bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent H5N1 avian Influenza A virus increases rapidly in virulence to mice after a single passage in mice
Authors: Mase Masaji , Tanimura Nobuhiko , Imada Tadao , Okamatsu Masatoshi , Tsukamoto Kenji , Yamaguchi Shigeo
Published: November 2006

To evaluate the potential pathogenicity to mammals of the recent H5N1 avian Influenza A virus, viruses recovered from dead mice infected with A/chicken/Yamaguchi/7/2004 isolated in Japan were examined. All recovered viruses from the brains of dead mice infected with this strain (without any prior adaptation to mice) had substituted the amino acid at position 627 of the PB2 protein from glutamic acid to lysine. Their mouse lethality had increased by approximately 5×104 times over that of the original virus. Histopathological analysis reinforced the finding that these variants caused more rapid and severe damage to mice than the original virus. This revealed that it might be useful to characterize the recovered virus to assess its potential pathogenicity to mammals.
De novo infection and propagation of wild-type Hepatitis C virus in human T lymphocytes in vitro
Authors: MacParland Sonya A. , Pham Tram N. Q. , Gujar Shashi A. , Michalak Tomasz I.
Published: November 2006

While exploring previous findings that ex vivo treatment of lymphoid cells from Hepatitis C virus (HCV)-infected individuals with T cell-stimulating mitogens augments detection of the residing virus, an in vitro HCV replication system was established, in which mitogen-induced T cell-enriched cultures served as HCV targets and the derived T cells multiplied virus during repeated serial passage. HCV replication was ascertained by detecting HCV RNA positive and negative strands, HCV NS5a and E2 proteins, release of HCV virions and nucleocapsids (confirmed by immunoelectron microscopy) and de novo infection of mitogen-induced T cells prepared from healthy donors. Further, affinity-purified normal human T lymphocytes were also susceptible to HCV infection in vitro and HCV replication was detected in pure T cells isolated from a patient with chronic hepatitis C. These results document that T cells can support propagation of HCV both in vivo and in vitro. The infection system established offers a valuable tool for in vitro studies on the entire cycle of HCV replication, virus cytopathogenicity and evaluation of antiviral agents against wild-type HCV in the natural host-cell milieu.
Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59)
Authors: Cordier C. , Bencsik A. , Philippe S. , Bétemps D. , Ronzon F. , Calavas D. , Crozet C. , Baron T.
Published: November 2006

Transgenic mice expressing the prion protein (PrP) of species affected by transmissible spongiform encephalopathies (TSEs) have recently been produced to facilitate experimental transmission of these diseases by comparison with wild-type mice. However, whilst wild-type mice have largely been described for the discrimination of different TSE strains, including differentiation of agents involved in bovine spongiform encephalopathy (BSE) and scrapie, this has been only poorly described in transgenic mice. Here, two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59), expressing the ovine PrP (A136 R154 Q171) under control of the neuron-specific enolase promoter, were studied; they were challenged with brainstem or spinal cord from experimentally BSE-infected sheep (AA136 RR154 QQ171 and AA136 RR154 RR171 genotypes) or brainstem from cattle BSE and natural sheep scrapie. The disease was transmitted successfully from all of these sources, with a mean of approximately 300 days survival following challenge with material from two ARQ-homozygous BSE-infected sheep in TgOvPrP4 mice, whereas the survival period in mice challenged with material from the ARR-homozygous BSE-infected sheep was 423 days on average. It was shown that, in the two ovine transgenic mouse lines, the Western blot characteristics of protease-resistant PrP (PrPres) were similar, whatever the BSE source, with a low apparent molecular mass of the unglycosylated glycoform, a poor labelling by P4 monoclonal antibody and high proportions of the diglycosylated form. With all BSE sources, but not with scrapie, florid plaques were observed in the brains of mice from both transgenic lines. These data reinforce the potential of this recently developed experimental model for the discrimination of BSE from scrapie agents.
In vitro and in vivo identification of structural and sequence elements in the 5′ untranslated region of Ectropis obliqua picorna-like virus required for internal initiation
Authors: Lu Jie , Zhang Jiamin , Wang Xiaochun , Jiang Hong , Liu Chuanfeng , Hu Yuanyang
Published: November 2006

Ectropis obliquapicorna-like virus (EoPV) is a newly described insect virus that is classified as a putative member of the genusIflavirus. The virus possesses a large, positive-sense RNA genome encoding a single polyprotein that shares physicochemical properties with those of members of the familyPicornaviridae. The 5′ untranslated region (5′ UTR) plays an important role in picornavirus translation initiation, as it contains an internal ribosome entry site (IRES) that mediates cap-independent translation. To investigate translation in EoPV, an extensive range of mutations were engineered within the 5′ UTR and the effects of these changes were examinedin vitroandin vivoby using a bicistronic construct. Results showed that deletions within the first 63 nt had little impact on IRES activity, whilst core IRES function was contained within stem–loops C and D, as their removal abrogated IRES activity significantly. In contrast to these findings, removal of stem–loop G containing two cryptic AUGs caused a remarkable increase in IRES activity, which was further investigated by site-directed mutagenesis at these two positions. It was also confirmed that initiation of protein synthesis occurs at AUG6 (position 391–394) and not at the AUG immediately downstream of the polypyrimidine tract. Mutation of the polypyrimidine tract (CCTTTC) had a slight effect on EoPV IRES activity. Furthermore, mutations of the RAAA motif led to a decrease in IRES activity of approximately 40 %in vitro, but these results were not supported byin vivoexperiments. In conclusion, this study reveals that the EoPV IRES element is unique, although it has features in common with the type II IRESs.
Characterization of the 5′ internal ribosome entry site of Plautia stali intestine virus
Authors: Shibuya Norihiro , Nakashima Nobuhiko
Published: November 2006

The RNA genome of Plautia stali intestine virus (PSIV; Cripavirus, Dicistroviridae) contains two open reading frames, the first of which is preceded by a 570 nt untranslated region (5′ UTR). The 5′ UTR was confirmed to be an internal ribosome entry site (IRES) using an insect cell lysate translation system: translation of a second cistron increased 14-fold in the presence of the 5′ UTR and a cap analogue did not inhibit translation of the second cistron. Deletion analysis showed that 349 bases corresponding to nt 225–573 in the PSIV genome were necessary for internal initiation. The PSIV 5′ IRES did not function in rabbit reticulocyte lysate or wheatgerm translation systems; however, the intergenic IRES for capsid translation of PSIV was functional in both systems, indicating that the 5′ IRES and the intergenic IRES have distinct requirements for their activities. Chemical and enzymic analyses of the 5′ IRES of PSIV indicate that its structure is distinct from that of Rhopalosiphum padi virus. Because 5′ IRES elements in some dicistroviruses have been reported to be active in plant and mammalian cell-free translation systems, there appears to be variation among dicistroviruses in the mechanism of translation initiation mediated by 5′ IRES elements.
Novel noncoding RNA from human Y distal heterochromatic block (Yq12) generates testis-specific chimeric CDC2L2
Authors: Jehan Zeenath , Vallinayagam Sambandam , Tiwari Shrish , Pradhan Suman , Singh Lalji , Suresh Amritha , Reddy Hemakumar M. , Ahuja Y.R. , Jesudasan Rachel A.
Published: November 2006

The human Y chromosome, because it is enriched in repetitive DNA, has been very intractable to genetic and molecular analyses. There is no previous evidence for developmental stage- and testis-specific transcription from the male-specific region of the Y (MSY). Here, we present evidence for the first time for a developmental stage- and testis-specific transcription from MSY distal heterochromatic block. We isolated two novel RNAs, which localize to Yq12 in multiple copies, show testis-specific expression, and lack active X-homologs. Experimental evidence shows that one of the above Yq12 noncoding RNAs (ncRNAs) trans-splices with CDC2L2 mRNA from chromosome 1p36.3 locus to generate a testis-specific chimeric β sv13 isoform. This 67-nt 5′UTR provided by the Yq12 transcript contains within it a Y box protein-binding CCAAT motif, indicating translational regulation of the β sv13 isoform in testis. This is also the first report of trans-splicing between a Y chromosomal and an autosomal transcript.
The transition to menopause reinforces adiponectin production and its contribution to improvement of insulin‐resistant state
Authors: Tamakoshi Koji , Yatsuya Hiroshi , Wada Keiko , Matsushita Kunihiro , Otsuka Rei , Yang Pei Ou , Sugiura Kaichiro , Hotta Yo , Mitsuhashi Hirotsugu , Takefuji Seiko , Kondo Takaaki , Toyoshima Hideaki
Published: November 2006

Objective  To evaluate the influence of menopausal status on the serum adiponectin concentration and investigate whether the contribution of adiponectin to insulin resistance is modified by menopausal status.

Subjects  We conducted a population‐based, cross‐sectional study of 207 premenopausal and 206 postmenopausal Japanese women.

Measurements  Data on anthropometric characteristics, fasting serum adiponectin, glucose and insulin concentrations were used. Insulin resistance (homeostasis model assessment of insulin resistance: HOMA‐IR) was calculated.

Results  Postmenopausal women had significantly higher HOMA‐IRs than premenopausal women [1·50 (1·42, 1·59) vs 1·18 (1·12, 1·24), geometric mean (1 standard error range), P = 0·005]. Paradoxically, adiponectin levels in postmenopausal women were also significantly higher than those in premenopausal women [10·3 (9·95, 10·7) vs 9·04 (8·71, 9·39), P = 0·028]. Multiple regression analysis showed that body mass index (BMI) was the only significantly independent predictor [standardized partial regression coefficients (sβ) = 0·319, P < 0·001] for HOMA‐IR among premenopausal women, whereas both BMI and adiponectin were the significant predictors among postmenopausal (sβ = 0·334 and −0·141, P < 0·001 and < 0·05, respectively). When the subjects were restricted to those without metabolic disorders including high blood pressure, hypertriglyceridaemia, hypo‐HDL cholesterolaemia and high fasting glucose, adiponectin (sβ = −0·249, P < 0·05) was the only significant predictor for HOMA‐IR among postmenopausal women but BMI was not significant (sβ = 0·223, P = 0·075).

Conclusions  The transition to menopause increases serum adiponectin concentrations. And the significant and negative association between adiponectin and HOMA‐IR was observed only after menopause. Therefore, adiponectin may play a role in the improvement of an incipient insulin‐resistant state after, rather than before, menopause.
Population estimation methods to quantify temporal variation in fish accumulations downstream of a weir
Authors: BAUMGARTNER L. J.
Published: November 2006

Abstract  Temporal changes in the population sizes of seven migratory species were assessed over a 2‐year period prior to the construction of a fishway on the Murrumbidgee River, Australia. Mark‐recapture (Chapman–Petersen) and Jackknife removal methods were used at 3‐month intervals to determine the composition and sizes of migratory fish populations. No difference in population size estimate was detected between the two methods. However, the Jackknife removal estimator generally provided less variable estimates for a greater number of species. Population sizes were greatest during summer and autumn when bony herring, Nematalosa erebi Günther, and common carp, Cyprinus carpio L., dominated the migratory community. Both estimators provided data essential to further the development of an appropriate fish passage facility and could be applied to other sites where the size of migratory fish populations is of interest.
Yields of European perch from Upper Lake Constance from 1910 to present
Authors: ECKMANN R. , GERSTER S. , KRAEMER A.
Published: November 2006

Abstract  Commercial yields of perch, Perca fluviatilis (L.), from Upper Lake Constance changed markedly during the 20th century. The perch boom in the 1950s and 1960s is attributed to higher fishing intensity and lake eutrophication. Decreasing yields in recent decades are mainly because of slower growth of perch, while a gradual decrease in year‐class strength, and an overall reduction of fishing intensity, might also have contributed to yield reduction. Slower growth is mainly attributed to lake re‐oligotrophication and infestation of perch with the pike tapeworm Triaenophorus nodulosus (Pallas). Competition for food with non‐native ruffe, Gymnocephalus cernua (L.) is likely of minor importance, while the invasion of the lake by alien macrozoobenthos species has the potential to reduce the food supply for benthivorous perch. Perch yields are assumed to remain at the low level attained at the beginning of the 21st century; however, under changing climate conditions, fluctuations around the long‐term mean will probably be wider than in the past.
Aspects in spawning biology and migration of the mud crab Scylla olivacea in the Andaman Sea, Thailand
Authors: KOOLKALYA S. , THAPANAND T. , TUNKIJJANUJIJ S. , HAVANONT V. , JUTAGATE T.
Published: November 2006

Abstract  Spawning biology and migration of the mud crab, Scylla olivacea (Herbst), in the Andaman Sea were examined from November 2002 to March 2004 at Klong Ngoa Mangrove area, Ranong Province, Thailand. Mature females were dominant from July to November. The changes in monthly gonadosomatic index of females ranged from 1.9 (±3.3) to 8.2 (±5.8) and size at first maturity was 9.4 cm internal carapace width (ICW). Fecundity (F) correlated ICW according to F=3.02 ×ICW2.98. A total of 1013 female crabs were double tagged with spaghetti and bottom tags. The recaptured rate was 36.7% and showed that females migrated from coastal area to the open sea during the spawning season. A closed season during the north‐east monsoon season and a minimum legal ICW size of 10 cm are recommended for sustainable management of the fishery.
Global spatial patterns and temporal trends of burned area between 1981 and 2000 using NOAA‐NASA Pathfinder
Authors: RIAÑO D. , MORENO RUIZ J. A. , ISIDORO D. , USTIN S. L.
Published: November 2006

An analysis of the spatial and temporal patterns of global burned area with the Daily Tile US National Oceanic and Atmospheric Administration‐Advanced Very High‐Resolution Radiometer Pathfinder 8 km Land dataset between 1981 and 2000 is presented. Nine distinct temporal and spatial fire patterns were identified at the global scale using principal components and cluster analysis. Three major fire seasons were identified from June to December and from February to June for different areas of the northern hemisphere and from October to March for the southern hemisphere. The area burned primarily followed the annual cycle and secondarily, an important 6‐month cycle. Temporal cycles were unimportant in some equatorial and tropical areas in the northern hemisphere. The total annual burned area has not increased in the last 20 years but a significant increase was found in the mid‐latitude and subtropical areas of the northern hemisphere which was offset by a slight decrease in burned area in tropical southeast Asia and Central America. Additionally, burned area has significantly increased during the summer in the mid‐latitudes of the northern hemisphere and in the boreal region, and the fire season starts earlier in the mid‐latitudes. Total burned area was explained by the extent of savanna (wooded grassland) cover. Latitude was not determinative as divergent fire patterns were encountered and did not have an impact on extent of burned area at our spatial level of analysis.
An overview of the history, clinical practice concerns, comparative studies and strategies to optimize therapy of bypassing agents
Authors: MEHTA R. , PARAMESWARAN R. , SHAPIRO A. D.
Published: November 2006

Summary. Despite significant advances in the treatment of haemophilia, including availability of recombinant coagulation factor replacement products and the use of prophylactic infusion regimens, the segment of haemophilic patients who develop inhibitory antibodies remain at higher risk for morbidity and mortality associated with recurrent or uncontrolled bleeding events. Bypassing agents represent the mainstay of treatment and prevention of bleeding. The most commonly used of the currently available therapeutic agents are a plasma‐based therapy, factor eight inhibitor bypassing activity, vapour heated, and a recombinant therapy, NovoSeven (recombinant activated factor VIIa). A substantial body of literature exists to document efficacy and adverse event profiles for these two products. There is, however, a paucity of data arising from adequately powered prospective trials to determine optimal treatment and dosing in various clinical situations. Certain clinical circumstances, patient profiles, individual responses, or provider predilection may lead to preferential use of one of these products over the other; however, the continued presence of both agents in the therapeutic armamentarium remains critically important to this fragile population. The historical use, clinical practice concerns, published comparative studies and methods for optimization of these two bypassing agents are reviewed.
Organizational configuration of hospitals succeeding in attracting and retaining nurses
Authors: Stordeur Sabine , D'Hoore William ,   the NEXT‐Study Group
Published: November 2006

Title. Organizational configuration of hospitals succeeding in attracting and retaining nurses

Aim.  This paper contrasts structural and managerial characteristics of low‐ and high‐turnover hospitals, and describes the organizational configuration of attractive hospitals.

Background.  In countries facing nurse shortages and turnover, some hospitals succeed in recruiting and retaining nurses. In Magnet Hospitals, managerial practices and environmental characteristics increase nurses’ job satisfaction and their commitment to the organization, which in turn decreases nurse turnover. Such an approach suggests that organizations are best understood as clusters of interconnected structures and practices, i.e. organizational configurations rather than entities whose components can be understood in isolation.

Method.  From a sample of 12 hospitals whose nurse turnover was studied for 1 year, structural and organizational features of hospitals in the first and fourth quartiles, i.e. attractive (turnover <3·1%) vs. conventional (turnover >11·8%) were contrasted. A questionnaire, including perceptions of health‐related factors, job demands, stressors, work schedules, organizational climate, and work adjustments antecedent to turnover, was received from 401 nurses working in attractive hospitals (response rate = 53·8%) and 774 nurses in conventional hospitals (response rate = 54·5%).

Findings.  Structural characteristics did not differentiate attractive and conventional hospitals, but employee perceptions towards the organization differed strikingly. Differences were observed for risk exposure, emotional demands, role ambiguity and conflicts, work‐family conflicts, effort‐reward imbalance and the meaning of work, all in favour of attractive hospitals (P < 0·001). Relationships with nursing management, work ability and satisfaction with working time, handover shifts and schedules were also better in attractive hospitals (P < 0·001). Job satisfaction and commitment were higher in attractive hospitals, whereas burnout and intention to leave were lower (P < 0·001).

Conclusion.  Organizational characteristics are key factors in nurse attraction and retention. Nurses face difficulties in their work situations, but some hospitals are perceived as healthy organizations. The concept of attractive institutions could serve as a catalyst for improvement in nurses’ work environments in Europe.
Dietetic guidelines on food and nutrition in the secondary prevention of cardiovascular disease – evidence from systematic reviews of randomized controlled trials (second update, January 2006)
Authors: Mead A. , Atkinson G. , Albin D. , Alphey D. , Baic S. , Boyd O. , Cadigan L. , Clutton L. , Craig L. , Flanagan C. , Greene P. , Griffiths E. , Lee N. J. , Li M. , McKechnie L. , Ottaway J. , Paterson K. , Perrin L. , Rigby P. , Stone D. , Vine R. , Whitehead J. , Wray L. , Hooper L. ,   on behalf of the UK Heart Health and Thoracic Dietitians Interest Group (Specialist group of the British Dietetic Association)
Published: November 2006

Aim  To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention).

Methods  The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD. Each review was critically appraised by at least two members of the UK Heart Health and Thoracic Dietitians Group. The quality and results of each review were discussed and summarized at a group meeting.

Results  Evidence‐based strategies that reduce cardiovascular events in those with CVD include reduction in saturated fat and substitution with unsaturated fats. Individuals who have suffered a myocardial infarction may also benefit from adopting a Mediterranean type diet and increasing intake of omega 3 fats, but it is not clear whether they are beneficial for all patients with CVD. There is no systematic review evidence to support the use of antioxidant vitamins supplements, low glycaemic index diets, or homocysteine lowering therapies in this group.

Conclusion  There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.
Oestrogen, Cognition and the Maturing Female Brain
Authors: Craig M. C. , Murphy D. G.
Published: November 2006

Many women complain of memory and other cognitive difficulties at times that are associated with changes in ovarian steroid levels. However, the biological mechanisms through which ovarian steroids exert these effects remains poorly understood. Furthermore, the effect of hormone therapy, especially oestrogen therapy, on cognition and brain function in healthy women, and its role in the prevention of Alzheimer's disease, remains controversial. Here, we review the evidence that, in healthy women, ovarian steroids/oestrogen affects brain regions crucial to higher cognitive function at the macroscopic, microscopic, functional and neurotransmitter levels.
Prolonged antiviral therapy for hepatitis B virus‐infected health care workers: a feasible option to prevent work restriction without jeopardizing patient safety
Authors: Buster E. H. C. J. , Van Der Eijk A. A. , De Man R. A. , Janssen H. L. A. , Schalm S. W.
Published: November 2006

Summary.  To prevent transmission of hepatitis B virus (HBV) from health care workers (HCWs) to patients, highly viraemic HCWs are often advised to restrict performing exposure prone procedures (EPPs). To prevent loss of highly qualified medical personnel and simultaneously minimize transmission risk to patients, we offered highly viraemic HCWs antiviral therapy and evaluated the effects of this strategy. Eighteen chronic HBV‐infected HCWs have been monitored every 3–6 months for a median period of 5.6 years (range 1.1–12.5 years). Antiviral therapy was offered if HBV DNA was above 105 copies/mL and EPPs were performed or active liver disease was present. Median HBV DNA levels, the percentage of days with HBV DNA above 103, 104 and 105 copies/mL, and reduction of HBV DNA during antiviral treatment have been analysed for hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative HCWs separately. Prolonged viral suppression was achieved in both HBeAg‐positive, as well as HBeAg‐negative HCWs. In HBeAg‐negative HCWs treatment with interferon or lamivudine maintained HBV DNA levels below 105 copies/mL. For HBeAg‐positive HCWs continuous treatment with tenofovir or entecavir was essential for reaching low viraemia persistently. In 2004, median HBV DNA levels in both HBeAg‐negative and HBeAg‐positive HCWs were below 103 copies/mL and all HCWs executed their professional work full‐range. For both HBeAg‐positive and HBeAg‐negative HCWs, antiviral treatment is effective in persistent suppression of virus levels below 105 copies/mL. This observation supports antiviral therapy as a viable management option instead of work restriction, with the provision of regular expert monitoring including quantification of HBV DNA.
Therapeutic issues in HIV/HCV‐coinfected patients
Authors: Sulkowski M. S. , Benhamou Y.
Published: November 2006

Summary.  The importance of treating hepatitis C virus (HCV)‐associated morbidities in a growing population of patients coinfected with human immunodeficiency virus (HIV) has increased since the introduction of highly active antiretroviral therapy. As a result, investigative attention is turning to HCV‐related liver disease and treatment‐associated issues in coinfection. HIV/HCV‐coinfected patients have higher HCV RNA loads and show more rapid progression of fibrosis than do monoinfected patients. Combination therapy with pegylated interferon plus ribavirin (RBV) is the standard of care for HCV in coinfected patients. Therapy slows fibrosis progression, but toxicity prevents identification of the most effective RBV dose. Coinfected patients have about a threefold greater risk of antiretroviral therapy‐associated hepatotoxicity than patients with HIV only. Other challenges include anaemia, mitochondrial toxicity, drug–drug interactions and leucopenia. Thus, chronic hepatitis C should be treated in HIV/HCV‐coinfected patients, but steps must be taken to prevent and treat potential toxicities. The first European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co‐infected Patients was held March 2005 in Paris to address these issues. This article reviews the peer‐reviewed literature and expert opinion published from 1990 to 2005, and compares results with presentations and recommendations from the Consensus Conference to best present current issues in coinfection.
Sealing efficiency of shales
Authors: Luo Xiaorong , Vasseur Guy
Published: November 2006

The sealing efficiency of shale layers is studied through the hydraulic parameters which are required for sustaining overpressure during geologically significant periods. Assuming a 1D sedimentary complex composed of a sealing layer overlying a permeable one, we give approximate solutions for the dissipation of a given initial overpressure. The time constant for relaxation involves the thickness, hydraulic conductivity and specific storage of the seal and also those of the permeable layer. The values of the various hydraulic parameters are discussed. It is argued first that the specific storage corresponding to plastic deformation during burial compaction is larger than the one which would correspond to elastic deformation. When taking into account (i) plausible values for specific storage of the upper shale layer and (ii) the storage effect of the lower permeable layer, it is found that a shale layer of several tens of m with an hydraulic conductivity of the order of 10‐15 ms‐1 maintains overpressure for 1 Myr. For such hydraulic parameter values, in the absence of on‐going pressuring forces, initial overpressures would decay with a time constant (corresponding to a decrease by a factor e ∼, 2.7) of 1 Myr. This is interpreted as supporting a dynamic origin for observed abnormal pressures.
Modelling the effects of sub‐lethal doses of herbicide and nitrogen fertilizer on crop–weed competition
Authors: KIM D S , MARSHALL E J P , BRAIN P , CASELEY J C
Published: November 2006

The effects of sub‐lethal dose of herbicide and nitrogen fertilizer on crop–weed competition were investigated. Biomass increases of winter wheat and a model weed, Brassica napus, at no‐herbicide treatment with increasing nitrogen were successfully described by the inverse quadratic model and the linear model respectively. Increases in weed competitivity (β0) of the rectangular hyperbola and parameter B in the dose–response curve for weed biomass, with increasing nitrogen were also successfully described by the exponential model. New models were developed by incorporating inverse quadratic and exponential models into the combined rectangular hyperbola with the standard dose–response curve for winter wheat biomass yield and the combined standard dose—response model with the rectangular hyperbola for weed biomass, to describe the complex effects of herbicide and nitrogen on crop–weed competition. The models developed were used to predict crop yield and weed biomass and to estimate the herbicide doses required to restrict crop yield loss caused by weeds and weed biomass production to an acceptable level at a range of nitrogen levels. The model for crop yield was further modified to estimate the herbicide dose and nitrogen level to achieve a target crop biomass yield. For the target crop biomass yield of 1200 g m−2 with an infestation of 100 B. napus plants m−2, the model recommended various options for nitrogen and herbicide combinations: 140 and 2.9, 180 and 0.9 and 360 kg ha−1 and 1.7 g a.i. ha−1 of nitrogen and metsulfuron‐methyl respectively.
Mutations in the RSK2(RPS6KA3) gene cause Coffin–Lowry syndrome and nonsyndromic X‐linked mental retardation
Authors: Field M , Tarpey P , Boyle J , Edkins S , Goodship J , Luo Y , Moon J , Teague J , Stratton MR , Futreal PA , Wooster R , Raymond FL , Turner G
Published: November 2006

We describe three families with X‐linked mental retardation, two with a deletion of a single amino acid and one with a missense mutation in the proximal domain of the RSK2(RPS6KA3) (ribosomal protein S6 kinase, 90 kDa, polypeptide 3) protein similar to mutations found in Coffin–Lowry syndrome (CLS). In two families, the clinical diagnosis had been nonsyndromic X‐linked mental retardation. In the third family, although CLS had been suspected, the clinical features were atypical and the degree of intellectual disability much less than expected. These families show that strict reliance on classical clinical criteria for mutation testing may result in a missed diagnosis. A less targeted screening approach to mutation testing is advocated.
Sphingosine 1‐phosphate receptor modulators: a new class of immunosuppressants
Authors: Yopp Adam C , Ledgerwood Levi G , Ochando Jordi C , Bromberg Jonathan S
Published: November 2006

Abstract:  In this review, we summarize how FTY720 came from the lab bench to the bedside by examining its structural similarities to natural occuring sphingosine analogues, the mechanism of action, and clinical applicability to not only transplantation but also autoimmune, oncological, and neurobiological fields. FTY720, a sphingosine 1‐phosphate (S1P) analogue, promotes the survival of human and animal allografts by sequestering T lymphocytes within peripheral lymphoid tissue. The mechanism of sequestration is three‐fold:(1) T lymphocytes are driven into peripheral lymph nodes in a chemokine dependent manner by FTY720;(2) FTY720 downregulates sphingosine 1‐phosphate receptors (S1PRs) on the T lymphocyte surface, rendering it unable to migrate along a S1P gradient; and (3) FTY720 closes stromal gates on the abluminal side of the lymphatic endothelium. Future areas of investigation include developing S1P analogues that have specific agonist binding to S1PRs avoiding side effects seen in non‐specific binding.
Long‐term follow‐up of peripheral blood stem cell transplantation from mismatched related and unrelated donors
Authors: Blau I.W , Schmidt‐Hieber M , Basara N , Hopfenmüller W , Bischoff M , Günzelmann S , Kirsten D , Schmetzer B , Roemer E , Kiehl M.G , Thiel E , Fauser A.A
Published: November 2006

Abstract:  Allogeneic stem cell transplantation (SCT) is best performed with an HLA‐identical sibling donor (matched related donor, MRD) to reduce the risk of early complications such as acute graft‐vs.‐host disease (aGvHD). However, as only about 30% of recipients have an MRD for this potentially curative approach, the use of family donors with one or two mismatches in the HLA‐antigens (mismatch related donor, MMRD) or fully matched unrelated donors (MUD) (‘‘alternative donors’’) has been introduced in the allogeneic SCT setting in recent years. To evaluate the feasibility of allogeneic SCT from alternative donors by using peripheral blood stem cells (PBSC) we initiated a prospective, phase II study in 1996. From April 1996 to July 1998, 18 patients with various hematological malignancies underwent allogeneic SCT from alternative donors (two patients with MUD and 16 patients with MMRD). All patients received stable engraftment and none of the patients had graft rejection. The rate of aGvHD (grades II–IV) and the relapse rate at last follow‐up (seven to nine yr after SCT) were with 40% and 24%, respectively, comparable with those found in patients receiving allogeneic SCT from MRD. However, five yr after allogeneic SCT only 17% were alive, which was mainly due to the treatment‐related mortality (TRM) rate of 59%. We conclude that allogeneic PBSC transplantation by using alternative donors is associated with an unsatisfying long‐term TRM rate. The significance of TRM and particular late deaths has to be evaluated further in this transplantation setting.
Cytomegalovirus in transplantation – challenging thestatus quo
Authors: Fishman Jay A , Emery Vincent , Freeman Richard , Pascual Manuel , Rostaing Lionel , Schlitt Hans J , Sgarabotto Dino , Torre‐Cisneros Julian , Uknis Marc E
Published: November 2006

Abstract: Background: Cytomegalovirus (CMV) infection of solid organ transplant (SOT) recipients causes both ‘‘direct’’ and ‘‘indirect’’ effects including allograft rejection, decreased graft and patient survival, and predisposition to opportunistic infections and malignancies. Options for CMV prevention include pre‐emptive therapy, whereby anti‐CMV agents are administered based on sensitive viral assays, or universal prophylaxis of all at‐risk patients. Each approach has advantages and disadvantages in terms of efficacy, costs, and side effects. Standards of care for prophylaxis have not been established.

Methods: A committee of international experts was convened to review the available data regarding CMV prophylaxis and to compare preventative strategies for CMV after transplantation from seropositive donors or in seropositive recipients.

Results: Pre‐emptive therapy requires frequent monitoring with subsequent treatment of disease and associated costs, while universal prophylaxis results in greater exposure to potential toxicities and costs of drugs. The advantages of prophylaxis include suppressing asymptomatic viremia and prevention of both direct and indirect effects of CMV infection. Meta analyses reveal decreased in mortality for patients receiving CMV prophylaxis. Costs associated with prophylaxis are less than for routine monitoring and pre‐emptive therapy. The optimal duration of antiviral prophylaxis remains undefined. Extended prophylaxis may improve clinical outcomes in the highest‐risk patient populations including donor‐seropositive/recipient‐seronegative renal transplants and in CMV‐infected lung and heart transplantation.

Conclusions: Prophylaxis is beneficial in preventing direct and indirect effects of CMV infection in transplant recipients, affecting both allograft and patient survival. More studies are necessary to define optimal prophylaxis regimens.
Histology of Diplodia pinea in diseased and latently infected Pinus nigra shoots
Authors: Flowers J. L. , Hartman J. R. , Vaillancourt L. J.
Published: November 2006

Diplodia tip blight is a serious disease of >30 conifer species worldwide. Symptoms are particularly severe on non‐native, two‐needled Pinus species, and typically include stunted, necrotic needles and shoots and a general decline of the tree. Latent Diplodia pinea infections occur in current‐year shoots of some symptomless pines, and in some apparently healthy current‐year shoots of diseased pines. Latent infections also occur in symptomless terminal buds. A histological approach was used to investigate the nature of latent infections in shoot stems and terminal buds of landscape Pinus nigra. Fungal colonization was compared in healthy, diseased and latently infected tissues. A nested‐PCR technique that is specific for D. pinea was used to differentiate latently infected tissues from uninfected ones. Latent D. pinea infections were localized in the outer stem cortex, usually in the vicinity of needle scales at leaf axes. In contrast, pathogenic D. pinea infections were characterized by fungal colonization throughout the shoot stem tissues, even very early in symptom development. The presence of necrophylatic periderms in two of the latently infected samples suggests that host defences play a role in the production and maintenance of latent stem infections. Latent infections of terminal buds appeared to originate from the distal bud scales of axillary buds in the terminal bud cluster, and not from the subtending shoot. Fungal tissues were never observed inside asymptomatic, PCR‐negative shoots.
Neurodevelopmental outcomes and surgery in neonates
Authors: Walker Karen , Holland Andrew JA , Winlaw David , Sherwood Megan , Badawi Nadia
Published: November 2006

Abstract:  A neonate requiring major surgery in 2006 has a greater prospect of survival than ever before. Increasingly, however, there is awareness that critical illness may affect later neurodevelopment. Pre‐existing conditions in addition to the physiologic stresses associated with cardiac and general surgery are implicated but remain unavoidable in the case of significant structural abnormalities such as transposition of the great arteries or congenital diaphragmatic hernia. For those affected by neurodevelopmental impairment, there is a significant cost to the child, family and society. Current research focuses on the preventable causes of brain injury, before, during and after the intervention, and the rate of impairment in apparently uncomplicated procedures. In contrast to the quantity of neurodevelopmental outcome data following cardiac surgery, there remain few outcome studies dealing with non‐cardiac surgery despite such intervention being two to three times more common. There appear to be compelling clinical and economic arguments for the instigation of formalised population‐based developmental assessments for all infants undergoing major surgery.
Hypernatraemia in preterm infants born at less than 27 weeks gestation
Authors: Gawlowski Zuzanna , Aladangady Narendra , Coen Pietro G
Published: November 2006

Aims:  To study the incidence of hypernatraemia (plasma sodium >145 mmol/L), identify predisposing factors to and associated complications of hypernatraemia in preterm infants born less than 27 weeks gestation in the first 5 days of life.

Methods:  Preterm infants less than 27 week gestation over an 18‐month period were studied by retrospective analysis of patient records. Data were collected on gestation, birthweight, sex, antenatal steroid use, phototherapy, incubator humidity, time of transfer to incubator, plasma sodium, urea and creatinine. Actual fluid and sodium intake was calculated for the first 5 days of life. Data were collected on chronic lung disease, patent ductus arteriosus, intraventricular haemorrhage, necrotising enterocolitis and death.

Results:  In this study 46 (69.7%) of 66 infants studied developed hypernatraemia (>145 mmol/L), occurring most frequently between 24 and 48 h of age. The median gestation of hypernatraemic babies was significantly lower. There was no significant difference in median birthweight, or factors associated with increased insensible water loss between the hypernatraemic and the non‐hypernatraemic groups. Fluid intake was significantly higher on days 2, 3 and 4 in the hypernatraemic group. There was no difference in sodium intake between the two groups. More hypernatraemic babies compared with controls developed chronic lung disease, patent ductus arteriosus, significant intraventricular haemorrhage, necrotising enterocolitis and died, but was not significant.

Conclusion:  Hypernatraemia occurs commonly in preterm infants less than 27 weeks gestation and was not associated with significant morbidity. The more immature infants developed hypernatraemia and all cases resolved after increasing fluid intake.
Cefepime monotherapy for treatment of febrile neutropenia in children
Authors: Ariffin Hany , Ai Chong Lee , Lee Chan Lee , Abdullah Wan Ariffin
Published: November 2006

Aim:  Empirical therapy for children with febrile neutropenia has traditionally consisted of combination antibiotics, usually a beta‐lactam and an aminoglycoside. However, recent trends and international guidelines have now made monotherapy a feasible option in the management of this group of patients. We prospectively evaluated the efficacy and safety of cefepime monotherapy in our population of paediatric cancer patients with febrile neutropenia.

Methods:  An audit was performed on children aged 16 years and younger presenting with fever and neutropenia who were managed with empirical single‐agent cefepime. The patients were analysed for clinical outcome, documented infections and side‐effects of the study drug. Success was defined as clinical improvement without treatment modification. Death or any change to the empirical antibiotic was considered as failure.

Results:  In this study 79 children (median age 5.2 years) with 133 episodes of febrile neutropenia were prospectively studied between August 2004 and August 2005. A microbiologically documented infection was seen in 26 episodes. The success rate of cefepime monotherapy was 60%. The rate of survival through neutropenia (with or without modification) was 98%. No significant adverse effects were seen.

Conclusion:  Cefepime monotherapy is a safe and feasible option for treatment of childhood cancer patients with febrile neutropenia.
Acne, anxiety, depression and suicide in teenagers: A cross‐sectional survey of New Zealand secondary school students
Authors: Purvis Diana , Robinson Elizabeth , Merry Sally , Watson Peter
Published: November 2006

Aim:  To examine the associations between acne and depressive symptoms, anxiety and suicidal behaviours.

Methods:  This was a secondary analysis of a cross‐sectional survey –‘Youth2000’ (New Zealand national survey of youth health). A total of 9567 secondary school students aged 12–18 years participated in the survey. The main outcome measures were self‐reported acne, depressive symptoms (Reynolds Adolescent Depression Scale > 77), anxiety (Anxiety Disorder Index from Multidimensional Anxiety Scale for Children) and self‐reported suicide attempts.

Results:  ‘Problem acne’ was associated with an increased probability of depressive symptoms, odds ratio 2.04 (95% confidence interval 1.70–2.45); anxiety, odds ratio 2.3 (1.74–3.00); and suicide attempts, odds ratio 1.83 (1.51–2.22) in a logistic model that included age, gender, ethnicity, school decile and socio‐economic status. The association of acne with suicide attempts remained after controlling for depressive symptoms and anxiety, odds ratio 1.50 (1.21–1.86).

Conclusion:  Young people presenting with acne are at increased risk of depression, anxiety and suicide attempts. Attention should be paid to their mental health, and the importance of asking directly regarding suicide is emphasised.
Venous thromboembolic disease: A single‐centre case series study
Authors: Newall Fiona , Wallace Tim , Crock Catherine , Campbell Janine , Savoia Helen , Barnes Chris , Monagle Paul
Published: November 2006

Aim:  The epidemiology of venous thromboembolism in children has likely changed since first being described a decade ago because of evolving management strategies and a greater awareness of predisposing factors for thrombosis in children. The Royal Children's Hospital commenced a 4‐year prospective registry of venous thrombosis in 1999 to determine the current Australian epidemiology of venous thrombosis in infants and children.

Methods:  A prospective, single‐centre registry was established to determine the prevalence, aetiology, diagnostic criteria, management and outcome of venous thromboembolism in an Australian tertiary paediatric centre.

Results:  The incidence of venous thrombosis was 8.0/10 000 hospital admissions. Fifty‐eight per cent of infants and 49% of children were male. Seventy‐seven per cent of venous thromboses in infants were associated with central venous cannulation compared with 47% in children. Doppler ultrasonography was the most frequently used diagnostic tool. Treatment strategies varied between age groups. The all‐cause mortality rate for infants and children in this study was 8.4% (direct thrombus‐related mortality 0%). Fifteen per cent of all patients demonstrated complete resolution of their venous thrombosis at discharge, with 48% demonstrating complete resolution at follow‐up assessment. Fifteen per cent of patients experienced significant thrombosis‐related morbidity at follow‐up assessment.

Conclusion:  In this single‐centre registry, venous thrombosis in infants and children occurred with greater frequency than has previously been reported and its epidemiology varied. Central venous catheterisation continues to be a common precipitant to venous thrombosis. Optimal diagnostic and treatment interventions for venous thromboembolism have not yet been determined for infants and children, despite the significant incidence of long‐term sequelae.
Effect of formula thickened with locust bean gum on gastric emptying in infants
Authors: Miyazawa Reiko , Tomomasa Takeshi , Kaneko Hiroaki , Morikawa Akihiro
Published: November 2006

Aim:  We investigated the effects of milk‐based formulas thickened with two different concentrations of locust bean gum on gastric emptying in infants with recurrent regurgitation episodes.

Methods:  Thirty‐nine infants with three or more episodes of regurgitation per day but no complications who were fed mainly with infant formula were studied. We first compared gastric emptying in infants fed with formulas thickened with two different concentrations of locust bean gum (HL‐350, 0.35 g/100 mL; HL‐450, 0.45 g/100 mL) or a regular formula (HL‐00). To evaluate gastric emptying, we measured antral cross‐sectional areas ultrasonographically at various time points after feeding. Next, to investigate the clinical effect of thickened formulas on regurgitation episodes, 27 infants with episodes were assigned randomly to receive HL‐350 and HL‐00 or HL‐450 and HL‐00 for 1 week each.

Results:  Antral cross‐sectional areas at 60, 90, 120 and 150 min with HL‐450, and at 60 min with HL‐350, were greater than with HL‐00. The median gastric emptying rate at 120 min with HL‐450 (52.8%) was lower than with HL‐00 (97.9%; P = 0.0019), while HL‐350 (80.3%) and HL‐00 did not differ significantly. The mean number of regurgitation episodes was significantly smaller when infants were fed with either HL‐350 or HL‐450 than with HL‐00.

Conclusions:  HL‐450, a thickened formula with typical commercially available concentrations of locust bean gum, slowed gastric emptying in infants with gastroesophageal reflux.