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Using multilevel models, we examined mother-, father-, and child-reported (N = 1,336 families) externalizing behavior problem trajectories from age 7 to 14 in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States). The intercept and slope of children's externalizing behavior trajectories varied both across individuals within culture and across cultures, and the variance was larger at the individual level than at the culture level. Mothers’ and children's endorsement of aggression as well as mothers’ authoritarian attitudes predicted higher age 8 intercepts of child externalizing behaviors. Furthermore, prediction from individual-level endorsement of aggression and authoritarian attitudes to more child externalizing behaviors was augmented by prediction from cultural-level endorsement of aggression and authoritarian attitudes, respectively. Cultures in which father-reported endorsement of aggression was higher and both mother- and father-reported authoritarian attitudes were higher also reported more child externalizing behavior problems at age 8. Among fathers, greater attributions regarding uncontrollable success in caregiving situations were associated with steeper declines in externalizing over time. Understanding cultural-level as well as individual-level correlates of children's externalizing behavior offers potential insights into prevention and intervention efforts that can be more effectively targeted at individual children and parents as well as targeted at changing cultural norms that increase the risk of children's and adolescents’ externalizing behavior.
OBJECTIVES/SPECIFIC AIMS: Gliomas are the most lethal and common
primary tumor type in the central nervous system across all age groups; affected
adults have a life expectancy of just 14 months. As glioma cells invade the
surrounding normal parenchyma they remodel the composition and ultrastructure of
the surrounding extracellular matrix (ECM), suggesting that the native (i.e.,
“normal”) microenvironment is not ideal for their survival
and proliferation. Recent reports describe suppressive and/or lethal
effects of mammalian ECM hydrogels derived from normal (nonneoplastic) sources
upon various cancer types. ECM-based bioscaffolds placed at sites of neoplastic
tissue resection in humans have never been reported to facilitate cancer
recurrence. The objective of the present research is to evaluate mammalian ECM
as a novel approach to glioma therapy. METHODS/STUDY POPULATION: ECM
hydrogels from porcine dermis, small intestine, and urinary bladder were
produced as described previously. Primary glioma cells were graciously supplied
by Drs. Nduka Amankulor and Johnathan Engh, and U-87 MG were ordered through
ATCC. Cells were plated onto tissue culture plastic at
~60% confluence and allowed to attach for 24 hours before
treatment. The saline-soluble fraction (SSF) of ECM was obtained by mixing
lyophilized, comminuted ECM with 0.9% saline for 24 hours then
filtering the resulting mixture through a 10 kDa molecular weight cutoff column.
All assays and kits were followed according to the manufacturer’s
instructions. Cell viability was measured via MTT assay
(Vybrant® MTT Cell Proliferation Assay, Invitrogen)
and by live/dead staining
(LIVE/DEAD® Cell Imaging Kit, Invitrogen). Time
lapse videos were created by taking images every 20 minutes for 18 hours
(phase-contrast) or every 10 minutes for 12 hours (darkfield). NucView reagent
was ordered from Biotium. Temozolomide was ordered through Abmole. All in vivo
work was conducted according to protocols approved by the University of
Pittsburgh’s IACUC office. RESULTS/ANTICIPATED RESULTS:
ECM hydrogels derived from porcine dermis, small intestine, or urinary bladder
all decreased the viability of primary glioma cells in vitro, with urinary
bladder extracellular matrix (UBM) having the most dramatic effects. The SSF of
UBM (UBM-SSF), devoid of the fibrillar, macromolecular components of ECM, was
sufficient to recapitulate this detrimental effect upon neoplastic cells in
vitro and was used for the remainder of the experiments described herein. In a
cell viability assay normalized to the media treatment, non-neoplastic CHME5 and
N1E-115 cells scored 103% and 114% after 48 hours when
treated with UBM-SSF and 2 primary high-grade glioma cell types scored
17% and 30.5% with UBM-SSF (n=2).
Phase-contrast time-lapse video showed CHME5 and HFF thriving in the presence of
UBM-SSF for 18 hours while most primary glioma cells shriveled and died within
this time. Darkfield time-lapse video of wells containing Nucview dye,
fluorescent upon cleavage by active caspase-3, confirmed that within 12 hours
most primary glioma cells underwent apoptosis while CHME5 and HFF did not. In
culture with primary astrocytes, high grade primary glioma cells, and U-87 MG
glioma cells for 24 hours, UBM-SSF was found to significantly increase the
population of primary astrocytes compared with media
(p<0.05) while decreasing the 2 glioma cell types to
approximately one-third as many cells as the media control
(p<0.0001). A dose-response of temozolomide from 0
to 10,000 μM showed that when treating 2 non-neoplastic cell types
(CHME5 and HFF) and 2 types of primary glioma cell there was no difference in
survivability at any concentration. Contrasted to this, a dose-response of
UBM-SSF from 350 to 7000 μg/mL showed that the
non-neoplastic cells survived significantly better than the glioma cells at
concentrations of 875 μg/mL and upward
(p<0.05). In preliminary animal experiments, large
primary glioma tumors in the flanks of athymic nude mice were resected and
replaced with either UBM SSF or Matrigel (an ECM product of neoplastic cell
origin). After 7 days the resection sites with UBM-SSF had little tumor regrowth
if any compared with the dramatic recurrence seen in the Matrigel injection
sites (n=2). In a separate survival study comparing PBS to UBM-SSF
injections in the flank-resection model, all animals given PBS had to be
sacrificed at 9, 11, and 11 days (n=3) whereas animals given UBM-SSF
were sacrificed at 15, 24, and 39 days (n=3), indicating a moderate
increase in survival due to the UBM-SSF. DISCUSSION/SIGNIFICANCE OF
IMPACT: Since the introduction of the pan-cytotoxic chemotherapeutic agent TMZ
in 2005, the standard of care for patients with glioblastoma multiforme has not
improved. These findings indicate that non-neoplastic ECM contains potent
bioactive regulators capable of abrogating malignancy. Our in vitro data suggest
these molecules appear to have no deleterious effect on non-neoplastic cells
while specifically inducing apoptosis in glioma cells. Our in vivo data suggest
that these molecules may be useful in delaying glioma recurrence, thus resulting
in extended lifespan. Delivering soluble fractions of ECM to a tumor site may
represent a novel approach to glioma therapy, sidestepping traditional cytotoxic
therapies in favor of utilizing putative endogenous anti-tumor pathways.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Using data from 1,177 families in eight countries (Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States), we tested a conceptual model of direct effects of childhood family adversity on subsequent externalizing behaviors as well as indirect effects through psychological mediators. When children were 9 years old, mothers and fathers reported on financial difficulties and their use of corporal punishment, and children reported perceptions of their parents’ rejection. When children were 10 years old, they completed a computerized battery of tasks assessing reward sensitivity and impulse control and responded to questions about hypothetical social provocations to assess their hostile attributions and proclivity for aggressive responding. When children were 12 years old, they reported on their externalizing behavior. Multigroup structural equation models revealed that across all eight countries, childhood family adversity had direct effects on externalizing behaviors 3 years later, and childhood family adversity had indirect effects on externalizing behavior through psychological mediators. The findings suggest ways in which family-level adversity poses risk for children's subsequent development of problems at psychological and behavioral levels, situated within diverse cultural contexts.
This study presents a new groove profile using the slant groove depth arrangements to enhance the performance of micro-HGJBs. The computational analysis was based on the steady-state three-dimensional conservation equations of mass and momentum in conjunction with the cavitation model to examine the complex lubricated flow field. The simulated results of load capacity and circumferential pressure distribution of lubricant film are in good agreement with the measurement data and the predictions cited in the literature. Numerical experiments were extended to determine the pressure distribution, load capacity, radial stiffness and friction torque by varying the slant ratio of groove depth, eccentricity ratio, rotational speed and attitude angle. The cavitation extent of lubricant film was also studied for different slant groove patterns.
A family of structure-dependent integration methods has been proposed by Gui et al. for time integration. Although it has desirable numerical properties, such as unconditional stability, explicit formulation and second-order accuracy, it has some adverse properties, such as a poor capability to capture structural nonlinearity, an overshoot in a high frequency steady- state response and a weak instability in the high frequency response of nonzero initial conditions. The causes of these adverse properties are explored. A poor capability to capture structural nonlinearity may originate from the convergence rate of 1 in velocity error. This family method has an overshoot in a high frequency steady-state response and this overshoot can be eliminated by adding a load-dependent term into the displacement difference equation. It is also analytically verified that the family method generally has no weak instability. However, the special member with λ = 4, i.e., CR explicit method, is shown to have a weak instability. Thus, it must be prohibited from practical applications although many applications of this method were found in the literature.
Following the success of static analysis of free-free 2-D plane trusses by using a self-regularization approach uniquely, we further extend the technique to deal with 3-D problems of space trusses. The inherent singular stiffness of a free-free structure is expanded to a bordered matrix by adding r singular vectors corresponding to zero singular values, where r is the nullity of the singular stiffness matrix. Besides, r constraints are accompanied to result in a nonsingular matrix. Only the pure particular solution with nontrivial strain is then obtained but without the homogeneous solution of no deformation. To link with the Fredholm alternative theorem, the slack variables with zero values indicate the infinite solutions while those with nonzero values imply the case of no solutions. A simple space truss is used to demonstrate the validity of the proposed model. An alternative way of reasonable support system to result in a nonsingular stiffness matrix is also addressed. In addition, the finite-element commercial code ABAQUS is also implemented to check the results.
During April 1995, a field and aircraft experiment was conducted in central Alaska in support of the Moderate Resolution Imaging Spectroradiometer (MODIS) snow-mapping project. The MODIS Airborne Simulator (MAS), a 50 channel spectroradiometer, was flown on board the NASA ER-2 aircraft. An objective of the mission was to determine the accuracy of mapping snow in different surface covers using an algorithm designed to map global snow cover after the launch of MODIS in 1998. The surface cover in this area of central Alaska is typically spruce, birch, aspen, mixed forest and muskeg. Integrated reflectance, Ri was calculated from the visible/near-infrared channels of the MAS sensor. The Ri was used to estimate different vegetation-cover densities because there is an inverse relationship between vegetation-cover density and albedo in snow-covered terrain. A vegetation-cover density map was constructed using MAS data acquired on 13 April 1995 over central Alaska. In the part of the scene that was mapped as having a vegetation-cover density of < 50%, the snow-mapping algorithm mapped 96.41% snow cover. These areas are generally composed of muskeg and mixed forests and include frozen lake. In the part of the scene that was estimated to have a vegetation-cover density of ≥50%, the snow-mapping algorithm mapped 71.23% snow cover. These areas are generally composed of dense coniferous or deciduous forests. Overall, the accuracy of the snow-mapping algorithm is > 87.41% for a 13 April MAS scene with a variety of surface covers (coniferous and deciduous and mixed forests, muskeg, tundra and frozen lake).
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males.
The 94 participants (aged 9–19 years) – 20 male youth with ASD, 20 unaffected brothers and 54 TD males – received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference.
We found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers.
Atypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.
To systematically search for studies reporting outcomes for adenoidectomy alone as a treatment for paediatric obstructive sleep apnoea and use the data to perform a meta-analysis.
Nine databases, including PubMed and Medline, were systematically searched through to 1 April 2016. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed.
A total of 1032 articles were screened and 126 full texts were reviewed. Three paediatric studies (47 patients) reported outcomes. Overall, apnoea–hypopnoea index values decreased from 18.1 ± 16.8 to 3.1 ± 5.5 events per hour (28 patients). Random-effects modelling demonstrated a mean difference of −14.43 events per hour (I2 = 23 per cent (low inconsistency)). The apnoea–hypopnoea index standardised mean difference was −1.14 (large magnitude of effect). The largest reduction in apnoea–hypopnoea index was observed in children aged less than 12 months (reduction of 56.6−94.9 per cent). Lowest oxygen saturation values improved from 80.0 ± 9.5 to 85.5 ± 6.0 per cent (13 children).
Adenoidectomy alone has improved obstructive sleep apnoea in children, especially in those aged less than 12 months; however, given the low number of studies, isolated adenoidectomy remains an area for additional research.
The aim of the study was to evaluate the comparative risk of self-harm associated with the use of different antidepressants.
A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 751 606 new antidepressant users with depressive disorders were included. The study outcome was hospitalization due to self-harm (International Classification of Diseases, Ninth Revision, Clinical Modification codes: E950–E958 and E980–E988). Cox proportional hazards models with stratification of the propensity score deciles were used to estimate the hazard ratios of self-harm hospitalization during the first year following the initiation of antidepressant treatment.
There were 1038 hospitalization episodes due to self-harm that occurred during the follow-up of 149 796 person-years, with an overall incidence rate of 6.9 [95% confidence interval (CI) 6.5–7.4] per 1000. Compared with fluoxetine, the risk of self-harm hospitalization was higher for maprotiline [adjusted hazard ratio (aHR) = 3.00, 95% CI 1.40–6.45], milnacipran (aHR = 2.34, 95% CI 1.24–4.43) and mirtazapine (aHR = 1.40, 95% CI 1.06–1.86), lower for bupropion (aHR = 0.51, 95% CI 0.30–0.86), and similar level of risk was found for other selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline).
The risk of self-harm may vary across different antidepressant drugs. It would be of importance to conduct further research to investigate the influence of antidepressant use on self-harm behaviors.
We describe a hybrid pixel array detector (electron microscope pixel array detector, or EMPAD) adapted for use in electron microscope applications, especially as a universal detector for scanning transmission electron microscopy. The 128×128 pixel detector consists of a 500 µm thick silicon diode array bump-bonded pixel-by-pixel to an application-specific integrated circuit. The in-pixel circuitry provides a 1,000,000:1 dynamic range within a single frame, allowing the direct electron beam to be imaged while still maintaining single electron sensitivity. A 1.1 kHz framing rate enables rapid data collection and minimizes sample drift distortions while scanning. By capturing the entire unsaturated diffraction pattern in scanning mode, one can simultaneously capture bright field, dark field, and phase contrast information, as well as being able to analyze the full scattering distribution, allowing true center of mass imaging. The scattering is recorded on an absolute scale, so that information such as local sample thickness can be directly determined. This paper describes the detector architecture, data acquisition system, and preliminary results from experiments with 80–200 keV electron beams.
This study advances understanding of predictors of child abuse and neglect at multiple levels of influence. Mothers, fathers, and children (N = 1,418 families, M age of children = 8.29 years) were interviewed annually in three waves in 13 cultural groups in nine countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and the United States). Multilevel models were estimated to examine predictors of (a) within-family differences across the three time points, (b) between-family within-culture differences, and (c) between-cultural group differences in mothers' and fathers' reports of corporal punishment and children's reports of their parents' neglect. These analyses addressed to what extent mothers' and fathers' use of corporal punishment and children's perceptions of their parents' neglect were predicted by parents' belief in the necessity of using corporal punishment, parents' perception of the normativeness of corporal punishment in their community, parents' progressive parenting attitudes, parents' endorsement of aggression, parents' education, children's externalizing problems, and children's internalizing problems at each of the three levels. Individual-level predictors (especially child externalizing behaviors) as well as cultural-level predictors (especially normativeness of corporal punishment in the community) predicted corporal punishment and neglect. Findings are framed in an international context that considers how abuse and neglect are defined by the global community and how countries have attempted to prevent abuse and neglect.
In Taiwan, avian influenza virus (AIV) subtypes H5N2, H6N1 and H7N3 have been identified in domestic poultry, and several strains of these subtypes have become endemic in poultry. To evaluate the potential of avian-to-human transmission due to occupational exposure, an exploratory analysis of AIV antibody status in poultry workers was conducted. We enrolled 670 poultry workers, including 335 live poultry vendors (LPVs), 335 poultry farmers (PFs), and 577 non-poultry workers (NPWs). Serum antibody titres against various subtypes of viruses were analysed and compared. The overall seropositivity rates in LPVs and PFs were 2·99% (10/335) and 1·79% (6/335), respectively, against H5N2; and 0·6% (2/335) and 1·19% (4/335), respectively, for H7N3 virus. Of NPWs, 0·35% (2/577) and 0·17% (1/577) were seropositive for H5N2 and H7N3, respectively. Geographical analysis revealed that poultry workers whose workplaces were near locations where H5N2 outbreaks in poultry have been reported face greater risks of being exposed to viruses that result in elevated H5N2 antibody titres. H6N1 antibodies were detected in only one PF, and no H7N9 antibodies were found in the study subjects. Subclinical infections caused by H5N2, H6N1 and H7N3 viruses were thus identified in poultry workers in Taiwan. Occupational exposure is associated with a high risk of AIV infection, and the seroprevalence of particular avian influenza strains in humans reflects the endemic strains in poultry in this region.