able to agree about where we would like to end up after the economic crisis, but we can surely agree on some elements of a socially just response to the recession. Applying the principle of ‘progressive social justice’, along the lines indicated by Amartya Sen (2009) in The idea of justice, the article proposes two particular United Kingdom (UK) policy responses to the crisis: the restoration of effective unemployment insurance at home, and the cementing of the commitment to overseas aid as part of the UK's global responsibilities.
The implications of the changes to Housing Benefit
Authors: Harding Roger
Published: September 2011

In the short period since the 2010 United Kingdom (UK) General Election, state support to help people with their housing costs has been subject to a series of damaging cuts. This paper examines not only the likely direct impact of these changes, particularly on more vulnerable claimants, but also why the cost has risen and is perceived to be high. It concludes by arguing that policy makers should not ignore the spatial impact of housing and welfare policy; a vital opportunity to create and sustain better communities will be missed if they are considered purely in the terms of people avoiding rooflessness.
Building bridges: the third sector responding locally to diversity
Authors: Harris Margaret , Young Patricia
Published: September 2011

This paper focuses on a hitherto unstudied segment of the broad ‘third sector’: organisations and groupings that aim to build bridges (that is, increase interpersonal contacts) between people of different faiths and/or ethnic group. We draw on the findings of an empirical study, conducted in three diverse urban areas of England, of community-level projects with bridge building as an explicit aim. We describe the characteristics of bridge-building activities and the challenges they face; both the organisational challenges and those that arise from the nature of bridge building itself. We conclude by exploring the implications of our findings for an understanding of the third sector generally and for the potential role of the sector in responding to our diverse society.
Challenges of governance for small voluntary organisations
Authors: Nunan Kevin
Published: September 2011

The academic and practitioner literature pays little attention to the distinctive issues of governance found in small voluntary organisations. There are three key factors in developing more effective boards – board assessment, governance development and the relationship between the senior staff member and the members of the board. Board effectiveness is also constrained by regulation – by the Charity Commission, Companies House and wider legislation. More evidence is needed to enable small organisations to address these challenges.
Observations on incivility: blind spots in third sector research and policy
Authors: Evers Adalbert
Published: September 2011

Incivility is not only a moral or political challenge but also something that should make the third sector research community think about the appropriateness of some of its widely used basic concepts. This paper sketches three different types of attitudes in the third sector that are a threat to civil society, each of them pointing to challenges for third sector research. Altogether, this leads to a fourth and final point, where it is argued that the world of associations (the third sector) and civil society are different subjects. Civicness and civility should be seen as qualities of society at large. And it is questionable to assume that association building has a kind of natural and privileged link with the making of active citizens and the building of civil society.
Hackney Advice Forum: taking back the power
Authors: Benson Andy
Published: September 2011

Many statutory authorities are abandonning grant schemes for funding voluntary agencies in favour of more tightly prescribed commissioning regimes. These changes in funding arrangements fundamentally alter the relationship between statutory and non-statutory sectors and challenge the autonomy and independence of voluntary action. This paper describes the response of the Hackney Advice Forum to the perceived threat of commissioning and highlights issues arising from this.
Anatomy of a crisis and lessons for third sector governing boards
Authors: Leadbeater Simon
Published: September 2011

This paper analyses the key aspects of a crisis that beset an apparently effective and well-regarded third sector training provider. It describes how management responded to this crisis and assesses the efficacy of its actions. Finally – from the experience of two tumultuous years – the article attempts to draw lessons and offer guidance on how to interpret the early signs of potentially multilayered and sometimes intractable problems that can easily lead to organisational collapse.
Recent developments in volunteering and citizenship
Authors: Strickland Alan
Published: September 2011

Policy makers have recently sought to use volunteering as a vehicle to develop citizenship, and to offer elements of citizenship as a reward to develop volunteering. Policy proposals have focused on developing citizenship among young people and regard the emergence of volunteering as a form of currency, able to secure access to social goods and to repay social ills. This paper suggests four key changes that underlie this shift, including an increased role for the state and moves towards coercive forms of incentivisation.
The emergence of structured subnational voluntary sector–government relationships in Canada: a historical institutional analysis
Authors: Elson Peter R.
Published: September 2011

Building on prior research at the federal level, this paper examines the emergent institutional relationships between government and the voluntary sector in seven Canadian provinces. Prior to the release of a national survey in 2005, little collective attention was paid to the size and impact of the voluntary sector at the provincial level by either the sector or governments. This subnational historical institutional analysis reveals that there is a new and growing appetite for policy dialogue, representing a notable shift in attention to voluntary sector–government relations at the provincial level. Trends and informative exceptions in this emerging relationship are profiled.
The use of UK charity accounts data for researching the performance of voluntary organisations
Authors: Morgan Gareth G.
Published: September 2011

The published accounts of charities offer a fruitful data source for voluntary sector researchers. This paper presents a critique of some of the risks associated with charity accounts data. It argues that without proper consideration of these risks, research using charity accounts may offer less certainty than is often assumed. It nevertheless highlights ways in which charity accounts can be used with a reasonable level of confidence. Finally, the paper discusses more broadly the central purpose of charity financial reporting and the extent to which this may or may not align with the needs of researchers.
“I'm Supposed to Be In Charge”: Self-Advocates' Perspectives on Their Self-Determination Support Needs
Authors: Nonnemacher Stacy L , Bambara Linda M
Published: September 2011

In this qualitative interview study, we explored the perceptions of adults with intellectual disability regarding interpersonal or social supports needed to express their own self-determination. Specifically, 10 adults, all members of a self-advocacy group, were asked to discuss their understanding of the term self-determination and ways in which support staff have either supported or inhibited their self-determination. Ten themes characterizing supportive and impeding staff actions were identified. The need for greater exploration of environmental and social influences on self-determination is emphasized.
Gendered Service Delivery: A Masculine and Feminine Perspective on Staff Gender
Authors: Wilson Nathan J , Stancliffe Roger J , Parmenter Trevor R , Shuttleworth Russell P
Published: September 2011

Despite acknowledgement that paid caregivers have a significant impact on the lives of people with intellectual disability, the subjective experience of staff gender is rarely considered in research. Qualitative data from a study on the sexual health needs of men and boys with intellectual disability is presented. We designed this study to determine what impact staff gender has on the sexual health needs of men and boys with intellectual disability. Findings suggest that although staff traverse the same geographies of care, they do it in uniquely gendered ways. Staff gender is an important consideration when dealing with sexual health matters and can enhance the type and quality of relationships between people with intellectual disability.
Convergent Validity of the Mullen Scales of Early Learning and the Differential Ability Scales in Children With Autism Spectrum Disorders
Authors: Bishop Somer L , Guthrie Whitney , Coffing Mia , Lord Catherine
Published: September 2011

Despite widespread use of the Mullen Scales of Early Learning (MSEL; E. M. Mullen, 1995) as a cognitive test for children with autism spectrum disorders and other developmental disabilities, the instrument has not been independently validated for use in these populations. Convergent validity of the MSEL and the Differential Ability Scales (DAS; C. D. Elliott, 1990, 2007) was examined in 53 children with autism spectrum disorder and 19 children with nonspectrum diagnoses. Results showed good convergent validity with respect to nonverbal IQ (NVIQ), verbal IQ (VIQ), and NVIQ–VIQ profiles. These findings provide preliminary support for the practice of using MSEL age-equivalents to generate NVIQ and VIQ scores. Establishing convergent validity of cognitive tests is needed before IQs derived from different tests can be conceptualized as a uniform construct.
Effect of Incorporating Adaptive Functioning Scores on the Prevalence of Intellectual Disability
Authors: Obi Obianuju , Van Naarden Braun Kim , Baio Jon , Drews-Botsch Carolyn , Devine Owen , Yeargin-Allsopp Marshalyn
Published: September 2011

Surveillance and epidemiologic research on intellectual disability often do not incorporate adaptive functioning (AF) data. Exclusion of AF data leads to overestimation of the prevalence of intellectual disability, the extent of which is not known. In this study, the authors evaluated the effect of incorporating AF data on overall intellectual disability prevalence according to sociodemographic, economic, and severity characteristics. Between 2002 and 2006, the Metropolitan Atlanta Developmental Disabilities Surveillance Program identified 1,595 8-year-old children who met the study's intellectual disability surveillance-case definition of IQ ≤ 70. AF scores were not available for 9.2% of the case children, specifically those with mild intellectual disability and low socioeconomic backgrounds. Prevalence estimates showed few substantive changes when incorporating AF data. The authors conclude that use of IQ data alone appears to be appropriate for measuring population intellectual disability prevalence.
Changes in Maladaptive Behaviors From Midchildhood to Young Adulthood in Autism Spectrum Disorder
Authors: Anderson Deborah K , Maye Melissa P , Lord Catherine
Published: September 2011

The current study prospectively examined trajectories of change in symptoms of irritability, hyperactivity, and social withdrawal, as well as predictors of such behaviors, for ages 9–18 years for youths with autism spectrum disorder and a comparison group with nonspectrum developmental delays. Children with more severe core features of autism had consistently higher irritability and hyperactivity scores over time than those with broader autism spectrum disorder and nonspectrum delays. Across all diagnoses, behaviors related to hyperactivity showed the greatest improvement. Social withdrawal worsened with age for a substantial proportion of youths with autism spectrum disorder but not for the nonspectrum comparison group. Compared with youths without autism spectrum disorder, children with the disorder showed greater heterogeneity in trajectories for maladaptive behaviors.
A New Functional CYP3A4 Intron 6 Polymorphism Significantly Affects Tacrolimus Pharmacokinetics in Kidney Transplant Recipients
Authors: Elens Laure , Bouamar Rachida , Hesselink Dennis A , Haufroid Vincent , van der Heiden Ilse P , van Gelder Teun , van Schaik Ron HN
Published: September 2011

BACKGROUND

Tacrolimus (Tac) is a potent immunosuppressant with considerable toxicity. Tac pharmacokinetics varies between individuals and thus complicates its use in preventing rejection after kidney transplantation. This variability might be caused by genetic polymorphisms in metabolizing enzymes.

METHODS

We used TaqMan analyses to evaluate the impact of a newly discovered CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) single-nucleotide polymorphism (SNP) (rs35599367C>T; CYP3A4*22) on Tac pharmacokinetics in 185 renal transplant recipients who participated in an international randomized controlled clinical trial (fixed-dose, concentration-controlled study).

RESULTS

The overall mean daily-dose requirement to reach the same predose Tac blood concentration was 33% lower for carriers of the T variant allele than for rs35599367CC patients (95% CI, −46% to −20%; P = 0.018). When combined with the *3 genotype of the CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5) gene, the rs35599367C>T SNP was also associated with a risk of supratherapeutic Tac concentrations (>15 μg/L) during the first 3 days after surgery, with an odds ratio of 8.7 for carriers of the CYP3A4 T allele plus CYP3A5*3/*3 (P = 0.027) and 4.2 for the CYP3A4 CC homozygotes plus CYP3A5*3/*3 (P = 0.002), compared with CYP3A4 CC homozygotes having 1 or 2 CYP3A5*1 alleles. The overall increase in the Tac dose-adjusted trough blood concentration was +179% for carriers of the CYP3A4 T allele with CYP3A5*3/*3 (P < 0.001), +101% for CYP3A4 CC homozygotes with CYP3A5*3/*3 (P < 0.001), and +64% for CYP3A4 T allele carriers with CYP3A5*1 (P = 0.020),compared with CYP3A4 CC homozygotes with CYP3A5*1.

CONCLUSIONS

The CYP3A4 rs35599367C>T polymorphism is associated with a significantly altered Tac metabolism and therefore increases the risk of supratherapeutic Tac concentrations early after transplantation. Analysis of this CYP3A4*22 SNP may help in identifying patients at risk of Tac overexposure.
Correlation of cortisol in 1-cm hair segment with salivary cortisol in human: hair cortisol as an endogenous biomarker
Authors: Xie Qiaozhen , Gao Wei , Li Jifeng , Qiao Ting , Jin Jing , Deng Huihua , Lu Zuhong
Published: September 2011

Cortisol level in human hair would be an endogenous biomarker for the retrospective assessment of long-term central hypothalamo-pituitary-adrenal activity. However, no direct evidence supports that blood-related diffusion is a biologically endogenous source of hair cortisol in humans. The present study aims to validate the direct correlation between cortisol in 1-cm hair segments and salivary cortisol in healthy humans.

We collected three saliva samples from the same participant at Time 1, Time 2 (1 week later) and Time 3 (2 weeks later), and hair 4 weeks later. Cortisol levels in 1-cm hair segments and saliva were determined with high performance liquid chromatography tandem mass spectrometry.

Salivary cortisol at Time 1 was significantly associated with that at Time 2 (r=0.514, p=0.003), but not with that at Time 3 (r=0.187, p=0.305); and the one at Time 2 was significantly associated with that at Time 3 (r=0.380, p=0.032). Hair cortisol was significantly correlated with salivary cortisol at Time 2 (r=0.389, p<0.05) and average salivary cortisol (r=0.383, p<0.05) from three sampling.

Our results confirmed that blood-related diffusion mechanism is a biologically endogenous source of hair cortisol.
Simultaneous determination of cyclophosphamide and 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry – application to Chinese systemic lupus erythematosus patients
Authors: Shu Wenying , Wang Xueding , Yang Xiuyan , Liang Liuqin , Li Jiali , Chen Zhuojia , Chen Xiao , Jin Jing , Li Ruiming , Zhao Lizi , Huang Min
Published: September 2011

A pharmacogenomics study of cyclophosphamide in systemic lupus erythematosus patients is being conducted in our laboratory in which the plasma concentrations of cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide should be assayed rapidly and sensitively.

A rapid, stable and sensitive liquid chromato-graphy/electrospray ionization tandem mass spectrometry method was developed to simultaneously determine cyclophosphamide and 4-hydroxycyclophosphamide in human plasma with ifosfomide as an internal standard. After a protein precipitation with cold acetonitrile and stabilization of 4-hydroxycyclophosphamide by ansyldrazine and extraction with ethyl acetate, separation was performed on a C18 3.5 μm 2.1×50 mm column with mobile phase of acetonitrile and water (50:50, v/v) with 0.1% formic acid at 200 μL/min. The chromatographic run time was 3 min.

The linear calibration curves ranged from 5 to 5000 ng/mL for cyclophosphamide and 5–500 ng/mL for 4-hydroxycyclophosphamide. The recoveries of the liquid extraction were 54.5%–58.5% for cyclophosphamide and 103.5%–105.5% for 4-hydroxycyclophosphamide. The lower limit of quantification was 5 ng/mL for both analytes. The intra- and inter-day precision was <15% for quality control samples at 4000, 500, 50 ng/mL for cyclophosphamide and 4-hydroxycyclophosphamide at 400, 100, 20 ng/mL. The method was applied in this pharmacogenomics study in Chinese systemic lupus erythematosus patients treated with low-dose cyclophosphamide.

The method was efficient with shorter running time and lower limit of quantification compared to previous reports and has been successfully applied in this pharmacogenomics study.
Natural and artificial ageing of spruce wood as observed by FTIR-ATR and UVRR spectroscopy
Authors: Ganne-Chédeville Christelle , Jääskeläinen Anna-Stiina , Froidevaux Julien , Hughes Mark , Navi Parviz
Published: September 2011

Spruce samples, naturally aged for 200, 400 and 500 years, artificially aged by a hydrothermal treatment (at 180, 160 or 130°C, relative air humidities of 14%, 40%, or 60% and for treatment times between 1 to 50 h), as well as reference samples, were analysed by Fourier transform infrared spectroscopy (FTIR) attenuated total reflection (FTIR-ATR) and ultraviolet resonance Raman (UVRR) spectroscopy. Natural ageing mostly affected the hemicelluloses and lignin, as observed from the FTIR-ATR and UVRR spectra, respectively. The UVRR spectra of the same samples after acetone extraction indicated that lignin was partially degraded and quinone structures were possibly formed. Artificial ageing at 160°C showed a significant change in the lignin structure, a well-known effect in the thermal treatment of wood, whereas treatment at 130°C did not alter the wood structure to any significant extent. Principal component analysis of the UVRR spectra confirmed that the spectra of artificially aged wood up to 160°C are dissimilar to naturally aged wood and which are also dissimilar to unaged wood.