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Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
We examined multistate outbreaks attributed to raw tomatoes in the United States from 1990 to 2010. We summarized the demographic and epidemiological characteristics of 15 outbreaks resulting in 1959 illnesses, 384 hospitalizations, and three deaths. Most (80%) outbreaks were reported during 2000–2010; 73% occurred May–September. Outbreaks commonly affected adult (median age 34 years) women (median 58% of outbreak cases). All outbreaks were caused by Salmonella [serotypes Newport (n = 6 outbreaks), Braenderup (n = 2), Baildon, Enteritidis, Javiana, Montevideo, Thompson, Typhimurium (n = 1 each); multiple serotypes (n = 1)]. Red, round (69% of outbreaks), Roma (23%), and grape (8%) tomatoes were implicated. Most (93%) outbreaks were associated with tomatoes served predominantly in restaurants. However, traceback investigations suggested that contamination occurred on farms, at packinghouses, or at fresh-cut processing facilities. Government agencies, academia, trade associations, and the fresh tomato industry should consider further efforts to identify interventions to reduce contamination of tomatoes during production and processing.
During the 2004–2005 influenza season two independent influenza surveillance systems operated simultaneously in three United States counties. The New Vaccine Surveillance Network (NVSN) prospectively enrolled children hospitalized for respiratory symptoms/fever and tested them using culture and RT–PCR. The Emerging Infections Program (EIP) and a similar clinical-laboratory surveillance system identified hospitalized children who had positive influenza tests obtained as part of their usual medical care. Using data from these systems, we applied capture–recapture analyses to estimate the burden of influenza related-hospitalizations in children aged <5 years. During the 2004–2005 influenza season the influenza-related hospitalization rate estimated by capture–recapture analysis was 8·6/10 000 children aged <5 years. When compared to this estimate, the sensitivity of the prospective surveillance system was 69% and the sensitivity of the clinical-laboratory based system was 39%. In the face of limited resources and an increasing need for influenza surveillance, capture–recapture analysis provides better estimates than either system alone.
The role played by Cenozoic deformation in denudation and landscape development in Ireland has historically been difficult to assess because of the lack of widespread pre-glacial Cenozoic deposits onshore. Here we combine analysis of apatite fission-track data and geomorphic observations to place constraints on the timing, kinematics and magnitude of onshore deformation in southeastern Ireland. Relationships between apatite fission-track central age and elevation for samples from the Wicklow and Blackstairs Mountains and Tullow Lowland suggest that these rocks record an exhumed apatite partial annealing zone, which after cooling was dismembered by differential vertical displacements of up to several hundred metres. We use inverted models of sample thermal history to show that samples across the region experienced very similar thermal histories up to and including a cooling event in late Paleocene or early Eocene time. This effectively rules out strongly spatially heterogeneous denudation, and implies that differential rock uplift occurred in post-early Eocene time. The central age–elevation relationships define at least three spatial domains with internally consistent apatite fission-track data, separated by known faults or topographic escarpments. Geomorphic analysis of these structures shows that patterns of catchment incision and sinuosity, as well as the presence of antecedent drainage, are best explained by differential vertical displacements at or near the domain boundaries. The kinematics and magnitudes of these displacements are consistent with those implied by the apatite fission-track results, and are compatible with other examples of known Cenozoic deformation from Ireland and the adjacent continental margin.
We present the preliminary results of a frequency analysis of 1457 fundamental mode RR Lyrae (RR0) stars in the Large Magellanic Cloud (LMC) from MACHO Project photometry. We find the same classes of pulsational behavior as were found in our earlier survey of first overtone RR Lyrae (RR1) stars. Variables whose prewhitened power spectra contain one or two peaks close to the main frequency component in the original power spectra are commonly known as Blazhko-type variables. The present analysis shows the overall frequency of Blazhko-type stars in the total RR0 population analysed to date to be ≈ 10%. This is lower than the often cited Galactic field/globular rate of 20-30% (Szeidl, 1988).
The incidence rate of Blazhko-type variability in the LMC appears to be about three times higher in RR0 stars than in RR1 stars. This puts important constraints on possible models of the Blazhko effect.
The AS/AGU rat provides an alternative to experimentally produced laboratory models of basal ganglia
disorders. This mutant is characterised by disturbances of movement including clumsy gait, whole body
tremor, rigidity and difficulty in initiating movement. From an early age, there is a profound depletion of
extracellular dopamine in the dorsal caudate-putamen as measured via in vivo microdialysis; levels are only
10–20% of those found in the parent Albino Swiss (AS) strain. Subsequently a depletion of whole tissue
dopamine levels occurs and, later still, loss of dopaminergic cells in the substantia nigra pars compacta. The
dysfunction in movement and the nigrostriatal dopaminergic system are clearly linked, since movement can
be ameliorated by L-DOPA administration. Furthermore, there are depletions in glucose utilisation in several
regions of the basal ganglia circuitry, including the substantia nigra pars compacta, the subthalamic nucleus
and the ventrolateral thalamus. The AS/AGU rat represents a unique opportunity to investigate the
intrinsic factors controlling the integrity of dopaminergic systems and the recent successful positional cloning
of the agu gene will allow the molecular mechanisms underlying this interesting phenotype to be analysed.
A review of the properties of Type II Cepheids and RV Tauri stars in the Magellanic Clouds is presented. In the behaviour of their light and colour curves, the RV Tauri stars appear to be a direct extension of the Type II Cepheids to longer periods. A single P – L – C relationship describes both the Type II Cepheids and RV Tauri stars in the LMC. The derived high intrinsic magnitudes for the RV Tauri variables supports the proposition that these objects are luminous stars evolving off the AGB. Preliminary analysis of the long time-series MACHO photometry indicates one star (MACHO*05:37:45.0–69:54:16) has an obvious ‘period-quadrupled’ periodicity, which is supporting evidence for a period-doubling bifurcation transition to chaotic pulsations.
We present the first results of the analysis of 22 Blazhko stars. We find: 1) Blazhko RRab stars that are nearly pure amplitude modulators; 2) Blazhko RRab stars that have both amplitude and phase modulation; 3) A Blazhko RRab star that has an abrupt period change; 4) Proof of the Blazhko effect in RRc stars. Our data show the character of the amplitude and phase modulations of the light curves over the Blazhko cycles far better than has been previously possible.
We present the first massive frequency analysis of the 1200 first overtone RR Lyrae stars in the Large Magellanic Cloud observed in the first 4.3 yr of the MACHO project. Besides the many new double-mode variables, we also discovered stars with closely spaced frequencies. These variables are most probably nonradial pulsators.
It is generally accepted that the reservoir hosts of cowpox virus are wild rodents, although
direct evidence for this is lacking for much of the virus's geographic range. Here, through a
combination of serology and PCR, we demonstrate conclusively that the main hosts in Great
Britain are bank voles, wood mice and short-tailed field voles. However, we also suggest that
wood mice may not be able to maintain infection alone, explaining the absence of cowpox
from Ireland where voles are generally not found. Infection in wild rodents varies seasonally,
and this variation probably underlies the marked seasonal incidence of infection in accidental
hosts such as humans and domestic cats.
The MACHO data base has been used to examine light curves of all red giant stars brighter than Mbol ∼ −2 in a 0.5° × 0.5° area of the LMC bar. Periods, often multiple, have been searched for in all stars found to be variable. Five distinct period-luminosity sequences have been found on the low mass (M ≲ 2.25M⊙) giant branch. Comparison of observed periods, luminosities and period ratios with theoretical models identifies Miras unambiguously as radial fundamental mode pulsators, while semi-regular variables can be pulsating in the 1st, 2nd or 3rd overtone, or even the fundamental. All these variables lie on just 3 of the 5 distinct sequences, and they all appear to be on the AGB.
The fourth sequence contains red giants on the first giant branch (FGB) or at the red end of the core-helium burning loops of intermediate mass stars (M ≳ 2.25M⊙). The light curves of these stars strongly suggest that they are contact binaries, and they make up ∼0.5% of stars within 1 mag. of the FGB tip. Stars on the fifth sequence show semi-regular, eclipse-like light curves. The light curves and periods of these stars suggest that they are in semi-detached binaries, transfering mass to an invisible companion via a stellar wind or Roche lobe overflow. They make up ∼25% of AGB stars. If the existence of these red giant contact and semi-detached binaries is confirmed, then extant theories of binary star evolution will require substantial modification.
We have analyzed a sample of 1150 type ab, and 550 type c RR Lyrae stars found in 24 of 94 bulge fields of the MACHO database. These fields cover a range in Galactocentric distances from 0.3 to 1.6 kpc. In combination with the data on the outer bulge fields of Alard (1997) and Wesselink (1987), here we present the surface density distribution of bulge RR Lyrae between 0.3 and 3 kpc.
Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen
flutamide during the period from
gestational day (d) 10 to birth resulted in feminisation of the external
genitalia and the suppression of
growth of the male reproductive tract. In adulthood, testes were found to be
located in diverse positions.
True cryptorchidism occurred in 10% of cases, whereas 50% of testes descended
to the scrotum and 40%
were located in a suprainguinal ectopic region. Varying degrees of tubule
abnormality were seen in the testes
of flutamide-treated animals, ranging from completely normal tubules with full
spermatogenesis (and the
expected frequency of the stages of spermatogenesis) to severely abnormal
tubules lined with Sertoli cells
only. For each individual testis, the overall severity of tubule damage was
strongly correlated with its adult
location, with intra-abdominal testes worst affected and scrotally-located
testes least; only the latter
contained normal tubules. Similarly, intra-abdominal testes were the smallest
in weight and contained the
least testosterone. By contrast, postnatal treatment of male rats with flutamide
from birth to postnatal d 14
did not impair development of the external genitalia, the process of
testicular descent or adult
spermatogenesis. These findings confirm that androgen blockade during embryonic
with testicular descent but also demonstrate that (1) prenatal flutamide treatment
per se has a detrimental
effect on adult testis morphology but (2) the degree of abnormality of the
testes is strongly influenced by location.
Modified lead titanate of 0.9PbTiO3 −0.1Pb(Mg0.5 W0.5)O3 thin films have been deposited onto Pt-coated Si substrates by pulsed laser deposition. Films were crystallized in situ during deposition or by post-depositional heat treatment (post-annealing). Compositional and structural characterization showed that the phase formation and microstructure of the films were highly sensitive to deposition conditions. Perovskite single phase films were formed in situ at 650 °C, PO2 = 40 Pa as well as by post-annealing amorphous films at 650 °C. In the post-annealing process, the amorphous as-deposited phase was crystallized to perovskite and/or pyrochlore, and the ratio of perovskite to pyrochlore was found to be influenced by the depositional PO2. Depending on the deposition temperature, the grain structures of the crystallized films were columnar or equiaxed. A relatively homogeneous surface morphology was obtained by deposition at a lower pressure (PO2 = 13 Pa). The in situ crystallized films showed variable crystallographic orientation. The more (111) oriented films had the lowest remanent polarizations and the highest coercive fields. A method for preparing randomly oriented films, via a two-step deposition process with intermediate annealing, is believed to give the most consistent results and the best ferroelectric properties at the present level of development.
Compact, efficient, spectroscopic detector arrays which preferably operate without cooling have applications in the fields of x-ray astronomy, nuclear medicine and radioactive materials management. We have fabricated a 16 element CdZnTe detector array that provides a stopping efficiency of greater than 80%, a photopeak fraction of 44% and an energy resolution of 3.2 keV FWHM at 122 keV. The 4 × 4 array uses a pixel size of(1.5 mm)2 with 0.2 mm spacing on a 5 mm thick substrate. The variation in spectroscopic properties amongst pixels has been characterized in terms of energy resolution and detection efficiency. Operation in current (or flux) mode for transmission imaging has also been investigated.