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This Element is broadly about the geometrization of physics, but mostly it is about gauge theories. Gauge theories lie at the heart of modern physics: in particular, they constitute the Standard Model of particle physics. At its simplest, the idea of gauge is that nature is best described using a descriptively redundant language; the different descriptions are said to be related by a gauge symmetry. The over-arching question this Element aims to answer is: why is descriptive redundancy fruitful for physics? I will provide three inter-related answers to the question: ``Why gauge theory?'', that is: why introduce redundancies in our models of nature in the first place? The first is pragmatic, or methodological; the second is based on geometrical considerations, and the third is broadly relational.
Cocoa is an important agricultural product that plays a crucial role in local communities in South America. In Brazil, it is traditionally grown in agroforestry systems, which are more sustainable and contribute to biodiversity conservation. However, the recent expansion of intensive monocultures in tropical forests poses significant threats to this activity. Using historical data on land use and cocoa productivity at the municipality level from Brazil’s primary cocoa-producing states, we show that maintaining and restoring forest cover are positively correlated with cocoa productivity, particularly in areas with less anthropogenic disturbance. This highlights the dependence of cocoa production on ecosystem services. Recent data reveal that in municipalities where local agriculture is less reliant on cocoa, only larger farms have benefitted from increased forest cover, probably due to their greater dependence on fragments of natural habitat for ecosystem services. In municipalities that are more reliant on cocoa, the effects of forest cover were not detected, while strong negative effects of forest fragmentation were observed in both small- and large-scale farms. We emphasize the importance of preserving natural forests near cocoa plantations to optimize productivity in Amazon and Atlantic Forest agroforestry, especially in deforested areas.
Members of Sinistroporomonorchis Wee, Cutmore, Pérez-del-Olmo & Cribb, 2020 represent a small group of trematodes belonging to the Monorchiidae Odhner, 1911 with 5 species described from mugilid hosts. Specimens consistent with the generic concept of Sinistroporomonorchis were obtained from Floridichthys polyommus (Cyprinodontidae); most of them were juveniles from 4 localities within the Yucatán Peninsula. After a detailed morphological examination including scanning electron microscopy images and a principal component analysis, the specimens collected represented a new species, Sinistroporomonorchis bolini n. sp. The new species can be differentiated by the presence of an overall large pharynx including the proportion of pharynx width to oral sucker width, a uterus arranged in 2 main lateral fields, and by presenting robust caeca. In addition, sequences of the 28S of large subunit of nuclear ribosomal RNA and cox1 of the mitochondrial DNA were obtained. Phylogenetic trees inferred from each dataset, placed all the specimens in a monophyletic clade, confirming that the isolates belonged to the same species. The new species is the sixth described for the genus Sinistroporomonorchis, the fifth described from the Yucatán Peninsula and the first described from a non-mugilid host.
Digital-era music videos are a crucial part of singers’ mediatic performances. Lip-synching is often central to such products, supplying situations in which singers can mouth their voices while dislodging themselves from the struggles of singing. Looking into music videos by focusing on their lip-synching practices, this paper aims to understand the part voice takes on in the medium while also investigating how gestural lip-sync performances work as accounts of oneself that produce a musical subject, sometimes updating or overcoming social regulations. In this sense, lip-synching is theorized as a way of framing music videos’ gestural labour.
There are few studies on the use medicinal herbs by pregnant women in Brazil, even though there is a wealth of knowledge about medicinal herbs among Brazilians of Indigenous, African, and European ancestry. The aim of this study was to assess the prevalence and type of herbs used by pregnant women living in the Amazon region.
Methods
This was a cross-sectional study conducted with 811 pregnant women attending 10 public antenatal clinics in Manaus, Amazonas state, Brazil. The consumption of medicinal herbs was assessed through individual 24-hour dietary recall.
Results
A total of 811 women in their second trimester (16 to 20 weeks) of pregnancy were included and 69 (8.5%) reported that they used herbs to make teas. There was a significant difference between users and non-users of medicinal teas, with a higher proportion of overweight women in the group that used teas (46.4% versus 31.9%; p=0.005). Nearly half (47.8%) of those who used medicinal teas consumed herbs with sedative effects, 23 percent consumed herbs for the relief of urinary tract symptoms, and 13 percent used herbs with digestive properties. Most women reported using natural herbs from their own gardens.
Conclusions
Approximately 10 percent of Brazilian women in the Amazon region consumed medicinal herbs to alleviate common symptoms of pregnancy. The most frequently used plants had sedative, urinary tract, or gastrointestinal effects. Most plants were obtained in natura from local gardens. Many of these plants have known adverse effects and their use is contraindicated during pregnancy.
The decision-making process for health technology assessment (HTA) in ultra-rare diseases faces a significant challenge for agencies worldwide. This study sought to offer an analytical overview of the clinical evidence outlined in the recommendations of the Brazilian National Committee for Health Technology Incorporation (Conitec) in ultra-rare diseases.
Methods
Data were extracted from recommendation reports for the ultra-rare diseases evaluated between 2012 and 2022. To classify a disease as ultra-rare, the epidemiological criterion or a consultation with the Orphanet platform was used (prevalence of ≤1/50,000 inhabitants). The extracted variables included the type of evidence synthesis, type of studies, instrument, the result of the assessment of the methodological quality of the studies, the format of evidence synthesis presentation, whether the evidence was graded, and the result.
Results
Among 53 analyzed reports, 70 percent relied on randomized controlled trials, followed by systematic reviews (SR), and observational studies. Reports with positive recommendations based on SR comprised 63 percent. GRADE applied to 27 reports and indicated low or very low results for the first two outcomes (62% and 65%). No clear link between evidence quality and final recommendations was observed. Meta-analysis-based reports had 83 percent positive recommendation rate, compared to 55 percent without meta-analysis. Surrogate outcomes were predominant. Clinical characteristics significantly influenced final decisions, especially when new data emerged in public consultation or had the potential to alter disease progression, reduce severe events, or enhance survival.
Conclusions
Ultra-rare diseases pose challenges in evidence quantity and quality. Traditional HTA frameworks seem inadequate, lacking robust evidence for these conditions. The difficulties in ultra-rare disease HTA underscore the need for specialized frameworks. This analysis acknowledges limitations, notably the heterogeneity in older report structures compared to recent ones, reflecting evolving HTA methodologies in Brazil.
The decision-making process for incorporating technologies for ultrarare diseases (URD) has been a challenge for health technology assessment agencies worldwide. These challenges have been presented in debates about the budget impact of incorporating technologies for URD. This is an important issue because there are other dimensions of the economic and social impact of URD that require consideration.
Methods
Data were extracted from National Committee for Health Technology Incorporation (CONITEC) reports (2012 to 2022) on technologies for the treatment of URD in Brazil. Diseases were classified using an epidemiological criterion or Orphanet consultation (prevalence ≤1 per 50,000 inhabitants). Variables included eligible patient count, population estimation method, incremental impact values for one and five years, and diffusion rate in the first and fifth year. Univariate logistic regression was used to adjust the relationship between the budget impact analysis and the final recommendation, considering factors associated with incorporation in univariate regression and p-values less than 0.10 in a multivariate regression.
Results
Among 53 reports, 48 percent exclusively employed the epidemiological approach for incremental impact assessment population estimation, rising to 69.5 percent when combined with measured demand. Population data were nearly evenly sourced from national and international platforms, with the UK, the USA, and multicenter studies being the most cited internationally. Notable differences were found between favorable and unfavorable CONITEC recommendations, with lower values being associated with incorporation. Market share diffusion rates favored the option of 100 percent diffusion in both the first year and the cumulative five years. The analysis highlighted the influence of demand characteristics and technology type on the budget impact value over one and five years.
Conclusions
The study found that budget impact data significantly influenced the final recommendation for technology incorporation, indicating a criterion favoring technologies with a lower budget impact. However, requester characteristics and technology type also played a role in the decision-making process, suggesting that additional factors influence recommendations.
The decision-making process for health technology assessment (HTA) in ultra-rare diseases is a global challenge. Establishing a comprehensive analytical framework for these unique diseases poses difficulties. This study aims to descriptively analyze arguments reported by the Brazilian National Committee for Health Technology Incorporation (Conitec) in deciding whether to include technology for ultra-rare diseases.
Methods
Data from recommendation reports (2012 to 2022) were analyzed. Diseases with a prevalence of fewer than one per 50,000 inhabitants were classified as ultra-rare. Extracted variables included preliminary and final recommendation results and justifications by Conitec. Six argument categories were created (method-related issues; evidence; cost; technology effectiveness or safety; context; innovation). Word clouds were generated based on word frequency in each category to present the data.
Results
In the analysis of 45 reports, the word clouds highlight frequent terms in favorable arguments, emphasizing evidence quality, cost reduction, and applicability in the healthcare system. Conversely, unfavorable arguments also revolve around evidence quality and cost impact. The analysis of the arguments according to categories, 16 arguments were identified: seven concern evidence issues, five cite methodological problems in presented studies, four relate to costs, and three pertain to technology effectiveness or safety. Unfavorable arguments primarily stem from evidence-related concerns. In favorable arguments, cost (seven) and safety (six) are prominent, with innovation (one) and context (three) being additional categories not found in the unfavorable group.
Conclusions
While technology assessment processes for ultra-rare diseases have evolved, the justifications for recommending or not incorporating new technologies remain unchanged. Over time, reports have become more detailed, focusing on evidence and methodological specifics. This highlights the importance of scrutinizing evidence characteristics and determining relevant criteria and data types for this unique context.
Several countries established health technology assessment (HTA) processes to support decision-making. Considering the high volume of submissions processed by HTA agencies, approaches to determine factors associated with the approval would be beneficial. This study aimed to predict the final recommendation of the National Committee for Health Technology Incorporation (Conitec) using a natural language processing (NLP) algorithm for text extraction.
Methods
Conitec’s 2012 to 2022 reports (n=389) were split into 75 percent training and 25 percent testing data. Tokenization enabled NLP models: Least Absolute Shrinkage and Selection Operator (LASSO), logistic regression, support vector machine (SVM), random forest, neural network, and Extreme Gradient Boosting (XGBOOST). Evaluation criteria included accuracy, area under the receiver operating characteristic curve (ROC AUC) score, precision, and recall. Cluster analysis with k-modes identified two clusters (group 0 = approved, group 1 = rejected).
Results
The neural network model demonstrated the best accuracy metrics with a precision of 0.815, accuracy of 0.769, ROC AUC of 0.871, and a recall of 0.746. Some tokenization identified that linguistic markers could contribute to the prediction of incorporation decision by the Brazilian HTA Committee, such as international HTA agencies’ experience and the government as the main requester. Cluster and XGBOOST analysis identified similar results with approved technologies with a predominance of drugs assessment, mainly requested by the government, and not approved mostly assessing drugs, the industry as the main requester.
Conclusions
The NLP model could identify predictors for the final decision process on the incorporation of health technologies in Brazil’s Unified Health System, opening paths for future work using HTA reports coming from other agencies. This model could potentially improve the throughput of HTA systems by supporting experts with prediction/factors/criteria for approval or nonapproval as an earlier step.
Ultrarare diseases (URD) represent a challenge to health technology assessment (HTA). The traditional framework for assessing efficacy and cost effectiveness may be biased to include clinically relevant outcomes, leaving patient-centered outcomes doomed to neglect. Here we explore patient-centered outcomes in the context of patient and citizen involvement in the assessment of URD by the Brazilian National Committee for Health Technology Incorporation (CONITEC).
Methods
We assessed 53 HTA reports from CONITEC that evaluated URD-related technologies (and included highlights of patients’ and citizens’ perspectives during recommendation meetings) published from 2012 to 2022. Data extraction was performed by two independent researchers. Data on year of report, sex, ethnicity, category (patient or family), and previous experience with the assessed technology were extracted and analyzed using descriptive statistics. Patients’ and citizens’ narratives were collated from the reports. A thematic analysis was conducted according to patient-centered outcomes and technology-related outcomes and was then compared with the evidence synthesis protocol described in the HTA.
Results
Only seven URD-related HTA reports registered patient or citizen participation, all of which were published in 2022. The age of two participants was reported (both 17 years). Six participants were women. Ethnicity was not reported. All participants had previous experience with the technology. Four participants were family or caregivers and three were patients. Considering patient-centered outcomes, physical (muscular strength) and emotional (self-confidence) improvements that positively affected independence in basic daily functions were reported. These functions included activities such as dressing, self-care, cooking, and leisure. Advantages listed for the assessed technologies included the possibility of self-administration of medication (e.g., swallowing a pill, opening a medicine bottle, and using a syringe).
Conclusions
The results show that although, in some cases, primary outcomes reported in evidence synthesis protocols include patient-centered outcomes (e.g., activities of daily living), in other cases the evidence synthesis failed to identify relevant studies. In other cases, the reports failed to differentiate between primary and secondary outcomes or to fully account for patient-centered outcomes.
Incorporating technologies for ultrarare diseases (URD) poses challenges for global health technology assessment (HTA) agencies. Difficulties include defining an analytical framework and establishing differentiated cost-effectiveness thresholds. The rise of technological innovations intensifies demands from healthcare professionals, media, and the general population, placing pressure on healthcare systems in developing countries.
Methods
To analyze ultrarare medicine costs in submissions to the Brazilian National Committee for Health Technology Incorporation (CONITEC), data from HTA reports on URD (from 2012 to 2022) were extracted. Diseases were classified as URD based on an epidemiological criterion or Orphanet consultation (prevalence ≤1 per 50,000 inhabitants). Extracted variables included initial and final prices, annual patient cost, incremental cost-effectiveness ratio (ICER), and initial and final CONITEC recommendations. Price differences were calculated by the Brazilian Medicines Market Regulation Chamber.
Results
Among 53 reports, 30 featured economic evaluations, with only 13.3 percent initially receiving positive recommendations. However, eight gained favor, including post-consultation, price-conditioned, and risk sharing-based approvals. Annual medication costs ranged from USD17,439.20 to USD1,108,237.00 per patient, with discounts of between 25 and 64 percent. Despite some technologies having ICERs that were significantly higher than the national threshold, no statistical relationship was found between ICERs and recommendations. Monthly and annual costs varied, with higher costs for heterogeneous diseases and lower costs for metabolic conditions. Sensitivity analyses, using both deterministic and probabilistic analyses, were conducted in 58 percent of the reports.
Conclusions
Incorporation of technologies for URD does not correlate with lower annual costs or increased discounts because costs are not considered in isolation by CONITEC’s decision-making process. Recognizing URD as a subgroup with distinct criteria may enhance the implementation of HTA processes tailored to the unique challenges of these conditions.
Cytogenetic analyses have been widely used to understand evolutionary processes and to resolve taxonomic uncertainties in insects. In particular, the mapping of specific chromosomal regions can provide insights about the genome organisation and interspecific relationships. Considering the importance of this approach and the scarcity of chromosomal data in some groups of Hymenoptera, this study provides the first cytogenetic characterisation of the parasitoid wasp, Brachymeria (Pseudobrachymeria) vesparum Bouček, 1992 (Hymenoptera: Chalcididae). This species was characterised by 2n = 10 metacentric chromosomes. The heterochromatin was located at pericentromeric and terminal regions, being particularly conspicuous due to occupying a large part of chromosomes from pair 2. In addition, guanine–cytosine-rich blocks (GC+) were detected in the interstitial region of two chromosomal pairs. The data obtained were found to be useful for inferring the chromosomal rearrangements involved in speciation within Brachymeria, in addition to providing cytotaxonomic markers for further comparative cytogenetic studies.
Some epilepsy syndromes are more common in females such as genetic generalized epilepsy (GGE) including juvenile myoclonic epilepsy (JME). JME is also more frequently transmitted to offspring by the women affected with epilepsy than by men. Other epilepsy syndromes limited to females are frequently associated to pathogenic variants in genes located on the X chromosome such as Rett syndrome, CDKL5 deficiency disorder, subcortical band heterotopia, PCDH19 epilepsy and Aicardi syndrome. In this chapter we described these conditions and summarize the most relevant diagnostic features and treatment considerations. Recognizing these syndromes helps the clinician in selecting appropriate treatment, explains some spontaneous miscarriages and is a tool in counseling patients and family members about the risk of transmission. Genetic diagnosis can be made through several tests, with whole exome sequencing having the higher cost-effectiveness when compared to epilepsy panel and microarray. Treatment can be difficult and there might be some role for the use of Cannabidiol, Fenfluramine and Ganaloxone in some of these diseases. Advances in molecular genetics will likely lead to a better understanding of these epilepsy in women, and hopefully result in tailored precision medicine treatments.
Sleep is a topic of scientific and technological relevance, as it is closely related to cognition, emotional well-being, and human health. In addition, health-related geopolitical and social changes have significant implications for sleep research, which in turn is linked to the sustainable development goals (SDGs). An integrative review is conducted to analyze multidisciplinary studies in the field of sleep, considering the socioecological model of sleep health and the SDGs. Sleep was found to play a key role in promoting several SDG: (1) Social and economic inclusion: sleep is linked to poverty eradication, food security, reducing inequalities, and promoting peace and justice; (2) Promoting well-being and quality of life: sleep quality directly affects health, education, gender equality, environmental protection, and combating climate change; (3) Economic and environmental sustainability: Adequate sleep contributes to decent work, innovation, infrastructure, responsible consumption, sustainable communities and collaboration through partnerships. This thematic organization provides an overview of the different aspects of the intersection between sleep health disparities and the SDG.
Black and Latino individuals are underrepresented in COVID-19 treatment and vaccine clinical trials, calling for an examination of factors that may predict willingness to participate in trials.
Methods:
We administered the Common Survey 2.0 developed by the Community Engagement Alliance (CEAL) Against COVID-19 Disparities to 600 Black and Latino adults in Baltimore City, Prince George’s County, Maryland, Montgomery County, Maryland, and Washington, DC, between October and December 2021. We examined the relationship between awareness of clinical trials, social determinants of health challenges, trust in COVID-19 clinical trial information sources, and willingness to participate in COVID-19 treatment and vaccine trials using multinomial regression analysis.
Results:
Approximately half of Black and Latino respondents were unwilling to participate in COVID-19 treatment or vaccine clinical trials. Results showed that increased trust in COVID-19 clinical trial information sources and trial awareness were associated with greater willingness to participate in COVID-19 treatment and vaccine trials among Black and Latino individuals. For Latino respondents, having recently experienced more challenges related to social determinants of health was associated with a decreased likelihood of willingness to participate in COVID-19 vaccine trials.
Conclusions:
The willingness of Black and Latino adults to participate in COVID-19 treatment and vaccine clinical trials is influenced by trial awareness and trust in trial information sources. Ensuring the inclusion of these communities in clinical trials will require approaches that build greater awareness and trust.
The objective was to evaluate the performance of suckling piglets based on their choice of mammary gland. A completely randomized design was used, considering the position of the mammary glands pair and their respective piglets as experimental unit. The mammary gland position was considered for the treatments, being 1st, 4th and 7th pair. The ration and leftovers were weighed daily to obtain daily feed intake of the sow. On post-natal day (PND) 3 and 21, 80 ml of milk was collected to analyse crude protein, fat, lactose, non-fatty solids, mineral matter and total solids. On PND 3 and 21, the piglets were weighed to determine weight gain and estimate milk consumption. The piglets' longitudinal length and head circumference were measured in the same period and estimated body surface area/mass ratio. Blood samples from the sows and piglets were collected on PND 3 and 21 to analyse total cholesterol, triglycerides, total protein, fractions and glucose. There was an effect of mammary gland position on piglets at PND 21 suckling on the 7th pair, which had a 23.88 cm2/kg greater body surface/mass ratio compared to those who suckled in the 1st pair. In turn, at PND 21, the piglets that suckled in the 1st pair presented higher weight, weight gain and milk consumption (0.685, 0.033 and 0.127 kg, respectively) than those that suckled in the 7th pair. Anterior mammary glands result in better productive performance and better chances of maintaining piglet homeostasis at PND 21.
The Cardiovascular Health Diet Index (CHDI) is a diet quality score based on the dietary guidelines of the American Heart Association for cardiovascular health but with some adaptations, such as red meat, dairy products, beans and ultra-processed foods in its components. The CHDI has shown good relative validity parameters; however, its association with health outcomes is still unclear. Thus, our aim was to investigate the association between the CHDI score with subclinical atherosclerosis. Data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort were used. Subclinical atherosclerosis was assessed by measuring coronary artery calcification at baseline (2008–2010) and second wave (2012–2014) and carotid intima-media thickness at baseline and at the third wave (2017–2019). The CHDI score (ranges from 0 to 110 points) was applied to dietary data obtained from an FFQ at baseline. Poisson regression with robust variance, linear regression and linear mixed-effects models were used to evaluate the association of the CHDI score with coronary artery calcification incidence (n 2224), coronary artery calcification progression (n 725) and changes in carotid intima-media thickness (n 7341) over time, respectively. After a median 8-year follow-up period, a 10-point increase in the CHDI score was associated with a decrease in carotid intima-media thickness of 0·002 mm (95 % CI –0·005, –0·001). No association was observed between the CHDI score and coronary artery calcification incidence and progression after a 4-year follow-up period. Higher scores in the CHDI were prospectively associated with decreased subclinical atherosclerosis after an 8-year follow-up period.
We describe a new species of the genus Alippistrongylus (Nematoda: Trichostrongylina) in the small intestine of Delomys dorsalis (Rodentia: Sigmodontinae) found in Itatiaia National Park (Parque Nacional do Itatiaia, PNI), state of Rio de Janeiro, Brazil. The new species can be distinguished between the other two species previously described by the following morphological characteristics: pattern of the rays from the caudal bursa rays in males and the spherical-shaped appendage in the female. Additionally, we provide molecular genetic data from the new species. The discovery of Alippistrongylus itatiaiaensis sp. n. expands our understanding of nematode diversity and underscores the importance of parasite studies in biodiversity conservation. Its occurrence in a preserved area like the PNI emphasises the role of such habitats in maintaining unique ecological interactions.
This study aimed to assess the association between emotional attitudes towards diabetes, eating behaviour styles and glycaemic control in outpatients with type 2 diabetes.
Design:
Observational study.
Setting:
Endocrinology Division of Hospital de Clínicas de Porto Alegre, Brazil.
Participants:
Ninety-one outpatients diagnosed with type 2 diabetes. Baseline assessments included data on clinical parameters, lifestyle factors, laboratory results, eating behaviour styles and emotional attitudes. All patients received nutritional counseling following diabetes recommendations. A follow-up visit was scheduled approximately 90 days later to evaluate changes in weight, medication dosages and glycated Hb (HbA1c) values. Patients were categorised based on their emotional attitude scores towards diabetes (positive or negative), and their characteristics were compared using appropriate statistical tests.
Results:
At baseline, no differences were observed in the proportion of patients with good glycaemic control, eating behaviour styles and emotional attitudes. However, patients with a positive attitude towards the disease exhibited a significantly better response in glycaemic control compared with the reference group (OR = 3·47; 95 % CI = 1·12, 10·75), after adjusting for diabetes duration, sex and medication effect score. However, when BMI was included in the model, the association did not reach statistical significance. Therefore, these results should be interpreted with caution.
Conclusions:
Patients with a positive attitude towards diabetes showed a greater reduction in HbA1c levels following nutritional counseling. However, baseline BMI could be a potential confounding factor.