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The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework’s major proposition is that it situates D&I sciences as targeted “sub-sciences” of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages.
Adolescent psychotic experiences increase risk for schizophrenia and other severe psychopathology in adulthood. Converging evidence implicates urban and adverse neighborhood conditions in the etiology of adolescent psychotic experiences, but the role of young people's personal perceptions of disorder (i.e., physical and social signs of threat) in their neighborhood is unknown. This was examined using data from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2,232 British twins. Participants were interviewed at age 18 about psychotic phenomena and perceptions of disorder in the neighborhood. Multilevel, longitudinal, and genetically sensitive analyses investigated the association between perceptions of neighborhood disorder and adolescent psychotic experiences. Adolescents who perceived higher levels of neighborhood disorder were significantly more likely to have psychotic experiences, even after accounting for objectively/independently measured levels of crime and disorder, neighborhood- and family-level socioeconomic status, family psychiatric history, adolescent substance and mood problems, and childhood psychotic symptoms: odds ratio = 1.62, 95% confidence interval [1.27, 2.05], p < .001. The phenotypic overlap between adolescent psychotic experiences and perceptions of neighborhood disorder was explained by overlapping common environmental influences, rC = .88, 95% confidence interval [0.26, 1.00]. Findings suggest that early psychological interventions to prevent adolescent psychotic experiences should explore the role of young people's (potentially modifiable) perceptions of threatening neighborhood conditions.
Theorem. Suppose that k = (K,
) is an ℵ0-presentable abstract elementary class with Löwenheim–Skolem number ℵ0, satisfying the joint embedding and amalgamation properties in ℵ0. If K has only countably many models in ℵ1, then all are small. If, in addition, k is almost Galois ω-stable then k is Galois ω-stable. Suppose that k = (K,
) is an ℵ0-presented almost Galois ω-stable AEC satisfying amalgamation for countable models, and having a model of cardinality ℵ1. The assertion that K is ℵ1-categorical is then absolute.
Post-conflict mental health studies in low-income countries have lacked
pre-conflict data to evaluate changes in psychiatric morbidity resulting
from political violence.
This prospective study compares mental health before and after exposure
to direct political violence during the People's War in Nepal.
An adult cohort completed the Beck Depression Inventory and Beck Anxiety
Inventory in 2000 prior to conflict violence in their community and in
2007 after the war.
Of the original 316 participants, 298 (94%) participated in the
post-conflict assessment. Depression increased from 30.9 to 40.6%.
Anxiety increased from 26.2 to 47.7%. Post-conflict post-traumatic stress
disorder (PTSD) was 14.1%. Controlling for ageing, the depression
increase was not significant. The anxiety increase showed a dose–response
association with conflict exposure when controlling for ageing and daily
stressors. No demographic group displayed unique vulnerability or
resilience to the effects of conflict exposure.
Conflict exposure should be considered in the context of other types of
psychiatric risk factors. Conflict exposure predicted increases in
anxiety whereas socioeconomic factors and non-conflict stressful life
events were the major predictors of depression. Research and
interventions in postconflict settings therefore should consider
differential trajectories for depression v. anxiety and
the importance of addressing chronic social problems ranging from poverty
to gender and ethnic/caste discrimination.
Plague, which is most often caused by the bite of Yersinia pestis-infected fleas, is a rapidly progressing, serious disease that can be fatal without prompt antibiotic treatment. In late December 2007, an outbreak of acute gastroenteritis occurred in Nimroz Province of southern Afghanistan. Of the 83 probable cases of illness, 17 died (case fatality 20·5%). Being a case was associated with consumption or handling of camel meat (adjusted odds ratio 4·4, 95% confidence interval 2·2–8·8, P<0·001). Molecular testing of patient clinical samples and of tissue from the camel using PCR/electrospray ionization–mass spectrometry revealed DNA signatures consistent with Yersinia pestis. Confirmatory testing using real-time PCR and immunological seroconversion of one of the patients confirmed that the outbreak was caused by plague, with a rare gastrointestinal presentation. The study highlights the challenges of identifying infectious agents in low-resource settings; it is the first reported occurrence of plague in Afghanistan.
We identify emission lines of post-iron peak elements in very high signal-to-noise spectra of a sample of planetary nebulae. Analysis of lines from ions of Kr and Xe reveals enhancements in most of the PNe, in agreement with theories of $s$-process in AGB stars. Surprisingly, we did not detect lines from Br even though $s$-process calculations indicate that it should be produced with Kr at detectable levels.
NGC 7027 is justifiably THE template spectrum for PNe. Its vast range of emission species – from molecular and neutral to ions with ionization potential > 120eV – its high surface brightness and accessibiliy for northern observatories make it the PN laboratory of choice. However the quality of the spectra from the UV to the IR is mixed, many line fluxes and identifications still remaining unchecked from photographic or image tube spectra. Very deep spectra of NGC 7027 (emission line strengths <10-4 of Hβ) in the 0.65 to 1.05μm region (Baluteau et al. 1995) showed the presence of many faint emission lines. Pequignot & Baluteau (1994) showed that heavy elements from the 4th, 5th and 6th rows of the Periodic Table have much higher abundances than Solar, confirming the synthesis of neutron capture elements in low mass stars and providing new constraints on stellar evolution theory.
Lamination of metal-coated elastomeric stamps against thin films of electroactive organics provides non-invasive, high resolution electrical contacts for investigations of charge transport in these materials. This approach uses the features of relief on the stamps to define, with nanometer resolution, the geometry and separation of electrodes that are formed by uniform evaporation of a thin metal film onto the stamp. Soft, room temperature contact of an element of this type with an organic semiconductor film on a gate dielectric and a gate yields a high performance top contact transistor with source/drain electrodes supported by the stamp. We review here our use of this approach to study the electrical properties of the organic semiconductor pentacene in thin film transistors structures. We also introduce a method for using the same techniques and structures to probe transport through organic monolayers.
The Ure2 protein from Saccharomyces cerevisiae
has been proposed to undergo a prion-like autocatalytic
conformational change, which leads to inactivation of the
protein, thereby generating the [URE3]
phenotype. The first 65 amino acids, which are dispensable
for the cellular function of Ure2p in nitrogen metabolism,
are necessary and sufficient for [URE3]
(Masison & Wickner, 1995), leading to designation of
this domain as the Ure2 prion domain (UPD). We expressed
both UPD and Ure2 as glutathione-S-transferase
(GST) fusion proteins in Escherichia coli and
observed both to be initially soluble. Upon cleavage of
GST-UPD by thrombin, the released UPD formed ordered fibrils
that displayed amyloid-like characteristics, such as Congo
red dye binding and green-gold birefringence. The fibrils
exhibited high β-sheet content by Fourier transform
infrared spectroscopy. Fiber formation proceeded in an
autocatalytic manner. In contrast, the released, full-length
Ure2p formed mostly amorphous aggregates; a small amount
polymerized into fibrils of uniform size and morphology.
Aggregation of Ure2p could be seeded by UPD fibrils. Our
results provide biochemical support for the proposal that
the [URE3] state is caused by a self-propagating
inactive form of Ure2p. We also found that the uncleaved
GST-UPD fusion protein could polymerize into amyloid fibrils
by a strictly autocatalytic mechanism, forcing the GST
moiety of the protein to adopt a new, β-sheet-rich
conformation. The findings on the GST-UPD fusion protein
indicate that the ability of the prion domain to mediate
a prion-like conversion process is not specific for or
limited to the Ure2p.
Electrospray ionization mass spectrometry (ESI-MS)
was used to measure the binding of Cu2+ ions
to synthetic peptides corresponding to sections of the
sequence of the mature prion protein (PrP). ESI-MS demonstrates
that Cu2+ is unique among divalent metal ions
in binding to PrP and defines the location of the major
Cu2+ binding site as the octarepeat region in
the N-terminal domain, containing multiple copies of the
repeat ProHisGlyGlyGlyTrpGlyGln. The stoichiometries of
the complexes measured directly by ESI-MS are pH dependent:
a peptide containing four octarepeats chelates two Cu2+
ions at pH 6 but four at pH 7.4. At the higher pH, the
binding of multiple Cu2+ ions occurs with a
high degree of cooperativity for peptides C-terminally
extended to incorporate a fifth histidine. Dissociation
constants for each Cu2+ ion binding to the octarepeat
peptides, reported here for the first time, are mostly
in the low micromolar range; for the addition of the third
and fourth Cu2+ ions to the extended peptides
at pH 7.4, KD's are <100 nM.
N-terminal acetylation of the peptides caused some reduction
in the stoichiometry of binding at both pH's. Cu2+
also binds to a peptide corresponding to the extreme N-terminus
of PrP that precedes the octarepeats, arguing that this
region of the sequence may also make a contribution to
the Cu2+ complexation. Although the structure
of the four-octarepeat peptide is not affected by pH changes
in the absence of Cu2+, as judged by circular
dichroism, Cu2+ binding induces a modest change
at pH 6 and a major structural perturbation at pH 7.4.
It is possible that PrP functions as a Cu2+
transporter by binding Cu2+ ions from the extracellular
medium under physiologic conditions and then releasing
some or all of this metal upon exposure to acidic pH in
endosomes or secondary lysosomes.
Direct-drive laser fusion received a number of setbacks from the experimental observation in the 1960s and 1970s of very complex interactions in laser plasma experiments caused by a number of nonlinear and anomalous phenomena. Although smoothing methods were introduced intuitively or empirically–succeeding in reducing these difficulties–it was not until a few years ago that the 20-ps stochastic pulsation mechanism was discovered. We assume here that this 20-ps stochastic pulsation may be the major obstacle to achieving direct-drive fusion, even though it is now generally assumed that the major challenge to the achievement of direct-drive fusion is the Rayleigh-Taylor instability. While we do not discount the importance of the Rayleigh-Taylor mechanisms, we concentrate here on the analysis of the pulsation process. A method of analysis was developed, using time-dependent real-time computations employing a genuine two-fluid model, which includes the interior electric fields and the very large amplitude longitudinal plasma oscillations that are driven by the laser field. These mechanisms, which were first suggested in 1974, reveal themselves now as self-generated von-Laue gratings, preventing the propagation of laser radiation through the outermost plasma corona and preventing energy deposition by temporal interruption caused by thermal relaxation and the subsequent reestablishment of these gratings, and so on. The abolition of this pulsation by broad-band laser irradiation or other smoothing methods is now well understood. A synopsis of these developments is presented here, consistent with Rubbia's proposition of using the MJ drivers for laser fusion, the technology for which is now available.
The asymmetrical forward versus reverse - bias DC electrical conductivity (macroscopic and also nanoscopic) through Langmuir-Blodgett multilayers and monolayers of γ-(nhexadecyl) quinolinum tricyanoquinodimethanide, C16H33Q-3CNQ (1) is attributable to rectification of electrical current by a single molecule.