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.

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.

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.

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.

Ovarian adrenal interactions during the menopausal transition.

Observations over the past decade using longitudinal data reveal a gender-specific shift in adrenal steroid production. This shift is represented by an increase in the circulating concentrations of delta 5 steroids in 85% of all women and is initiated only after the menopausal transition has begun. While the associated rise in the major adrenal androgen, dehydroepiandrosterone sulfate (DHEAS), is modest, the parallel rises in dehydroepiandrosteone (DHEA) and androstenediol (Adiol) are much more robust. These increases in circulating steroid concentrations are qualitatively similar on average between ethnicities but quantitatively different between individual women. Both circulating testosterone (T) and androstenedione (Adione) also rise concomitantly but modestly by comparison. This phenomenon presents a new and provocative aspect to the endocrine foundations of the menopausal transition and may provide important clues to understanding the fundamentals of mid-aged women's healthy aging, particularly an explanation for the wide diversity in phenotypes observed during the MT as well as their different responses to hormone replacement therapies. Experimental studies using the nonhuman primate animal model show an acute adrenal response to human chorionic gonadotropin (hCG) challenge as well as the presence of luteinizing hormone receptors (LHR) in their adrenal cortices. These experimental results support the concept that LHRs are recruited to the adrenal cortices of mid-aged women that subsequently function to respond to increasing circulating LH to shunt pregnenolone metabolites towards the delta 5 pathway. Future investigations are required to determine the relationship of these changes in adrenal function to symptoms and health outcomes of mid-aged women.

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.

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.

Evaluation of the trade-offs encountered in planning and treating locally advanced head and neck cancer: intensity-modulated radiation therapy vs dual-arc volumetric-modulated arc therapy.

OBJECTIVE: The primary purpose of this study was to assess the practical trade-offs between intensity-modulated radiation therapy (IMRT) and dual-arc volumetric-modulated arc therapy (DA-VMAT) for locally advanced head and neck cancer (HNC). METHODS: For 15 locally advanced HNC data sets, nine-field step-and-shoot IMRT plans and two full-rotation DA-VMAT treatment plans were created in the Pinnacle(3) v. 9.0 (Philips Medical Systems, Fitchburg, WI) treatment planning environment and then delivered on a Clinac iX (Varian Medical Systems, Palo Alto, CA) to a cylindrical detector array. The treatment planning goals were organised into four groups based on their importance: (1) spinal cord, brainstem, optical structures; (2) planning target volumes; (3) parotids, mandible, larynx and brachial plexus; and (4) normal tissues. RESULTS: Compared with IMRT, DA-VMAT plans were of equal plan quality (p>0.05 for each group), able to be delivered in a shorter time (3.1 min vs 8.3 min, p<0.0001), delivered fewer monitor units (on average 28% fewer, p<0.0001) and produced similar delivery accuracy (p>0.05 at γ(2%/2mm) and γ(3%/3mm)). However, the VMAT plans took more planning time (28.9 min vs 7.7 min per cycle, p<0.0001) and required more data for a three-dimensional dose (20 times more, p<0.0001). CONCLUSIONS: Nine-field step-and-shoot IMRT and DA-VMAT are both capable of meeting the majority of planning goals for locally advanced HNC. The main trade-offs between the techniques are shorter treatment time for DA-VMAT but longer planning time and the additional resources required for implementation of a new technology. Based on this study, our clinic has incorporated DA-VMAT for locally advanced HNC. ADVANCES IN KNOWLEDGE: DA-VMAT is a suitable alternative to IMRT for locally advanced HNC.

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.

Attention deficit/hyperactivity disorder's effects on individuals' scan paths during a simulated drive.

Individuals who have Attention Deficit/Hyperactivity Disorder (ADHD) experience adverse effects relating to driving; additionally, they experience deficits in scanning ability. The present study examined the effects of ADHD on eye tracking while driving. This study consisted of ten participants, of which, five have ADHD. It was hypothesized that individuals who have ADHD will make more saccadic eye movements and thus shorter fixations than individuals without ADHD (Control). Furthermore, it was hypothesized that despite the fact that individuals who have ADHD will make more saccadic eye movements than individuals without ADHD, those individuals with ADHD will commit more traffic violations including collisions compared to the control group. Findings indicated that hypothesis one was not supported by the data, whereas hypothesis two was supported in that ADHD individuals' had more collisions and committed more traffic violations than the control group. Additionally, a significant difference was found in the spatial distributions of the fixations between the ADHD and Control groups. The findings of this study could help better understand the factors involved in ADHD driving and could be used to train individuals with ADHD to become more aware of their surroundings and driving habits and thus become safer drivers.

Determining skill transferability of action games as a method to reduce in-vehicle phone distractions.

Distracted driving has been shown to be a safety issue in numerous studies. To combat this problem, in-vehicle technology, legislation, media interventions, and other methods have been proposed and attempted. However research indicates that the drivers themselves may circumvent, ignore, or not be able to react in time for these interventions to be effective. Therefore research into training programs for drivers may improve reaction time under distraction. Research indicates that action game players have faster reaction times and more attentional resources than non-players on paper-based tests. However, transferability to driving has not been studied yet. This paper outlines a study to determine if action game players perform better at a driving task based on frequency of game-play. Participants will be placed into two groups of play (high vs. low) and tested against two levels of distraction (none vs. phone conversation). It is expected that participants who play higher frequency of action games will perform better under distraction than lower frequency players. Driver performance, conversation recall, frequency and durations of eye fixations will be analyzed based on previous research which has validated those variables as a measure of distraction and higher workload.

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.

Ten year secular declines in the cardiorespiratory fitness of affluent English children are largely independent of changes in body mass index.

Secular changes in body mass index (BMI) and cardiorespiratory fitness (20 m shuttle-run test performance) were assessed in 10-year-old children from an affluent area of England in 1998 (n = 303; 158 boys and 145 girls) and 2008 (n = 315; 158 boys and 157 girls). Girls' BMI did not change over the 10 year period. There was a significant increase in boys' BMI (p = 0.02). Cardiorespiratory fitness declined significantly (p<0.001) in both boys (7%) and girls (9%). This study shows a large and worrying decline in cardiorespiratory fitness in children from an affluent area of England.

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.

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.