bluuebunny/crossref_metadata_2025 huggingface dataset:
The origin and evolution of Indomalesian, Australasian and Pacific island biotas: insights from Aglaieae (Meliaceae, Sapindales)
Authors: Muellner Alexandra N. , Pannell Caroline M. , Coleman Annette , Chase Mark W.
Published: July 2008

Aim  The role of long‐distance dispersal in the Indomalesian, Australasian and Pacific flora is currently hotly debated. The lack of well‐resolved phylogenetic trees for Pacific plants has been a major limitation for biogeographical analysis. Here, we present a well‐resolved phylogenetic tree for the tribe Aglaieae in the mahogany family, Meliaceae, and use it to investigate the origin, evolution and dispersal history of biotas in this area. The subfamily Melioideae, including the tribe Aglaieae (Meliaceae, Sapindales), is a plant group with good representation in the region in terms of biomass and species numbers, wide ecological attributes and known animal vectors. The family has a good fossil record (especially from North America and Europe). Genera and species in the tribe Aglaieae therefore provide an excellent model group for addressing this debate.

Location  Indomalesia, Australasia, Pacific islands.

Methods  Results from nuclear internal transcribed spacer ribosomal DNA analyses of 82 taxa, based on sequence alignment guided by secondary structure models, were combined with evidence from fossils and distribution data. We used strict and relaxed molecular clock approaches to estimate divergence times within Aglaieae. Putative ancestral areas were investigated through area‐based and event‐based biogeographical approaches. Information on dispersal routes and their direction was inferred from the investigation of dispersal asymmetries between areas.

Results  Our study indicates that the crown group of Aglaieae dates back at least to the Late Eocene, with major divergence events occurring during the Oligocene and Miocene. It also suggests that dispersal routes existed during Miocene–Pliocene times from the area including Peninsular Malaysia, Sumatra and Borneo to Wallacea, India and Indochina, and from the area including New Guinea, New Ireland and New Britain further east to the Pacific islands at the peripheries of the distribution range. The origin of the Fijian species dates back to the Pliocene.

Main conclusions  Dispersal over oceanic water barriers has occurred during geological time and seems to have been a major driving force for divergence events in Aglaieae, with some old Gondwanan land masses (e.g. Australia) colonized only during recent times. Movement from the ancestral area was predominantly towards the east. Extant Fijian species of Aglaia are monophyletic and share morphological features rarely found in species of other areas, suggesting speciation within an endemic clade. Divergence of living taxa from their closest living relatives took place during both the Miocene and the Pliocene, and peaked in the Pliocene. The present‐day distribution of many species in the tribe must therefore have arisen as a result of dispersal rather than vicariance events. Furthermore, colonization from Indomalesia to Australasia and the Pacific has frequently been followed by speciation.
What clinical characteristics of children with autism influence their inclusion in regular classrooms?
Authors: Yianni‐Coudurier C. , Darrou C. , Lenoir P. , Verrecchia B. , Assouline B. , Ledesert B. , Michelon C. , Pry R. , Aussilloux C. , Baghdadli A.
Published: July 2008

Background  This study took place in the context of recent legislation enacted in several countries – including France – and aimed at promoting inclusion of children with intellectual disabilities. It focuses on young children with autism and examines the links between the children's characteristics and their weekly hours of regular‐classroom inclusion and intervention in specialised setting.

Method  Standardised clinical and sociodemographic data were collected for 77 children with autism, along with data about their interventional programmes.

Results  The study showed that the number of hours of inclusion at school was influenced by the children's behavioural and adaptive characteristics, as well as by the socioprofessional category of their parents, although these factors did not affect the number of hours spent in specialised setting. Moreover, the total amount of time per week spent in interventional services of any kind was very small for some of the children.

Conclusion  The time spent in special‐intervention services and regular classrooms combined did not add up to an adequate number of weekly hours for these children, particularly those exhibiting at least one of the following characteristics: low adaptation level, major behavioural problems or low socioprofessional category of parents.
The combined effect of albuminuria and inflammation on all‐cause and cardiovascular mortality in nondiabetic persons
Authors: Jørgensen L. , Jenssen T. , Heuch I. , Jacobsen B. K.
Published: July 2008

Objectives and design.  Recent studies have shown that albuminuria accompanied by evidence of subclinical inflammation is more strongly associated with metabolic abnormalities and the development of atherosclerosis than albuminuria alone. The aim of this population‐based prospective study was to examine the combined effect of albuminuria and inflammatory markers on all‐cause and cardiovascular‐mortality in nondiabetic individuals without macroalbuminuria.

Subjects and methods.  Urinary albumin and creatinine, some inflammatory markers (fibrinogen, white blood cell and monocyte count) and cardiovascular risk factors were measured in 5702 persons in Tromsø, Norway. Baseline data were collected in 1994–1995 and follow‐up was through 2005.

Results.  For a one standard deviation higher value of the log‐transformed ratio between albumin and creatinine (ACR), the mortality rate ratio for all‐cause mortality was 1.21 when adjusted for age, gender, established cardiovascular risk factors as well as fibrinogen and white blood cell count (P < 0.001). The corresponding mortality rate ratio for cardiovascular mortality was 1.24 (P < 0.001). Persons in the upper quartile of both ACR and either of the inflammatory markers had an age‐ and gender‐adjusted all‐cause and cardiovascular mortality rate that was four times that of subjects in the lowest quartiles (P < 0.001).

Conclusion.  ACR predicts all‐cause and cardiovascular mortality in persons without known diabetes and macroalbuminuria. The mortality is especially high amongst individuals with elevated levels of both ACR and inflammatory markers.
Endocannabinoids and the Neurochemistry of Gluttony
Authors: Kirkham Tim
Published: July 2008

Cannabis exerts its actions by mimicking ‘endocannabinoid’ neuromodulators at CB1 receptors in brain and peripheral tissues. The endocannabinoids both stimulate appetite by increasing food craving and enjoyment and promote the deposition of energy as fat in adipose tissues. These findings have raised the possibility of CB1 antagonists as a novel class of anti‐obesity agents.
The compatibility of psychosocial interventions (PSI) and assertive outreach: a survey of managers and PSI‐trained staff working in UK assertive outreach teams
Authors: GRIFFITHS R. , HARRIS N.
Published: July 2008

In recent years, there has been an increased emphasis on providing psychosocial interventions (PSI) and assertive outreach (AO) for people with severe and enduring mental illness living in the UK. This paper presents the findings of a telephone survey conducted with managers and PSI‐trained staff working for AO teams in the Northwest of England. The aim of the study was to gain an insight into staff attitudes regarding the compatibility of PSI and AO. The survey also gathered more general information about the nature of the AO teams and the number of PSI‐trained staff working within them. The results indicate that, although PSI‐trained staff believe that PSI and AO are compatible, AO is not immune to the barriers to PSI implementation that exist in other service areas. There also appears to be a question regarding the extent to which teams are maintaining fidelity to the original AO model that was outlined by Stein and Test.
Dermatophagoides farinae‐specific IgG responses in atopic dogs undergoing allergen‐specific immunotherapy with aqueous vaccines
Authors: Hou Chia‐Chun , Griffin Craig E. , Hill Peter B.
Published: July 2008

The molecular and immunologic mechanisms associated with successful allergen‐specific immunotherapy (ASIT) have not been completely elucidated. The aim of this study was to characterize the changes in Dermatophagoides farinae‐specific IgG in atopic dogs undergoing ASIT using aqueous vaccines. Fifteen atopic dogs with a positive skin test reaction to D. farinae were treated with aqueous vaccines for a minimum of 2 months following a standard protocol. Serum samples were collected before and during therapy and used to probe Western blots containing separated proteins of D. farinae. IgG responses were detected using a polyclonal goat anticanine IgG antibody and a chromogenic substrate 3,3′‐diaminobenzidine. The blots were analysed using a semiquantitative digital image analysis system that evaluated the number and molecular weight of bands, as well as their intensity, which was related to IgG concentration. Prior to ASIT, all dogs showed allergen‐specific IgG responses to various antigens of D. farinae. During ASIT, there was a significant increase in the total quantity of D. farinae‐specific IgG antibodies to various antigens from the mite (P = 0.015). Significant increases were observed for a 98‐kDa band (P = 0.015), likely to be Der f 15; bands with molecular weights between 50 and 70 kDa (P = 0.012); and bands between 30 and 45 kDa (P = 0.035). These findings provide support for the hypothesis that ASIT induces IgG blocking antibodies to allergens known to be relevant in canine atopic dermatitis.
Preoperative pulmonary assessment of children for liver transplantation
Authors: Alves Luciane , Sant’Anna Clemax Couto , March Maria de Fátima B. P. , Ferreira Sidnei , Marsillac Marise , Tura Mônica , Oñate Hermes
Published: July 2008

Abstract:  Pulmonary assessment should be part of the preoperative investigation of pediatric patients with chronic liver disease undergoing liver transplantation, as it allows the identification of pulmonary alterations that influence candidacy for transplantation and survival. To describe pulmonary changes found in pediatric patients who were candidates for liver transplantation. Retrospective study of 17 pediatric liver transplant candidates undergoing preoperative pulmonary evaluation assessing pulmonary clinical data, arterial blood gas analysis, CXR, respiratory function test by spirometry, pulmonary scintigraphy, and CEE. Ten patients presented normal chest roentgenograms. The most common radiographic change was interstitial infiltrate in the lung bases. Of the five patients with PaO2 <70 mmHg, four had cyanosis and dyspnea and two were diagnosed with HPS with intrapulmonary shunt evidenced by contrast echocardiogram. Two patients presented with intrapulmonary shunt but without hypoxemia. Spirometry was normal in six patients, restrictive disturbance was evidenced in one patient, obstructive in three, and combined in two. The most common scintigraphic change was heterogeneous pulmonary perfusion. Pulmonary assessment should be performed routinely in pediatric patients prior to liver transplantation, even in asymptomatic patients. Pulmonary assessment may indicate changes such as HPS that can increase postoperative morbidity/mortality.
Chronic active Epstein–Barr virus infection with mosquito allergy successfully treated with reduced‐intensity unrelated allogeneic bone marrow transplantation in a boy
Authors: Matsunaga Takayuki , Kurosawa Hidemitsu , Okuya Mayuko , Nakajima Daisuke , Hagisawa Susumu , Sato Yuya , Fukushima Keitaro , Sugita Kenichi , Arisaka Osamu
Published: July 2008

Abstract:  EBV‐infected T‐/NK cells play an important role in the pathogenesis of mosquito allergy, and the prognosis of most patients with mosquito allergy is poor without proper treatment. We describe a 13‐yr‐old boy who had CAEBV with mosquito allergy and was successfully treated with BMT from an unrelated donor after reduced‐intensity preconditioning. Because combination chemotherapy failed to achieve CR, we performed unrelated BMT to reconstitute normal immunity and eradicate any residual EBV‐infected cells. To reduce complications after BMT, we selected a reduced‐intensity preconditioning regimen consisting of fludarabine, l‐phenylalanine mustard, and antithymocyte Ig instead of a conventional myeloablative preconditioning. Although grade II acute GVHD developed, it was successfully controlled with immunosuppressive therapy. After 27 months, the patient has been well without any signs of CAEBV, and the EBV DNA has been undetectable with real‐time PCR analysis. We conclude that RIST from the bone marrow of an unrelated donor is indicated for some patients who have CAEBV that is refractory to chemotherapy and who have no HLA‐matched related donors or cord blood as a source of stem cells.
Real‐time PCR on the first galactomannan‐positive serum sample for diagnosing invasive aspergillosis in liver transplant recipients
Authors: Botterel F. , Farrugia C. , Ichai P. , Costa J.‐M. , Saliba F. , Bretagne S.
Published: July 2008

Abstract: Invasive aspergillosis (IA) is a life‐threatening complication of liver transplantation. Detection of circulating galactomannan (GM) in serum samples is a method to improve the microbiological diagnosis in patients at risk for IA. However, the assay is hampered by false‐positive results. The search for circulating Aspergillus DNA in the first GM‐positive sample could improve the specificity of the test. Among 484 liver transplant recipients followed in a single center over 4 years, 25 patients had at least 1 GM‐positive serum sample. The threshold of GM positivity was a ratio ≥1. These 25 patients were classified by the clinicians as probable IA (n=11), possible IA (n=2), and no IA (n=12) using the EORTC/MSG criteria with blinding to the polymerase chain reaction (PCR) results. After 1 mL aliquots of the first GM‐positive serum sample were thawed, 2 independent DNA extractions were performed using the MagNA Pure Compact apparatus. Real‐time amplification targeted at Aspergillus fumigatus mitochondrial DNA was performed on 10 μL of the final eluate in duplicate in the 2 independent DNA extractions using a LightCycler instrument. A sample was considered positive when the crossing point was ≤43 cycles in at least 2 out of the 4 replicates. Among the 13 probable or possible IA, 8 patients were PCR positive. The other 12 patients who had no IA were all PCR negative. Our data suggest that a concomitant real‐time PCR performed on the first GM‐positive sample improves the specificity of the first GM‐positive assay result.
Use of the cytomegalovirus pp65 antigenemia assay for preemptive therapy in allogeneic hematopoietic stem cell transplantation: a real‐world review
Authors: Tan B.H. , Chlebicka N.L. , Hong Low J.G. , Chong T.Y.R. , Chan K.P. , Goh Y.T.
Published: July 2008

Abstract: Despite advances in surveillance strategies and antivirals, cytomegalovirus (CMV) infection continues to pose problems to patients receiving hematopoietic stem cell transplants (HSCTs). The bone marrow transplant (BMT) unit at the Singapore General Hospital embraced the preemptive strategy in late 2003. Although several studies have demonstrated its usefulness, we conducted this review to document CMV‐related events at our institution. Forty‐six patients underwent CMV surveillance using the CMV pp65 antigenemia (CMV Ag) assay from January 2004 to December 2005. Twenty‐seven patients had CMV infection, and 19 remained antigenemia‐negative. No differences were found between the 2 groups for the following potential risk factors for CMV infection: age, total number of co‐morbidities, duration of neutropenia after conditioning, baseline creatinine, type of conditioning regimen (conventional vs. reduced intensity), type of transplant (matched sibling vs. others), recipient CMV status, donor CMV status, and use of total body irradiation. Two patients received alemtuzumab; both developed CMV Ag. Twelve episodes of CMV infection occurred after the 100th post‐HSCT day. Two patients developed CMV disease. One of them could be considered a failure of the preemptive strategy, as she had CMV gastritis diagnosed on the same day that she became pp65‐positive. The other developed CMV disease despite prompt institution of ganciclovir, although she had multiple post‐HSCT complications requiring enhanced immunosuppression, as well as relapsed disease. One‐year disease‐free survival was 55.5% in those with CMV infection and 52.3% in those without infection. Survival was not affected by CMV infection.
Prolongation of corneal xenotransplant survival by T‐cell vaccination‐induced T‐regulatory cells
Authors: Wang Jing , Jiang Shibo , Shi Haiming , Lin Ying , Wang Jufang , Wang Xiaoning
Published: July 2008

Abstract:  Background:  Corneal xenotransplantation is an alternative approach for overcoming shortage of allograft in clinics. However, the mechanism of acute corneal xenograft rejection and the method of prolonging xenograft survival have not been well defined.

Methods:  In this study, we used an orthotopic corneal guinea pig‐to‐rat xenotransplantation model to study the effects of CD4 and CD8 T cells, T‐cell vaccination (TCV) and TCV‐induced T‐regulatory (Treg) cells on xenograft survival.

Results:  The acute rejection of xenografts occurred in untreated rats as early as 6 days post‐transplantation, while TCV significantly prolonged xenograft survival from 6–12 to 21–27 days. The lymph node cells of the TCV‐treated rats exhibited significant response to the anti‐guinea pig T cells and the responding cell populations contained two Treg cell subsets, CD4+ CD25− and CD8+ CD28− T cells, both of which lack expression of Foxp3. Adoptive transfer of CD8+ CD28− T cells resulted in profound inhibition of corneal xenograft rejection, while transfer of CD4+ CD25− T cells alone exhibited no significant inhibition. However, transfer of the CD4+ CD25− and CD8+ CD28− T‐cell mixture remarkably enhanced the in vivo protective activity against xenograft rejection.

Conclusions:  These data suggest that TCV induces the activation of specific Treg cell subsets, CD4+ CD25− and CD8+ CD28− T cells, which may act cooperatively to mediate prolongation of corneal xenograft survival. Therefore, TCV can be used as immunotherapy for suppression of acute xenograft rejection.
Autoantibodies to basement membrane proteins BP180 and BP230 are commonly detected in normal subjects by immunoblotting
Authors: Desai Nemesha , Allen Jill , Ali Iaisha , Venning Vanessa , Wojnarowska Fenella
Published: July 2008

Autoantibodies to basement membrane proteins BP180 and BP230 are characteristic of bullous pemphigoid and other subepidermal immunobullous disorders. These antibodies are, however, reported in other pruritic dermatoses, non‐bullous disorders and non‐cutaneous disease. Few studies have assessed basement membrane antibodies in normal subjects; antibody prevalence in this population is not clear. This study aims to examine basement membrane zone antibodies in normal middle‐aged to elderly subjects. Sera from 61 healthy subjects (majority age 50–70 years) were assessed by immunoblot, indirect immunofluorescence and enzyme‐linked immunosorbent assay. Ninety‐one bullous pemphigoid patients acted as positive controls. Antigenic target, antibody class and titre were examined; sera binding BP180 were assessed for reactivity to the non‐collagenous 16A (NC16A) domain. Thirty‐six normal subjects (59%) had antibodies to either BP180 or BP230 on immunoblot analysis. BP180 was the commonest target antigen, detected in 35 subjects; binding to the immunodominant NC16A domain was not detected. Immunofluorescence was positive in three subjects. Of the bullous pemphigoid sera, 88% were positive on immunoblot or immunofluorescence; a higher frequency had antibodies against BP230. In conclusion, significant numbers of normal healthy subjects have circulating autoantibodies to basement membrane proteins, chiefly BP180 detectable by immunoblot, but these do not bind the NC16A domain.
From biologic to biologic to biologic: Lessons to learn for erythrodermic and recalcitrant chronic plaque psoriasis
Authors: Yip Leona , Harrison Shannon , Foley Peter
Published: July 2008

Differences in mode of action between biologic agents could explain why one agent is more efficacious than another in the treatment of recalcitrant and erythrodermic flares of chronic plaque psoriasis. Here, we present our experience using a case series of three patients with chronic plaque psoriasis who showed consistent and similar responses to three different biologic agents. All three patients who were refractory to efalizumab developed erythrodermic flares 2–12 weeks after a direct switch to etanercept. Switching from efalizumab to etanercept could provoke paradoxical flaring of psoriasis, which might be prevented by transitioning to systemic agents. The erythrodermic flares in all three patients responded dramatically to infliximab with marked and maintained improvements in Psoriasis Area and Severity Index scores.
Public support for anti‐smoking legislation varies with smoking status
Authors: Dwyer Trudy , Bradshaw Julie , Mummery William K. , Searl Kerry R. , Rossi Dolene , Broadbent Marc
Published: July 2008

Objective:  Rural Australians have higher rates of smoking than their urban counterparts, contributing to poorer health outcomes. In 2004, the Queensland Government introduced legislation to reduce the impact of environmental tobacco smoke on the community. The aims of the study were to describe smoking behaviours and associations between smoking behaviour and agreement with current anti‐smoking laws.

Participants:  A total of 1208 people over the age of 18 years and living in rural, remote and very remote central Queensland participated in this telephone survey.

Results:  About 22% (n = 130) of female and 21% of male (n = 125) participants identified themselves as smokers. No difference existed between the mean age of smokers (47.3 years) and non‐smokers (47.1 years). While there is high level of support for smoking restrictions in public places (75%), attitudes vary with smoking status. Smokers were less likely than smokers to agree that the legislation would create a healthier environment, reduce exposure to passive smoking or agree that ‘it is right to ban smoking in public places’. Smokers were significantly more likely to agree that the legislation had gone too far.

Conclusion:  The gradual implementation of the anti‐smoking legislation is changing social beliefs on what are acceptable smoking practices. It is likely that the legislation within Queensland and the subsequent forced changes in social conditions for smokers will continue to reduce the number of people smoking and reduce exposure to environmental tobacco smoke.
Rural inpatient rehabilitation by specialist outreach: Comparison with a city unit
Authors: Bowman Malcolm , Faux Steven , Wilson Stephen
Published: July 2008

Objective:  To examine the effectiveness of a rural inpatient rehabilitation service provided by specialist outreach, and to compare outcomes with a large inner city unit.

Design:  Descriptive study using health service outcome data.

Setting:  Rural base hospital and inner city tertiary referral centre.

Participants:  A total of 329 patients (234 city and 95 rural) admitted for inpatient rehabilitation.

Main outcome measures:  Length of hospital stay, Functional Independence Measure, discharge destination.

Results:  Functional Independence Measure gain per week was 5.4 for the rural outreach unit, compared with 5.5 for the city unit. Length of stay was shorter for the rural unit, with a higher proportion of patients discharged to nursing home.

Conclusions:  Similar rates of functional improvement are achievable with rural inpatient rehabilitation provided by specialist outreach compared with a large inner city unit. Local factors probably account for the shorter length of stay in the rural unit.
Creating a database to facilitate multilevel analyses of mental health determinants and outcomes in rural and remote areas
Authors: Lane Philip , Stain Helen J. , Kelly Brian , Lewin Terry J. , Higginbotham Nick
Published: July 2008

Objective:  The lack of consistent findings regarding comparisons of mental health between rural and urban areas has been attributed in part to methodological shortcomings, including poor conceptualisation of ‘rurality’. To address the diversity of rural and remote communities, an interdisciplinary collaboration sought to establish a database incorporating a range of domains hypothesised to be major influences on the mental health of individuals, families and communities.

Design:  The database domains included health (physical and mental), health service utilisation, sociodemographic characteristics, climate patterns, agricultural activity and primary industry. Important steps in the development of the database were addressing issues related to ethics, ownership, accessing data sources, sustainability of the database and integration of differing outcomes sought by the collaborators.

Results:  The paper describes the database while an illustrative example of analysis demonstrates its application. The potential for multilevel analyses between the database and other datasets is discussed as well as challenges for the future development of this valuable resource for rural mental health research.

Conclusion:  The Centre for Rural and Remote Mental Health database will be a valuable resource for rural mental health research.
Real‐time polymerase chain reaction quantification of specific butyrate‐producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer
Authors: Balamurugan Ramadass , Rajendiran Ethendhar , George Sarah , Samuel G Vijay , Ramakrishna Balakrishnan S
Published: July 2008

Background and Aim:  Bacterial metabolites produced in the bowel are potentially related to the genesis of colorectal cancer. Butyrate is protective against cancer, whereas hydrogen sulfide and oxygen free radicals can be toxic to the epithelium. The present study was designed to quantitate Eubacterium rectale, Faecalibacterium prausnitzii (both butyrate‐producing bacteria), Desulfovibrio (sulfate‐reducing bacteria), and Enterococcus faecalis (that produces extracellular superoxide) in the feces of patients with colorectal cancer.

Methods:  DNA was extracted from feces of 20 patients with colorectal cancer, nine patients with upper gastrointestinal cancer and 17 healthy volunteers. Real‐time polymerase chain reaction using primers aimed at 16S rDNA was used to quantitate the above bacterial species or genus, and this was expressed relative to amplification of universal sequences conserved among all bacteria.

Results:  Levels of E. rectale and F. prausnitzii were decreased approximately fourfold (P = 0.0088 and 0.0028, respectively) in colorectal cancer patients compared to healthy control volunteers. Levels of Desulfovibrio were not significantly different between the three groups. E. faecalis populations were significantly higher in colorectal cancer patients compared to healthy volunteers (P = 0.0294).

Conclusions:  Butyrate producers were decreased and E. faecalis increased in the feces of colon cancer patients. These shifts in the colonic bacterial population could potentially lead to epithelial cell damage and increased turnover and may be a factor leading to colon cancer.
Clinical features and survival in Chinese patients with hepatitis B e antigen‐negative hepatitis B virus‐related cirrhosis
Authors: Ma Hui , Wei Lai , Guo Fang , Zhu Sainan , Sun Yan , Wang Hao
Published: July 2008

Aim:  To compare the clinical features of hepatitis B e antigen (HBeAg)‐negative and HBeAg‐positive cirrhosis, and to define the survival and prognostic indicators of Chinese HBeAg‐negative hepatitis B virus (HBV)‐related cirrhosis.

Methods:  Two hundred and seventeen patients with chronic hepatitis B cirrhosis were studied. Survival was calculated using the Kaplan–Meier method. Proportional hazards Cox regression procedure was used to identify independent predictors of survival. The relationship between HBV‐DNA viral load and prognosis was also investigated.

Results:  The mean follow‐up time was 35 months (3–47 months). HBeAg‐negative liver cirrhosis patients comprised the greatest number of cirrhosis patients. Median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, median total leukocytes (WBC), hemoglobin (Hb), platelet (Plt) and HBV‐DNA levels and the proportion of HBV‐DNA > 105 copies/mL were lower in HBeAg‐negative patients. There were fewer complications in patients treated with lamivudine than in other patients. Survival rates were significantly reduced in patients with HBeAg‐negative cirrhosis (P = 0.0024). The baseline Child–Pugh scores and more than one decompensation during follow up were independent variables correlated with survival of HBeAg‐negative liver cirrhosis patients (P = 0.006 and P = 0.001, respectively). The HBV‐DNA viral load did not correlate with any complications or mortality rates of HBeAg‐negative patients.

Conclusions:  The clinical features of HBeAg‐negative and ‐positive liver cirrhosis differ. Survival was significantly reduced for Chinese patients with HBeAg‐negative than ‐positive cirrhosis. Factors contributing to the prognosis were baseline Child–Pugh scores and the presence of more than one decompensation during follow up.
Discussing withholding and withdrawing of life‐sustaining medical treatment in paediatric inpatients: Audit of current practice
Authors: Stark Zornitza , Hynson Jenny , Forrester Mike
Published: July 2008

Aim:  To understand the circumstances of inpatient deaths at a tertiary paediatric hospital and current practices regarding the timing and documentation of discussions concerning the withholding and withdrawing of life‐sustaining medical treatment (WWLSMT).

Methods:  Retrospective review of the medical records of 50 consecutive inpatient deaths.

Results:  In total, 84% of inpatient deaths occurred in an intensive care setting. In all, 74% of patients had an underlying life‐limiting or life‐threatening condition and death was documented as having been expected in the short term in 88% of patients. Life‐sustaining treatment was either withdrawn or limited prior to death in 84% of cases. There was documented family involvement in the decision‐making process in 98% of cases. A total of 83% of discussions first took place on the day of death itself or in the week leading up to the child's death. Although medical staff frequently documented the outcome of these discussions, the content, clarity and accessibility of documentation varied widely.

Conclusions:  The majority of inpatient deaths at The Royal Children's Hospital occur in acute circumstances and involve patients with chronic conditions. In most cases, death follows WWLSMT. Discussions with families are documented as first occurring relatively late in the course of the final admission although opportunities for earlier discussions may exist. Further research is needed to understand more about how and when discussions actually take place, what the barriers to communication are and to what extent opportunities exist for discussions to be initiated earlier in the illness course.
Ghrelin and leptin modulate immunity and liver function in overweight children
Authors: Okamatsu Yuki , Matsuda Kentaro , Hiramoto Ikue , Tani Hidekazu , Kimura Koichi , Yada Yoichi , Kakuma Tatsuyuki , Higuchi Sadanobu , Kojima Masayasu , Matsuishi Toyojiro
Published: July 2008

Background:  The rising prevalence of obesity represents a growing worldwide public health problem. Interactions of adipocytokines and low‐grade systemic inflammation presently are considered important in the development of obesity, as well as associated chronic disease including bronchial asthma, obesity‐related liver disease and type 2 diabetes mellitus. The purpose of the present study was to investigate metabolic, hormonal, immunologic and inflammatory factors in overweight children and to further clarify possible immunomodulatory effects of obesity‐related hormones and cytokines.

Methods:  Forty‐nine prepubertal overweight children and 49 age‐matched controls of normal weight without underlying disease were enrolled. Levels of plasma ghrelin and serum leptin, cytokines (interleukin [IL]‐4, IL‐10, IL‐12, 1L‐13), C‐reactive protein, immunoglobulin, and insulin were measured, and liver function tests were done to better understand their status in the setting of obesity.

Results:  Overweight subjects had significantly higher measures of adiposity (body mass indexI, % body fat) and had significantly higher serum levels of IgG, IgA and IgE than non‐obese children (P = 0.038, 0.0043, 0.0034, respectively); the opposite was true for IgM (P = 0.025). The incidence of presumed non‐alcoholic fatty liver disease was 28.6% in overweight children. In overweight children, serum leptin levels were associated with liver function index (aspartate aminotransferase/alanine aminotransferase ratio) and serum insulin levels. Some elevated immunoglobulin levels significantly correlated with plasma ghrelin levels and liver function index.

Conclusions:  It is possible that appetite‐regulating hormones modulate both humoral immunity and liver function. Further studies with a larger number of subjects are needed to clarify the precise mechanisms of this association.
Detection of a novel silent deletion, a missense mutation and a nonsense mutation in TCOF1
Authors: Fujioka Hirotaka , Ariga Tadashi , Horiuchi Katsumi , Ishikiriyama Satoshi , Oyama Kimie , Otsu Makoto , Kawashima Kunihiro , Yamamoto Yuhei , Sugihara Tsuneki , Sakiyama Yukio
Published: July 2008

Background: Treacher Collins syndrome (TCS) is a disorder of craniofacial development, that is caused by mutations in the TCOF1 gene. TCS is inherited as an autosomal dominant trait, and haploinsufficiency of the TCOF1 gene product treacle is proposed to be etiologically involved.

Methods: Mutational analysis of the TCOF1 gene was done in 10 patients diagnosed with TCS using single‐strand conformation polymorphism and direct sequencing.

Results: Among these 10 patients, a novel 9 bp deletion was found, together with a previously reported 2 bp deletion, a novel missense mutation and a novel nonsense mutation in three different families. Familial studies allowed judgment of whether these abnormal findings were responsible for the TCS phenotype, or not. The 9 bp deletion of three amino acids Lys‐Glu‐Lys (1378–1380), which was located in the nuclear localization domain of treacle, seemed not essential for the treacle function. In contrast, the novel mutation of Ala26Val is considered to affect the LisH domain, an important domain of treacle. All of the mutations thus far detected in exon 5 have resulted in frameshift, but a nonsense mutation was detected (Lys159Stop).

Conclusion: The information obtained in the present study provides additional insights into the functional domains of treacle.
Anatomic relationship between the internal jugular vein and the carotid artery in preschool children – an Ultrasonographic Study
Authors: ROTH BENJAMIN , MARCINIAK BRUNO , ENGELHARDT THOMAS , BISSONNETTE BRUNO
Published: July 2008

Background:  Central venous cannulation in young children is technically difficult and may lead to potentially serious complications especially when performed blindly or using anatomical landmarks only.

Aim:  The aim of this study was to determine the anatomical relationship of the internal jugular vein (IJV) and the common carotid artery (CA) in preschool children using ultrasound.

Methods:  Forty five children aged 60 months and under were included prospectively and divided into three groups: group 1: <6 months, group 2: 7–18 months and group 3: 19–60 months. With the head in neutral position the location of the left and right IJV was noted as anterior (A), anterolateral (AL), lateral (L) or medial (M) in relation to the CA at the level of the cricoid cartilage. Depths of IJV and CA as well as time taken to locate the vessels were recorded.

Results:  The IJV was more commonly found in the AL position in all groups. The mean depth was 0.96 cm in group 1, 0.95 cm in group 2 and 3. Mean duration for localization of the vessels was 4.2 s in group 1, 4 s in group 2 and 4.3 s in group 3. The differences between the groups were not significant.

Conclusion:  This study demonstrates that the IJV cover the CA in the majority of young children. Depth of the IJV is rarely more than 1 cm deep to the skin. Ultrasound location of the IJV and CA is easy and does not necessarily delay the procedure. The findings of this study support the use of ultrasound guidance for CVC in children.
Ketamine anesthesia in children – exploring infusion regimens
Authors: DALLIMORE DANIEL , ANDERSON BRIAN J. , SHORT TIMOTHY G. , HERD DAVID W.
Published: July 2008

Aim:  We aimed to produce a racemic ketamine manual infusion regimen capable of maintaining a steady‐state blood concentration associated with anesthesia in children aged 1.5–12 years.

Method:  The literature was searched for a ketamine blood concentration associated with anesthesia in humans. Pharmacokinetic parameter estimates were taken from published studies of infusion data in children and used in a pharmacokinetic simulation program to predict likely ketamine blood concentrations during infusions. A variability of 10% was allowed about the chosen target concentration.

Results:  A target concentration of 3 mg·l−1 was chosen for simulation modeling. This target is greater than that associated with anesthesia when supplemented by nitrous oxide or midazolam in adults. Arousal to light touch or voice appears to occur at a mean plasma concentration of 0.5 mg·l−1 in both children and adults. A loading dose of 2 mg·kg−1 followed by an infusion rate of 11 mg·kg−1·h−1 for the first 20 min, 7 mg·kg−1·h−1 from 20 to 40 min, 5 mg·kg−1·h−1 from 40 to 60 min and 4 mg·kg−1·h−1 from 1 to 2 h resulted in a steady‐state target concentration of 3 mg·l−1 in children 1.5–12 years. Arousal, either spontaneous or to speech, is anticipated 3 h 47 min after a 2 h infusion in an average 6‐year‐old child. The context sensitive half‐time in children was shorter than in adults after 1.5 h, rising from 30 min at 1 h to 55 min at 5 h after an infusion of 3 mg·kg−1·h−1 in a 10 kg child.

Conclusion:  Children require higher infusion rates than adults to maintain steady‐state concentrations of 3 mg·l−1 and have shorter context sensitive half‐times than adults after prolonged infusion. These differences can be attributed to age‐related pharmacokinetics. We anticipate slow return to full consciousness after prolonged infusion, suggesting that a lower target concentration with supplementation from adjuvant short acting anesthetic drugs may be advantageous.
Beneficial acclimation and the Bogert effect
Authors: Marais Elrike , Chown Steven L.
Published: July 2008

Few studies have examined the extent to which phenotypic plasticity in a given trait might be influenced by behavioural responses to an environmental cue. Regulatory behaviour might eliminate environmental variation such that little selection for physiological change would take place. Here, to test this Bogert effect on acclimation, we use two life‐stages of a kelp fly that inhabit the same habitat, but differ profoundly in their behaviour. We predicted that when denied opportunities for behavioural regulation, mobile, though brachypterous adults would show a performance advantage in most thermal environments following acclimation to their preferred temperature(s). By contrast, in the less mobile larvae, that have a broader thermal preference, beneficial acclimation would be more evident. Ordered factor anova with orthogonal polynomial contrasts revealed that adults recovered faster from chill coma following any one of six short‐term temperature treatments if they had been acclimated at low temperature, whilst larvae showed beneficial acclimation.
Why equalising trade‐offs aren’t always neutral
Authors: Turnbull Lindsay A. , Rees Mark , Purves Drew W.
Published: July 2008

Equalising trade‐offs, such as seed mass vs. number, have been invoked to reconcile neutral theory with observed differences between species. This is an appealing explanation for the dramatic seed size variation seen within guilds of otherwise similar plants: under size‐symmetric competition, where resource capture is proportional to mass, the outcome of competition should be insensitive to whether species produce many small seeds or few large ones. However, under this assumption, stochastic variation in seed rain leads to exclusion of all but the smallest‐seeded species. Thus stochasticity in seed arrivals, a process that was previously thought to generate drift, instead results in deterministic competitive exclusion. A neutral outcome is possible under one special case of a more general equalising framework, where seed mass affects survival but not competition. Further exploration of the feasibility of neutral trade‐offs is needed to understand the respective roles of neutrality and niche structure in community dynamics.
Temporal dynamics within a contemporary latitudinal diversity gradient
Authors: Fisher Jonathan A. D. , Frank Kenneth T. , Petrie Brian , Leggett William C. , Shackell Nancy L.
Published: July 2008

Poleward declines in species diversity [latitudinal diversity gradients (LDG)] remain among the oldest and most widespread of macroecological patterns. However, their contemporary dynamics remain largely unexplored even though changing ecological conditions, including global change, may modify LDG and their respective ecosystems. Here, we examine temporal variation within a temperate Northwest Atlantic LDG using 31 years of annual fisheries‐independent surveys and explore its dynamics in relation to a dominant climate signal [the wintertime North Atlantic Oscillation (NAO)] that varies interannually and alters the latitudinal gradient of Northwest Atlantic continental shelf bottom water temperatures. We found that the slopes of the annual LDG vary dramatically due to changes in geographic distributions of 100+ species, variations that are concealed within the cumulative, static LDG. These changes are strongly associated with changes in NAO sign and strength. This is the first illustration of temporal dynamics in a contemporary LDG and the first demonstration of the speed at which local environmental variations can alter an LDG. Our findings underscore the need to investigate factors that modify LDG separately from those that contribute to their origins.
Corneal squamous cell carcinoma in a dog: a case report
Authors: Montiani‐Ferreira Fabiano , Kiupel Matti , Muzolon Patricia , Truppel Jesse
Published: July 2008

Purpose: To report a case of primary corneal squamous cell carcinoma (SCC) in an English Bulldog. In addition, immunohistochemistry of the corneal tissue mass was performed using a panel of antibodies. A prominent feature of the present case was the clinical history of chronic keratitis due to eyelid abnormalities.

Results: No papillomavirus antigen was detected in section of normal or neoplastic corneal tissue. The corneal epithelial cells were positive for pancytokeratins AE1/AE3 and MNF116, and E‐cadherin. The neoplastic cells in close proximity to the normal epithelial lining were positive for both pancytokeratins and E‐cadherin with gradual loss of staining toward the center of the neoplastic mass. Rare neoplastic cells demonstrated positive staining for caspase 3 and a large number was strongly positive for GADD45 and p53.

Conclusion and discussion: The observed loss of the various cytokeratins, the strong p53 expression, and low numbers of caspase 3 positive cells were suggestive that a p53 mutation may have caused this primary corneal SCC. Over‐expression of the tumor‐suppressor gene p53 is likely to be a consequence of ultraviolet radiation exposure. Two factors, however, may have played a role in the formation of this primary corneal SCC: chronic irritation of the corneal surface (microtrauma) and exposure to UV radiation.
Diversity and functional importance of coral‐feeding fishes on tropical coral reefs
Authors: Cole Andrew J. , Pratchett Morgan S. , Jones Geoffrey P.
Published: July 2008

Fishes that feed from live corals (corallivores) are a conspicuous component of healthy coral reef environments. However, knowledge of the occurrence and ecological significance of this feeding mode is fragmentary. Historically, very few fish were considered capable of feeding from live coral, and those few that did were considered ecologically insignificant. More recently, the role of corallivores has been re‐evaluated; published records document 128 corallivorous fish species from 11 different families, with 69 of these belonging to the family Chaetodontidae. Other families, including the Labridae, Tetraodontidae, Balistidae, Monacanthidae, Pomacentridae and Scaridae, all have between seven and ten coral‐feeding species. One‐third of coral‐feeding fishes feed almost exclusively on corals, with more than 80% of their diet based on coral. Corallivorous fish show distinct prey preferences and consume only a small subset of available corals, usually the genera Acropora, Pocillopora and Porites. This selective predation by corallivores can limit abundance and distribution of preferred corals. Chronic predation by corallivores may also exacerbate effects of coral disturbance (e.g. climate‐induced coral bleaching), impeding reef recovery and causing further coral loss. Conversely, the cover of preferred corals can be a primary determinant of corallivore abundance and physiological condition. Owing to this close association, obligate corallivores invariably decline in response to loss of coral cover. Increased knowledge of the number of corallivores and their diets suggest that this feeding mode is more important to coral reef food webs than traditionally thought.
A Cre::FLP fusion protein recombines FRT or loxP sites in transgenic maize plants†
Authors: Djukanovic Vesna , Lenderts Brian , Bidney Dennis , Lyznik L. Alexander
Published: July 2008

The coding sequences of Cre (site‐specific recombinase from bacteriophage P1) and FLP (yeast 2‐µm plasmid site‐specific recombinase) were fused in frame to produce a novel, dual‐function, site‐specific recombinase gene. Transgenic maize plants containing the Cre::FLP fusion expression vector were crossed to transgenic plants containing either the loxP or FRT excision substrate. Complete and precise excisions of chromosomal fragments flanked by the respective target sites were observed in the F1 and F2 progeny plants. The episomal DNA recombination products were frequently lost. Non‐recombined FRT substrates found in the F1 plants were recovered in the F2 generation after the Cre::FLP gene segregated out. They produced the recombination products in the F3 generation when crossed back to the FLP‐expressing plants. These observations may indicate that the efficiency of site‐specific recombination is affected by the plant developmental stage, with site‐specific recombination being more prevalent in developing embryos. The Cre::FLP fusion protein was also tested for excisions catalysed by Cre. Excisions were identified in the F1 plants and verified in the F2 plants by polymerase chain reaction and Southern blotting. Both components of the fusion protein (FLP and Cre) were functional and acted with similar efficiency. The crossing strategy proved to be suitable for the genetic engineering of maize using the FLP or Cre site‐specific recombination system.