499 research outputs found
Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder:results from a randomized, controlled trial
Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6–17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners’ Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment − placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours)
An Opsonophagocytic Killing Assay for the Evaluation of Group A Streptococcus Vaccine Antisera
Group A Streptococcus (GAS) is a major cause of global mortality, yet there are no licensed GAS vaccines. Vaccine progress has been hampered, in part, by a lack of standardized assays able to quantify antibody function in test antisera. The most widely used assay was developed over 50Â years ago by Rebecca Lancefield and relies on human whole blood as a source of complement and neutrophils. Recently, an opsonophagocytic killing (OPK) assay has been developed for GAS by adapting the OPK methods utilized in Streptococcus pneumoniae vaccine testing. This assay uses dimethylformamide (DMF)-differentiated human promyelocytic leukemia cells (HL-60 cells) as a source of neutrophils and baby rabbit complement, thus removing the major sources of variation in the Lancefield assays. This protocol outlines methods for performing a GAS OPK assay including titering test sera to generate an opsonic index. This in vitro assay could aid in selecting vaccine candidates by demonstrating whether candidate-induced antibodies lead to complement deposition and opsonophagocytic killing
The nonlinear anomalous lattice elasticity associated with the high-pressure phase transition in spodumene: A high precission static compression study
The high-pressure behavior of the lattice elasticity of spodumene, LiAlSi2O6,
was studied by static compression in a diamond-anvil cell up to 9.3 GPa.
Investigations by means of single-crystal XRD and Raman spectroscopy within the
hydrostatic limits of the pressure medium focus on the pressure ranges around
similar to 3.2 and similar to 7.7 GPa, which have been reported previously to
comprise two independent structural phase transitions. While our measurements
confirm the well-established first-order C2/c-P2(1)/c transformation at 3.19
GPa (with 1.2% volume discontinuity and a hysteresis between 0.02 and 0.06
GPa), both unit-cell dimensions and the spectral changes observed in
high-pressure Raman spectra give no evidence for structural changes related to
a second phase transition. Monoclinic lattice parameters and unit-cell volumes
at in total 59 different pressure points have been used to re-calculate the
lattice-related properties of spontaneous strain, volume strain, and the bulk
moduli as a function of pressure across the transition. A modified Landau free
energy expansion in terms of a one component order parameter has been developed
and tested against these experimentally determined data. The Landau solution
provides a much better reproduction of the observed anomalies than any
equation-of-state fit to data sets truncated below and above P (tr), thus
giving Landau parameters of K (0) = 138.3(2) GPa, K' = 7.46(5), lambda (V) =
33.6(2) GPa, a = 0.486(3), b = -29.4(6) GPa and c = 551(11) GPa
Long-term follow up of factual knowledge after a single, randomised problem-based learning course
BACKGROUND: The long-term effect of problem-based learning (PBL) on factual knowledge is poorly investigated. We took advantage of a previous randomised comparison between PBL and traditional teaching in a 3(rd )year course to follow up factual knowledge of the students during their 4(th )and 5(th )year of medical school training. METHODS: 3(rd )year medical students were initially randomized to participate in a problem-based (PBL, n = 55), or a lecture-based (LBL, n = 57) course in basic pharmacology. Summative exam results were monitored 18 months later (after finishing a lecture-based course in clinical pharmacology). Additional results of an unscheduled, formative exam were obtained 27 months after completion of the first course. RESULTS: Of the initial sample of 112 students, 90 participated in the second course and exam (n = 45, 45). 32 (n = 17 PBL, n = 15 LBL) could be exposed to the third, formative exam. Mean scores (± SD) were 22.4 ± 6.0, 27.4 ± 4.9 and 20.1 ± 5.0 (PBL), or 22.2 ± 6.0, 28.4 ± 5.1 and 19.0 ± 4.7 (LBL) in the first, second and third test, respectively (maximum score: 40). No significant differences were found between the two groups. CONCLUSION: A small-scale exposure to PBL, applied under randomized conditions but in the context of a traditional curriculum, does not sizeably change long-term presence of factual knowledge within the same discipline
Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex
Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences
Magnetic vortex oscillator driven by dc spin-polarized current
Transfer of angular momentum from a spin-polarized current to a ferromagnet
provides an efficient means to control the dynamics of nanomagnets. A peculiar
consequence of this spin-torque, the ability to induce persistent oscillations
of a nanomagnet by applying a dc current, has previously been reported only for
spatially uniform nanomagnets. Here we demonstrate that a quintessentially
nonuniform magnetic structure, a magnetic vortex, isolated within a nanoscale
spin valve structure, can be excited into persistent microwave-frequency
oscillations by a spin-polarized dc current. Comparison to micromagnetic
simulations leads to identification of the oscillations with a precession of
the vortex core. The oscillations, which can be obtained in essentially zero
magnetic field, exhibit linewidths that can be narrower than 300 kHz, making
these highly compact spin-torque vortex oscillator devices potential candidates
for microwave signal-processing applications, and a powerful new tool for
fundamental studies of vortex dynamics in magnetic nanostructures.Comment: 14 pages, 4 figure
Climate change promotes parasitism in a coral symbiosis.
Coastal oceans are increasingly eutrophic, warm and acidic through the addition of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa to these changes are scleractinian corals, which engineer the most biodiverse ecosystems on Earth. Corals' sensitivity is a consequence of their evolutionary investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the coral holobiont has dominated oligotrophic tropical marine habitats. However, warming destabilizes this association and reduces coral fitness. It has been theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium sequester more resources for their own growth, thus parasitizing their hosts of nutrition. Here, we tested the hypothesis that sub-bleaching temperature and excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and the assimilation and translocation of both carbon (energy) and nitrogen (growth; both benefits) within Orbicella faveolata hosting one of two Symbiodinium phylotypes using a dual stable isotope tracer incubation at ambient (26 °C) and sub-bleaching (31 °C) temperatures under elevated nitrate. Warming to 31 °C reduced holobiont net primary productivity (NPP) by 60% due to increased respiration which decreased host %carbon by 15% with no apparent cost to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation increased by 14 and 32%, respectively while increasing their mitotic index by 15%, whereas hosts did not gain a proportional increase in translocated photosynthates. We conclude that the disparity in benefits and costs to both partners is evidence of symbiont parasitism in the coral symbiosis and has major implications for the resilience of coral reefs under threat of global change
The geography of recent genetic ancestry across Europe
The recent genealogical history of human populations is a complex mosaic
formed by individual migration, large-scale population movements, and other
demographic events. Population genomics datasets can provide a window into this
recent history, as rare traces of recent shared genetic ancestry are detectable
due to long segments of shared genomic material. We make use of genomic data
for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of
recent genealogical ancestry over the past three thousand years at a
continental scale. We detected 1.9 million shared genomic segments, and used
the lengths of these to infer the distribution of shared ancestors across time
and geography. We find that a pair of modern Europeans living in neighboring
populations share around 10-50 genetic common ancestors from the last 1500
years, and upwards of 500 genetic ancestors from the previous 1000 years. These
numbers drop off exponentially with geographic distance, but since genetic
ancestry is rare, individuals from opposite ends of Europe are still expected
to share millions of common genealogical ancestors over the last 1000 years.
There is substantial regional variation in the number of shared genetic
ancestors: especially high numbers of common ancestors between many eastern
populations likely date to the Slavic and/or Hunnic expansions, while much
lower levels of common ancestry in the Italian and Iberian peninsulas may
indicate weaker demographic effects of Germanic expansions into these areas
and/or more stably structured populations. Recent shared ancestry in modern
Europeans is ubiquitous, and clearly shows the impact of both small-scale
migration and large historical events. Population genomic datasets have
considerable power to uncover recent demographic history, and will allow a much
fuller picture of the close genealogical kinship of individuals across the
world.Comment: Full size figures available from
http://www.eve.ucdavis.edu/~plralph/research.html; or html version at
http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm
Phase II study of intraperitoneal recombinant interleukin-12 (rhIL-12) in patients with peritoneal carcinomatosis (residual disease < 1 cm) associated with ovarian cancer or primary peritoneal carcinoma
<p>Abstract</p> <p>Background</p> <p>Pharmacokinetic advantages of intraperitoneal (IP) rhIL-12, tumor response to IP delivery of other cytokines as well as its potential anti-angiogenic effect provided the rationale for further evaluation of IPrhIL-12 in patients with persistent ovarian or peritoneal carcinoma.</p> <p>Methods</p> <p>A phase 2 multi-institutional trial (NCI Study #2251) of IP rIL-12 (300 nanogram/Kg weekly) was conducted in patients with ovarian carcinoma or primary peritoneal carcinoma.</p> <p>Patients treated with primary therapy for ovarian cancer who had no extraabdominal/parenchymal disease or bulky peritoneal disease were eligible. Four to 8 weeks from last chemotherapy, eligible patients underwent a laparotomy/laparoscopy. Patients with residual disease ≤ 1 cm were registered for the treatment phase 2–5 weeks post surgery. The effect of IP rIL-12 on the expression of TNFα , INFα , IL-10, IP-10, IL-8, FGF, VEGF was also studied.</p> <p>Results</p> <p>Thirty-four patients were registered for the first screening phase of the study. Median age was 56.6 years (range: 31–71); 12 completed the second phase and were evaluable for response/toxicity. Performance scores of IL-12 treated patients were 0 (11 pts) and 1 (1 pt). There were no treatment related deaths, peritonitis or significant catheter related complications. Toxicities included grade 4 neutropenia (1), grade 3 fatigue (4), headache (2), myalgia (2), non-neutropenic fever (1), drug fever (1), back pain (1), and dizziness (1). The best response observed was SD. Two patients had SD and 9 had PD, and 1 was evaluable for toxicity only.</p> <p>Peritoneal fluid cytokine measurements demonstrated a ≥ 3 fold relative increase post-rhIL-12: IFN-γ, 5/5 pts; TNF-α , 1/5; IL-10, 4/5; IL-8, 5/5; and VEGF, 3/5. IP10 levels were increased in 5/5 patients. Cytokine response profiles suggest either NK or T-cell mediated effects of IP rhIL-12. Cytokine/chemokine results also suggest a pleiotropic response since proteins with potential for either anti-tumor (IFN-γ , IP-10) or pro-tumor growth effects (VEGF, IL-8) were detected.</p> <p>Conclusion</p> <p>IP IL-12 can safely be administered at this dose and schedule to patients after first line chemotherapy for ovarian/peritoneal carcinoma. The maximum response was stable disease. Future IP therapies with rhIL-12 will require better understanding and control of pleiotropic effects of IL-12.</p
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Output from VIP cells of the mammalian central clock regulates daily physiological rhythms
The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing
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