bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasmacytoma of bone, extramedullary plasmacytoma, and multiple myeloma: incidence and survival in the United States, 1992–2004
Authors: Dores Graça M. , Landgren Ola , McGlynn Katherine A. , Curtis Rochelle E. , Linet Martha S. , Devesa Susan S.
Published: November 2008

Population‐based plasmacytoma incidence and survival data are sparse. We analyzed incidence rates (IRs), IR ratios (IRRs), and 5‐year relative survival for plasmacytoma overall and by site – bone (P‐bone) and extramedullary (P‐extramedullary) – in the Surveillance, Epidemiology and End Results (SEER) Program (1992–2004). For comparison, we included cases of multiple myeloma (MM) diagnosed over the same time period in SEER. Incidence of MM (n = 23 544; IR 5·35/100 000 person‐years) was 16‐times higher than plasmacytoma overall (n = 1543; IR = 0·34), and incidence of P‐bone was 40% higher than P‐extramedullary (P < 0·0001). The male‐to‐female IRRs for P‐bone, P‐extramedullary, and MM were 2·0, 2·6, and 1·5, respectively. For plasmacytoma and MM, IRs were highest in Blacks, intermediate in Whites, and lowest in Asian/Pacific Islanders. Compared with Whites, the Black IR was ∼30% higher for P‐extramedullary and P‐bone and 120% higher for MM. IRs for all neoplasms increased exponentially with advancing age, less prominently at older ages for plasmacytoma than MM. Distinct age, gender, and race incidence patterns of plasma cell disorders suggest underlying differences in clinical detection, susceptibility, disease biology and/or aetiological heterogeneity. Five‐year relative survival for P‐bone, P‐extramedullary, and MM varied significantly by age (<60/60+ years), supporting age‐related differences in disease burden at presentation, disease biology, and/or treatment approaches.
Abnormal serum free light chain ratios are associated with poor survival and may reflect biological subgroups in patients with chronic lymphocytic leukaemia
Authors: Pratt Guy , Harding Stephen , Holder Roger , Fegan Chris , Pepper Chris , Oscier David , Gardiner Anne , Bradwell Arthur R. , Mead Graham
Published: November 2008

The measurement of immunoglobulin serum free light chains (sFLC) has prognostic significance in plasma cell dyscrasias but its role in chronic lymphocytic leukaemia (CLL) is unknown. This retrospective study from three UK hospitals analysed sFLC in 181 untreated/pre‐treatment CLL patients and 78 treated CLL patients, with samples taken later in their disease. An abnormal sFLC ratio was significantly associated with poor overall survival for the 181 untreated/pre‐treatment patients (P = 0·0001) and for all patients (P = 0·002), irrespective of cause of death. Using multivariate analysis (n = 194), four independent prognostic variables for overall survival were identified namely Zap‐70 (P = 0·0001), β2M (P = 0·01), IGHV mutation status (P = 0·017) and an abnormal sFLC ratio (P = 0·024). For CLL patients with unmutated IGHV genes, elevated κ/λ ratios were adversely prognostic. For patients with mutated IGHV genes, reduced κ/λ ratios were adversely prognostic and associated with the poor prognostic IGHV3‐21, IGHV3‐48 and IGHV3‐53 subgroups, suggesting an abnormal sFLC ratio may reflect biological subgroups within CLL. Abnormal sFLC ratios need to be studied prospectively in CLL patients and the biological rationale for their abnormality investigated.
The presence of CD56/CD16 in T‐cell acute lymphoblastic leukaemia correlates with the expression of cytotoxic molecules and is associated with worse response to treatment
Authors: Dalmazzo Leandro F. F. , Jácomo Rafael H. , Marinato André F. , Figueiredo‐Pontes Lorena L. , Cunha Renato L. G. , Garcia Aglair B. , Rego Eduardo M. , Falcão Roberto P.
Published: November 2008

Some cases of T‐cell acute lymphoblastic leukaemia (ALL) express markers found in natural‐killer (NK) cells, such as CD56 and CD16. Out of 84 T‐cell ALL cases diagnosed at our Institution, CD56 and/or CD16 was detected in 24 (28·5%), which we designated T/NK‐ALL group. Clinical features, laboratory characteristics, survival and expression of cytotoxic molecules were compared in T/NK‐ALL and T‐ALL patients. Significant differences were observed regarding age (24·9 vs. 16·4 years in T/NK‐ALL and T‐ALL, respectively, P = 0·006) and platelet counts (177 × 109/l vs. 75 × 109/l in T/NK‐ALL and T‐ALL, respectively, P = 0·03). Immunophenotypic analysis demonstrated that CD34, CD45RA and CD33 were more expressed in T/NK‐ALL patients, whereas CD8 and terminal deoxynucleotidyl transferase were more expressed in T‐ALL patients (P < 0·05). The mean overall survival (863 vs. 1869 d, P = 0·02) and disease‐free survival (855 vs. 2095 d, P = 0·002) were shorter in patients expressing CD56/CD16. However, multivariate analysis identified CD56/CD16 as an independent prognostic factor only for DFS. Cytotoxic molecules were highly expressed in T/NK‐ALL compared to T‐ALL. Perforin, granzyme B and TIA‐1 were detected in 12/17, 4/17 and 7/24 T/NK‐ALL patients and in 1/20, 0/20 and 1/20 T‐ALL respectively (P < 0·001, P = 0·036 and P = 0·054). Therefore, the presence of CD56/CD16 was associated with distinct clinical features and expression of cytotoxic molecules in the blasts.
An adolescent ward; ‘in name only?’
Authors: Hutton Alison
Published: November 2008

Aims and objectives.  The aim of the study was to explore how an adolescent ward was used by the two main users, nurses and adolescents, on a purpose‐built adolescent ward.

Background.  In Australia, caring for the adolescent is part of paediatric nursing and many Australian hospitals boast of ‘adolescent‐only facilities’. These wards are established on the premise that adolescent patients are a ‘special’ group deserving their own ward space. With the development of adolescent wards, set ideals around what this type of environment provides have also arisen. These ideals are increased privacy and independence for the patient, a chance for peer interaction, to be nursed by specially trained staff and to provide opportunities for adolescent patients to participate in their own care.

Methods.  This study used ethnography to gain a perspective of how ward space was used. Data were collected using participant observation and formal and informal interviews. Data were then analysed using the works of Lefebvre and Foucault.

Results.  This study found that patient allocation, nursing observation and patient labels impact on how adolescent patients are nursed. Patients are expected to fit in, accepting all ministrations of nursing and staff.

Conclusions.  On this ward, nursing work was paramount. Nurses treated the adolescent patient like any other. In saying this, the adolescent patient still found ways to adapt to the ward space and its rules and routines; so in this sense, the ward still worked for them, even if nursing work was paramount.

Relevance to clinical practice.  This study contributes to current discourse on the formation of specialized facilities in general, as it shows that no matter how a ward space is set up, if the space is not used in that way, then the purported purpose of that ward space will be lost.
Parents’ narratives about their experiences of their child's reconstructive genital surgeries for ambiguous genitalia
Authors: Sanders Caroline , Carter Bernie , Goodacre Lynne
Published: November 2008

Aim.  The aim of this study was to initiate an exploration of parents’ understanding and experiences of their child’s reconstructive genital surgeries for ambiguous genitalia.

Background.  The determination of gender for a child born with ambiguous genitalia is a complex medical and social process influenced by biological, psychological, social and cultural factors. Two main approaches exist; one promotes interventions (optimal gender policy) while the other suggests delaying interventions (informed consent policy) until the child can contribute to the decision.

Methods.  An exploratory narrative inquiry design was chosen. Data were collected through narrative interviews with a purposive non‐random sample of 10 parents of eight children (aged 0–11 years) who had ambiguous genitalia.

Results.  Parents’ stories reflected strong protective instincts towards their children along with feelings of shock and disbelief. Parents’ social construction of gender influenced their attitudes and beliefs about their child’s ambiguous genitalia and the need for surgery. Parents’ desired to be ‘good parents’ and do what they perceived as ‘right’ for their child. They considered genital surgery as a necessity primarily relying on medical advice to guide them at times of uncertainty and confusion. Parents rarely shared stories about their child’s surgeries/genitalia outside of the couple relationship and these stories were often referred to as ‘secrets’.

Conclusion.  Having a child with ambiguous genitalia was perceived as problematic and brought about changes in roles, responsibilities, goals and social status as a parent beyond those usually associated with parenthood.

Relevance to clinical practice.  These early findings help increase awareness of parents’ experiences and of the problems and emotional challenges that parents face when their child is born with genital ambiguity.
Who does what? How staff in England and Denmark perceive roles in the coordination of children’s inpatient care: a comparison of questionnaire survey data
Authors: Beringer Antonia J , Fletcher Margaret E
Published: November 2008

Aims and objectives.  To explore and compare staff perceptions of their own and others roles in the coordination of care for children in hospital in Denmark and England.

Background.  The provision of well‐coordinated care is a declared aim of health care providers; however, there is no universally held model for achieving this. Staff have developed ways of coordinating care in response to local conditions creating diversity and inconsistency in practice.

Design.  Survey.

Methods.  A structured self‐administered questionnaire was used to gather perceptions of clinical staff (n = 85) about who should perform a range of specific care coordination activities. The study sites were two Danish and two English hospitals that provided local and regional children’s services. Data were coded and analysis assisted by using Excel spreadsheets.

Results.  In both countries care coordination was perceived to involve many different staff groups. Of these, nurses and doctors were named most frequently as being responsible for coordination activities. There was consensus between countries about who should perform half the activities listed. Where there was not consensus, this was due to more frequent naming of administrative staff in the English sites and more frequent naming of nurses in the Danish sites. Overall, greater clarity about who should perform specific activities was recorded by the Danish staff.

Conclusions.  Staff in England and Denmark hold many shared perceptions in relation to the performance of care coordination activities and their own roles in relation to these. However, the lack of clarity about who should perform specific tasks revealed by the English respondents indicates a greater potential here for omission or duplication of care coordination activities.

Relevance to clinical practice.  Clarification of who should perform specific activities may contribute to improved coordination of care by reducing the opportunity for duplication or omission in the process of care.
Iranian nurses’ preparation for loss: finding a balance in end‐of‐life care
Authors: Boroujeni Ali Zargham , Mohammadi Rakhshandeh , Oskouie Sayede Fatemeh Haghdoost , Sandberg Jonas
Published: November 2008

Aim.  To explore the nurse–patient interaction in terminally ill situations in acute care, focusing on the nurses’ preparation for loss.

Background.  Caring for dying patients can be a distressing and sometimes even threatening experience for nurses. Despite the vast body of literature on nurse/patient interaction and the quality of end‐of‐life care, few studies focus specifically on nurses’ experience.

Design.  A grounded theory approach was used to explore nurses’ interaction with dying patients and their families and examine how nurses deal with situations in which the patient’s death is inevitable.

Method.  Eighteen nurses were interviewed up to three times each at three teaching hospitals in Isfahan, Iran, during autumn 2006. A shortlist of possible participants was obtained by means of theoretical sampling and those who had experienced the death of patients and were able to express their feelings verbally were selected.

Results.  The results clarified a core consideration: striking a balance between restorative and palliative care, information and hope, expectations and abilities and intimacy and distance.

Conclusion.  Attaining a balance in caring for dying patients is a major challenge to nurses: it concerns not only their interactions with patients and their families, but also their perceptions of themselves and their actions in end‐of‐life care.

Relevance to clinical practice.  In end‐of‐life care, it is important for nurses to be able to change the focus of their care when the patient’s condition is diagnosed as irreversible. They also need to be well equipped to maintain a balance, thereby preparing themselves for the patient’s forthcoming death.
Children’s nurses’ research involvement: making practice‐focused research happen
Authors: Darbyshire Philip
Published: November 2008

Aims of the paper.  In this paper I hope to, at least partially, succeed in demystifying the research process, especially as it may be perceived by clinicians, encourage their involvement and participation in clinical research and propose practical and rewarding strategies that all children’s nurses can adopt to begin to create a vibrant research culture in any clinical area.

Background.  The professional and organisational expectation that all nurses will, in some way, be involved in research is growing and will not go away. Despite the historic, toxic dualism that has seen research as essentially the prerogative of ‘The Academy’, clinicians are beginning to take more of an interest and role in research, despite the many obstacles that they face. In today’s health care system, children’s nurses cannot afford to abdicate responsibility for research or to postpone their involvement until the ideal conditions for their engagement come along. This paper suggests approaches and strategies that clinicians, educators, managers and researchers can use as a basis for productive and mutually beneficial collaborative research initiatives.

Design.  Position paper.

Conclusions.  Developing clinical‐focused, collaborative, interdisciplinary research is now a worldwide policy and practice imperative. There is no reason why children’s nurses cannot take a leading role in this movement. Previous models of research where research has been undertaken by academics and then ‘disseminated’ to clinicians who are expected to ‘implement’ it (and who are then subsequently blamed for failure) has been less than successful and small wonder.

Relevance to clinical practice.  Where clinicians are directly involved as genuine research partners in both the research process and the project from day 1, there is a real prospect that both the benefits of the inquiry process and any research findings will be more readily adopted by the clinical areas concerned.
Dealing with chaos and complexity: the reality of interviewing children and families in their own homes
Authors: MacDonald Kath , Greggans Alison
Published: November 2008

Aims.  The aim of this paper is to share our experiences of dealing with chaos and complexity in interview situations in the home with children and young people. We highlight dilemmas relevant to dealing with multiple interruptions, building a rapport, consent and confidentiality. Furthermore, we discuss issues regarding the locus of power and control and offer some solutions based on our experiences.

Background.  Creating a safe environment is essential for qualitative research. Participants are more likely to open up and communicate if they feel safe, comfortable and relaxed. We conclude that interviewing parents and their children with cystic fibrosis in their own homes, is chaotic and appears to threaten the rigour of data collection processes. Limited attention or print space is paid to this issue, with published articles frequently sanitising the messiness of real world qualitative research.

Design.  Position paper.

Methods.  In this position paper, we use two case studies to illustrate ethical and pragmatic challenges of interviewing out in the field. These case studies, typical of families we encountered, help emphasise the concerns we had in balancing researcher–participant rapport with the quality of the research process.

Conclusions.  Dealing with perceived chaos is hard in reality, but capturing it is part of the complexity of qualitative enquiry. The context is interdependent with children’s perceived reality, because they communicate with others through their environment.

Relevance to practice.  This paper gives researchers an insight into the tensions of operating out in the field and helps raise the importance of the environmental ‘chaos’ in revealing significant issues relevant to peoples daily lives. Knowing that unexpected chaos is part and parcel of qualitative research, will equip researchers with skills fundamental for balancing the well being of all those involved with the quality of the research process.
Parental presence during resuscitation in the PICU: the parents’ experience
Authors: Maxton Fiona JC
Published: November 2008

Aim and objective.  To provide in‐depth understanding of the meaning for parents who were present or absent during a resuscitation attempt on their child in the PICU.

Background.  Family presence during resuscitation remains a topic of debate with both benefits and disadvantages identified, yet few studies have asked parents of children in PICU to describe their experiences of being present or absent during this resuscitation and what this means to their understanding and coping. Additionally, minimal research has investigated parental presence during a successful resuscitation.

Design.  A qualitative design was used based upon van Manen’s interpretative phenomenological approach.

Methods.  Fourteen parents of critically ill children from one paediatric intensive care unit in Australia, who had either survived or died following a resuscitation attempt were interviewed.

Results.  Four main themes were identified: (1) being only for a child; (2) making sense of a living nightmare; (3) maintaining hope in the face of reality; (4) living in a relationship with staff.

Conclusions.  The findings underpin the inherent need for parents to choose to be present during resuscitation to make sense of the situation. Memories of the resuscitation were not long‐lasting and distress was for the potential death of a child, rather than the resuscitation scene. Parents who did not witness their child’s resuscitation were more distressed than those who did. Having the opportunity to make the decision to stay or leave was important for parents. Support during the resuscitation was best provided by experienced clinical nurses.

Relevance to practice.  Recognition of the parents’ compelling need to stay will improve nurses’ understanding of how witnessing this event may assist family coping and functioning. Ways in which parents may be better supported in making the decision to stay or leave during resuscitation are identified.
The experience of living with a chronic illness during adolescence: a critical review of the literature
Authors: Taylor Rachel M , Gibson Faith , Franck Linda S
Published: November 2008

Aims.  To identify and critique literature on the adolescent lived experience of chronic illness; describe the lived experience; and to make recommendations for clinical practice.

Background.  Young people with chronic illness have the same developmental issues as those who are healthy. However, development can be disrupted by treatment and repeated hospitalisation. While the physical consequences of chronic illness on development have been established, the subjective personal experience is less known.

Design.  Literature review.

Methods.  Electronic databases and hand searches were made of the literature published between January 1990–September 2007. Literature was eligible for inclusion if it involved adolescents between 10–19 years, and published in English and used qualitative methods of data collection. Methodological quality was assessed using the criteria described by Cesario et al. [Journal of Obstetrics, Gynaecology and Neonatal Nursing 31 (2002) 31].

Conclusions.  Twenty studies were identified involving young people with a wide variety of chronic illnesses. The study quality was variable, however, generally the majority was assessed as being good or fair. Seven common themes were found between the identified studies: developing and maintaining friendships; being normal/getting on with life; the importance of family; attitude to treatment; experiences of school; relationship with the healthcare professionals; and the future.

Relevance to practice.  As there was commonality in themes between studies strategies to lessen the burden of chronic illness during adolescence do not necessarily need to be disease specific. Nurses need to focus on treating the young person rather than their illness.
Evaluating the impact of involving young people in developing children’s services in an acute hospital trust
Authors: Coad Jane , Flay Julia , Aspinall Mandy , Bilverstone Ben , Coxhead Elodie , Hones Becky
Published: November 2008

Aims and objectives.  The aim of this paper is to reflect on how an acute hospital trust involved a youth council comprising 17 young people aged 11–18 years to improve children’s service delivery in one NHS trust in the UK.

Background.  Over the last decade, there has been an increased emphasis on the active involvement and participation of children and young people in the decision‐making processes that affect them. However, one challenge in involving users in acute hospital trusts is how their views are used to develop services. For this reason, University Hospitals Coventry and Warwickshire NHS Trust, UK (University Hospitals Coventry and Warwickshire NHS Trust have given permission to have their name cited in the publication of this article) recognising the emerging national patient and public involvement agenda, planned and developed a youth council for the Trust in 2006.

Process.  The process of setting up the youth council is outlined. An evaluation workshop took place with 15 members of the youth council and their views are incorporated around three specific areas:

• Evidence that their involvement has improved trust services;

• Barriers to young people’s voices being heard in service delivery;

• What could promote young people’s involvement in healthcare services.

Conclusion/Relevance to clinical practice.  This paper describes the setting up of a youth council but also discusses the potential barriers and how to overcome them to promote young people’s involvement in hospital trust service planning and development. Whilst the focus of the council was young people, the principles are of use to a wide range of clinical professionals faced with similar challenges.
Solving nursing shortages: a common priority
Authors: Buchan James , Aiken Linda
Published: November 2008

Aims and objectives.  This paper provides a context for this special edition. It highlights the scale of the challenge of nursing shortages, but also makes the point that there is a policy agenda that provides workable solutions.

Results.  An overview of nurse:population ratios in different countries and regions of the world, highlighting considerable variations, with Africa and South East Asia having the lowest average ratios. The paper argues that the ‘shortage’ of nurses is not necessarily a shortage of individuals with nursing qualifications, it is a shortage of nurses willing to work in the present conditions. The causes of shortages are multi‐faceted, and there is no single global measure of their extent and nature, there is growing evidence of the impact of relatively low staffing levels on health care delivery and outcomes. The main causes of nursing shortages are highlighted: inadequate workforce planning and allocation mechanisms, resource constrained undersupply of new staff, poor recruitment, retention and ‘return’ policies, and ineffective use of available nursing resources through inappropriate skill mix and utilisation, poor incentive structures and inadequate career support.

Conclusions.  What now faces policy makers in Japan, Europe and other developed countries is a policy agenda with a core of common themes. First, themes related to addressing supply side issues: getting, keeping and keeping in touch with relatively scarce nurses. Second, themes related to dealing with demand side challenges. The paper concludes that the main challenge for policy makers is to develop a co‐ordinated package of policies that provide a long term and sustainable solution.

Relevance to clinical practice.  This paper highlights the impact that nursing shortages has on clinical practice and in health service delivery. It outlines scope for addressing shortage problems and therefore for providing a more positive staffing environment in which clinical practice can be delivered.
Poor work environments and nurse inexperience are associated with burnout, job dissatisfaction and quality deficits in Japanese hospitals
Authors: Kanai‐Pak Masako , Aiken Linda H , Sloane Douglas M , Poghosyan Lusine
Published: November 2008

Aims.  To describe nurse burnout, job dissatisfaction and quality of care in Japanese hospitals and to determine how these outcomes are associated with work environment factors.

Background.  Nurse burnout and job dissatisfaction are associated with poor nurse retention and uneven quality of care in other countries but comprehensive data have been lacking on Japan.

Design.  Cross‐sectional survey of 5956 staff nurses on 302 units in 19 acute hospitals in Japan.

Methods.  Nurses were provided information about years of experience, completed the Maslach Burnout Inventory and reported on resource adequacy and working relations with doctors using the Nursing Work Index‐Revised.

Results.  Fifty‐six per cent of nurses scored high on burnout, 60% were dissatisfied with their jobs and 59% ranked quality of care as only fair or poor. About one‐third had fewer than four years of experience and more than two‐thirds had less than 10. Only one in five nurses reported there were enough registered nurses to provide quality care and more than half reported that teamwork between nurses and physicians was lacking. The odds on high burnout, job dissatisfaction and poor–fair quality of care were twice as high in hospitals with 50% inexperienced nurses than with 20% inexperienced nurses and 40% higher in hospitals where nurses had less satisfactory relations with physicians. Nurses in poorly staffed hospitals were 50% more likely to exhibit burnout, twice as likely to be dissatisfied and 75% more likely to report poor or fair quality care than nurses in better staffed hospitals.

Conclusions.  Improved nurse staffing and working relationships with physicians may reduce nurse burnout, job dissatisfaction and low nurse‐assessed quality of care.

Relevance to clinical practice.  Staff nurses should engage supervisors and medical staff in discussions about retaining more experienced nurses at the bedside, implementing strategies to enhance clinical staffing and identifying ways to improve nurse‐physician working relations.
Challenges in getting workforce research in nursing used for decision‐making in policy and practice: a Canadian perspective
Authors: O’Brien‐Pallas Linda , Hayes Laureen
Published: November 2008

Aims and objectives.  This paper draws upon empirical research and other published sources to discuss nursing workforce issues, the challenges of using health human resource research in policy decisions and the importance of evidence‐based policies and practices for nursing care and outcomes.

Background.  Increasing evidence points to the critical relationship between registered nurse care and improved patient outcomes. The negative impact that insufficient nurse staffing has on patient, nursing and system outcomes has influenced health human resource researchers to further examine nurses’ work environments to determine factors that are amenable to policy change.

Design.  Survey of literature was conducted.

Methods.  Electronic databases were searched using keywords.

Results.  Sustained health human resource planning efforts by policy makers are difficult given changing governments and political agendas. The health human resource conceptual framework provides researchers and planners with a guide to decision‐making that considers current circumstances as well as those factors that need to be accounted for in predicting future requirements. However, effective use of research depends on communication of findings between researchers and policymakers.

Conclusions.  Health care managers and other decision‐makers in health care organisations often lack an understanding of the research process and do not always have easy access to current evidence. Also, managerial decisions are often constrained by organisational requirements such as resource availability and policies and procedures.

Relevance to clinical practice.  Unless nursing workplace issues are addressed, the physiological and psychological stress in the work environments of nurses will continue. Effective health human resource policy and planning (at the macro level) and management strategies (at the micro level) would stabilise the nursing workforce and reduce job stress. Furthermore, the efficiency and cost‐effectiveness of the health system could be enhanced through improved health outcomes of care providers and health care clients.
A cryptic invasion within an invasion and widespread introgression in the European water frog complex: consequences of uncontrolled commercial trade and weak international legislation
Authors: HOLSBEEK G. , MERGEAY J. , HOTZ H. , PLÖTNER J. , VOLCKAERT F. A. M. , DE MEESTER L.
Published: November 2008

In Western Europe, many pond owners introduce amphibians for ornamental purposes. Although indigenous amphibians are legally protected in most European countries, retailers are circumventing national and international legislation by selling exotic nonprotected sibling species. We investigated to what extent non‐native species of the European water frog complex (genus Pelophylax) have become established in Belgium, using morphological, mitochondrial and nuclear genetic markers. A survey of 87 sampling sites showed the presence of non‐native water frogs at 47 locations, mostly Marsh frogs (Pelophylax ridibundus). Surprisingly, at least 19% of all these locations also harboured individuals with mitochondrial haplotypes characteristic of Anatolian water frogs (Pelophylax cf. bedriagae). Nuclear genotyping indicated widespread hybridization and introgression between P. ridibundus and P. cf. bedriagae. In addition, water frogs of Turkish origin obtained through a licensed retailer, also contained P. ridibundus and P. cf. bedriagae, with identical haplotypes to the wild Belgian populations. Although P. ridibundus might have invaded Belgium by natural range expansion from neighbouring countries, our results suggest that its invasion was at least partly enhanced by commercial trade, with origins as far as the Middle East. Also the invasion and rapid spread of Anatolian lineages, masked by their high morphological similarity to P. ridibundus, is likely the result of unregulated commercial trade. We expect that Anatolian frogs will further invade the exotic as well as the native range of P. ridibundus and other Pelophylax species elsewhere in Western and Central Europe, with risks of large‐scale hybridization and introgression.
Across the southern Andes on fin: glacial refugia, drainage reversals and a secondary contact zone revealed by the phylogeographical signal of Galaxias platei in Patagonia
Authors: ZEMLAK TYLER S. , HABIT EVELYN M. , WALDE SANDRA J. , BATTINI MIGUEL A. , ADAMS EMILY D. M. , RUZZANTE DANIEL E.
Published: November 2008

We employed DNA sequence variation at two mitochondrial (control region, COI) regions from 212 individuals of Galaxias platei (Pisces, Galaxiidae) collected throughout Patagonia (25 lakes/rivers) to examine how Andean orogeny and the climatic cycles throughout the Quaternary affected the genetic diversity and phylogeography of this species. Phylogenetic analyses revealed four deep genealogical lineages which likely represent the initial division of G. platei into eastern and western lineages by Andean uplift, followed by further subdivision of each lineage into separate glacial refugia by repeated Pleistocene glacial cycles. West of the Andes, refugia were likely restricted to the northern region of Patagonia with small relicts in the south, whereas eastern refugia appear to have been much larger and widespread, consisting of separate northern and southern regions that collectively spanned most of Argentinean Patagonia. The retreat of glacial ice following the last glacial maximum allowed re‐colonization of central Chile from nonlocal refugia from the north and east, representing a region of secondary contact between all four glacial lineages. Northwestern glacial relicts likely followed pro‐glacial lakes into central Chilean Patagonia, whereas catastrophic changes in drainage direction (Atlantic → Pacific) for several eastern palaeolakes were the likely avenues for invasions from the east. These mechanisms, combined with evidence for recent, rapid and widespread population growth could explain the extensive contemporary distribution of G. platei throughout Patagonia.
Descriptive epidemiology of congenital heart disease in Northern England
Authors: Dadvand Payam , Rankin Judith , Shirley Mark D. F. , Rushton Stephen , Pless‐Mulloli Tanja
Published: November 2008

Congenital heart disease (CHD) is the most prevalent group of congenital anomalies. There is considerable variation in the reported epidemiology of CHD, mainly attributable to methodological differences. Using register‐based data, the current study describes the epidemiology of CHD in a geographically well‐defined population of the North of England during 1985–2003.

The total prevalence of CHD was 85.9 per 10 000 births and terminations of pregnancy for fetal anomaly. Livebirth prevalence was 79.7 per 10 000 livebirths. Both total and livebirth prevalence increased during the study period. Ninety‐two per cent of affected pregnancies resulted in a livebirth, 5% were terminated, 2% resulted in a stillbirth, and 1% in a late miscarriage. Almost a quarter (23%) of cases had one or more coincident anomalies of other organs, with chromosomal abnormalities the most frequent group. A total of 89.2% of cases survived to 1 year and the survival improved during the study period. This population‐based study has demonstrated an increasing trend in both prevalence and survival among children with CHD.
Changing roles and responses of health care workers in HIV treatment and care
Authors: Rajaraman Divya , Palmer Natasha
Published: November 2008

A key limiting factor in the scale up and sustainability of HIV care and treatment programmes is the global shortage of trained health care workers. This paper discusses why it is important to move beyond conceptualising health care workers simply as ‘inputs’ in the delivery of HIV treatment and care, and to also consider their roles as partners and agents in the process of health care. It suggests a framework for thinking about their roles and responses in HIV care, considers the current evidence base, and concludes by identifying key areas for future research on health care workers’ responses in HIV treatment and care in low and middle income settings.
The safety of sublingual immunotherapy with one or multiple pollen allergens in children
Authors: Agostinis F. , Foglia C. , Landi M. , Cottini M. , Lombardi C. , Canonica G. W. , Passalacqua G.
Published: November 2008

Background:  Since the majority of allergic patients are polysensitized, it is often necessary to prescribe immunotherapy with multiple allergens. It is crucial to know if the administration of multiple allergens with sublingual immunotherapy (SLIT) increases the risk of side‐effects in children.

Methods:  Consecutive children with respiratory allergy because of pollens, receiving SLIT for multiple or single allergens were followed‐up in a postmarketing survey. Inclusion criteria were those for prescribing SLIT according to guidelines. Parents recorded in a diary card the side‐effects (eye symptoms, rhinitis/ear itching, asthma, oral itching/swelling, nausea, vomiting, abdominal pain, diarrhoea, urticaria, angioedema and anaphylaxis). The side‐effects were graded as mild, moderate and severe.

Results:  Four hundred and thirty‐three children (285 male, age range 3–18 years) receiving SLIT were surveyed. Of them, 179 received a single extract, and 254 multiple allergens. The total number of doses given was 40 169 (17 143 with single allergen). Overall, 178 episodes were reported. Of them, 76 occurred with the single allergen (42.46% patients, 4.43/1000 doses) and 102 (40.3% patients, 4.42/1000 doses) with multiple allergens (P = NS). 165 episodes (92.5%) were mild and self‐resolving and were equally distributed in the two groups. In 13 cases, the events were judged of moderate severity and medical advice was required. Three patients discontinued SLIT, despite the local side‐effects being mild. No emergency treatment was required at all.

Conclusion:  The use of multiple allergens for SLIT does not increase the rate of side‐effects in children.
Effects of cucumber mosaic virus infection on electron transport and antioxidant system in chloroplasts and mitochondria of cucumber and tomato leaves
Authors: Song Xing‐Shun , Wang Yan‐Jie , Mao Wei‐Hua , Shi Kai , Zhou Yan‐Hong , Nogués Salvador , Yu Jing‐Quan
Published: November 2008

We examined the responses of the photosynthetic and respiratory electron transport and antioxidant systems in cell organelles of cucumber (Cucumis sativus L.) and tomato (Lycopersicon esculentum Mill.) leaves to infection of cucumber mosaic virus (CMV) by comparing the gas exchange, Chl fluorescence, respiratory electron transport, superoxide dismutase (SOD, EC 1.15.1.1) and ascorbate–glutathione (AsA–GSH) cycle enzymes and the production of H2O2 in chloroplasts, mitochondria and soluble fraction in virus‐infected and non‐infected leaves. Long‐term CMV infection resulted in decreased photosynthesis and respiration rates. Photosynthetic electron flux to carbon reduction, respiratory electron transport via both complex I and complex II and also the Cyt respiration rate all significantly decreased, while photosynthetic alternative electron flux and alternative respiration significantly increased. These changes in electron transport were accompanied by a general increase in the activities of SOD/AsA–GSH cycle enzymes followed by an increased H2O2 accumulation in chloroplasts and mitochondria. These results demonstrated that disturbance of photosynthetic and respiratory electron transport by CMV also affected the antioxidative systems, thereby leading to oxidative stress in various organelles.
Newer immunosuppressive drugs in concordant xenografting—Transplantation of hamster heart to rat
Authors: Kemp E. , Dieperink H. , Jensen J. , Kemp G. , Kuhlmann I.‐L , Larsen S. , Lilievang S.T. , Nielsen B. , Salomon S. , Steinbrüchel D. , Svendsen M. , Thomsen F. Nielsen
Published: November 2008

Abstract: Recently several promising new immunosuppressive drugs have appeared. In hamster heart to rat transplantation—a commonly used concordant xenograft model—we have investigated the effect of cyclophosphamide, cyclosporine, rapamycin, FK‐506, and leflunomide. When four drugs were given as therapy in combination, we found almost normal morphology of the graft, but over‐immunosuppression was a problem. Leflunomide as a single drug was superior to the other agents. When used in combination leflunomide and cyclosporine offered the best protection of all combinations in our trials, with a mean survival of about 3 months. Further, splenectomy of leflunomide treated xenograft recipients further prolonged graft acceptance. Additional treatment with donor cells from spleen, thymus, and bone marrow did not influence the survival time of the transplanted heart and tolerance was not obtained in any of our studies. The future seems to be a drug combination therapy with decreased side effects due to immunosuppression.
Is the Galα(1,3)Gal epitope a major target for human xenoantibodies on pig fetal islet cells?
Authors: Rydberg Lennart , Groth Carl‐Gustav , Möller Erna , Tibell Annika , Samuelsson Bo E.
Published: November 2008

Abstract: The immune antibodies produced in diabetic patients by the challenge of the immune system with pig fetal islet‐like cell clusters were analyzed in regard to carbohydrate specificity. Binding of antibodies to total non‐acid glycosphingolipid fractions from pig aorta and pig erythrocytes was tested in a radioimmunoassay using native serum, serum adsorbed on solid phase columns with either Galα(1,3)Gal specificity or Galα(1,4)Gal specificity. The eluates from the columns were also tested. Adsorption on the Galα(1,3)Gal column completely eliminated binding both to aortic and erythrocytic fractions, while adsorption on the Galα(1,4)Gal column reduced the binding but did not eliminate it. This can be explained by the presence of at least two kinds of antibodies, one recognizing terminal α‐linked galactose and the other recognizing the Galα(1,3)Gal epitope, thus requiring a disaccharide for binding. A total non‐acid glycolipid fraction was prepared from porcine fetal islet‐like cell clusters and tested against immune serum from a patient transplanted with such cells. Binding was only found to the pentaglycosylceramide region with an identical retention time as the “linear B” antigen for pig aorta. This indicates the presence of that structure also in porcine fetal islet‐like cell clusters.
Tissue culture prevents hyperacute rejection of islet xenografts
Authors: Gray D.W.R. , Song Z. , Glover L. , Welsh K.I. , Morris P.J.
Published: November 2008

Abstract: Despite some notable successes in recent years, it has become clear that the use of human islets of the purpose of curing diabetes by isle transplantation is not a practical solution for the treatment of the large number of diabetic patients who could potentially benefit from such a procedure. The major reason for this conclusion is that the yield of islets obtainable from the average human pancreas is relatively low, and the numbers of suitable human cadaveric donors are few. By using islets obtained from the pancreas of an ethically acceptable nonhuman donor such as the pig, it should be easily possible to obtain sufficient islet tissue to transplant as many patients as necessary, but the problems of tissue availability are replaced by those of xenograft rejection.
Neonatal pig pancreata as a source of insulin‐producing tissue for xenotransplantation
Authors: Korbutt Gregory S. , Ao Ziliang , Warnock Garth L. , Rajotte Ray V.
Published: November 2008

Abstract: Islet transplantation has been proven as a viable option for treating type 1 diabetics; however, widespread clinical application of this technique will necessitate an alternative source of insulin‐producing tissue. Porcine pancreata may be a potential source of islets, but adult porcine islets are difficult to isolate, are fragile, and have a tendency to fall apart during culture. In this study, we investigated the feasibility of preparing functionally viable islet cells in large quantities from the neonatal pig pancreas. Following collagenase digestion and 7 days of tissue culture, a mean of 48,000 neonatal islet cell (NIC) aggregates were recovered per pancreas. These NICs were responsive to glucose in vitro and were capable of correcting hyperglycemia in alloxan‐induced diabetic nude mice. These results indicate that the neonatal porcine pancreas can be used to produce large numbers of functionally viable islet cells.
Studies of the isolation, viability, and preservation of purified islets after surgical pancreatectomy in large pigs
Authors: Warnock Garth L. , Katyal Deepak , Okamura James , Lakey Jonathan R.T. , Rajotte Ray V.
Published: November 2008

Abstract: Previous studies have shown separation of mass quantities of islets from slaughterhouse pig pancreases. In these studies, we examined the isolation, viability, and preservation of pig islets obtained by surgical pancreatectomy. Pigs aged 6 to 30 months weighing 100 to 200 kg were subjected to laparotomy under general anesthesia. The splenic lobe of pancreas was mobilized without warm ischemia. Islets were immediately isolated by collagenase perfusion through the duct, automated dissociation, and Ficoll purification. Yields of islets (150 μm size) were 8500 to 9300/g for two different collagenases before purification. Purification yielded 90% pure islets, but yields decreased to 400 to 600/g. Perifusate insulin release was biphasic after glucose/theophylline with 3 to 5‐fold stimulation. Following culture/cryopreservation marked islet losses occurred but viability was preserved. Quantities of 1,500 islet equivalents resulted in euglycemia in nude mice. These data show that mass quantities of viable islets can be isolated after pancreatectomy, but there is marked islet loss during purification and subsequent preservation due to inherent islet fragility.
Histomorphological characteristics of the porcine pancreas as a basis for the isolation of islets of Langerhans
Authors: Ulrichs Karin , Bosss Matthias , Heiser Axel , Eckstein Volker , Wacker Hans‐Heinrich , Thiede Arnulf , Muller‐Ruchhoitz Wolfgang
Published: November 2008

Abstract: Isolation of porcine islets of Langerhans for future clinical xenotransplantation in type I diabetic patients is limited by the difficulty to isolate sufficiently functioning islets and by their particular fragility. Seven domestic pig races and the wild boar were investigated histologically to obtain detailed information on islet profiles, numbers, sizes, and volume density of the endocrine tissue. Theoretically calculated islet numbers were correlated with those obtained after islet isolation. Results: 1) Porcine islets are round, oval, dumbbell‐like and triangular, and, as expected, occur in all intermediate profiles. Round and oval islets predominate. These profiles are also detected in crude islet preparations, which indicates that they can withstand the enzymatic digestion process. 2) The total number of islets varies greatly in all eight pig races, with, e.g., the wild boar showing twice as many islets (approx. 500/cm2 tissue section) as the minipig (approx. 250/ cm2). 3) The tail of the pancreas, which is usually used for islet isolation, accounts for about 50% of the pancreas mass. 4) The majority of islets, 64.3% (range 59.8–68.9%), of the seven domestic races are 50–100 μm in diameter. With its 86% the wild boar is a remarkable exception. German landrace pigs show the greatest number (2%) of large islets (250 to >300 μm. 5) With 3.4%, German landrace pigs reveal the greatest islet volume density of all pig races (range 2.6–4.2%). 6) Only 25% of all islets are surrounded by a collagen “capsule” that covers >75% of the islet surface. Roughly 33% of all islets are “capsulated” by collagen type I, III, and IV fibers to an extent of <25%. 7) In young pure bred pigs (7–12 month old) only 3.0–10.6% of all theoretically available islets can be isolated during the enzymatic digestion. However, much better islet yields (30.1%) can be obtained from adult hybrid pigs (3 years old) much better islet yields (30.1%) can be obtained than from young hybrid pigs (7.6%). It may be concluded from our results that histological parameters‐besides those already known (pH of the isolation medium, trypsin inhibition by Pefabloc‐may have a greater influence on porcine pancreatic islet isolation than was assumed so far.