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1.
Sci Rep ; 14(1): 1171, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216654

RESUMO

Ireland has > 50% of the EU's ocean-raised bogs; however, degradation through land-use activities has transformed them from carbon (C) sinks to sources. Given their significant role in climate mitigation, it is essential to quantify the emissions resulting from land use degradation of these ecosystems. A seven-class land-use classification system for Irish peatlands (LUCIP) was developed and mapped using Sentinel-2 imagery, random forest machine learning and Google Earth Engine. The results revealed that agricultural grassland comprised 43% of the land use on raised bogs, followed by, forestry (21%), cutover (11%), cutaway (10%) remnant peatlands (13%), waterbodies and built-up ~ 1% each. The overall accuracy of the map was 89%. The map was used to estimate CO2 emissions for four classes constituting 85% of raised bogs: cutover, cutaway, grassland, and forestry using the IPCC wetlands supplement and literature-based emission factors, we estimated emissions at ~ 1.92 (± 1.58-2.27 Mt CO2-C-yr-1) and ~ 0.68 Mt CO2-C-yr-1 (± 0.44-0.91 Mt CO2-C-yr-1) respectively. This is the first study to spatially quantify land use and related emissions from raised bogs. The results have revealed widespread degradation of these globally rare habitats, making them net emitters of CO2. The map is vital for the conservation of these ecosystems through restoration efforts, and the methodology can also be applied to other regions with similar peatland land use issues.

2.
J Cardiothorac Vasc Anesth ; 38(1): 118-122, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37923595

RESUMO

More than 300,000 adults have cardiac surgery in the United States annually, and most undergo intraoperative transesophageal echocardiography (TEE). This patient population is often older with multiple comorbidities, increasing their risk for complications for even routine procedures. Major morbidity or mortality caused by TEE is rare, and it is unknown how often such complications lead to malpractice lawsuits. The authors identified 13 cases out of 2,564 in a closed claims database that involved TEE and reviewed their etiology. Esophageal injury accounted for most of the suits, and only 2 were related to diagnosis. Most expert reviews deemed the care provided by the anesthesiologist to be appropriate.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Imperícia , Adulto , Humanos , Estados Unidos , Anestesiologistas , Ecocardiografia Transesofagiana/efeitos adversos , Bases de Dados Factuais
3.
Heliyon ; 9(9): e19416, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37674820

RESUMO

To establish meaningful and sustainable policy directives for sustainable pesticide use in agriculture, baseline knowledge of pesticide levels in soils is required. To address this, five pesticides and one metabolite widely used in Irish agriculture and five neonicotinoid compounds pesticides were screened from soils from 25 fields. These sites represented a diversity of soil and land use types. Prothioconazole was detected in 16 of the 18 sites where it had been recently applied, with the highest maximum concentration quantified of 46 µg/kg. However, a week after application only four fields had prothioconazole concentrations above the limit of quantification (LOQ). Fluroxypyr was applied in 11 sites but was not detected above LOQ. Glyphosate and AMPA were not detected. Interestingly, neonicotinoids were detected in 96% of all sampling sites, even though they were not reported as recently applied. Excluding neonicotinoids, 60% of sites were found to contain pesticide residues of compounds that were not previously applied, with boscalid and azoxystrobin detected in 15 of the 25 sites sampled. The total number of pesticides detected in Irish soils were significantly negatively correlated with clay fraction, while average pesticide concentrations were significantly positively correlated with log Kow values. 17 fields were found to have total pesticide concentrations in excess of 0.5 µg/kg, even when recently applied pesticides were removed from calculations. Theoretical consideration of quantified pesticides determined that azoxystrobin has high leaching risk, while boscalid, which was detected but not applied, has an accumulation risk. This information provides insight into the current level of pesticide contamination in Irish agricultural soil and contributes to the European-level effort to understand potential impacts of pesticide contamination in soil.

4.
Sci Rep ; 13(1): 11997, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491422

RESUMO

Wetlands are one of the major contributors of methane (CH4) emissions to the atmosphere and the intensity of emissions is driven by local environmental variables and spatial heterogeneity. Peatlands are a major wetland class and there are numerous studies that provide estimates of methane emissions at chamber or eddy covariance scales, but these are not often aggregated to the site/ecosystem scale. This study provides a robust approach to map dominant vegetation communities and to use these areas to upscale methane fluxes from chamber to site scale using a simple weighted-area approach. The proposed methodology was tested at three peatlands in Ireland over a duration of 2 years. The annual vegetation maps showed an accuracy ranging from 83 to 99% for near-natural to degraded sites respectively. The upscaled fluxes were highest (2.25 and 3.80 gC m-2 y-1) at the near-natural site and the rehabilitation (0.17 and 0.31 gC m-2 y-1), degraded (0.15 and 0.27 gC m-2 y-1) site emissions were close to net-zero throughout the study duration. Overall, the easy to implement methodology proposed in this study can be applied across various landuse types to assess the impact of peatland rehabilitation on methane emissions by mapping ecological change.

5.
Forensic Sci Int ; 350: 111791, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37499373

RESUMO

Glass fragments are often recovered from garments worn by the authors of certain types of crimes and are useful as they present strong connections to the scene at both the source and activity level. It is known that the transfer of glass fragments is impacted when recipient garments are dampened, such as by rain, however, the details of the effect are not clear. This research aimed to determine the impact of substrate dampness on glass retention. Across the three test garments, a cotton t-shirt was found to increase in retentiveness with increasing dampness, while a wool/polyester blend jumper and a cotton hoodie were both found to increase only to a point, before decreasing again when the garment was saturated. This is attributed to the construction of the fabrics, as it does not appear to be related to the identity of the textile itself. It was also found that the size distribution of fragments changed with dampness. All the garments retained a smaller proportion of fragments less than 0.5 mm in size when saturated or dampened than when dry, along with an increase in the proportion of fragments in the 1-1.5 mm and greater than 1.5 mm size categories. These results indicate that is important to consider the impact of substrate dampening when relevant, and that this consideration must be done holistically as different substrates respond to dampening in different ways. It also indicates that consideration of the size distribution in fragment populations may reveal additional information in complex scenarios.

6.
Sci Rep ; 13(1): 567, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631484

RESUMO

The majority of mammalian proteins are glycosylated, with the glycans serving to modulate a wide range of biological activities. Variations in protein glycosylation can have dramatic effects on protein stability, immunogenicity, antibody effector function, pharmacological safety and potency, as well as serum half-life. The glycosylation of therapeutic biologicals is a critical quality attribute (CQA) that must be carefully monitored to ensure batch-to-batch consistency. Notably, many factors can affect the composition of the glycans during glycoprotein production, and variations in glycosylation are among the leading causes of pharmaceutical batch rejection. Currently, the characterization of protein glycosylation relies heavily on methods that employ chromatography and/or mass spectrometry, which require a high level of expertise, are time-consuming and costly and, because they are challenging to implement during in-process biologics production or during in vitro glycan modification, are generally performed only post-production. Here we report a simplified approach to assist in monitoring glycosylation features during glycoprotein engineering, that employs flow cytometry using fluorescent microspheres chemically coupled to high-specificity glycan binding reagents. In our GlycoSense method, a range of carbohydrate-sensing microspheres with distinct optical properties may be combined into a multiplex suspension array capable of detecting multiple orthogonal glycosylation features simultaneously, using commonplace instrumentation, without the need for glycan release. The GlycoSense method is not intended to replace more detailed post-production glycan profiling, but instead, to complement them by potentially providing a cost-effective, rapid, yet robust method for use at-line as a process analytic technology (PAT) in a biopharmaceutical workflow or at the research bench. The growing interest in using in vitro glycoengineering to generate glycoproteins with well-defined glycosylation, provides motivation to demonstrate the capabilities of the GlycoSense method, which we apply here to monitor changes in the protein glycosylation pattern (GlycoPrint) during the in vitro enzymatic modification of the glycans in model glycoproteins.


Assuntos
Anticorpos , Glicoproteínas , Animais , Glicosilação , Glicoproteínas/metabolismo , Anticorpos/metabolismo , Espectrometria de Massas , Mamíferos/metabolismo , Polissacarídeos/metabolismo
7.
PeerJ ; 10: e13586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35855900

RESUMO

Besides the benefits of plant protection products (PPPs) for agricultural production, there is an increasing acknowledgement of the associated potential environmental risks. Here, we examine the feasibility of summarizing the extent of PPP usage at the country level, using Ireland as a case study, as well as at the European level. We used the area over which PPPs are applied (basic area) as an example variable that is relevant to initially assess the geographic extent of environmental risk. In Irish agricultural systems, which are primarily grass-based, herbicides fluroxypyr and glyphosate are the most widely applied active substances (ASs) in terms of basic area, followed by the fungicides chlorothalonil and prothioconazole that are closely associated with arable crops. Although all EU countries are subject to Regulation (EC) No 1185/2009, which sets the obligation of PPP usage data reporting at the national level, we only found usable data that met our criteria for Estonia, Germany, Finland, and Spain (4 of 30 countries reviewed). Overall, the most widely applied fungicide and herbicide in terms of basic area were prothioconazole (20%, 7% and 5% of national cultivated areas of Germany, Estonia and Ireland) and glyphosate (11%, 8% and 5% of national cultivated areas of Spain, Estonia and Ireland) respectively, although evaluations using application frequency may result in the observation of different trends. Several recommendations are proposed to tackle current data gaps and deficiencies in accessibility and usability of pesticide usage data across the EU in order to better inform environmental risk assessment and promote evidence-based policymaking.


Assuntos
Fungicidas Industriais , Herbicidas , Magnoliopsida , Praguicidas , Agricultura , Irlanda
8.
Lancet Glob Health ; 10(4): e543-e554, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35303463

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a global health emergency. We aimed to evaluate treatment outcomes among people with MDR-TB in Sierra Leone and investigate social and health factors associated with adverse treatment outcomes. METHODS: This national, retrospective cohort study recruited all people notified with MDR-TB to the Sierra Leone National TB Programme, admitted to Lakka hospital (Lakka, Western Area Rural District, Freetown, Sierra Leone) between April, 2017, and September, 2019. Participants were followed up to May, 2021. People who were eligible but had no social or health data available, or were subsequently found to have been misdiagnosed, were excluded from participation. MDR-TB treatment was with the 2017 WHO-recommended short (9-11 month) or long (18-24 month) aminoglycoside-containing regimens. Multivariable logistic regression models examined associations of programmatic social and health data with WHO-defined adverse treatment outcomes (death, treatment failure, loss to follow-up). FINDINGS: Of 370 notified MDR-TB cases, 365 (99%) were eligible for study participation (five participants were excluded due to lack of social or health data or misdiagnosis). Treatment was started by 341 (93%) of 365 participants (317 received the short regimen, 24 received the long regimen, and 24 received no treatment). Median age was 35 years (IQR 26-45), 263 (72%) of 365 were male and 102 (28%) were female, 71 (19%) were HIV-positive, and 127 (35%) were severely underweight (body-mass index <16·5 kg/m2). Overall, 267 (73%) of 365 participants had treatment success, 95 (26%) had an adverse outcome, and three (1%) were still on treatment in May, 2021. Age 45-64 years (adjusted odds ratio [aOR] 2·4, 95% CI 1·2-5·0), severe underweight (aOR 4·2, 1·9-9·3), untreated HIV (aOR 10, 2·6-40·0), chronic lung disease (aOR 2·0, 1·0-4·2), previously unsuccessful drug-sensitive tuberculosis retreatment (aOR 4·3, 1·0-19), and a long regimen (aOR 6·5, 2·3-18·0) were associated with adverse outcomes. A sensitivity analysis showed that prothionamide resistance (aOR 3·1, 95% CI 1·5-10·0) and aminoglycoside-related complete deafness (aOR 6·6, 1·3-35) were independently associated with adverse outcomes. INTERPRETATION: MDR-TB treatment success in Sierra Leone approached WHO targets and the short regimen was associated with higher success. The social and health factors associated with adverse outcomes in this study suggest a role for integrated tuberculosis, HIV, and non-communicable disease services alongside nutritional and socioeconomic support for people with MDR-TB and emphasise the urgent need to scale up coverage of all-oral aminoglycoside-sparing regimens. FUNDING: Wellcome Trust, Joint Global Health Trials.


Assuntos
Infecções por HIV , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Adulto , Aminoglicosídeos , Antituberculosos/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Serra Leoa/epidemiologia , Magreza , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
9.
Langmuir ; 38(9): 2840-2851, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35192365

RESUMO

Molecular dynamics (MD) force fields for lipids and ions are typically developed independently of one another. In simulations consisting of both lipids and ions, lipid-ion interaction energies are estimated using a predefined set of mixing rules for Lennard-Jones (LJ) interactions. This, however, does not guarantee their reliability. In fact, compared to the quantum mechanical reference data, Lorentz-Berthelot mixing rules substantially underestimate the binding energies of Na+ ions with small-molecule analogues of lipid headgroups, yielding errors on the order of 80 and 130 kJ/mol, respectively, for methyl acetate and diethyl phosphate. Previously, errors associated with mixing force fields have been reduced using approaches such as "NB-fix" in which LJ interactions are computed using explicit cross terms rather than those from mixing rules. Building on this idea, we derive explicit lipid-ion cross terms that also may implicitly include many-body cooperativity effects. Additionally, to account for the interdependency between cross terms, we optimize all cross terms simultaneously by performing high-dimensional searches using our ParOpt software. The cross terms we obtain reduce the errors due to mixing rules to below 10 kJ/mol. MD simulation of the lipid bilayer conducted using these optimized cross terms resolves the structural discrepancies between our previous simulations and small-angle X-ray and neutron scattering experiments. These results demonstrate that simulations of lipid bilayers with ions that are accurate up to structural data from scattering experiments can be performed without explicit polarization terms. However, it is worth noting that such NB-fix cross terms are not based on any physical principle; a polarizable lipid model would be more realistic and is still desired. Our approach is generic and can be applied to improve the accuracies of simulations employing mixed force fields.


Assuntos
Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Íons/química , Bicamadas Lipídicas/química , Reprodutibilidade dos Testes , Termodinâmica
10.
Wellcome Open Res ; 7: 92, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37224318

RESUMO

Background : People with tuberculosis disease and their household members may suffer direct out-of-pocket expenses and indirect costs of lost income. These tuberculosis-related costs can worsen poverty, make tuberculosis treatment completion unaffordable, impair quality of life and increase the risk of death. Costs due to tuberculosis are usually defined as catastrophic if they exceed 20% of the pre-disease annual household income. The World Health Organisation strategy to "End TB" and the United Nations Sustainable Development Goals include the target that no households should face catastrophic costs due to tuberculosis. However, there is limited evidence and policy concerning how this global priority of eliminating catastrophic costs due to tuberculosis should be achieved. This systematic review and meta-analysis aims to address this knowledge gap. Methods : Publications assessing interventions that aimed to eliminate catastrophic costs will be identified by searching three electronic databases (PubMed, Scopus and Web of Science) together with reference lists from pertinent publications. We will screen eligible studies, extract data, and assess the risk of bias with the quality assessment tool from the National Heart, Lung, and Blood Institute. Discrepancies will be resolved by discussion between the reviewers. If we find sufficient comparable studies quantifying strategies to eliminate catastrophic costs then a meta-analysis will be performed. This systematic review and meta-analysis is registered with the PROSPERO database (CRD42022292410). Conclusion : This systematic review and meta-analysis aims to rigorously assess the evidence for strategies to eliminate catastrophic costs due to tuberculosis.

12.
Sci Total Environ ; 754: 142433, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254846

RESUMO

The ability of peatlands to remove and store atmospheric carbon (C) depends on the drainage characteristics, which can be challenging to accommodate in biogeochemical models. Many studies indicate that restoration (by rewetting) of damaged peatlands can re-establish their capacity as a natural C sink. The purpose of this research was to improve the biogeochemical modelling of peatlands using the ECOSSE process-based model, which will account for the effects of drainage and rewetting during simulation, and potentially contribute towards improved estimation of carbon dioxide (CO2) fluxes from peatlands, using the IPCC Tier 3 approach. In this study, we present a new drainage factor with seasonal variability Dfa (i) developed specifically for ECOSSE, using empirical data from two drained and rewetted Irish peatlands. Dfa(i) was developed from the Blackwater drained bare-peat site (BWdr), and its application was tested at the vegetated Moyarwood peatland site under drained (MOdr) and rewetted conditions (MOrw). Dfa(i) was applied to the rainfall model inputs for the periods of active drainage in conjunction with the measured water table (WT) inputs. The results indicate that Dfa(i) application can improve the model performance to predict model-estimated water level (WL) and CO2 fluxes under drained conditions [WL: r2 = 0.89 (BWdr) and 0.94 (Modr); CO2: r2 = 0.66 (BWdr) and 0.78 (MOdr)] along with model-ability to capture their seasonal trends. The prediction of WL for the rewetted period was less successful at the MOrw site, where the simulation was run for drained to rewetted, which would suggest that additional work on the water model component is still needed. Despite this, the application of Dfa(i) showed successful model simulation of CO2 fluxes at MOrw (r2 = 0.75) and model ability to capture seasonal trends. This work hopes to positively contribute towards potential future development of Tier 3 methodology for estimating emissions/sinks in peatlands.

13.
Eur Respir J ; 56(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32366485

RESUMO

BACKGROUND: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights the lack of evidence concerning tuberculosis-related quality of life (QOL). METHODS: Participants were recruited in 32 Peruvian communities between July 13, 2016 and February 24, 2018 and followed-up until November 8, 2019. Inclusion criteria were age ≥15 years for "patients" (n=1545) starting treatment for tuberculosis disease in health centres; "contacts" (n=3180) who shared a patient's household for ≥6 h·week-1; and randomly selected "controls" (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with QOL, health, energy, activities of daily living (ADL), self, relationships, money and living place. FINDINGS: Newly diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p≤0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13 points had 4.2-fold (95% CI 2.3-7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later, and for patients with successful treatment QOL became similar to participants who had never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001). CONCLUSIONS: Tuberculosis was associated with impaired psychosocioeconomic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL eight-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care.


Assuntos
Qualidade de Vida , Tuberculose Resistente a Múltiplos Medicamentos , Atividades Cotidianas , Adolescente , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Resultado do Tratamento
15.
Lancet Infect Dis ; 20(1): 110-122, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678031

RESUMO

BACKGROUND: The epidemiological impact and cost-effectiveness of social protection and biomedical interventions for tuberculosis-affected households might be improved by risk stratification. We therefore derived and externally validated a household-level risk score to predict tuberculosis among contacts of patients with tuberculosis. METHODS: In this prospective cohort study, we recruited tuberculosis-affected households from 15 desert shanty towns in Ventanilla and 17 urban communities in Callao, Lima, Peru. Tuberculosis-affected households included index patients with a new diagnosis of tuberculosis and their contacts who reported being in the same house as the index patient for more than 6 h per week in the 2 weeks preceding index patient diagnosis. Tuberculosis-affected households were not included if the index patient had no eligible contacts or lived alone. We followed contacts until 2018 and defined household tuberculosis, the primary outcome, as any contact having any form of tuberculosis within 3 years. We used logistic regression to identify characteristics of index patients, contacts, and households that were predictive of household tuberculosis, and used these to derive and externally validate a household-level score. FINDINGS: Between Dec 12, 2007, and Dec 31, 2015, 16 505 contacts from 3 301 households in Ventanilla were included in a derivation cohort. During the 3-year follow-up, tuberculosis occurred in contacts of index patients in 430 (13%, 95% CI 12-14) households. Index patient predictors were pulmonary tuberculosis and sputum smear grade, age, and the maximum number of hours any contact had spent with the index patient while they had any cough. Household predictors were drug use, schooling of the female head of a household, and lower food spending. Contact predictors were if any of the contacts were children, number of lower-weight (body-mass index [BMI] <20·0 kg/m2) adult contacts, number of normal-weight (BMI 20·0-24·9 kg/m2) adult contacts, and number of past or present household members who previously had tuberculosis. In this derivation cohort, the score c statistic was 0·77 and the risk of household tuberculosis in the highest scoring quintile was 31% (95% CI 25-38; 65 of 211) versus 2% (95% CI 0-4; four of 231) in the lowest scoring quintile. We externally validated the risk score in a cohort of 4248 contacts from 924 households in Callao recruited between April 23, 2014, and Dec 31, 2015. During follow-up, tuberculosis occurred in contacts of index patients in 120 (13%, 95% CI 11-15) households. The score c statistic in this cohort was 0·75 and the risk of household tuberculosis in the highest scoring quintile was 28% (95% CI 21-36; 43 of 154) versus 1% (95% CI 0-5; two of 148) in the lowest scoring quintile. The highest-scoring third of households captured around 70% of all tuberculosis among contacts. A simplified risk score including only five variables performed similarly, with only a small reduction in performance. INTERPRETATION: This externally validated score will enable comprehensive biosocial, household-level interventions to be targeted to tuberculosis-affected households that are most likely to benefit. FUNDING: Wellcome Trust, Medical Research Council, Department of Health and Social Care, Department for International Development, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Innovation for Health and Development.


Assuntos
Busca de Comunicante/estatística & dados numéricos , Características da Família , Inquéritos e Questionários , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Tosse/etiologia , Feminino , Humanos , Drogas Ilícitas , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Escarro/microbiologia , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
17.
Lancet Infect Dis ; 19(5): 519-528, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30910427

RESUMO

BACKGROUND: Active case-finding among contacts of patients with tuberculosis is a global health priority, but the effects of active versus passive case-finding are poorly characterised. We assessed the contribution of active versus passive case-finding to tuberculosis detection among contacts and compared sex and disease characteristics between contacts diagnosed through these strategies. METHODS: In shanty towns in Callao, Peru, we identified index patients with tuberculosis and followed up contacts aged 15 years or older for tuberculosis. All patients and contacts were offered free programmatic active case-finding entailing sputum smear microscopy and clinical assessment. Additionally, all contacts were offered intensified active case-finding with sputum smear and culture testing monthly for 6 months and then once every 4 years. Passive case-finding at local health facilities was ongoing throughout follow-up. FINDINGS: Between Oct 23, 2002, and May 26, 2006, we identified 2666 contacts, who were followed up until March 1, 2016. Median follow-up was 10·0 years (IQR 7·5-11·0). 232 (9%) of 2666 contacts were diagnosed with tuberculosis. The 2-year cumulative risk of tuberculosis was 4·6% (95% CI 3·5-5·5), and overall incidence was 0·98 cases (95% CI 0·86-1·10) per 100 person-years. 53 (23%) of 232 contacts with tuberculosis were diagnosed through active case-finding and 179 (77%) were identified through passive case-finding. During the first 6 months of the study, 23 (45%) of 51 contacts were diagnosed through active case-finding and 28 (55%) were identified through passive case-finding. Contacts diagnosed through active versus passive case-finding were more frequently female (36 [68%] of 53 vs 85 [47%] of 179; p=0·009), had a symptom duration of less than 15 days (nine [25%] of 36 vs ten [8%] of 127; p=0·03), and were more likely to be sputum smear-negative (33 [62%] of 53 vs 62 [35%] of 179; p=0·0003). INTERPRETATION: Although active case-finding made an important contribution to tuberculosis detection among contacts, passive case-finding detected most of the tuberculosis burden. Compared with passive case-finding, active case-finding was equitable, helped to diagnose tuberculosis earlier and usually before a positive result on sputum smear microscopy, and showed a high burden of undetected tuberculosis among women. FUNDING: Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and IFHAD: Innovation for Health and Development.


Assuntos
Busca de Comunicante/estatística & dados numéricos , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adulto , Características da Família , Feminino , Seguimentos , Humanos , Incidência , Masculino , Peru/epidemiologia , Estudos Prospectivos , Fatores Sexuais , Escarro/microbiologia , Tuberculose/prevenção & controle , Adulto Jovem
18.
Biochim Biophys Acta Biomembr ; 1861(5): 907-915, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30742804

RESUMO

A distinguishing feature of Archaeal plasma membranes is that their phospholipids contain ether-links, as opposed to bacterial and eukaryotic plasma membranes where phospholipids primarily contain ester-links. Experiments show that this chemical difference in headgroup-tail linkage does produce distinct differences in model bilayer properties. Here we examine the effects of salt on bilayer structure in the case of an ether-linked lipid bilayer. We use molecular dynamics simulations and compare equilibrium properties of two model lipid bilayers in NaCl salt solution - POPC and its ether-linked analog that we refer to as HOPC. We make the following key observations. The headgroup region of HOPC "adsorbs" fewer ions compared to the headgroup region of POPC. Consistent with this, we note that the Debye screening length in the HOPC system is ∼ 10% shorter than that in the POPC system. Herein, we introduce a protocol to identify the lipid-water interfacial boundary that reproduces the bulk salt distribution consistent with Gouy-Chapman theory. We also note that the HOPC bilayer has excess solvent in the headgroup region when compared to POPC, coinciding with a trough in the electrostatic potential. Waters in this region have longer autocorrelation times and smaller lateral diffusion rates compared to the corresponding region in the POPC bilayer, suggesting that the waters in HOPC are more strongly coordinated to the lipid headgroups. Furthermore, we note that it is this region of tightly coordinated waters in the HOPC system that has a lower density of Na+ ions. Based on these observations we conclude that an ether-linked lipid bilayer has a lower binding affinity for Na+ compared to an ester-linked lipid bilayer.


Assuntos
Ésteres/química , Éteres/química , Bicamadas Lipídicas/química , Fosfolipídeos/química , Cloreto de Sódio/química , Simulação de Dinâmica Molecular , Estrutura Molecular , Água/química
19.
Trop Med Int Health ; 23(8): 850-859, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29862612

RESUMO

OBJECTIVES: Mobile phone interventions have been advocated for tuberculosis care, but little is known about access of target populations to mobile phones. We studied mobile phone access among patients with tuberculosis, focusing on vulnerable patients and patients who later had adverse treatment outcomes. METHODS: In a prospective cohort study in Callao, Peru, we recruited and interviewed 2584 patients with tuberculosis between 2007 and 2013 and followed them until 2016 for adverse treatment outcomes using national treatment registers. Subsequently, we recruited a further 622 patients between 2016 and 2017. Data were analysed using logistic regression and by calculating relative risks (RR). RESULTS: Between 2007 and 2013, the proportion of the general population of Peru without mobile phone access averaged 7.8% but for patients with tuberculosis was 18% (P < 0.001). Patients without access were more likely to hold a lower socioeconomic position, suffer from food insecurity and be older than 50 years (all P < 0.01). Compared to patients with mobile phone access, patients without access at recruitment were more likely to subsequently have incomplete treatment (20% vs. 13%, RR = 1.5; P = 0.001) or an adverse treatment outcome (29% vs. 23% RR = 1.3; P = 0.006). Between 2016 and 2017, the proportion of patients without access dropped to 8.9% overall, but remained the same (18%) as in 2012 among the poorest third. CONCLUSION: Access to mobile phones among patients with tuberculosis is insufficient, and rarest in patients who are poorer and later have adverse treatment outcomes. Thus, mobile phone interventions to improve tuberculosis care may be least accessed by the priority populations for whom they are intended. Such interventions should ensure access to mobile phones to enhance equity.


Assuntos
Telefone Celular/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Tuberculose/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Peru , Pobreza/estatística & dados numéricos , Estudos Prospectivos , Envio de Mensagens de Texto/estatística & dados numéricos , Tuberculose/terapia
20.
Am J Trop Med Hyg ; 98(6): 1614-1623, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29692300

RESUMO

Early detection and diagnosis of tuberculosis (TB) is a global priority. Prolonged symptom duration before TB diagnosis is associated with increased morbidity, mortality, and risk of transmission. We aimed to determine socioeconomic and behavioral factors associated with diagnostic delays among patients with TB. Data were collected from 105 patients with TB using a semi-structured interview guide in Lima, Peru. Factors associated with diagnostic delay were analyzed using negative binomial regression. The median delay from when symptoms commenced and the first positive diagnostic sample in public health facilities was 57 days (interquartile range: 28-126). In multivariable analysis, greater diagnostic delay was independently associated with patient older age, female gender, lower personal income before diagnosis, living with fewer people, and having more visits to professional health facilities before diagnosis (all P < 0.05). Patients who first sought care at a private health facility had more visits overall to professional health facilities before diagnosis than those who first sought care from public or insured employee health facilities and had longer diagnostic delay in analysis adjusted for age and gender. Patients with TB were significantly more likely to first self-medicate than to visit professional health facilities before diagnosis (P = 0.003). Thus, diagnostic delay was prolonged, greatest among older, low-income women, and varied according to the type of care sought by individuals when their symptoms commenced. These findings suggest that TB case-finding initiatives should target vulnerable groups in informal and private health facilities, where many patients with TB first seek health care.


Assuntos
Diagnóstico Tardio/estatística & dados numéricos , Comportamentos Relacionados com a Saúde , Tuberculose/diagnóstico , Adulto , Fatores Etários , Assistência Ambulatorial/estatística & dados numéricos , Estudos Transversais , Diagnóstico Tardio/economia , Diagnóstico Tardio/psicologia , Escolaridade , Feminino , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peru , Análise de Regressão , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos , Fatores de Tempo , Adulto Jovem
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