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We report a laser-plasma experiment that was carried out at the LMJ-PETAL facility and realized the first magnetized, turbulent, supersonic (Ma_{turb}≈2.5) plasma with a large magnetic Reynolds number (Rm≈45) in the laboratory. Initial seed magnetic fields were amplified, but only moderately so, and did not become dynamically significant. A notable absence of magnetic energy at scales smaller than the outer scale of the turbulent cascade was also observed. Our results support the notion that moderately supersonic, low-magnetic-Prandtl-number plasma turbulence is inefficient at amplifying magnetic fields compared to its subsonic, incompressible counterpart.
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BACKGROUND: The human resources for health crisis has generated much debate as to the radical changes necessary to mitigate the risks to universal health coverage. Nurses can make a significant impact on global health, if only they feel empowered to take their seat at the political table. AIM: The aim of this paper was to outline nurse-led initiatives to enhance organizational culture and clinical processes at the Combined Military Hospital in Rawalpindi, Pakistan. These have been designed and implemented by the United Kingdom (UK) Defence Medical Services to empower the nursing workforce in Pakistan. OUTCOME: An educational model has been developed that will build capacity, within a workforce constrained by numbers, by bridging the gap between nursing theory and practice. It is geared to actively engage Pakistani nurses in quality improvement to ensure care is based on best evidence that will enhance patient outcomes. CONCLUSION AND IMPLICATIONS FOR NURSING & HEALTH POLICY: The wider impact of the model has already been evidenced by nurses, country-wide, who are gaining the necessary skills and confidence to realize their true potential in influencing the patient care pathway and future policy. This is crucial to the recruitment and retention of nurses who might otherwise seek alternative career paths if they lack a sense of value within the profession. Their renewed sense of value will enable them to find their voice and ability to contribute to the sustainable development goals adopted by the United Nations General Assembly in 2015.
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Empoderamento , Modelos Educacionais , Recursos Humanos de Enfermagem , Atenção à Saúde , Política de Saúde , Humanos , Enfermeiras e Enfermeiros , Paquistão , Melhoria de QualidadeRESUMO
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular nonreceptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression. The effects of prophylactic or therapeutic Syk inhibition on allergic airway inflammation, hyperresponsiveness, and airway remodeling were analyzed in allergen-sensitized and airway-challenged mice. The effects of Syk inhibitors BAY 61-3606 or BI 1002494 on airway function were investigated in isolated lungs of wild-type, PKCα-deficient, mast cell-deficient, or eNOS-deficient mice. RESULTS: Spleen tyrosine kinase expression was found in human and murine airway smooth muscle cells. Syk inhibition reduced allergic airway inflammation, airway hyperresponsiveness, and pulmonary collagen deposition. In naïve mice, Syk inhibition diminished airway responsiveness independently of mast cells, or PKCα or eNOS expression and rapidly reversed established bronchoconstriction independently of NO. Simultaneous inhibition of Syk and PKC revealed additive dilatory effects, whereas combined inhibition of Syk and rho kinase or Syk and p38 MAPK did not cause additive bronchodilation. CONCLUSIONS: Spleen tyrosine kinase inhibition directly attenuates airway smooth muscle cell contraction independent of its protective immunomodulatory effects on allergic airway inflammation, hyperresponsiveness, and airway remodeling. Syk mediates bronchoconstriction in a NO-independent manner, presumably via rho kinase and p38 MAPK, and Syk inhibition might present a promising therapeutic approach in chronic asthma as well as acute asthma attacks.
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Remodelação das Vias Aéreas/efeitos dos fármacos , Remodelação das Vias Aéreas/imunologia , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/metabolismo , Broncoconstrição/efeitos dos fármacos , Quinase Syk/antagonistas & inibidores , Células Th2/imunologia , Células Th2/metabolismo , Alérgenos/imunologia , Animais , Hiper-Reatividade Brônquica/tratamento farmacológico , Hiper-Reatividade Brônquica/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Modelos Animais de Doenças , Feminino , Receptor Quinase 1 Acoplada a Proteína G/metabolismo , Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Naftiridinas/farmacologia , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Proteína Quinase C-alfa , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Pirrolidinonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Quinase Syk/genética , Quinase Syk/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The UK Defence Medical Service's Pre-Hospital Emergency Care (PHEC) capability includes rapid-deployment Medical Emergency Response Teams (MERTs) comprising tri-service trauma consultants, paramedics and specialised nurses, all of whom are qualified to administer emergency care under extreme conditions to improve the survival prospects of combat casualties. The pre-deployment training of MERT personnel is designed to foster individual knowledge, skills and abilities in PHEC and in small team performance and cohesion in 'mission-specific' contexts. Until now, the provision of airborne pre-deployment MERT training had been dependent on either the availability of an operational aircraft (eg, the CH-47 Chinook helicopter) or access to one of only two ground-based facsimiles of the Chinook's rear cargo/passenger cabin. Although MERT training has high priority, there will always be competition with other military taskings for access to helicopter assets (and for other platforms in other branches of the Armed Forces). This paper describes the development of an inexpensive, reconfigurable and transportable MERT training concept based on 'mixed reality' technologies-in effect the 'blending' of real-world objects of training relevance with virtual reality reconstructions of operational contexts.
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Serviços Médicos de Emergência , Medicina Militar/educação , Treinamento por Simulação , Humanos , Manequins , Reino UnidoRESUMO
BACKGROUND: With the end of UK military operations in Iraq and Afghanistan, it is essential that peacetime training of Defence Medical Services (DMS) trauma teams ensures appropriate future preparedness. A new model of pre-deployment training involves placement of formed military trauma teams into civilian trauma centres. This study evaluates the benefit of 'live training during an exercise period' (LIVEX) for DMS trauma teams. METHODS: A cross-sectional questionnaire-based survey of participants was conducted. Quantitative data were collected prior to the start and on the final day. Written reports were collected from the coordinators. Thematic analysis was used to identify emergent themes in a supplementary, qualitative analysis. RESULTS: Each team comprised 13 personnel and results should be interpreted with knowledge of this small sample size. The response rate for both the pre-LIVEX and post-LIVEX questionnaire was 100%. By the end of the week, 89% of participants (n=23) stated LIVEX was an 'appropriate or very appropriate' way of preparing for an operational role compared with 40% (n=9) before the exercise (p<0.01). However, completing LIVEX made no difference to participants' personal perception of their own operational preparedness. Thematic analysis suggested greater training benefit for more junior members of the team; from Regulars and Reservists training together; and from two-way exchange of information between DMS and National Health Service medical staffs. CONCLUSIONS: Completing LIVEX made no statistically significant difference to participants' personal perception of their own operational preparedness, but the perception of LIVEX as an appropriate training platform improved significantly after conducting the training exercise.
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Pessoal Técnico de Saúde/educação , Medicina Militar/educação , Enfermagem Militar/educação , Militares/educação , Ensino , Traumatologia/educação , Ferimentos e Lesões/terapia , Adulto , Estudos Transversais , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Enfermeiras e Enfermeiros , Médicos , Projetos Piloto , Pesquisa Qualitativa , Inquéritos e Questionários , Centros de Traumatologia , Reino UnidoRESUMO
Interaction between a central outflow and a surrounding wind is common in astrophysical sources powered by accretion. Understanding how the interaction might help to collimate the inner central outflow is of interest for assessing astrophysical jet formation paradigms. In this context, we studied the interaction between two nested supersonic plasma flows generated by focusing a long-pulse high-energy laser beam onto a solid target. A nested geometry was created by shaping the energy distribution at the focal spot with a dedicated phase plate. Optical and x-ray diagnostics were used to study the interacting flows. Experimental results and numerical hydrodynamic simulations indeed show the formation of strongly collimated jets. Our work experimentally confirms the "shock-focused inertial confinement" mechanism proposed in previous theoretical astrophysics investigations.
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OBJECTIVE: The involvement of optic and auditory pathways has rarely been studied in demyelinating polyneuropathies. We here aimed to study this further in a cohort of patients with acquired and gentic demyelinating neuropathy. METHODS: We studied eight patients with hereditary neuropathy with liability to pressure palsies (HNPP), six with Charcot-Marie-Tooth disease type 1A (CMT1A), ten with chronic inflammatory demyelinating polyneuropathy (CIDP) and seven with antimyelin-associated glycoprotein (MAG) neuropathy using visual evoked potentials and brainstem auditory evoked potentials. RESULTS: Optic pathway dysfunction was detected in 6/7 anti-MAG neuropathy patients, about half of those with CIDP and HNPP, but only in 1/6 patients with CMT1A. Peripheral auditory nerve dysfunction appeared common in all groups except HNPP. Brainstem involvement was exceptional in all groups. CONCLUSIONS: We conclude optic nerve involvement may be frequent in all demyelinating polyneuropathies, particularly anti-MAG neuropathy, except in CMT1A. Peripheral auditory nerves may be spared in HNPP possibly due to absence of local compression. Evidence for central brainstem pathology appeared infrequent in all four studied neuropathies. This study suggests that acquired and genetic demyelinating polyneuropathies may be associated with optic and auditory nerve involvement, which may contribute to neurological disability, and require greater awareness.
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Vias Auditivas/fisiopatologia , Doenças Desmielinizantes/fisiopatologia , Polineuropatias/fisiopatologia , Vias Visuais/fisiopatologia , Adulto , Idoso , Doenças Desmielinizantes/complicações , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/complicaçõesRESUMO
Healthcare provided by the Defence Medical Services (DMS) is acknowledged to be of a high standard but patients' experiences of it has not been measured and collated in a consistent and meaningful way, which has limited strategic quality improvement initiatives. Responsibility for implementing and delivering a programme of healthcare governance and assurance for the DMS rests with the Inspector General (IG). An important aspect of this role is to nurture a culture of continuous improvement in the DMS and under this leadership the IG team has prioritised a number of projects to address this. The project to improve patient experience data capture was prioritised in the work schedule as it incorporated initiatives that would lead to improved quality in DMS healthcare, information exploitation and ultimately patient safety. This is the first in a series of articles that will document this important work and describe the methodological considerations associated with the initial questionnaire design, collaboration with NHS partners, the pilot study and progress towards the introduction of the definitive DMS tool later this year.
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Medicina Militar , Garantia da Qualidade dos Cuidados de Saúde/métodos , Inquéritos e Questionários , Humanos , Satisfação do Paciente , Projetos Piloto , Reino UnidoRESUMO
The interactions and coordination of biomolecules are crucial for most cellular functions. The observation of protein interactions in live cells may provide a better understanding of the underlying mechanisms. After fluorescent labeling of the interacting partners and live-cell microscopy, the colocalization is generally analyzed by quantitative global methods. Recent studies have addressed questions regarding the individual colocalization of moving biomolecules, usually by using single-particle tracking (SPT) and comparing the fluorescent intensities in both color channels. Here, we introduce a new method that combines SPT and correlation methods to obtain a dynamical 3D colocalization analysis along single trajectories of dual-colored particles. After 3D tracking, the colocalization is computed at each particle's position via the local 3D image cross correlation of the two detection channels. For every particle analyzed, the output consists of the 3D trajectory, the time-resolved 3D colocalization information, and the fluorescence intensity in both channels. In addition, the cross-correlation analysis shows the 3D relative movement of the two fluorescent labels with an accuracy of 30 nm. We apply this method to the tracking of viral fusion events in live cells and demonstrate its capacity to obtain the time-resolved colocalization status of single particles in dense and noisy environments.
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Imageamento Tridimensional/métodos , Transporte Biológico , Sobrevivência Celular , Cor , Citosol/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Células HeLa , Humanos , Microesferas , Reprodutibilidade dos Testes , Spumavirus/metabolismoRESUMO
Lung disease is the major cause of death in cystic fibrosis (CF), but there is no evidence for overt lung involvement at birth. We show here that the same is true for the gene targeted cftrm1HGU mutant mouse. Furthermore, this CF mouse model demonstrates an impaired capacity to clear Staphylococcus aureus and Burkholderia (Pseudomonas) cepacia, two opportunistic lung pathogens closely associated with lung disease in CF subjects. The cftrm1HGU homozygotes display mucus retention and frank lung disease in response to repeated microbial exposure. Thus, lung disease in the cftrm1HGU mouse develops in response to bacterial infection, establishing a model to dissect the pathogenesis of CF pulmonary disease and providing a clinically relevant end point to assess the efficacy of pharmacologic or genetic interventions.
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Infecções Bacterianas/etiologia , Fibrose Cística/complicações , Fibrose Cística/genética , Pneumopatias/etiologia , Infecções Oportunistas/etiologia , Animais , Infecções Bacterianas/patologia , Burkholderia cepacia , Fibrose Cística/patologia , Modelos Animais de Doenças , Homozigoto , Humanos , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias/patologia , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Infecções Oportunistas/patologia , Infecções por Pseudomonas/etiologia , Infecções por Pseudomonas/patologia , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/patologiaRESUMO
Recruitment and retention of doctors have been highlighted as some of the leading causes of the current perceived crisis within civilian emergency care. Indeed, the NHS recognises the contribution made by other healthcare professionals by supporting accreditation in advanced practice to mitigate the risks associated with these capability gaps. Consequently, roles such as the advanced clinical practitioner are now well established. Previous research and clinical experience in the civilian sector suggest that the advanced practitioner (AP) role could be used within Defence. Operationally, the role could be advantageous for the Defence Medical Services in the delivery of deployed healthcare. However, there is no available research that defines the role of UK military APs and, more specifically, their potential to support deployed prehospital care. Further work is required to determine how an AP might be effectively used within the military prehospital patient care pathway.
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Serviços Médicos de Emergência , Militares , Humanos , Reino UnidoRESUMO
INTRODUCTION: The challenges faced by healthcare workers, not least during the response to the COVID-19 pandemic, have been extensively studied, and concerns continue to be highlighted in relation to their long-term mental health. Identifying the need to support their personnel, a leader-led structured programme of reflection: the recovery, readjustment and reintegration programme (R3P) was designed by the UK Defence Medical Services to mitigate the potential stressors associated with this outbreak and enhance the resilience of the workforce. METHODS: 128 military personnel completed an evaluation of R3P. A survey included measures of anxiety before and after the intervention, perceptions of the discussion themes and whether these brought a sense of closure to areas of distress, and attitudes to help-seeking. RESULTS: Most respondents (86%-92%) rated the five discussion themes either 'helpful' or 'very helpful', 51% of respondents reported a sense of closure about an issue that had been causing distress and 72% of respondents felt better able to seek help should it be necessary. Evaluating the effect R3P had on anxiety, a Wilcoxon signed rank test elicited a statistically significant difference in anxiety pre-R3P and post-R3P; Z=-3.54, p<0.001. The median anxiety rating was 3.5 (IQR 4.75, 95% CI 1.25 to 6.00) before undertaking R3P, which decreased to 3 (IQR 4.75, 95% CI 1.00 to 5.75) after undertaking R3P. 39.1% of participants reported decreased anxiety, 18.8% reported increased anxiety and 42.2% reported no change. CONCLUSION: This evaluation has identified several positive aspects to R3P with many personnel reporting a reduction in anxiety, a sense of closure and increased likelihood of help-seeking. Several participants did report an increase in anxiety and the long-term impact of R3P on mental health and well-being is unclear. Further mixed-methods evaluation incorporating a longer follow-up is required.
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Gamma-ray bursts (GRBs) and their afterglows are the most brilliant transient events in the Universe. Both the bursts themselves and their afterglows have been predicted to be visible out to redshifts of z approximately 20, and therefore to be powerful probes of the early Universe. The burst GRB 000131, at z = 4.50, was hitherto the most distant such event identified. Here we report the discovery of the bright near-infrared afterglow of GRB 050904 (ref. 4). From our measurements of the near-infrared afterglow, and our failure to detect the optical afterglow, we determine the photometric redshift of the burst to be z = 6.39 - 0.12 + 0.11 (refs 5-7). Subsequently, it was measured spectroscopically to be z = 6.29 +/- 0.01, in agreement with our photometric estimate. These results demonstrate that GRBs can be used to trace the star formation, metallicity, and reionization histories of the early Universe.
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Prostate cancer mortality results from metastasis to bone and hormone-independent tumor growth. Models to study these progressive changes are lacking. Here we describe the propagation of advanced human prostate cancer by direct transfer of surgical samples from patients into immune-deficient male SCID mice. Explants from six of eight patients formed prostate tumors and two showed unique cytogenetic, biologic and molecular features that were retained through six or more passages. One grew in an androgen-independent fashion, whereas the second formed tumors that regressed following castration then regrew. Micrometastatic disease was detected in the hematopoietic tissues of half of the recipient mice. Thus selected specimens of advanced human prostate cancer can be propagated in SCID mice in a manner that recapitulates the clinical transition from androgen-sensitive to androgen-independent growth, accompanied by micrometastasis.
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Androgênios/metabolismo , Transplante de Neoplasias/métodos , Neoplasias da Próstata/patologia , Transplante Heterólogo/métodos , Animais , Humanos , Masculino , Camundongos , Camundongos SCID , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/secundárioRESUMO
Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.
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Single bouts of exercise increase hexokinase activity in red and white skeletal muscle of guinea pigs. Multiple bouts of exercise cause two-fold increases. In contrast to other enzymes associated with glycolysis, hexokinase activity is higher in red than in white skeletal muscle.
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Hexoquinase/metabolismo , Músculos/enzimologia , Esforço Físico , Animais , Glicogênio/metabolismo , Glicólise , Cobaias , Masculino , Contração Muscular , Músculos/metabolismo , NADP/metabolismo , Pigmentação , EspectrofotometriaRESUMO
INTRODUCTION: The WHO Constitution enshrines ' the highest attainable standard of health as a fundamental right of every human being.' Strengthening delivery of health services confers benefits to individuals, families and communities, and can improve national and regional stability and security. In attempting to build international healthcare capability, UK Defence Medical Services (DMS) assets can contribute to the development of healthcare within overseas nations in a process that is known as Defence Healthcare Engagement (DHE). METHODS: In the first bespoke DMS DHE tasking, a team of 12 DMS nurses and doctors deployed to a 1000-bedded urban hospital in a partner nation and worked alongside indigenous healthcare workers (doctors, nurses and paramedical staff) during April and May 2016. The DMS nurses focused on nursing hygiene skills by demonstrations of best practice and DMS care standards, clinical leadership and female empowerment. A Quality Improvement Programme was initiated that centred on hand hygiene (HH) compliance before and after patient contact, and the introduction of peripheral cannula care and surveillance. RESULTS: After a brief induction on the ward, it was apparent that compliance with HH was poor. Peripheral cannulas were secured with adhesive zinc oxide tape and no active surveillance process (such as venous infusion phlebitis (VIP) scoring) was in place. After intensive education and training, initial week-long audits were undertaken and repeated after a further 2 weeks of training and coworking. In the second audit cycle, HH compliance had increased to 69% and VIP scoring compliance to 99%. In the final audit cycle, it was noted that nursing compliance with HH (75/98: 77%) was significantly higher than the doctors' HH compliance (76/200: 38%); p<0.0001. CONCLUSIONS: DHE is a long-term collaborative process based on the establishment and development of comprehensive relationships that can help transform indigenous healthcare services towards patient-centred systems with a focus on safety and quality of care. Short deployments to allow clinical immersion of UK healthcare workers within indigenous teams can have an immediate impact. Coworking is a powerful method of demonstrating standards of care and empowering staff to institute transformative change. A multidisciplinary group of Quality Improvement Champions has been identified and a Hospital Oversight Committee established, which will offer the prospect of longer term sustainability and development.