Longitudinal vocabulary development in Australian urban Aboriginal children: Protective and risk factors.

BACKGROUND: Vocabulary is a key component of language that can impact on children's future literacy and communication. The gap between Australian Aboriginal and non-Aboriginal children's reading and academic outcomes is well reported and similar to Indigenous/non-Indigenous gaps in other nations. Determining factors that influence vocabulary acquisition over time and may be responsive to treatment is important for improving Aboriginal children's communication and academic outcomes. AIM: To determine what factors influence Australian urban Aboriginal children's receptive vocabulary acquisition and whether any of these are risks or protective for vocabulary development. METHOD: One hundred thirteen Aboriginal children in South Western Sydney from the longitudinal birth cohort Gudaga study were assessed on The Peabody Picture Vocabulary Test multiple times: 3 years, just prior to school entry, at the end of the first and second years of formal schooling. Multilevel models were used to determine the effects of 13 fixed and manipulable maternal, child, and family variables drawn from previous research. RESULTS: Higher maternal education was found to be protective at 3 years and over time. The number of children in urban Australian Aboriginal households made an impact on vocabulary development and this varied over time. From 3 to 6 years, those with early poor non-verbal cognitive skills had vocabulary skills that remained below those with stronger non-verbal skills at 3 years. Girls exhibit an earlier advantage in vocabulary acquisition, but this difference is not sustained after 4 years of age. CONCLUSIONS: The risk and protective factors for vocabulary development in Australian Aboriginal children are similar to those identified in other studies with some variation related to the number of children in the home. In this limited set of predictors, maternal education, gender, non-verbal cognitive skills, and the number of children in households were all shown to impact on the acquisition of vocabulary to 3 years and or the developmental trajectory over time.

Developmental vulnerability--don't investigate without a model in mind.

Children who are developmentally vulnerable are at risk of a difficult start to school, and ongoing educational challenges which may adversely impact on long term health outcomes. Clinicians, researchers and service providers need a thorough understanding of both risk and protective factors and their complex interplay to understand their impact on early childhood development, in order to plan effective and comprehensive prevention and interventions strategies. In this opinion piece we recommend that investigation of developmental vulnerability should only proceed if underpinned by both a theoretical model through which the interaction between risk and protective factors may be investigated, and analytical models that are appropriate to assess these impacts.

Measuring perinatal mental health risk.

The purpose of this review was to critically analyse existing tools to measure perinatal mental health risk and report on the psychometric properties of the various approaches using defined criteria. An initial literature search revealed 379 papers, from which 21 papers relating to ten instruments were included in the final review. A further four papers were identified from experts (one excluded) in the field. The psychometric properties of six multidimensional tools and/or criteria were assessed. None of the instruments met all of the requirements of the psychometric properties defined. Some had used large sample sizes but reported low positive predictive values (Antenatal Risk Questionnaire (ANRQ)) or insufficient information regarding their clinical performance (Antenatal Routine Psychosocial Assessment (ARPA)), while others had insufficient sample sizes (Antenatal Psychosocial Health Assessment Tool, Camberwell Assessment of Need-Mothers and Contextual Assessment of Maternity Experience). The ANRQ has fulfilled the requirements of this analysis more comprehensively than any other instrument examined based on the defined rating criteria. While it is desirable to recommend a tool for clinical practice, it is important that clinicians are made aware of their limitations. The ANRQ and ARPA represent multidimensional instruments commonly used within Australia, developed within large samples with either cutoff scores or numbers of risk factors related to service outcomes. Clinicians can use these tools, within the limitations presented here, to determine the need for further intervention or to refer women to mental health services. However, the effectiveness of routine perinatal psychosocial assessment continues to be debated, with further research required.

Insights into the structure/function of hepatocyte growth factor/scatter factor from studies with individual domains.

Hepatocyte growth factor/scatter factor (HGF/SF), the ligand for the receptor tyrosine kinase encoded by the c-Met proto-oncogene, is a multidomain protein structurally related to the pro-enzyme plasminogen and with major roles in development, tissue regeneration and cancer. We have expressed the N-terminal (N) domain, the four kringle domains (K1 to K4) and the serine proteinase homology domain (SP) of HGF/SF individually in yeast or mammalian cells and studied their ability to: (i) bind the Met receptor as well as heparan sulphate and dermatan sulphate co-receptors, (ii) activate Met in target cells and, (iii) map their binding sites onto the beta-propeller domain of Met. The N, K1 and SP domains bound Met directly with comparable affinities (K(d)=2.4, 3.3 and 1.4 microM). The same domains also bound heparin with decreasing affinities (N>K1>>SP) but only the N domain bound dermatan sulphate. Three kringle domains (K1, K2 and K4) displayed agonistic activity on target cells. In contrast, the N and SP domains, although capable of Met binding, displayed no or little activity. Further, cross-linking experiments demonstrated that both the N domain and kringles 1-2 bind the beta-chain moiety (amino acid residues 308-514) of the Met beta-propeller. In summary, the K1, K2 and K4 domains of HGF/SF are sufficient for Met activation, whereas the N and SP domains are not, although the latter domains contribute additional binding sites necessary for receptor activation by full length HGF/SF. The results provide new insights into the structure/function of HGF/SF and a basis for engineering the N and K1 domains as receptor antagonists for cancer therapy.

Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors.

The receptor tyrosine kinase Met and its ligand HGF/SF (hepatocyte growth factor/scatter factor) are essential in the signalling pathways required for embryogenesis and tissue regeneration. Aberrant signalling of this complex is also a feature of many tumours and appears to contribute to the growth, invasiveness and metastasis of both carcinomas and sarcomas. HGF/SF, like many other angiogenic growth factors, employs heparan sulphate as co-receptor. The role of this interaction has not been completely defined but appears to be physiologically relevant. Thus the presence of heparin increases the potency of HGF/SF in experiments with cells in culture leading to elevated downstream signalling effects and, although not vital for the Met-HGF/SF interaction, heparin or heparan sulphate is essential for the activity of certain isoforms of HGF/SF, such as NK1 and NK2. Here, we summarize the progress made in understanding the interaction between heparin and heparan sulphate and NK1, NK2 and HGF/SF and we discuss their role in HGF/SF-Met signalling.

Influenza A virus surveillance in wild birds in Northern Europe in 1999 and 2000.

Using reverse transcription/polymerase chain reaction (RT-PCR), we have screened more than 8500 wild birds in Northern Europe in 1999 and 2000 for the presence of influenza A virus. Although our primary focus was on ducks, geese, and shorebirds, we have also tested thousands of samples from other bird species. Approximately 1% of our samples were positive for influenza A virus by RT-PCR, and from half of these we were able to isolate influenza A virus in embryonated chicken eggs. A wide variety of isolates was obtained representing hemagglutinin (HA) subtypes 1 through 7, 10, 11, 13, an unidentifiable HA, and neuraminidase (NA) subtypes 1 through 8.

Structure and reactivity in the non-mevalonate pathway of isoprenoid biosynthesis.

The function, structure and mechanism of two Escherichia coli enzymes involved in the non-mevalonate route of isoprenoid biosynthesis, 2C-methyl-D-erythritol 4-phosphate cytidylyltransferase and 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, are reviewed. Comparisons of each with enzymes from microbial pathogens highlight important conservation of sequence suggestive of similarities in secondary structure, subunit folds, quaternary structure and active sites. Since both enzymes are validated drug targets, the models provide templates for structure-based design of anti-microbial agents targeting a number of serious human diseases.

Care and services for spinal injured people with, and without, neurological deficit.

PURPOSE: To describe the care and service usage characteristics of the spinal injured (SI) population of New South Wales (NSW), Australia, including people without significant permanent neurological deficits. METHOD: A cross-sectional mailed survey was undertaken with all persons admitted to the two spinal injury hospital units in NSW following traumatic spinal injury in the period 1977 - 1992 who were not known to be deceased (n=2432). Response was gained from 75.8% of the 932 persons whose address was able to be confirmed (n=706). RESULTS: SI persons were primarily males who incurred a motor related trauma at a young age. Over one third had minimal or no permanent neurological impairment. Over half of the respondents received assistance with everyday living (59.5%), including older persons with minimal or no motor or sensory problems, and a large number made use of professional services (40.5%). People with lower-level incomplete lesions were more likely to use paramedical services than some groups of people with quadriplegia. CONCLUSIONS: The relatively high use of care and paramedical services by some persons with minimal physical functional limitations indicates the importance of including such persons when considering the provision of long-term care and rehabilitation services for people with spinal injury.

Crystallization and preliminary X-ray diffraction studies of recombinant Escherichia coli 4-diphosphocytidyl-2-C-methyl-D-erythritol synthetase.

Diphosphocytidyl-methylerythritol (DPCME) synthetase is involved in the mevalonate-independent pathway of isoprenoid biosynthesis, where it catalyses the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from 2-C-methyl-D-erythritol 4-phosphate and CTP. The Escherichia coli enzyme has been cloned, expressed in high yield, purified and crystallized. Elongated tetragonal prismatic crystals grown by the hanging-drop vapour-diffusion method using polyethylene glycol (PEG) 4000 as the precipitant belong to space group P4(1)2(1)2 (or P4(3)2(1)2), with unit-cell parameters a = b = 73.60, c = 175.56 A. Diffraction data have been recorded to 2.4 A resolution using synchrotron radiation.

Detection of influenza A viruses from different species by PCR amplification of conserved sequences in the matrix gene.

The recently raised awareness of the threat of a new influenza pandemic has stimulated interest in the detection of influenza A viruses in human as well as animal secretions. Virus isolation alone is unsatisfactory for this purpose because of its inherent limited sensitivity and the lack of host cells that are universally permissive to all influenza A viruses. Previously described PCR methods are more sensitive but are targeted predominantly at virus strains currently circulating in humans, since the sequences of the primer sets display considerable numbers of mismatches to the sequences of animal influenza A viruses. Therefore, a new set of primers, based on highly conserved regions of the matrix gene, was designed for single-tube reverse transcription-PCR for the detection of influenza A viruses from multiple species. This PCR proved to be fully reactive with a panel of 25 genetically diverse virus isolates that were obtained from birds, humans, pigs, horses, and seals and that included all known subtypes of influenza A virus. It was not reactive with the 11 other RNA viruses tested. Comparative tests with throat swab samples from humans and fecal and cloacal swab samples from birds confirmed that the new PCR is faster and up to 100-fold more sensitive than classical virus isolation procedures.

Vacuum-assisted stereotactic breast biopsy: histologic underestimation of malignant lesions.

HYPOTHESIS: The histopathologic correlation between stereotactic core needle biopsy and subsequent surgical excision of mammographically detected nonpalpable breast abnormalities is improved with a larger-core (11-gauge) device. DESIGN: Retrospective medical record and histopathologic review. SETTING: University-based academic practice setting. PATIENTS: Two hundred one patients who underwent surgical excision of mammographic abnormalities that had undergone biopsy with an 11-gauge vacuum-assisted stereotactic core biopsy device. MAIN OUTCOME MEASURE: Correlation between stereotactic biopsy histologic results and the histologic results of subsequent surgical specimens. RESULTS: Results of stereotactic biopsy performed on 851 patients revealed atypical hyperplasia in 46 lesions, ductal carcinoma in situ (DCIS) in 89 lesions, and invasive cancer in 73 mammographic abnormalities. Subsequent surgical excision of the 46 atypical lesions revealed 2 cases of DCIS (4.3%) and 4 cases of invasive carcinoma (8.7%). Lesions diagnosed as DCIS on stereotactic biopsy proved to be invasive carcinoma in 10 (11.2%) of 89 patients on subsequent excision. Stereotactic biopsy completely removed 21 (23.6%) of 89 DCIS lesions and 20 (27.4%) of 73 invasive carcinomas. CONCLUSIONS: In summary, 11-gauge vacuum-assisted core breast biopsy accurately predicts the degree of disease in the majority of malignant lesions; however, understaging still occurs in 11% to 13% of lesions showing atypical hyperplasia or DCIS.

Word recognition by children listening to speech processed into a small number of channels: data from normal-hearing children and children with cochlear implants.

OBJECTIVE: The aims of this study were 1) to determine the number of channels of stimulation needed by normal-hearing adults and children to achieve a high level of word recognition and 2) to compare the performance of normal-hearing children and adults listening to speech processed into 6 to 20 channels of stimulation with the performance of children who use the Nucleus 22 cochlear implant. DESIGN: In Experiment 1, the words from the Multisyllabic Lexical Neighborhood Test (MLNT) were processed into 6 to 20 channels and output as the sum of sine waves at the center frequency of the analysis bands. The signals were presented to normal-hearing adults and children for identification. In Experiment 2, the wideband recordings of the MLNT words were presented to early-implanted and late-implanted children who used the Nucleus 22 cochlear implant. RESULTS: Experiment 1: Normal-hearing children needed more channels of stimulation than adults to recognize words. Ten channels allowed 99% correct word recognition for adults; 12 channels allowed 92% correct word recognition for children. Experiment 2: The average level of intelligibility for both early- and late-implanted children was equivalent to that found for normal-hearing adults listening to four to six channels of stimulation. The best intelligibility for implanted children was equivalent to that found for normal-hearing adults listening to six channels of stimulation. The distribution of scores for early- and late-implanted children differed. Nineteen percent of the late-implanted children achieved scores below that allowed by a 6-channel processor. None of the early-implanted children fell into this category. CONCLUSIONS: The average implanted child must deal with a signal that is significantly degraded. This is likely to prolong the period of language acquisition. The period could be significantly shortened if implants were able to deliver at least eight functional channels of stimulation. Twelve functional channels of stimulation would provide signals near the intelligibility of wideband signals in quiet.

New modification of hot-water irrigation in the treatment of posterior epistaxis.

BACKGROUND: Tamponade treatment for epistaxis is painful and traumatic to the nasal mucosa, and may necessitate hospitalization for several days. Hot-water irrigation (HWI) was introduced as a treatment of epistaxis more than 100 years ago. In a previous study the treatment proved to be effective, less painful, and less traumatic, and required a shorter hospital stay than tamponade treatment. However, HWI has the risk of aspiration during treatment. To minimize this risk, a special catheter has been designed. OBJECTIVES: To evaluate the modified HWI and to compare the results with tamponade treatment, with respect to patient compliance, effectiveness, recurrence of bleeding, pain, complications, and length of hospital stay. PATIENTS: A total of 122 patients, hospitalized for posterior epistaxis, were randomized to receive either HWI or tamponade treatment. RESULTS: In the HWI group, 31 (55%) of the patients could be discharged from the hospital after the initial treatment only, compared with 29 (44%) of the patients treated with tamponade. Using a 10-cm visual analog scale, the mean pain score during treatment was 4.7 in the HWI group compared with 7.5 in the tamponade group. The mean hospital stay was 2.9 days for the HWI group vs. 4.0 days for the tamponade group. After discharge from the hospital, necrosis or synechia was found on rhinoscopy in 12 patients (40%) in the tamponade group compared with none in the HWI group. CONCLUSIONS: Compared with tamponade treatment, HWI is as effective, requires a significantly shorter hospital stay, is less traumatic to the nose, and is significantly less painful.

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action.

Regulation of gene activation by the estrogen receptor (ER) is complex and involves co-regulatory proteins, oncoproteins (such as Fos and Jun), and phosphorylation signaling pathways. Here we report the cloning and initial characterization of a novel protein, Brx, that contains a region of identity to the oncogenic Rho-guanine nucleotide exchange (Rho-GEF) protein Lbc, and a unique region capable of binding to nuclear hormone receptors, including the ER. Western and immunohistochemistry studies showed Brx to be expressed in estrogen-responsive reproductive tissues, including breast ductal epithelium. Brx bound specifically to the ER via an interaction that required distinct regions of ER and Brx. Furthermore, overexpression of Brx in transfection experiments using an estrogen-responsive reporter revealed that Brx augmented gene activation by the ER in an element-specific and ligand-dependent manner. Moreover, activation of ER by Brx could be specifically inhibited by a dominant-negative mutant of Cdc42Hs, but not by dominant negative mutants of RhoA or Rac1. Taken together, these data suggest that Brx represents a novel modular protein that may integrate cytoplasmic signaling pathways involving Rho family GTPases and nuclear hormone receptors.

Retinoid X receptor and peroxisome proliferator-activated receptor activate an estrogen responsive gene independent of the estrogen receptor.

Estrogen receptors regulate transcription of genes essential for sexual development and reproductive function. Since the retinoid X receptor (RXR) is able to modulate estrogen responsive genes and both 9-cis RA and fatty acids influenced development of estrogen responsive tumors, we hypothesized that estrogen responsive genes might be modulated by RXR and the fatty acid receptor (peroxisome proliferator-activated receptor, PPAR). To test this hypothesis, transfection assays in CV-1 cells were performed with an estrogen response element (ERE) coupled to a luciferase reporter construct. Addition of expression vectors for RXR and PPAR resulted in an 11-fold increase in luciferase activity in the presence of 9-cis RA. Furthermore, mobility shift assays demonstrated binding of RXR and PPAR to the vitellogenin A2-ERE and an ERE in the oxytocin promoter. Methylation interference assays demonstrated that specific guanine residues required for RXR/PPAR binding to the ERE were similar to residues required for ER binding. Moreover, RXR domain-deleted constructs in transfection assays showed that activation required RXR since an RXR delta AF-2 mutant completely abrogated reporter activity. Oligoprecipitation binding studies with biotinylated ERE and (35)S-labeled in vitro translated RXR constructs confirmed binding of delta AF-2 RXR mutant to the ERE in the presence of baculovirus-expressed PPAR. Finally, in situ hybridization confirmed RXR and PPAR mRNA expression in estrogen responsive tissues. Collectively, these data suggest that RXR and PPAR are present in reproductive tissues, are capable of activating estrogen responsive genes and suggest that the mechanism of activation may involve direct binding of the receptors to estrogen response elements.

Rhesus immunization after renal transplantation.

Previous reports, before the advent of cyclosporine, suggest that the small amount of blood transplanted with a kidney can result in rhesus D (RhD) antibody production. We looked for retrospective and current evidence of primary RhD antibody production following renal transplantation in RhD-negative recipients of an RhD-positive kidney. Of 42 patients, all on triple immunosuppressive therapy, 2 (5%) were found to have an RhD antibody identified for the first time after transplantation. As the number of pregnancies in transplant recipients increases, the small risk of primary immunization and subsequent risk of hemolytic disease of the newborn will become more important. Therefore, we recommend that all RhD-negative women of child-bearing age receiving an RhD-positive solid organ transplant are given a prophylactic dose of 500 IU of anti-D immunoglobulin intramuscularly at the time of transplantation.

Increasing attendance at immunisation clinics: lessons from a trial program that failed.

Previous studies suggested that the use of a baby-enrolment and reminder system for early childhood immunisation increased public immunisation clinic attendance. It was decided to run a trial to assess the effects of introducing a baby-enrolment program on attendances at local government immunisation clinics. Enrolment leaflets were distributed to each mother of a new child in six areas of greater Sydney while the mother was in the postnatal ward of the local hospital. Clinic attendance figures were monitored, interviews were conducted with mothers as well as professionals involved in early childhood health services, and the conduct of clinics was observed. The trial failed to increase attendance at public clinics. Mothers' reasons for choice of service, particularly their desire for what they believed to be a more personalised service, and the attitude of the professionals (particularly community nurses) with whom they came in contact were considered to be more influential in determining their use (or lack of use) of public immunisation services. Baby enrolment may be effective in increasing attendance at public immunisation clinics only where there is willing cooperation of all stakeholders in supporting public immunisation services.