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This study used data from 12 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and United States; N = 1,315) to investigate bidirectional associations between parental warmth and control, and child externalizing and internalizing behaviors. In addition, the extent to which these associations held across mothers and fathers and across cultures with differing normative levels of parent warmth and control were examined. Mothers, fathers, and children completed measures when children were ages 8 to 13. Multiple-group autoregressive cross-lagged structural equation models revealed that evocative child-driven effects of externalizing and internalizing behavior on warmth and control are ubiquitous across development, cultures, mothers, and fathers. Results also reveal that parenting effects on child externalizing and internalizing behaviors, though rarer than child effects, extend into adolescence when examined separately in mothers and fathers. Father-based parent effects were more frequent than mother effects. Most parent- and child-driven effects appear to emerge consistently across cultures. The rare culture-specific parenting effects suggested that occasionally the effects of parenting behaviors that run counter to cultural norms may be delayed in rendering their protective effect against deleterious child outcomes.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Analysis and understanding of the role of hydrogen in metals is a significant challenge for the future of materials science, and this is a clear objective of recent work in the atom probe tomography (APT) community. Isotopic marking by deuteration has often been proposed as the preferred route to enable quantification of hydrogen by APT. Zircaloy-4 was charged electrochemically with hydrogen and deuterium under the same conditions to form large hydrides and deuterides. Our results from a Zr hydride and a Zr deuteride highlight the challenges associated with accurate quantification of hydrogen and deuterium, in particular associated with the overlap of peaks at a low mass-to-charge ratio and of hydrogen/deuterium containing molecular ions. We discuss possible ways to ensure that appropriate information is extracted from APT analysis of hydrogen in zirconium alloy systems that are important for nuclear power applications.
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.
Pneumococcal serotype replacement is an important issue after the introduction of pneumococcal conjugate vaccine (PCV) in children. After the introduction of 13-valent PCV, the incidence of invasive pneumococcal diseases (IPD) caused by Streptococcus pneumoniae serotype 12F (Sp12F) have increased in some countries; however, an outbreak of Sp12F has not reported in the post-13-valent PCV era. We experienced a local outbreak of Sp12F during March through May 2016 in Tsuruoka city, Japan after the introduction of 13-valent PCV in 2013. The IPD patients were two children and seven adults, three of whom died with a rapid disease progress. Although the clear transmission route was not determined, eight of the nine patients (89%) had close contact with children, which suggests that transmitted colonisation of Sp12F among children and adults might be the source of transmission. Continuous monitoring of IPDs, along with the determination of pneumococcal serotypes, is warranted in the post–13-valent PCV era. New IPD control strategies may be needed if this fatal outbreak continues to occur.
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.
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.
In the present paper, the low-velocity impact of an elastic rod with a flat end upon a viscoelastic Timoshenko type beam has been considered. Viscoelastic properties of the beam out of the contact zone are described by the standard linear solid model with integer derivatives, while inside this zone they are governed by the fractional derivative standard linear solid model. The contact force for a concrete target has been defined experimentally at the concrete age of 7, 14, 28, 56, and 91 days. It has been found that an average maximum of the contact force increases with concrete age, whereas the contact duration decreases. Moreover, the most remarkable changes of both, contact force and contact time, occur at the concrete age earlier than 14 days, after that the rate of changes slows down. Experimental results have a good coincidence with theoretical expectations.
A nationwide population-based cohort was used to examine the severity of liver cirrhosis and risk of mortality from oral cancer.
The cohort consisted of 3583 patients with oral cancer treated by surgery between 2008 and 2011 in Taiwan. They were grouped on the basis of normal liver function (n = 3471), cirrhosis without decompensation (n = 72) and cirrhosis with decompensation (n = 40). The primary endpoint was mortality. Hazard ratios of death were also determined.
The mortality rates in the respective groups were 14.8 per cent, 20.8 per cent and 37.5 per cent at one year (p < 0.001). The adjusted hazard ratios of death at one year for each group compared to the normal group were 2.01 (p = 0.021) for cirrhotic patients without decompensation, 4.84 (p < 0.001) for those with decompensation and 2.65 (p < 0.001) for those receiving chemotherapy.
Liver cirrhosis can be used to predict one-year mortality in oral cancer patients. Chemotherapy should be used with caution and underlying co-morbidities should be managed in cirrhotic patients to reduce mortality risk.
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.