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We argue that how players perceive the attack-defense game might matter far more than its actual underlying structure in determining the outcomes of intergroup conflict. Leaders can use various tactics to dynamically modify these perceptions, from collective victimization to the distortion of the perceived payoffs, with some followers being more receptive than others to such leadership tactics.
In recent years, the discovery of massive quasars at
has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
Despite its numerous side effects, clozapine is still the most effective antipsychotics making it an ideal reference substance to validate the efficacy of novel compounds for the treatment of schizophrenia. However, blood–brain barrier permeability for most new molecular entities is unknown, requiring central delivery. Thus, we performed a dose-finding study for chronic intracerebroventricular (icv) delivery of clozapine in mice.
Specifically, we implanted wild-type C57BL/6J mice with osmotic minipumps (Alzet) delivering clozapine at a rate of 0.15 µl/h at different concentrations (0, 3.5, 7 and 14 mg/ml, i.e. 0, 12.5, 25 and 50 µg/day). Mice were tested weekly in a modified SHIRPA paradigm, for locomotor activity in the open field and for prepulse inhibition (PPI) of the acoustic startle response (ASR) for a period of 3 weeks.
None of the clozapine concentrations caused neurological deficits or evident gross behavioural alterations in the SHIRPA paradigm. In male mice, clozapine had no significant effect on locomotor activity or PPI of the ASR. In female mice, the 7 and 14 mg/ml dose of clozapine significantly affected both open field activity and PPI, while 3.5 mg/ml of clozapine increased PPI but had no effects on locomotor activity.
Our findings indicate that 7 mg/ml may be the optimal dose for chronic icv delivery of clozapine in mice, allowing comparison to screen for novel antipsychotic compounds.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
In this talk, the focus will be on recent experiments performed on superconducting doped SrTiO3 films using the ferroelectric field effect. Using thin single crystal films of Nb-doped SrTiO3, we have used the polarization field of ferroelectric Pb(Zr,Ti)O3 to electrostatically tune the electronic properties of Nb-doped SrTiO3. Atomic force microscopy was used to locally reverse the ferroelectric polarization, inducing large resistivity and carrier modulations, resulting in a clear shift in the superconducting critical temperature . By poling sub-micron scale domains, the carrier density and the electronic properties of the superconducting channel were locally modified. Transport measurements reveal a steplike behavior in the current-voltage and resistance-magnetic field characteristics. This behavior, not observed in homogeneously poled samples, is ascribed to phase slip lines which are more easily generated in inhomogeneous superconductors. More generally, the technique developed should allow Josephson junctions, SQUIDS and superconducting circuits to be directly written in a Nb-doped SrTiO3 film using atomic force microscopy, an idea proposed in 1997 by C.H. Ahn et al. .  K. Takahashi, D. Jaccard, M. Gabay, K. Shibuya, T. Ohnishi, M. Lippmaa, J.-M. Triscone, Nature 441,195 (2006).  C.H. Ahn, T. Tybell, L. Antognazza, K. Char, R.H. Hammond, M.R. Beasley, Ø. Fischer, and J.-M. Triscone. Science 276, 1100 (1997).
This is a copy of the slides presented at the meeting but not formally
written up for the volume.
Cell surface carbohydrates play unique roles in a host of biologically
relevant events such as cell differentiation, adhesion and development.
They also mediate many undesired processes such as pathogenic infection
and tumor metastasis. A common feature of all tumor cells is the altered
expression and presentation of surface glycans that serve as “non-self”
structures that can be recognized by the immune system. For many years,
these tumor-associated carbohydrate antigens (TACA’s) have been employed
in the development of tumor vaccines with varying degrees of success. In
addition, these sugars may mediate tumor cell adhesion during the
metastatic cascade. We have previously succeeded in preparing both gold
nanoparticles and quantum dot nanocrystals that were coated with specific
TACA’s. We have concentrated on the Thomsen Friedenreich (TF) antigen
disaccharide (Galβ1-3GalNAcα-O-Ser/Thr) and have shown that gold
particles coated with TF antigen can either promote or inhibit metastasis
in vivo. Here we describe our progress toward the synthesis of a number
of these multivalent nanoscaffolds and report on our characterization
efforts and how the size and surface chemistry of the particles relates
to their biological activities.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
To determine the association between excess body fat, assessed by skinfold thickness, and the incidence of type 2 diabetes mellitus (T2DM) and hypertension (HT).
Data from the ongoing PERU MIGRANT Study were analysed. The outcomes were T2DM and HT, and the exposure was skinfold thickness measured in bicipital, tricipital, subscapular and suprailiac areas. The Durnin–Womersley formula and SIRI equation were used for body fat percentage estimation. Risk ratios and population attributable fractions (PAF) were calculated using Poisson regression.
Rural (Ayacucho) and urban shantytown district (San Juan de Miraflores, Lima) in Peru.
Adults (n 988) aged ≥30 years (rural, rural-to-urban migrants, urban) completed the baseline study. A total of 785 and 690 were included in T2DM and HT incidence analysis, respectively.
At baseline, age mean was 48·0 (sd 12·0) years and 47 % were males. For T2DM, in 7·6 (sd 1·3) years, sixty-one new cases were identified, overall incidence of 1·0 (95 % CI 0·8, 1·3) per 100 person-years. Bicipital and subscapular skinfolds were associated with 2·8-fold and 6·4-fold risk of developing T2DM. On the other hand, in 6·5 (sd 2·5) years, overall incidence of HT was 2·6 (95 % CI 2·2, 3·1) per 100 person-years. Subscapular and overall fat obesity were associated with 2·4- and 2·9-fold risk for developing HT. The PAF for subscapular skinfold was 73·6 and 39·2 % for T2DM and HT, respectively.
We found a strong association between subscapular skinfold thickness and developing T2DM and HT. Skinfold assessment can be a laboratory-free strategy to identify high-risk HT and T2DM cases.
We examined maternal depression and maternal sensitivity as mediators of the association between maternal childhood adversity and her child's temperament in 239 mother–child dyads from a longitudinal, birth cohort study. We used an integrated measure of maternal childhood adversity that included the Childhood Trauma Questionnaire and the Parental Bonding Index. Maternal depression was assessed with the Edinburgh Postnatal Depression Scale at 6 months postpartum. Maternal sensitivity was assessed with the Ainsworth maternal sensitivity scales at 6 months. A measure of “negative emotionality/behavioral dysregulation” was derived from the Early Childhood Behaviour Questionnaire administered at 36 months. Bootstrapping-based mediation analyses revealed that maternal depression mediated the effect of maternal childhood adversity on offspring negative emotionality/behavioral dysregulation (95% confidence interval [0.026, 0.144]). We also found a serial, indirect effect of maternal childhood adversity on child negative emotionality/behavioral mediated first by maternal depression and then by maternal sensitivity (95% confidence interval [0.031, 0.156]). Results suggest the intergenerational transmission of the effects of maternal childhood adversity to the offspring occurs through a two-step, serial pathway, involving maternal depression and maternal sensitivity.
Correction of tetralogy of Fallot during infancy usually eliminates the risks associated with general anaesthesia. In rare cases of uncorrected defects persisting into adulthood, anaesthetic management during non-cardiac surgery may therefore be challenging. We describe the use of continuous spinal anaesthesia to successfully circumvent the operative risk of major abdominal surgery in an adult patient with uncorrected tetralogy of Fallot.
Transgenic crops are being developed with herbicide resistance traits to expand innovative weed management solutions for crop producers. Soybean with traits that confer resistance to the hydroxyphenylpyruvate dioxygenase herbicide isoxaflutole is under development and will provide a novel herbicide mode of action for weed management in soybean. Ten field experiments were conducted over 2 years (2017 and 2018) on five soil textures with isoxaflutole-resistant soybean to evaluate annual weed control using one- and two-pass herbicide programs. The one-pass weed control programs included isoxaflutole plus metribuzin, applied PRE, at a low rate (52.5 + 210 g ai ha−1), medium rate (79 + 316 g ai ha−1), and high rate (105 + 420 g ai ha−1); and glyphosate applied early postemergence (EPOST) or late postemergence (LPOST). The two-pass weed control programs included isoxaflutole plus metribuzin, applied PRE, followed by glyphosate applied LPOST, and glyphosate applied EPOST followed by LPOST. At 4 weeks after the LPOST application, control of common lambsquarters, pigweed species, common ragweed, and velvetleaf was variable at 25% to 69%, 49% to 86%, and 71% to 95% at the low, medium, and high rates of isoxaflutole plus metribuzin, respectively. Isoxaflutole plus metribuzin at the low, medium, and high rates controlled grass species evaluated (i.e., barnyardgrass, foxtail, crabgrass, and witchgrass) 85% to 97%, 75% to 99%, and 86% to 100%, respectively. All two-pass weed management programs provided 98% to 100% control of all species. Weed control improved as the rate of isoxaflutole plus metribuzin increased. Two-pass programs provided excellent, full-season annual grass and broadleaf weed control in isoxaflutole-resistant soybean.
Here, we report that a marine sandworm Nereis virens jaw protein, Nvjp1, nucleates hemozoin with similar activity as the native parasite hemozoin protein, HisRPII. X-ray diffraction and scanning electron microscopy confirm the identity of the hemozoin produced from Nvjp1-containing reactions. Finally, we observed that nAl assembled with hemozoin from Nvjp1 reactions has a substantially higher energetic output when compared to analogous thermite from the synthetic standard or HisRPII-nucleated hemozoin. Our results demonstrate that a marine sandworm protein can nucleate malaria pigment and set the stage for engineering recombinant hemozoin production for nanoenergetic applications.
Heavy alcohol use is pervasive and one of our most significant global health burdens. Early theories posited that certain alcohol response phenotypes, notably low sensitivity to alcohol (‘low-level response’) imparts risk for alcohol use disorder (AUD). However, other theories, and newer measures of subjective alcohol responses, have challenged that contention and argued that high sensitivity to some alcohol effects are equally important for AUD risk. This study presents results of a unique longitudinal study in 294 young adult non-dependent drinkers examined with alcohol and placebo testing in the laboratory at initial enrolment and repeated 5 years later, with regular follow-up intervals assessing AUD (trial registration: http://clinicaltrials.gov/ct2/show/NCT00961792). Findings showed that alcohol sedation was negatively correlated with stimulation across the breath alcohol curve and at initial and re-examination testing. A higher rather than lower alcohol response phenotype was predictive of future AUD. The findings underscore a new understanding of factors increasing vulnerability to AUD.
Resonant optical dipole antennas, consisting either of two arms coupled by a small gap or of a single, uncoupled arm only, are fabricated by the application of electron beam lithography and gold evaporation. Using dark-field microscopy, scattering spectra of structures with varied antenna arm length and varied gap size are obtained. The results show not only a spectral redshift for coupled structures compared to single arm structures, but also that the far-field scattering intensity is significantly higher for two arm structures with gap. In addition to the dipole structures, first fabrication results on quadrupole antennas and split-ring antennas are presented, offering novel pathways for an enhancement of the optical response function.
Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.
There are increasing efforts aiming to utilise endophytes as biological control agents (BCAs) to improve crop production. However, reliability remains a major practical constraint for the development of novel BCAs. Many organisms are adapted to their specific habitat; it is optimistic to expect that a new organism added can find a niche or even out-compete those adapted and already present. Our approach for isolating novel BCAs for specific plant diseases is therefore to look in healthy plants in a habitat where disease is a problem, since we predict that it is more likely to find competitive strains among those present and adapted. In vitro inhibitory activities often do not correlate with in planta efficacy, especially since endophytes rely on intimate plant contact. They can, however, be useful to indicate modes of action. We therefore screen for in planta biological activity as early as possible in the process in order to minimise the risk of discarding valuable strains. Finally, some fungi are endophytic in one situation and pathogenic in another (the mutualism–parasitism continuum). This depends on their biology, environmental conditions, the formulation of inoculum, the health, developmental stage and cultivar of the host plant, and the structure of the plant microbiome.
Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated.
Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms.
All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86–96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47–82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly ‘very good’ (κ = 0.86–0.96).
The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.