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Sexual dysfunction occurs in 40%-60% of patients with major depressive disorder (MDD), due to either the illness itself and/or the effects of antidepressant treatment. The phase-2 CLARITY trial recently demonstrated the efficacy of adjunctive pimavanserin (PIM) for MDD when added to ongoing selective serotonin or serotonin–norepinephrine reuptake inhibitor (SSRI/SNRI) treatment. No new safety observations were reported in this study. This post-hoc analysis examines the potential impact of PIM treatment on sexual function.
Study methodology has been presented previously (APA 2019). Adult male and female patients with moderate-to-severe MDD were randomized to PIM 34 mg/day (n=51) or placebo (PBO, n=152) added to ongoing SSRI/SNRI treatment. Massachusetts General Hospital–Sexual Functioning Inventory (MGH-SFI) and Hamilton Depression Rating Scale, 17-item version (HAMD-17) item 14 (sexual interest) scores were examined by analysis of covariance.
Adjunctive PIM resulted in significantly greater 5-week reduction (improvement) relative to SSRI/SNRI treatment plus placebo on mean MGH-SFI scores (difference –0.634, SE 0.167; P<0.001; effect size [ES], Cohen’s d 0.614). Similarly, PIM resulted in greater improvement compared with placebo on individual MGH-SFI items that applied to both males and females: Interest in Sex (P=0.006; ES=0.483), Ability to Get Sexually Aroused/Excited (P=0.001; ES=0.560), Ability to Achieve Orgasm (P<0.001; ES=0.609), Overall Sexual Satisfaction (P=0.003; ES=0.524). HAMD-17 item 14 scores were also significantly more reduced (improved) with PIM (P<0.001; ES=0.574).
These results underscore the potential of adjunctive PIM for improving sexual function in patients with MDD and inadequate response to SSRIs/SNRIs. Potential benefits should be confirmed in further studies.
Executive functions (EF) drive health and educational outcomes and therefore are increasingly common treatment targets. Most treatment trials rely on questionnaires to capture meaningful change because ecologically valid, pediatric performance-based EF tasks are lacking. The Executive Function Challenge Task (EFCT) is a standardized, treatment-sensitive, objective measure which assesses flexibility and planning in the context of provocative social interactions, making it a “hot” EF task.
We investigate the structure, reliability, and validity of the EFCT in youth with autism (Autism Spectrum Disorder; n = 129), or attention deficit hyperactivity disorder with flexibility problems (n = 93), and typically developing (TD; n = 52) youth.
The EFCT can be coded reliably, has a two-factor structure (flexibility and planning), and adequate internal consistency and consistency across forms. Unlike a traditional performance-based EF task (verbal fluency), it shows significant correlations with parent-reported EF, indicating ecological validity. EFCT performance distinguishes youth with known EF problems from TD youth and is not significantly related to visual pattern recognition, or social communication/understanding in autistic children.
The EFCT demonstrates adequate reliability and validity and may provide developmentally appropriate, treatment-sensitive, and ecologically valid assessment of “hot” EF in youth. It can be administered in controlled settings by masked administrators.
The diurnal feeding patterns of dairy cows affects the 24 h robot utilisation of pasture-based automatic milking systems (AMS). A decline in robot utilisation between 2400 and 0600 h currently occurs in pasture-based AMS, as cow feeding activity is greatly reduced during this time. Here, we investigate the effect of a temporal variation in feed quality and quantity on cow feeding behaviour between 2400 and 0600 h as a potential tool to increase voluntary cow trafficking in an AMS at night. The day was allocated into four equal feeding periods (0600 to 1200, 1200 to 1800, 1800 to 2400 and 2400 to 0600 h). Lucerne hay cubes (CP = 19.1%, water soluble carbohydrate = 3.8%) and oat, ryegrass and clover hay cubes with 20% molasses (CP = 11.8%, water soluble carbohydrate = 10.7%) were offered as the ‘standard’ and ‘preferred’ (preference determined previously) feed types, respectively. The four treatments were (1) standard feed offered ad libitum (AL) throughout 24 h; (2) as per AL, with preferred feed replacing standard feed between 2400 and 0600 h (AL + P); (3) standard feed offered at a restricted rate, with quantity varying between each feeding period (20:10:30:60%, respectively) as a proportion of the (previously) measured daily ad libitum intake (VA); (4) as per VA, with preferred feed replacing standard feed between 2400 and 0600 h (VA + P). Eight non-lactating dairy cows were used in a 4 × 4 Latin square design. During each experimental period, treatment cows were fed for 7 days, including 3 days habituation and 4 days data collection. Total daily intake was approximately 8% greater (P < 0.001) for the AL and AL + P treatments (23.1 and 22.9 kg DM/cow) as compared with the VA and VA + P treatments (21.6 and 20.9 kg DM/cow). The AL + P and VA treatments had 21% and 90% greater (P < 0.001) dry matter intake (DMI) between 2400 and 0600 h, respectively, compared with the AL treatment. In contrast, the VA + P treatment had similar DMI to the VA treatment. Our experiment shows ability to increase cow feeding activity at night by varying feed type and quantity, though it is possible that a penalty to total DMI may occur using VA. Further research is required to determine if the implementation of variable feed allocation on pasture-based AMS farms is likely to improve milking robot utilisation by increasing cow feeding activity at night.
Sprays are a class of multiphase flows which exhibit a wide range of drop size and velocity scales spanning several orders of magnitude. The objective of the current work is to experimentally investigate the prospect of dynamical similarity in these flows. We are also motivated to identify a choice of length and time scales which could lead towards a universal description of the drop size and velocity spectra. Towards this end, we have fabricated a cohort of geometrically similar pressure swirl atomizers using micro-electromechanical systems (MEMS) as well as additive manufacturing technology. We have characterized the dynamical characteristics of the sprays as well as the drop size and velocity spectra (in terms of probability density functions, p.d.f.s) over a wide range of Reynolds (
) and Weber numbers (
) using high-speed imaging and phase Doppler interferometry, respectively. We show that the dimensionless Sauter mean diameter (
) scaled to the boundary layer thickness in the liquid sheet at the nozzle exit (
) exhibits self-similarity in the core region of the spray, but not in the outer zone. In addition, we show that global drop size spectra in the sprays show two distinct characteristics. The spectra from varying
collapse onto a universal p.d.f. for drops of size
, a residual effect of
persists in the size spectra. We explain this characteristic by the fact that the physical mechanisms that cause large drops is different from that which is responsible for the small drops. Similarly, with the liquid sheet velocity at the nozzle exit (
) as the choice of velocity scale, we show that drops moving with a velocity
collapse onto a universal p.d.f., while drops with
exhibit a residual effect of
. From these observations, we suggest that physically accurate models for drop size and velocity spectra should rely on piecewise descriptions of the p.d.f. rather than invoking a single mathematical form for the entire distribution. Finally, we show from a dynamical modal analysis that the conical liquid sheet flapping characteristics exhibit a sharp transition in Strouhal number (
) at a critical
Achieving a consistent level of robot utilisation throughout 24 h maximises automatic milking system (AMS) utilisation. However, levels of robot utilisation in the early morning hours are typically low, caused by the diurnal feeding behaviour of cows, limiting the inherent capacity and total production of pasture-based AMS. Our objective was to determine robot utilisation throughout 24 h by dairy cows, based on milking frequency (MF; milking events per animal per day) in a pasture-based AMS. Milking data were collected from January and February 2013 across 56 days, from a single herd of 186 animals (Bos taurus) utilising three Lely A3 robotic milking units, located in Tasmania, Australia. The dairy herd was categorised into three equal sized groups (n=62 per group) according to the cow’s mean daily MF over the duration of the study. Robot utilisation was characterised by an interaction (P< 0.001) between the three MF groups and time of day, with peak milking time for high MF cows within one h of a fresh pasture allocation becoming available, followed by the medium MF and low MF cows 2 and 4 h later, respectively. Cows in the high MF group also presented for milking between 2400 and 0600 h more frequently (77% of nights), compared to the medium MF group (57%) and low MF group (50%). This study has shown the formation of three distinct groups of cows within a herd, based on their MF levels. Further work is required to determine if this finding is replicated across other pasture-based AMS farms.
Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms.
In a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids [(Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites)] were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency [Severity of Dependence Scale (SDS), DSM-IV-TR] and acute psychotic-like symptoms [Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS)].
Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS.
Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes.
The number of people entering specialist drug treatment for cannabis problems has increased considerably in recent years. The reasons for this are unclear, but rising cannabis potency could be a contributing factor.
Cannabis potency data were obtained from an ongoing monitoring programme in the Netherlands. We analysed concentrations of δ-9-tetrahydrocannabinol (THC) from the most popular variety of domestic herbal cannabis sold in each retail outlet (2000–2015). Mixed effects linear regression models examined time-dependent associations between THC and first-time cannabis admissions to specialist drug treatment. Candidate time lags were 0–10 years, based on normative European drug treatment data.
THC increased from a mean (95% CI) of 8.62 (7.97–9.27) to 20.38 (19.09–21.67) from 2000 to 2004 and then decreased to 15.31 (14.24–16.38) in 2015. First-time cannabis admissions (per 100 000 inhabitants) rose from 7.08 to 26.36 from 2000 to 2010, and then decreased to 19.82 in 2015. THC was positively associated with treatment entry at lags of 0–9 years, with the strongest association at 5 years, b = 0.370 (0.317–0.424), p < 0.0001. After adjusting for age, sex and non-cannabis drug treatment admissions, these positive associations were attenuated but remained statistically significant at lags of 5–7 years and were again strongest at 5 years, b = 0.082 (0.052–0.111), p < 0.0001.
In this 16-year observational study, we found positive time-dependent associations between changes in cannabis potency and first-time cannabis admissions to drug treatment. These associations are biologically plausible, but their strength after adjustment suggests that other factors are also important.
The age-metallicity relation (AMR) is a fundamental observational constraint for understanding how the Galactic disc formed and evolved chemically in time. However, there is not yet an agreement on the observational properties of the AMR, primarily due to the difficulty in obtaining accurate ages for individual field stars. We have started an observational campaign for providing new observational input by using wide white dwarf-main sequence (WDMS) binaries. WDs are natural clocks and can be used to derive accurate ages. Metallicities can be obtained from the MS companions. Since the progenitors of WDs and the MS stars were born at the same time, WDMS provide a unique opportunity to constrain in a robust way the properties of the AMR. We present the AMR derived from analysing a pilot sample of 23 WDMS and provide clear evidence for the lack of correlation between age and metallicity at young and intermediate ages.
We use the Sloan Digital Sky Survey Data Release 12, which is the largest available white dwarf catalog to date, to study the evolution of the kinematical properties of the population of white dwarfs in the Galactic disc. We derive masses, ages, photometric distances and radial velocities for all white dwarfs with hydrogen-rich atmospheres. For those stars for which proper motions from the USNO-B1 catalog are available the true three-dimensional components of the stellar space velocity are obtained. This subset of the original sample comprises 20,247 objects, making it the largest sample of white dwarfs with measured three-dimensional velocities. Furthermore, the volume probed by our sample is large, allowing us to obtain relevant kinematical information. In particular, our sample extends from a Galactocentric radial distance RG = 7.8 kpc to 9.3 kpc, and vertical distances from the Galactic plane ranging from Z = −0.5 kpc to 0.5 kpc. We examine the mean components of the stellar three-dimensional velocities, as well as their dispersions with respect to the Galactocentric and vertical distances. We confirm the existence of a mean Galactocentric radial velocity gradient, ∂〈VR〉/∂RG = −3 ± 5 km s−1 kpc−1. We also confirm North-South differences in 〈Vz〉. Specifically, we find that white dwarfs with Z > 0 (in the North Galactic hemisphere) have 〈Vz〉 < 0, while the reverse is true for white dwarfs with Z < 0. The age-velocity dispersion relation derived from the present sample indicates that the Galactic population of white dwarfs may have experienced an additional source of heating, which adds to the secular evolution of the Galactic disc.
A pneumocele occurs when an aerated cranial cavity pathologically expands; a pneumatocele occurs when air extends from an aerated cavity into adjacent soft tissues forming a secondary cavity. Both pathologies are extremely rare with relation to the mastoid. This paper describes a case of a mastoid pneumocele that caused hypoglossal nerve palsy and an intracranial pneumatocele.
A 46-year-old man presented, following minor head trauma, with hypoglossal nerve palsy secondary to a fracture through the hypoglossal canal. The fracture occurred as a result of a diffuse temporal bone pneumocele involving bone on both sides of the hypoglossal canal. Further slow expansion of the mastoid pneumocele led to a secondary middle fossa pneumatocele. The patient refused treatment and so has been managed conservatively for more than five years, and he remains well.
While most patients with otogenic pneumatoceles have presented acutely in extremis secondary to tension pneumocephalus, our patient has remained largely asymptomatic. Aetiology, clinical features and management options of temporal bone pneumoceles and otogenic pneumatoceles are reviewed.
The decomposition of the 21 cm rotation curve of galaxies into contribution from the disk and dark halo depends on the adopted mass to light ratio (M/L) of the disk. Given the vertical velocity dispersion (σz) of stars in the disk and its scale height (hz), the disk surface density and hence the M/L can be estimated. Earlier works have used this technique to conclude that galaxy disks are submaximal. Here we address an important conceptual problem: star-forming spirals have an old (kinematically hot) disk population and a young cold disk population. Both of these populations contribute to the integrated light spectra from which σz is measured. The measured scale height hz is for the old disk population. In the Jeans equation, σz and hz must pertain to the same population. We have developed techniques to extract the velocity dispersion of the old disk from integrated light spectra and from samples of planetary nebulae. We present the analysis of the disk kinematics of the galaxy NGC 628 using IFU data in the inner regions and planetary nebulae as tracers in the outer regions of the disk. We demonstrate that using the scale height of the old thin disk with the vertical velocity dispersion of the same population, traced by PNe, results in a maximal disk for NGC 628. Our analysis concludes that previous studies underestimate the disk surface mass density by ~ 2, sufficient to make a maximal disk for NGC 628 appear like a submaximal disk.
Toxigenic strains of Vibrio cholerae serogroups O1 and O139 have caused cholera epidemics, but other serogroups – such as O75 or O141 – can also produce cholera toxin and cause severe watery diarrhoea similar to cholera. We describe 31 years of surveillance for toxigenic non-O1, non-O139 infections in the United States and map these infections to the state where the exposure probably originated. While serogroups O75 and O141 are closely related pathogens, they differ in how and where they infect people. Oysters were the main vehicle for O75 infection. The vehicles for O141 infection include oysters, clams, and freshwater in lakes and rivers. The patients infected with serogroup O75 who had food traceback information available ate raw oysters from Florida. Patients infected with O141 ate oysters from Florida and clams from New Jersey, and those who only reported being exposed to freshwater were exposed in Arizona, Michigan, Missouri, and Texas. Improving the safety of oysters, specifically, should help prevent future illnesses from these toxigenic strains and similar pathogenic Vibrio species. Post-harvest processing of raw oysters, such as individual quick freezing, heat-cool pasteurization, and high hydrostatic pressurization, should be considered.
The Galactic bulge of the Milky Way is made up of stars with a broad range of metallicity, –3.0 < [Fe/H] < 1 dex. The mean of the metallicity distribution function decreases as a function of height z from the plane and, more weakly, with galactic radius RGC. The most metal-rich stars in the inner Galaxy are concentrated to the plane and the more metal-poor stars are found predominantly further from the plane, with an overall vertical gradient in the mean of the metallicity distribution function of about − 0.45 dex kpc−1. This vertical gradient is believed to reflect the changing contribution with height of different populations in the innermost region of the Galaxy. The more metal-rich stars of the bulge are part of the boxy/peanut structure and comprise stars in orbits which trace out the underlying X-shape. There is still a lack of consensus on the origin of the metal-poor stars ([Fe/H] < −0.5) in the region of the bulge. Some studies attribute the more metal-poor stars of the bulge to the thick disk and stellar halo that are present in the inner region, and other studies propose that the metal-poor stars are a distinct ‘old spheroid’ bulge population. Understanding the origin of the populations that make up the metallicity distribution function of the bulge, and identifying if there is a unique bulge population which has formed separately from the disk and halo, has important consequences for identifying the relevant processes in the formation and evolution of the Milky Way.
The formation mechanism of boxy/peanut-shaped bulges in spiral galaxies has been a problem for many years. We briefly review here the possible formation scenarios for boxy/peanut bulges, concentrating on both the bar-buckling and accretion hypotheses, and then describe an observational program aimed at testing those various theories and studying the vertical structure of edge-on bars. Our program includes optical long-slit spectroscopy, Hi line-imaging, near-infrared imaging, and multi-band optical imaging. New spectroscopic results (both optical and Hi) are presented on seven galaxies, including five boxy/peanut-bulge spirals. Based on Kuijken & Merrifield's (1995) idea for detecting edge-on bars, we argue that these observations constitute a strong case in favour of the bar-buckling mechanism for the formation of boxy/peanut-shaped bulges, but they also raise many questions and prompt for more detailed modelling to be made. The implications of the observations concerning the determination of rotation curves and of the physical conditions in bulges are also discussed.
Photo-electric observations of the occultation of BD —17°4388 by Neptune on 1968 April 7 were made with instruments and techniques as listed in Table I. A preliminary report of these observations has been given in IAU Circular No. 2067.
Globular clusters in the Galaxy are all old objects, with ages of about 1010 years. The LMC is quite different: its globular clusters have ages anywhere between about 5 × 106 years and 1010 years. It is important to find out why globular clusters can form now in the LMC but not in the Galaxy; the galactic globulars play a major role in our picture of the early history of the Galaxy, and it is obviously desirable that we should understand the conditions under which these clusters can form.
Hodge 11 (= SL 868) is a red, globular-like cluster (V ≅ 12.1, B—V = 0.62), situated on the east side of the LMC about 5 kpc projected distance from its centre (Gascoigne 1966). It was included in a programme to study the chemical evolution of the LMC by determining ages and metal abundances for a number of its clusters. Figure 1 shows a preliminary colour-magnitude diagram, found from four AAT plates calibrated with the AAT two-channel photometer. The choice of the radius, 1′.37 (23 pc), within which the stars were measured, was guided by the surface photometry of the cluster described later (Figure 3). But while it makes the number of “clean” stars inside the radius rather small, those outside it are too unlikely to be cluster members. As yet the calibration extends only to V = 19.6, and the nature of the cluster cannot be determined unambiguously. But Figure 1 already shows an unusual feature, in the very blue colour of the group of stars at V ≅ 19, B—V = 0.60, which on the usual interpretation would point to a metal abundance possibly lower than any yet encountered.
Several extragalactic HI surveys using a λ21 cm 13-beam focal plane array will begin in early 1997 using the Parkes 64 m telescope. These surveys are designed to detect efficiently nearby galaxies that have failed to be identified optically because of low optical surface brightness or high optical extinction. We discuss scientific and technical aspects of the multibeam receiver, including astronomical objectives, feed, receiver and correlator design and data acquisition. A comparison with other telescopes shows that the Parkes multibeam receiver has significant speed advantages for any large-area λ21 cm galaxy survey in the velocity range range 0–14000 km s−1.
The Circinus galaxy (CG) was discovered on a plate of an atlas of the nebulae of the southern Milky Way (Lyngå and and Hansson 1972). The detailed optical properties of this galaxy have been investigated by Freeman, Karlsson, Lyngå and Burrell and will be published in a paper by Freeman et al. (1976). The coordinates of the optical nucleus are (1950).
The occultation of a star by a planet of similar brightness allows accurate determination of the planet’s radius R, mean density ρ and of the ratio T/μ, where T and μ are the planetary atmospheric temperature and mean molecular weight. These quantities are important for the formation theory of the planet and of its atmosphere (see e.g. Öpik).