Participation of Australian Aboriginal and Torres Strait Islander families in a parent support programme: longitudinal associations between playgroup attendance and child, parent and community outcomes.

BACKGROUND: Playgroups are a relatively unique form of family support programme that is common in Australia which has high community acceptance and significant government investment. However, limited evidence exists regarding the effectiveness of playgroups to achieve better outcomes for children and their parents. This study describes patterns of playgroup participation for Aboriginal and Torres Strait Islander families with young children and examines the extent to which participation from birth to three years is associated with subsequent child, parent and community outcomes. METHODS: This study uses three years of longitudinal data for 622 Aboriginal and Torres Strait Islander children who were participants in the Longitudinal Study of Indigenous Children (LSIC). Longitudinal associations between playgroup attendance when children were age 2 and 3 years and outcome measures for child vocabulary, motor skills, behaviour problems, prosocial development, parent home learning engagement, resilience, advice-seeking and health service use, and community trustworthiness were examined using path analysis. RESULTS: Rates of playgroup participation in this sample group were generally lower than for Australian children overall. Playgroup attendance when children were age 2 to 3 years was associated with higher parental engagement in home learning activities when children were aged 4 years which, in turn, was associated with stronger expressive vocabulary scores for children. CONCLUSION: The findings from this study suggest that playgroup participation can enhance the home learning environments for Aboriginal and Torres Strait Islander children. Playgroups as a parent support programme hold strong potential to reach and engage families, particularly in areas of high geographic isolation, which can realize improved outcomes for children, parents and communities.

Molecular phenotypes of DCIS predict overall and invasive recurrence.

BACKGROUND: Molecular phenotypes of invasive breast cancer predict early recurrence. Ductal carcinoma in situ (DCIS) exhibits similar phenotypes, but their frequency and significance remain unclear. To determine whether DCIS molecular phenotypes predict recurrence, 314 women (median age 57.7 years) with primary DCIS who were screened or entered DCIS trials in a specialist breast unit from 1990 to 2010 were studied. PATIENTS AND METHODS: Expression of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) within primary DCIS was established using immunohistochemistry (IHC). Patients were subdivided into molecular phenotypes using IHC surrogates [Luminal A (ER/PR+HER2-), Luminal B (ER/PR+/HER2+), HER2 type (ER and PR-/HER2+) or triple negative (ER/PR/HER2)] and recurrence rates compared. RESULTS: Overall, there were 57 (18.2%) recurrences, 35 (11.2%) DCIS and 22 (7%) invasive cancer. A low rate of recurrence at 5 years was seen in Luminal A DCIS (7.6%), compared with 15.8%-36.1% in other phenotypes. Independent predictors of overall recurrence on multivariate analysis were involved (<1 mm) surgical margins (HR 4.31, P < 0.001), high-grade lesions (HR 2.28, P < 0.024) and molecular phenotype (HR 5.14, P = 0.001 for Luminal B; HR 6.46, P < 0.001 for HER2 type and HR 3.27, P = 0.028 for triple-negative disease compared with Luminal A DCIS). Independent predictors for invasive recurrence were high Ki67 expression (HR 1.04, P = 0.021) and molecular phenotype (HR 13.4, P = 0.014 for Luminal B; HR 11.4, P = 0.027 for HER2 type and HR 10.3, P = 0.031 for triple negative compared with Luminal A DCIS). CONCLUSIONS: DCIS molecular phenotype predicts for both overall and invasive recurrence. HER2 testing of DCIS could help clinicians individualise the treatment of patients with DCIS.

Quantitative studies of pinocytosis. II. Kinetics of protein uptake and digestion by rat yolk sac cultured in vitro.

Pinocytic uptake of 125I-labeled bovine serum albumin by 17.5-day rat visceral yolk sac cultured in vitro has been examined. Uptake was followed by intracellular digestion and, after an initial period, the content of radioactivity in the tissue itself remained constant during the incubation. Radiolabel was returned to the culture medium predominantly as (125I)iodotyrosine; exocytosis of undigested protein did not occur. The rate of uptake of labeled protein, which was constant within an experiment and reproducible between experiments, was much higher than that of a nondigestible macromolecule, 125I-labeled polyvinylpyrrolidone. The higher rate of uptake was a consequence of the protein entering the cells chiefly by adsorption to the plasma membrane being internalized; 125I-labeled albumin did not stimualte, nor did 125I-labeled polyvinylpyrrolidone inhibit pinocytosis. Different preparations of 125I-labeled albumin had characteristically different rates of uptake, probably reflecting differences in affinity for plasma membrane receptors. The physiological significance of the findings is discussed.

Quantitative studies of pinocytosis. I. Kinetics of uptake of (125I)polyvinylpyrrolidone by rat yolk sac cultured in vitro.

A method is described for the in vitro culture of 17.5-day rat visceral yolk sac. Tissue survival was good as judged by light and electron microscopy. The rate of pinocytic uptake of 125I-labeled polyvinylpyrrolidone by the tissue was constant both within and between experiments. Within the concentration range 0.15-24 mug/ml, the 125I-labeled polyvinylpyrrolidone neither stimulated nor inhibited pinocytosis. The system offers many advantages in the quantitative study of the physical basis of pinocytosis.

Cognitive effects of memantine in postmenopausal women at risk of dementia: a pilot study.

BACKGROUND: To determine the effects of memantine on cognition in a normal population of postmenopausal women with putative risk factors for Alzheimer's disease (AD) using a built-in control for the genetic risk factor for AD (apoE-epsilon4 status). METHODS: A prospective, open-label, 6-month pilot medication trial with memantine and follow-up after discontinuance conducted at the Center for Neuroscience in Women's Health, Stanford University School of Medicine. Neuropsychological data were collected on 22 community-dwelling postmenopausal women (11 apoE-epsilon4 carriers and 11 apoE-epsilon4 non-carriers) with at least one putative risk factor for AD. RESULTS: ApoE-epsilon4 status was not a significant predictor of change in neuropsychological performance. Changes associated with memantine treatment for entire sample included significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal. A positive medication effect was noted with executive functions and possibly category fluency. Trend-level improvements were seen in motor dexterity of the non-dominant hand and maintained even after drug discontinuance. CONCLUSIONS: Treatment with memantine appeared to have differential effects on cognitive performance in a population of women with putative risk factors for AD. ApoE-epsilon4 carrier status did not account for observed changes in cognition.

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial.

BACKGROUND: Varenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). A study was undertaken to compare a 12-week standard regimen of varenicline with a 10-week standard regimen of transdermal nicotine replacement therapy (NRT) for smoking cessation. METHODS: In this 52-week, open-label, randomised, multicentre, phase 3 trial conducted in Belgium, France, The Netherlands, UK and USA, participants were randomly assigned (1:1) to receive varenicline uptitrated to 1 mg twice daily for 12 weeks or transdermal NRT (21 mg/day reducing to 7 mg/day) for 10 weeks. Non-treatment follow-up continued to week 52. The primary outcome was the biochemically confirmed (exhaled carbon monoxide < or = 10 ppm) self-reported continuous abstinence rate (CAR) for the last 4 weeks of the treatment period in participants who had taken at least one dose of treatment. Secondary outcomes included CAR from the last 4 weeks of treatment through weeks 24 and 52, and measures of craving, withdrawal and smoking satisfaction. RESULTS: A total of 376 and 370 participants assigned to varenicline and NRT, respectively, were eligible for analysis. The CAR for the last 4 weeks of treatment was significantly greater for varenicline (55.9%) than NRT (43.2%; OR 1.70, 95% CI 1.26 to 2.28, p<0.001). The week 52 CAR (NRT, weeks 8-52; varenicline, weeks 9-52) was 26.1% for varenicline and 20.3% for NRT (OR 1.40, 95% CI 0.99 to 1.99, p = 0.056). Varenicline significantly reduced craving (p<0.001), withdrawal symptoms (p<0.001) and smoking satisfaction (p<0.001) compared with NRT. The most frequent adverse event was nausea (varenicline, 37.2%; NRT, 9.7%). CONCLUSIONS: The outcomes of this trial established that abstinence from smoking was greater and craving, withdrawal symptoms and smoking satisfaction were less at the end of treatment with varenicline than with transdermal NRT. TRIAL REGISTRATION NUMBER: NCT00143325.

The use of a psychological intervention to increase adherence during factor administration in a child with haemophilia.

While factor replacement treatments allow children with haemophilia to lead near normal lives, these treatments can be difficult to administer, especially to younger children. The intervenous infusions required by these treatments can be painful and result in children attempting to avoid treatment by exhibiting a range of inappropriate behaviours. Their children's uncooperative behaviour during prophylaxis was cited by parents as a significant barrier to treatment adherence. This study provides a case illustration of the use of psychological interventions to increase adherence during factor administration. Single-case methodology was used to demonstrate the effectiveness of the psychological interventions including counterconditioning, distraction, and positive differential reinforcement. The intervention resulted in increased adherence across several months of intervention. Psychological interventions can be effectively used by caregivers and care providers to increase adherence in the treatment of haemophilia.

The effects of snow and salt on ice table stability in University Valley, Antarctica.

The Antarctic Dry Valleys represent a unique environment where it is possible to study dry permafrost overlaying an ice-rich permafrost. In this paper, two opposing mechanisms for ice table stability in University Valley are addressed: i) diffusive recharge via thin seasonal snow deposits andii) desiccation via salt deposits in the upper soil column. A high-resolution time-marching soil and snow model was constructed and applied to University Valley, driven by meteorological station atmospheric measurements. It was found that periodic thin surficial snow deposits (observed in University Valley) are capable of drastically slowing (if not completely eliminating) the underlying ice table ablation. The effects of NaCl, CaCl2 and perchlorate deposits were then modelled. Unlike the snow cover, however, the presence of salt in the soil surface (but no periodic snow) results in a slight increase in the ice table recession rate, due to the hygroscopic effects of salt sequestering vapour from the ice table below. Near-surface pore ice frequently forms when large amounts of salt are present in the soil due to the suppression of the saturation vapour pressure. Implications for Mars high latitudes are discussed.

Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid.

The preclinical pharmacology of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline, a novel smoking cessation agent is described. Varenicline binds with subnanomolar affinity only to alpha4beta2 nAChRs and in vitro functional patch clamp studies in HEK cells expressing nAChRs show that varenicline is a partial agonist with 45% of nicotine's maximal efficacy at alpha4beta2 nAChRs. In neurochemical models varenicline has significantly lower (40-60%) efficacy than nicotine in stimulating [(3)H]-dopamine release from rat brain slices in vitro and in increasing dopamine release from rat nucleus accumbens in vivo, while it is more potent than nicotine. In addition, when combined with nicotine, varenicline effectively attenuates the nicotine-induced dopamine release to the level of the effect of varenicline alone, consistent with partial agonism. Finally, varenicline reduces nicotine self-administration in rats and supports lower self-administration break points than nicotine. These data suggest that varenicline can reproduce to some extent the subjective effects of smoking by partially activating alpha4beta2 nAChRs, while preventing full activation of these receptors by nicotine. Based on these findings, varenicline was advanced into clinical development and recently shown to be an effective and safe aid for smoking cessation treatment.

Memorable objects are more susceptible to forgetting: Evidence for the inhibitory account of retrieval-induced forgetting.

Retrieval of target information can cause forgetting for related, but non-retrieved, information - retrieval-induced forgetting (RIF). The aim of the current studies was to examine a key prediction of the inhibitory account of RIF - interference dependence - whereby 'strong' non-retrieved items are more likely to interfere during retrieval and therefore, are more susceptible to RIF. Using visual objects allowed us to examine and contrast one index of item strength -object typicality, that is, how typical of its category an object is. Experiment 1 provided proof of concept for our variant of the recognition practice paradigm. Experiment 2 tested the prediction of the inhibitory account that the magnitude of RIF for natural visual objects would be dependent on item strength. Non-typical objects were more memorable overall than typical objects. We found that object memorability (as determined by typicality) influenced RIF with significant forgetting occurring for the memorable (non-typical), but not non-memorable (typical), objects. The current findings strongly support an inhibitory account of retrieval-induced forgetting.

Multiple vaccine and pyridostigmine interactions: effects on EEG and sleep in the common marmoset.

Following active service during the 1990/1991 Gulf conflict, a number of UK and US veterans presented with a diverse range of symptoms, collectively known as Gulf Veterans' Illnesses (GVI). The administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (PB), given to Armed Forces personnel during the Gulf conflict has been implicated as a possible factor in the aetiology of these illnesses. The possibility that long-term health effects may result from the administration of these vaccines (anthrax, pertussis, plague, yellow fever, polio, typhoid, tetanus, hepatitis B, meningococcal meningitis and cholera) and/or PB, have been investigated using a non-human primate model, the common marmoset. This paper reports the results from two aspects of the study, brain electrical activity (EEG, collected during performance of a touchscreen mediated discrimination task) and sleep. There were no marked long-term changes in EEG or sleep patterns that could be attributed to vaccines and/or PB administration. The changes that were detected were predominantly time related and independent of treatment. Where statistical differences were detected between treatments, the magnitudes of the difference were relatively minor and therefore not regarded as having long term biological significance.

Activation of the Saccharomyces cerevisiae filamentation/invasion pathway by osmotic stress in high-osmolarity glycogen pathway mutants.

Mitogen-activated protein kinase (MAPK) cascades are frequently used signal transduction mechanisms in eukaryotes. Of the five MAPK cascades in Saccharomyces cerevisiae, the high-osmolarity glycerol response (HOG) pathway functions to sense and respond to hypertonic stress. We utilized a partial loss-of-function mutant in the HOG pathway, pbs2-3, in a high-copy suppressor screen to identify proteins that modulate growth on high-osmolarity media. Three high-copy suppressors of pbs2-3 osmosensitivity were identified: MSG5, CAK1, and TRX1. Msg5p is a dual-specificity phosphatase that was previously demonstrated to dephosphorylate MAPKs in yeast. Deletions of the putative MAPK targets of Msg5p revealed that kss1delta could suppress the osmosensitivity of pbs2-3. Kss1p is phosphorylated in response to hyperosmotic shock in a pbs2-3 strain, but not in a wild-type strain nor in a pbs2-3 strain overexpressing MSG5. Both TEC1 and FRE::lacZ expressions are activated in strains lacking a functional HOG pathway during osmotic stress in a filamentation/invasion-pathway-dependent manner. Additionally, the cellular projections formed by a pbs2-3 mutant on high osmolarity are absent in strains lacking KSS1 or STE7. These data suggest that the loss of filamentation/invasion pathway repression contributes to the HOG mutant phenotype.

A novel method for activity monitoring in small non-human primates.

Patterns of spontaneous activity are valuable reflections of well-being in animals and humans and, because of this, investigations have frequently incorporated some form of activity monitoring into their studies. It is widely believed that activity monitoring, alongside assessments of general behaviour, should be included in initial CNS safety pharmacology screening. As the number of marmoset studies having actimetry as their focus, or as an adjunct, is increasing, we wished to evaluate an alternative approach to those commonly used. The method is based on miniaturized accelerometer technologies, currently used for human activity monitoring.Actiwatch-Minis were used to monitor the activity of two groups of differently housed marmosets for 14 consecutive days. Group A consisted of four mixed-sex pairs of animals and group B comprised eight group-housed males. Activity profiles were generated for weekday and weekend periods. The devices captured quantifiable data which showed differences in total activity between the two differently housed groups and revealed intragroup variations in the temporal spread of activity between weekdays and weekends. The Actiwatch-Mini has been shown to generate retrospective, data-logged activity counts recorded from multiple animals in a single arena by means of non-invasive monitoring.

Glycogen metabolism in the rat visceral yolk sac. I. Glycogen content and gestational age.

The glycogen content of the rat visceral yolk sac was determined between 13.5 and 20.5 days of gestation by the best available colorimetric method. The concentration of glycogen in the tissue increased ten-fold between 13.5 and 18.5 days, to reach a value similar to that for mammalian muscle, but then decreased by 50 per cent between 18.5 and 20.5 days. Determination of the iodine-iodide spectra and fractionation of the glycogen particles by a novel sodium citrate centrifugation method indicated broad similarities between the structures of glycogen particles, isolated by a mild phenol-water method, from the yolk sac and the liver of the rat. However, the proportion of 'high'-molecular-weight glycogen in the yolk sac increases between 18.5 and 20.5 days, as a result of the preferential loss of 'low'-molecular-weight glycogen, so that at term the proportion approaches that found in liver glycogen.

Glycogen metabolism in the rat visceral yolk sac. 2. Activity of glycogen-degrading enzymes.

In an attempt to explain the previous observation of the rise and subsequent fall in glycogen content of the rat visceral yolk sac during the latter half of gestation, the activities of glycogen phosphorylase, glucose-6-phosphatase and lysosomal alpha-glucosidase were measured. Glycogen phosphorylase was found to be present in the yolk sac and, as in adult rat liver, was predominantly in the 'a' (active) form. The specific activity of the enzyme was lower than in adult rat liver, when expressed per mg tissue protein or per mg tissue wet weight, but similar when expressed per mg tissue glycogen. Phosphorylase activity in yolk sac was similar at 16.5 and 18.5 days of gestation. Glucose-6-phosphatase activity was not detectable in the yolk sac at either 15.5 or 18.5 days of gestation. Two lysosomal enzymes, acid alpha-glucosidase and N-acetyl-beta-hexosaminidase, were shown to be present in the yolk sac at higher specific activity than in adult liver. Alpha-Glucosidase activity in yolk sac was similar at 15.5 and 18.5 days of gestation. It is concluded that the net degradation of yolk sac glycogen initiated around 18.5 days of gestation does not serve to provide glucose for the fetus, and may indicate an increased demand for metabolic energy within the yolk sac itself.

Concordance between p53 protein overexpression and gene mutation in a large series of common human carcinomas.

Immunohistochemical (IHC) detection of p53 protein was compared with the presence of p53 gene mutation in many colorectal (n = 100), breast (n = 92), endometrial (n = 122), and gastric (n = 116) carcinomas. Two commercially available antibodies, DO7 and CM1, were used for IHC analysis of paraffin-embedded tissue sections. Screening for gene mutations in frozen and paraffin-embedded tumor samples was carried out using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The frequency of nuclear staining with DO7 or CM1 for each tumor type, respectively, was colorectal (36%, 23%); breast (15%, 19%); endometrial (21%, 33%); and gastric (23%,-). Overall correlation between the two antibodies for nuclear staining was 90% for the 314 tumors analyzed. Cytoplasmic staining was observed with DO7 in 7% of breast and 5% of gastric carcinomas and with CM1 in 17% of breast and 54% of endometrial carcinomas. p53 gene mutation was found in 39% of colorectal, 28% of breast, 13% of endometrial, and 25% of gastric cancers. The concordance between p53 nuclear overexpression and gene mutation (both positive or both negative) was 68% for colorectal, 79% for breast, 76% for endometrial, and 73% for gastric carcinomas. This study provides further evidence that IHC detection of p53 protein accumulation does not always indicate the presence of a gene mutation and vice versa. Discordant results were observed in approximately 20% to 30% of the tumors studied, highlighting the need for careful characterization of both p53 gene and protein alterations when assessing the relationship between p53 status and tumor behavior.

Obsessive-compulsive disorder in pregnancy, the puerperium, and the premenstruum.

BACKGROUND: Recent reports suggest that pregnancy and the puerperium may precipitate or exacerbate obsessive-compulsive disorder (OCD). The influence of this illness on other reproductive events, such as the premenstruum, is unknown. We examined retrospectively the relationships of pregnancy, the puerperium, and premenstruum to the course of OCD in 57 women. METHOD: Women outpatients with OCD meeting DSM-III-R criteria completed a standardized telephone interview administered by a psychiatric resident. They were asked retrospectively about the clinical course of their illness premenstrually and during and after pregnancy. RESULTS: Of 72 women eligible for the study, 79% (N = 57) completed the interview. Premenstrual worsening of OCD was described by 24 (42%) of the 57 women, and 12 (21%) described premenstrual dysphoria. Of the 57 women, 38 (67%) had been pregnant at least once; 31 (54%) had delivered at least one child. Pregnancy was associated with the onset of OCD in only 5 (13%) of the 38 women. Of the 29 women with preexisting OCD who became pregnant, 20 (69%) described no change in symptoms during pregnancy, 5 (17%) described worsening, and 4 (14%) described improvement. Postpartum exacerbation of OCD symptoms was reported by 7 (29%) of the 24 women with preexisting OCD who completed full-term pregnancies. Nine (37%) of the 24 women with both preexisting OCD and completed pregnancies also reported postpartum depression. CONCLUSION: The premenstrual and postpartum exacerbation of OCD symptoms in some women suggests that the course of this disorder may, in some cases, be influenced by changes in gonadal hormones. Our finding that women with OCD may be at increased risk for postpartum depression underscores the importance of careful postpartum evaluation of women with OCD to prevent maternal and infant morbidity.

Registration of births, stillbirths and infant deaths in Jamaica.

BACKGROUND: Vital statistics underestimate the prevalence of perinatal and infant deaths. This is particularly significant when these parameters affect eligibility for international assistance for newly emerging nations. OBJECTIVE: To determine the level of registration of livebirths, stillbirths and infant deaths in Jamaica. METHODOLOGY: Births, stillbirths and neonatal deaths identified during a cross-sectional study (1986); and infant deaths identified in six parishes (1993) were matched to vital registration documents filed with the Registrar General. RESULTS: While 94% of livebirths were registered by one year of age (1986), only 13% of stillbirths (1986) and 25% of infant deaths (1993) were registered. Post neonatal deaths were more likely to be registered than early neonatal deaths. Frequently the birth was not registered when the infant died. Birth registration rates were highest in parishes with high rates of hospital deliveries (rs = 0.97, P < 0.001) where institutions notify the registrar of each birth. Hospital deaths, however, were less likely to be registered than community deaths as registrars are not automatically notified of these deaths. CONCLUSIONS: To improve vital registration, institutions should become registration centres for all vital events occurring there (births, stillbirths, deaths). Recommendations aimed at modernizing the vital registration system in Jamaica and other developing countries are also made.

PIP: Vital statistics indicate only part of the actual prevalence of perinatal and infant mortality. Findings are reported from a study conducted to determine the level of registration of live births, stillbirths, and infant deaths in Jamaica. Births, stillbirths, and neonatal deaths identified during a 1986 cross-sectional study and infant deaths identified in six parishes during 1993 were matched to vital registration documents filed with the Registrar General. While 94% of live births were registered by one year of age, only 13% of stillbirths and 25% of infant deaths were so registered. Post neonatal deaths were more likely to be registered than early neonatal deaths. Frequently the birth was not registered when the infant died. Birth registration rates were highest in parishes with high rates of hospital deliveries where institutions notify the registrar of each birth. Hospital deaths, however, were less likely to be registered than community deaths since registrars are not automatically noticed of such deaths. Institutions should register all vital events occurring there.

Pneumonia with pleural effusion due to Legionella pneumophila serogroup Lansing 3.

We describe a case of pneumonia with pleural effusion due to Legionella pneumophila serogroup Lansing 3 in a human immunodeficiency virus-infected person. The 55-year-old man had been treated with immunosuppressive agents for hypersensitivity pneumonitis.

Localisation of experimental staphylococcal abscesses by 99MTC-technetium-labelled liposomes.

The accumulation of 99mTc-technetium-labelled liposomes in abscesses was studied. Abscesses were produced in the thighs of albino rats by intramuscular injection of Staphylococcus aureus. After 4 days these abscesses were used to determine the localisation of 99mTc-technetium-labelled anionic, cationic and neutral liposomes in the abscess area. This was achieved by radionuclide images produced by a gamma camera and an associated data-processing system. There was a pronounced uptake of 99mTc-technetium-labelled anionic liposomes in the abscess area compared with the corresponding unaffected thigh. Similar uptake was not shown by the 99mTc-technetium-labelled cationic and neutral liposomes. Abscess uptake of anionic liposomes was maximal at or before 30 min after injection and was not enhanced by prior opsonisation with aggregated rat immunoglobulin.