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1.
Nature ; 615(7954): 817-822, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36746190

RESUMEN

Quantum computation features known examples of hardware acceleration for certain problems, but is challenging to realize because of its susceptibility to small errors from noise or imperfect control. The principles of fault tolerance may enable computational acceleration with imperfect hardware, but they place strict requirements on the character and correlation of errors1. For many qubit technologies2-21, some challenges to achieving fault tolerance can be traced to correlated errors arising from the need to control qubits by injecting microwave energy matching qubit resonances. Here we demonstrate an alternative approach to quantum computation that uses energy-degenerate encoded qubit states controlled by nearest-neighbour contact interactions that partially swap the spin states of electrons with those of their neighbours. Calibrated sequences of such partial swaps, implemented using only voltage pulses, allow universal quantum control while bypassing microwave-associated correlated error sources1,22-28. We use an array of six 28Si/SiGe quantum dots, built using a platform that is capable of extending in two dimensions following processes used in conventional microelectronics29. We quantify the operational fidelity of universal control of two encoded qubits using interleaved randomized benchmarking30, finding a fidelity of 96.3% ± 0.7% for encoded controlled NOT operations and 99.3% ± 0.5% for encoded SWAP. The quantum coherence offered by enriched silicon5-9,16,18,20,22,27,29,31-37, the all-electrical and low-crosstalk-control of partial swap operations1,22-28 and the configurable insensitivity of our encoding to certain error sources28,33,34,38 all combine to offer a strong pathway towards scalable fault tolerance and computational advantage.

2.
Curr Issues Mol Biol ; 45(7): 6055-6066, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37504298

RESUMEN

Bovine tuberculosis is endemic in Nigeria with control measures as provided by the laws of the country being minimally enforced mostly at the abattoirs only. This study focused on bovine tuberculosis in Adamawa and Gombe States. Tuberculosis lesions were observed in 183 of 13,688 slaughtered cattle in the regions between June and December 2020. Analysis of tissue samples resulted in 17 Mycobacterium bovis isolates, predominantly from Gombe State. Spoligotyping identified four spoligotypes, including SB0944, SB1025, SB1104, and one novel pattern. MIRU-VNTR analysis further differentiated these spoligotypes into eight profiles. All isolates belonged to the Af1 clonal complex. The study emphasises the need for broader coverage and more isolates to comprehensively understand the molecular epidemiology of bovine tuberculosis in Nigeria. To enhance research and surveillance, a cost-effective approach is proposed, utilising a discriminatory VNTR panel comprising five or nine loci. The five-locus panel consists of ETR-C, QUB26, QUB11b, MIRU04, and QUB323. Alternatively, the nine-locus panel includes ETR-A, ETR-B, QUB11a, and MIRU26. Implementing this approach would provide valuable insights into the genetic diversity of M. bovis strains in Nigeria. These findings are crucial for developing effective control measures and minimising the impact of bovine tuberculosis on both animal and human health.

3.
J Environ Manage ; 345: 118325, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37390730

RESUMEN

Spatial management of the deep sea is challenging due to limited available data on the distribution of species and habitats to support decision making. In the well-studied North Atlantic, predictive models of species distribution and habitat suitability have been used to fill data gaps and support sustainable management. In the South Atlantic and other poorly studied regions, this is not possible due to a massive lack of data. In this study, we investigated whether models constructed in data-rich areas can be used to inform data-poor regions (with otherwise similar environmental conditions). We used a novel model transfer approach to identify to what extent a habitat suitability model for Desmophyllum pertusum reef, built in a data-rich basin (North Atlantic), could be transferred usefully to a data-poor basin (South Atlantic). The transferred model was built using the Maximum Entropy algorithm and constructed with 227 presence and 3064 pseudo-absence points, and 200 m resolution environmental grids. Performance in the transferred region was validated using an independent dataset of D. pertusum presences and absences, with assessments made using both threshold-dependent and -independent metrics. We found that a model for D. pertusum reef fitted to North Atlantic data transferred reasonably well to the South Atlantic basin, with an area under the curve of 0.70. Suitable habitat for D. pertusum reef was predicted on 20 of the assessed 27 features including seamounts. Nationally managed Marine Protected Areas provide significant protection for D. pertusum reef habitat in the region, affording full protection from bottom trawling to 14 of the 20 suitable features. In areas beyond national jurisdiction (ABNJ), we found four seamounts that provided suitable habitat for D. pertusum reef to be at least partially protected from bottom trawling, whilst two did not fall within fisheries closures. There are factors to consider when developing models for transfer including data resolution and predictor type. Nevertheless, the promising results of this application demonstrate that model transfer approaches stand to provide significant contributions to spatial planning processes through provision of new, best available data. This is particularly true for ABNJ and areas that have previously undergone little scientific exploration such as the global south.


Asunto(s)
Algoritmos , Ecosistema , Explotaciones Pesqueras , Arrecifes de Coral
4.
Glob Chang Biol ; 28(1): 8-20, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34658117

RESUMEN

Global warming is causing significant losses of marine ice around the polar regions. In Antarctica, the retreat of tidewater glaciers is opening up novel, low-energy habitats (fjords) that have the potential to provide a negative feedback loop to climate change. These fjords are being colonized by organisms on and within the sediment and act as a sink for particulate matter. So far, blue carbon potential in Antarctic habitats has mainly been estimated using epifaunal megazoobenthos (although some studies have also considered macrozoobenthos). We investigated two further pathways of carbon storage and potential sequestration by measuring the concentration of carbon of infaunal macrozoobenthos and total organic carbon (TOC) deposited in the sediment. We took samples along a temporal gradient since time of last glacier ice cover (1-1000 years) at three fjords along the West Antarctic Peninsula. We tested the hypothesis that seabed carbon standing stock would be mainly driven by time since last glacier covered. However, results showed this to be much more complex. Infauna were highly variable over this temporal gradient and showed similar total mass of carbon standing stock per m2 as literature estimates of Antarctic epifauna. TOC mass in the sediment, however, was an order of magnitude greater than stocks of infaunal and epifaunal carbon and increased with time since last ice cover. Thus, blue carbon stocks and recent gains around Antarctica are likely much higher than previously estimated as is their negative feedback on climate change.


Asunto(s)
Cambio Climático , Cubierta de Hielo , Regiones Antárticas , Carbono , Ecosistema , Estuarios , Retroalimentación
5.
Glob Chang Biol ; 28(8): 2555-2577, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34951743

RESUMEN

A multitude of actions to protect, sustainably manage and restore natural and modified ecosystems can have co-benefits for both climate mitigation and biodiversity conservation. Reducing greenhouse emissions to limit warming to less than 1.5 or 2°C above preindustrial levels, as outlined in the Paris Agreement, can yield strong co-benefits for land, freshwater and marine biodiversity and reduce amplifying climate feedbacks from ecosystem changes. Not all climate mitigation strategies are equally effective at producing biodiversity co-benefits, some in fact are counterproductive. Moreover, social implications are often overlooked within the climate-biodiversity nexus. Protecting biodiverse and carbon-rich natural environments, ecological restoration of potentially biodiverse and carbon-rich habitats, the deliberate creation of novel habitats, taking into consideration a locally adapted and meaningful (i.e. full consequences considered) mix of these measures, can result in the most robust win-win solutions. These can be further enhanced by avoidance of narrow goals, taking long-term views and minimizing further losses of intact ecosystems. In this review paper, we first discuss various climate mitigation actions that evidence demonstrates can negatively impact biodiversity, resulting in unseen and unintended negative consequences. We then examine climate mitigation actions that co-deliver biodiversity and societal benefits. We give examples of these win-win solutions, categorized as 'protect, restore, manage and create', in different regions of the world that could be expanded, upscaled and used for further innovation.


Asunto(s)
Cambio Climático , Ecosistema , Biodiversidad , Carbono , Clima , Conservación de los Recursos Naturales/métodos
6.
Glob Chang Biol ; 28(9): 2846-2874, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35098619

RESUMEN

The two most urgent and interlinked environmental challenges humanity faces are climate change and biodiversity loss. We are entering a pivotal decade for both the international biodiversity and climate change agendas with the sharpening of ambitious strategies and targets by the Convention on Biological Diversity and the United Nations Framework Convention on Climate Change. Within their respective Conventions, the biodiversity and climate interlinked challenges have largely been addressed separately. There is evidence that conservation actions that halt, slow or reverse biodiversity loss can simultaneously slow anthropogenic mediated climate change significantly. This review highlights conservation actions which have the largest potential for mitigation of climate change. We note that conservation actions have mainly synergistic benefits and few antagonistic trade-offs with climate change mitigation. Specifically, we identify direct co-benefits in 14 out of the 21 action targets of the draft post-2020 global biodiversity framework of the Convention on Biological Diversity, notwithstanding the many indirect links that can also support both biodiversity conservation and climate change mitigation. These relationships are context and scale-dependent; therefore, we showcase examples of local biodiversity conservation actions that can be incentivized, guided and prioritized by global objectives and targets. The close interlinkages between biodiversity, climate change mitigation, other nature's contributions to people and good quality of life are seldom as integrated as they should be in management and policy. This review aims to re-emphasize the vital relationships between biodiversity conservation actions and climate change mitigation in a timely manner, in support to major Conferences of Parties that are about to negotiate strategic frameworks and international goals for the decades to come.


Asunto(s)
Conservación de los Recursos Naturales , Calidad de Vida , Biodiversidad , Cambio Climático , Ecosistema , Humanos
7.
BMC Cancer ; 22(1): 629, 2022 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-35672690

RESUMEN

The phase III clinical study of adjuvant liposomal muramyl tripeptide (MTP-PE) in resected high-grade osteosarcoma (OS) documented positive results that have been translated into regulatory approval, supporting initial promise for innate immune therapies in OS. There remains, however, no new approved treatment such as MTP-PE for either metastatic or recurrent OS. Whilst the addition of different agents, including liposomal MTP-PE, to surgery for metastatic or recurrent high-grade osteosarcoma has tried to improve response rates, a mechanistic hiatus exists in terms of a detailed understanding the therapeutic strategies required in advanced disease. Here we report a Bayesian designed multi-arm, multi-centre, open-label phase II study with randomisation in patients with metastatic and/or recurrent OS, designed to investigate how patients with OS might respond to liposomal MTP-PE, either given alone or in combination with ifosfamide. Despite the trial closing because of poor recruitment within the allocated funding period, with no objective responses in eight patients, we report the design and feasibility outcomes for patients registered into the trial. We demonstrate the feasibility of the Bayesian design, European collaboration, tissue collection with genomic analysis and serum cytokine characterisation. Further mechanistic investigation of liposomal MTP-PE alone and in combination with other agents remains warranted in metastatic OS.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Teorema de Bayes , Biomarcadores , Neoplasias Óseas/patología , Humanos , Liposomas , Recurrencia Local de Neoplasia/tratamiento farmacológico , Osteosarcoma/patología , Fosfatidiletanolaminas
8.
Subst Use Misuse ; 57(8): 1248-1256, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35611936

RESUMEN

BACKGROUND: Unintentional drug overdose has increased markedly in the United States. Studies document an association between psychiatric disorder and unintentional overdose; we extend this research through a preliminary test of a causal model of recurrent injection drug use mediating this relationship. METHODS: In a cross-sectional study of 241 adults in New York City with a possible current substance use disorder, we conducted conventional and Imai's mediation analyses to examine if psychiatric disorder is associated with increased prevalence of ever overdosing and if recurrent injection drug use mediates this association. Our cross-sectional data permit the first step of assessing causal models: testing if statistical associations are consistent with the model. RESULTS: Fifty-eight percent of the sample endorsed previous psychiatric disorder diagnosis and 35.7% reported ever overdosing. Imai's mediation analysis showed that, adjusting for covariates, the total association between psychiatric diagnosis and ever overdosing (adjusted prevalence difference [aPD] = 0.16, 95% CI 0.04-0.28) was composed of a direct effect (aPD = 0.09, 95% CI -0.03 - 0.21, p = 0.136) and an indirect effect (aPD = 0.07, 95% CI 0.02-0.13). Recurrent injecting drug use contributed to 42% (ratio of indirect effect to total effect; 95% CI 12 - 100%, p = 0.02) of the association between psychiatric diagnosis and ever overdosing. Conventional mediation analysis produced similar results. CONCLUSIONS: Our results provide a warrant for taking the necessary next step for assessing a causal model using longitudinal data, potentially providing a strong rationale for intervening on psychiatric disorders to stem overdose.


Asunto(s)
Sobredosis de Droga , Trastornos Mentales , Abuso de Sustancias por Vía Intravenosa , Trastornos Relacionados con Sustancias , Adulto , Estudios Transversales , Sobredosis de Droga/epidemiología , Humanos , Trastornos Mentales/epidemiología , Prevalencia , Abuso de Sustancias por Vía Intravenosa/epidemiología , Trastornos Relacionados con Sustancias/epidemiología
9.
Glob Chang Biol ; 27(13): 3157-3165, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33861505

RESUMEN

All coastal systems experience disturbances and many across the planet are under unprecedented threat from an intensification of a variety of stressors. The West Antarctic Peninsula is a hotspot of physical climate change and has experienced a dramatic loss of sea-ice and glaciers in recent years. Among other things, sea-ice immobilizes icebergs, reducing collisions between icebergs and the seabed, thus decreasing ice-scouring. Ice disturbance drives patchiness in successional stages across seabed assemblages in Antarctica's shallows, making this an ideal system to understand the ecosystem resilience to increasing disturbance with climate change. We monitored a shallow benthic ecosystem before, during and after a 3-year pulse of catastrophic ice-scouring events and show that such systems can return, or bounce back, to previous states within 10 years. Our long-term data series show that recovery can happen more rapidly than expected, when disturbances abate, even in highly sensitive cold, polar environments.


Asunto(s)
Cambio Climático , Ecosistema , Regiones Antárticas , Cubierta de Hielo
10.
Glob Chang Biol ; 27(1): 5-12, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33064891

RESUMEN

Precautionary conservation and cooperative global governance are needed to protect Antarctic blue carbon: the world's largest increasing natural form of carbon storage with high sequestration potential. As patterns of ice loss around Antarctica become more uniform, there is an underlying increase in carbon capture-to-storage-to-sequestration on the seafloor. The amount of carbon captured per unit area is increasing and the area available to blue carbon is also increasing. Carbon sequestration could further increase under moderate (+1°C) ocean warming, contrary to decreasing global blue carbon stocks elsewhere. For example, in warmer waters, mangroves and seagrasses are in decline and benthic organisms are close to their physiological limits, so a 1°C increase in water temperature could push them above their thermal tolerance (e.g. bleaching of coral reefs). In contrast, on the basis of past change and current research, we expect that Antarctic blue carbon could increase by orders of magnitude. The Antarctic seafloor is biophysically unique and the site of carbon sequestration, the benthos, faces less anthropogenic disturbance than any other ocean continental shelf environment. This isolation imparts both vulnerability to change, and an avenue to conserve one of the world's last biodiversity refuges. In economic terms, the value of Antarctic blue carbon is estimated at between £0.65 and £1.76 billion (~2.27 billion USD) for sequestered carbon in the benthos around the continental shelf. To balance biodiversity protection against society's economic objectives, this paper builds on a proposal incentivising protection by building a 'non-market framework' via the 2015 Paris Agreement to the United Nations Framework Convention on Climate Change. This could be connected and coordinated through the Antarctic Treaty System to promote and motivate member states to value Antarctic blue carbon and maintain scientific integrity and conservation for the positive societal values ingrained in the Antarctic Treaty System.


Asunto(s)
Carbono , Ecosistema , Regiones Antárticas , Secuestro de Carbono , Paris
11.
Eur J Cancer Care (Engl) ; 30(6): e13492, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34312918

RESUMEN

OBJECTIVE: Lung cancer patients from ethnic minorities have poorer outcomes than their Caucasian counterparts. We compared lung cancer intervals between culturally and linguistically diverse (CALD) and Anglo-Australian patients to identify ethnic disparities. METHODS: This was a prospective, observational cohort study comprising a patient survey and reviews of patients' hospital and general practice records. Across three states, 577 (407 Anglo-Australian and 170 CALD) patients were recruited and their hospital records reviewed. The survey was returned by 189 (135 Anglo-Australian and 54 CALD) patients, and a review was completed by general practitioners (GPs) of 99 (76 Anglo-Australian and 23 CALD) patients. Survival and Cox regression analyses were conducted. RESULTS: CALD patients had longer hospital diagnostic interval [median 30 days, 95% confidence interval (CI) 26-34] than Anglo-Australian patients (median 17, 95% CI 14-20), p = 0.005, hazard ratio (HR) = 1.32 (95% CI 1.09-1.60). This difference persisted after relevant factors were taken into consideration, adjusted HR = 1.26 (95% CI 1.03-1.54, p = 0.022). CALD patients also reported longer prehospital intervals; however, these differences were not statistically significant. CONCLUSION: Target interventions need to be developed to address ethnic disparity in hospital diagnostic interval.


Asunto(s)
Etnicidad , Neoplasias Pulmonares , Australia , Humanos , Estudios Prospectivos , Población Blanca
12.
Harm Reduct J ; 18(1): 39, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33794927

RESUMEN

BACKGROUND: Between December 2018 and January of 2019, we evaluated the accuracy of the point-of-care Hepatitis C (HCV) antibody test (POC; OraQuick HCV) used at a community-based needle and syringe exchange program serving persons who inject drugs in Tallinn, Estonia. METHODS: We compared the results of screening for HCV antibodies by OraQuick (oral swab) and enzyme immunoassay (EIA; blood draw) and assessed test results implications in a high prevalence setting. Findings Of the 100 participants, 88 (88%) had reactive POC test results, and 93 were HCV antibody positive on EIA testing. Sensitivity, specificity and negative predictive value (NPV) for the POC assay with EIA as the relevant reference test were as follows: 94.6% (95% CI 90.0-99.2%), 100% and 58.3% (95% CI 30.4-86.2%). Of the 12 testing, HCV-negative with the POC only 7 (58.3%) were true negatives. CONCLUSIONS: Oral swab rapid testing HCV screening in this nonclinical setting was sensitive and specific but had unacceptably low NPV. In high prevalence settings, POC tests with high sensitivity and that directly measure HCV RNA may be warranted.


Asunto(s)
Consumidores de Drogas , Hepatitis C , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa , Estonia/epidemiología , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C , Humanos , Sistemas de Atención de Punto , Prevalencia , Abuso de Sustancias por Vía Intravenosa/epidemiología
13.
Int J Mol Sci ; 22(21)2021 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-34769007

RESUMEN

TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation.


Asunto(s)
Encéfalo/metabolismo , Inflamación/metabolismo , Macrófagos/metabolismo , Esclerosis Múltiple/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Células Cultivadas , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Microglía/metabolismo , ARN Mensajero/metabolismo
14.
Glob Chang Biol ; 26(5): 2750-2755, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32108972

RESUMEN

Rising atmospheric CO2 is intensifying climate change but it is also driving global and particularly polar greening. However, most blue carbon sinks (that held by marine organisms) are shrinking, which is important as these are hotspots of genuine carbon sequestration. Polar blue carbon increases with losses of marine ice over high latitude continental shelf areas. Marine ice (sea ice, ice shelf and glacier retreat) losses generate a valuable negative feedback on climate change. Blue carbon change with sea ice and ice shelf losses has been estimated, but not how blue carbon responds to glacier retreat along fjords. We derive a testable estimate of glacier retreat driven blue carbon gains by investigating three fjords in the West Antarctic Peninsula (WAP). We started by multiplying ~40 year mean glacier retreat rates by the number of retreating WAP fjords and their time of exposure. We multiplied this area by regional zoobenthic carbon means from existing datasets to suggest that WAP fjords generate 3,130 tonnes of new zoobenthic carbon per year (t zC/year) and sequester >780 t zC/year. We tested this by capture and analysis of 204 high resolution seabed images along emerging WAP fjords. Biota within these images were identified to density per 13 functional groups. Mean stored carbon per individual was assigned from literature values to give a stored zoobenthic Carbon per area, which was multiplied up by area of fjord exposed over time, which increased the estimate to 4,536 t zC/year. The purpose of this study was to establish a testable estimate of blue carbon change caused by glacier retreat along Antarctic fjords and thus to establish its relative importance compared to polar and other carbon sinks.


Asunto(s)
Carbono , Estuarios , Regiones Antárticas , Ecosistema , Cubierta de Hielo
15.
Glob Chang Biol ; 26(4): 2702-2716, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31930639

RESUMEN

The Antarctic is considered to be a pristine environment relative to other regions of the Earth, but it is increasingly vulnerable to invasions by marine, freshwater and terrestrial non-native species. The Antarctic Peninsula region (APR), which encompasses the Antarctic Peninsula, South Shetland Islands and South Orkney Islands, is by far the most invaded part of the Antarctica continent. The risk of introduction of invasive non-native species to the APR is likely to increase with predicted increases in the intensity, diversity and distribution of human activities. Parties that are signatories to the Antarctic Treaty have called for regional assessments of non-native species risk. In response, taxonomic and Antarctic experts undertook a horizon scanning exercise using expert opinion and consensus approaches to identify the species that are likely to present the highest risk to biodiversity and ecosystems within the APR over the next 10 years. One hundred and three species, currently absent in the APR, were identified as relevant for review, with 13 species identified as presenting a high risk of invading the APR. Marine invertebrates dominated the list of highest risk species, with flowering plants and terrestrial invertebrates also represented; however, vertebrate species were thought unlikely to establish in the APR within the 10 year timeframe. We recommend (a) the further development and application of biosecurity measures by all stakeholders active in the APR, including surveillance for species such as those identified during this horizon scanning exercise, and (b) use of this methodology across the other regions of Antarctica. Without the application of appropriate biosecurity measures, rates of introductions and invasions within the APR are likely to increase, resulting in negative consequences for the biodiversity of the whole continent, as introduced species establish and spread further due to climate change and increasing human activity.

16.
Thorax ; 74(4): 362-370, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30630891

RESUMEN

BACKGROUND: International research has focused on screening and mass media campaigns to promote earlier patient presentation and detect lung cancer earlier. This trial tested the effect of a behavioural intervention in people at increased risk of lung cancer on help-seeking for respiratory symptoms. METHODS: Parallel, individually randomised controlled trial. Eligible participants were long-term smokers with at least 20 pack-years, aged 55 and above. The CHEST intervention entailed a consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to encourage help-seeking for respiratory symptoms. The control group received a brief discussion about lung health. Both groups had baseline spirometry. Telephone randomisation was conducted, 1:1, stratified Medical Research Council (MRC) dyspnoea score and general practice. Participants could not be blinded; data extraction and statistical analyses were performed blinded to group assignment. The primary outcome was respiratory consultation rates. RESULTS: We randomised 551 participants (274 intervention, 277 control) from whom the primary outcome was determined for 542 (269 intervention, 273 control). There was a 40% relative increase in respiratory consultations in the intervention group: (adjusted rates (95% CI) intervention 0.57 (0.47 to 0.70), control 0.41 (0.32 to 0.52), relative rate 1.40 (1.08 to 1.82); p=0.0123). There were no significant differences in time to first respiratory consultation, total consultation rates or measures of psychological harm. The incremental cost-effectiveness ratio was $A1289 per additional respiratory consultation. CONCLUSIONS: A behavioural intervention can significantly increase consulting for respiratory symptoms in patients at increased risk of lung cancer. This intervention could have an important role in primary care as part of a broader approach to improve respiratory health in patients at higher risk. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (1261300039 3752). This was registered pre-results.


Asunto(s)
Neoplasias Pulmonares/diagnóstico , Aceptación de la Atención de Salud/estadística & datos numéricos , Fumadores/psicología , Anciano , Australia , Autoevaluación Diagnóstica , Detección Precoz del Cáncer/métodos , Femenino , Conductas Relacionadas con la Salud , Humanos , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Trastornos Respiratorios/etiología , Autocuidado , Fumar/efectos adversos
17.
J Org Chem ; 84(8): 4837-4845, 2019 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-30716275

RESUMEN

( R)-Boc-2-methylproline (3a) was synthesized in good yield with excellent stereochemical control from alanine benzyl ester hydrochloride 11. The process, which is based on a modification of one described by Kawabata, proceeds in four steps and requires no chromatography. The product ( R)-Boc-2-methylproline (3a) was then carried forward in three steps to produce veliparib 1, a poly(ADP-ribose) polymerase inhibitor.


Asunto(s)
Antineoplásicos/farmacología , Bencimidazoles/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Prolina/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Bencimidazoles/síntesis química , Bencimidazoles/química , Ciclización , Humanos , Estructura Molecular , Inhibidores de Poli(ADP-Ribosa) Polimerasas/síntesis química , Inhibidores de Poli(ADP-Ribosa) Polimerasas/química , Prolina/análogos & derivados , Prolina/síntesis química , Prolina/química
18.
J Org Chem ; 84(8): 4873-4892, 2019 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-30629443

RESUMEN

Dasabuvir (1) is an HCV polymerase inhibitor which has been developed as a part of a three-component direct-acting antiviral combination therapy. During the course of the development of the synthetic route, two novel coupling reactions were developed. First, the copper-catalyzed coupling of uracil with aryl iodides, employing picolinamide 16 as the ligand, was discovered. Later, the palladium-catalyzed sulfonamidation of aryl nonaflate 33 was developed, promoted by electron-rich palladium complexes, including the novel phosphine ligand, VincePhos (50). This made possible a convergent, highly efficient synthesis of dasabuvir that significantly reduced the mutagenic impurity burden of the process.


Asunto(s)
Antivirales/farmacología , Inhibidores Enzimáticos/farmacología , Hepacivirus/efectos de los fármacos , Paladio/química , Sulfonamidas/farmacología , Uracilo/análogos & derivados , Proteínas no Estructurales Virales/antagonistas & inhibidores , 2-Naftilamina , Antivirales/síntesis química , Antivirales/química , Catálisis , Desarrollo de Medicamentos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Hepacivirus/enzimología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Sulfonamidas/síntesis química , Sulfonamidas/química , Uracilo/síntesis química , Uracilo/química , Uracilo/farmacología , Proteínas no Estructurales Virales/metabolismo
19.
AIDS Behav ; 23(9): 2304-2314, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30879209

RESUMEN

We tested the hypothesis that an updated "Break the Cycle" (BtC) intervention, based in social cognitive theory and motivational interviewing, would reduce the likelihood that current persons who inject drugs (PWID) would assist persons who do not inject drugs (non-PWID) with first injections in Tallinn, Estonia and Staten Island, New York City. 402 PWID were recruited, a baseline interview covering demographics, drug use, and assisting non-PWID with first drug injections was administered, followed by BtC intervention. 296 follow-up interviews were conducted 6 months post-intervention. Percentages assisting with first injections declined from 4.7 to 1.3% (73% reduction) in Tallinn (p < 0.02), and from 15 to 6% (60% reduction) in Staten Island (p < 0.05). Persons assisted with first injections declined from 11 to 3 in Tallinn (p = 0.02) and from 32 to 13 in Staten Island. (p = 0.024). Further implementation research on BtC interventions is urgently needed where injecting drug use is driving HIV/HCV epidemics and areas experiencing opioid epidemics.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Consumidores de Drogas/psicología , Epidemias , Trastornos Relacionados con Opioides/psicología , Adulto , Analgésicos Opioides/efectos adversos , Estonia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Entrevista Motivacional , Ciudad de Nueva York/epidemiología , Trastornos Relacionados con Opioides/epidemiología , Asunción de Riesgos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Abuso de Sustancias por Vía Intravenosa/prevención & control , Abuso de Sustancias por Vía Intravenosa/psicología
20.
Support Care Cancer ; 27(2): 485-493, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29980906

RESUMEN

PURPOSE: Improving the coordination of care for people with lung cancer is a health priority. This study aimed to tailor an existing care coordination survey for a lung cancer population, investigate coordination experiences for patients who had received hospital-based treatment and identify any factors that may be associated with poor care coordination. METHODS: We conducted a cross-sectional survey of lung patients within two tertiary hospitals in Sydney, Australia. The Cancer Care Coordination Questionnaire for Patients (CCCQ-P) is a psychometrically valid and reliable survey originally developed for colorectal cancer. We pilot tested a survey adaptation with lung cancer patients, support group members and medical specialists (n = 49). A revised survey was mailed to eligible patients via their medical specialist. RESULTS: Fifty-three of 118 eligible participants (45%) completed the CCCQ-P; most had early-stage disease and were about 70 years old. Overall, participants reported positive experiences of care coordination (mean total score 78.1), with high scores on communication and navigation subscales. The most problematic areas related to administrative aspects of care coordination and communication and information provision. Two patient groups (those residing in regional and rural areas, or no experience with the health system prior to diagnosis) reported significantly lower scores on the navigation subscale. CONCLUSIONS: This study found that lung cancer patients' experience of care coordination was positive, but highlighted the need for strategies to assist patients living in rural areas, and those with no experience of the health care system. The CCCQ-P survey instrument can be used in future lung cancer studies.


Asunto(s)
Atención a la Salud/tendencias , Neoplasias Pulmonares/diagnóstico , Anciano , Comunicación , Estudios Transversales , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Encuestas y Cuestionarios
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