329 research outputs found
Svestka's Research: Then and Now
Zdenek Svestka's research work influenced many fields of solar physics,
especially in the area of flare research. In this article I take five of the
areas that particularly interested him and assess them in a "then and now"
style. His insights in each case were quite sound, although of course in the
modern era we have learned things that he could not readily have envisioned.
His own views about his research life have been published recently in this
journal, to which he contributed so much, and his memoir contains much
additional scientific and personal information (Svestka, 2010).Comment: Invited review for "Solar and Stellar Flares," a conference in honour
of Prof. Zden\v{e}k \v{S}vestka, Prague, June 23-27, 2014. This is a
contribution to a Topical Issue in Solar Physics, based on the presentations
at this meeting (Editors Lyndsay Fletcher and Petr Heinzel
Spectrally-resolved UV photodesorption of CH4 in pure and layered ices
Context. Methane is among the main components of the ice mantles of
insterstellar dust grains, where it is at the start of a rich solid-phase
chemical network. Quantification of the photon-induced desorption yield of
these frozen molecules and understanding of the underlying processes is
necessary to accurately model the observations and the chemical evolution of
various regions of the interstellar medium. Aims. This study aims at
experimentally determining absolute photodesorption yields for the CH4 molecule
as a function of photon energy. The influence of the ice composition is also
investigated. By studying the methane desorption from layered CH4:CO ice,
indirect desorption processes triggered by the excitation of the CO molecules
is monitored and quantified. Methods. Tunable monochromatic VUV light from the
DESIRS beamline of the SOLEIL synchrotron is used in the 7 - 13.6 eV (177 - 91
nm) range to irradiate pure CH4 or layers of CH4 deposited on top of CO ice
samples. The release of species in the gas phase is monitored by quadrupole
mass spectrometry and absolute photodesorption yields of intact CH4 are
deduced. Results. CH4 photodesorbs for photon energies higher than ~9.1 eV
(~136 nm). The photodesorption spectrum follows the absorption spectrum of CH4,
which confirms a desorption mechanism mediated by electronic transitions in the
ice. When it is deposited on top of CO, CH4 desorbs between 8 and 9 eV with a
pattern characteristic of CO absorption, indicating desorption induced by
energy transfer from CO molecules. Conclusions. The photodesorption of CH4 from
the pure ice in various interstellar environments is around 2.0 x 10^-3
molecules per incident photon. Results on CO-induced indirect desorption of CH4
provide useful insights for the generalization of this process to other
molecules co-existing with CO in ice mantles
Gene–environment interactions in Leber hereditary optic neuropathy
Leber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to confirm this to be the case. LHON has no treatment, so identifying environmental triggers is the key to disease prevention, whilst potentially revealing new mechanisms amenable to therapeutic manipulation. To address this issue, we conducted a large, multicentre epidemiological study of 196 affected and 206 unaffected carriers from 125 LHON pedigrees known to harbour one of the three primary pathogenic mtDNA mutations: m.3460G>A, m.11778G>A and m.14484T>C. A comprehensive history of exposure to smoking, alcohol and other putative environmental insults was collected using a structured questionnaire. We identified a strong and consistent association between visual loss and smoking, independent of gender and alcohol intake, leading to a clinical penetrance of 93% in men who smoked. There was a trend towards increased visual failure with alcohol, but only with a heavy intake. Based on these findings, asymptomatic carriers of a LHON mtDNA mutation should be strongly advised not to smoke and to moderate their alcohol intake
Evidence of multidecadal salinity variability in the eastern tropical North Atlantic
Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 21 (2006): PA3010, doi:10.1029/2005PA001257.Ocean circulation and global climate are strongly influenced by
seawater density, which is itself controlled by salinity and temperature.
Although adequate instrumental sea-surface temperature (SST) records
exist for most of the surface oceans over the past 100-150 years, records of
salinity really only exist for the last 40-50 years. Here we show that
longer proxy records from corals (Siderastrea radians) in the eastern
tropical North Atlantic are dominated by multi-decadal variations in
salinity which are correlated with the relationship between SST and the
North Atlantic Oscillation (NAO) over the course of the 20th century. The
data reveal an increase in eastern tropical North Atlantic salinity of +0.5
psu between about 1950-1990. Rather than a monotonic secular increase,
as indicated by some instrumental records, the pre-instrumental coral
proxy records presented here suggest that salinity in the tropical North
Atlantic is periodic on a decadal to multi-decadal scale
Antipsychotic medication versus psychological intervention versus a combination of both in adolescents with first-episode psychosis (MAPS): a multicentre, three-arm, randomised controlled pilot and feasibility study
Background
Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy [CBT] and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis.
Methods
We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14–18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433.
Findings
Of 101 patients referred to the study, 61 patients (mean age 16·3 years [SD 1·3]) were recruited from April 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 [84%] participants retained at the 6-month primary endpoint), a high rate of adherence to psychological intervention (defined as six or more sessions of CBT; in 32 [82%] of 39 participants in the monotherapy and combined groups), and a moderate rate of adherence to antipsychotic medication (defined as at least 6 consecutive weeks of exposure to antipsychotics; in 28 [65%] of 43 participants in the monotherapy and combined groups). Mean scores for PANSS total at the 6-month primary endpoint were 68·6 (SD 17·3) for antipsychotic monotherapy (6·2 points lower than at randomisation), 59·8 (13·7) for psychological intervention (13·1 points lower than at randomisation), and 62·0 (15·9) for antipsychotics plus psychological intervention (13·9 points lower than at randomisation). A good clinical response at 6 months (defined as ≥50% improvement in PANSS total score) was achieved in four (22%) of 18 patients receiving antipsychotic monotherapy, five (31%) of 16 receiving psychological intervention, and five (29%) of 17 receiving antipsychotics plus psychological intervention. In as-treated groups, serious adverse events occurred in eight [35%] of 23 patients in the combined group, two [13%] of 15 in the antipsychotics group, four [24%] of 17 in the psychological intervention group, and four [80%] of five who did not receive any treatment. No serious adverse events were considered to be related to participation in the trial.
Interpretation
This trial is the first to show that a head-to-head clinical trial comparing psychological intervention, antipsychotics, and their combination is safe in young people with first-episode psychosis. However, the feasibility of a larger trial is unclear because of site-specific recruitment challenges, and amendments to trial design would be needed for an adequately powered clinical and cost-effectiveness trial that provides robust evidence
Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G > A mitochondrial DNA mutation: a case report
<p>Abstract</p> <p>Background</p> <p>Leigh Syndrome (LS) is a severe neurodegenerative disorder characterized by bilateral symmetrical necrotic lesions in the basal ganglia and brainstem. Onset is in early infancy and prognosis is poor. Causative mutations have been disclosed in mitochondrial DNA and nuclear genes affecting respiratory chain subunits and assembly factors.</p> <p>Case presentation</p> <p>Here we report the clinical and molecular features of a 15-month-old female LS patient. Direct sequencing of her muscle-derived mtDNA revealed the presence of two apparently homoplasmic variants: the novel m.14792C > G and the already known m.14459G > A resulting in p.His16Asp change in cytochrome b (MT-CYB) and p.Ala72Val substitution in ND6 subunit, respectively. The m.14459G > A was heteroplasmic in the mother's blood-derived DNA.</p> <p>Conclusions</p> <p>The m.14459G > A might lead to LS, complicated LS or Leber Optic Hereditary Neuropathy. A comprehensive re-evaluation of previously described 14459G > A-mutated patients does not explain this large clinical heterogeneity.</p
Network-driven plasma proteomics expose molecular changes in the Alzheimer’s brain
Background Biological pathways that significantly contribute to sporadic
Alzheimer’s disease are largely unknown and cannot be observed directly.
Cognitive symptoms appear only decades after the molecular disease onset,
further complicating analyses. As a consequence, molecular research is often
restricted to late-stage post-mortem studies of brain tissue. However, the
disease process is expected to trigger numerous cellular signaling pathways
and modulate the local and systemic environment, and resulting changes in
secreted signaling molecules carry information about otherwise inaccessible
pathological processes. Results To access this information we probed relative
levels of close to 600 secreted signaling proteins from patients’ blood
samples using antibody microarrays and mapped disease-specific molecular
networks. Using these networks as seeds we then employed independent genome
and transcriptome data sets to corroborate potential pathogenic pathways.
Conclusions We identified Growth-Differentiation Factor (GDF) signaling as a
novel Alzheimer’s disease-relevant pathway supported by in vivo and in vitro
follow-up experiments, demonstrating the existence of a highly informative
link between cellular pathology and changes in circulatory signaling proteins
Network-Driven Plasma Proteomics Expose Molecular Changes in the Alzheimer\u27s Brain
Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes. Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using antibody microarrays and mapped disease-specific molecular networks. Using these networks as seeds we then employed independent genome and transcriptome data sets to corroborate potential pathogenic pathways. Conclusions: We identified Growth-Differentiation Factor (GDF) signaling as a novel Alzheimer’s disease-relevant pathway supported by in vivo and in vitro follow-up experiments, demonstrating the existence of a highly informative link between cellular pathology and changes in circulatory signaling proteins
- …