A role for cell sex in stem cell-mediated skeletal muscle regeneration: Female cells have higher muscle regeneration efficiency

We have shown that muscle-derived stem cells (MDSCs) transplanted into dystrophic (mdx) mice efficiently regenerate skeletal muscle. However, MDSC populations exhibit heterogeneity in marker profiles and variability in regeneration abilities. We show here that cell sex is a variable that considerably influences MDSCs' regeneration abilities. We found that the female MDSCs (F-MDSCs) regenerated skeletal muscle more efficiently. Despite using additional isolation techniques and cell cloning, we could not obtain a male subfraction with a regeneration capacity similar to that of their female counterparts. Rather than being directly hormonal or caused by host immune response, this difference in MDSCs' regeneration potential may arise from innate sex-related differences in the cells' stress responses. In comparison with F-MDSCs, male MDSCs have increased differentiation after exposure to oxidative stress induced by hydrogen peroxide, which may lead to in vivo donor cell depletion, and a proliferative advantage for F-MDSCs that eventually increases muscle regeneration. These findings should persuade researchers to report cell sex, which is a largely unexplored variable, and consider the implications of relying on cells of one sex. © The Rockefeller University Press

Methane storms as a driver of Titan's dune orientation

Titan's equatorial regions are covered by eastward propagating linear dunes. This direction is opposite to mean surface winds simulated by Global Climate Models (GCMs), which are oriented westward at these latitudes, similar to trade winds on Earth. Different hypotheses have been proposed to address this apparent contradiction, involving Saturn's gravitational tides, large scale topography or wind statistics, but none of them can explain a global eastward dune propagation in the equatorial band. Here we analyse the impact of equinoctial tropical methane storms developing in the superrotating atmosphere (i.e. the eastward winds at high altitude) on Titan's dune orientation. Using mesoscale simulations of convective methane clouds with a GCM wind profile featuring superrotation, we show that Titan's storms should produce fast eastward gust fronts above the surface. Such gusts dominate the aeolian transport, allowing dunes to extend eastward. This analysis therefore suggests a coupling between superrotation, tropical methane storms and dune formation on Titan. Furthermore, together with GCM predictions and analogies to some terrestrial dune fields, this work provides a general framework explaining several major features of Titan's dunes: linear shape, eastward propagation and poleward divergence, and implies an equatorial origin of Titan's dune sand.Comment: Published online on Nature Geoscience on 13 April 201

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Complementary classifications of aeolian dunes based on morphology, dynamics, and fluid mechanics

Dunes form where winds blow over a bed of mobile sediment grains – conditions that are common in our solar system. On Earth, dunes abound in arid continental interiors and along sandy coastlines. Dune fields have also been recognized on Venus, Mars, Saturn's moon Titan, and Pluto. In response to the different boundary conditions and other environmental forcings, dunes adopt a rich diversity of shapes, sizes, and behaviors. Thus, people around the globe and over centuries have developed a rich vocabulary to describe dunes and their complexity. As a result, existing dune nomenclature often includes redundant terms with differing definitions across scientific communities. Previous studies have endeavored to link dune shape to environmental forcing, usually by means of correlation. Although instructive, correlation-based classifications can be misleading if not based on an underlying mechanics and if dune morphogenetic classes are not uniquely defined. Here, we synthesize existing dune terminology and use the last two decades of research on dune morphodynamics to propose three complementary dune classification schemes based on: (1) descriptive dune gemorphology, (2) morphodynamic processes, and (3) fluid mechanics and physics of sediment transport. The first classification relates dune types to geomorphic setting, presence or absence of vegetation or obstacles, and dune shape (including planform shape, and cross-sectional symmetry or asymmetry). Dune classes can be further subdivided where the direction of sand transport is known independently. The second classification relates dune types and shapes to bed properties (sand-covered vs partially starved bed) and wind forcing (directional variability or the relative strengths and directions of wind modes) that together influence dune dynamics (growth, migration, elongation) and select the dominant processes by which dunes are shaped and oriented relative to the resultant transport direction. The third classification relates, for different planetary environments, the range of possible dune sizes, from minimum to maximum wavelength, to flow regime (rough or smooth) and response of sediment transport, which influence the coupling between sand bed topography, fluid flow, and sediment transport. These characteristic lengths are useful scales for comparative geomorphology. The three classification schemes provide complementary information. Together, they form a unified framework for geomorphologists, sedimentologists, geographers, physicists, and others to describe windblown sand dunes on Earth and beyond through their shape, dynamics, and size as a response to winds and boundary conditions

A methodology pruning the search space of six compiler transformations by addressing them together as one problem and by exploiting the hardware architecture details

Today’s compilers have a plethora of optimizations-transformations to choose from, and the correct choice, order as well parameters of transformations have a significant/large impact on performance; choosing the correct order and parameters of optimizations has been a long standing problem in compilation research, which until now remains unsolved; the separate sub-problems optimization gives a different schedule/binary for each sub-problem and these schedules cannot coexist, as by refining one degrades the other. Researchers try to solve this problem by using iterative compilation techniques but the search space is so big that it cannot be searched even by using modern supercomputers. Moreover, compiler transformations do not take into account the hardware architecture details and data reuse in an efficient way. In this paper, a new iterative compilation methodology is presented which reduces the search space of six compiler transformations by addressing the above problems; the search space is reduced by many orders of magnitude and thus an efficient solution is now capable to be found. The transformations are the following: loop tiling (including the number of the levels of tiling), loop unroll, register allocation, scalar replacement, loop interchange and data array layouts. The search space is reduced (a) by addressing the aforementioned transformations together as one problem and not separately, (b) by taking into account the custom hardware architecture details (e.g., cache size and associativity) and algorithm characteristics (e.g., data reuse). The proposed methodology has been evaluated over iterative compilation and gcc/icc compilers, on both embedded and general purpose processors; it achieves significant performance gains at many orders of magnitude lower compilation time

Enjoyment, Exploration and Education: Understanding the Consumption of Pornography among Young Men with Non-Exclusive Sexual Orientations

This qualitative research examines the influence of pornography consumption on young men with non-exclusive sexual orientations. Drawing on 35 in-depth interviews with young men from an elite university in the north-eastern United States, we examine how pornography was experienced as a leisure activity to be consumed in free time. Rather than focusing on the potential harms of pornography, we use an inductive analytic approach to explore the broader range of experiences that participants had, since the time they first consumed pornography. We demonstrate that pornography had educational benefits for these young men, related to their sexual desires, emerging sexual identities and for developing new sexual techniques. This study is part of a growing body of research that seeks to develop a holistic understanding of pornography in society, addressing the absence of the lived experience of the consumer in most pornography research

Barrett’s oESophagus trial 3 (BEST3): study protocol for a randomised controlled trial comparing the Cytosponge-TFF3 test with usual care to facilitate the diagnosis of oesophageal pre-cancer in primary care patients with chronic acid reflux

Abstract Background Early detection of oesophageal cancer improves outcomes; however, the optimal strategy for identifying patients at increased risk from the pre-cancerous lesion Barrett’s oesophagus (BE) is not clear. The Cytosponge, a novel non-endoscopic sponge device, combined with the biomarker Trefoil Factor 3 (TFF3) has been tested in four clinical studies. It was found to be safe, accurate and acceptable to patients. The aim of the BEST3 trial is to evaluate if the offer of a Cytosponge-TFF3 test in primary care for patients on long term acid suppressants leads to an increase in the number of patients diagnosed with BE. Methods The BEST3 trial is a pragmatic multi-site cluster-randomised controlled trial set in primary care in England. Approximately 120 practices will be randomised 1:1 to either the intervention arm, invitation to a Cytosponge-TFF3 test, or the control arm usual care. Inclusion criteria are men and women aged 50 or over with records of at least 6 months of prescriptions for acid-suppressants in the last year. Patients in the intervention arm will receive an invitation to have a Cytosponge-TFF3 test in their general practice. Patients with a positive TFF3 test will receive an invitation for an upper gastro-intestinal endoscopy at their local hospital-based endoscopy clinic to test for BE. The primary objective is to compare histologically confirmed BE diagnosis between the intervention and control arms to determine whether the offer of the Cytosponge-TFF3 test in primary care results in an increase in BE diagnosis within 12 months of study entry. Discussion The BEST3 trial is a well-powered pragmatic trial testing the use of the Cytosponge-TFF3 test in the same population that we envisage it being used in clinical practice. The data generated from this trial will enable NICE and other clinical bodies to decide whether this test is suitable for routine clinical use. Trial registration This trial was prospectively registered with the ISRCTN Registry on 19/01/2017, trial number ISRCTN68382401

Terrorism in Australia: factors associated with perceived threat and incident-critical behaviours

<p>Abstract</p> <p>Background</p> <p>To help improve incident preparedness this study assessed socio-demographic and socio-economic predictors of perceived risk of terrorism within Australia and willingness to comply with public safety directives during such incidents.</p> <p>Methods</p> <p>The terrorism perception question module was incorporated into the New South Wales Population Health Survey and was completed by a representative sample of 2,081 respondents in early 2007. Responses were weighted against the New South Wales population.</p> <p>Results</p> <p>Multivariate analyses indicated that those with no formal educational qualifications were significantly more likely (OR = 2.10, 95%CI:1.32–3.35, p < 0.001) to think that a terrorist attack is very or extremely likely to occur in Australia and also more likely (OR = 3.62, 95%CI:2.25–5.83, p < 0.001) to be very or extremely concerned that they or a family member would be directly affected, compared to those with a university-level qualification. Speaking a language other than English at home predicted high concern (very/extremely) that self or family would be directly affected (OR = 3.02, 95%CI:2.02–4.53, p < 0.001) and was the strongest predictor of having made associated changes in living (OR = 3.27, 95%CI:2.17–4.93, p < 0.001). Being female predicted willingness to evacuate from public facilities. Speaking a language other than English at home predicted low willingness to evacuate.</p> <p>Conclusion</p> <p>Low education level is a risk factor for high terrorism risk perception and concerns regarding potential impacts. The pattern of concern and response among those of migrant background may reflect secondary social impacts associated with heightened community threat, rather than the direct threat of terrorism itself. These findings highlight the need for terrorism risk communication and related strategies to address the specific concerns of these sub-groups as a critical underpinning of population-level preparedness.</p

Typology of adults diagnosed with mental disorders based on socio-demographics and clinical and service use characteristics

<p>Abstract</p> <p>Background</p> <p>Mental disorder is a leading cause of morbidity worldwide. Its cost and negative impact on productivity are substantial. Consequently, improving mental health-care system efficiency - especially service utilisation - is a priority. Few studies have explored the use of services by specific subgroups of persons with mental disorder; a better understanding of these individuals is key to improving service planning. This study develops a typology of individuals, diagnosed with mental disorder in a 12-month period, based on their individual characteristics and use of services within a Canadian urban catchment area of 258,000 persons served by a psychiatric hospital.</p> <p>Methods</p> <p>From among the 2,443 people who took part in the survey, 406 (17%) experienced at least one episode of mental disorder (as per the Composite International Diagnostic Interview (CIDI)) in the 12 months pre-interview. These individuals were selected for cluster analysis.</p> <p>Results</p> <p>Analysis yielded four user clusters: people who experienced mainly anxiety disorder; depressive disorder; alcohol and/or drug disorder; and multiple mental and dependence disorder. Two clusters were more closely associated with females and anxiety or depressive disorders. In the two other clusters, males were over-represented compared with the sample as a whole, namely, substance abuses with or without concomitant mental disorder. Clusters with the greatest number of mental disorders per subject used a greater number of mental health-care services. Conversely, clusters associated exclusively with dependence disorders used few services.</p> <p>Conclusion</p> <p>The study found considerable heterogeneity among socio-demographic characteristics, number of disorders, and number of health-care services used by individuals with mental or dependence disorders. Cluster analysis revealed important differences in service use with regard to gender and age. It reinforces the relevance of developing targeted programs for subgroups of individuals with mental and/or dependence disorders. Strategies aimed at changing low service users' attitude (youths and males) or instituting specialised programs for that particular clientele should be promoted. Finally, as concomitant disorders are frequent among individuals with mental disorder, psychological services and/or addiction programs must be prioritised as components of integrated services when planning treatment.</p

Reciprocity as a foundation of financial economics

This paper argues that the subsistence of the fundamental theorem of contemporary financial mathematics is the ethical concept ‘reciprocity’. The argument is based on identifying an equivalence between the contemporary, and ostensibly ‘value neutral’, Fundamental Theory of Asset Pricing with theories of mathematical probability that emerged in the seventeenth century in the context of the ethical assessment of commercial contracts in a framework of Aristotelian ethics. This observation, the main claim of the paper, is justified on the basis of results from the Ultimatum Game and is analysed within a framework of Pragmatic philosophy. The analysis leads to the explanatory hypothesis that markets are centres of communicative action with reciprocity as a rule of discourse. The purpose of the paper is to reorientate financial economics to emphasise the objectives of cooperation and social cohesion and to this end, we offer specific policy advice