The dispersion-brightness relation for fast radio bursts from a wide-field survey.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.

The impact of autism services on mothers' psychological wellbeing.

BACKGROUND: Families with a child diagnosed with autism spectrum disorder (ASD) often utilize a variety of professional services. The provision of these services has many potential benefits for families; however, these services also place demands on parents, particularly mothers, to access, navigate and participate. Little is known about how involvement with these services and service systems influences the psychological wellbeing of mothers of children diagnosed with ASD. We examined the relationship between professional services and psychological wellbeing for mothers of children diagnosed with ASD. METHODS: Mothers (n = 119) of children (mean child age 10.1 years; range 2-24 years) diagnosed with ASD anonymously completed a comprehensive survey. The survey included data related to maternal psychological wellbeing, professional services received and perceptions of these services, and child, mother and household characteristics. RESULTS: Regression analyses revealed that maternal psychological wellbeing was positively associated with the perceived continuity of services, and negatively associated with the number of professionals involved. Child and maternal age, and household income were also statistically significant predictors of maternal psychological wellbeing. CONCLUSIONS: The study findings draw attention to the potentially negative impact of systems-level challenges, especially fragmentation of services, on maternal psychological wellbeing, despite positive front-line services. In particular, our data suggest that psychological wellbeing among mothers of children with ASD may vary more as a function of service system variables than practitioner-level or child-level variables.

Predictors of recovery of ovarian function during aromatase inhibitor therapy.

BACKGROUND: Aromatase inhibitors (AIs) may cause a rise in estrogen levels due to ovarian function recovery in women with clinical chemotherapy-induced ovarian failure (CIOF). We carried out a prospective registry trial to identify predictors of ovarian function recovery during AI therapy. PATIENTS AND METHODS: Women with hormone receptor (HR)-positive breast cancer who remained amenorrheic and had hormonal levels consistent with ovarian failure after adjuvant chemotherapy were enrolled in a multi-institutional clinical trial of anastrozole. Subjects underwent frequent assessment using an ultrasensitive estradiol assay. Multivariable analysis was used to evaluate clinical and biochemical predictors of ovarian function recovery within 48 weeks. RESULTS: Recovery of ovarian function during AI therapy was observed in 13 of 45 (28.9%) assessable subjects after a median 2.1 months (range 0.6-11.9). Median age at chemotherapy initiation was statistically significantly different between those who regained ovarian function (43 years, range 40-51) and those who remained postmenopausal (49 years, range 44-52; P < 0.0001). CONCLUSIONS: A significant proportion of women with CIOF recover ovarian function during AI therapy, including a woman over age 50 at initiation of chemotherapy. Tamoxifen remains the standard of care for women with CIOF. If an AI is used, patients should be monitored frequently with high-quality estradiol assays. CLINICALTRIALS.GOV: NCT00555477.

Phosphorus losses from low-emission slurry spreading techniques.

Low emission slurry spreading techniques are known to improve nitrogen use efficiency, but their impact on phosphorus (P) losses in surface runoff has received little attention. The current study was designed to examine the effect of slurry spreading technique on P losses in runoff. Twelve treatments were examined on 0.5- m by 1.0-m plots in a nominal 2 × 6 factorial design experiment. Treatments comprised grass swards at two different stages of growth, a stubble and a 4-wk regrowth, and six different slurry application treatments: control (no slurry), and slurry applied to simulate splash-plate, injection (across and down slope), and trailing shoe (across and down slope) spreading. Slurry was applied by hand (40 m ha). Rainfall simulations (40 mm h) were conducted at 2, 9, and 28 d post-slurry application. When slurry was applied to the stubble, dissolved reactive P (DRP) concentrations in runoff at Day 2 were 47 and 37% lower ( < 0.05) from the injection and trailing shoe treatments compared with the splash-plate treatment. Similarly, at Day 2, TP concentrations in runoff from the injection treatments were 27% lower ( < 0.05) than the splash-plate treatment. In contrast, application technique had no effect ( 0.05) on P concentrations in runoff following slurry application to the regrowth treatment. Phosphorus concentrations in runoff were unaffected by direction of slurry spreading (across or down) at both applications. Our results indicate that trailing shoe and injection techniques offer the potential to reduce DRP concentrations in runoff during the period immediately after slurry application.

Cost of the Defence Medical Services Patient Group Directive for a 10-minute tranexamic acid (TXA) infusion in trauma: a bolus is safe and saves lives.

Tranexamic acid (TXA) is a life-saving drug that reduces the risk of death from haemorrhage. Intervention is time critical with benefit decreasing with delayed administration. The current Joint Service Publication Patient Group Directive (PGD) for giving TXA during the tactical field care phase of the operational patient care pathway specifies it is given over 10 min via intravenous infusion based on TXA's Summary of Product Characteristics. This paper aims to explore the risks of administering TXA as a bolus rather than a 10-minute infusion. There is little evidence to support the risk of quoted adverse events from bolus administration of TXA, good-quality evidence for the mortality benefit of early administration and some evidence that bolus dosing is safe. The Defence Medical Service should consider a default PGD of rapid TXA administration to maximise mortality benefit.

Adjunctive GnRH-a treatment attenuates depletion of ovarian reserve associated with cyclophosphamide therapy in premenopausal SLE patients.

BACKGROUND: We measured antimullerian hormone (AMH), a marker of ovarian reserve, in women with lupus treated with cyclophosphamide (CYC) (group I), CYC plus gonadotropin-releasing hormone agonist (GnRH-a) (group II) or neither (group III). We hypothesized that AMH would be diminished in women exposed to CYC versus women receiving adjunctive GnRH-a treatment or no CYC exposure. METHODS: Forty-eight premenopausal lupus patients were retrospectively divided into three treatment groups: CYC alone (group I, n = 11), CYC + GnRH-a (group II, n = 10) and neither (group III, n = 27). Serum AMH levels between groups were compared using a nonparametric test (Wilcoxon rank-sum). Multiple linear regression adjusting for age was performed. RESULTS: AMH (ng/mL) levels at the last collection were significantly lower in group I versus group III (mean ± SD: 0.18 ± 0.20 group I vs 1.33 ± 1.59 group III; p = 0.015), and versus group II (mean ± SD: 0.86 ± 1.06; p = 0.018). When centered on age 30 years, average AMH levels for group I, group II and group III were 0.20, 0.44 and 1.00, respectively. When adjusted for age, AMH between all groups was significantly different (p<0.0001). CONCLUSION: Posttreatment AMH levels were significantly higher among patients receiving CYC + GnRH-a compared to CYC alone, suggesting that GnRH-a coadministration mitigates CYC-induced ovarian injury.

From financial hardship to child difficulties: main and moderating effects of perceived social support.

BACKGROUND: There is an unequivocal relationship between socio-economic status and child well-being. The Family Stress Model of economic hardship proposes that this relationship is mediated by financial hardship, parenting stress and parenting behaviours. In this study, the Family Stress Model is tested and analysis is extended to examine main and moderating effects of social support. METHODS: A survey incorporating well-validated measures of financial hardship, parenting stress, parenting behaviours and child difficulties was sent to 1296 parents who had utilized universal family support services in Alberta, Canada. A total of 923 parents (71%) responded. Hierarchical linear regression was employed to investigate the mediating roles of financial hardship, parenting stress and parenting behaviours, and to investigate main and moderating influences of parental social support. RESULTS: The study findings generally support the Family Stress Model. The relationship between socio-economic status and child difficulties was mediated by financial hardship and parenting stress. Higher levels of parental social support were associated with lower levels of parenting stress, ineffective parenting and child difficulties. Parental social support was important irrespective of parenting stress levels. CONCLUSIONS: The study findings add to the now critical mass of data showing that parent-child health and well-being is inextricably linked with parental social support. While there is a burgeoning literature on parent training, far less research attention has been given to the development and evaluation of strategies to strengthen parents' social relationships. This is an important direction for future research.

Testosterone, sex hormone-binding globulin and free androgen index among adult women: chronological and ovarian aging.

BACKGROUND: In this study, levels and rates of change in total testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were related to chronological age and to the final menstrual period (FMP) as an indicator of ovarian aging. METHODS: Data were annually acquired over a 15-year period in 629 women of the Michigan Bone Health and Metabolism Study cohort. Data were censored for hormone therapy use. Endogenous androgen patterns over time were described with stochastic processes and bootstrapping. RESULTS: With ovarian aging, T levels rose from a mean of 18 ng/dl commencing 10 years prior to the FMP to 27 ng/dl at the FMP. Over the 20-year period encompassing the FMP, modeled mean SHBG levels changed from 58 to 34 nM and the FAI ratio increased from 1.6 to 2.9 in a non-linear manner. With chronological aging, total T levels increased (P < 0.0001) from 43 to 50 years, but not thereafter. SHBG declined steadily with age with a modestly greater rate of change between 49 and 54 years. The FAI increased from 1.3 to 2.5 from 34 to 58 years. CONCLUSIONS: T increased from approximately age 40 until the FMP whereas SHBG had rate of change patterns reflecting both chronological and ovarian aging components. These data provide new insight into the endogenous androgen patterns at mid-life.

Biologic precipitation of fluorite.

X-ray diffraction patterns show that the statoliths of marine mysid crustaceans are composed of fluorite, and that this mineral is also a principal phase of the gizzard plates of some tectibranch gastropods. A phosphatic phase is also indicated by chemical analyses in the gizzard plates, but its crystallochemical characterization has not been feasible by x-ray diffraction. The occurrence of fluorite in mysid statoliths confirms the earlier interpretations based on insufficient documentation. Fixation of fluorine in hard tissues of marine invertebrates is extensive in the shelf seawaters and minor in the bathyal zone of the oceans.

Aluminum-rich apatite.

More than 25 atomic percent of aluminum can susbtitute for other cations in the structure of apatite [A(10)(XO(4)) (6)Z(2)]. Such a synthetic product was obtained by expelling volatile constituents (H(2)O and F) from morinite during thermal treatment. Infrared absorption spectra, chemical analysis, and x-ray powder diffraction demonstrate that the aluminum has two coordination numbers, and more than twice as much aluminum substitutes for calcium (A position) as for phosphorus (X position).

The 1990 to 1991 Sudan earthquake sequence and the extent of the East african rift system.

One of the largest earthquakes ever recorded in Africa (surface wave magnitude M(s) = 7.2) occurred about 50 kilometers east of the Upper River Nile on 20 May 1990. Four days later, two more large earthquakes (M(s) = 6.4 and 7.0) occurred about 50 kilometers to the northwest in the Nile Valley. In the following months, a further 60 events were recorded by seismic stations worldwide. The earthquakes are associated with two fault systems: one east of the Nile with azimuth southeast and one along the Nile Valley with azimuth north-northeast. The activity alternated between the two fault systems and indicates that the northern extremity of the western branch of the East African Rift System extends at least 350 kilometers north of Lake Albert.

Chromatographic silica gel: surface area determined by adsorption.

The surface area of silicic acid, a form of silica gel, has been determined by adsorption of methanol from a benzene solvent. The method is straightforward, uses inexpensive apparatus, and should be applicable to other particulate adsorbents.

Intracranial calcification after cord blood neonatal transplantation for krabbe disease.

Infantile-onset Krabbe disease results from a deficiency of the lysosomal enzyme galactocerebrosidase and leads to death from profound central and peripheral demyelination. Neonatal hematopoietic cell transplantation may result in near-normal cognitive development and partial rescue of gross motor development. The long-term course of the disorder for treated patients seems to involve slowly progressive neurological impairment. We describe the detailed 3-year outcomes of this experimental procedure using umbilical cord blood in a prenatally-diagnosed newborn with Krabbe disease. Substantial perivascular calcifications and atrophy of the white matter developed in the first year post-transplantation. Despite persistent neuroradiological and electrophysiological evidence of leukodystrophy, at age 3 years she has had only mildly impaired non-motor development and moderately impaired motor skills. The cause of these severe white matter changes may have been due to ongoing Krabbe disease or to effects of the chemotherapy regimen or to an interaction of these factors. Extended long-term follow-up of children neonatally transplanted for Krabbe disease is needed before the full utility and limitations of neonatal transplantation can be determined.

Factors related to declining luteal function in women during the menopausal transition.

CONTEXT: Reproductive hormones are incompletely characterized during the menopause transition (MT). HYPOTHESIS: Increased anovulation and decreased progesterone accompany progress through the MT. DESIGN: The Daily Hormone Study (DHS) of the Study of Women's Health Across the Nation (SWAN) included 848 women aged 43-53 yr at baseline who collected daily urine for one cycle or up to 50 d annually for 3 yr. MAIN OUTCOME MEASURES: LH, FSH, estrone conjugates, and pregnanediol glucuronide levels were assessed. Cycles were classified by presumed luteal (ovulatory) status and bleeding. Hormones were related to time in study, age, menopausal status, and selected variables. RESULTS: Ovulatory-appearing cycles declined from 80.9% at baseline to 64.7% by the third assessment (H3). Cycles presumed anovulatory and not ending with bleeding by 50 d (anovulatory/nonbleeding) increased from 8.4 to 24% by H3 and were associated with progress to early perimenopause [odds ratio (OR) = 2.66; confidence interval (CI) = 1.17-6.04] or late perimenopause (OR = 56.21; CI = 18.79-168.12; P < 0.0001), African-American ethnicity (OR = 1.91; CI = 1.06-3.43), and less than high school education (OR = 3.51; CI = 1.62-7.62). Anovulatory cycles ending with bleeding remained at about 10% from baseline to H3; compared with ovulatory cycles, they were associated with obesity (OR = 4.68; CI = 1.33-16.52) and more than high school education (OR = 2.12; CI = 1.22-3.69; P = 0.02). Serum estradiol in both the highest and lowest categories was associated with anovulatory/nonbleeding collections. Pregnanediol glucuronide decreased 6.6% for each year on study. Insulin sensitivity measures did not relate strongly to menstrual cycle hormones. CONCLUSIONS: Anovulation without bleeding represents progression of the MT. A small but detectable decrease in luteal progesterone excretion occurs as women progress through the MT.

Women with intellectual disability at risk of adverse pregnancy and birth outcomes.

BACKGROUND: An increasing number of women with intellectual disability (ID) have children. Cross-sectional, clinical population data suggest that these women face an increased risk of delivering preterm and/or low birthweight babies. The aim of this study was to explore the prevalence of poor pregnancy and birth outcomes in women with ID and/or self-reported learning difficulties in an antenatal population. METHODS: A total of 878 pregnant women attending their first antenatal clinic visit were 'screened' for ID. Pregnancy and birth outcomes data were extracted from medical records post-partum. These data included pregnancy-related health conditions, including pre-eclampsia and gestational diabetes, and birth outcomes, including gestational age, birthweight, Apgar score and admission to neonatal intensive care and/or special care nursery. RESULTS: A total of 57 (6.5%) pregnant women with ID and/or self-reported learning difficulties were identified. These women experienced an unusually high rate of pre-eclampsia (odds ratio = 2.85). Their children more often had low birthweights (odds ratio = 3.08), and they were more frequently admitted to neonatal intensive care or special care nursery (odds ratio = 2.51). CONCLUSION: Further research is needed to understand the reasons for the adverse findings of this study and identify potentially changeable factors contributing to adverse pregnancy and birth outcomes for women with ID and/or self-reported learning difficulties and their children. To ensure quality antenatal care, health professionals may need to consider innovations such as extended consultation times, communication aids and audio-taping consultations.

Meningococcal Disease in Northern Ireland - Past, Present & Future: MeningoNI Forum.

Meningococcal disease has had devastating consequences in Northern Ireland since its first description locally in 1859. The incidence of this disease has significantly declined in recent years, however it is important to understand reasons for this changing epidemiology and to acknowledge the diagnostic and clinical management developments that have been made locally. This review aims to examine the changing face of this disease in Northern Ireland over the years, with particular reference to local disease prevention, epidemiology, diagnosis, clinical treatment and management, post-disease sequelae and the role of meningitis charities locally, in terms of patient support and research.

Inhibitors of kallikrein in human plasma.

Human plasma was fractionated by ammonium sulfate precipitation, DEAE-cellulose chromatography, and Sephadex G-200 gel filtration to determine which method would give the greatest number of clearly separable kallikrein inhibitory peaks. With G-200 gel filtration three peaks could be separated which were demonstrated to contain alpha(2)-macroglobulin, C1 inactivator, and alpha(1)-antitrypsin. No other kallikrein inhibitors could be identified. The fractions containing C1 inactivator and alpha(2)-macroglobulin appeared to be more effective against kallikrein than that containing alpha(1)-antitrypsin. A patient with hereditary angioneurotic edema was shown to have an abnormal C1 inactivator protein capable of interfering with kallikrein's biologic, but not its esterolytic activity. Heat-treated human plasma, a commonly used source of kininogen for experiments with kallikrein, was shown to have kallikrein inhibitory activity.

Expression of a gene family in the dimorphic fungus Mucor racemosus which exhibits striking similarity to human ras genes.

Sporulation, spore germination, and yeast-hypha dimorphism in the filamentous fungus Mucor racemosus provide useful model systems to study cell development in eucaryotic cells. Three RAS genes (MRAS1, MRAS2, and MRAS3) from M. racemosus have been cloned, and their nucleotide sequences have been determined. The predicted amino acid sequences and the sizes of the three MRAS proteins exhibit a high degree of similarity with other ras proteins, including that encoded by H-ras, which have been implicated in regulation of proliferation and development in eucaryotic cells by mediating signal transduction pathways. The MRAS proteins show conservation of functional domains proposed for ras proteins, including guanine nucleotide interaction domains, an effector domain, a binding epitope for neutralizing antibody Y13-259, and the COOH-terminal CAAX box, which is a site of thiocylation and membrane attachment. Amino acid sequences unique to each MRAS protein occur adjacent to the CAAX box, consistent with the location of the hypervariable region in other ras proteins. Northern (RNA) analysis was used to study expression of the three MRAS genes in relation to cell development. Gene-specific probes for two of these genes, MRAS1 and MRAS3, hybridized to different 1.3-kb mRNA transcripts. The accumulation of these transcripts depended on the developmental stage, and this pattern was different between the two MRAS genes. No transcript for MRAS2 was detected in the developmental stages examined. The unique patterns of MRAS transcript accumulation suggest that individual MRAS genes and proteins may play distinct roles in cell growth or development.

Cyclic nucleotide phosphodiesterases associated with bovine retinal outer-segment fragments.

ATP-dependent cyclic GMP phosphodiesterase activity (EC 3.1.4.16) associated with bovine retinal outer-segment fragment preparations was stimulated an order of magnitude by light, confirming the results of Miki et al. (1973) Proc. Natl. Acad. Sci. U.S. 70, 3820-3824 at Yale for the frog system. In contrast to the results of the Yale group, however, light stimulation was not observed for cyclic AMP as substrate. A direct relationship of bovine rhodopsin bleaching to phosphodiesterase activation differs from a previous report by the Yale group that full activation of the frog enzyme was achieved by bleaching of a maximum of 2% rhodopsin. Phosphodiesterase activity could be qualitatively removed from the fresh outer-segment preparations with isotonic sucrose which apparently did not disrupt the plasmalemma or discs. Activity recovered from the washing was not light sensitive. Two Km values were determined for cyclic AMP, 5 and 0.05 mM; for cyclic GMP a Km of 0.22 mM was found. All Km values were determined in the presence of 1 mM ATP in the dark. Sonication of fresh outer segments or storing at -20 degrees C abolished the light response. However, storage at -76 degrees C fully preserved it.