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1.
Nature ; 561(7722): 206-210, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30209369

RESUMO

Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind plasma that fills interplanetary space. As the solar wind slows and deflects to flow around Earth, or any other obstacle, a 'bow shock' forms within the flow. Under almost all solar-wind conditions, planetary bow shocks such as Earth's are collisionless, supercritical shocks, meaning that they reflect and accelerate a fraction of the incident solar-wind ions as an energy dissipation mechanism1,2, which results in the formation of a region called the ion foreshock3. In the foreshock, large-scale, transient phenomena can develop, such as 'hot flow anomalies'4-9, which are concentrations of shock-reflected, suprathermal ions that are channelled and accumulated along certain structures in the upstream magnetic field. Hot flow anomalies evolve explosively, often resulting in the formation of new shocks along their upstream edges5,10, and potentially contribute to particle acceleration11-13, but there have hitherto been no observations to constrain this acceleration or to confirm the underlying mechanism. Here we report observations of a hot flow anomaly accelerating solar-wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000 kiloelectronvolts. The acceleration mechanism depends on the mass and charge state of the ions and is consistent with first-order Fermi acceleration14,15. The acceleration that we observe results from only the interaction of Earth's bow shock with the solar wind, but produces a much, much larger number of energetic particles compared to what would typically be produced in the foreshock from acceleration at the bow shock. Such autogenous and efficient acceleration at quasi-parallel bow shocks (the normal direction of which are within about 45 degrees of the interplanetary magnetic field direction) provides a potential solution to Fermi's 'injection problem', which requires an as-yet-unexplained seed population of energetic particles, and implies that foreshock transients may be important in the generation of cosmic rays at astrophysical shocks throughout the cosmos.

2.
Eur J Prosthodont Restor Dent ; 32(1): 75-82, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-37721541

RESUMO

INTRODUCTION: This in-vitro study investigated limitations of intra-oral scanners (IOS) in capturing palatal defects at decreased mouth openings. The trueness and precision of composite 3D-printed models from Cone-Beam Computed Tomography (CBCT) and IOS were measured. METHODS: A partially dentate palatal defect model was scanned with IOS (3M™TrueDefinition) at various simulated mouth openings. Five silicone impressions were poured in gypsum. Scans were taken using 3M™TrueDefinition; Planmeca Planscan®, n=5 each. Model was scanned on two CBCT (PlanmecaProFace®; Accuitomo170®CBCT, n=5 each). Geomagic®Control2014™ was used to create composite-models merging CBCT with IOS. Thirty composite-models were 3D-printed. Trueness and precision were measured. Pearson Correlation Coefficients measured correlation between mouth opening and data capture. Data analysed using Kruskal-Wallis, Wilcoxon rank-sum, and ANOVA. Statistical significance inferred when p⟨0.05. RESULTS: Mouth openings ⟨20mm, IOS didn't capture information of soft tissue. Increased mouth opening positively correlated with increased data capture(r=0.93, p=0.001). AccuitomoCBCT and TrueDefinition IOS composite-models had the highest (trueness) and [precision](median (IQR) 0.172 mm(0.062-0.426)); [mean [SD] 0.080 mm [0.008]]. Casts had the lowest results (median (IQR) 0.289 mm(0.119-1.565));[mean [SD] 0.338 mm [0.089]](p⟨0.001). CONCLUSION: Mouth opening ⟨20mm resulted in insufficient data capture by IOS for clinical applications. Composite digital models showed promising trueness and precision results.


Assuntos
Desenho Assistido por Computador , Imageamento Tridimensional , Técnica de Moldagem Odontológica , Modelos Dentários , Tomografia Computadorizada de Feixe Cônico
3.
Colorectal Dis ; 25(7): 1479-1488, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37237447

RESUMO

AIM: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC. METHOD: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs. RESULTS: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient-led but clinician-informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0-100). Key informational needs related to medical therapy were benefits and risks of long-term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery. CONCLUSION: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Pessoa de Meia-Idade , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Preferência do Paciente , Inquéritos e Questionários , Emoções
4.
Occup Med (Lond) ; 73(6): 300-303, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37772966

RESUMO

BACKGROUND: Compensation for industrial disease in the UK may be obtained in two ways. A State scheme includes a list of accepted associations between occupations and diseases with evidence of a causative association. Epidemiological evidence of a doubled risk in the occupation concerned is usually required. This takes no account of variation of exposures within occupations, excluding many occupations where risk is less than doubled. In such cases, compensation for a perceived industrial illness may be obtained in Civil Courts, where excessive exposures can be considered. AIMS: To show that in the Civil Courts evidence of excessive exposure may lead to compensation for diseases which are not yet compensable as Industrial Injuries in the UK and to draw attention to the association of multiple sclerosis (MS) with solvent exposure. METHODS: We report the case of an industrial spray painter, who claimed his MS had been caused by high-level exposure to organic solvents, and our examination of the epidemiological evidence submitted. RESULTS: The painter received compensation by an out-of-court settlement, despite the overall epidemiological risk in relation to solvent exposure having been shown to be less than doubled. The evidence hinged on individual risk in relation to high exposure, genetic susceptibility and demonstration of a plausible mechanism. CONCLUSIONS: High organic solvent exposure may lead to the development of MS. Those giving evidence in Court need to be able to discuss the epidemiological and toxicological issues in relation to exposure in the individual case.


Assuntos
Esclerose Múltipla , Exposição Ocupacional , Humanos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/etiologia , Solventes/toxicidade , Ocupações , Exposição Ocupacional/efeitos adversos
5.
Artigo em Inglês | MEDLINE | ID: mdl-36049728

RESUMO

High CO2 (hypercapnia) can impose significant physiological challenges associated with acid-base regulation in fishes, impairing whole animal performance and survival. Unlike other environmental conditions such as temperature and O2, the acute CO2 tolerance thresholds of fishes are not understood. While some fish species are highly tolerant, the extent of acute CO2 tolerance and the associated physiological and ecological traits remain largely unknown. To investigate this, we used a recently developed ramping assay, termed the Carbon Dioxide maximum (CDmax), that increases CO2 exposure until loss of equilibrium (LOE) is observed. We investigated if there was a relationship between CO2 tolerance and the Root effect, ß-adrenergic sodium proton exchanger (ßNHE), air-breathing, and fish habitat in 17 species. We hypothesized that CO2 tolerance would be higher in fishes that lack both a Root effect and ßNHE, breathe air, and reside in tropical habitats. Our results showed that CDmax ranged from 2.7 to 26.7 kPa, while LOE was never reached in four species at the maximum PCO2 we could measure (26.7 kPa); CO2 tolerance was only associated with air-breathing, but not the presence of a Root effect or a red blood cell (RBC) ßNHE, or fish habitat. This study demonstrates that the diverse group of fishes investigated here are incredibly tolerant of CO2 and that although this tolerance is associated with air-breathing, further investigations are required to understand the basis for CO2 tolerance.


Assuntos
Dióxido de Carbono , Prótons , Adrenérgicos , Animais , Ecossistema , Eritrócitos/fisiologia , Peixes/fisiologia , Sódio
6.
Philos Trans A Math Phys Eng Sci ; 379(2190): 20200216, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33342387

RESUMO

The instrumental advances made in this new era of 4 m class solar telescopes with unmatched spectropolarimetric accuracy and sensitivity will enable the study of chromospheric magnetic fields and their dynamics with unprecedented detail. In this regard, spectropolarimetric diagnostics can provide invaluable insight into magneto-hydrodynamic (MHD) wave processes. MHD waves and, in particular, Alfvénic fluctuations associated with particular wave modes were recently recognized as important mechanisms not only for the heating of the outer layers of the Sun's atmosphere and the acceleration of the solar wind, but also for the elemental abundance anomaly observed in the corona of the Sun and other Sun-like stars (also known as first ionization potential) effect. Here, we take advantage of state-of-the-art and unique spectropolarimetric Interferometric BIdimensional Spectrometer observations to investigate the relation between intensity and circular polarization (CP) fluctuations in a sunspot chromosphere. Our results show a clear link between the intensity and CP fluctuations in a patch which corresponds to a narrow range of magnetic field inclinations. This suggests the presence of Alfvénic perturbations in the sunspot. This article is part of the Theo Murphy meeting issue 'High-resolution wave dynamics in the lower solar atmosphere'.

7.
Colorectal Dis ; 23(1): 18-33, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32777171

RESUMO

AIM: Approximately 20%-30% of patients with ulcerative colitis (UC) will undergo surgery during their disease course, the vast majority being elective due to chronic refractory disease. The risks of elective surgery are reported variably. The aim of this systematic review and meta-analysis is to summarize the outcomes after elective surgery for UC. METHODS: A systematic review was conducted that analysed studies reporting outcomes for elective surgery in the modern era (>2002). It was prospectively registered on the PROSPERO database (ref: CRD42018115513). Searches were performed of Embase and MEDLINE on 15 January 2019. Outcomes were split by operation performed. Primary outcome was quality of life; secondary outcomes were early, late and functional outcomes after surgery. Outcomes reported in five or more studies underwent a meta-analysis of incidence using random effects. Heterogeneity is reported with I2 , and publication bias was assessed using Doi plots and the Luis Furuya-Kanamori index. RESULTS: A total of 34 studies were included (11 774 patients). Quality of life was reported in 12 studies, with variable and contrasting results. Thirteen outcomes (eight early surgical complications, five functional outcomes) were included in the formal meta-analysis, all of which were outcomes for ileal pouch-anal anastomosis (IPAA). A further 71 outcomes were reported (50 IPAA, 21 end ileostomy). Only 14 of 84 outcomes received formal definitions, with high inter-study variation of definitions. CONCLUSION: Outcomes after elective surgery for UC are variably defined. This systematic review and meta-analysis highlights the range of reported incidences and provides practical information that facilitates shared decision making in clinical practice.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Colite Ulcerativa/cirurgia , Humanos , Ileostomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Proctocolectomia Restauradora/efeitos adversos , Qualidade de Vida , Resultado do Tratamento
8.
Clin Exp Immunol ; 202(2): 193-209, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32978971

RESUMO

Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses, SARS-CoV-2 has evolved strategies to circumvent innate immune detection, including low cytosine-phosphate-guanosine (CpG) levels in the genome, glycosylation to shield essential elements including the receptor-binding domain, RNA shielding and generation of viral proteins that actively impede anti-viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion, SARS-CoV-2 infection activates innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or, alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin-angiotensin system due to down-regulation of angiotensin-converting enzyme 2, the receptor for SARS-CoV-2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system, but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS-CoV-2 infection, much of which is based on the knowledge from SARS-CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID-19 may help to explain factors that contribute to the variety of clinical manifestations and outcome of SARS-CoV-2 infection.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Hipóxia/imunologia , Pneumonia Viral/imunologia , Doenças Vasculares/imunologia , Enzima de Conversão de Angiotensina 2 , Animais , Coagulação Sanguínea , COVID-19 , Humanos , Evasão da Resposta Imune , Imunidade Inata , Interferon Tipo I/metabolismo , Pandemias , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina , SARS-CoV-2
9.
Clin Exp Immunol ; 202(2): 149-161, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32671831

RESUMO

Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Vacinas Virais/imunologia , Animais , Antígenos CD20/imunologia , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/prevenção & controle , Humanos , Depleção Linfocítica , SARS-CoV-2 , Vacinação
10.
Br J Dermatol ; 182(3): 698-707, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31141158

RESUMO

BACKGROUND: The Ehlers-Danlos syndromes (EDS) consist of 13 subtypes with overlapping features including joint hypermobility, skin and vascular fragility and generalized connective tissue friability. As DNA analysis has become the gold standard for investigation of EDS, transmission electron microscopy (TEM) in clinical practice is decreasing. However, owing to the use of next-generation sequencing, the frequency of variants of uncertain significance (VUS) identified using DNA analysis is increasing. We hypothesized that TEM can provide evidence for or against pathogenicity of VUS. OBJECTIVES: The aim of this study was to evaluate the role of TEM in the diagnosis of EDS subtypes. METHODS: Data were collected from patients who underwent a skin biopsy between October 2012 and March 2017 at the London EDS National Diagnostic Service. TEM biopsies were categorized as 'normal' or 'abnormal' according to the description and conclusion in the TEM reports. Definitive diagnoses were reached via a combination of clinical features, structural and functional studies and DNA investigations. RESULTS: The analysis included 177 patients, comprising 30 abnormal and 147 normal TEM reports. A definitive diagnosis of monogenic EDS subtypes was made in 24 patients. Overall, 17 of these 24 patients (71%) had an abnormal biopsy report and seven (29%) had a normal biopsy report. No TEM findings were specifically associated with any EDS subtype, although collagen flowers were present in most patients with a genetically confirmed diagnosis of classical EDS. CONCLUSIONS: TEM analysis of collagen structure may have the potential to provide evidence for or against the pathogenicity of a VUS, but more work is needed to establish a clear role for TEM in this process. What's already known about this topic? Collagen fibril abnormalities can be seen in several Ehlers-Danlos syndrome (EDS) subtypes. What does this study add? This study provides clinical data, transmission electron microscopy (TEM) data and molecular data of one of the largest groups of patients suspected to have a monogenetic EDS subtype. No TEM findings were specifically associated with an EDS subtype. There was a higher percentage (71%) of abnormal biopsy findings in patients with a definitive diagnosis of a monogenetic EDS subtype and where a class 4/5 genetic variant was present.


Assuntos
Síndrome de Ehlers-Danlos , Colágeno , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Humanos , Londres , Microscopia Eletrônica , Síndrome
11.
J Exp Biol ; 223(Pt 7)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32127382

RESUMO

Acute (<96 h) exposure to elevated environmental CO2 (hypercarbia) induces a pH disturbance in fishes that is often compensated by concurrent recovery of intracellular and extracellular pH (pHi and pHe, respectively; coupled pH regulation). However, coupled pH regulation may be limited at CO2 partial pressure (PCO2 ) tensions far below levels that some fishes naturally encounter. Previously, four hypercarbia-tolerant fishes had been shown to completely and rapidly regulate heart, brain, liver and white muscle pHi during acute exposure to >4 kPa PCO2  (preferential pHi regulation) before pHe compensation was observed. Here, we test the hypothesis that preferential pHi regulation is a widespread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning six orders, eight families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests that preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia, and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing.


Assuntos
Acidose Respiratória , Dióxido de Carbono , Equilíbrio Ácido-Base , Animais , Peixes , Humanos , Concentração de Íons de Hidrogênio
12.
Eur J Neurol ; 27(2): 221-228, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31617269

RESUMO

Clinical trials are probably the most informative experiments to help an understanding of multiple sclerosis (MS) biology. Recent successes with CD20-depleting antibodies have focused attention towards B cell subsets as important mediators in MS. The trial of tabalumab (NTC00882999), which inhibits B cell activation factor (BAFF), is reported and reviewed and this trial is contrasted with the trial on the inhibition of a proliferation-inducing ligand (APRIL) and BAFF using atacicept (NCT00642902). Both tabalumab and atacicept induce depletion of mature B cells and inhibit antibody formation, but they fail to deplete memory B cells and do not inhibit relapsing MS. Atacicept is reported to augment memory B cell responses and may precipitate relapse, suggesting the importance of APRIL. However, BAFF inhibition can enhance peripheral blood memory B cell responses, which was not associated with augmented relapse. Although other interpretations are possible, these data further support the hypothesis that memory B cells may be of central importance in relapsing MS, as they are the major CD20+ B cell subset expressing APRIL receptors. They also suggest that quantitative and/or qualitative differences in B cell responses or other factors, such as an immune-regulatory effect associated with APRIL, may be important in determining whether MS reactivates following neutralization of peripheral B cell maturation and survival factors.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfócitos B/imunologia , Fator B do Complemento/antagonistas & inibidores , Memória Imunológica , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Fator Ativador de Células B , Humanos , Resultados Negativos , Falha de Tratamento , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral
13.
Bioorg Chem ; 95: 103559, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911310

RESUMO

This study was designed to evaluate the antioxidant, antibacterial and cytotoxicity effects of Satureja hortensis (S. hortensis) essential oil (EO). The GC-MS analysis of S. hortensis EO (SEO) has identified seven compounds, representing 96.84% of the oil. The two main constituents of the oil were; carvacrol (48.51%) and γ-terpinene (36.63%). The total phenolics and flavonoids contents of SEO were 199.1 ± 0.5 µg GAE/mg (GAE-gallic acid equivalent) and 161.5 ± 0.9 µg CE/mg (CE-catechin equivalent), respectively. SEO showed superior antioxidant potential (ABTS, 1038.66 and DPPH, 12.679 mg Trolox/g), and exhibited antibacterial activity against five food born bacterial strains, exerting the minimum inhibitory concentration (MIC) ranging from 2 to 4 mg/mL. On the other hand, using of SEO at inhibiting concentrations for pathogenic bacteria can affect the beneficial bacteria negatively. Moreover, SEO showed toxicity on normal cells (WI-38, THLE2, and phoenx-eco) and consequently, it is worthwhile for extensive toxicity studies in normal cells and animal models. As our-knowledge, this is the first study on antioxidant, antimicrobial and cytotoxicity of Egyptian S. hortensis.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Óleos Voláteis/farmacologia , Satureja/química , Egito , Flavonoides/análise , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Fenóis/análise
14.
Nature ; 515(7528): 531-4, 2014 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-25428500

RESUMO

Early observations indicated that the Earth's Van Allen radiation belts could be separated into an inner zone dominated by high-energy protons and an outer zone dominated by high-energy electrons. Subsequent studies showed that electrons of moderate energy (less than about one megaelectronvolt) often populate both zones, with a deep 'slot' region largely devoid of particles between them. There is a region of dense cold plasma around the Earth known as the plasmasphere, the outer boundary of which is called the plasmapause. The two-belt radiation structure was explained as arising from strong electron interactions with plasmaspheric hiss just inside the plasmapause boundary, with the inner edge of the outer radiation zone corresponding to the minimum plasmapause location. Recent observations have revealed unexpected radiation belt morphology, especially at ultrarelativistic kinetic energies (more than five megaelectronvolts). Here we analyse an extended data set that reveals an exceedingly sharp inner boundary for the ultrarelativistic electrons. Additional, concurrently measured data reveal that this barrier to inward electron radial transport does not arise because of a physical boundary within the Earth's intrinsic magnetic field, and that inward radial diffusion is unlikely to be inhibited by scattering by electromagnetic transmitter wave fields. Rather, we suggest that exceptionally slow natural inward radial diffusion combined with weak, but persistent, wave-particle pitch angle scattering deep inside the Earth's plasmasphere can combine to create an almost impenetrable barrier through which the most energetic Van Allen belt electrons cannot migrate.

15.
Sci Eng Ethics ; 26(3): 1477-1498, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31970596

RESUMO

Bainbridge's well known "Ironies of Automation" (in: Johannsen, Rijnsdorp (eds) Analysis, design and evaluation of man-machine systems. Elsevier, Amsterdam, pp 129-135, 1983. https://doi.org/10.1016/B978-0-08-029348-6.50026-9) laid out a set of fundamental criticisms surrounding the promises of automation that, even 30 years later, remain both relevant and, in many cases, intractable. Similarly, a set of ironies in technologies for sensor driven self-quantification (often referred to broadly as wearables) is laid out here, spanning from instrumental problems in human factors design (such as disagreement over physiological norms) to much broader social problems (such as loss of freedom). As with automation, these ironies stand in the way of many of the promised benefits of these wearable technologies. It is argued here that without addressing these ironies now, the promises of wearables may not come to fruition, and instead users may experience outcomes that are opposite to those which the designers seek to afford, or, at the very least, those which consumers believe they are being offered. This paper describes four key ironies of sensor driven self-quantification: (1) know more, know better versus no more, no better; (2) greater self-control versus greater social control; (3) well-being versus never being well enough; (4) more choice versus erosion of choice.


Assuntos
Dispositivos Eletrônicos Vestíveis , Humanos
16.
Mol Psychiatry ; 23(5): 1145-1156, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28630453

RESUMO

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.


Assuntos
Epigênese Genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Estudos de Coortes , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Estudos Longitudinais , Masculino , Militares/psicologia , Estudos Prospectivos , Proteínas Repressoras , Transtornos de Estresse Pós-Traumáticos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Mol Psychiatry ; 23(3): 666-673, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28439101

RESUMO

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.


Assuntos
Esquizofrenia/genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Negro ou Afro-Americano/genética , Transtorno Bipolar/genética , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais , População Branca/genética
18.
Ecol Appl ; 29(5): e01918, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31162764

RESUMO

Anthropogenic environmental change is driving the rapid loss of biodiversity. Large declines in the abundance of historically common species are now emerging as a major concern. Identifying declining populations through long-term biodiversity monitoring is vital for implementing timely conservation measures. It is, therefore, critical to evaluate the likelihood that persistent long-term population trends of a given size could be detected using existing monitoring data and methods. Here, we test the power to detect declines in Australia's common landbirds using long-term citizen science monitoring. We use spatially explicit simulations of occupancy dynamics and virtual sampling, designed to mimic bird monitoring in better-sampled regions of Australia, to assess likely power in these data to detect trends relevant for conservation. We predict the statistical power for 326 common species that meet minimum requirements for monitoring data across 10 regions of Australia, estimating the number of species for which we would have a high (≥80%) chance of detecting declines of different sizes. The power to detect declines of ≥30% per decade was predicted to be high for at least one-third of the common species in 7 of 10 regions, with a total of 103 (32% of 326) unique species sufficiently monitored in at least one region. These species spanned 12 taxonomic orders, four orders of magnitude in body mass, and a broad diversity of dietary guilds, suggesting the current species pool will likely serve as robust indicators for a broad range of environmental states and pressures. Power was strongly affected by species' detectability, and power to detect even large declines was negligible when species are detected on ≤50% of visits to an occupied site. Predicted power for many species fell just short of the 80% threshold in one or more regions, which suggests an increase in effort targeting these species could greatly enhance the species and regional representation of these data. Against the backdrop of unprecedented biodiversity losses, this study shows how critical evaluation of existing monitoring schemes is valuable both for assessing the contribution of citizen science schemes to biodiversity monitoring and for designing strategic monitoring to significantly improve the knowledge these schemes provide.


Assuntos
Biodiversidade , Aves , Animais , Austrália , Conservação dos Recursos Naturais , Coleta de Dados , Dinâmica Populacional
19.
Nature ; 504(7480): 411-4, 2013 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-24352287

RESUMO

Recent analysis of satellite data obtained during the 9 October 2012 geomagnetic storm identified the development of peaks in electron phase space density, which are compelling evidence for local electron acceleration in the heart of the outer radiation belt, but are inconsistent with acceleration by inward radial diffusive transport. However, the precise physical mechanism responsible for the acceleration on 9 October was not identified. Previous modelling has indicated that a magnetospheric electromagnetic emission known as chorus could be a potential candidate for local electron acceleration, but a definitive resolution of the importance of chorus for radiation-belt acceleration was not possible because of limitations in the energy range and resolution of previous electron observations and the lack of a dynamic global wave model. Here we report high-resolution electron observations obtained during the 9 October storm and demonstrate, using a two-dimensional simulation performed with a recently developed time-varying data-driven model, that chorus scattering explains the temporal evolution of both the energy and angular distribution of the observed relativistic electron flux increase. Our detailed modelling demonstrates the remarkable efficiency of wave acceleration in the Earth's outer radiation belt, and the results presented have potential application to Jupiter, Saturn and other magnetized astrophysical objects.

20.
Eur Arch Otorhinolaryngol ; 276(11): 3213-3219, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31388759

RESUMO

PURPOSE: Total laryngectomy and end tracheal stoma formation are often required to treat advanced laryngeal cancer. Resources on the internet are commonly accessed by patients as a source of healthcare information. YouTube™, the most popular video-hosting website, is one such resource. The aims of this study were to assess the thematic content of the most viewed YouTube™ videos concerning laryngectomy for laryngeal cancer and to evaluate user response to these videos. METHOD: A search of YouTube™ was performed and data were extracted from videos with > 100 views. Upload source, number of views, likes, dislikes and comments were collected and the content of comments was analysed. User response was compared between upload sources using Kruskal-Wallis testing. Inductive thematic analysis of video content was performed to identify overarching themes and subthemes. RESULTS: A total of 96 videos were identified, 16 uploaded by patients, 24 by individual healthcare professionals and 56 by professional healthcare institutions. There were 1214,503 views and no significant differences in the number of views, likes or dislikes between upload sources. Three overarching themes and 17 subthemes were identified. Comments were most frequently characterised as offering praise. CONCLUSION: YouTube™ has been shown to be a popular platform for sharing information about laryngectomy for laryngeal cancer. There is a lack of data concerning the quality of this information, however, and future work should focus on assessing this. Trusted institutions could make use of this medium to disseminate high-quality information to their patients, and to the wider public.


Assuntos
Disseminação de Informação/métodos , Internet , Neoplasias Laríngeas , Laringectomia/métodos , Mídias Sociais , Humanos , Comportamento de Busca de Informação , Neoplasias Laríngeas/psicologia , Neoplasias Laríngeas/cirurgia , Gravação em Vídeo
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