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Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
In 1964 (Solar Cycle 20; SC 20), Patrick McIntosh began creating hand-drawn synoptic maps of solar magnetic features, based on Hα images. These synoptic maps were unique in that they traced magnetic polarity inversion lines, and connected widely separated filaments, fibril patterns, and plage corridors to reveal the large-scale organization of the solar magnetic field. Coronal hole boundaries were later added to the maps, which were produced, more or less continuously, into 2009 (i.e., the start of SC 24). The result was a record of ~45 years (~570 Carrington rotations), or nearly four complete solar cycles of synoptic maps. We are currently scanning, digitizing and archiving these maps, with the final, searchable versions publicly available at NOAA's National Centers for Environmental Information. In this paper we present preliminary scientific studies using the archived maps from SC 23. We show the global evolution of closed magnetic structures (e.g., sunspots, plage, and filaments) in relation to open magnetic structures (e.g., coronal holes), and examine how both relate to the shifting patterns of large-scale positive and negative polarity regions.
The Cosmology Distinction Course is a new one-year course to be introduced for Year 12 candidates in the 1994 Higher School Certificate examinations in NSW. It is one of three challenging courses of study that will enrich the HSC for talented students who accelerate and complete part of the HSC one year early. The courses will be taught through distance learning and will include residential seminars. They will be implemented on behalf of the Board of Studies by Charles Sturt University and the University of New England.
The Cosmology Course is organised into nine modules of course work covering historical and social aspects of cosmology, observational techniques, key observations and the various models developed—Newtonian, de Sitter, Friedmann, Lemaitre, steady-state, quasi-steady-state and big bang. Assessment will be through assignments, exams and a major project.
As the first Distinction Course in a scientific area, the Cosmology Course represents an exciting and important educational initiative that needs the cooperation of NSW astronomers and, in return, promises to benefit the astronomical and general scientific community in Australia.
It is unclear whether cryoablation or radiofrequency ablation offers better value for treating atrioventricular nodal re-entrant tachycardia in children. We aimed to compare the value of these procedures for treating atrioventricular nodal re-entrant tachycardia in children, with value being outcomes relative to costs.
We performed a retrospective cohort study of all atrioventricular nodal re-entrant tachycardia ablations for children (age⩽18 years) from July, 2009 to June, 2011 at our institution. Costs included fixed costs, miscellaneous hospital costs, and labour costs, and key outcomes were acute and long-term success (6 months) of the ablations. We conducted T-tests and regression analyses to investigate the associations between the ablation procedure type and the cost and success of the ablations.
Of 96 unique cases performed by three paediatric electrophysiologists, 48 were cryoablation only, 42 radiofrequency ablation only, and six were a combination. Acute success was 100% for the cryoablation only and radiofrequency ablation only cases and 83% for the combination cases. There were no notable adverse events. The average total cost was $9636 for cryoablation cases, $9708 for radiofrequency ablation cases, and $10,967 for combination cases (p=0.51 for cryoablation only versus radiofrequency ablation only). The long-term success rate was 79.1% for cryoablation only, 92.8% for radiofrequency ablation only, and 66.7% for the combination (p=0.01 for cryoablation only versus radiofrequency ablation only), but long-term success varied notably by provider.
Cryoablation and radiofrequency ablation offer similar value in the short term for the treatment of atrioventricular nodal re-entrant tachycardia in children. Differences in long-term success may vary substantially by physician, and thus may lead to differences in long-term value.
Risk for post-traumatic stress disorder (PTSD) varies in part due to the nature of the traumatic event involved. Both injury and return from combat pose high risk of PTSD symptoms. How different injuries may predispose towards PTSD is less well understood.
A retrospective record review was conducted from 1402 service members who had returned to Naval Medical Center San Diego from Iraq or Afghanistan and who had completed the PTSD Checklist as part of their post-deployment screening. Rates of PTSD were examined in relation to mechanism of injury.
Of those without injury, 8% met Diagnostic and Statistical Manual criteria for PTSD. Thirteen percent of those with a penetrating injury, 29% with blunt trauma, and 33% with combination injuries met criteria for PTSD. PTSD severity scores varied significantly according to type of injury.
The World War I concept of “shell shock” implied that blast-related injuries were more likely to result in psychological symptoms than were other injuries. These data may support that idea. Circumstance of injury, population differences, and reporting bias could also have influenced the results.
These results suggest that service members with blunt or combination injuries merit particular attention when screening for PTSD.
In 1994 and 2002, respectively, the World Health Organisation proposed that treatment for hookworm and schistosomiasis could be provided during pregnancy. It was hoped that this might have benefits for maternal anaemia, fetal growth and perinatal mortality; a beneficial effect on the infant response to immunisation was also hypothesised. Three trials have now been conducted. Two have examined the effects of benzimidazoles; one (the Entebbe Mother and Baby Study) the effects of albendazole and praziquantel. All three were conducted in settings of high prevalence but low intensity helminth infection. Results suggest that, in such settings and given adequate provision of haematinics, the benefit of routine anthelminthics during pregnancy for maternal anaemia may be small; none of the other expected benefits has yet been demonstrated. The Entebbe Mother and Baby Study found a significant adverse effect of albendazole on the incidence of infantile eczema in the whole study population, and of praziquantel on the incidence of eczema among infants of mothers with Schistosoma mansoni. Further studies are required in settings that differ in helminth species and infection intensities. Further research is required to determine whether increased rates of infantile eczema translate to long-term susceptibility to allergy, and to explore the underlying mechanisms of these effects. The risks and benefits of routine anthelminthic treatment in antenatal clinics may need to be reconsidered.
Fibroblast growth factor (FGF)-2 (basic) is a potent angiogenic molecule involved in tumor progression, and is one of several growth factors with a central role in ovarian carcinogenesis. We hypothesized that common single nucleotide polymorphisms (SNPs) in the FGF2 gene may alter angiogenic potential and thereby susceptibility to ovarian cancer. We analyzed 25 FGF2 tgSNPs using five independent study populations from the United States and Australia. Analysis was restricted to non-Hispanic White women with serous ovarian carcinoma (1269 cases and 2829 controls). There were no statistically significant associations between any FGF2 SNPs and ovarian cancer risk. There were two nominally statistically significant associations between heterozygosity for two FGF2 SNPs (rs308379 and rs308447; p < .05) and serous ovarian cancer risk in the combined dataset, but rare homozygous estimates did not achieve statistical significance, nor were they consistent with the log additive model of inheritance. Overall genetic variation in FGF2 does not appear to play a role in susceptibility to ovarian cancer.
Drop-on-demand inkjet printing is a fabrication technique that is capable of depositing materials layer-by-layer to form complex 3-dimensional (3-D) constructs. Here we present a new single drop delivery method in which both the matrix and cross-linker are present but separated through the use of vesicle packaging. Changing the printing parameters has little effect on the integrity of the calcium(II)-loaded vesicles, with calcium(II) released selectively by warming after printing. Alginate solutions containing calcium(II)-loaded vesicles were successfully printed and the printed layers were shown to gel on demand at 37 °C. The printed alginate layers were evaluated with regards to their potential to provide 3-D structures for cell culture.
This review includes a brief discussion, from the perspective of the pediatric cardiologist, of the rationale for creation and maintenance of multi-institutional databases of outcomes of the treatment of patients with congenital and paediatric cardiac disease, together with a history of the evolution of such databases, and a description of the current state of the art. A number of projects designed to have broad-based impact are currently in the design phase, or have already been implemented. Not surprisingly, most of the efforts thus far have focused on catheterization procedures and interventions, although some work examining other aspects of paediatric cardiology practice is also beginning. This review briefly describes several European and North American initiatives related to databases for pediatric and congenital cardiology including the Central Cardiac Audit Database of the United Kingdom, national database initiatives for pediatric cardiology in Switzerland and Germany, various database initiatives under the leadership of the Working Groups of The Association for European Paediatric Cardiology, the IMPACT Registry™ (IMproving Pediatric and Adult Congenital Treatment) of the National Cardiovascular Data Registry® of The American College of Cardiology Foundation® and The Society for Cardiovascular Angiography and Interventions (SCAI), the Mid-Atlantic Group of Interventional Cardiology (MAGIC) Catheterization Outcomes Project, the Congenital Cardiac Catheterization Project on Outcomes (C3PO), the Congenital Cardiovascular Interventional Study Consortium (CCISC), and the Joint Council on Congenital Heart Disease (JCCHD) National Quality Improvement Initiative. These projects, each leveraging multicentre data and collaboration, demonstrate the enormous progress that has occurred over the last several years to improve the quality and consistency of information about nonsurgical treatment for congenital cardiac disease. The paediatric cardiology field is well-poised to move quickly beyond outcome assessment and benchmarking, to collaborative quality improvement.
To develop a service development plan supporting recovery-based practice through collaborative service user-led methodology, and contribute to the National Institute for Mental Health in England (NIMHE) pilot evaluation of recovery sensitive measures. Staff, residents and service user group representatives collaborated in implementing the Developing Recovery Enhancing Environments Measure (DREEM) in a residential rehabilitation service.
Staff and residents demonstrated a shared vision of recovery. Many areas were being addressed to a high level but others showed areas of deficiency, and illustrated discrepant views between staff and residents, which provided a focus for the development of a clinical service action plan.
As an experimental measure DREEM provides a user-led structure, which enables services to measure their commitment to, and effectiveness in, providing recovery-based care. It focuses service development and enhances collaborative work with service users, thus mirroring the principles of recovery it measures. It merits further evaluation and consolidation.
The failure of a lava dam 165,000 yr ago produced the largest known flood on the Colorado River in Grand Canyon. The Hyaloclastite Dam was up to 366 m high, and geochemical evidence linked this structure to outburst-flood deposits that occurred for 32 km downstream. Using the Hyaloclastite outburst-flood deposits as paleostage indicators, we used dam-failure and unsteady flow modeling to estimate a peak discharge and flow hydrograph. Failure of the Hyaloclastite Dam released a maximum 11 × 109 m3 of water in 31 h. Peak discharges, estimated from uncertainty in channel geometry, dam height, and hydraulic characteristics, ranged from 2.3 to 5.3 × 105 m3 s−1 for the Hyaloclastite outburst flood. This discharge is an order of magnitude greater than the largest known discharge on the Colorado River (1.4 × 104 m3 s−1) and the largest peak discharge resulting from failure of a constructed dam in the USA (6.5 × 104 m3 s−1). Moreover, the Hyaloclastite outburst flood is the oldest documented Quaternary flood and one of the largest to have occurred in the continental USA. The peak discharge for this flood ranks in the top 30 floods (>105 m3 s−1) known worldwide and in the top ten largest floods in North America.
Yohanan bar Zechariah, known as ‘the baptizer’, to Yeshua bar Ioseph, my disciple. Shalom. May the God of our forefathers grant you strength.
I remember when I first heard whispered behind my back the nickname that people had given me – ‘the baptizer’ – I was furious. How dare they mock the means God provided for them to express repentance in these last days! I gradually came to realize that they were probably only expressing their amazement at seeing me stand in the Jordan to help people perform their immersion. Well, it has been a few months now since Herod Antipas had me arrested. How I wish I could be a ‘baptizer’ again, for I had grown used to having easy access to water. Here in this arid region the guards barely provide me enough water for drinking. And there is certainly none for me to bathe, even though water is not scarce here due to the cisterns built by the father of Herod Antipas.
You were away when Antipas' soldiers came to arrest me, so let me tell you what happened. As you know, we were considering moving the focus of our baptizing and preaching to the western bank of the Jordan, in Judaea. There we would have been safe from Antipas, for though he rules over Peraea and Galilee, he has no power in Judea (of course, Pontius Pilate, the prefect of Judea may then have begun watching us).
Modern financial economic theory suggests that changes in speculative prices should follow simple time series processes in an informationally efficient capital market. Moreover, this theoretical implication enjoys substantial support in the empirical financial economic literature (see Fama 1970). Yet, the implications of the observed time series behavior of speculative price changes for the structure of equilibrium models of asset pricing or information theory do not appear to be fully appreciated. Simply stated, financial economists have not attempted to integrate time series analysis with econometric model building along the lines suggested by Zellner (1979b) and Zellner and Palm (1974).
Changes in speculative prices in an efficient capital market: theory and evidence
Fama (1970) has defined an efficient capital market as one in which speculative prices fully (and correctly) reflect available information. In such a market, changes in speculative prices occur only in response to new information or to reassessments of existing information. The pioneering empirical work of Working (1934), Kendall (1953), Roberts (1959), and Bachelier (1964) suggested that changes in various speculative price series appeared to follow simple time series processes or “fair game” models (in particular, random or quasi-random walks). Excepting Bachelier, the first rigorous economic theory consistent with the above empirical evidence was developed by Samuelson (1965).
Samuelson demonstrates that changes in futures prices will follow martingale or submartingale processes under very general assumptions concerning the stochastic behavior of spot commodity prices.