Primordial Black Holes: sirens of the early Universe

Primordial Black Holes (PBHs) are, typically light, black holes which can form in the early Universe. There are a number of formation mechanisms, including the collapse of large density perturbations, cosmic string loops and bubble collisions. The number of PBHs formed is tightly constrained by the consequences of their evaporation and their lensing and dynamical effects. Therefore PBHs are a powerful probe of the physics of the early Universe, in particular models of inflation. They are also a potential cold dark matter candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

Sodium bicarbonate and high-intensity-cycling capacity: variability in responses

Purpose: The aim of this study was to determine whether gastrointestinal (GI) distress affects the ergogenicity of sodium bicarbonate and whether the degree of alkalaemia or other metabolic responses are different between individuals who improve exercise capacity and those who do not. Methods: Twenty-one males completed two cycling capacity tests at 110% of maximum power output. Participants were supplemented with 0.3 g∙kg-1BM of either placebo (maltodextrin) or sodium bicarbonate (SB). Blood pH, bicarbonate, base excess and lactate were determined at baseline, pre-exercise, immediately post-exercise and 5 minutes post-exercise. Results: SB supplementation did not significantly increase total work done (TWD) (P = 0.16, 46.8 ± 9.1 vs. 45.6 ± 8.4 kJ, d = 0.14), although magnitude based inferences suggested a 63% likelihood of a positive effect. When data were analysed without four participants who experienced GI discomfort, TWD (P = 0.01) was significantly improved with SB. Immediately post-exercise blood lactate was higher in SB for the individuals who improved but not for those who didn’t. There were also differences in the pre to post-exercise change in blood pH, bicarbonate and base excess between individuals who improved and individuals who did not. Conclusions: SB improved high intensity cycling capacity, but only with the exclusion of participants experiencing GI discomfort. Differences in blood responses suggest that sodium bicarbonate may not be beneficial to all individuals. Magnitude based inferences suggested that the exercise effects are unlikely to be negative; therefore individuals should determine whether they respond well to sodium bicarbonate supplementation prior to competition

L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults

INTRODUCTION: Millions of people worldwide take medications such as L-DOPA that increase dopamine to treat Parkinson's disease. Yet, we do not fully understand how L-DOPA affects sleep and memory. Our earlier research in Parkinson's disease revealed that the timing of L-DOPA relative to sleep affects dopamine's impact on long-term memory. Dopamine projections between the midbrain and hippocampus potentially support memory processes during slow wave sleep. In this study, we aimed to test the hypothesis that L-DOPA enhances memory consolidation by modulating NREM sleep. METHODS: We conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65-79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning. RESULTS: The single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1-4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects. DISCUSSION: Our results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slow-wave sleep and long-term memory may have clinical implications. CLINICAL TRIAL REGISTRATION: Eudract number: 2015-002027-26; https://doi.org/10.1186/ISRCTN90897064, ISRCTN90897064

Vortices and Superfluidity in a Strongly Interacting Fermi Gas

Quantum-degenerate Fermi gases provide a remarkable opportunity to study strongly interacting fermions. In contrast to other Fermi systems, such as superconductors, neutron stars or the quark-gluon plasma, these gases have low densities and their interactions can be precisely controlled over an enormous range. Here we report observations of vortices in such a gas that provide definitive evidence for superfluidity. By varying the pairing strength between two fermions near a Feshbach resonance, one can explore the crossover from a Bose-Einstein condensate (BEC) of molecules to a Bardeen-Cooper-Schrieffer (BCS) superfluid of loosely bound pairs whose size is comparable to, or even larger than, the interparticle spacing. The crossover realizes a novel form of high-T_C superfluidity and it may provide new insight for high-T_C superconductors. Previous experiments with Fermi gases have revealed condensation of fermion pairs. While these and other studies were consistent with predictions assuming superfluidity, the smoking gun for superfluid behavior has been elusive. Our observation of vortex lattices directly displays superfluid flow in a strongly interacting, rotating Fermi gas.Comment: 14 pages, including 7 figures, submitted to Natur

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Prion Shedding from Olfactory Neurons into Nasal Secretions

This study investigated the role of prion infection of the olfactory mucosa in the shedding of prion infectivity into nasal secretions. Prion infection with the HY strain of the transmissible mink encephalopathy (TME) agent resulted in a prominent infection of the olfactory bulb and the olfactory sensory epithelium including the olfactory receptor neurons (ORNs) and vomeronasal receptor neurons (VRNs), whose axons comprise the two olfactory cranial nerves. A distinct glycoform of the disease-specific isoform of the prion protein, PrPSc, was found in the olfactory mucosa compared to the olfactory bulb, but the total amount of HY TME infectivity in the nasal turbinates was within 100-fold of the titer in the olfactory bulb. PrPSc co-localized with olfactory marker protein in the soma and dendrites of ORNs and VRNs and also with adenylyl cyclase III, which is present in the sensory cilia of ORNs that project into the lumen of the nasal airway. Nasal lavages from HY TME-infected hamsters contained prion titers as high as 103.9 median lethal doses per ml, which would be up to 500-fold more infectious in undiluted nasal fluids. These findings were confirmed using the rapid PrPSc amplification QuIC assay, indicating that nasal swabs have the potential to be used for prion diagnostics. These studies demonstrate that prion infection in the olfactory epithelium is likely due to retrograde spread from the olfactory bulb along the olfactory and vomeronasal axons to the soma, dendrites, and cilia of these peripheral neurons. Since prions can replicate to high levels in neurons, we propose that ORNs can release prion infectivity into nasal fluids. The continual turnover and replacement of mature ORNs throughout the adult lifespan may also contribute to prion shedding from the nasal passage and could play a role in transmission of natural prion diseases in domestic and free-ranging ruminants

Internet-based medical education: a realist review of what works, for whom and in what circumstances

http://creativecommons.org/licenses/by/2.0

Deep Theorizing in International Relations

This paper starts from the observation that, at a time when the popularity of grand theory is in decline among IR scholars, they do not agree on what they mean by theory. In fact, the celebration of theoretical pluralism is accompanied by the relative absence of a serious conversation about what ‘theory’ is, could, or should be. Taking the view that we need such a conversation, this puts forward the notion of ‘deep theorizing’. Countering both the shallow theorizing of modern scholarship that conflates theory with scientific method, and the postmodern view that abstract narratives must be deconstructed and rejected, it offers a reading of the parameters along which substantial theorizing proceeds. Specifically, it suggests that ‘deep theorizing’ is the conceptual effort of explaining (inter)action by developing a reading of drives/basic motivations and the ontology of its carrier through an account of the human condition, that is, a particular account of how the subject (the political actor) is positioned in social space and time. The paper illustrates the plausibility of this meta-theoretical angle in a discussion of realist, liberal and postcolonial schools of thought

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed