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1.
Lancet Reg Health Eur ; 33: 100706, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37601339

RESUMEN

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations.

2.
Hydrogeol J ; 31(1): 1-6, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36687384

RESUMEN

Groundwater's role in maintaining the well-being of the planet is increasingly acknowledged. Only recently has society recognised groundwater as a key component of the water cycle. To improve public understanding and the proper use of groundwater, the hydrogeological community must expand its efforts in groundwater assessment, management, and communication. The International Association of Hydrogeologists (IAH) intends to help achieve the United Nation's water-related Sustainable Development Goals (SDGs) by the adoption of innovative hydrogeological strategies. This essay introduces a topical collection that encapsulates IAH's 2022 'Year for Groundwater'.


Le rôle des eaux souterraines dans le maintien du bien-être de la planète est de plus en plus reconnu. Ce n'est que récemment que la société a reconnu les eaux souterraines comme un élément clé du cycle de l'eau. Pour améliorer la compréhension du public et l'utilisation appropriée des eaux souterraines, la communauté hydrogéologique doit étendre ses efforts en matière d'évaluation, de gestion des eaux souterraines et de communication à leur sujet. L'Association Internationale des Hydrogéologues (AIH) entend contribuer à la réalisation des objectifs du développement durable (ODDs) des Nations unies liés à l'eau par l'adoption de stratégies hydrogéologiques innovantes. Cet essai présente une collection thématique qui résume l''Année pour les eaux souterraines' 2022 de l'AIH.


El papel de las aguas subterráneas para mantener el bienestar del planeta está cada vez más reconocido. Sólo recientemente la sociedad ha reconocido que las aguas subterráneas son un componente clave del ciclo del agua. Para mejorar la comprensión pública y el uso adecuado de las aguas subterráneas, la comunidad hidrogeológica debe aumentar sus esfuerzos en materia de evaluación, gestión y comunicación de las aguas subterráneas. La Asociación Internacional de Hidrogeólogos (AIH) pretende contribuir a la concreción de los Objetivos de Desarrollo Sostenible (ODS) de las Naciones Unidas relacionados con el agua mediante la adopción de estrategias hidrogeológicas innovadoras. Este artículo presenta una colección temática que engloba el 2022 como 'Año Internacional para las Aguas Subterráneas' de la AIH.


O papel das águas subterrâneas na manutenção do bem-estar do planeta é cada vez mais reconhecido. Só recentemente a sociedade reconheceu as águas subterrâneas como um componente chave do ciclo da água. Para melhorar a compreensão pública e o uso adequado das águas subterrâneas, a comunidade hidrogeológica deve expandir seus esforços na avaliação, gestão e comunicação das águas subterrâneas. A Associação Internacional de Hidrogeólogos (AIH) pretende ajudar a alcançar os Objetivos de Desenvolvimento Sustentável (ODS) das Nações Unidas relacionados à água por meio da adoção de estratégias hidrogeológicas inovadoras. Este ensaio apresenta uma coleção tópica que encapsula o 'Ano para as Águas Subterrâneas' de 2022 da AIH.

3.
Sci Total Environ ; 858(Pt 3): 159765, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36309251

RESUMEN

Groundwater is an essential resource for natural and human systems throughout the world and the rates at which aquifers are recharged constrain sustainable levels of consumption. However, recharge estimates from global-scale models regularly disagree with each other and are rarely compared to ground-based estimates. We compare long-term mean annual recharge and recharge ratio (annual recharge/annual precipitation) estimates from eight global models with over 100 ground-based estimates in Africa. We find model estimates of annual recharge and recharge ratio disagree significantly across most of Africa. Furthermore, similarity to ground-based estimates between models also varies considerably and inconsistently throughout the different landscapes of Africa. Models typically showed both positive and negative biases in most landscapes, which made it challenging to pinpoint how recharge prediction by global-scale models can be improved. However, global-scale models which reflected stronger climatic controls on their recharge estimates compared more favourably to ground-based estimates. Given this significant uncertainty in recharge estimates from current global-scale models, we stress that groundwater recharge prediction across Africa, for both research investigations and operational management, should not rely upon estimates from a single model but instead consider the distribution of estimates from different models. Our work will be of particular interest to decision makers and researchers who consider using such recharge outputs to make groundwater governance decisions or investigate groundwater security especially under the potential impact of climate change.


Asunto(s)
Humanos , África
4.
Environ Microbiol ; 24(12): 5840-5858, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35706139

RESUMEN

The retreat of glaciers in response to climate change has major impacts on the hydrology and ecosystems of glacier forefield catchments. Microbes are key players in ecosystem functionality, supporting the supply of ecosystem services that glacier systems provide. The interaction between surface and groundwaters in glacier forefields has only recently gained much attention, and how these interactions influence the microbiology is still unclear. Here, we identify the microbial communities in groundwater from shallow (<15 m deep) boreholes in a glacial forefield floodplain ('sandur') aquifer at different distances from the rapidly retreating Virkisjökull glacier, Iceland, and with varying hydraulic connectivity with the glacial meltwater river that flows over the sandur. Groundwater communities are shown to differ from those in nearby glacial and non-glacial surface water communities. Groundwater-meltwater interactions and groundwater flow dynamics affect the microbial community structure, leading to different microbial communities at different sampling points in the glacier forefield. Groundwater communities differ from those in nearby glacial and non-glacial surface waters. Functional potential for microbial nitrogen and methane cycling was detected, although the functional gene copy numbers of specific groups were low.


Asunto(s)
Agua Subterránea , Microbiota , Cubierta de Hielo/microbiología , Islandia , Ríos
5.
Sci Total Environ ; 828: 154283, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35247396

RESUMEN

In Africa groundwater is the principal source of drinking water (https://washdata.org/) and has significant potential to improve food production as a source of irrigation water. Although volumes of stored groundwater are high when compared to surface water, not all the available groundwater is suitable for irrigation. One of the principal factors that limit the development of groundwater is salinity, but quantitative evidence regarding the scale of salinization in Africa has been lacking. This paper presents an initial analysis of the extent of groundwater salinization in Africa, bringing together groundwater salinity data (n = 12,255) from across the continent. In our dataset c.80% of the samples have electrical conductivity values less than 2000 µS/cm. Samples with high conductivity values of more than 2000 µS/cm are restricted to limited geological and climatic environments. The data reveals salinity does not affect the water security status of most countries in Africa. However, salinity compounds water insecurity issues in arid low groundwater recharge environments. The paper discusses the role of anthropogenic processes such as river valley water resources development, extensive groundwater pumping, inter-basin groundwater transfer, and irrigation in altering the salinity of groundwater bodies. The paper further elucidates the origin of groundwater salinity by critically reviewing the natural and human-induced factors that control the salinization of the various groundwater bodies across Africa. Existing case studies reveal several causes of salinization, including i) human-induced salinization, ii) climate and hydrological change-induced paleo groundwater salinity, iii) rock dissolution, and iv), saltwater encroachment.


Asunto(s)
Agua Potable , Agua Subterránea , Contaminantes Químicos del Agua , Agua Potable/análisis , Monitoreo del Ambiente , Agua Subterránea/análisis , Humanos , Salinidad , Contaminantes Químicos del Agua/análisis
6.
J Alzheimers Dis ; 85(2): 889-903, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34897095

RESUMEN

BACKGROUND: Infections by bacterial or viral agents have been hypothesized to influence the etiology of neurodegenerative diseases. OBJECTIVE: This study examined the potential presence of Borrelia burgdorferi spirochete, the causative agent of Lyme disease, in brain autopsy tissue of patients diagnosed with either Alzheimer's (AD) or Parkinson's diseases. METHODS: Brain tissue sections from patients with age-matched controls were evaluated for antigen and DNA presence of B. burgdorferi using various methods. Positive Borrelia structures were evaluated for co-localization with biofilm and AD markers such as amyloid and phospho-tau (p-Tau) using immunohistochemical methods. RESULTS: The results showed the presence of B. burgdorferi antigen and DNA in patients with AD pathology and among those, one of them was previously diagnosed with Lyme disease. Interestingly, a significant number of Borrelia-positive aggregates with a known biofilm marker, alginate, were found along with the spirochetal structures. Our immunohistochemical data also showed that Borrelia-positive aggregates co-localized with amyloid and phospho-tau markers. To further prove the potential relationship of B. burgdorferi and amyloids, we infected two mammalian cell lines with B. burgdorferi which resulted in a significant increase in the expression of amyloid-ß and p-Tau proteins in both cells lines post-infection. CONCLUSION: These results indicate that B. burgdorferi can be found in AD brain tissues, not just in spirochete but a known antibiotics resistant biofilm form, and its co-localized amyloid markers. In summary, this study provides evidence for a likely association between B. burgdorferi infections and biofilm formation, AD pathology, and chronic neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer/microbiología , Enfermedad de Alzheimer/patología , Borrelia burgdorferi/aislamiento & purificación , Encéfalo/microbiología , Encéfalo/patología , Anciano , Enfermedad de Alzheimer/metabolismo , Proteínas Amiloidogénicas/metabolismo , Amiloidosis/patología , Biopelículas/efectos de los fármacos , Biomarcadores/metabolismo , Borrelia burgdorferi/genética , Línea Celular Tumoral , ADN Bacteriano , Humanos , Neuroborreliosis de Lyme/complicaciones , Proteínas tau/metabolismo
7.
Water Res ; 206: 117734, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34655933

RESUMEN

Faecal indicator organisms (FIOs) are limited in their ability to protect public health from the microbial contamination of drinking water because of their transience and time required to deliver a result. We evaluated alternative rapid, and potentially more resilient, approaches against a benchmark FIO of thermotolerant coliforms (TTCs) to characterise faecal contamination over 14 months at 40 groundwater sources in a Ugandan town. Rapid approaches included: in-situ tryptophan-like fluorescence (TLF), humic-like fluorescence (HLF), turbidity; sanitary inspections; and total bacterial cells by flow cytometry. TTCs varied widely in six sampling visits: a third of sources tested both positive and negative, 50% of sources had a range of at least 720 cfu/100 mL, and a two-day heavy rainfall event increased median TTCs five-fold. Using source medians, TLF was the best predictor in logistic regression models of TTCs ≥10 cfu/100 mL (AUC 0.88) and best correlated to TTC enumeration (ρs 0.81), with HLF performing similarly. Relationships between TLF or HLF and TTCs were stronger in the wet season than the dry season, when TLF and HLF were instead more associated with total bacterial cells. Source rank-order between sampling rounds was considerably more consistent, according to cross-correlations, using TLF or HLF (min ρs 0.81) than TTCs (min ρs 0.34). Furthermore, dry season TLF and HLF cross-correlated more strongly (ρs 0.68) than dry season TTCs (ρs 0.50) with wet season TTCs, when TTCs were elevated. In-situ TLF or HLF are more rapid and resilient indicators of faecal contamination risk than TTCs.


Asunto(s)
Agua Potable , Agua Subterránea , Monitoreo del Ambiente , Heces , Espectrometría de Fluorescencia , Microbiología del Agua
8.
J Environ Manage ; 288: 112384, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33773213

RESUMEN

Groundwater resources in South Asian cities are facing immense stress due to over-extraction leading to environmental, social and economic instabilities. The perennial mega rivers of Himalayas form the lifeline for South Asia, underpinning food and water security for a large population both directly and indirectly through exchange with groundwater systems. The present study delineates the spatio-temporal variation in patterns and processes of sub-hourly to annual-scale hydrological exchanges between the Ganges and its adjoining highly exploited aquifer in a urban-peri urban reach. Multivariate statistical analyses established river water-groundwater interaction in this region with ~40% loading of first principal component, i.e river water during monsoon on the shallow aquifer. The part of the aquifer detached from the main confined aquifer show an influence of precipitation (the second principal component) with loading of ~90%. Again the part of the aquifer suffering infiltration of local surface water bodies show effect of precipitation with a second principal loading of ~80%. Fourier transformation is used in the hydrograph to remove influence of heavy urbanization on the hydrographs. This study proves that the phenomenon of infiltrating river water during monsoon plays a primary role in controlling aquifer storage although contaminating the aquifer simultaneously. However, during pre and post-monsoon the flow path reversal helps in maintaining river baseflow. Cross-correlation between the river and piezometric series show increased delay of pressure head propagation of the infiltrating river waterfront, with increasing distance. These observations are also substantiated by stable isotope signatures. The present study provides an understanding of potential groundwater vulnerability resulting from waste water and irrigational contamination through river water intrusion which would eventually lead the government to implement proper water and environmental management policies towards availability of long-term sustainable water resources for the residents.


Asunto(s)
Agua Potable , Agua Subterránea , Contaminantes Químicos del Agua , Asia , Ciudades , Monitoreo del Ambiente , Ríos , Estaciones del Año , Contaminantes Químicos del Agua/análisis
10.
Sci Total Environ ; 750: 141284, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33182170

RESUMEN

Regular monitoring of drinking water quality is vital to identify contamination of potable water supplies. Testing for microbial contamination is important to prevent transmission of waterborne disease, but establishing and maintaining a water quality monitoring programme requires sustained labour, consumables and resources. In low resource settings such as developing countries, this can prove difficult, but measuring microbial contamination is listed as a requirement of reaching the UN's Sustainable Development Goal 6 for water and sanitation. A nine-month water quality monitoring programme was conducted in rural Malawi to assess the suitability of tryptophan-like fluorescence (TLF), an emerging method for rapidly detecting microbial contamination, as a drinking water quality monitoring tool. TLF data was compared with thermotolerant coliforms (TTCs, E. coli) and inorganic hydrochemical parameters. A large (n = 235) temporal dataset was collected from five groundwater drinking water sources, with samples collected once or twice weekly depending on the season. The results show that TLF can indicate a broader contamination risk but is not as sensitive to short term variability when compared to other faecal indicators. This is likely due to a broad association of TLF with elevated DOC concentrations from a range of different sources. Elevated TLF may indicate preferential conditions for the persistence of TTCs and/or E. coli, but not necessarily a public health risk from microbial contamination. TLF is therefore a more precautionary risk indicator than microbial culturing techniques and could prove useful as a high-level screening tool for initial risk assessment. For widespread use of TLF to be successful, standardisation of TLF values associated with different levels of risk is required, however, this study highlights the difficulties of equating TLF thresholds to TTCs or E. coli data because of the influence of DOC/HLF on the TLF signal.


Asunto(s)
Agua Potable , Monitoreo del Ambiente , Escherichia coli , Fluorescencia , Humanos , Malaui , Triptófano , Microbiología del Agua , Calidad del Agua , Abastecimiento de Agua
12.
Sci Rep ; 10(1): 15379, 2020 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-32958794

RESUMEN

Fluorescent natural organic matter at tryptophan-like (TLF) and humic-like fluorescence (HLF) peaks is associated with the presence and enumeration of faecal indicator bacteria in groundwater. We hypothesise, however, that it is predominantly extracellular material that fluoresces at these wavelengths, not bacterial cells. We quantified total (unfiltered) and extracellular (filtered at < 0.22 µm) TLF and HLF in 140 groundwater sources across a range of urban population densities in Kenya, Malawi, Senegal, and Uganda. Where changes in fluorescence occurred following filtration they were correlated with potential controlling variables. A significant reduction in TLF following filtration (ΔTLF) was observed across the entire dataset, although the majority of the signal remained and thus considered extracellular (median 96.9%). ΔTLF was only significant in more urbanised study areas where TLF was greatest. Beneath Dakar, Senegal, ΔTLF was significantly correlated to total bacterial cells (ρs 0.51). No significant change in HLF following filtration across all data indicates these fluorophores are extracellular. Our results suggest that TLF and HLF are more mobile than faecal indicator bacteria and larger pathogens in groundwater, as the predominantly extracellular fluorophores are less prone to straining. Consequently, TLF/HLF are more precautionary indicators of microbial risks than faecal indicator bacteria in groundwater-derived drinking water.


Asunto(s)
Heces/microbiología , Colorantes Fluorescentes/química , Agua Subterránea/microbiología , Triptófano/química , África , Agua Potable/química , Agua Potable/microbiología , Monitoreo del Ambiente/métodos , Fluorescencia , Agua Subterránea/química , Microbiología del Agua , Abastecimiento de Agua/métodos
13.
Sci Total Environ ; 744: 140674, 2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-32755770

RESUMEN

Faecally-contaminated drinking water is a risk to human health, with the greatest risks to those living in developing countries. UN Sustainable Development Goal 6 aims to address this issue. Tryptophan-like fluorescence (TLF) shows potential as a rapid method for detecting microbial contamination in drinking water, which could reduce the spread of waterborne diseases. This study is the first to investigate the effectiveness of TLF for a large-scale survey using a randomised, spot-sampling approach. The large-scale survey took place in Malawi, sub-Saharan Africa, in the dry season (n = 183). A subset of sources were revisited at the end of the following wet season (n = 41). The effectiveness of TLF was assessed by comparing TLF results to thermotolerant coliforms (TTC), humic-like fluorescence (HLF), inorganic hydrochemical data and sanitary risk scores. The most prominent differences in microbial water quality were observed between source types, with little variation between districts and seasons. TLF, TTCs, turbidity and sanitary risk scores were all elevated at alternative sources (shallow wells and tap stands) compared to hand-pumped boreholes. In the dry season, 18% of hand-pumped boreholes showed TTC contamination, which increase to 21% in the wet season. Groundwater recharge processes are likely responsible for seasonal variability of inorganic hydrochemistry at hand-pumped boreholes. TLF was able to distinguish no and low WHO risk classes (TTC 0-9 cfu/100 mL) from medium, high and very high risk classes (TTC 10 - >1000 cfu/100 mL). TLF failed to distinguish between no and low risk classes, which limits the use of TLF for assessing water quality to drinking water standards. This dataset indicates that HLF may raise baseline TLF for samples with low TLF values, increasing false positives. Therefore, TLF is better suited as a rapid high-level water quality screening tool to assess moderate and high levels of faecal contamination.


Asunto(s)
Agua Potable , Monitoreo del Ambiente , Humanos , Malaui , Estaciones del Año , Encuestas y Cuestionarios , Triptófano , Microbiología del Agua , Calidad del Agua , Abastecimiento de Agua
14.
Sci Total Environ ; 738: 139419, 2020 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-32521357

RESUMEN

We explore in-situ fluorescence spectroscopy as an instantaneous indicator of total bacterial abundance and faecal contamination in drinking water. Eighty-four samples were collected outside of the recharge season from groundwater-derived water sources in Dakar, Senegal. Samples were analysed for tryptophan-like (TLF) and humic-like (HLF) fluorescence in-situ, total bacterial cells by flow cytometry, and potential indicators of faecal contamination such as thermotolerant coliforms (TTCs), nitrate, and in a subset of 22 samples, dissolved organic carbon (DOC). Significant single-predictor linear regression models demonstrated that total bacterial cells were the most effective predictor of TLF, followed by on-site sanitation density; TTCs were not a significant predictor. An optimum multiple-predictor model of TLF incorporated total bacterial cells, nitrate, nitrite, on-site sanitation density, and sulphate (r2 0.68). HLF was similarly related to the same parameters as TLF, with total bacterial cells being the best correlated (ρs 0.64). In the subset of 22 sources, DOC clustered with TLF, HLF, and total bacterial cells, and a linear regression model demonstrated HLF was the best predictor of DOC (r2 0.84). The intergranular nature of the aquifer, timing of the study, and/or non-uniqueness of the signal to TTCs can explain the significant associations between TLF/HLF and indicators of faecal contamination such as on-site sanitation density and nutrients but not TTCs. The bacterial population that relates to TLF/HLF is likely to be a subsurface community that develops in-situ based on the availability of organic matter originating from faecal sources. In-situ fluorescence spectroscopy instantly indicates a drinking water source is impacted by faecal contamination but it remains unclear how that relates specifically to microbial risk in this setting.


Asunto(s)
Carbono , Microbiología del Agua , Monitoreo del Ambiente , Fluorescencia , Senegal , Espectrometría de Fluorescencia
15.
Nat Commun ; 11(1): 1279, 2020 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-32152271

RESUMEN

Climate change and urbanization can increase pressures on groundwater resources, but little is known about how groundwater quality will change. Here, we use a global synthesis (n = 9,404) to reveal the drivers of dissolved organic carbon (DOC), which is an important component of water chemistry and substrate for microorganisms that control biogeochemical reactions. Dissolved inorganic chemistry, local climate and land use explained ~ 31% of observed variability in groundwater DOC, whilst aquifer age explained an additional 16%. We identify a 19% increase in DOC associated with urban land cover. We predict major groundwater DOC increases following changes in precipitation and temperature in key areas relying on groundwater. Climate change and conversion of natural or agricultural areas to urban areas will decrease groundwater quality and increase water treatment costs, compounding existing constraints on groundwater resources.

16.
Nature ; 572(7768): 230-234, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31391559

RESUMEN

Groundwater in sub-Saharan Africa supports livelihoods and poverty alleviation1,2, maintains vital ecosystems, and strongly influences terrestrial water and energy budgets3. Yet the hydrological processes that govern groundwater recharge and sustainability-and their sensitivity to climatic variability-are poorly constrained4,5. Given the absence of firm observational constraints, it remains to be seen whether model-based projections of decreased water resources in dry parts of the region4 are justified. Here we show, through analysis of multidecadal groundwater hydrographs across sub-Saharan Africa, that levels of aridity dictate the predominant recharge processes, whereas local hydrogeology influences the type and sensitivity of precipitation-recharge relationships. Recharge in some humid locations varies by as little as five per cent (by coefficient of variation) across a wide range of annual precipitation values. Other regions, by contrast, show roughly linear precipitation-recharge relationships, with precipitation thresholds (of roughly ten millimetres or less per day) governing the initiation of recharge. These thresholds tend to rise as aridity increases, and recharge in drylands is more episodic and increasingly dominated by focused recharge through losses from ephemeral overland flows. Extreme annual recharge is commonly associated with intense rainfall and flooding events, themselves often driven by large-scale climate controls. Intense precipitation, even during years of lower overall precipitation, produces some of the largest years of recharge in some dry subtropical locations. Our results therefore challenge the 'high certainty' consensus regarding decreasing water resources4 in such regions of sub-Saharan Africa. The potential resilience of groundwater to climate variability in many areas that is revealed by these precipitation-recharge relationships is essential for informing reliable predictions of climate-change impacts and adaptation strategies.


Asunto(s)
Agua Subterránea/análisis , Lluvia , África del Sur del Sahara , Clima Desértico , Sequías/estadística & datos numéricos
17.
Int J Antimicrob Agents ; 54(1): 16-22, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31085298

RESUMEN

The global public health threat of antibiotic-resistant infections as well as the lack of new treatments in clinical development is a critical issue. Reasons for this include diminished commercial incentives for pharmaceutical companies to develop new antibiotics, which part-reflects a shift in antibiotic marketing paradigm from broad deployment to targeted therapy in relatively small patient populations. Such changes are encouraged by antimicrobial stewardship (AMS). Other factors include a lack of recognition in the traditional assessment of new antibiotics by regulators, health technology assessors and payers of the broad range of benefits of new agents, particularly their value to health care, economies and society. Recognising the seriousness of the situation, there have been recent changes and proposals by regulators for modification of the assessment process to accommodate a broader range of acceptable data supporting new drug applications. There is also increasing recognition by some payers of the societal benefit of new antibiotics and the need for financial incentives for those developing high-priority antibiotics. However, progress is slow, with recent publications focusing on industry and strategic perspectives rather than clinical implications. In this opinion piece, we therefore focus on clinicians and the practical steps they can take to drive and contribute to increasing awareness and understanding of the value of antibiotics. This includes identifying and gathering appropriate alternative data sources, educating on AMS and prescribing habits, and contributing to international antibiotic susceptibility surveillance models.


Asunto(s)
Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Infecciones Bacterianas/tratamiento farmacológico , Farmacorresistencia Bacteriana , Utilización de Medicamentos/normas , Médicos , Antibacterianos/farmacología , Hospitales , Humanos , Pautas de la Práctica en Medicina
18.
Clin Cancer Res ; 25(5): 1574-1587, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30559170

RESUMEN

PURPOSE: To determine whether inhibition of mTOR kinase-mediated signaling represents a valid therapeutic approach for chronic lymphocytic leukemia (CLL). EXPERIMENTAL DESIGN: Stratification of mTOR activity was carried out in patients with primary CLL samples and an aggressive CLL-like mouse model. The potency of dual mTOR inhibitor AZD8055 to induce apoptosis in primary CLL cells was assessed in the presence/absence of B-cell receptor (BCR) ligation. Furthermore, we addressed the molecular and functional impact of dual mTOR inhibition in combination with BTK inhibitor ibrutinib. RESULTS: Differential regulation of basal mTORC1 activity was observed in poor prognostic CLL samples, with elevated p4EBP1T37/46 and decreased p70S6 kinase activity, suggesting that dual mTORC1/2 inhibitors may exhibit improved response in poor prognostic CLL compared with rapalogs. AZD8055 treatment of primary CLL cells significantly reduced CLL survival in vitro compared with rapamycin, preferentially targeting poor prognostic subsets and overcoming BCR-mediated survival advantages. Furthermore, AZD8055, and clinical analog AZD2014, significantly reduced CLL tumor load in mice. AKT substrate FOXO1, while overexpressed in CLL cells of poor prognostic patients in LN biopsies, peripheral CLL cells, and mouse-derived CLL-like cells, appeared to be inactive. AZD8055 treatment partially reversed FOXO1 inactivation downstream of BCR crosslinking, significantly inhibiting FOXO1T24 phosphorylation in an mTORC2-AKT-dependent manner, to promote FOXO1 nuclear localization, activity, and FOXO1-mediated gene regulation. FOXO1 activity was further significantly enhanced on combining AZD8055 with ibrutinib. CONCLUSIONS: Our studies demonstrate that dual mTOR inhibitors show promise as future CLL therapies, particularly in combination with ibrutinib.


Asunto(s)
Proteína Forkhead Box O1/metabolismo , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/mortalidad , Diana Mecanicista del Complejo 2 de la Rapamicina/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos B/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Femenino , Proteína Forkhead Box O1/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Masculino , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Ratones , Ratones Transgénicos , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Sci Total Environ ; 622-623: 1250-1257, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29890592

RESUMEN

We assess the use of fluorescent dissolved organic matter at excitation-emission wavelengths of 280nm and 360nm, termed tryptophan-like fluorescence (TLF), as an indicator of faecally contaminated drinking water. A significant logistic regression model was developed using TLF as a predictor of thermotolerant coliforms (TTCs) using data from groundwater- and surface water-derived drinking water sources in India, Malawi, South Africa and Zambia. A TLF threshold of 1.3ppb dissolved tryptophan was selected to classify TTC contamination. Validation of the TLF threshold indicated a false-negative error rate of 15% and a false-positive error rate of 18%. The threshold was unsuccessful at classifying contaminated sources containing <10 TTC cfu per 100mL, which we consider the current limit of detection. If only sources above this limit were classified, the false-negative error rate was very low at 4%. TLF intensity was very strongly correlated with TTC concentration (ρs=0.80). A higher threshold of 6.9ppb dissolved tryptophan is proposed to indicate heavily contaminated sources (≥100 TTC cfu per 100mL). Current commercially available fluorimeters are easy-to-use, suitable for use online and in remote environments, require neither reagents nor consumables, and crucially provide an instantaneous reading. TLF measurements are not appreciably impaired by common intereferents, such as pH, turbidity and temperature, within typical natural ranges. The technology is a viable option for the real-time screening of faecally contaminated drinking water globally.


Asunto(s)
Agua Potable/microbiología , Monitoreo del Ambiente/métodos , Triptófano/química , Microbiología del Agua , Contaminantes del Agua/análisis , Agua Potable/química , Heces/química , Fluorescencia , India , Malaui , Sudáfrica , Triptófano/análisis , Zambia
20.
Hydrogeol J ; 26(2): 367-370, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-31983889

RESUMEN

The Sustainable Development Goals have set an agenda for transformational change in water access, aiming for secure household connections globally. Despite this goal, communal groundwater supplies are likely to remain the main source of improved water supplies for many rural areas in Africa and South Asia for decades to come. Understanding the poor functionality of existing communal supplies remains, therefore, a priority. A critical first step is to establish a sector-wide definition of borehole supply functionality and a standard method of its assessment.


Les objectifs du développement durable ont mis en place un programme de changement transformationnel de l'accès à l'eau, visant à assurer des connexions sûres des ménages à l'échelle mondiale. Malgré cet objectif, les approvisionnements en eaux souterraines à l'échelle communale sont susceptibles de demeurer le sujet principal à améliorer pour de nombreuses régions rurales d'Afrique et d'Asie du Sud pour les décennies à venir. La compréhension de la piètre fonctionnalité des approvisionnements existants à l'échelle communale reste donc une priorité. Une première étape cruciale consiste à établir une définition sectorielle de la fonctionnalité de l'approvisionnement par forage et une méthode normalisée de son évaluation.


Los objetivos de desarrollo sostenible han establecido una agenda para un cambio transformacional en el acceso al agua, con la finalidad de establecer conexiones domiciliarias seguras a nivel mundial. A pesar de este objetivo, es probable que los suministros comunales de agua subterránea sigan siendo la principal fuente de mejoras en el abastecimiento de agua para muchas áreas rurales en África y el sur de Asia en las próximas décadas. Entender la funcionalidad deficiente de los suministros comunales existentes sigue siendo, por lo tanto, una prioridad. Un primer paso crítico es establecer una definición sectorial de la funcionalidad del suministro de los pozos y un método estándar para su evaluación.


Os Objetivos de Desenvolvimento Sustentável estabeleceram uma agenda para mudanças de paradigmas no acesso à água, visando abastecimento doméstico em escala global. Apesar desse objetivo, os suprimentos comunitários de águas subterrâneas provavelmente continuarão a ser a principal fonte de abastecimento de água potável para muitas áreas rurais da África e do sul da Ásia por décadas. Compreender a baixa funcionalidade desses atuais suprimentos comunitários torna-se, portanto, prioritária. Um primeiro passo crítico é estabelecer uma definição setorial de funcionalidade de fornecimento de poços e um método padrão de avaliação.

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