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There is little evidence in China regarding the cost-effectiveness of non-invasive prenatal testing (NIPT) for Down syndrome (DS). This study aims to evaluate the cost-effectiveness of NIPT and provide evidence to inform decision-making.
To determine the cost-effectiveness of NIPT for DS, a decision-analytic model was developed using the TreeAge Pro software from a societal perspective in a simulated cohort of 10 000 pregnant women. Main indicators were based on field surveys from sampled hospitals in four locations in China and a literature review.
The conventional maternal serum screening (CMSS) strategy, contingent screening strategy (NIPT delivered to high risk pregnant women after CMSS), and universal screening strategy could prevent 3.02, 7.53, and 9.97 DS births, respectively. NIPT would decrease unnecessary invasive procedures, resulting in fewer procedure-related miscarriages. The cost-effectiveness ratio of the contingent screening strategy was the lowest. When compared with the CMSS strategy, the incremental cost per DS birth averted by the contingent screening strategy and universal screening strategy were USD 20,160 and 352,388, respectively. One-way sensitivity analysis showed that, if the cost of NIPT could be decreased to USD 76.92, the cost-effectiveness ratio of the universal screening strategy would be lower than the CMSS strategy.
Although NIPT has the merits of greater effectiveness and safety, CMSS is unlikely to be replaced by NIPT at this time because of NIPT's higher cost. Contingent screening may be an appropriate strategy to balance the effectiveness and cost factors of the new genetic testing technology.
The clouded leopard Neofelis nebulosa is a potent ambassador species for conservation, occurring from the Himalayan foothills eastwards to Indochina, between which Myanmar is a biogeographical land bridge. In Myanmar's Northern Forest Complex, the species co-occurs with the tiger Panthera tigris, leopard Panthera pardus, marbled cat Pardofelis marmorata, golden cat Catopuma temminckii and leopard cat Prionailurus bengalensis. We deployed cameras within the Htamanthi Wildlife Sanctuary over 2 consecutive years. In 2014–2015 we deployed 82 camera stations around the Nam Pa Gon stream (Catchment 1) for 7,365 trap days. In 2015–2016 we deployed 80 camera stations around the Nam E Zu stream (Catchment 2) for 7,192 trap days. In Catchment 1 we identified five tigers from 26 detections, five clouded leopards from 41 detections (68 photographs) and 11 marbled cats from 13 detections. Using Bayesian-based spatial capture–recapture we estimated the densities of tigers and clouded leopards to be 0.81 ± SD 0.40 and 0.60 ± SD 0.24 individuals per 100 km2, respectively. In Catchment 2 we identified two tigers from three detections, nine clouded leopards from 55 detections and 12 marbled cats from 37 detections. Densities of clouded leopards and marbled cats were 3.05 ± SD 1.03 and 8.80 ± SD 2.06 individuals per 100 km2, respectively. These differences suggest that human activities, in particular gold mining, are affecting felid populations, and these are a paramount concern in Htamanthi. We demonstrate the importance of Htamanthi within the Northern Forest Complex and highlight the Yawbawmee corridor as a candidate for protection.
There is increasing evidence of a relationship between underweight or obesity and dementia risk. Several studies have investigated the relationship between body weight and brain atrophy, a pathological change preceding dementia, but their results are inconsistent. Therefore, we aimed to evaluate the relationship between body mass index (BMI) and cortical atrophy among cognitively normal participants.
We recruited cognitively normal participants (n = 1,111) who underwent medical checkups and detailed neurologic screening, including magnetic resonance imaging (MRI) in the health screening visits between September 2008 and December 2011. The main outcome was cortical thickness measured using MRI. The number of subjects with five BMI groups in men/women was 9/9, 148/258, 185/128, 149/111, and 64/50 in underweight, normal, overweight, mild obesity, and moderate to severe obesity, respectively. Linear and non-linear relationships between BMI and cortical thickness were examined using multiple linear regression analysis and generalized additive models after adjustment for potential confounders.
Among men, underweight participants showed significant cortical thinning in the frontal and temporal regions compared to normal weight participants, while overweight and mildly obese participants had greater cortical thicknesses in the frontal region and the frontal, temporal, and occipital regions, respectively. However, cortical thickness in each brain region was not significantly different in normal weight and moderate to severe obesity groups. Among women, the association between BMI and cortical thickness was not statistically significant.
Our findings suggested that underweight might be an important risk factor for pathological changes in the brain, while overweight or mild obesity may be inversely associated with cortical atrophy in cognitively normal elderly males.
Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD).
We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years).
As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD.
Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.
Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents.
To assess the efficacy of aripiprazole once-monthly compared with oral aripiprazole for maintenance treatment of schizophrenia.
A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to aripiprazole once-monthly 400 mg, oral aripiprazole (10–30 mg/day) or aripiprazole once-monthly 50mg (a dose below the therapeutic threshold for assay sensitivity). (Trial registration: clinicaltrials.gov, NCT00706654.)
A total of 1118 patients were screened, and 662 responders to oral aripiprazole were randomised. Kaplan–Meier estimated impending relapse rates at week 26 were 7.12% for aripiprazole once-monthly 400mg and 7.76% for oral aripiprazole. This difference (−0.64%, 95% CI −5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments were superior to aripiprazole once-monthly 50mg (21.80%, P⩽0.001).
Aripiprazole once-monthly 400mg was non-inferior to oral aripiprazole, and the reduction in Kaplan–Meier estimated impending relapse rate at week 26 was statistically significant v. aripiprazole once-monthly 50 mg.
After an outbreak of pandemic influenza A/H1N1 (pH1N1) virus, we had previously reported the emergence of a recombinant canine influenza virus (CIV) between the pH1N1 virus and the classic H3N2 CIV. Our ongoing routine surveillance isolated another reassortant H3N2 CIV carrying the matrix gene of the pH1N1 virus from 2012. The infection dynamics of this H3N2 CIV variant (CIV/H3N2mv) were investigated in dogs and ferrets via experimental infection and transmission. The CIV/H3N2mv-infected dogs and ferrets produced typical symptoms of respiratory disease, virus shedding, seroconversion, and direct-contact transmissions. Although indirect exposure was not presented for ferrets, CIV/H3N2mv presented higher viral replication in MDCK cells and more efficient transmission was observed in ferrets compared to classic CIV H3N2. This study demonstrates the effect of reassortment of the M gene of pH1N1 in CIV H3N2.
Glutathione peroxidase (GPx; EC 220.127.116.11) is an important antioxidant enzyme that catalyses the reduction of organic and inorganic hydroperoxides to water in oxygen-consuming organisms, using glutathione as an electron donor. Here, we report the characterization of a GPx of Cryptosporidium parvum (CpGPx). CpGPx contained a standard UGU codon for cysteine instead of a UGA opal codon for seleno-cysteine (SeCys) at the active site, and no SeCys insertion sequence (SECIS) motif was identified within the 3′-untranslated region (UTR) of CpGPx, which suggested its selenium-independent nature. In silico and biochemical analyses indicated that CpGPx is a cytosolic protein with a monomeric structure. Recombinant CpGPx was active over a wide pH range and was stable under physiological conditions. It showed a substrate preference against organic hydroperoxides, such as cumene hydroperoxide and t-butyl hydroperoxide, but it also showed activity against inorganic hydroperoxide, hydrogen peroxide. Recombinant CpGPx was not inhibited by potassium cyanide or by sodium azide. The enzyme effectively protected DNA and protein from oxidative damage induced by hydrogen peroxide, and was functionally expressed in various developmental stages of C. parvum. These results collectively suggest the essential role of CpGPx for the parasite's antioxidant defence system.
The Slewing Mirror Telescope (SMT) is the UV/optical telescope of UFFO-pathfinder. The
SMT optical system is a Ritchey-Chrétien (RC) telescope of 100 mm diameter pointed by
means of a gimbal-mounted flat mirror in front of the telescope. The RC telescope has a
17 × 17arcmin2 in Field of View and 4.3 arcsec resolution (full width half
maximum of the point spread function) The beam-steering mirror enables the SMT to access a
35 × 35degree region and point and settle within 1 sec. All mirrors were fabricated to
about 0.02 wavelengths RMS in wave front error (WFE) and 84.7% average reflectivity over
200 nm ~ 650 nm. The RC telescope was aligned to 0.05 wavelengths RMS in WFE (test
wavelength 632.8 nm). In this paper, the technical details of the RC telescope and slewing
mirror system assembly, integration, and testing are given shortly, and performance tests
of the full SMT optical system are reported.
The Ultra-Fast Flash Observatory (UFFO) is a space observatory for optical follow-ups of
gamma ray bursts (GRBs), aiming to explore the first 60 seconds of GRBs optical emission.
UFFO is utilized to catch early optical emissions from GRBs within few sec after trigger
using a Gimbal mirror which redirects the optical path rather than slewing entire
spacecraft. We have developed a 15 cm two-axis Gimbal mirror stage for the UFFO-Pathfinder
which is going to be on board the Lomonosov satellite which is to be launched in 2013. The
stage is designed for fast and accurate motion with given budgets of 3 kg of mass and 3
Watt of power. By employing stepping motors, the slewing mirror can rotate faster than 15
deg/sec so that objects in the UFFO coverage (60 deg × 60 deg) can be targeted in
~1 sec. The obtained targeting resolution is better 2 arcmin using a close-loop
control with high precision rotary encoder. In this presentation, we will discuss details
of design, manufacturing, space qualification tests, as well as performance tests.
The UFFO (Ultra-Fast Flash Observatory) is a GRB detector on board the Lomonosov
satellite, to be launched in 2013. The GRB trigger is provided by an X-ray detector,
called UBAT (UFFO Burst Alarm & Trigger Telescope), which detects X-rays from the GRB
and then triggers to determine the direction of the GRB and then alerts the Slewing Mirror
Telescope (SMT) to turn in the direction of the GRB and record the optical photon fluxes.
This report details the calibration of the two components: the MAPMTs and the YSO crystals
and simulations of the UBAT. The results shows that this design can observe a GRB within a
field of view of ±35° and can trigger in a time scale as short as 0.2 – 1.0 s
after the appearance of a GRB X-ray spike.
One of the key aspects of the upcoming Ultra-Fast Flash Observatory (UFFO) pathfinder for
Gamma Ray Bursts (GRBs) identification is the UFFO Burst Alert & Trigger Telescope
(UBAT). The scientific propose of UBAT is to detect and locate as fast as possible the
GRBs in the sky. This is achieved by using a coded mask aperture camera scheme with a wide
field of view (FOV) and selecting a X-ray detector of high quantum efficiency and large
detection area. This X-ray detector of high quantum efficiency and large detection area is
called the UBAT detector. The UBAT detector consists of 48 × 48 Yttrium Oxyorthosilicate
(YSO) scintillator crystal arrays and Multi Anode Photomultiplier Tubes (MAPMTs), analog
electronics equipped with ASIC chips, digital electronics equipped with Field Programmable
Gate Array (FPGA) chips, and a mechanical structure that supports all components of the
UBAT detector. The total number of the pixels in the UBAT detector is 2304, and the total
effective detection area is 191 cm2. We will present the design and
construction, and performance of the UBAT detector including the responses of the UBAT
detector to X-ray sources.
The Ultra-Fast Flash Observatory (UFFO) aims to detect the earliest moment of Gamma-Ray
Bursts (GRBs) which is not well known, resulting into the enhancement of GRB mechanism
understanding. The pathfinder mission was proposed to be a scaled-down version of UFFO,
and only contains the UFFO Burst Alert & Trigger Telescope (UBAT) measuring the
X-ray/gamma-ray with the wide-field of view and the Slewing Mirror Telescope (SMT) with a
rapid-response for the UV/optical photons. Once the UBAT detects a GRB candidate with the
position accuracy of 10 arcmin, the SMT steers the UV/optical photons from the candidate
to the telescope by the fast rotatable mirror and provides the early UV/optical photons
measurements with 4 arcsec accuracy. The SMT has a modified Ritchey-Chrètien telescope
with the aperture size of 10 cm diameter including the rotatable mirror and the image
readout by the intensified charge-coupled device. There is a key board called the UFFO
Data Acquisition system (UDAQ) that manages the communication of each telescope and also
of the satellite and the UFFO overall operation. This pathfinder is designed and built
within the limited size and weight of ~20 kg and the low power consumption up to
~30 W. We will discuss the design and performance of the UFFO-pathfinder, and its
integration to the Lomonosov satellite.
The Ultra-Fast Flash Observatory (UFFO) Pathfinder for Gamma-Ray Bursts (GRBs) consists
of two telescopes. The UFFO Burst Alert & Trigger Telescope (UBAT) handles the
detection and localization of GRBs, and the Slewing Mirror Telescope (SMT) conducts the
measurement of the UV/optical afterglow. UBAT is equipped with an X-ray detector, analog
and digital signal readout electronics that detects X-rays from GRBs and determines the
location. SMT is equipped with a stepping motor and the associated electronics to rotate
the slewing mirror targeting the GRBs identified by UBAT. First the slewing mirror points
to a GRB, then SMT obtains the optical image of the GRB using the intensified CCD and its
readout electronics. The UFFO Data Acquisition system (UDAQ) is responsible for the
overall function and operation of the observatory and the communication with the satellite
main processor. In this paper we present the design and implementation of the electronics
of UBAT and SMT as well as the architecture and implementation of UDAQ.
The Ultra-Fast Flash Observatory (UFFO), which will be launched onboard the
Lomonosov spacecraft, contains two crucial instruments: UFFO Burst
Alert & Trigger Telescope (UBAT) for detection and localization of Gamma-Ray Bursts
(GRBs) and the fast-response Slewing Mirror Telescope (SMT) designed for the observation
of the prompt optical/UV counterparts. Here we discuss the in-space calibrations of the
UBAT detector and SMT telescope. After the launch, the observations of the standard X-ray
sources such as pulsar in Crab nebula will provide data for necessary calibrations of
UBAT. Several standard stars will be used for the photometric calibration of SMT. The
celestial X-ray sources, e.g. X-ray binaries with bright optical sources
in their close angular vicinity will serve for the cross-calibration of UBAT and SMT.
One of the unexplored domains in the study of gamma-ray bursts (GRBs) is the early time
phase of the optical light curve. We have proposed Ultra-Fast Flash Observatory (UFFO) to
address this question through extraordinary opportunities presented by a series of small
space missions. The UFFO is equipped with a fast-response Slewing Mirror Telescope that
uses a rapidly moving mirror or mirror array to redirect the optical beam rather than
slewing the entire spacecraft or telescope to aim the optical instrument at the GRB
position. The UFFO will probe the early optical rise of GRBs with sub-second response, for
the first time, opening a completely new frontier in GRB and transient studies. Its fast
response measurements of the optical emission of dozens of GRB each year will provide
unique probes of the burst mechanism and test the prospect of GRB as a new standard
candle, potentially opening up the z > 10 universe. We describe the current limit in
early photon measurements, the aspects of early photon physics, our soon-to-be-launched
UFFO-pathfinder mission, and our next planned mission, the UFFO-100.
The purpose of this study was to analyze the expression of the placenta-specific microRNA miR-517a in maternal serum and in placental tissue from low birth weight newborns and try to detect the effects of miR-517a expression on invasion potential of trophoblasts. Placental tissue and maternal serum were collected from both low birth weight newborns (n = 10) and normal birth weight newborns (n = 20). Expression of miR-517a was assessed in placenta and serum samples by real-time qRT-PCR. In addition, human trophoblast HTR8/SVneo cells were transfected with a miR-517a 2′-O-methyl oligonucleotide or a negative control RNA, and invasion was measured using transwell migration assays. Expression of miR-517a was significantly increased in placentas from low birth weight newborns (61.79 ± 23.06) in comparison with those of normal birth weight newborns (5.01 ± 1.97; P < 0.05). The expression of miR-517a was also increased in maternal serum isolated from the low birth weight newborn (25.78 ± 8.69) compared with the normal birth weight newborn (3.21 ± 1.07; P < 0.05). Overexpression of miR-517a significantly inhibited invasion of HTR8/SVneo cells (P < 0.05). These data indicate that miR-517a overexpression could potentially lead to low birth weight, likely through the inhibition of trophoblast invasion.
Equine influenza virus (EIV) causes a highly contagious respiratory disease in equids, with confirmed outbreaks in Europe, America, North Africa, and Asia. Although China, Mongolia, and Japan have reported equine influenza outbreaks, Korea has not. Since 2011, we have conducted a routine surveillance programme to detect EIV at domestic stud farms, and isolated H3N8 EIV from horses showing respiratory disease symptoms. Here, we characterized the genetic and biological properties of this novel Korean H3N8 EIV isolate. This H3N8 EIV isolate belongs to the Florida sublineage clade 1 of the American H3N8 EIV lineage, and surprisingly, possessed a non-structural protein (NS) gene segment, where 23 bases of the NS1-encoding region were naturally truncated. Our preliminary biological data indicated that this truncation did not affect virus replication; its effect on biological and immunological properties of the virus will require further study.
Aqueous corrosion of zirconium alloys has become the major factor limiting prolonged fuel campaigns in nuclear plant. Studies using SEM, TEM and electrochemical impedance measurements have been interpreted as showing a dense inner-most oxide layer, and an increased thickness of the layer has been correlated to a better corrosion resistance. Many authors have reported that an ‘intermediate layer’ at the metal oxide interface has a complex structure or/and stochiometry different to that of both the bulk oxide and bulk metal, sometimes claimed to be a suboxide phase. Diffraction evidence has suggested the presence of both cubic ZrO and rhombohedral Zr3O phases, and compositional analysis has revealed similar variations in local oxygen stoichiometry.
We have carried out a systematic investigation of the structure and chemistry of the metal/oxide interface in samples of commercial ZIRLO corroded for times up to 180 days. We have developed new experimental techniques for the study of these interfaces both by Electron Energy Loss Spectroscopy (EELS) analysis in the Transmission Electron Microscope (TEM) and by Atom Probe Tomography (APT), and exactly the same samples have been investigated by both techniques. Our results show the development of a clearly defined suboxide layer of stoichiometry close to ZrO, and the subsequent disappearance of this layer at the first of the characteristic ‘breakaway’ transitions in the oxidation kinetics. We can correlate this behaviour with changes in the structure of the oxide layer, and particularly the development of interconnected porosity that links the corroding interface with the aqueous environment. Using high resolution SIMS analysis of isotopically spiked samples we demonstrate the penetration of the oxidising species through these porous outer oxide layers.
Cysteine proteases of pathogenic protozoan parasites play pivotal roles in the life cycle of parasites, but strict regulation of their activities is also essential for maintenance of parasite physiology and interaction with hosts. In this study, we identified and characterized cryptostatin, a novel inhibitor of cysteine protease (ICP) of Cryptosporidium parvum. Cryptostatin showed low sequence identity to other chagasin-family ICPs, but 3 motifs (NPTTG, GXGG, and RPW/F motifs), which are evolutionarily conserved in chagasin-family ICPs, were found in the sequence. The overall structure of cryptostatin consisted of 8 β-strands that progressed in parallel and closely resembled the immunoglobulin fold. Recombinant cryptostatin inhibited various cysteine proteases, including papain, human cathepsin B, human cathepsin L, and cryptopain-1, with Ki's in the picomolar range. Cryptostatin was active over a wide pH range and was highly stable under physiological conditions. The protein was thermostable and retained its inhibitory activity even after incubation at 95°C. Cryptostatin formed tight complexes with cysteine proteases, so the complexes remained intact in the presence of sodium dodecyl sulfate and β-mercaptoethanol, but they were disassembled by boiling. An immunogold electron microscopy analysis demonstrated diffused localization of cryptostatin within oocystes and meronts, but not within trophozoites, which suggests a possible role for cryptostatin in host cell invasion by C. parvum.
The Ultra-Fast Flash Observatory (UFFO) is a space mission to detect the early moments of an explosion from Gamma-ray bursts (GRBs), thus enhancing our understanding of the GRB mechanism. It consists of the UFFO Burst & Trigger telescope (UBAT) for the recognition of GRB positions using hard X-ray from GRBs. It also contains the Slewing Mirror Telescope (SMT) for the fast detection of UV-optical photons from GRBs. It is designed to begin the UV-optical observations in less than a few seconds after the trigger. The UBAT is based on a coded-mask X-ray camera with a wide field of view (FOV) and is composed of the coded mask, a hopper and a detector module. The SMT has a fast rotatable mirror which allows a fast UV-optical detection after the trigger. The telescope is a modified Ritchey-Chrétien telescope with the aperture size of 10 cm diameter, and an image intensifier readout by CCD. The UFFO pathfinder is scheduled to launch into orbit on 2012 June by the Lomonosov spacecraft. It is a scaled-down version of UFFO in order to make the first systematic study of early UV/optical light curves, including the rise phase of GRBs. We expect UBAT to trigger ~44 GRBs/yr and expect SMT to detect ~10 GRBs/yr.