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Two randomized, controlled trials of L-methylfolate augmentation of SSRIs for major depressive disorder (MDD) were conducted using a novel study design (sequential parallel comparison design- SPCD).
To evaluate the efficacy of L-methylfolate augmentation using the Hamilton Depression Rating Scale.
In study one (TRD-1), 148 outpatients with SSRI-resistant MDD were enrolled in a 60-day, SPCD study, divided into two 30-day periods (phases 1 and 2). Patients were randomized 2:3:3 to receive L-methylfolate (7.5mg/d in phase 1, 15mg/d in phase 2), placebo in phase 1 followed by L-methylfolate 7.5mg/d in phase 2, or placebo for both phases. Study two (TRD-2) involved 75 patients and was identical in design to TRD-1 except for the dose of L-methylfolate (15mg only).
In the TRD-1 Study, L-methylfolate 7.5 mg/d was not found to be more effective than placebo. In phase 1 of the TRD-2 Study, 37% of patients on L-methylfolate 15mg/d responded and 18% of placebo patients responded, while in phase 2 among placebo non-responders, the response rates were 28% on L-methylfolate 15mg/d and 9.5% on placebo. When phases 1 and 2 were pooled according to the SPCD model, the difference in response rates was statistically significant in favor of L-methylfolate (p = 0.0399). The rates of spontaneously reported AEs and rates of study discontinuation appear r comparable between L-methylfolate and placebo in both studies. Rates of study discontinuation were also comparable
These studies suggest that L-methylfolate 15 mg/d may be a safe and effective augmentation strategy for inadequate response to SSRIs.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences.
Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24–42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project.
The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37–0.81)] and women [rG = 0.56 (0.49–0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01–0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females.
Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.
To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing.
A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network.
The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing.
In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some “usually” or “always” preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48–72 hours, but only 55% reported “always” doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care.
Barriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs.
While our fascination with understanding the past is sufficient to warrant an increased focus on synthesis, solutions to important problems facing modern society require understandings based on data that only archaeology can provide. Yet, even as we use public monies to collect ever-greater amounts of data, modes of research that can stimulate emergent understandings of human behavior have lagged behind. Consequently, a substantial amount of archaeological inference remains at the level of the individual project. We can more effectively leverage these data and advance our understandings of the past in ways that contribute to solutions to contemporary problems if we adapt the model pioneered by the National Center for Ecological Analysis and Synthesis to foster synthetic collaborative research in archaeology. We propose the creation of the Coalition for Archaeological Synthesis coordinated through a U.S.-based National Center for Archaeological Synthesis. The coalition will be composed of established public and private organizations that provide essential scholarly, cultural heritage, computational, educational, and public engagement infrastructure. The center would seek and administer funding to support collaborative analysis and synthesis projects executed through coalition partners. This innovative structure will enable the discipline to address key challenges facing society through evidentially based, collaborative synthetic research.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Measurements made by an underwater glider deployed near the Ross Ice Shelf were used to identify the presence of Ice Shelf Water (ISW), which is defined as seawater with its potential temperature lower than its surface freezing point temperature. Properties logged by the glider included in situ temperature, electrical conductivity, pressure, GPS location at surfacings and time. For most of the first 30 recorded dives of its deployment, evidence suggests the glider was prevented from surfacing due to being under the ice shelf. For dives under the ice shelf, farthest from the ice shelf front, ISW layers of varying thicknesses and depth locations were observed; between 2 m thick (centred at 231 m depth) to >93 m thick (centred at >360 m). For dives under the ice shelf, close to the ice shelf front, either no ISW was observed or ISW layers were centred at shallower depths (116–127 m). Thicker ISW layers (e.g. up to 250 m thickness centred at 421 m) were observed for some glider dives in open water in front of the Ross Ice Shelf. No in situ supercooling (water colder than the pressure-dependent freezing point temperature) was observed.
The Parkes 64 m telescope has been used to survey a complete sample of nearby red giants (i.e. not members of close binaries or showing strong emission lines of CaII). The sample consisted of all 82 stars in the Bright Star Catalogue within 30 pc having spectral types G, K, M and luminosity classes I, II, III south of the celestial equator.
The design and scientific applications of a 96-channel filter spectrograph of 1 MHz resolution are presented. The spectrograph is currently under construction and will be installed on the Parkes telescope in 1987-1988. Its main scientific objective is dynamic spectral studies of decimetre- and metre-wavelength bursts from flare stars. However, it will also be used for performing large-scale pulsar surveys, and dynamic spectral observations of interplanetary scintillation of compact sources, interstellar scintillation of compact extragalactic sources, and interesting radio sources in general.
We show that plasma emission generated in the coronae of flare stars should be detectable at metre- and decimetre-wavelengths. We plan to search for fundamental and second-harmonic plasma radiation by observing in two harmonically related bands, 200 to 250 MHz and 400 to 500 MHz. With noise-adding to stabilize receiver gain, the sensitivity (3σ) of each channel of the spectrograph is ∼ 1.5 Jy for a 1-s integration. Previous studies have reported peak flux densities of up to ∼ 35 Jy and ∼ 12 Jy at 240 MHz and 410 MHz respectively for radio bursts from flare stars.
In a previous paper of this issue (Stewart and Nelson 1979 — Paper A) we showed that for extended bursts a good correlation exists between the observed 100 keV X-ray slux density and the 3.75 or 9.4 GHz microwave flux density. We also showed that the microwave spectrum of these bursts was much flatter (S ∝ f1.0 on the average) than the optically thick (self-absorbed) spectrum observed for impulsive microwave bursts (Crannell et al. 1978; Dulk et al. 1978). Furthermore, the microwave turnover frequency was > 10 GHz in eight of the nine events studied and <20 GHz in four of these cases. The remaining event, which was severely occulted by the solar limb, had a turnover frequency of ∽ 1 GHz.
We describe bright microwave events that were first detected with the Parkes 64-m telescope at 8.4 or 22 GHz from six active-chromosphere stars. In some flares spectral data were obtained over a large frequency range from simultaneous measurements with the Parkes reflector (8.4 or 22 GHz), the Tidbinbilla interferometer (8.4 and 2.29 GHz), the Fleurs synthesis telescope (1.42 GHz) and the Molonglo Observatory synthesis telescope (0.843 GHz). Data on circular polarization were obtained from the Parkes observations at 8.4 GHz.
The stars were in a wide variety of evolutionary states, ranging from a single pre-main-sequence star (HD 36705), two RS CVn binaries (HD 127535, HD 128171), an Algol (HD 132742) and two apparently single K giants (HD 32918 and HD 196818). Their high brightness temperatures, positive spectral indices and low polarization are consistent with optically thick gyrosynchrotron emission from mildly relativistic electrons with average energies 0.5 to 3 MeV gyrating in inhomogeneous magnetic fields of 5 to 100 G.
It has generally been accepted that moving type IV bursts are generated as synchrotron radiation from energetic electrons high in the solar corona (Boischot and Denisse 1957). At 80 MHz the peak brightness temperature is usually ~ 108 K and the radiation becomes highly circularly polarized as the burst decays. This has led several authors (Kai 1969; Dulk 1970, 1973; Schmahl 1972; Robinson 1974, 1977; Nelson 1977) to the conclusion that the radiation comes from mildly relativistic (~ 100 keV) electrons and occurs at low harmonics of the gyro-frequency (gyro-synchrotron radiation). We present evidence of moving type IV bursts at 43, 80 and 160 MHz with brightness temperatures of ~ 109 K, and one at 43 MHz as high as 1010 K. The number (~ 1033) of energetic (≥ 1 MeV) electrons which is required in order to explain such high brightness temperatures by incoherent gyro-synchrotron emission is very large and near the upper limit for the number of fast electrons accelerated in the second phase of a solar flare. If amplification takes place a smaller number of electrons with energies ~ 100 keV would be required.
Type I storms generally occur in association with large sun-spots and the radiation is usually circularly polarized. Statistically it has been found that the sense of polarization, right-hand (RH) or left-hand (LH), usually corresponds to the ordinary magneto-ionic mode in the field of the dominant spot of the active region; when a following spot dominates, the polarization tends to be determined by this spot rather than by the leading field. One-dimensional position measurements show that the type I sources are usually not radially above the active region but are displaced by a few minutes of arc. The source sizes are about l′.2 to 4′.5 at 169 MHz and the sources frequently contain double, multiple or bipolar structure at 80 and 160 MHz.
Very sensitive low-noise amplifiers designed to receive transmissions from spacecraft are not necessarily suitable receivers for radio astronomy. In the former case a good signalto- noise ratio is required so that high data rates can be achieved. In the latter the ratio of signal to noise power may be as low as 10-4 and the stability of receiver gain and that of ail sources of noise during long integration times become of equal importance.
This paper describes a novel solution to the problem, which allowed important astronomy to be performed while the ruby maser receivers belonging to the European Space Agency were installed on the Parkes radio telescope for an extended period of time.
Although only three antennas of the Australia Telescope Compact Array are currently operational, we have made use of the technique of bandwidth synthesis to make an image of the radio galaxy 2152 – 69. The three baselines were used to observe the source at three different frequencies, effectively resulting in nine baselines, which have been used to produce an image with a surprisingly high dynamic range, and with a slightly higher resolution than any existing image.
The production of such a worthwhile result, despite being made with a small subset of the capabilities of the Australia Telescope, bodes well for the future operation of the instrument.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
Crannell et al. (1978) have reported an observed correlation between the time profiles and flux densities of impulsive hard X-ray and microwave solar bursts. We report here on a significant correlation between the flux density of extended bursts of hard X-rays and micowaves. These extended events follow after impulsive bursts and last much longer (see e.g. Fig. 1, Frost and Dennis 1971). However, as extended bursts only occur during very large flares the number of cases available for study is small. The significance of our observations follows from the suggestion of Wild et al. (1963) that the extended bursts are evidence for a second-phase acceleration process in the corona. We show that the observed characteristics of these extended microwave bursts (viz. a rather flat spectrum below a turnover frequency which is independent of intensity) can be explained by gyro-synchrotron radiation from the same population of energetic (E ≈ 100 keV) electrons as those emitting (thin-target) X-ray bremsstrahlung. A detailed source model is discussed in a companion paper (Nelson and Stewart 1979 — Paper B).
We present some preliminary results of an optical and radio study of the very active RS CVn binary HD 127535. Photometric measurements show the presence of a large amplitude wave which exhibits marked changes in shape and range on time scales as short as a few months. This photometric variation is almost certainly due to large cool starspots on the cooler, more luminous component. As part of a survey of southern active-chromosphere stars with the Parkes radio telescope, HD 127535 has been observed at 5, 8.4 and 22 GHz. No detection was made at 5 GHz, possibly because of confusion due to the angular proximity of the star to the galatic plane. However, it is one of the strongest sources detected in the 8.4 GHz survey, and is one of only two stars detected at 22 GHz. Photometry obtained two cycles before the 8.4 GHz observations suggest a possible correlation between the radio emission and the photometric wave, i.e. spot visibility, but more data are needed.