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2.
Anesth Analg ; 137(3): 665-675, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37205607

RESUMO

BACKGROUND: Postoperative nausea and vomiting (PONV) prophylaxis is consistently considered a key indicator of anesthesia care quality. PONV may disproportionately impact disadvantaged patients. The primary objectives of this study were to examine the associations between sociodemographic factors and the incidence of PONV and clinician adherence to a PONV prophylaxis protocol. METHODS: We conducted a retrospective analysis of all patients eligible for an institution-specific PONV prophylaxis protocol (2015-2017). Sociodemographic and PONV risk data were collected. Primary outcomes were PONV incidence and clinician adherence to PONV prophylaxis protocol. We used descriptive statistics to compare sociodemographics, procedural characteristics, and protocol adherence for patients with and without PONV. Multivariable logistic regression analysis followed by Tukey-Kramer correction for multiple comparisons was used to test for associations between patient sociodemographics, procedural characteristics, PONV risk, and (1) PONV incidence and (2) adherence to PONV prophylaxis protocol. RESULTS: Within the 8384 patient sample, Black patients had a 17% lower risk of PONV than White patients (adjusted odds ratio [aOR], 0.83; 95% confidence interval [CI], 0.73-0.95; P = .006). When there was adherence to the PONV prophylaxis protocol, Black patients were less likely to experience PONV compared to White patients (aOR, 0.81; 95% CI, 0.70-0.93; P = .003). When there was adherence to the protocol, patients with Medicaid were less likely to experience PONV compared to privately insured patients (aOR, 0.72; 95% CI, 0.64-1.04; P = .017). When the protocol was followed for high-risk patients, Hispanic patients were more likely to experience PONV than White patients (aOR, 2.96; 95% CI, 1.18-7.42; adjusted P = .022). Compared to White patients, protocol adherence was lower for Black patients with moderate (aOR, 0.76; 95% CI, 0.64-0.91; P = .003) and high risk (aOR, 0.57; 95% CI, 0.42-0.78; P = .0004). CONCLUSIONS: Racial and sociodemographic disparities exist in the incidence of PONV and clinician adherence to a PONV prophylaxis protocol. Awareness of such disparities in PONV prophylaxis could improve the quality of perioperative care.


Assuntos
Anestesia , Antieméticos , Humanos , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Antieméticos/uso terapêutico , Estudos Retrospectivos , Incidência
3.
BMC Public Health ; 23(1): 424, 2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36869343

RESUMO

BACKGROUND: A relationship between smoking and interpersonal influences has been well established within the literature. There have been cultural shifts in denormalisation and a reduction in tobacco smoking in many countries. Hence there is a need to understand social influences on adolescents' smoking across smoking normalisation contexts. METHODS: The search was conducted in July 2019 and updated in March 2022 within 11 databases and secondary sources. Search terms included schools, adolescents, smoking, peers, social norms and qualitative research. Screening was conducted by two researchers independently and in duplicate. Study quality was assessed using the eight-item Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-centre) tool for the appraisal of qualitative studies. Results were synthesised using a meta-narrative lens for meta-ethnography and compared across smoking normalisation contexts. RESULTS: Forty one studies were included and five themes were developed, mapping onto the socio ecological model. The social processes by which adolescents take up smoking differed according to a mixture of school type, peer group structure and the smoking culture within the school, as well as the wider cultural context. Data available from smoking denormalised contexts, described changes in social interactions around smoking to cope with its stigmatisation. This was manifested through i) direct peer influence, whereby subtle techniques were employed, ii) group belonging whereby smoking was less likely to be seen as a key determinant of group membership and smoking was less commonly reported to be used as a social tool, and iii) popularity and identity construction, whereby smoking was perceived more negatively in a denormalised context, compared with a normalised context. CONCLUSIONS: This meta-ethnography is the first study to demonstrate, drawing on international data, that peer processes in adolescent smoking may undergo changes as smoking norms within society change. Future research should focus on understanding differences across socioeconomic contexts, to inform the adaptation of interventions.


Assuntos
Amigos , Controle do Tabagismo , Adolescente , Humanos , Fumar , Fumar Tabaco , Pesquisa Qualitativa , Antropologia Cultural
4.
JDR Clin Trans Res ; : 23800844211056241, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844457

RESUMO

INTRODUCTION: In any health system, choices must be made about the allocation of resources (budget), which are often scarce. Economics has defined frameworks to aid resource allocation, and program budgeting marginal analysis (PBMA) is one such framework. In principle, patient and public values can be incorporated into these frameworks, using techniques such as willingness to pay (WTP). However, this has not been done before, and few formal resource allocation processes have been undertaken in dentistry. This study aimed to undertake a PBMA with embedded WTP values in a national dental setting. METHODS: The PBMA process was undertaken by a panel of participant-researchers representing commissioners, dentists, dental public health staff, and academics. The panel reviewed current allocations and generated a set of weighted criteria to evaluate services against. Services to be considered for removal and investment were determined by the panel and wider discussion and then scored against the criteria. Values from a nationally representative WTP survey of the public contributed to the scores for interventions. Final decisions on removal and investment were taken after panel discussion using individual anonymous electronic voting. RESULTS: The PBMA process resulted in recommendations to invest in new program components to improve access to general dentists, care home dentistry, and extra support for dental public health input into local government decisions. Disinvestments were recommended in orthodontics and to remove routine scaling and polishing of teeth. DISCUSSION: The PBMA process was successful in raising awareness of resource allocation issues. Implementation of findings will depend on the ability of decision makers to find ways of operationalizing the decisions. The process illustrates practical aspects of the process that future dental PBMAs could learn from. KNOWLEDGE TRANSFER STATEMENT: This study illustrates a framework for resource allocation in dental health services and will aid decision makers in implementing their own resource allocation systems.

5.
BMC Med Educ ; 21(1): 464, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465325

RESUMO

BACKGROUND: The COVID-19 pandemic significantly impacted residency recruitment in 2020, posing unique challenges for programs and applicants alike. Anesthesiology programs have adopted alternate methods of recruitment, including virtual open houses and social media, due to limiting personal contact rules implemented by AAMC. This study was undertaken to determine the frequency of virtual events hosted and social media accounts created by programs. METHODS: Anesthesiology residency programs and departments were examined for social media presence on Twitter, Instagram, and Facebook. Programs' websites and social media posts were reviewed for virtual open house opportunities. Available sub-internships were collected from the Visiting Student Application Service database. Data was collected after 2020-2021 pre-interview recruitment in October 2020. RESULTS: Of 153 total anesthesiology residency programs, 96 (63%) had some form of social media presence. The platforms of choice for programs with social media accounts included Twitter (71, or 46%), Instagram (67, or 44%), and Facebook (47, or 31%). Forty of seventy-six residency-affiliated accounts were created after March 1, 2020; Instagram accounts (26 of 40) represented most of these. Most Anesthesiology programs (59%) offered virtual open houses for prospective applicants. Twitter (25%), Instagram (22%), and Facebook (8%) were used by programs to advertise these events. CONCLUSIONS: Social media presence of anesthesiology residency programs has grown steadily over the past decade, with exponential growth experienced in 2020. This data suggests that anesthesiology residency programs are employing new, mostly virtual, methods to reach prospective applicants during an unprecedented application cycle amidst the COVID-19 pandemic.


Assuntos
Anestesiologia , COVID-19 , Internato e Residência , Mídias Sociais , Humanos , Pandemias , Estudos Prospectivos , SARS-CoV-2
6.
Space Sci Rev ; 217(2): 29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33678912

RESUMO

The NASA Perseverance rover Mast Camera Zoom (Mastcam-Z) system is a pair of zoomable, focusable, multi-spectral, and color charge-coupled device (CCD) cameras mounted on top of a 1.7 m Remote Sensing Mast, along with associated electronics and two calibration targets. The cameras contain identical optical assemblies that can range in focal length from 26 mm ( 25.5 ∘ × 19.1 ∘ FOV ) to 110 mm ( 6.2 ∘ × 4.2 ∘ FOV ) and will acquire data at pixel scales of 148-540 µm at a range of 2 m and 7.4-27 cm at 1 km. The cameras are mounted on the rover's mast with a stereo baseline of 24.3 ± 0.1  cm and a toe-in angle of 1.17 ± 0.03 ∘ (per camera). Each camera uses a Kodak KAI-2020 CCD with 1600 × 1200 active pixels and an 8 position filter wheel that contains an IR-cutoff filter for color imaging through the detectors' Bayer-pattern filters, a neutral density (ND) solar filter for imaging the sun, and 6 narrow-band geology filters (16 total filters). An associated Digital Electronics Assembly provides command data interfaces to the rover, 11-to-8 bit companding, and JPEG compression capabilities. Herein, we describe pre-flight calibration of the Mastcam-Z instrument and characterize its radiometric and geometric behavior. Between April 26 t h and May 9 t h , 2019, ∼45,000 images were acquired during stand-alone calibration at Malin Space Science Systems (MSSS) in San Diego, CA. Additional data were acquired during Assembly Test and Launch Operations (ATLO) at the Jet Propulsion Laboratory and Kennedy Space Center. Results of the radiometric calibration validate a 5% absolute radiometric accuracy when using camera state parameters investigated during testing. When observing using camera state parameters not interrogated during calibration (e.g., non-canonical zoom positions), we conservatively estimate the absolute uncertainty to be < 10 % . Image quality, measured via the amplitude of the Modulation Transfer Function (MTF) at Nyquist sampling (0.35 line pairs per pixel), shows MTF Nyquist = 0.26 - 0.50 across all zoom, focus, and filter positions, exceeding the > 0.2 design requirement. We discuss lessons learned from calibration and suggest tactical strategies that will optimize the quality of science data acquired during operation at Mars. While most results matched expectations, some surprises were discovered, such as a strong wavelength and temperature dependence on the radiometric coefficients and a scene-dependent dynamic component to the zero-exposure bias frames. Calibration results and derived accuracies were validated using a Geoboard target consisting of well-characterized geologic samples. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11214-021-00795-x.

7.
Sci Adv ; 5(11): eaax6642, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31807704

RESUMO

Seismic noise interferometry is an exciting technique for studying volcanoes, providing a continuous measurement of seismic velocity changes (dv/v), which are sensitive to magmatic processes that affect the surrounding crust. However, understanding the exact mechanisms causing changes in dv/v is often difficult. We present dv/v measurements over 10 years in central Iceland, measured using single-station cross-component correlation functions from 51 instruments across a range of frequency bands. We observe a linear correlation between changes in dv/v and volumetric strain at stations in regions of both compression and dilatation associated with the 2014 Bárðarbunga-Holuhraun dike intrusion. Furthermore, a clear seasonal cycle in dv/v is modeled as resulting from elastic and poroelastic responses to changing snow thickness, atmospheric pressure, and groundwater level. This study comprehensively explains variations in dv/v arising from diverse crustal stresses and highlights the importance of deformation modeling when interpreting dv/v, with implications for volcano and environmental monitoring worldwide.

8.
J Intellect Disabil Res ; 63(12): 1391-1400, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31397022

RESUMO

BACKGROUND: The development of a nurse-led approach to managing epilepsy in adults with an intellectual disability (ID) offers the potential of improved outcomes and lower costs of care. We undertook a cluster randomised trial to assess the impact on costs and outcomes of the provision of ID nurses working to a designated epilepsy nurse competency framework. Here, we report the impact of the intervention on costs. METHOD: Across the United Kingdom, eight sites randomly allocated to the intervention recruited 184 participants and nine sites allocated to treatment as usual recruited 128 participants. Cost and outcome data were collected mainly by telephone interview at baseline and after 6 months. Total costs at 6 months were compared from the perspective of health and social services and society, with adjustments for pre-specified participant and cluster characteristics at baseline including costs. Missing data were imputed using multiple imputation. Uncertainty was quantified by bootstrapping. RESULTS: The intervention was associated with lower per participant costs from a health and social services perspective of -£357 (2014/2015 GBP) (95% confidence interval -£986, £294) and from a societal perspective of -£631 (95% confidence interval -£1473, £181). Results were not sensitive to the exclusion of accommodation costs. CONCLUSIONS: Our findings suggest that the competency framework is unlikely to increase the cost of caring for people with epilepsy and ID and may reduce costs.


Assuntos
Competência Clínica , Serviços de Saúde Comunitária , Epilepsia/terapia , Custos de Cuidados de Saúde , Deficiência Intelectual/terapia , Enfermeiras e Enfermeiros , Equipe de Assistência ao Paciente , Avaliação de Processos em Cuidados de Saúde , Adulto , Comorbidade , Epilepsia/epidemiologia , Humanos , Deficiência Intelectual/epidemiologia
9.
J Public Health (Oxf) ; 40(4): e578-e585, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29726998

RESUMO

Background: Priority setting is necessary where competing demands exceed the finite resources available. The aim of the study was to develop and test a prioritization framework based upon programme budgeting and marginal analysis (PBMA) as a tool to assist National Health Service (NHS) commissioners in their management of resources for local NHS dental services. Methods: Twenty-seven stakeholders (5 dentists, 8 commissioners and 14 patients) participated in a case-study based in a former NHS commissioning organization in the north of England. Stakeholders modified local decision-making criteria and applied them to a number of different scenarios. Results: The majority of financial resources for NHS dental services in the commissioning organization studied were allocated to primary care dental practitioners' contracts in perpetuity, potentially constraining commissioners' abilities to shift resources. Compiling the programme budget was successful, but organizational flux and difficulties engaging local NHS commissioners significantly impacted upon the marginal analysis phase. Conclusions: NHS dental practitioners' contracts resemble budget-silos which do not facilitate local resource reallocation. 'Context-specific' factors significantly challenged the successful implementation and impact of PBMA. A local PBMA champion embedded within commissioning organizations should be considered. Participants found visual depiction of the cost-value ratio helpful during their initial priority setting deliberations.


Assuntos
Orçamentos/organização & administração , Assistência Odontológica/organização & administração , Prioridades em Saúde/organização & administração , Medicina Estatal/organização & administração , Adulto , Comitês Consultivos , Idoso , Idoso de 80 Anos ou mais , Orçamentos/métodos , Análise Custo-Benefício/métodos , Tomada de Decisões Gerenciais , Assistência Odontológica/economia , Assistência Odontológica/métodos , Inglaterra , Feminino , Prioridades em Saúde/economia , Humanos , Masculino , Pessoa de Meia-Idade , Medicina Estatal/economia , Adulto Jovem
10.
Phys Rev Lett ; 119(18): 184801, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29219603

RESUMO

Experimental results are presented of a broadband, high power, gyrotron traveling wave amplifier (gyro-TWA) operating in the (75-110)-GHz frequency band and based on a helically corrugated interaction region. The second harmonic cyclotron mode of a 55-keV, 1.5-A, axis-encircling electron beam is used to resonantly interact with a traveling TE_{21}-like eigenwave achieving broadband amplification. The gyro-TWA demonstrates a 3-dB gain bandwidth of at least 5.5 GHz in the experimental measurement with 9 GHz predicted for a wideband drive source with a measured unsaturated output power of 3.4 kW and gain of 36-38 dB. The approach may allow a gyro-TWA to operate at 1 THz.

11.
Clin Transl Med ; 6(1): 41, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29101500

RESUMO

BACKGROUND: Nintedanib has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). It was approved by the National Institute for Health and Care Excellence (NICE) in January 2016 for IPF patients with a forced vital capacity (FVC) of 50-80% in the United Kingdom (UK). AIM: To report real world data about our early clinical experience using nintedanib in 187 patients with a multi-disciplinary (MDT) diagnosis of IPF in a manufacturer funded patient in need scheme (three UK centres) prior to NICE approval. METHODS: All patients with a MDT diagnosis of IPF from December 2014 to January 2016 commenced on nintedanib were included. Demographic details, adverse events (AEs) and where available lung function results were retrospectively collected from clinical letters. RESULTS: 187 patients (76% males) with a median age of 72 years (49-89) were treated with nintedanib. The average pre-treatment FVC was 81.1 ± 19.8% and diffusion capacity of the lungs for carbon monoxide was 43.9 ± 15% (n = 82). Fifty percent of patients started nintedanib because they were ineligible for pirfenidone due to an FVC > 80%. The median treatment course was 8 ± 4 months. The majority of patients experienced 1-3 AEs with nintedanib (52%, n = 97). The most frequent AEs were diarrhoea (50%), nausea (36%), reduced appetite (24%), tiredness (20%) and gastro-oesophageal reflux (18%). The majority of AEs resulted in no change in treatment (64%, n = 461). 21% (n = 150) of AEs resulted in a dose reduction and 13% (n = 94) necessitated discontinuation of treatment. 1 in 5 patients discontinued treatment either temporarily or on a permanent basis during the monitoring period. In a select cohort of patients, a statistically significant greater proportion of patients remained stable or improved and a lower proportion declined, as depicted by FVC changes of > 5% after nintedanib commencement (P < 0.05 using Chi squared test). CONCLUSIONS: Nintedanib is well tolerated and has an acceptable safety profile. Only 8% of those reporting diarrhoea discontinued treatment either on a temporary or permanent basis. There were no signals with respect to increased cardiovascular morbidity or major bleeding risk. This is in keeping with the INPULSIS clinical trial findings but in a real world cohort.

12.
Br J Biomed Sci ; 74(4): 163-169, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28657840

RESUMO

The impact of warfarin therapy on the functions of extrahepatic vitamin K-dependent proteins (VKDP) is less clearly understood and less widely recognised in clinical practice than that on the hepatic counterparts (clotting factors II, VII, IX and X). Warfarin inhibits osteocalcin, an abundant extrahepatic VKDP involved in the mineralisation and maturation of bone and thus, primarily by this mechanism, may have an adverse effect on bone health. Whilst some studies do link warfarin use to an increase in osteoporosis and fracture risk others have not. Warfarin also inhibits the extrahepatic VKDP matrix gla protein (MGP) which acts to prevent ectopic calcification of the vasculature. Studies have consistently found a correlation between warfarin use and vascular calcification with inhibition of MGP believed to be the main cause. Inhibition of MGP also appears to explain warfarin's well established teratogenic effect. Further adverse effects may also arise from warfarin's inhibition of other known extrahepatic VKDPs. The available evidence is intriguing, and suggests that the impact of warfarin on the extrahepatic functions of vitamin K-dependent proteins warrants further careful consideration.


Assuntos
Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas/metabolismo , Calcificação Vascular/tratamento farmacológico , Vitamina K/farmacologia , Varfarina/uso terapêutico , Animais , Osso e Ossos/efeitos dos fármacos , Humanos , Vitamina K/antagonistas & inibidores , Varfarina/efeitos adversos
13.
Genome Announc ; 3(1)2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25676750

RESUMO

The genome sequence of human herpesvirus 6A (HHV-6A) strain AJ was determined in a comparison of target enrichment and long-range PCR using next-generation sequencing methodologies. The analyses show 85 predicted open reading frames (ORFs), conservation with sequenced HHV-6A reference strain U1102, and closest identity to the recently determined GS strain, despite different geographic origins (United States and Gambia).

14.
Br J Hosp Med (Lond) ; 76(1): C2-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25585193
15.
Int Endod J ; 48(12): 1137-46, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25400281

RESUMO

AIM: To elicit the factors affecting willingness to pay (WTP) values for the preferred options of participants for dealing with a molar tooth with a nonvital pulp, a common but difficult problem. METHODOLOGY: A total of 503 patients were recruited from dental practices in the North East of England and interviewed. Their preferred treatment option for a molar tooth with a nonvital pulp (endodontics, extraction and various prosthetic restorative options) and WTP for this preferred option were elicited. Factors affecting preferred option and WTP were analysed using econometric modelling. RESULTS: Overall, 53% of the sample wished to save the tooth with a mean WTP of £373. The variance in WTP was high. Of those opting for extraction, the majority chose to leave a gap or have an implant. The preferred option was influenced by previous treatment experience. WTP was only influenced by having a low income. CONCLUSIONS: The high level of variance in WTP and its relatively unpredictable nature pose difficult questions for policy makers trying to ensure the delivery of an equitable service. For dentists, it is important not to make assumptions about patient preference and strength of preference when making decisions. Ideally, WTP values should be considered alongside effectiveness data, and those on costs, in policy making.


Assuntos
Restauração Dentária Permanente/economia , Preferência do Paciente , Tratamento do Canal Radicular/economia , Extração Dentária/economia , Dente não Vital/terapia , Adolescente , Adulto , Idoso , Tomada de Decisões , Escolaridade , Inglaterra , Feminino , Humanos , Renda/estatística & dados numéricos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Modelos Econométricos , Dente Molar , Classe Social
16.
Nat Commun ; 5: 4199, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24947142

RESUMO

The origin of bimodal (mafic-felsic) rock suites is a fundamental question in volcanology. Here we use major and trace elements, high-resolution Sr, Nd and Pb isotope analyses, experimental petrology and thermodynamic modelling to investigate bimodal magmatism at the iconic Carlingford Igneous Centre, Ireland. We show that early microgranites are the result of extensive assimilation of trace element-enriched partial melts of local metasiltstones into mafic parent magmas. Melting experiments reveal the crust is very fusible, but thermodynamic modelling indicates repeated heating events rapidly lower its melt-production capacity. Granite generation ceased once enriched partial melts could no longer form and subsequent magmatism incorporated less fertile restite compositions only, producing mafic intrusions and a pronounced compositional gap. Considering the frequency of bimodal magma suites in the North Atlantic Igneous Province, and the ubiquity of suitable crustal compositions, we propose 'progressively inhibited crustal assimilation' (PICA) as a major cause of bimodality in continental volcanism.

17.
Small Rumin Res ; 117(1): 34-40, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25844019

RESUMO

Previous work showed that the Texel muscling QTL (TM-QTL) results in pronounced hypertrophy in the loin muscle, with the largest phenotypic effects observed in lambs inheriting a single copy of the allele from the sire. As the loin runs parallel to the spinal vertebrae, and the development of muscle and bone are closely linked, the primary aim of this study was to investigate if there were any subsequent associations between TM-QTL inheritance and underlying spine characteristics (vertebrae number, VN; spine region length, SPL; average length of individual vertebrae, VL) of the thoracic, lumbar, and thoracolumbar spine regions. Spine characteristics were measured from X-ray computed tomography (CT) scans for 142 purebred Texel lambs which had been previously genotyped. Least-squares means were significantly different between genotype groups for lumbar and thoracic VN and lumbar SPL. Similarly for these traits, contrasts were shown to be significant for particular modes of gene action but overall were inconclusive. In general, the results showed little evidence that spine trait phenotypes were associated with differences in loin muscling associated with the different TM-QTL genotypes.

18.
Br J Biomed Sci ; 70(3): 110-20, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24273897

RESUMO

Multiple myeloma is the most common haematological malignancy yet currently it remains incurable. For decades the mainstay in therapy has been non-targeted approaches including genotoxic agents and immunosuppressants. With myeloma predominantly affecting an elderly population, who are vulnerable to aggressive therapy, these non-specific approaches have resulted in poor survival. However, in recent years an explosion of collaborative research into myeloma has identified molecular interactions between myeloma cells and the bone marrow microenvironment as promoting myeloma development and associated complications such as bone lesions due to osteolysis. At the same time, a better understanding of the adhesion molecules, cytokines and signalling pathways involved in myeloma has led to the development of new targeted therapies, which are improving the quality of life for patients and significantly extending median patient survival. This review explores the current understanding of molecular pathways that promote myeloma progression and lead to bone destruction, with particular reference to the influence of interactions with the bone marrow microenvironment. It describes molecular targets for therapy with reference to the new therapeutics and their improved efficacy. While the outlook for myeloma patients has improved in recent years as a result of these new approaches, drug resistance remains a problem and future therapies will also need to address the molecular mechanisms of resistance in order to improve further the outcome for patients with this disease.


Assuntos
Medula Óssea/fisiologia , Terapia de Alvo Molecular , Mieloma Múltiplo/fisiopatologia , Microambiente Tumoral , Animais , Humanos , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/terapia
19.
Phys Rev Lett ; 110(16): 165101, 2013 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-23679610

RESUMO

Experimental results are presented of the first successful gyrotron backward wave oscillator (gyro-BWO) with continuous frequency tuning near the low-terahertz region. A helically corrugated interaction region was used to allow efficient interaction over a wide frequency band at the second harmonic of the electron cyclotron frequency without parasitic output. The gyro-BWO generated a maximum output power of 12 kW when driven by a 40 kV, 1.5 A, annular-shaped large-orbit electron beam and achieved a frequency tuning band of 88-102.5 GHz by adjusting the cavity magnetic field. The performance of the gyro-BWO is consistent with 3D particle-in-cell numerical simulations.

20.
J Anim Sci ; 91(2): 995-1004, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23243168

RESUMO

Implementing the use of spine traits in a commercial breeding program has been seen to improve meat production from the carcass of larger-bodied pigs. The aim of this study was to assess the extent of variation in spine characteristics within and between breeds of sheep and to investigate the association with body length and tissues traits to deliberate if a similar approach could be applicable in the sheep sector. Spine traits (vertebrae number, VN; spine region length, SPL; individual vertebra length, VL) of the thoracic (THOR) lumbar (LUM) and thoracolumbar (T+L) spine regions were measured using x-ray computed tomography (CT) on 254 Texel (TEX), 1100 Scottish Blackface (SBF), 326 Texel cross Mule (TEX × MULE), and 178 Poll Dorset cross Mule (PD × MULE) lambs. Simple descriptive statistics inform that variation in thoracolumbar VN exists within all breeds and crosses; TEX animals showed the largest range of variation in thoracolumbar VN (17 to 21) and the TEX × MULE the smallest (18 to 20). Significant differences were not observed between sexes, but did occur between breeds (P < 0.05), which is indicative of a genetic basis for these traits. Least-squares means identified that TEX had the least thoracolumbar VN (19.24) and SBF possessed the most (19.63); similarly the lowest measures for SPL and VL for each spine region were observed in TEX, but the greatest values for these traits were expressed predominantly in the crosses (TEX × MULE and PD × MULE). Correlation coefficients (r) within each breed or cross support the interpretation of additional vertebrae contributing to a longer length of the spine region in which they occur (P < 0.001; e.g., for PD × MULE lambs), r between traits VNTHOR and SPLTHOR (r = 0.59), VNLUM and SPLLUM (r = 0.94) and VNT+L and SPLT+L (r = 0.65) all reach moderate to very high values. In all breeds and crosses, this relationship is particularly strong for the lumbar region. The few significant (P < 0.05) correlations observed between spine and tissue traits [CT-predicted quantities of carcass fat and muscle (kg) and area of the LM (mm(2))] indicated no substantial relationships, r was small (ranging from -0.25 to 0.19) in each case. To conclude, significant vertebral variation exists within and between sheep breeds and crosses, which can contribute to an increase in body (and carcass) length. Including measurements taken for other primal cuts will further aid in assessing any potential increase in meat production from these longer-bodied sheep.


Assuntos
Ovinos/anatomia & histologia , Ovinos/genética , Coluna Vertebral/anatomia & histologia , Coluna Vertebral/crescimento & desenvolvimento , Animais , Cruzamento , Feminino , Masculino , Seleção Genética , Tomografia Computadorizada por Raios X
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