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1.
Cancers (Basel) ; 16(11)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38893135

RESUMEN

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for patients with acute myeloid leukemia (AML). However, the post-transplant relapse rate ranges from 40 to 70%, particularly with reduced intensity conditioning, and remains a major cause of treatment failure for these patients due to the limited efficacy of salvage therapy options. Strategies to mitigate this risk are urgently needed. In the past few years, the basic framework of post-transplant maintenance has been shaped by several clinical trials investigating targeted therapy, chemotherapy, and immunomodulatory therapies. Although the practice of post-transplant maintenance in AML has become more common, there remain challenges regarding the feasibility and efficacy of this strategy. Here, we review major developments in post-transplant maintenance in AML, along with ongoing and future planned studies in this area, outlining the limitations of available data and our future goals.

2.
EJHaem ; 5(3): 560-564, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38895080

RESUMEN

Relapse remains a major cause of treatment failure following allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We retrospectively investigated low-dose decitabine and venetoclax (DEC/VEN) as post-transplant maintenance in 26 older patients with AML and MDS. The cumulative incidence of day 100 gIII-IV acute graft versus host disease (GVHD) and 1-year moderate-severe chronic GVHD was 5% and 26%, respectively. One patient relapsed 14 m after transplant. The 1-year non-relapse mortality and survival were 11% and 84%, respectively. DEC/VEN is a safe and potentially effective strategy to reduce the risk of post-transplant relapse.

3.
Mol Plant Microbe Interact ; 31(10): 1095-1110, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29767548

RESUMEN

Chloroplasts play a central role in pathogen defense in plants. However, most studies explaining the relationship between pathogens and chloroplasts have focused on pathogens that infect mesophyll cells. In contrast, the family Luteoviridae includes RNA viruses that replicate and traffic exclusively in the phloem. Recently, our lab has shown that Potato leafroll virus (PLRV), the type species in the genus Polerovirus, forms an extensive interaction network with chloroplast-localized proteins that is partially dependent on the PLRV capsid readthrough domain (RTD). In this study, we used virus-induced gene silencing to disrupt chloroplast function and assess the effects on PLRV accumulation in two host species. Silencing of phytoene desaturase (PDS), a key enzyme in carotenoid, chlorophyll, and gibberellic acid (GA) biosynthesis, resulted in a substantial increase in the systemic accumulation of PLRV. This increased accumulation was attenuated when plants were infected with a viral mutant that does not express the RTD. Application of GA partially suppressed the increase in virus accumulation in PDS-silenced plants, suggesting that GA signaling also plays a role in limiting PLRV infection. In addition, the fecundity of the aphid vector of PLRV was increased when fed on PDS-silenced plants relative to PLRV-infected plants.


Asunto(s)
Áfidos/virología , Cloroplastos/enzimología , Nicotiana/virología , Oxidorreductasas/metabolismo , Floema/virología , Animales , Regulación hacia Abajo , Regulación Enzimológica de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Silenciador del Gen , Insectos Vectores , Luteoviridae , Oxidorreductasas/genética , Nicotiana/metabolismo
4.
BMJ Open Qual ; 6(2): e000223, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29435513

RESUMEN

Serious mental illness is reported to reduce a patient's life expectancy by 15-20 years. This disparity is thought to be related to lifestyle factors, access to healthcare, poor health monitoring and the common use of antipsychotics, which can cause serious metabolic and cardiogenic side effects. Therefore, to reduce the risk of cardiac complications, both national and local guidance recommends annual ECG monitoring for patients on antipsychotics. Unfortunately this monitoring is not completed consistently at Manchester Mental Health and Social Care Trust, especially within community mental health teams. A small team of healthcare professionals conducted a quality improvement (QI) project from June 2015 to May 2016 with the aim of addressing this deficiency in care. A multidisciplinary approach was used to implement improvement in four key areas. Awareness of the need for monitoring, patient engagement with this process, identification of patients requiring monitoring and access to ECG equipment were all addressed as separate primary drivers for change over an 8-month period using a 'Plan Do Study Act' model of QI. Outcome, process and balancing measures were gathered monthly to track progress and improvement following the application of change. Compliance with annual ECG monitoring nearly doubled throughout the course of the project from 43% in June 2015 to a peak of 83% in February 2016. Improvement appeared to be sustained as the percentage of patients receiving the required monitoring remained significantly higher than baseline even after no further change interventions were being implemented (76%, 71%, 77%, March, April, May 2016). This QI project has shown that improvements can be made and has documented a recipe for how this change was achieved.

5.
PLoS One ; 10(4): e0122721, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25856241

RESUMEN

Climate and land cover change are driving a major reorganization of terrestrial biotic communities in tropical ecosystems. In an effort to understand how biodiversity patterns in the tropics will respond to individual and combined effects of these two drivers of environmental change, we use species distribution models (SDMs) calibrated for recent climate and land cover variables and projected to future scenarios to predict changes in diversity patterns in Madagascar. We collected occurrence records for 828 plant genera and 2186 plant species. We developed three scenarios, (i.e., climate only, land cover only and combined climate-land cover) based on recent and future climate and land cover variables. We used this modelling framework to investigate how the impacts of changes to climate and land cover influenced biodiversity across ecoregions and elevation bands. There were large-scale climate- and land cover-driven changes in plant biodiversity across Madagascar, including both losses and gains in diversity. The sharpest declines in biodiversity were projected for the eastern escarpment and high elevation ecosystems. Sharp declines in diversity were driven by the combined climate-land cover scenarios; however, there were subtle, region-specific differences in model outputs for each scenario, where certain regions experienced relatively higher species loss under climate or land cover only models. We strongly caution that predicted future gains in plant diversity will depend on the development and maintenance of dispersal pathways that connect current and future suitable habitats. The forecast for Madagascar's plant diversity in the face of future environmental change is worrying: regional diversity will continue to decrease in response to the combined effects of climate and land cover change, with habitats such as ericoid thickets and eastern lowland and sub-humid forests particularly vulnerable into the future.


Asunto(s)
Biodiversidad , Cambio Climático , Ecosistema , Modelos Biológicos , Dispersión de las Plantas , Plantas/genética , Algoritmos , Geografía , Madagascar , Dinámica Poblacional , Clima Tropical
6.
Sci Total Environ ; 485-486: 329-339, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24727599

RESUMEN

This study addresses the consequences of widespread conversion of permeable front gardens to hard standing car parking surfaces, and the potential consequences in high-risk urban flooding hotspots, in the city of Southampton. The last two decades has seen a trend for domestic front gardens in urban areas to be converted for parking, driven by the lack of space and increased car ownership. Despite media and political attention, the effects of this change are unknown, but increased and more intense rainfall, potentially linked to climate change, could generate negative consequences as runoff from impermeable surfaces increases. Information is limited on garden permeability change, despite the consequences for ecosystem services, especially flood regulation. We focused on eight flooding hotspots identified by the local council as part of a wider urban flooding policy response. Aerial photographs from 1991, 2004 and 2011 were used to estimate changes in surface cover and to analyse permeability change within a digital surface model in a GIS environment. The 1, 30 and 100 year required attenuation storage volumes were estimated, which are the temporary storage required to reduce the peak flow rate given surface permeability. Within our study areas, impermeable cover in domestic front gardens increased by 22.47% over the 20-year study period (1991-2011) and required attenuation storage volumes increased by 26.23% on average. These increases suggest that a consequence of the conversion of gardens to parking areas will be a potential increase in flooding frequency and severity - a situation which is likely to occur in urban locations worldwide.


Asunto(s)
Monitoreo del Ambiente , Inundaciones , Jardinería , Modelos Teóricos , Suelo/química , Automóviles , Ciudades , Sistemas de Información Geográfica , Permeabilidad , Movimientos del Agua
7.
Inorg Chem ; 41(8): 2032-40, 2002 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-11952356

RESUMEN

35Cl, (79,81)Br, and (127)I NQR (nuclear quadrupole resonance) spectroscopy in conjunction with X-ray crystallography is potentially one of the best ways of characterizing secondary bonding of metal cations such as Ag(+) to halogen donor atoms on the surfaces of very weakly coordinating anions. We have determined the X-ray crystal structure of Ag(O(3)SCH(2)Cl) (a = 13.241(3) A; b = 7.544(2) A; c = 4.925(2) A; orthorhombic; space group Pnma; Z = 4) and compared it with the known structure of Ag(O(3)SCH(2)Br) (Charbonnier, F.; Faure, R.; Loiseleur, H. Acta Crystallogr., Sect. B 1978, 34, 3598-3601). The halogen atom in each is apical (three-coordinate), being weakly coordinated to two silver ions. (127)I NQR studies on Ag(O(3)SCH(2)I) show the expected NQR consequences of three-coordination of iodine: substantially reduced NQR frequencies nu(1) and nu(2) and a fairly small NQR asymmetry parameter eta. The reduction of the halogen NQR frequency of the coordinating halogen atom in Ag(O(3)SCH(2)X) becomes more substantial in the series X = Cl < Br < I, indicating that the coordination to Ag(+) strengthens in this series, as expected from hard-soft acid-base principles. The numbers of electrons donated by the organic iodine atom to Ag(+) have been estimated; these indicate that the bonding to the cation is weak but not insignificant. We have not found any evidence for the bonding of these organohalogen atoms to another soft-acid metal ion, thallium. A scheme for recycling of thallium halide wastes is included.

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