The 22-Year Hale Cycle in Cosmic Ray Flux – Evidence for Direct Heliospheric Modulation

Abstract The ability to predict times of greater galactic cosmic ray (GCR) fluxes is important for reducing the hazards caused by these particles to satellite communications, aviation, or astronauts. The 11-year solar-cycle variation in cosmic rays is highly correlated with the strength of the heliospheric magnetic field. Differences in GCR flux during alternate solar cycles yield a 22-year cycle, known as the Hale Cycle, which is thought to be due to different particle drift patterns when the northern solar pole has predominantly positive (denoted as qA>0 cycle) or negative (qA0 cycles than for qA0 and more sharply peaked for qA0 solar cycles, when the difference in GCR flux is most apparent. This suggests that particle drifts may not be the sole mechanism responsible for the Hale Cycle in GCR flux at Earth. However, we also demonstrate that these polarity-dependent heliospheric differences are evident during the space-age but are much less clear in earlier data: using geomagnetic reconstructions, we show that for the period of 1905 – 1965, alternate polarities do not give as significant a difference during the declining phase of the solar cycle. Thus we suggest that the 22-year cycle in cosmic-ray flux is at least partly the result of direct modulation by the heliospheric magnetic field and that this effect may be primarily limited to the grand solar maximum of the space-age

The role of place narratives in planning : a study of the evolution of planning and regeneration policies for the Lower Lea Valley in east London

In this thesis I explore the role of place narratives in the evolution of planning and regeneration policies for the Lower Lea Valley in east London between 1995 and 2015. The Lower Lea includes the site for the 2012 Olympic Games and is one of London’s designated growth areas in the London Plan. Focusing on qualitative dimensions of planning and regeneration policy, I undertake a narrative analysis of a selection of plans and regeneration strategy documents produced during that period and also transcripts of interviews held with twenty-five people who were closely involved in the production of plans and regeneration strategies. I address the concept of narrative in three senses: the study of stories of place in documents and conversation and their relationship to policy; the telling of a story as a way to organise and present research findings; and the use of the tools of narrative analysis in the investigation of the research and in drawing conclusions. I address the evolution of narrative themes and also consider the role that the structure of narrative plays in contributing to policy and its influence on change. My central proposition is that narrative plays a key role in the evolution of ideas within a community of policy and decision makers. While planning documents and policy documents are not structured in a storied form, the narrativity of aspects of those policy documents plays an active role in the shifting place narratives for the Lea Valley over time, as I observe in the stories told by the policy makers involved

Global solar wind variations over the last four centuries

The most recent “grand minimum” of solar activity, the Maunder minimum (MM, 1650–1710), is of great interest both for understanding the solar dynamo and providing insight into possible future heliospheric conditions. Here, we use nearly 30 years of output from a data-constrained magnetohydrodynamic model of the solar corona to calibrate heliospheric reconstructions based solely on sunspot observations. Using these empirical relations, we produce the first quantitative estimate of global solar wind variations over the last 400 years. Relative to the modern era, the MM shows a factor 2 reduction in near-Earth heliospheric magnetic field strength and solar wind speed, and up to a factor 4 increase in solar wind Mach number. Thus solar wind energy input into the Earth’s magnetosphere was reduced, resulting in a more Jupiter-like system, in agreement with the dearth of auroral reports from the time. The global heliosphere was both smaller and more symmetric under MM conditions, which has implications for the interpretation of cosmogenic radionuclide data and resulting total solar irradiance estimates during grand minima

Radial Evolution of Sunward Strahl Electrons in the Inner Heliosphere

The heliospheric magnetic field (HMF) exhibits local inversions, in which the field apparently “bends back” upon itself. Candidate mechanisms to produce these inversions include various configurations of upstream interchange reconnection; either in the heliosphere, or in the corona where the solar wind is formed. Explaining the source of these inversions, and how they evolve in time and space, is thus an important step towards explaining the origins of the solar wind. Inverted heliospheric magnetic field lines can be identified by the anomalous sunward (i.e. inward) streaming of the typically anti-sunward propagating, field-aligned (or anti-aligned), beam of electrons known as the “strahl”. We test if the pitch angle distribution (PAD) properties of sunward-propagating strahl are different from those of outward strahl. We perform a statistical study of strahl observed by the Helios spacecraft, over heliocentric distances spanning ≈0.3 – 1 AU. We find that sunward strahl PADs are broader and less intense than their outward directed counterparts; particularly at distances 0.3 – 0.75 AU. This is consistent with sunward strahl being subject to additional, path-length dependent, scattering in comparison to outward strahl. We conclude that the longer and more variable path from the Sun to the spacecraft, along inverted magnetic field, leads to this additional scattering. The results also suggest that the relative importance of scattering along this additional path length drops off with heliocentric distance. These results can be explained by a relatively simple, constant-rate, scattering process

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort.

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA-mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.MethodsThe study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.ResultsThe total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98-1.46), P  = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18-2.14), P = 0.002).ConclusionThe rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort

Graphical evidence for the solar coronal structure during the Maunder minimum: Comparative study of the total eclipse drawings in 1706 and 1715

We discuss the significant implications of three eye-witness drawings of the total solar eclipse on 1706 May 12 in comparison with two on 1715 May 3, for our understanding of space climate change. These events took place just after what has been termed the "deep Maunder Minimum"but fall within the "extended Maunder Minimum"being in an interval when the sunspot numbers start to recover. Maria Clara Eimmert's image in 1706 is particularly important because she was both a highly accomplished astronomical observer and an excellent artist: It was thought lost and was only re-discovered in 2012. Being the earliest coronal drawings of observational value yet identified, these drawings corroborate verbal accounts a corona without significant streamers, seen at totality of this and another eclipse event in 1652 during the Maunder Minimum. The graphical evidence implies that the coronal solar magnetic field was not lost but significantly weakened and the lack of coronal structure means there was little discernable open flux (either polar or at lower latitudes) even during the recovery phase of the Maunder Minimum. These observations provide evidence for a different state of oscillation of the solar dynamo, and hence behaviour of the Sun, in comparison with that during normal solar cycle minima (when a streamer belt between two polar coronal holes is visible) or near normal sunspot maxima (when coronal structure is caused by coronal holes at all latitudes) even to observers without a telescope

Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate.

BACKGROUND: Safe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. Oral activated charcoal (oAC) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. In preparation for possible efficacy trials in human malaria, we sought to determine whether oAC would i) reduce mortality due to experimental cerebral malaria (ECM) in mice, ii) modulate immune and inflammatory responses associated with ECM, and iii) affect the pharmacokinetics of parenteral artesunate in human volunteers. METHODS/PRINCIPAL FINDINGS: We found that oAC provided significant protection against P. berghei ANKA-induced ECM, increasing overall survival time compared to untreated mice (p<0.0001; hazard ratio 16.4; 95% CI 6.73 to 40.1). Protection from ECM by oAC was associated with reduced numbers of splenic TNF(+) CD4(+) T cells and multifunctional IFNgamma(+)TNF(+) CD4(+) and CD8(+) T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, we conducted a randomized controlled open label trial in 52 human volunteers (ISRCTN NR. 64793756), administering artesunate (AS) in the presence or absence of oAC. We demonstrated that co-administration of oAC was safe and well-tolerated. In the 26 subjects further analyzed, we found no interference with the pharmacokinetics of parenteral AS or its pharmacologically active metabolite dihydroartemisinin. CONCLUSIONS/SIGNIFICANCE: oAC protects against ECM in mice, and does not interfere with the pharmacokinetics of parenteral artesunate. If future studies succeed in establishing the efficacy of oAC in human malaria, then the characteristics of being inexpensive, well-tolerated at high doses and requiring no sophisticated storage would make oAC a relevant candidate for adjunct therapy to reduce mortality from severe malaria, or for immediate treatment of suspected severe malaria in a rural setting. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64793756

Coronal mass ejections are not coherent magnetohydrodynamic structures

Coronal mass ejections (CMEs) are episodic eruptions of solar plasma and magnetic flux that travel out through the solar system, driving extreme space weather. Interpretation of CME observations and their interaction with the solar wind typically assumes CMEs are coherent, almost solid-like objects. We show that supersonic radial propagation of CMEs away from the Sun results in geometric expansion of CME plasma parcels at a speed faster than the local wave speed. Thus information cannot propagate across the CME. Comparing our results with observed properties of over 400 CMEs, we show that CMEs cease to be coherent magnetohydrodynamic structures within 0.3 AU of the Sun. This suggests Earth-directed CMEs are less like billiard balls and more like dust clouds, with apparent coherence only due to similar initial conditions and quasi homogeneity of the medium through which they travel. The incoherence of CMEs suggests interpretation of CME observations requires accurate reconstruction of the ambient solar wind with which they interact, and that simple assumptions about the shape of the CMEs are likely to be invalid when significant spatial/temporal gradients in ambient solar wind conditions are present

Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved