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Alternative splicing allows multiple transcripts to be generated from the same gene to diversify the protein repertoire and gain new functions despite a limited coding genome. It can impact a wide spectrum of biological processes, including disease. However, its significance has long been underestimated due to limitations in dissecting the precise role of each splicing isoform in a physiological context. Furthermore, identifying key regulatory elements to correct deleterious splicing isoforms has proven equally challenging, increasing the difficulty of tackling the role of alternative splicing in cell biology. In this work, we take advantage of dCasRx, a catalytically inactive RNA targeting CRISPR-dCas13 ortholog, to efficiently switch alternative splicing patterns of endogenous transcripts without affecting overall gene expression levels cost-effectively. Additionally, we demonstrate a new application for the dCasRx splice-editing system to identify key regulatory RNA elements of specific splicing events. With this approach, we are expanding the RNA toolkit to better understand the regulatory mechanisms underlying alternative splicing and its physiological impact in various biological processes, including pathological conditions.
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The design of novel low-dimensional carbon materials is at the forefront of modern chemistry. Recently, on-surface covalent synthesis has emerged as a powerful strategy to synthesize previously precluded compounds and polymers. Here, we report a scanning probe microscopy study, complemented by theoretical calculations, about the sequential skeletal rearrangement of sumanene-based precursors into a coronene-based organometallic network by stepwise intra- and inter-molecular reactions on Au(111). Interestingly, upon higher annealing, the formed organometallic networks evolve into two-dimensional coronene-based covalently-linked patches through intermolecular homocoupling reactions. A new reaction mechanism is proposed based on the role of C-Au-C motifs to promote two stepwise carbon-carbon couplings to form cyclobutadiene bridges. Our results pave avenues for the conversion of molecular precursors on surfaces, affording the design of unexplored two-dimensional organometallic and covalent materials.
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BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease that in many cases produces disability, having a high impact in patients' lives, reducing significantly their quality of life. The aim of this study was to agree on a set of proposals to improve the current management of MS within the Spanish National Health System (SNHS) and apply the Social Return on Investment (SROI) method to measure the potential social impact these proposals would create. METHODS: A Multidisciplinary Working Team of nine experts, with representation from the main stakeholders regarding MS, was set up to agree on a set of proposals to improve the management of MS. A forecast SROI analysis was carried out, with a one-year timeframe. Data sources included an expert consultation, a narrative literature review and a survey to 532 MS patients. We estimated the required investment of a hypothetical implementation, as well as the potential social value that it could create. We calculated outcomes in monetary units and we measured intangible outcomes through financial proxies. RESULTS: The proposed ideal approach revealed that there are still unmet needs related to MS that can be addressed within the SNHS. Investment would amount to 148 million and social return to 272 million , so each euro invested could yield almost 2 of social return. CONCLUSIONS: This study could guide health interventions, resulting in money savings for the SNHS and increases in patients' quality of life.
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Esclerose Múltipla/terapia , Programas Nacionais de Saúde/economia , Valores Sociais , Análise Custo-Benefício , Humanos , Investimentos em Saúde , Esclerose Múltipla/economia , EspanhaRESUMO
BACKGROUND: Whole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual transmission links within clusters is limited. Here, we used a 2-step approach based on Bayesian transmission reconstruction to (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, and (3) estimate when transmission happened. METHODS AND FINDINGS: We developed our transmission reconstruction method using genomic and epidemiological data from a population-based study from Valencia Region, Spain. Tuberculosis (TB) incidence during the study period was 8.4 cases per 100,000 people. While the study is ongoing, the sampling frame for this work includes notified TB cases between 1 January 2014 and 31 December 2016. We identified a total of 21 transmission clusters that fulfilled the criteria for analysis. These contained a total of 117 individuals diagnosed with active TB (109 with epidemiological data). Demographic characteristics of the study population were as follows: 80/109 (73%) individuals were Spanish-born, 76/109 (70%) individuals were men, and the mean age was 42.51 years (SD 18.46). We found that 66/109 (61%) TB patients were sputum positive at diagnosis, and 10/109 (9%) were HIV positive. We used the data to reveal individual transmission links, and to identify index cases, missing cases, likely transmitters, and associated transmission risk factors. Our Bayesian inference approach suggests that at least 60% of index cases are likely misidentified by local public health. Our data also suggest that factors associated with likely transmitters are different to those of simply being in a transmission cluster, highlighting the importance of differentiating between these 2 phenomena. Our data suggest that type 2 diabetes mellitus is a risk factor associated with being a transmitter (odds ratio 0.19 [95% CI 0.02-1.10], p < 0.003). Finally, we used the most likely timing for transmission events to study when TB transmission occurred; we identified that 5/14 (35.7%) cases likely transmitted TB well before symptom onset, and these were largely sputum negative at diagnosis. Limited within-cluster diversity does not allow us to extrapolate our findings to the whole TB population in Valencia Region. CONCLUSIONS: In this study, we found that index cases are often misidentified, with downstream consequences for epidemiological investigations because likely transmitters can be missed. Our findings regarding inferred transmission timing suggest that TB transmission can occur before patient symptom onset, suggesting also that TB transmits during sub-clinical disease. This result has direct implications for diagnosing TB and reducing transmission. Overall, we show that a transition to individual-based genomic epidemiology will likely close some of the knowledge gaps in TB transmission and may redirect efforts towards cost-effective contact investigations for improved TB control.
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Busca de Comunicante/métodos , Genoma Bacteriano , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/transmissão , Sequenciamento Completo do Genoma , Adolescente , Adulto , Idoso , Teorema de Bayes , Biomarcadores , Feminino , Genômica , Soropositividade para HIV/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Filogenia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Espanha/epidemiologia , Resultado do Tratamento , Tuberculose Pulmonar/epidemiologia , Adulto JovemRESUMO
The objective of this study is to compare the efficacy and cost of specialised individually delivered parent training (PT) for preschool children with attention-deficit/hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). This is a multi-centre three-arm, parallel group randomised controlled trial conducted in National Health Service Trusts. The participants included in this study were preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. New Forest Parenting Programme (NFPP)-12-week individual, home-delivered ADHD PT programme; Incredible Years (IY)-12-week group-based, PT programme initially designed for children with behaviour problems were the interventions. Primary outcome-Parent ratings of child's ADHD symptoms (Swanson, Nolan & Pelham Questionnaire-SNAP-IV). Secondary outcomes-teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputations). Intervention and other costs were estimated using standardized approaches. NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms [mean difference - 0.009 95% CI (- 0.191, 0.173), p = 0.921] or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms [- 0.189 95% CI (- 0.380, 0.003), p = 0.053]. NFPP significantly reduced parent-rated conduct problems compared to TAU across scales (p values < 0.05). No significant benefits of IY over TAU were seen for parent-rated SNAP, ADHD symptoms [- 0.16 95% CI (- 0.37, 0.04), p = 0.121] or parent-rated conduct problems (p > 0.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1591 versus £2103). Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches.
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Transtorno do Deficit de Atenção com Hiperatividade/terapia , Terapia Familiar/métodos , Poder Familiar , Pais/educação , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pais/psicologia , Comportamento Problema , Inquéritos e Questionários , Resultado do TratamentoRESUMO
At industrial scale, thermal hydrolysis is the most used process to enhance biodegradability of the sludge produced in wastewater treatment plants. Through statistically guided Box-Behnken experimental design, the present study analyses the effect of TH as pre-treatment applied to activated sludge. The selected process variables were temperature (130-180 °C), time (5-50 min) and decompression mode (slow or steam-explosion effect), and the parameters evaluated were sludge solubilisation and methane production by anaerobic digestion. A quadratic polynomial model was generated to compare the process performance for the 15 different combinations of operation conditions by modifying the process variables evaluated. The statistical analysis performed exhibited that methane production and solubility were significantly affected by pre-treatment time and temperature. During high intensity pre-treatment (high temperature and long times), the solubility increased sharply while the methane production exhibited the opposite behaviour, indicating the formation of some soluble but non-biodegradable materials. Therefore, solubilisation is not a reliable parameter to quantify the efficiency of a thermal hydrolysis pre-treatment, since it is not directly related to methane production. Based on the operational parameters optimization, the estimated optimal thermal hydrolysis conditions to enhance of sewage sludge digestion were: 140-170 °C heating temperature, 5-35min residence time, and one sudden decompression.
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Biodegradação Ambiental , Esgotos , Anaerobiose , Hidrólise , Metano/biossíntese , TemperaturaRESUMO
INTRODUCTION: The introduction of conjugated anti-pneumonia vaccines has led to a change in the epidemiology of Invasive Pneumococcal Disease (IPD). The aim of this study is to describe the trends in IPD in the Community of Valencia during the period 2007-2012. MATERIAL AND METHODS: A retrospective, descriptive and longitudinal study was conducted on IPD in the Community of Valencia during the period 2007-2012, The information sources used were the Epidemiological Surveillance Analysis (Análisis de la Vigilancia Epidemiológica (AVE)) and the Valencian Microbiology Network (Red Microbiológica Valenciana (RedMIVA)) of the Valencia Health Department. RESULTS: The incidence of IPD decreased between 2007 and 2012 in all age groups, mainly in the under 5 year-olds, dropping from 30.5 cases to 12.3 cases per 10(5) inhabitants (p< .001). Pneumonia was the principal presentation of the disease, with a decrease in its rates from 6.9 to 4.1 cases per 10(5) inhabitants (p< .001). A gradual, non-significant, reduction from 26% to 12% (p=.23) was observed in the proportion of cases due to the serotypes contained in the heptavalent vaccine (PCV7), mainly in the under 5 year-olds. The cases due to additional serotypes in 13-valent conjugated vaccine (1, 3, 5, 6A, 7F and 19A) also showed a decreasing trend, mainly in vaccinated under 5 year-olds (52.6% vs 14.3%; p=.03), while the cases due to non-vaccine serotypes significantly increased from 42.3% to 56.7% in the general population (p=.002), and from 47.4% to 78.6% in vaccinated under 5 year-olds (p=.08). CONCLUSIONS: The results of this study show a reduction in the incidence of IPD, with a decrease in the proportion of cases produced by vaccine serotypes, and an increase in the proportion of those not vaccinated. Epidemiological Surveillance is necessary to monitor the trends in the disease.
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Monitoramento Epidemiológico , Infecções Pneumocócicas/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Estudos Retrospectivos , Espanha/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
Thermal steam-explosion is the most extended hydrolysis pretreatment to enhance anaerobic digestion of sludge. Thermal hydrolysis key parameters are temperature (T) and time (t), and the generally accepted values reported from full-scale information are: 150-230 °C and 20-60 min. This study assesses the influence of different temperature-time-flash combinations (110-180 °C, 5-60 min, 1-3 re-flashing) on the anaerobic degradation of secondary sludge through biochemical methane potential (BMP) tests. All the conditions tested presented higher methane production compared to the untreated sludge, and both solubilization (after the hydrolysis) and degradation (by anaerobic digestion) increased linearly when increasing the severity (T-t) of the pretreatment, reaching 40% solubilization and degradation of the particulate matter at 180° C-60 min. However, for the 180 °C temperature, the treatment time impacted negatively on the lag phase. No influence of re-flashing the pretreated matter was observed. In conclusion, thermal steam-explosion at short operation times (5 min) and moderate temperatures (145 °C) seems to be very attractive from a degradation point of view thus presenting a methane production enhancement similar to the one obtained at 180°C and without negative influence of the lag phase.
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Biocombustíveis , Reatores Biológicos , Esgotos , Vapor , Anaerobiose , Explosões , Hidrólise , Metano/metabolismo , TemperaturaRESUMO
Two-phase anaerobic systems are being increasingly implemented for the treatment of both sewage sludge and organic fraction of municipal solid waste. Despite the good amount of mathematical models in anaerobic digestion, few have been applied in two-phase systems. In this study, a three-reaction mechanistic model has been developed, implemented and validated by using experimental data from a long-term anaerobic two-phase (TPAD) digester treating sewage sludge. A sensitivity analysis shows that the most influential parameters of the model are the ones related to the hydrolysis reaction and the activity of methanogens in the thermophilic reactor. The calibration procedure highlights a noticeable growth rate of the thermophilic methanogens throughout the evaluation period. Overall, all the measured variables are properly predicted by the model during both the calibration and the cross-validation periods. The model's representation of the organic matter behaviour is quite good. The most important disagreements are observed for the biogas production especially during the validation period. The whole application procedure underlines the ability of the model to properly predict the behaviour of this bioprocess.
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Modelos Teóricos , Esgotos , Gerenciamento de Resíduos , Anaerobiose , Reatores BiológicosRESUMO
INTRODUCTION: the aim of this study is to test the encoding deficit hypothesis in Alzheimer disease (AD) using a recent method for correcting memory tests. To this end, a Spanish-language adaptation of the Free and Cued Selective Reminding Test was interpreted using the Item Specific Deficit Approach (ISDA), which provides three indices: Encoding Deficit Index, Consolidation Deficit Index, and Retrieval Deficit Index. METHODS: We compared the performances of 15 patients with AD and 20 healthy control subjects and analysed results using either the task instructions or the ISDA approach. RESULTS: patients with AD displayed deficient encoding of more than half the information, but items that were encoded properly could be retrieved later with the help of the same semantic clues provided individually during encoding. Virtually all the information retained over the long-term was retrieved by using semantic clues. Encoding was shown to be the most impaired process, followed by retrieval and consolidation. Discriminant function analyses showed that ISDA indices are more sensitive and specific for detecting memory impairments in AD than are raw scores. CONCLUSIONS: These results indicate that patients with AD present impaired information encoding, but they benefit from semantic hints that help them recover previously learned information. This should be taken into account for intervention techniques focusing on memory impairments in AD.
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Doença de Alzheimer/psicologia , Transtornos da Memória/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Rememoração Mental , Testes Neuropsicológicos , Semântica , Aprendizagem VerbalRESUMO
Aging is generally associated with a decline in important cognitive functions that can be observed in EEG. Physical activity in older adults should be considered one of the main strategies to promote health and prevent disease in the elderly. The present study aimed to systematically review studies of EEG activity and cognitive function changes associated with physical activity in older adults. Records from PubMed, Scopus, and EBSCO databases were searched and, following the PRISMA guidelines, nine studies were included in the present systematic review. A risk of bias assessment was performed using the National Institute of Health Quality Assessment Tool for Case-control Studies instrument. The studies analyzed used two main strategies to determine the effects of physical activity on cognition and EEG: (1) multiscale entropy and power frequencies; and (2) event-related potentials. In terms of EEG activity, it can be concluded that exercise-induced neuroplasticity underlies improvements in cognitive function in healthy older adults.
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BACKGROUND: In June, 2021, WHO published the most complete catalogue to date of resistance-conferring mutations in Mycobacterium tuberculosis. Here, we aimed to assess the performance of genome-based antimicrobial resistance prediction using the catalogue and its potential for improving diagnostics in a real low-burden setting. METHODS: In this retrospective population-based genomic study M tuberculosis isolates were collected from 25 clinical laboratories in the low-burden setting of the Valencia Region, Spain. Culture-positive tuberculosis cases reported by regional public health authorities between Jan 1, 2014, and Dec 31, 2016, were included. The drug resistance profiles of these isolates were predicted by the genomic identification, via whole-genome sequencing (WGS), of the high-confidence resistance-causing variants included in the catalogue and compared with the phenotype. We determined the minimum inhibitory concentration (MIC) of the isolates with discordant resistance profiles using the resazurin microtitre assay. FINDINGS: WGS was performed on 785 M tuberculosis complex culture-positive isolates, and the WGS resistance prediction sensitivities were: 85·4% (95% CI 70·8-94·4) for isoniazid, 73·3% (44·9-92·2) for rifampicin, 50·0% (21·1-78·9) for ethambutol, and 57·1% (34·0-78·2) for pyrazinamide; all specificities were more than 99·6%. Sensitivity values were lower than previously reported, but the overall pan-susceptibility accuracy was 96·4%. Genotypic analysis revealed that four phenotypically susceptible isolates carried mutations (rpoB Leu430Pro and rpoB Ile491Phe for rifampicin and fabG1 Leu203Leu for isoniazid) known to give borderline resistance in standard phenotypic tests. Additionally, we identified three putative resistance-associated mutations (inhA Ser94Ala, katG Leu48Pro, and katG Gly273Arg for isoniazid) in samples with substantially higher MICs than those of susceptible isolates. Combining both genomic and phenotypic data, in accordance with the WHO diagnostic guidelines, we could detect two new multidrug-resistant cases. Additionally, we detected 11 (1·6%) of 706 isolates to be monoresistant to fluoroquinolone, which had been previously undetected. INTERPRETATION: We showed that the WHO catalogue enables the detection of resistant cases missed in phenotypic testing in a low-burden region, thus allowing for better patient-tailored treatment. We also identified mutations not included in the catalogue, relevant at the local level. Evidence from this study, together with future updates of the catalogue, will probably lead in the future to the partial replacement of culture testing with WGS-based drug susceptibility testing in our setting. FUNDING: European Research Council and the Spanish Ministerio de Ciencia.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Espanha/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Mutação/genética , Genômica , Organização Mundial da SaúdeRESUMO
The present study examines the effects of the frequency of phoneme, syllable, and word units in the Granada corpus of Spanish phonological speech errors. We computed several measures of phoneme and syllable frequency and selected the most sensitive ones, along with word (lexeme) frequency to compare the frequencies of source, target, and error units at the phoneme, syllable, and word levels. Results showed that phoneme targets have equivalent frequency to matched controls, whereas source phonemes are lower in frequency than chance (the Weak Source effect) and target phonemes (the David effect). Target, source, and error syllables and words also were of lower frequency than chance, and error words (when they occur) were lowest in frequency. Contrary to most current theories, which focus on faulty processing of the target units, present results suggest that faulty processing of the source units (phonemes, syllables, and words) is an important factor contributing to phonological speech errors. Low-frequency words and syllables have more difficulty ensuring that their phonemes, especially those of low frequency, are output only in their correct locations.
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The aim of this work was to study in depth the behavior and optimization of a novel process, called advanced thermal hydrolysis (ATH), to determine its utility as a pretreatment (sludge solubilization) or postreatment (organic matter removal) for anaerobic digestion (AD) in the sludge line of wastewater treatment plants (WWTPs). ATH is based on a thermal hydrolysis (TH) process plus hydrogen peroxide (H(2)O(2)) addition and takes advantage of a peroxidation/direct steam injection synergistic effect. On the basis of the response surface methodology (RSM) and a modified Doehlert design, an empirical second-order polynomial model was developed for the total yield of: (a) disintegration degree [DD (%)] (solubilization), (b) filtration constant [F(c) (cm(2)/min)] (dewaterability), and (c) organic matter removal (%). The variables considered were operation time (t), temperature reached after initial heating (T), and oxidant coefficient (n = oxygen(supplied)/oxygen(stoichiometric)). As the model predicts, in the case of the ATH process with high levels of oxidant, it is possible to achieve an organic matter removal of up to 92%, but the conditions required are prohibitive on an industrial scale. ATH operated at optimal conditions (oxygen amount 30% of stoichiometric, 115 °C and 24 min) gave promising results as a pretreatment, with similar solubilization and markedly better dewaterability levels in comparison to those obtained with TH at 170 °C. The empirical validation of the model was satisfactory.
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Esgotos/análise , Temperatura , Purificação da Água/métodos , Análise da Demanda Biológica de Oxigênio , Carbono/análise , Filtração , Hidrólise , Compostos Orgânicos/isolamento & purificação , Solubilidade , Espanha , Água/químicaRESUMO
Experimental data obtained from the operation in a pilot plant are used to perform mass and energy balances to a global process combining units of thermal hydrolysis (TH) of secondary sludge, anaerobic digestion (AD) of hydrolysed secondary sludge together with fresh primary sludge, and cogeneration from biogas by using a gas engine in which the biogas produces electricity and heat from the exhaust gases. Three scenarios were compared, corresponding to the three digesters operated: C (conventional AD, 17 days residence time), B (combined TH + AD, same time), and A (TH + AD at half residence time). The biogas production of digesters B and A was 33 and 24% better, respectively when compared with C. In the case of the combined TH + AD process (scenarios A and B), the key factors in the energy balance were the recovery of heat from hot streams, and the concentration of sludge. The results of the balances showed that for 8% DS concentration of the secondary sludge tested in the pilot plant, the process can be energetically self-sufficient, but a fraction of the biogas must by-pass the gas engine to be directly burned. From an economic point of view, scenario B is more profitable in terms of green energy and higher waste removal, while scenario A reduces the digester volume required by a half. Considering a population of 100,000 inhabitants, the economic benefit is 87,600 /yr for scenario A and 132,373 /yr for B. This value can be increased to 223,867 /yr by increasing the sludge concentration of the feeding to the TH unit to a minimum value that allows use of all the biogas to produce green energy. This concentration is 13% DS, which is still possible from a practical point of view. Additional benefits gained with the combined TH + AD process are the enhancement of the digesters rheology and the possibility of getting Class A biosolids. The integration study presented here set the basis for the scale-up to a demonstration plant.
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Biocombustíveis , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Bactérias Anaeróbias/metabolismo , Reatores Biológicos , Hidrólise , Espanha , Temperatura , Termodinâmica , Eliminação de Resíduos Líquidos/economiaRESUMO
This study presents an evaluation of the hydrolytic activity of a continuous thermophilic anaerobic reactor in long-term operation. The hydrolytic coefficient was estimated by fitting a three-reaction model of the anaerobic digestion process with experimental data obtained from a pilot thermophilic digester operated for about 2 years. The model fitting and the cross-validation indicate that this model can represent the behavior of the system in a proper way; moreover, the results show a variation of the hydrolytic capacity of the system throughout the evaluation period. The increase in the hydrolytic coefficient is in agreement with the increase in the organic load applied to the reactor, which shows the capacity of the continuous reactor to select populations according to the input conditions of the system.
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Reatores Biológicos , Esgotos , Anaerobiose , Biomassa , Temperatura Alta , Hidrólise , Modelos Teóricos , Projetos PilotoRESUMO
Transmission is a driver of tuberculosis (TB) epidemics in high-burden regions, with assumed negligible impact in low-burden areas. However, we still lack a full characterization of transmission dynamics in settings with similar and different burdens. Genomic epidemiology can greatly help to quantify transmission, but the lack of whole genome sequencing population-based studies has hampered its application. Here, we generate a population-based dataset from Valencia region and compare it with available datasets from different TB-burden settings to reveal transmission dynamics heterogeneity and its public health implications. We sequenced the whole genome of 785 Mycobacterium tuberculosis strains and linked genomes to patient epidemiological data. We use a pairwise distance clustering approach and phylodynamic methods to characterize transmission events over the last 150 years, in different TB-burden regions. Our results underscore significant differences in transmission between low-burden TB settings, i.e., clustering in Valencia region is higher (47.4%) than in Oxfordshire (27%), and similar to a high-burden area as Malawi (49.8%). By modeling times of the transmission links, we observed that settings with high transmission rate are associated with decades of uninterrupted transmission, irrespective of burden. Together, our results reveal that burden and transmission are not necessarily linked due to the role of past epidemics in the ongoing TB incidence, and highlight the need for in-depth characterization of transmission dynamics and specifically tailored TB control strategies.
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Epidemias , Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/genética , Dinâmica Populacional , Tuberculose/epidemiologia , Sequenciamento Completo do GenomaRESUMO
Anaerobic digestion (AD) is the preferred option to stabilize sludge. However, the rate limiting step of solids hydrolysis makes it worth modifing the conventional mesophilic AD in order to increase the performance of the digester. The main strategies are to introduce a hydrolysis pre-treatment, or to modify the digestion temperature. Among the different pre-treatment alternatives, the thermal hydrolysis (TH) at 170 degrees C for 30 min, and the ultrasounds pre-treatment (US) at 30 kJ/kg TS were selected for the research, while for the non-conventional anaerobic digestion, the thermophilic (TAD) and the two-stage temperature phased AD (TPAD) were considered. Four pilot plants were operated, with the same configuration and size of anaerobic digester (200 L, continuously fed). The biogas results show a general increase compared to the conventional digestion, being the highest production per unit of digester for the process combining the thermal pre-treatment and AD (1.4 L biogas/L digester day compared to the value of 0.26 obtained in conventional digesters). The dewaterability of the digestate became enhanced for processes TH + AD and TPAD when compared with the conventional digestate, while it became worse for processes US + AD and TAD. In all the research lines, the viscosity in the digester was smaller compared to the conventional (which is a key factor for process performance and economics), and both thermal pre-treatment and thermophilic digestion (TAD and TPAD) assure a pathogen free digestate.
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Esgotos , Anaerobiose , Hidrólise , Solubilidade , TemperaturaRESUMO
The application of steam explosion between two stages of anaerobic digestion may improve energy recovery from sludge while increasing organic matter removal. The influence of the operating conditions of the thermal process: temperature (130-210 °C), retention time (5-45 min) and TS concentration (5.4-10.8%), on the efficiency of VS removal, the biochemical methane potential of hydrolysed sludge and the kinetic constant of the degradation were evaluated using a Taguchi design. Increasing temperature and time increased the removal of VS and the potential of methane production but the kinetic constant was higher at lower temperatures. An optimal operating scheme was found at 170 °C (6 barg), 25 min at the greatest TS concentration in the feeding. Under such conditions, the thermal energy obtained from biogas combustion in a CHP covered the requirements for vapour generation and a profit of 3.54 m-3 of sludge was estimated.
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Metano , Esgotos , Anaerobiose , Biocombustíveis , Reatores Biológicos , Hidrólise , Eliminação de Resíduos LíquidosRESUMO
Learning disabilities (LDs) have an estimated prevalence between 5% and 9% in the pediatric population and are associated with difficulties in reading, arithmetic, and writing. Previous electroencephalography (EEG) research has reported a lag in alpha-band development in specific LD phenotypes, which seems to offer a possible explanation for differences in EEG maturation. In this study, 40 adolescents aged 10-15 years with LDs underwent 10 sessions of Live Z-Score Training Neurofeedback (LZT-NF) Training to improve their cognition and behavior. Based on the individual alpha peak frequency (i-APF) values from the spectrogram, a group with normal i-APF (ni-APF) and a group with low i-APF (li-APF) were compared in a pre-and-post-LZT-NF intervention. There were no statistical differences in age, gender, or the distribution of LDs between the groups. The li-APF group showed a higher theta absolute power in P4 (p = 0.016) at baseline and higher Hi-Beta absolute power in F3 (p = 0.007) post-treatment compared with the ni-APF group. In both groups, extreme waves (absolute Z-score of ≥1.5) were more likely to move toward the normative values, with better results in the ni-APF group. Conversely, the waves within the normal range at baseline were more likely to move out of the range after treatment in the li-APF group. Our results provide evidence of a viable biomarker for identifying optimal responders for the LZT-NF technique based on the i-APF metric reflecting the patient's neurophysiological individuality.