On the Relationship between Code Verifiability and Understandability

Proponents of software verification have argued that simpler code is easier to verify: that is, that verification tools issue fewer false positives and require less human intervention when analyzing simpler code. We empirically validate this assumption by comparing the number of warnings produced by four state-of-the-art verification tools on 211 snippets of Java code with 20 metrics of code comprehensibility from human subjects in six prior studies. Our experiments, based on a statistical (meta-)analysis, show that, in aggregate, there is a small correlation (r = 0.23) between understandability and verifiability. The results support the claim that easy-to-verify code is often easier to understand than code that requires more effort to verify. Our work has implications for the users and designers of verification tools and for future attempts to automatically measure code comprehensibility: verification tools may have ancillary benefits to understandability, and measuring understandability may require reasoning about semantic, not just syntactic, code properties.Comment: to appear at Proceedings of the 31st ACM Joint European Software Engineering Conference and Symposium on the Foundations of Software Engineering (ESEC/FSE'23

Environmentally induced phenotypic variation in wild yellow-bellied marmots

We thank all the marmoteers who helped in data collection and 2 anonymous reviewers who helped us to clarify our message. AM-C was supported by a Fulbright Fellowship, and JGAM was supported by Fond Québécois de Recherche sur la Nature et les Technologies. KBA was supported by the National Science Foundation between 1962 and 2000. DTB was supported by the National Geographic Society, UCLA (Faculty Senate and the Division of Life Sciences), a Rocky Mountain Biological Laboratory research fellowship, and by the National Science Foundation (IDBR-0754247 and DEB-1119660 to DTB as well as DBI 0242960 and 0731346 to the Rocky Mountain Biological Laboratory).Peer reviewedPostprin

Cost-Effectiveness of a Comprehensive Approach for Hypertension Control in Low-Income Settings in Argentina: Trial-Based Analysis of the Hypertension Control Program in Argentina

Background: A recent cluster randomized trial evaluating a multicomponent intervention showed significant reductions in blood pressure in low-income hypertensive subjects in Argentina. Objectives: To assess the cost-effectiveness of this intervention. Methods: A total of 1432 hypertensive participants were recruited from 18 primary health care centers. The intervention included home visits led by community health workers, physician education, and text messaging. Resource use and quality of life data using the three-level EuroQol five-dimensional questionnaire were prospectively collected. The study perspective was that of the public health care system, and the time horizon was 18 months. Intention-to-treat analysis was used to analyze cost and health outcomes (systolic blood pressure [SBP] change and quality-adjusted life-years [QALYs]). A 1 time gross domestic product per capita per QALY was used as the cost-effectiveness threshold (US $14,062). Results: Baseline characteristics were similar in the two arms. QALYs significantly increased by 0.06 (95$304 in the intervention group and US $154 in the control group (adjusted difference of US$140.18; 95% CI US $75.41–US$204.94). The incremental cost-effectiveness ratio was $3299 per QALY (95$26 per mm Hg of SBP (95% credible interval 13–46). Subgroup analysis showed that the intervention was cost-effective in all prespecified subgroups (age, sex, cardiovascular risk, and body mass index). Conclusions: The multicomponent intervention was cost-effective for blood pressure control among low-income hypertensive patients.Fil: Augustovski, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Chaparro, Martin. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Palacios, Alfredo. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Shi, Lizheng. University of Tulane; Estados UnidosFil: Beratarrechea, Andrea Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Mills, Katherine. University of Tulane; Estados UnidosFil: He, Jiang. University of Tulane; Estados UnidosFil: Pichón-Riviere, Andrés. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Transmisión congénita y factores maternos de la enfermedad de Chagas en niños al nacer y sus hermanos en la provincia del Chaco, Argentina.

Introducción. Luego de la transmisión vectorial, la congénita, es la forma más importante para mantener la endemia. La probabilidad de transmisión congénita puede depender de factores que varían entre los diferentes países y áreas geográficas. Se realizó este trabajo con el objetivo de estimar la proporción de transmisión congénita y explorar factores maternos asociados a la  enfermedad de Chagas en niños al nacer y sus respectivos hermanos en cuatro hospitales de la Provincia del Chaco. Métodos. Estudio transversal. Se realizó una visita al domicilio de niños de 10 meses de edad o mayores,  nacidos durante el año 2011, hijos de mujeres con infección por T cruzi. Se extrajeron muestras sanguíneas tanto de los niños al nacer como de sus hermanos y se procesaron para diagnóstico de infección por T cruzi con HAI y ELISA. Resultados. Se localizaron a 247 madres infectadas con T. cruzi, y se obtuvieron muestras de sangre de 246 niños al nacer y de 556 de sus hermanos. Del total de nacidos en el año 2011, el 6,1% (IC 95%= 3,6-9,6) resultaron con serología positiva,  así como 7,7%; de sus  hermanos (IC 95%= 5,7-10,1) y el control de salud de ambos niños en el centro de atención primaria  se asoció con una menor probabilidad de transmisión congénita (OR=0,21 y 0,36 respectivamente).Conclusión. La tasa de transmisión es consistente con los valores reportados en el país y solo la multiparidad fue un factor asociado a la mayor  probabilidad de transmisión congénita

The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities

Uncontrolled host immunological reactions directed against tissue-trapped eggs precipitate a potentially lethal, pathological cascade responsible for schistosomiasis. Blocking schistosome egg production, therefore, presents a strategy for simultaneously reducing immunopathology as well as limiting disease transmission in endemic or emerging areas. We recently demonstrated that the ribonucleoside analogue 5-azacytidine (5-AzaC) inhibited Schistosoma mansoni oviposition, egg maturation and ovarian development. While these anti-fecundity effects were associated with a loss of DNA methylation, other molecular processes affected by 5-AzaC were not examined at the time. By comparing the transcriptomes of 5-AzaC-treated females to controls, we provide evidence that this ribonucleoside analogue also modulates other crucial aspects of schistosome egg-laying biology. For example, S. mansoni gene products associated with amino acid-, carbohydrate-, fatty acid-, nucleotide- and tricarboxylic acid (TCA)- homeostasis are all dysregulated in 5-AzaC treated females. To validate the metabolic pathway most significantly affected by 5-AzaC, amino acid metabolism, nascent protein synthesis was subsequently quantified in adult schistosomes. Here, 5-AzaC inhibited this process by 68% ?16.7% (SEM) in male- and 81% ?4.8% (SEM) in female-schistosomes. Furthermore, the transcriptome data indicated that adult female stem cells were also affected by 5-AzaC. For instance, 40% of transcripts associated with proliferating schistosome cells were significantly down-regulated by 5-AzaC. This finding correlated with a considerable reduction (95%) in the number of 5-ethynyl-2?-deoxyuridine (EdU) positive cells found in 5-AzaC-treated females. In addition to protein coding genes, the effect that 5-AzaC had on repetitive element expression was also assessed. Here, 46 repeats were found differentially transcribed between 5-AzaC-treated and control females with long terminal repeat (LTR) and DNA transposon classes being amongst the most significant. This study demonstrates that the anti-fecundity activity of 5-AzaC affects more than just DNA methylation in schistosome parasites. Further characterisation of these processes may reveal novel targets for schistosomiasis controlauthorsversionPeer reviewe

Toward estimation of seasonal water dynamics of winter wheat from ground-based L-band radiometry: a concept study

peer reviewedThe vegetation optical depth (VOD) variable contains information on plant water content and biomass. It can be estimated alongside soil moisture from currently operating satellite radiometer missions, such as SMOS (ESA) and SMAP (NASA). The estimation of water fluxes, such as plant water uptake (PWU) and transpiration rate (TR), from these earth system parameters (VOD, soil moisture) requires assessing water potential gradients and flow resistances in the soil, the vegetation and the atmosphere. Yet water flux estimation remains an elusive challenge especially on a global scale. In this concept study, we conduct a field-scale experiment to test mechanistic models for the estimation of seasonal water fluxes (PWU and TR) of a winter wheat stand using measurements of soil moisture, VOD, and relative air humidity (RH) in a controlled environment. We utilize microwave L-band observations from a tower-based radiometer to estimate VOD of a wheat stand during the 2017 growing season at the Selhausen test site in Germany. From VOD, we first extract the gravimetric moisture of vegetation and then determine the relative water content (RWC) and vegetation water potential (VWP) of the wheat field. Although the relative water content could be directly estimated from VOD, our results indicate this may be challenging for the phenological phases, when rapid biomass and plant structure development take place within the wheat canopy. We estimate water uptake from the soil to the wheat plants from the difference between the soil and vegetation potentials divided by the flow resistance from soil into wheat plants. The TR from the wheat plants into the atmosphere was obtained from the difference between the vegetation and atmosphere water potentials divided by the flow resistances from plants to the atmosphere. For this, the required soil matric potential (SMP), the vapor pressure deficit (VPD), and the flow resistances were obtained from on-site observations of soil, plant, and atmosphere together with simple mechanistic models. This pathfinder study shows that the L-band microwave radiation contains valuable information on vegetation water status that enables the estimation of water dynamics (up to fluxes) from the soil via wheat plants into the atmosphere, when combined with additional information of soil and atmosphere water content. Still, assumptions have to be made when estimating the vegetation water potential from relative water content as well as the water flow resistances between soil, wheat plants, and atmosphere. Moreover, direct validation of water flux estimates for the assessment of their absolute accuracy could not be performed due to a lack of in situ PWU and TR measurements. Nonetheless, our estimates of water status, potentials, and fluxes show the expected temporal dynamics, known from the literature, and intercompare reasonably well in absolute terms with independent TR estimates of the NASA ECOSTRESS mission, which relies on a Priestly-Taylor type of retrieval model. Our findings support that passive microwave remote-sensing techniques qualify for the estimation of vegetation water dynamics next to traditionally measured stand-scale or plot-scale techniques. They might shed light on future capabilities of monitoring water dynamics in the soil-plant-atmosphere system including wide-area, remote-sensing-based earth observation data

Barriers and facilitators for the implementation and evaluation of community-based interventions to promote physical activity and healthy diet: A mixed methods study in Argentina

Background: Obesogenic environments promote sedentary behavior and high dietary energy intake. The objective of the study was to identify barriers and facilitators to the implementation and impact evaluation of projects oriented to promote physical activity and healthy diet at community level. We analyzed experiences of the projects implemented within the Healthy Municipalities and Communities Program (HMCP) in Argentina. Methods: A mixed methods approach included (1) in-depth semi-structured interviews, with 44 stakeholders; and (2) electronic survey completed by 206 individuals from 96 municipalities across the country. Results: The most important barriers included the lack of: adequate funding (43%); skilled personnel (42%); equipment and material resources (31%); technical support for data management and analysis (20%); training on project designs (12%); political support from local authorities (17%) and acceptance of the proposed intervention by the local community (9%). Facilitators included motivated local leaders, inter-sectorial participation and seizing local resources. Project evaluation was mostly based on process rather than outcome indicators. Conclusions: This study contributes to a better understanding of the difficulties in the implementation of community-based intervention projects. Findings may guide stakeholders on how to facilitate local initiatives. There is a need to improve project evaluation strategies by incorporating process, outcome and context specific indicators.Fil: Belizan, Maria. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Chaparro, Raul Martin. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Santero, Marilina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Elorriaga, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Kartschmit, Nadja. No especifíca;Fil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentin

Effects of golimumab and ustekinumab on circulating dendritic cell migratory capacity in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic condition which includes ulcerative colitis (UC) and Crohn’s disease (CD), the origins of which are not yet fully understood. Both conditions involve an exacerbated immune response in the intestinal tract, leading to tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells crucial for maintaining tolerance in the gastrointestinal mucosa. Previous research has indicated that DC recruitment to the intestinal mucosa is more pronounced in individuals with IBD, but the specific mechanisms governing this migration remain unclear. This study aimed to assess the expression of various homing markers and the migratory abilities of circulating DC subsets in response to intestinal chemotactic signals. Additionally, this study examined how golimumab and ustekinumab impact these characteristics in individuals with IBD compared to healthy controls. The findings revealed that a particular subset of DCs known as type 2 conventional DCs (cDC2) displayed a more pronounced migratory profile compared to other DC subsets. Furthermore, the study observed that golimumab and ustekinumab had varying effects on the migratory profile of cDC1 in individuals with CD and UC. While CCL2 did not exert a chemoattractant effect on DC subsets in this patient cohort, treatment with golimumab and ustekinumab enhanced their migratory capacity towards CCL2 and CCL25 while reducing their migration towards MadCam1. In conclusion, this study highlights that cDC2 exhibits a heightened migratory profile towards the gastrointestinal mucosa compared to other DC subsets. This finding could be explored further for the development of new diagnostic biomarkers or the identification of potential immunomodulatory targets in the context of IB