Search

The COVID-19 pandemic has underscored the critical role of observational studies in evaluating the effectiveness of public health strategies. However, although many studies have explored the true impact of vaccination on preventive behavior, their results may be skewed by potential biases and confounding variables. This study examines the application of covariate adjustment and propensity score (PS) estimation, particularly through inverse probability treatment weighting (IPTW), to assess their performance in reducing bias in a framework featuring ordinal outcomes and cumulative logistic regression models, as commonly used in observational studies related to social sciences and psychology. Before applying these methods to the case study, we conducted a simulation study that accounted for the presence or absence of model misspecification in an observational scenario with ordinal outcomes, binary treatment, and a continuous confounder. Our findings demonstrate the effectiveness of combining covariate adjustment with PS methods in reducing bias and improving causal inference. These methods were subsequently applied to an Italian observational study on COVID-19 vaccine hesitancy conducted during the initial phase of the vaccination campaign (April-May 2021). Our analysis revealed that vaccination status had a limited short-term impact on the adoption of preventive measures. This study highlights the importance of employing appropriate adjustment techniques in observational research, particularly when evaluating complex behavioral outcomes. The results support the combined use of covariate adjustment and PS methods to enhance the reliability of findings, ultimately contributing to more informed public health decision-making.

The site of San Valentino in San Vito al Tagliamento is one of the main urnfield cemeteries in northeastern Italy. Archaeological excavations carried out in the seventies brought to light a cremation cemetery consisting of mainly urn graves with pottery and metal artefacts as grave goods. These materials suggest that the individuals buried in San Valentino were not an isolated local community but had intense contacts with other north-Adriatic communities, in particular with the neighbouring Veneto area, as suggested by the close similarity of the biconical vessels with those recovered in the graves of Este. This paper provides the first osteological study of a preserved sample of individuals buried at San Valentino and uses an innovative multi-proxy approach to refine the chronology of the site through radiocarbon dating of bone apatite, investigate human mobility using strontium isotopes on calcined human remains, and reconstruct the funerary practices by combining FTIR-ATR data with carbon and oxygen isotope ratios on cremated bones. The results date the cemetery to the end of the Late Bronze Age and the Early Iron Age, with a sporadic occupation in the fourth century BC. Strontium isotopes and concentrations show the analysed individuals buried at San Valentino were a local community that exploited nearby food resources. Interestingly, variations in cremation conditions were detected between San Valentino and the contemporary sites of Velzeke, Blicquy, Grand Bois, and Herstal, located in Belgium, by using FTIR-ATR and carbon and oxygen isotope data. This multi-proxy approach applied to the study of cremated human remains can open new research possibilities, being potentially extendable to the study of many pre- and proto-historic and historic communities that practised cremation.

The COVID-19 pandemic has underscored the critical role of observational studies in evaluating the effectiveness of public health strategies. However, although many studies have explored the true impact of vaccination on preventive behavior, their results may be skewed by potential biases and confounding variables. This study examines the application of covariate adjustment and propensity score (PS) estimation, particularly through inverse probability treatment weighting (IPTW), to assess their performance in reducing bias in a framework featuring ordinal outcomes and cumulative logistic regression models, as commonly used in observational studies related to social sciences and psychology. Before applying these methods to the case study, we conducted a simulation study that accounted for the presence or absence of model misspecification in an observational scenario with ordinal outcomes, binary treatment, and a continuous confounder. Our findings demonstrate the effectiveness of combining covariate adjustment with PS methods in reducing bias and improving causal inference. These methods were subsequently applied to an Italian observational study on COVID-19 vaccine hesitancy conducted during the initial phase of the vaccination campaign (April-May 2021). Our analysis revealed that vaccination status had a limited short-term impact on the adoption of preventive measures. This study highlights the importance of employing appropriate adjustment techniques in observational research, particularly when evaluating complex behavioral outcomes. The results support the combined use of covariate adjustment and PS methods to enhance the reliability of findings, ultimately contributing to more informed public health decision-making. [ABSTRACT FROM AUTHOR]

The site of San Valentino in San Vito al Tagliamento is one of the main urnfield cemeteries in northeastern Italy. Archaeological excavations carried out in the seventies brought to light a cremation cemetery consisting of mainly urn graves with pottery and metal artefacts as grave goods. These materials suggest that the individuals buried in San Valentino were not an isolated local community but had intense contacts with other north-Adriatic communities, in particular with the neighbouring Veneto area, as suggested by the close similarity of the biconical vessels with those recovered in the graves of Este. This paper provides the first osteological study of a preserved sample of individuals buried at San Valentino and uses an innovative multi-proxy approach to refine the chronology of the site through radiocarbon dating of bone apatite, investigate human mobility using strontium isotopes on calcined human remains, and reconstruct the funerary practices by combining FTIR-ATR data with carbon and oxygen isotope ratios on cremated bones. The results date the cemetery to the end of the Late Bronze Age and the Early Iron Age, with a sporadic occupation in the fourth century BC. Strontium isotopes and concentrations show the analysed individuals buried at San Valentino were a local community that exploited nearby food resources. Interestingly, variations in cremation conditions were detected between San Valentino and the contemporary sites of Velzeke, Blicquy, Grand Bois, and Herstal, located in Belgium, by using FTIR-ATR and carbon and oxygen isotope data. This multi-proxy approach applied to the study of cremated human remains can open new research possibilities, being potentially extendable to the study of many pre- and proto-historic and historic communities that practised cremation. [ABSTRACT FROM AUTHOR]

The absence of a chronic kidney disease (CKD) registry in Ecuador makes it difficult to assess the burden of disease, but there is an anticipated increase in the incidence of CKD along with increasing diabetes, hypertension and population age. From 2012, augmented funding for renal replacement therapy expanded dialysis clinics and patient coverage. We conducted 73 in-depth sociological interviews with healthcare providers in eight provinces and collected quantitative epidemiological data on patients with CKD diagnoses from six national-level databases between 2015 and 2018. Datasets show a total of 17,484 dialysis patients in 2018, or 567 patients per million population (pmp), with an annual cost exceeding 11% of Ecuador's public health budget. Each year, there were 139-162 pmp new dialysis patients, while doctors reported waiting lists. The number of patients on peritoneal dialysis was static; those on hemodialysis increased over time. Only 13 of 24 provinces were found to have dialysis services, and nephrologists were clustered in major cities, which limits access, delays medical attention, and adds a travel burden on patients. Prevention and screening programs are scarce, while hospitalization is an important reality for CKD patients. CKD is an emerging public health crisis that has increased dramatically over the last decade in Ecuador and is expected to continue, making coverage for all patients impossible and the current structure, unsustainable. A patient registry would help health policymakers and administrators estimate the demand and progression of patients with consideration for comorbidities, disease stage, requirements and costs, mortality and follow-up. This should be used to help identify where to focus prevention and improved treatment efforts. Organized monitoring of CKD patients would benefit from improvements in patient referral. Community-based education and prevention programs, the strengthening of primary healthcare capacity (including basic routine tests) and improved nephrology services are also urgently needed.

Snake venom thrombin-like enzymes (SVTLEs) are serine proteinases that clot fibrinogen. SVTLEs are distributed mainly in venoms from snakes of the Viperidae family, comprising venomous pit viper snakes. Bothrops snakes are distributed throughout Central and South American and are responsible for most venomous snakebites. Most Bothrops snakes display thrombin-like activity in their venoms, but it has been shown that some species do not present it. In this work, to understand SVTLE polymorphism in Bothrops snake venoms, we studied individual samples from two species of medical importance in Brazil: Bothrops jararaca, distributed in Southeastern Brazil, which displays coagulant activity on plasma and fibrinogen, and Bothrops erythromelas, found in Northeastern Brazil, which lacks direct fibrinogen coagulant activity but shows plasma coagulant activity. We tested the coagulant activity of venoms and the presence of SVTLE genes by a PCR approach. The SVTLE gene structure in B. jararaca is similar to the Bothrops atrox snake, comprising five exons. We could not amplify SVTLE sequences from B. erythromelas DNA, except for a partial pseudogene. These genes underwent a positive selection in some sites, leading to an amino acid sequence diversification, mostly in exon 2. The phylogenetic tree constructed using SVTLE coding sequences confirms that they are related to the chymotrypsin/kallikrein family. Interestingly, we found a B. jararaca specimen whose venom lacked thrombin-like activity, and its gene sequence was a pseudogene with SVTLE structure, presenting nonsense and frameshift mutations. Our results indicate an association of the lack of thrombin-like activity in B. jararaca and B. erythromelas venoms with mutations and deletions of snake venom thrombin-like enzyme genes.

In the context of colorectal cancer screening, we aimed to compare the effectiveness of different emotion-laden narratives, to investigate the specific emotions elicited at both subjective and physiological levels, and to test the effects of emotions explicitly expressed by the narrative character. Study 1 used a between-participants design comparing four conditions: relief-based narrative, regret-based narrative, control (test-uptake only) narrative, and standard invitation material (no-narrative condition). Study 2 used a mixed design, with the narrative content as a within-participants factor and whether emotions were expressed by the narrative character or not as between-participants factor. The main outcome measures were: intention to undergo testing (Studies 1 and 2), knowledge, risk perception, proportion of informed choices (Study 1), subjective emotional responses, changes in skin conductance, heart rate, and corrugator muscle activity (Study 2). In Study 1, relative to the non-narrative condition (51%), only the relief-based narrative significantly increased intention to undergo testing (86%). Relative to the standard invitation material, the narrative conditions did not decrease knowledge, alter risk perception, or decrease the proportion of informed choices. In Study 2, the relief-based narrative elicited the lowest self-reported negative affect, and received greater implicit attention, as suggested by the larger heart rate decrease. Making the emotions experienced by the narrative character explicit decreased negative affect, as indicated by the lower skin conductance and corrugator responses during reading. Our findings provide support for the use of a relief-based narrative with emotions expressed by the character in addition to the standard information material to promote colorectal cancer screening.

The knowledge on health interests of a given population of Internet users might contribute to the increase of evidence on community's dental needs, and consequently, to the improvement of public health planning. The frequency of searches for specific issues on Google can be analyzed by the application of Google Trends.In this study, we aimed to characterize the interests on toothache information of Google users from the United States, United Kingdom, Australia and Brazil.The monthly variation of relative search volume (RSV) and the lists of main toothache-related queries were determined from January 2004 through April 2016 using Google Trends. Autoregressive Integrated Moving Average (ARIMA) forecasting models were developed to determine predictive RSV values for toothache for additional 12 months. Autocorrelation plots and general additive model (GAM) were applied to determine trends and seasonality in RSV curves. Through linear regression models, we assessed the association between the variation of annual means of RSV values and national statistics for toothache in the U.S. and U.K. Subsequently, the distribution of main queries according to the identification of endodontic pain, type of searching information, and the interest in self-management of toothache was evaluated for the four countries.The autocorrelation plots showed patterns of non-stationary time series. The monthly variation influenced the data of the U.S. and U.K., with the higher RSV values found respectively in January/July and December. Also, the interest on toothache in the U.K. increases in the second semester and in the fourth quarter, especially in December. Additionally, an annual variation affected significantly all time series, with the increment of RSV means over the years, varying from 265% in the U.S. to 745% in Brazil. In parallel, the increments in RSV values were also observed in all predictive curves. The annual variation of observed and fitted RSV values was directly associated with the increase of toothache visits in the U.S. and urgent dental treatments in the U.K. Moreover, the queries typed on Google were markedly linked to searches on endodontic pain information, especially in Brazil, where the residents usually searched for relief and/or self-management of pain.Therefore, these findings indicate an increasing interest of Google users on toothache-related topics, regardless of country and season. The Internet activity can be used by policy makers as a complementary source of data for the development and implementation of strategies to control and prevent toothache complications.

Hepatitis E virus (HEV) is a single-stranded RNA virus that can cause hepatitis in an epidemic fashion. HEV usually causes asymptomatic or limited acute infections in immunocompetent individuals, whereas in immunosuppressed individuals such as transplant recipients, HEV can cause chronic infections. The risks and outcomes of HEV co-infection in patients infected with human immunodeficiency virus (HIV) are poorly characterized. We used a third generation immunoassay to measure serum IgG antibodies specific for HEV in 204 HIV-infected individuals from Argentina and a control group of 433 HIV-negative individuals. We found 15 of 204 (7.3%, 95%CI 3.74-10.96%) individuals in the HIV-positive group to have positive HEV IgG levels suggestive of previous infection, compared to 19 of 433 (4.4%, 95% CI 2.5-6.3%) individuals in the HIV-negative control group (p = 0.12). Among HIV-positive individuals, those with HEV seropositivity had lower CD4 counts compared to those that were HEV seronegative (average CD4 count of 234 vs 422 mm3, p = 0.01), indicating that patients with lower CD4 counts were more likely to be HEV IgG positive. Moreover, HEV seropositivity in patients with CD4 counts 200 mm3 (p = 0.012). We found a positive PCR result for HEV in one individual. Our study found that increased seroprevalence of HEV IgG correlated with lower CD4 counts in HIV-infected patients in Argentina.

ObjectiveThe Helping Babies Breathe" (HBB) program is an evidence-based curriculum in basic neonatal care and resuscitation, utilizing simulation-based training to educate large numbers of birth attendants in low-resource countries. We analyzed its cost-effectiveness at a faith-based Haydom Lutheran Hospital (HLH) in rural Tanzania.MethodsData about early neonatal mortality and fresh stillbirth rates were drawn from a linked observational study during one year before and one year after full implementation of the HBB program. Cost data were provided by the Tanzanian Ministry of Health and Social Welfare (MOHSW), the research department at HLH, and the manufacturer of the training material Lærdal Global Health.FindingsCosts per life saved were USD 233, while they were USD 4.21 per life year gained. Costs for maintaining the program were USD 80 per life saved and USD 1.44 per life year gained. Costs per disease adjusted life year (DALY) averted ranged from International Dollars (ID; a virtual valuta corrected for purchasing power world-wide) 12 to 23, according to how DALYs were calculated.ConclusionThe HBB program is a low-cost intervention. Implementation in a very rural faith-based hospital like HLH has been highly cost-effective. To facilitate further global implementation of HBB a cost-effectiveness analysis including government owned institutions, urban hospitals and district facilities is desirable for a more diverse analysis to explore cost-driving factors and predictors of enhanced cost-effectiveness.

BackgroundPeople have fought for their civil rights, primarily the right to live in dignity. At present, the development of technology in medicine and healthcare led to an apparent paradox: many people are fighting for the right to die. This study was aimed at testing whether different moral principles are associated with different attitudes towards end-of-life decisions for patients with a severe brain damage.MethodologyWe focused on the ethical decisions about withdrawing life-sustaining treatments in patients with severe brain damage. 202 undergraduate students at the University of Padova were given one description drawn from four profiles describing different pathological states: the permanent vegetative state, the minimally conscious state, the locked-in syndrome, and the terminal illness. Participants were asked to evaluate how dead or how alive the patient was, and how appropriate it was to satisfy the patient's desire.Principal findingsWe found that the moral principles in which people believe affect not only people's judgments concerning the appropriateness of the withdrawal of life support, but also the perception of the death status of patients with severe brain injury. In particular, we found that the supporters of the Free Choice (FC) principle perceived the death status of the patients with different pathologies differently: the more people believe in the FC, the more they perceived patients as dead in pathologies where conscious awareness is severely impaired. By contrast, participants who agree with the Sanctity of Life (SL) principle did not show differences across pathologies.ConclusionsThese results may shed light on the complex aspects of moral consensus for supporting or rejecting end-of-life decisions.

Evidence is building to suggest that both chronic and acute warm temperature exposure, as well as other anthropogenic perturbations, may select for small adult fish within a species. To shed light on this phenomenon, we investigated physiological and anatomical attributes associated with size-specific responses to an acute thermal challenge and a fisheries capture simulation (exercise+air exposure) in maturing male coho salmon (Oncorhynchus kisutch). Full-size females were included for a sex-specific comparison. A size-specific response in haematology to an acute thermal challenge (from 7 to 20 °C at 3 °C h(-1)) was apparent only for plasma potassium, whereby full-size males exhibited a significant increase in comparison with smaller males ('jacks'). Full-size females exhibited an elevated blood stress response in comparison with full-size males. Metabolic recovery following exhaustive exercise at 7 °C was size-specific, with jacks regaining resting levels of metabolism at 9.3 ± 0.5 h post-exercise in comparison with 12.3 ± 0.4 h for full-size fish of both sexes. Excess post-exercise oxygen consumption scaled with body mass in male fish with an exponent of b = 1.20 ± 0.08. Jacks appeared to regain osmoregulatory homeostasis faster than full-size males, and they had higher ventilation rates at 1 h post-exercise. Peak metabolic rate during post-exercise recovery scaled with body mass with an exponent of b~1, suggesting that the slower metabolic recovery in large fish was not due to limitations in diffusive or convective oxygen transport, but that large fish simply accumulated a greater 'oxygen debt' that took longer to pay back at the size-independent peak metabolic rate of ~6 mg min(-1) kg(-1). Post-exercise recovery of plasma testosterone was faster in jacks compared with full-size males, suggesting less impairment of the maturation trajectory of smaller fish. Supporting previous studies, these findings suggest that environmental change and non-lethal fisheries interactions have the potential to select for small individuals within fish populations over time.

The perception of brightness depends on spatial context: the same stimulus can appear light or dark depending on what surrounds it. A less well-known but equally important contextual phenomenon is that the colour of a stimulus can also alter its brightness. Specifically, stimuli that are more saturated (i.e. purer in colour) appear brighter than stimuli that are less saturated at the same luminance. Similarly, stimuli that are red or blue appear brighter than equiluminant yellow and green stimuli. This non-linear relationship between stimulus intensity and brightness, called the Helmholtz-Kohlrausch (HK) effect, was first described in the nineteenth century but has never been explained. Here, we take advantage of the relative simplicity of this 'illusion' to explain it and contextual effects more generally, by using a simple Bayesian ideal observer model of the human visual ecology. We also use fMRI brain scans to identify the neural correlates of brightness without changing the spatial context of the stimulus, which has complicated the interpretation of related fMRI studies.Rather than modelling human vision directly, we use a Bayesian ideal observer to model human visual ecology. We show that the HK effect is a result of encoding the non-linear statistical relationship between retinal images and natural scenes that would have been experienced by the human visual system in the past. We further show that the complexity of this relationship is due to the response functions of the cone photoreceptors, which themselves are thought to represent an efficient solution to encoding the statistics of images. Finally, we show that the locus of the response to the relationship between images and scenes lies in the primary visual cortex (V1), if not earlier in the visual system, since the brightness of colours (as opposed to their luminance) accords with activity in V1 as measured with fMRI.The data suggest that perceptions of brightness represent a robust visual response to the likely sources of stimuli, as determined, in this instance, by the known statistical relationship between scenes and their retinal responses. While the responses of the early visual system (receptors in this case) may represent specifically the statistics of images, post receptor responses are more likely represent the statistical relationship between images and scenes. A corollary of this suggestion is that the visual cortex is adapted to relate the retinal image to behaviour given the statistics of its past interactions with the sources of retinal images: the visual cortex is adapted to the signals it receives from the eyes, and not directly to the world beyond.

In contrast to the classical view of development as a preprogrammed and deterministic process, recent studies have demonstrated that stochastic perturbations of highly non-linear systems may underlie the emergence and stability of biological patterns. Herein, we address the question of whether noise contributes to the generation of the stereotypical temporal pattern in gene expression during flower development. We modeled the regulatory network of organ identity genes in the Arabidopsis thaliana flower as a stochastic system. This network has previously been shown to converge to ten fixed-point attractors, each with gene expression arrays that characterize inflorescence cells and primordial cells of sepals, petals, stamens, and carpels. The network used is binary, and the logical rules that govern its dynamics are grounded in experimental evidence. We introduced different levels of uncertainty in the updating rules of the network. Interestingly, for a level of noise of around 0.5-10%, the system exhibited a sequence of transitions among attractors that mimics the sequence of gene activation configurations observed in real flowers. We also implemented the gene regulatory network as a continuous system using the Glass model of differential equations, that can be considered as a first approximation of kinetic-reaction equations, but which are not necessarily equivalent to the Boolean model. Interestingly, the Glass dynamics recover a temporal sequence of attractors, that is qualitatively similar, although not identical, to that obtained using the Boolean model. Thus, time ordering in the emergence of cell-fate patterns is not an artifact of synchronous updating in the Boolean model. Therefore, our model provides a novel explanation for the emergence and robustness of the ubiquitous temporal pattern of floral organ specification. It also constitutes a new approach to understanding morphogenesis, providing predictions on the population dynamics of cells with different genetic configurations during development.

BACKGROUND: The independent prognostic impact, as well as the possible causal role, of hyperhomocysteinemia (HHcy) in coronary artery disease (CAD) is controversial. No previous study specifically has addressed the relationship between HHcy and mortality after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the prognostic impact of HHcy after CABG surgery. METHODOLOGY AND PRINCIPAL FINDINGS: We prospectively followed 350 patients who underwent elective CABG between May 1996 and May 1999. At baseline, fasting total homocysteine (tHcy) levels were measured in all participants, and a post-methionine loading (PML) test was performed in 77.7% of them (n = 272). After a median follow-up of 58 months, 33 patients (9.4%) had died, 25 because of cardiovascular events. HHcy, defined by levels higher than the 90th percentile (25.2 micromol/L) of the population's distribution, was significantly associated to total and cardiovascular mortality (P = 0.018 [log-rank test 5.57]; P = 0.002 [log-rank test 9.76], respectively). The PML test had no prognostic value. After multiple adjustment for other univariate predictors by Cox regression, including statin therapy (the most powerful predictor in uni-/multivariate analyses), high-sensitivity C Reactive Protein (hs-CRP) levels, and all known major genetic (MTHFR 677C-->T polymorphism) and non-genetic (B-group vitamin status and renal function) tHcy determinants, HHcy remained an independent prognostic factor for mortality (HRs: 5.02, 95% CIs 1.88 to 13.42, P = 0.001). CONCLUSIONS: HHcy is an important prognostic marker after CABG, independent of modern drug therapy and biomarkers.