Evaluating accuracy and fairness of clinical decision support algorithms when health care resources are limited.

OBJECTIVE: Guidance on how to evaluate accuracy and algorithmic fairness across subgroups is missing for clinical models that flag patients for an intervention but when health care resources to administer that intervention are limited. We aimed to propose a framework of metrics that would fit this specific use case. METHODS: We evaluated the following metrics and applied them to a Veterans Health Administration clinical model that flags patients for intervention who are at risk of overdose or a suicidal event among outpatients who were prescribed opioids (N = 405,817): Receiver - Operating Characteristic and area under the curve, precision - recall curve, calibration - reliability curve, false positive rate, false negative rate, and false omission rate. In addition, we developed a new approach to visualize false positives and false negatives that we named 'per true positive bars.' We demonstrate the utility of these metrics to our use case for three cohorts of patients at the highest risk (top 0.5 %, 1.0 %, and 5.0 %) by evaluating algorithmic fairness across the following age groups: <=30, 31-50, 51-65, and >65 years old. RESULTS: Metrics that allowed us to assess group differences more clearly were the false positive rate, false negative rate, false omission rate, and the new 'per true positive bars'. Metrics with limited utility to our use case were the Receiver - Operating Characteristic and area under the curve, the calibration - reliability curve, and the precision - recall curve. CONCLUSION: There is no "one size fits all" approach to model performance monitoring and bias analysis. Our work informs future researchers and clinicians who seek to evaluate accuracy and fairness of predictive models that identify patients to intervene on in the context of limited health care resources. In terms of ease of interpretation and utility for our use case, the new 'per true positive bars' may be the most intuitive to a range of stakeholders and facilitates choosing a threshold that allows weighing false positives against false negatives, which is especially important when predicting severe adverse events.

NFIXing Cancer: The Role of NFIX in Oxidative Stress Response and Cell Fate.

NFIX, a member of the nuclear factor I (NFI) family of transcription factors, is known to be involved in muscle and central nervous system embryonic development. However, its expression in adults is limited. Similar to other developmental transcription factors, NFIX has been found to be altered in tumors, often promoting pro-tumorigenic functions, such as leading to proliferation, differentiation, and migration. However, some studies suggest that NFIX can also have a tumor suppressor role, indicating a complex and cancer-type dependent role of NFIX. This complexity may be linked to the multiple processes at play in regulating NFIX, which include transcriptional, post-transcriptional, and post-translational processes. Moreover, other features of NFIX, including its ability to interact with different NFI members to form homodimers or heterodimers, therefore allowing the transcription of different target genes, and its ability to sense oxidative stress, can also modulate its function. In this review, we examine different aspects of NFIX regulation, first in development and then in cancer, highlighting the important role of NFIX in oxidative stress and cell fate regulation in tumors. Moreover, we propose different mechanisms through which oxidative stress regulates NFIX transcription and function, underlining NFIX as a key factor for tumorigenesis.

Occurrence of larval anisakids in horse mackerel (Trachurus trachurus) caught in Portuguese waters.

The third-stage larvae (L3) of the Anisakidae family are parasitic nematodes with zoonotic impact and are frequently encountered in the organs and musculature of various fish intended for human consumption. Since Anisakis simplex (s.s.) and A. pegreffii are the major aetiological agents of human disease, this study aims to combine the morphological and molecular data on the recovered anisakid larvae to contribute to a simplified morphological distinction of those species and conducted a survey of anisakid larvae infection in horse mackerel (Trachurus trachurus). Here, 116 horse mackerel caught in Portuguese waters were analysed for the presence of L3 of anisakids, and 3148 larvae were collected, of which only 30% were retrieved during visual inspection. As such, visual inspection does not appear to be very effective in anisakid detection. A prevalence of 84.5% of infected fish was found, and the mean intensity and mean abundance were 32.1 and 27.1 parasites per fish, respectively. The morphological and molecular analyses of 196 L3 randomly chosen from the total sample of parasites demonstrated the presence of L3 of mostly Anisakis spp., with only one L3 of Hysterothylacium aduncum. Relative frequencies of 62.9% for A. pegreffii and 37.1% for A. simplex (s.s.) were obtained. The morphometry differences between these two sibling species were evaluated, and the results demonstrated significant differences between the length of the ventriculus and the length of the oesophagus. Precisely, A. simplex (s.s.) has a longer oesophagus and ventriculus than A. pegreffii. As such, these differences may be used to distinguish the two species through morphological analysis.

Towards a rapid sequencing-based molecular surveillance and mosaicism investigation of Toxoplasma gondii.

Advances in molecular epidemiology of Toxoplasma gondii are hampered by technical and cost-associated hurdles underlying the acquisition of genomic data from parasites. In order to implement an enhanced genotyping approach for molecular surveillance of T. gondii, we applied a multi-locus amplicon-based sequencing strategy to samples associated with human infection. This approach, targeting genome-dispersed polymorphic loci potentially involved in adaptation and virulence, genetically discriminated almost all 68 studied strains and revealed a scenario of marked genomic mosaicism. Two-thirds (n = 43) of all strains were classified as recombinant, although recombination seemed to be linked to the classical archetypal lineage. While 92% of the Sag2 archetype I strains revealed genetic mosaicism, only 45% of Sag2 archetype II strains were identified as recombinant. Contrarily to the virulence-associated archetype I, most type II strains (regardless of their recombination background) were non-virulent in mouse. Besides Sag2, some of the newly studied loci (namely the type I/I-like alleles of Sag1, B17, PK1, and Sag3 and type III/III-like alleles of TgM-A) constitute promising candidates to rapidly infer T. gondii mouse virulence. Our successful attempt to capture microsatellite length variation launches good perspectives for the straightforward transition from the laborious intensive historical method to more informative next-generation sequencing (NGS)/bioinformatics-based methodologies. Overall, while T. gondii whole-genome sequencing will be hardly feasible in most laboratories, this study shows that a discrete loci panel has the potential to improve the molecular epidemiology of T. gondii towards a better monitoring of circulating genotypes with clinical importance.

Docosahexaenoic acid (DHA) at the sn-2 position of triacylglycerols increases DHA incorporation in brown, but not in white adipose tissue, of hamsters.

We hypothesised that the incorporation of docosahexaenoic acid (DHA) across adipose tissues will be higher when it is ingested as triacylglycerols (TAG) structured at the sn-2 position. Ten-week old male hamsters were allocated to 4 dietary treatments (n = 10): linseed oil (LSO-control group), fish oil (FO), fish oil ethyl esters (FO-EE) and structured DHA at the sn-2 position of TAG (DHA-SL) during 12 weeks. In opposition to the large variations found for fatty acid composition in retroperitoneal white adipose tissue (WAT), brown adipose tissue (BAT) was less responsive to diets. DHA was not found in subcutaneous and retroperitoneal WAT depots but it was successfully incorporated in BAT reaching the highest percentage in DHA-SL. The PCA on plasma hormones (insulin, leptin, adiponectin) and fatty acids discriminated BAT from WATs pointing towards an individual signature on fatty acid deposition, but did not allow for full discrimination of dietary treatments within each adipose tissue.

Betaine and arginine supplementation of low protein diets improves plasma lipids but does not affect hepatic fatty acid composition and related gene expression profiling in pigs.

BACKGROUND: The individual and combined effects of betaine and arginine supplemented to reduced protein diets were investigated on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid-sensitive factors in commercial pigs. Betaine has previously been shown to reduce carcass fat deposition and arginine improves meat quality of finishing pigs. Forty male crossbred pigs were randomly assigned to one of five diets (n = 8): 160 g kg-1 of crude protein (NPD), 130 g kg-1 of crude protein (RPD), RPD with 3.3 g kg-1 of betaine, RPD with 15 g kg-1 of arginine, and RPD with 3.3 g kg-1 of betaine and 15 g kg-1 of arginine. RESULTS: The restriction of dietary protein increased total lipids (P < 0.001), total cholesterol (P < 0.001), high-density lipoprotein-cholesterol (P < 0.001) and low-density lipoprotein cholesterol (P < 0.001). Betaine and arginine, individually or combined, reduced the majority of plasma lipids (P < 0.05) without affecting total fatty acids in the liver and the overall gene expression pattern. CONCLUSION: These findings suggest a positive effect of betaine and arginine, singly or combined, by reversing plasma lipids increase promoted by dietary protein restriction. © 2017 Society of Chemical Industry.

Arginine supplementation modulates pig plasma lipids, but not hepatic fatty acids, depending on dietary protein level with or without leucine.

BACKGROUND: In the present study, the effect of arginine and leucine supplementation, and dietary protein level, were investigated in commercial crossbred pigs to clarify their individual or combined impact on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid sensitive factors. The experiment was conducted on fifty-four entire male pigs (Duroc × Pietrain × Large White × Landrace crossbred) from 59 to 92 kg of live weight. Each pig was randomly assigned to one of six experimental treatments (n = 9). The treatments followed a 2 × 3 factorial arrangement, providing two levels of arginine supplementation (0 vs. 1%) and three levels of basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet with 2% of leucine, RPDL). RESULTS: Significant interactions between arginine supplementation and protein level were observed across plasma lipids. While dietary arginine increased total lipids, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol and triacylglycerols in NPD, the inverse effect was observed in RPD. Overall, dietary treatments had a minor impact on hepatic fatty acid composition. RPD increased 18:1c9 fatty acid while the combination of leucine and RPD reduced 18:0 fatty acid. Arginine supplementation increased the gene expression of FABP1, which contributes for triacylglycerols synthesis without affecting hepatic fatty acids content. RPD, with or without leucine addition, upregulated the lipogenic gene CEBPA but downregulated the fat oxidation gene LPIN1. CONCLUSIONS: Arginine supplementation was responsible for a modulated effect on plasma lipids, which is dependent on dietary protein level. It consistently increased lipaemia in NPD, while reducing the correspondent metabolites in RPD. In contrast, arginine had no major impact, neither on hepatic fatty acids content nor on fatty acid composition. Likewise, leucine supplementation of RPD, regardless the presence of arginine, promoted no changes on total fatty acids in the liver. Ultimately, arginine, leucine and dietary protein reduction seem to be unrelated with fatty liver development.

Molecular and virulence characterization of Toxoplasma gondii strains isolated from humans in Portugal.

Toxoplasma gondii is an apicomplexan parasite responsible for toxoplasmosis which infects all warm-blooded vertebrates, including mammals and birds. The majority of studies conducted in Europe have revealed that more than 80 % of strains isolated from human infections belong to genotype II, whereas genotypes I and III are responsible for a small number of cases. Atypical and recombinant strains are generally associated with more severe infections. In Portugal, there is a lack of data concerning genetic diversity as the classical typing studies in humans have never been performed. We aimed to determine the Sag2 and microsatellite-based (TUB2, TgM-A, W35, B17, B18) genotypes of T. gondii isolated from humans in Portugal, as well as to study their virulence in mice. We analyzed 48 strains from congenital and acquired toxoplasmosis collected during the last two decades. Sag2-based genotyping of T. gondii was achieved in all 48 strains where 35 (73 %) were classified as type II and 13 (27 %) were type I. The multilocus PCR of five microsatellites allowed the classification of 10 strains (21 %) as recombinant strains that had been previously identified as type II or I by Sag2 typing. Seven out of the 48 strains, including three type I, three recombinant, and one type I, were virulent in mice. This study constitutes the first evidence of recombinant strains circulating in Portugal in humans from congenital infection, highlighting the need for a better evaluation of these strains as their phenotype is still barely understood.

Restriction of dietary protein does not promote hepatic lipogenesis in lean or fatty pigs.

The influence of genotype (lean v. fatty) and dietary protein level (normal v. reduced) on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid-sensitive factors is reported for the first time, using the pig as an experimental model. The experiment was conducted on forty entire male pigs (twenty lean pigs of Large White×Landrace×Pietrain cross-breed and twenty fatty pigs of Alentejana purebreed) from 60 to 93 kg of live weight. Each pig genotype was divided into two subgroups, which were fed the following diets: a normal protein diet (NPD) equilibrated for lysine (17·5 % crude protein and 0·7 % lysine) and a reduced protein diet (RPD) not equilibrated for lysine (13·1 % crude protein and 0·4 % lysine). The majority of plasma metabolites were affected by genotype, with lean pigs having higher contents of lipids, whereas fatty pigs presented higher insulin, leptin and urea levels. RPD increased plasma TAG, free fatty acids and VLDL-cholesterol compared with NPD. Hepatic total lipids were higher in fatty pigs than in the lean genotype. RPD affected hepatic fatty acid composition but had a slight influence on gene expression levels in the liver. Sterol regulatory element-binding factor 1 was down-regulated by RPD, and fatty acid desaturase 1 (FADS1) and fatty acid binding protein 4 (FABP4) were affected by the interaction between genotype and diet. In pigs fed RPD, FADS1 was up-regulated in the lean genotype, whereas FABP4 increased in the fatty genotype. Although there is a genotype-specific effect of dietary protein restriction on hepatic lipid metabolism, lipogenesis is not promoted in the liver of lean or fatty pigs.

Circulating miR-122-5p/miR-133b Ratio Is a Specific Early Prognostic Biomarker in Acute Myocardial Infarction.

BACKGROUND: MicroRNAs (miRNAs) are key players in cardiovascular development and disease. However, not only miRNAs of a cardiac origin have a critical role in heart function. Recent studies have demonstrated that miR-122-5p, a hepatic miRNA, increases in the bloodstream during ischemic cardiogenic shock and it is upregulated in the infarcted myocardium. The aim of the present study was to determine the potential of circulating miR-122-5p as a biomarker for early prognostic stratification of ST-segment elevation acute myocardial infarction (STEMI) patients. METHODS AND RESULTS: One hundred and forty-two consecutive STEMI patients treated with primary angioplasty were included in the study. Serum levels of miR-1-3p, -122-5p, -133a-3p, -133b, -208b-3p and -499a-5p were measured at the time of cardiac catheterization by quantitative polymerase chain reaction and related to in-hospital and long-term outcome. During a follow up of 20.8 months, 9 patients died, 6 had recurrence of myocardial infarction, and 26 patients suffered an adverse cardiovascular event. Event-free survival was significantly worse in patients with a higher miR-122-5p/133b ratio (3rd tertile distribution, above 1.42 Log(10)), having almost a 9-fold higher risk of death or myocardial infarction and a 4-fold higher risk of adverse cardiovascular events. CONCLUSIONS: This study showed that the miR-122-5p/133b ratio is a new prognostic biomarker for the early identification of STEMI patients at a higher risk of developing major adverse events after undergoing primary percutaneous coronary intervention. (Circ J 2016; 80: 2183-2191).

Adipocyte membrane glycerol permeability is involved in the anti-adipogenic effect of conjugated linoleic acid.

Conjugated linoleic acid (CLA), a group of minor fatty acids from ruminant origin, has long been recognized as a body fat lowering agent. Given the trans(t)10,cis(c)12-CLA well documented interference on lipolysis, we hypothesized for adipocytes altered permeation to glycerol when supplemented with this isomer. 3T3-L1 murine differentiated adipocytes were medium supplemented with linoleic acid (LA) and individual or combined c9,t11 and t10,c12-CLA isomers. Adipocytes treated with the t10,c12-CLA isomer and CLA mixture showed reduced triacylglycerols content (p < 0.001), re-enforcing the t10,c12-CLA as the anti-adipogenic CLA isomer. This finding was supported by decreased Δ9-desaturase index and adipocyte differentiation markers for the t10,c12-CLA group (p < 0.001), which suggest reduced lipogenesis and differentiation, respectively. The glycerol permeability was higher in all CLA treated cells compared to control and LA groups (p < 0.05). The increase in glycerol permeability agrees with both reduced triacylglycerols and non-osmotic cellular volume in the t10,c12-CLA and CLA mixture groups. Taken together, our data suggest that the increased adipocyte plasma membrane glycerol fluxes may be part of the anti-adipogenic response to CLA treatments.

Quality of care for patients with multiple chronic conditions: the role of comorbidity interrelatedness.

Multimorbidity--the presence of multiple chronic conditions in a patient--has a profound impact on health, health care utilization, and associated costs. Definitions of multimorbidity in clinical care and research have evolved over time, initially focusing on a patient's number of comorbidities and the associated magnitude of required care processes, and later recognizing the potential influence of comorbidity characteristics on patient care and outcomes. In this article, we review the relationship between multimorbidity and quality of care, and discuss how this relationship may be mediated by the degree to which conditions interact with one another to generate clinical complexity (comorbidity interrelatedness). Drawing on established theoretical frameworks from cognitive engineering and biomedical informatics, we describe how interactions among conditions result in clinical complexity and may affect quality of care. We discuss how this comorbidity interrelatedness influences the value of existing quality guidelines and performance metrics, and describe opportunities to quantify this construct using data widely available through electronic health records. Incorporating comorbidity interrelatedness into conceptualizations of multimorbidity has the potential to enhance clinical and research efforts that aim to improve care for patients with multiple chronic conditions.

Influence of feeding graded levels of canned sardines on the inflammatory markers and tissue fatty acid composition of Wistar rats.

Canned sardines are a ready-to-use fish product with excellent nutritional properties owing to its high n-3 long-chain PUFA content, mainly EPA (20 : 5n-3) and DHA (22 : 6n-3). The present study aimed to assess the effect of two dosages of canned sardines, recommended for the primary and secondary prevention of human CVD, on the inflammatory marker concentrations and fatty acid composition of erythrocytes and key metabolic tissues (liver, muscle, adipose tissue and brain) in the rat model. Wistar rats were fed a diet containing 11 % (w/w) of canned sardines (low-sardine (LS) diet) and a diet containing 22 % (w/w) of canned sardines (high-sardine (HS) diet) for 10 weeks. Daily food intake, weight gain, and organ and final body weights were not affected by the dietary treatments. The concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol decreased in both the LS and HS groups, while those of alanine aminotransferase and adiponectin increased. The concentrations of IL-1ß increased only with the highest dosage of sardine. The dose-dependent influence of the graded levels of EPA+DHA was tissue specific. Compared with that of other tissues and erythrocytes, the fatty acid composition of the brain was less affected by the canned sardine-supplemented diets. In contrast, the retroperitoneal adipose tissue was highly responsive. The deposition ratios of EPA and DHA indicated that the LS diet was optimal for DHA deposition across the tissues, except in the retroperitoneal adipose tissue. Taken together, our findings indicate that a LS diet positively affects plasma lipid profiles and inflammatory mediators, whereas a HS diet has contradictory effects on IL-1ß, which, in turn, is not associated with variations in the concentrations of other pro-inflammatory cytokines. This finding requires further investigation and pathophysiological understanding.

Chronic thromboembolic pulmonary hypertension: A comprehensive review of pathogenesis, diagnosis, and treatment strategies.

Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist.

Pulmonary arterial hypertension: Navigating the pathways of progress in diagnosis, treatment, and patient care.

Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension caused by a complex process of endothelial dysfunction and vascular remodeling. If left untreated, this progressive disease presents with symptoms of incapacitating fatigue causing marked loss of quality of life, eventually culminating in right ventricular failure and death. Patient management is complex and based on accurate diagnosis, risk stratification, and treatment initiation, with close monitoring of response and disease progression. Understanding the underlying pathophysiology has enabled the development of multiple drugs directed at different targets in the pathological chain. Vasodilator therapy has been the mainstay approach for the last few years, significantly improving quality of life, functional status, and survival. Recent advances in therapies targeting dysfunctional pathways beyond endothelial dysfunction may address the fundamental processes underlying the disease, raising the prospect of increasingly effective options for this high-risk group of patients with a historically poor prognosis.

Question-answering system extracts information on injection drug use from clinical notes.

BACKGROUND: Injection drug use (IDU) can increase mortality and morbidity. Therefore, identifying IDU early and initiating harm reduction interventions can benefit individuals at risk. However, extracting IDU behaviors from patients' electronic health records (EHR) is difficult because there is no other structured data available, such as International Classification of Disease (ICD) codes, and IDU is most often documented in unstructured free-text clinical notes. Although natural language processing can efficiently extract this information from unstructured data, there are no validated tools. METHODS: To address this gap in clinical information, we design a question-answering (QA) framework to extract information on IDU from clinical notes for use in clinical operations. Our framework involves two main steps: (1) generating a gold-standard QA dataset and (2) developing and testing the QA model. We use 2323 clinical notes of 1145 patients curated from the US Department of Veterans Affairs (VA) Corporate Data Warehouse to construct the gold-standard dataset for developing and evaluating the QA model. We also demonstrate the QA model's ability to extract IDU-related information from temporally out-of-distribution data. RESULTS: Here, we show that for a strict match between gold-standard and predicted answers, the QA model achieves a 51.65% F1 score. For a relaxed match between the gold-standard and predicted answers, the QA model obtains a 78.03% F1 score, along with 85.38% Precision and 79.02% Recall scores. Moreover, the QA model demonstrates consistent performance when subjected to temporally out-of-distribution data. CONCLUSIONS: Our study introduces a QA framework designed to extract IDU information from clinical notes, aiming to enhance the accurate and efficient detection of people who inject drugs, extract relevant information, and ultimately facilitate informed patient care.

There are many health risks associated with injection drug use (IDU). Identifying people who inject drugs early can reduce the likelihood of these issues arising. However, extracting information about any possible IDU from a person's electronic health records can be difficult because the information is often in text-based general clinical notes rather than provided in a particular section of the record or as numerical data. Manually extracting information from these notes is time-consuming and inefficient. We used a computational method to train computer software to be able to extract IDU details. Potentially, this approach could be used by healthcare providers to more efficiently and accurately identify people who inject drugs, and therefore provide better advice and medical care.

High dimensional predictions of suicide risk in 4.2 million US Veterans using ensemble transfer learning.

We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoses with varying choices of study design and prediction methodology. Each model used twenty cross-sectional and 190 longitudinal variables observed in eight time intervals covering 7.5 years prior to the time of prediction. Ensembles of seven base models were created and fine-tuned with ten variables expected to change with study design and outcome definition in order to predict suicide and combined outcome in a prospective cohort. The ensemble models achieved c-statistics of 0.73 on 2-year suicide risk and 0.83 on the combined outcome when predicting on a prospective cohort of [Formula: see text] 4.2 M veterans. The ensembles rely on nonlinear base models trained using a matched retrospective nested case-control (Rcc) study cohort and show good calibration across a diversity of subgroups, including risk strata, age, sex, race, and level of healthcare utilization. In addition, a linear Rcc base model provided a rich set of biological predictors, including indicators of suicide, substance use disorder, mental health diagnoses and treatments, hypoxia and vascular damage, and demographics.

Determination of gaseous polycyclic aromatic hydrocarbons by a simple direct method using thermal desorption-gas chromatography-mass spectrometry.

In the last decade, the development of novel analytical methodologies enabled the identification of several environmental pollutants responsible for health problems associated with indoor exposure. Polycyclic aromatic hydrocarbons (PAHs) are among the potential hazardous chemicals present in ambient air. Due to their bioaccumulation potential and carcinogenic/mutagenic effects, 16 PAHs are currently listed as priority air pollutants. The main goal of this work was to implement a new and simple method for sampling and determination of PAHs in air by using a thermal desorption (TD) technique followed by gas chromatography coupled with mass spectrometry analysis. A detailed study was carried out to optimise the experimental method in each of its phases, including (active) sampling, TD and chromatographic analysis. The results demonstrate that this approach allowed the detection and quantification of the six more volatile PAHs, namely, naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, and anthracene. Acceptable precision and good linearity over the explored range were obtained. No carry-over was observed during experimental tests and the method provided a reproducible answer. The applicability of the novel methodology was tested in real environment, namely, on the roof of a building in an urban area, in a domestic kitchen and in a collective car garage. The method enabled the identification of two PAHs in the field samples, specifically, naphthalene (two rings) and phenanthrene (three rings). With regard to PAHs sample composition, the most abundant PAH found, in the three different locations, was naphthalene, accounting for about 84-100 % of the total PAH mass detected.

Landscape and cultural heritage: Object and information.

Culture and Museology use information and communication technologies as mediating communication tools, enhancing the conservation and "socialisation" of museum collections, promoting access to cultural information, through the interdisciplinarity required between the museologist and other professionals who, together, organize and disseminate the collections. In the age of digital transformation, we live in, this reality is even more evident. The museum transforms objects into perceptible information as it is a repository of information. The common link between Museology and Information Science involves valuing the human action of creating, interpreting, using, selecting and distributing knowledge products and records, thus creating a connection with the concept of information. Information is central to the process of cultural development. This communication clarifies the relationship between Information Science, Heritage and Museology, presenting the information professional as a partner of Museology, working the object as a document with communicative properties, as a message intended for a specific audience and as information that impacts that audience.

QuilA® adjuvanted Coxevac® sustains Th1-CD8+-type immunity and increases protection in Coxiella burnetii-challenged goats.

Coxevac® is the EMA-approved veterinary vaccine for the protection of cattle and goats against Q fever, a zoonotic bacterial disease due to Coxiella burnetii. Since Coxevac® reduces bacterial shedding and clinical symptoms but does not prevent infection, novel, ready-to-use vaccine formulations are needed to increase its immunogenicity. Here, a goat vaccination-challenge model was used to evaluate the impact of the commercially available saponin-based QuilA® adjuvant on Coxevac® immunity. Upon challenge, the QuilA®-Coxevac® group showed a stronger immune response reflected in a higher magnitude of total IgG and an increase in circulating and splenic CD8+ T-cells compared to the Coxevac® and challenged-control groups. The QuilA®-Coxevac® group was characterized by a targeted Th1-type response (IFNγ, IP10) associated with increased transcripts of CD8+ and NK cells in spleens and γδ T cells in bronchial lymph nodes. Coxevac® vaccinated animals presented an intermediate expression of Th1-related genes, while the challenged-control group showed an immune response characterized by pro-inflammatory (IL1ß, TNFα, IL12), Th2 (IL4 and IL13), Th17 (IL17A) and other immunoregulatory cytokines (IL6, IL10). An intriguing role was observed for γδ T cells, which were of TBX21- and SOX4-types in the QuilA®-Coxevac® and challenged control group, respectively. Overall, the addition of QuilA® resulted in a sustained Th1-type activation associated with an increased vaccine-induced bacterial clearance of 33.3% as compared to Coxevac® only. QuilA® could be proposed as a readily-applied veterinary solution to improve Coxevac® efficacy against C. burnetii infection in field settings.