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Abstract Background The COVID-19 vaccination programme in South Africa was rolled out in February 2021 via five delivery channels- hospitals, primary healthcare (PHC), fixed, temporary, and mobile outreach channels. In this study, we estimated the financial and economic costs of the COVID-19 vaccination programme in the first year of roll out from February 2021 to January 2022 and one month prior, in one district of South Africa, the West Rand district. Methods Financial and economic costs were estimated from a public payer’s perspective using top-down and ingredient-based costing approaches. Data were collected on costs incurred at the national level and from the West Rand district. Total cost and cost per COVID-19 vaccine dose were estimated for each of the five delivery channels implemented in the district. In addition, we estimated vaccine delivery costs which we defined as total cost exclusive of vaccine procurement costs. Results Total financial and economic costs were estimated at US$8.5 million and US$12 million, respectively; with a corresponding cost per dose of US$15.31 (financial) and US$21.85 (economic). The two biggest total cost drivers were vaccine procurement which contributed 73% and 51% to total financial and economic costs respectively, and staff time which contributed 10% and 36% to total financial and economic costs, respectively. Total vaccine delivery costs were estimated at US$2.1 million (financial) and US$5.7 million (economic); and the corresponding cost per dose at US$3.84 (financial) and US$10.38 (economic). Vaccine delivery cost per dose (financial/economic) was estimated at US$2.93/12.84 and US$2.45/5.99 in hospitals and PHCs, respectively, and at US$7.34/20.29, US$3.96/11.89 and US$24.81/28.76 in fixed, temporary and mobile outreach sites, respectively. Staff time was the biggest economic cost driver for vaccine delivery in PHCs and hospitals while per diems and staff time were the biggest economic cost drivers for vaccine delivery in the three outreach delivery channels. Conclusion This study offers insights for budgeting and planning of COVID-19 vaccine delivery in South Africa’s public healthcare system. It also provides input for cost-effectiveness analyses to guide future strategies for maximizing vaccination coverage in the country.

Abstract There are limited data on first seizure (FS) among adults in low and middle‐income countries. We describe findings from a prospective cohort study involving 180 adults presenting with seizures in emergency departments in five Latin American countries. Overall, 102 participants (56.7%) had acute symptomatic seizures (ASyS) while 78 (43.3%) had unprovoked seizures (UPS). Among patients with ASyS, 55 (53.9%) had structural causes, with stroke (n = 24, 23.5%), tumor (n = 10, 9.8%), and trauma (n = 3, 3%) being the most frequent. Nineteen patients (18.6%) had infectious causes, including four (4%) with meningoencephalitis, three (3%) neurocysticercosis, and two (2%) bacterial meningoencephalitis. Twenty patients (19.6%) had metabolic/toxic evidence, including four (4%) with uremic encephalopathy, two (2%) hyponatremia, and three (3%) acute alcohol intoxication. Immune dysfunction was present in seven (7%) patients and neurodegenerative in two (2%). Among participants with UPS, 45 (57.7%) had unknown etiology, 24 (30.7%) had evidence of structural disorders (remote symptomatic), four (5%) were related to infectious etiology (>7 days before the seizure), and five (6.4%) had genetic causes. During the 3‐ and 6‐month follow‐up, 29.8% and 14% of patients with UPS, respectively, experienced seizure recurrence, while 23.9% and 24.5% of patients with ASyS had seizure recurrence. Longer follow‐up is necessary to assess seizure recurrence for patients with ASyS after the acute cause is resolved and to determine the 10‐year risk of recurrence, which is part of the definition of epilepsy. Plain Language Summary We monitored 180 adults who presented with their first seizure in emergency departments across five Latin American countries. Among these patients, 57% had acute symptomatic seizures, with structural causes such as stroke (23%), infection (17%), or tumor (10%) being more prevalent. Among the 43% with unprovoked seizures, 58% showed no identifiable acute cause, while 6.4% were due to genetics. Within 3 months after their initial seizure, 26.6% of individuals experienced a second seizure, with 11.9% continuing to have seizures in Months 3–6. Between Months 3 and 6, an additional 20% of patients encountered a second seizure. Research is needed to better understand the cause and prognosis of these patients to improve outcomes.

Here is presented a case of a 22-year-old female with an extensive cervical giant cell bone tumor comprising about 80% of the oropharynx and laryngopharynx. A combined posterior and transmandibular approach was needed to accomplish a complete resection and stabilization. The post-operative recovery was successful, and the patient experienced notable improvements in neurological function, pain relief, and cervical spine stability. This case highlights the effectiveness of this uncommon approach in treating upper cervical lesions.

Coastal ecosystems are vital for numerous demersal and benthopelagic species, offering critical habitats throughout their life cycles. Effective monitoring of these species in complex coastal environments is essential, yet traditional survey methodologies are often impractical due to environmental constraints like strong currents and high wave regimes. This study introduces a new cost-effective Baited Remote Underwater Video System (BRUVS) design featuring a vertical structure and 360° cameras developed to overcome limitations of traditional BRUVS, such as system anchoring, overturning, and restricted frame view. The new design was compared against a previous one used on the northwest Iberian coast. Key performance metrics included species detection, habitat identification, and operational efficiency under complex hydrodynamic conditions. Findings reveal that the two designs can effectively identify the common species typically observed in the study area. However, the new design outperformed the previous by significantly reducing equipment losses and anchoring issues. This enhancement in field operations’ simplicity, operability, portability, and resiliency underscores the new system’s potential as a cost-effective and efficient tool for demersal and benthopelagic ecological surveys in challenging coastal seascapes. This innovative BRUVS design offers advanced monitoring solutions, improving habitat assessment accuracy and responsiveness.

En la actualidad, como tantas veces se ha repetido, no faltan normas que prevean derechos, obligaciones, controles, procedimientos y toda una serie de exigencias y pautas de comportamientos jurídicamente condicionados que aseguren el papel de las Administraciones Públicas como esenciales instrumentos para la gobernanza democrática y la defensa del Estado de Derecho. Sin embargo, parece no evidenciarse, la importancia de acreditar en las prestaciones públicas un elevado perfil de integridad concretado en vectores de ética aplicada que eviten la creciente desafección ciudadana y falta de legitimación, cuando no, el establecimiento de una sistémica y abierta hostilidad hacia las instituciones y Administraciones Públicas. Se trata de una tarea colectiva en la que la responsabilidad propia de los servidores públicos (sean cargos electos o empleados públicos) no basta, necesitando el apoyo de una ciudadanía cuyos valores reflejen una obligada cultura sobre integridad pública.

Understanding species–habitat relationships is essential for ecosystem-based conservation. This study explores the significance of habitat characteristics and complexity for demersal and benthopelagic communities within a patchwork of coastal habitats, including rocky seabed, macroalgae formations, sandy bottoms, and a combination of rock and sand areas. Species and habitats were surveyed along the north-west (NW) Iberian continental shelf area of Viana do Castelo using baited remote underwater video stations (BRUVS). We found significant differences (p < 0.05) in species assemblages across habitats, with rocky substrates showing the highest diversity and abundance. Sand habitats showed the lowest species richness and abundance, underscoring the importance of habitat complexity to support marine life. Our study also emphasises the role of specific species in shaping the communities, identifying key species such as Trisopterus luscus, Diplodus vulgaris, and Ctenolabrus rupestris as the three most abundant in the region and significant contributors to the observed dissimilarities between habitats. By elucidating the impact of habitat complexity on marine life, our results offer essential baseline data, which serve as a kick-start point to inform sustainable management and conservation strategies for the long-term health and productivity of these vital ecological systems in the North-East Atlantic.

In this study we used the average annual temperature in Brazil and four warming predictions to propose a maximum thermal threshold for the predatory mite Cosmolaelaps brevistilis (Karg, 1978) (Mesostigmata: Laelapidae) as an experimental model. Then, we evaluated the effects of warming on the biological parameters of C. brevistilis for conservation biological control. We observed higher rates of oviposition and predation of the prey Tyrophagus putrescentiae (Schrank, 1781) (Astigmatina: Acaridae) under warmer conditions at 75 ± 10% RH. The highest rates of prey consumption and oviposition were observed at 28°C compared to the others tested (22, 24, and 26°C). However, the egg viability of C. brevistilis was reduced at the same temperature. Therefore, temperature increases both positive and negative effects on the biological parameters of C. brevistilis which are important for the ecological interactions that are essential for biological control programs.

Introduction: We aimed to identify clinical, pathologic, and treatment factors that are predictive of response and survival in patients with cervical cancer referred to phase I clinical trials. Methods: Patients with cervical cancer who received at least one dose of a phase I investigational agent at our institution between 2014 and 2022 were included. The log-rank test was used to analyze differences in progression-free survival (PFS) and overall survival (OS), and multivariable regression analysis was performed. Results: We included 65 patients with a median age of 41 years (range, 20–74), 3 prior therapies (range, 1–7), and 67.7% squamous carcinoma. The rate of distant metastasis at trial entry was 84.6%. The most common molecular alterations included PIK3CA (46.5%), PD-L1+ (46.2%), EPH (30.0%), and CREBBP (23.1%); 23.1% had received a prior checkpoint inhibitor. Phase I trials were for immunotherapy (58.5%) or targeted therapy (41.5%). The rate of biomarker matching was 21.5%. For all patients, median PFS was 3.6 months (95% CI, 2.0–5.2) and OS was 9.3 months (95% CI, 7.0–10.6). Factors at study entry associated with worse survival were presence of bone metastasis (PFS 1.6 vs 4.4 months: hazard ratio [HR], 2.8; p = 0.001; OS 3.8 vs 10.0 months: HR, 3.9; p < 0.0001) and absolute lymphocyte count below 1000/μL (PFS 1.8 vs 5.2 months: HR, 2.9; p = 0.0004; OS 7.0 vs 10.6 months: HR, 3.2; p = 0.0009). Factors associated only with worse OS were absolute neutrophil count above 4700/μL, hemoglobin below 10.5 g/dL, and smoking status. Grade 3+ treatment-related adverse events were seen in 16.9% of cases. Conclusion: Bone metastasis and absolute lymphocyte count below normal range at phase I study entry portend poor survival in patients with recurrent or metastatic cervical cancer.

Zooplankton are key components of estuarine trophic networks. However, routine monitoring is hindered by the difficulty of morphology-based identification. DNA-based methods allow us to circumvent some of these hurdles, providing precise species identifications regardless of the taxonomic expertise of the investigator or the developmental stage of the specimens. However, the process is dependent on the completeness of the reference libraries. In this study, we sought to evaluate the potential of DNA metabarcoding to assess the seasonal (summer, autumn, and early spring) and spatial dynamics of zooplankton (four locations spanning ca. 6 km) in the Lima estuary (NW Portugal). Two genetic markers were used: the cytochrome c oxidase subunit I and the V4 hypervariable region of the ribosomal 18S rRNA genes. Overall, 327 species were recovered, and both markers displayed minute overlap (7% were detected with both markers). Species richness, composition, and taxonomic distinctness were majorly influenced by the season, with a declining tendency from summer (highest number of exclusive species, n = 74) to spring. Second to season, the taxa composition was influenced by spatial variation where the most downstream site displayed the highest number of exclusive species, n = 53. A total of 16 non-indigenous species were detected using metabarcoding, but only one (Austrominus modestus) has been documented out in the estuary. In conclusion, both the seasonal and spatial gradients influenced the recovered richness, composition, and taxonomic distinctness, confirming the great aptitude of DNA metabarcoding for providing higher density monitoring and shedding new light on the composition and dynamics of complex zooplankton communities.

The purpose of this study was to understand the contribution of each performance indicator to evaluate match performance of football referees. Thirty-four elite Referee Match Observers (RMOs) from the Portuguese FA participated voluntarily in the study. From the official assessment sheet of each game, the referee's game score was categorized in two groups according to referee's game score: i) Referees with a Low Score (LFS) and ii) Referees with High Score (HFS). A multivariable binary logistic regression model was used to assess the relationship between the Performance Indicators (PIs) of the dimensions i) game difficulty and game intervention and ii) disciplinary actions and game management in relation to the referee's match assessment score. The model proposed revealed that only the PIs negative application of the laws of the game and referee teamwork, from the dimension disciplinary actions and game management, significantly defined the final game referee's assessment score. This study suggests that the PIs scored by the RMOs contributed in a different way to the referee's game score. The model explains 60.4% of the referee's game score based on the variables referee teamwork and negative application of the laws of the game.

The authors present CAMPI, a large-scale multi-lab comparison of diverse metaproteomics workflows. CAMPI provides insights into the robustness of current methods, suggests further improvements to the field, and may pave the way for future community-driven metaproteomics projects.

Abstract Background Patient interruption of antiretroviral therapy (ART) continues to limit HIV programs’ progress toward epidemic control. Multiple factors have been associated with client interruption in treatment (IIT)— including age, gender, CD4 count, and education level. In this paper, we explore the factors associated with IIT in people living with HIV (PLHIV) in United States Agency for International Development (USAID)-supported facilities under the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. Methods We conducted cross-sectional analyses on data obtained from Nigeria’s National Data Repository (NDR), representing a summarized record of 573 630 ART clients that received care at 484 PEPFAR/USAID-supported facilities in 16 states from 2000–2020. IIT was defined as no clinical contact for 28 days or more after the last expected clinical contact. Univariate and multivariate logistic regression models were computed to explore the factors associated with IIT. The variables included in the analysis were sex, age group, zone, facility level, regimen line, multi-month dispensing (MMD), and viral load category. Results Of the 573 630 clients analysed in this study, 32% have been recorded as having interrupted treatment. Of the clients investigated, 66% were female (32% had interrupted treatment), 39% were aged 25–34 at their last ART pick-up date (with 32% of them interrupted treatment), 59% received care at secondary level facilities (37% interrupted treatment) and 38% were last receiving between three- to five-month MMD (with 10% of these interrupted treatment). Those less likely to interrupt ART were males (aOR = 0.91), clients on six-month MMD (aOR = 0.01), adults on 2nd line regimen (aOR = 0.09), and paediatrics on salvage regimen (aOR = 0.02). Clients most likely to interrupt ART were located in the South West Zone (aOR = 1.99), received treatment at a tertiary level (aOR = 12.34) or secondary level facilities (aOR = 4.01), and had no viral load (VL) on record (aOR =10.02). Age group was not significantly associated with IIT. Conclusions Sex, zone, facility level, regimen line, MMD, and VL were significantly associated with IIT. MMD of three months and longer (especially six months) had better retention on ART than those on shorter MMD. Not having a VL on record was associated with a considerable risk of IIT.

This article examines the migration of reactionary antimodern thought from Europe to the United States of America. It assesses the impact that the work of two antimodern thinkers, Leo Strauss and Eric Voegelin, had on two distinct domains of American thought, namely, conservative political ideology and academic political science. The paper argues that the antimodern perspective, eagerly absorbed by many intellectuals, has pushed American conservatism not only in an anti-liberal, but also in an antidemocratic direction. On the other hand, in academic political science, Strauss's and Voegelin's critiques of modernity, though certainly audible and noted, were neither taken seriously nor confronted in depth by the mainstream of the discipline. This neglect should be corrected, I contend, for contemporary political science is in need of a mature and nuanced theory of modernity that is capable of rising up to the radical challenge of the antimoderns.

Patients with advanced prostate cancer (PCa) invariably develop resistance to anti-androgen therapy and taxane-based chemotherapy. Glucocorticoid receptor (GR) has been implicated in PCa therapy resistance; however, the mechanisms underlying GR-mediated chemoresistance remain unclear. Lens epithelium-derived growth factor p75 (LEDGF/p75, also known as PSIP1 and DFS70) is a glucocorticoid-induced transcription co-activator implicated in cancer chemoresistance. We investigated the contribution of the GR–LEDGF/p75 axis to docetaxel (DTX)-resistance in PCa cells. GR silencing in DTX-sensitive and -resistant PCa cells decreased LEDGF/p75 expression, and GR upregulation in enzalutamide-resistant cells correlated with increased LEDGF/p75 expression. ChIP-sequencing revealed GR binding sites in the LEDGF/p75 promoter. STRING protein–protein interaction analysis indicated that GR and LEDGF/p75 belong to the same transcriptional network, and immunochemical studies demonstrated their co-immunoprecipitation and co-localization in DTX-resistant cells. The GR modulators exicorilant and relacorilant increased the sensitivity of chemoresistant PCa cells to DTX-induced cell death, and this effect was more pronounced upon LEDGF/p75 silencing. RNA-sequencing of DTX-resistant cells with GR or LEDGF/p75 knockdown revealed a transcriptomic overlap targeting signaling pathways associated with cell survival and proliferation, cancer, and therapy resistance. These studies implicate the GR–LEDGF/p75 axis in PCa therapy resistance and provide a pre-clinical rationale for developing novel therapeutic strategies for advanced PCa.

Artificial substrates have been implemented to overcome the problems associated with quantitative sampling of marine epifaunal assemblages. These substrates provide artificial habitats that mimic natural habitat features, thereby standardizing the sampling effort and enabling direct comparisons among different sites and studies. This paper explores the potential of the “Artificial Seaweed Monitoring System” (ASMS) sampling methodology to evaluate the natural variability of assemblages along a coastline of more than 200 km, by describing the succession of the ASMS’ associated macrofauna at two Rías of the Galician Coast (NW Iberian Peninsula) after 3, 6, 9, and 12 months after deployment. The results show that macrofauna assemblages harbored by ASMS differ between locations for every type of data. The results also support the hypothesis that succession in benthic communities is not a linear process, but rather a mixture of different successional stages. The use of the ASMS is proved to be a successful standard monitoring methodology, as it is sensitive to scale-dependent patterns and captures the temporal variability of macrobenthic assemblages. Hence, the ASMS can serve as a replicable approach contributing to the “Good Environmental Status” assessment through non-destructive monitoring programs based on benthic marine macrofauna monitoring, capturing the variability in representative assemblages as long as sampling deployment periods are standard.

Abstract Numerous genomes are sequenced and made available to the community through the NCBI portal. However, and, unlike what happens for gene function annotation, annotation of promoter sequences and the underlying prediction of regulatory associations is mostly unavailable, severely limiting the ability to interpret genome sequences in a functional genomics perspective. Here we present an approach where one can download a genome of interest from NCBI in the GenBank Flat File (.gbff) format and, with a minimum set of commands, have all the information parsed, organized and made available through the platform web interface. Also, the new genomes are compared with a given genome of reference in search of homologous genes, shared regulatory elements and predicted transcription associations. We present this approach within the context of Community YEASTRACT of the YEASTRACT + portal, thus benefiting from immediate access to all the comparative genomics queries offered in the YEASTRACT + portal. Besides the yeast community, other communities can install the platform independently, without any constraints. In this work, we exemplify the usefulness of the presented tool, within Community YEASTRACT, in constructing a dedicated database and analysing the genome of the highly promising oleaginous red yeast species Rhodotorula toruloides currently poorly studied at the genome and transcriptome levels and with limited genome editing tools. Regulatory prediction is based on the conservation of promoter sequences and available regulatory networks. The case-study examined is focused on the Haa1 transcription factor—a key regulator of yeast resistance to acetic acid, an important inhibitor of industrial bioconversion of lignocellulosic hydrolysates. The new tool described here led to the prediction of a RtHaa1 regulon with expected impact in the optimization of R. toruloides robustness for lignocellulosic and pectin-rich residue biorefinery processes.

We examined the effect of physiological workload on gaze behaviour during defensive performance in 2 vs. 1 +goalkeeper game situations in football. Twenty-two players were assigned to either a high- or low-performing group based on a validated measure of tactical performance. A total of 12 game sequences (trials) were presented under high- and low-workload conditions. At the end of each sequence, participants were asked to indicate their perceived exertion using the Rating Scale of Mental Effort and the Borg Scale. The low- and high-workload conditions were defined when the players achieved 60 and 90% of their maximal heart rate, respectively, as per their performance in the Yo-Yo Intermittent Recovery Test. Visual search behaviours were recorded using Tobii Pro eye-movement registration glasses. Players reported higher rates of perceived exertion on the high- compared to low-workload condition. Participants in the low-performing group increased their average fixation duration and decreased the number of fixations and number of fixation locations from the low- to high-workload conditions. The low- and high-performing groups displayed different visual search strategies with regards the areas of interest fixated upon. Participants in the high-performing group focused on the SpaceFrontPlayer, followed by Ball, and AnotherOpponent. The low-performing group spent more time focusing on the SpaceFrontPlayer and SpacePlayer than Ball and AnotherOpponent. It appears that physiological workload and tactical expertise interact in constraining visual search behaviours in football players. Coaches and practitioners should consider ways to manipulate individual and task constraints while attending to the close interplay between physiological workload, visual behaviour, and tactical performance during practise.

Abstract Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.

Cytosolic ion gradients in growing pollen tubes are thought to be required for polar growth. Here the authors show that the Arabidopsis plasma membrane H+ ATPases, AHA6, AHA8, and AHA9, maintain tip-to-shank proton gradients, oscillations in cytosolic pH and actin organization to enable pollen tube elongation.

Mark Weiser coined the term Ubiquitous Computing (UbiComp) describing a future in which everyday life-objects would have embedded computers providing services anytime and anywhere. This paradigm is theme recurrent in many graduate courses of Computer Science around the world. To better understand the challenge of teaching Ubiquitous Computing (UbiComp), we surveyed 15 professors and 60 graduate and undergraduate students from 16 universities. According to this survey, the two most challenging Ubicomp concepts to explain in a lecture are context-awareness and middleware platforms. Results also showed professors’ difficulty in finding tools to assist the practical teaching of UbiComp’s concepts. Current UbiComp tools require high programming skills or they are not designed for educational purposes. Therefore, this work presents the design, development, and evaluation of LUCy (Learning Ubiquitous Computing Easily), a Virtual Learning Environment which aids UbiComp practical classes. LUCy has two main elements: a Web tool and an Android mobile app. The former provides UbiComp theory materials, videos, practices, and simulations. The latter uses smartphones features and sensors to run simulations of UbiComp concepts. We evaluated LUCy during Context-Awareness classes in UbiComp courses, at the same university, along with three distinct semesters. In different three sessions, we gathered information about LUCy’s pedagogical and usability issues. Then, we performed a quasi-experiment using a pretest and posttest design methodology with twenty-seven students. Results showed LUCy practices significantly improves students reasoning about Context-Aware concepts.

BackgroundDespite the growing number of patients with both coronary artery disease and gynecological cancer, there are no nationally representative studies of mortality and cost effectiveness for percutaneous coronary interventions (PCI) and this cancer type.MethodsBackward propagation neural network machine learning supported and propensity score adjusted multivariable regression was conducted for the above outcomes in this case-control study of the 2016 National Inpatient Sample (NIS), the United States' largest all-payer hospitalized dataset. Regression models were fully adjusted for age, race, income, geographic region, cancer metastases, mortality risk, and the likelihood of undergoing PCI (and also with length of stay [LOS] for cost). Analyses were also adjusted for the complex survey design to produce nationally representative estimates. Centers for Disease Control and Prevention (CDC)-based cost effectiveness ratio (CER) analysis was performed.ResultsOf the 30,195,722 hospitalized patients meeting criteria, 1.27% had gynecological cancer of whom 0.02% underwent PCI including 0.04% with metastases. In propensity score adjusted regression among all patients, the interaction of PCI and gynecological cancer (vs. not having PCI) significantly reduced mortality (OR 0.53, 95%CI 0.36–0.77; p = 0.001) while increasing LOS (Beta 1.16 days, 95%CI 0.57–1.75; p < 0.001) and total cost (Beta $31,035.46, 95%CI 26758.86–35312.06; p < 0.001). Among gynecological cancer patients, mortality was significantly reduced by PCI (OR 0.58, 95%CI 0.39–0.85; p = 0.006) and being in East North Central, West North Central, South Atlantic, and Mountain regions (all p < 0.03) compared to New England. PCI reduced mortality but not significantly for metastatic patients (OR 0.74, 95%CI 0.32–1.71; p = 0.481). Eighteen extra gynecological cancer patients' lives were saved with PCI for a net national cost of $3.18 billion and a CER of $176.50 million per averted death.ConclusionThis large propensity score analysis suggests that PCI may cost inefficiently reduce mortality for gynecological cancer patients, amid income and geographic disparities in outcomes.

The monospecific dense fine speckled (DFS) immunofluorescence assay (IFA) pattern is considered a potential marker to aid in exclusion of antinuclear antibody (ANA)-associated rheumatic diseases (AARD). This pattern is typically produced by autoantibodies against transcription co-activator DFS70/LEDGFp75, which are frequently found in healthy individuals and patients with miscellaneous inflammatory conditions. In AARD patients, these antibodies usually co-exist with disease-associated ANAs. Previous studies reported the occurrence of monospecific autoantibodies that generate a DFS-like or pseudo-DFS IFA pattern but do not react with DFS70/LEDGFp75. We characterized this pattern using confocal microscopy and immunoblotting. The target antigen associated with this pattern partially co-localized with DFS70/LEDGFp75 and its interacting partners H3K36me2, an active chromatin marker, and MLL, a transcription factor, in HEp-2 cells, suggesting a role in transcription. Immunoblotting did not reveal a common protein band immunoreactive with antibodies producing the pseudo-DFS pattern, suggesting they may recognize diverse proteins or conformational epitopes. Given the subjectivity of the HEp-2 IFA test, the awareness of pseudo-DFS autoantibodies reinforces recommendations for confirmatory testing when reporting patient antibodies producing a putative DFS pattern in a clinical setting. Future studies should focus on defining the potential diagnostic utility of the pseudo-DFS pattern and its associated antigen(s).

Scavenging fauna plays an integral role in ecosystem functioning, nutrient cycling and circulating organic matter. Thus, baseline data of scavenger assemblages on the NW coast of the Iberian Peninsula that provides information on the abundance of species in different habitats is crucial to understanding the distribution of this understudied group. Two different types of baited traps, to capture scavenging megafaunal and scavenging benthopelagic macrofaunal assemblages, were deployed to compare them among rocky, pebbled and sandy bottoms at shallow subtidal on the northern coast of Portugal. Results showed significant differences in the structure of scavenger assemblages. Scavenging megafaunal assemblages differed between sandy and the other two studied habitats, whereas benthopelagic macrofaunal assemblages differed between pebbles and rocky habitats. This suggests that different drivers seem to shape the structure of benthopelagic macrofauna and megafauna. Regarding megafauna, the dominance of Tritia gastropods in sand habitats in comparison with its absence in rock and its very low abundance in pebbles was mainly responsible for the differences. However, in benthopelagic macrofauna, differences in assemblages between pebbles and rock were more related to changes in the relative abundance of crustacean species (Cirolana cranchii and Socarnes erythrophthalmus) that were less abundant in pebbles.

La elevada tasa de empleo temporal en la Administración Pública española se ha convertido en un problema estructural, en un fallo activo, que impide desarrollar una correcta gestión del personal, restando capacidad de eficacia y eficiencia a la organización pública. Los servicios públicos, como pilares del Estado del bienestar, se ven negativamente afectados por la imposibilidad material de desarrollar políticas de personal adecuadas a las necesidades reales de los ciudadanos. Esta situación tiene como principal causa el continuado incumplimiento de las normas reguladoras de la temporalidad, convirtiendo en ordinario, abusivo incluso, el uso de técnicas excepcionales. Los negativos efectos de este incumplimiento se advierten a través de la observación de los colectivos afectados y, en síntesis, del evidente daño al interés general poniendo en riego el modelo constitucional de empleo público, además de restar legitimidad y fortaleza a la propia Democracia. Resolver el problema, más allá de soluciones inmediatas basadas en la consolidación de situaciones de temporalidad y el refuerzo de medidas disuasorias, pasa por una mirada a largo plazo en la que el respeto a la legalidad sea el reflejo de una obligada y elemental lealtad institucional con el Estado democrático y de Derecho.

Biodiesel can be produced from vegetable oils, animal fats, frying oils, and from microorganism-synthesized oils. These sources render biodiesel an easily biodegradable fuel. The aim of this work was to perform an advanced bibliometric analysis of primary studies relating to biodiesel production worldwide by identifying the key countries and regions that have shown a strong engagement in this area, and by understanding the dynamics of their collaboration and research outputs. Additionally, an assessment of the main primary feedstocks employed in this research was carried out, along with an analysis of the current and future trends that are expected to define new paths and methodologies to be used in the manufacture of biodegradable and renewable fuels. A total of 4586 academic outputs were selected, including peer-reviewed research articles, conference papers, and literature reviews related to biodiesel production, in the time period spanning from 2010 to 2021. Articles that focused on feedstocks for the production of biodiesel were also included, with a search that returned 330 papers. Lastly, 60 articles relating to biodiesel production via sewage were specifically included to allow for an analysis of this source as a promising feedstock in the future of the biofuel market. Via the geocoding and the document analyses performed, we concluded that China, Malaysia, and India are the largest writers of articles in this area, revealing a great interest in biofuels in Asia. Additionally, it was noted that environmental concerns have caused authors to conduct research on feedstocks that can address the sustainability challenges in the production of biodiesel.

Abstract Background Boolean models of biological signalling-regulatory networks are increasingly used to formally describe and understand complex biological processes. These models may become inconsistent as new data become available and need to be repaired. In the past, the focus has been shed on the inference of (classes of) models given an interaction network and time-series data sets. However, repair of existing models against new data is still in its infancy, where the process is still manually performed and therefore slow and prone to errors. Results In this work, we propose a method with an associated tool to suggest repairs over inconsistent Boolean models, based on a set of atomic repair operations. Answer Set Programming is used to encode the minimal repair problem as a combinatorial optimization problem. In particular, given an inconsistent model, the tool provides the minimal repairs that render the model capable of generating dynamics coherent with a (set of) time-series data set(s), considering either a synchronous or an asynchronous updating scheme. Conclusions The method was validated using known biological models from different species, as well as synthetic models obtained from randomly generated networks. We discuss the method’s limitations regarding each of the updating schemes and the considered minimization algorithm.

In cellular systems, information signals must be transmitted at high rates and with high reliability. One of the possible solutions to meet such criteria is the use of systems with multiple transmitting and/or receiving antenna arranged in the form of a multiple-input, multiple-output (MIMO) system. However, signal processing techniques in MIMO systems are developed under the assumption of transmission on Gaussian channels, which may lead to the decrease of efficiency in non-Gaussian communication scenarios. In this context, the widespread use of MIMO systems in recent years has motivated the development of new processing techniques that can be employed in scenarios that also consider the presence of non-Gaussian noise in communication channels. This work proposes a novel signal detection technique for MIMO systems, which is called maximum correntropy detector (MCD), being adequate to environments characterized by Gaussian and non-Gaussian noise. The introduced approach is based on complex correntropy function and can be seen as a generalization of the maximum likelihood detector (MLD) concept. The MCD is evaluated on Gaussian and non-Gaussian channels, where superior performance is achieved when compared with the classic detectors, without significant increase of the computational complexity.

Full-waveform inversion (FWI) is a powerful technique to obtain high-resolution subsurface models, from seismic data. However, FWI is an ill-posed problem, which means that the solution is not unique, and therefore the expert use of the information is required to mitigate the FWI ill-posedness, especially when wide-aperture seismic acquisitions are considered. In this way, we investigate the multiscale frequency-domain FWI by using a weighting operator according to the distances between each source-receiver pair. In this work, we propose a weighting operator that acts on the data misfit as preconditioning of the objective function that depends on the source-receiver distance (offset) and the frequency used during the inversion. The proposed operator emphasizes information from long offsets, especially at low frequencies, and as a consequence improves the update of deep geological structures. To demonstrate the effectiveness of our proposal, we perform numerical simulations on 2D acoustic Marmousi2 case study, which is widely used in seismic imaging tests, considering three different scenarios. In the first two ones, we have used an acquisition geometry with a maximum offset of 4 and 8 km, respectively. In the last one, we have considered all-offsets. The results show that our proposal outperforms similar strategies, for all scenarios, providing more reliable quantitative subsurface models. In fact, our inversion result has the lowest error and the highest similarity to the true model than similar approaches.

Bemisia tabaci (MEAM1) represents a species of economic importance in soybean. One of the obstacles to the management of B. tabaci is the quantification of damage by the pest because damage is indirectly inferred through losses in productivity. The objective of this study was to characterize the influence of B. tabaci feeding on soybean by assessing effects on photosynthetic parameters and the sugar and starch content of soybean leaves. The goal was to identify the optimal parameter to directly quantify pest damage on crop yield. Correlation networks were created among data on sugar content (fructose, glucose, and sucrose), starch and photosynthetic parameters (initial fluorescence, performance index on absorption basis, and turn-over number), and the number of nymphs at each of three infestations level (low, medium, and high) during both the vegetative and reproductive stage of the crop. In general, nymphs were more abundant during the vegetative stage. Starch content was strongly correlated with nymph density. A strong positive correlation was observed between fructose and nymph density during the vegetative stage. Among the photosynthetic parameters, the turn-over number N was positively correlated with nymph density at a low-infestation level and negatively correlated with nymphs when they occurred at a high-infestation level. B. tabaci feeding affected the plant’s physiology and its interaction is reflected in part by the relationships among photosynthetic parameters as well as the levels of sugars and starch. This understanding might be useful in developing better monitoring tools for pest management.

Abstract Background Health services for adolescents are increasingly recognised as a priority in low- and middle-income countries (LMICs). The Adolescent and Youth Friendly Service (AYFS) approach has been promoted in South Africa by the National Department of Health and partners, as a means of standardising the quality of adolescent health services in the country. The objective of this paper is to detail the evaluation of AYFS against defined standards to inform initiatives for strengthening these services. Methods A cross-sectional assessment of AYFS was carried out in 14 healthcare facilities in a sub-district of Gauteng Province and 16 in a sub-district in North West Province, South Africa. Data on adolescent care and service management systems were collected through interviews with healthcare providers, non-clinical staff and document review. Responses were scored using a tool based on national and World Health Organisation criteria for ten AYFS standards. Results Mean scores for the ten standards showed substantial variation across facilities in the two sub-Districts, with Gauteng Province scoring lower than the North West for 9 standards. The sub-district median for Gauteng was 38% and the North West 48%. In both provinces standards related to the general service delivery, such as Standards 4 and 5, scored above 75%. Assessment of services specifically addressing sexual, reproductive and mental health (Standard 3) showed that almost all these services were scored above 50%. Exploration of services related to psycho-social and physical assessments (Standard 8) demonstrated differences in the healthcare facilities’ management of adolescents’ presenting complaints and their comprehensive management including psycho-social status and risk profile. Additionally, none of the facilities in either sub-district was able to meet the minimum criteria for the five standards required for AYFS recognition. Conclusion Facilities had the essential components for general service delivery in place, but adolescent-specific service provision was lacking. AYFS is a government priority, but additional support for facilities is needed to achieve the agreed standards. Meeting these standards could make a major contribution to securing adolescents’ health, especially in preventing unintended pregnancies and HIV as well as improving psycho-social management.

Abstract Background HIV treatment and care for migrants is affected by their mobility and interaction with HIV treatment programs and health care systems in different countries. To assess healthcare needs, preferences and accessibility barriers of HIV-infected migrant populations in high HIV burden, borderland districts of Lesotho. Methods We selected 15 health facilities accessed by high patient volumes in three districts of Maseru, Leribe and Mafeteng. We used a mixed methods approach by administering a survey questionnaire to consenting HIV infected individuals on anti-retroviral therapy (ART) and utilizing a purposive sampling procedure to recruit health care providers for qualitative in-depth interviews across facilities. Results Out of 524 HIV-infected migrants enrolled in the study, 315 (60.1%) were from urban and 209 (39.9%) from rural sites. Of these, 344 (65.6%) were women, 375 (71.6%) were aged between 26 and 45 years and 240 (45.8%) were domestic workers. A total of 486 (92.7%) preferred to collect their medications primarily in Lesotho compared to South Africa. From 506 who responded to the question on preferred dispensing intervals, 63.1% (n = 319) preferred 5–6 month ARV refills, 30.2% (n = 153) chose 3–4 month refills and only 6.7% (n = 34) opted for the standard-of-care 1–2 month refills. A total of 126 (24.4%) defaulted on their treatment and the primary reason for defaulting was failure to get to Lesotho to collect medication (59.5%, 75/126). Treatment default rates were higher in urban than rural areas (28.3% versus 18.4%, p = 0.011). Service providers indicated a lack of transfer letters as the major drawback in facilitating care and treatment for migrants, followed by discrimination based on nationality or language. Service providers indicated that most patients preferred all treatment services to be rendered in Lesotho, as they perceive the treatment provided in South Africa to be different often less strong or with more serious side effects. Conclusion Existing healthcare systems in both South Africa and Lesotho experience challenges in providing proper care and treatment for HIV infected migrants. A need for a differentiated model of ART delivery to HIV infected migrants that allows for multi-month scripting and dispensing is warranted.

Abstract Background To report associations between different adiposity indices [anthropometric and dual-energy X-ray absorptiometry (DXA) measures] and blood pressure (BP) and hypertension in urban black South African adults. Methods Anthropometric and DXA whole body measures were performed on 1026 men and 982 women. Participants were classified as being hypertensive if they had a systolic BP (SBP) ≥ 140 mmHg and/or diastolic (DBP) ≥ 90 mmHg. Within each gender the relationship of adiposity with BP and hypertension risk was assessed using linear and logistic regression models respectively. Bivariate models were computed for each body composition variable. Furthermore, we computed a multiple regression model to illustrates how body composition parameters are associated with the outcome variables independent of each other. Results The males were significantly taller and had a higher fat free soft tissue mass (FFSTM), DBP and socio-economic status, and were more likely to use tobacco and be hypertensive (48.0% vs. 38.8%). The females had higher body mass index (BMI), waist circumference (WC), fat mass (FM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), FM/FFSTM ratio and body fat % than males. All body composition parameters were positively associated with hypertension. In both males and females, the FM/FFSTM ratio associated the strongest with hypertension illustrating the following odds ratios [males: 70.37 (18.47, 268.16) p ≤ 0.001; females 2.48 (0.86,7.21) p = 0.09]. The multiple regression model, indicated that the VAT and WC significantly associated with both SBP and DBP in the men and women respectively, whilst WC was the only significant predictor for hypertension. Conclusions All body composition parameters were associated with hypertension and FM/FFSTM ratio showed the strongest relationship. It was reassuring that WC remains a useful measure of central adiposity that can be used as a risk indicator for hypertension if more sophisticated measures are not available. Furthermore, our data in part, implies that reducing abdominal adiposity in aging adults could contribute to reducing the risk of elevated blood pressure and hypertension.

Patients with prostate cancer (PCa) receiving docetaxel chemotherapy invariably develop chemoresistance. The transcription co-activator lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 and PSIP1, is upregulated in several human cancers, including PCa and promotes resistance to docetaxel and other drugs. The C-terminal region of LEDGF/p75 contains an integrase binding domain (IBD) that tethers nuclear proteins, including the HIV-1 integrase and transcription factors, to active chromatin to promote viral integration and transcription of cellular survival genes. Here, we investigated the contribution of the LEDGF/p75 IBD interactome to PCa chemoresistance. Quantitative immunoblotting revealed that LEDGF/p75 and its IBD-interacting partners are endogenously upregulated in docetaxel-resistant PCa cell lines compared to docetaxel-sensitive parental cells. Using specific human autoantibodies, we co-immunoprecipitated LEDGF/p75 with its endogenous IBD-interacting partners JPO2, menin, MLL, IWS1, ASK1, and PogZ, as well as transcription factors c-MYC and HRP2, in docetaxel-resistant cells, and confirmed their nuclear co-localization by confocal microscopy. Depletion of LEDGF/p75 and selected interacting partners robustly decreased the survival, clonogenicity, and tumorsphere formation capacity of docetaxel-resistant cells. These results implicate the LEDGF/p75 IBD interactome in PCa chemoresistance and could lead to novel therapeutic strategies targeting this protein complex for the treatment of docetaxel-resistant tumors.

Abstract Background Persistent high-risk human papillomavirus (HR-HPV) infection is associated with the development of anogenital cancers, particularly in men living with HIV (MLWH). We describe the prevalence of anogenital HPV infection, abnormal anal cytology and anogenital warts (AGWs) in MLWH in Johannesburg, and explore whether HPV infection and receipt of antiretroviral treatment is associated with detection of abnormal anal cytology and AGWs. Methods We enrolled a cohort of 304 sexually-active MLWH ≥18 years, who completed a questionnaire and physical examination. Genital swabs were collected from all men and intra-anal swabs from 250 (82%). Swabs were tested for HPV DNA and genotypes, and anal smears graded using the Bethesda classification. Factors associated with anogenital disease were assessed by logistic regression models. Results Two thirds were receiving antiretroviral treatment, for a median 33 months (IQR = 15–58) and 54% were HIV-virologically suppressed. Only 5% reported ever having sex with men. Among 283 genital swabs with valid results, 79% had any HPV, 52% had HR-HPV and 27% had >1 HR-HPV infection. By comparison, 39% of the 227 valid intra-anal swabs had detectable HPV, 25% had any HR-HPV and 7% >1 HR infection. While most anal smears were normal (51%), 20% had ASCUS and 29% were LSIL. No cases had HSIL or cancer. Infection with >1 HR type (adjusted OR [aOR] = 2.39; 95%CI = 1.02–5.58) and alpha-9 types (aOR = 3.98; 95%CI = 1.42–11.16) were associated with having abnormal cytology. Prevalence of AGWs was 12%. Infection with any LR type (aOR = 41.28; 95%CI = 13.57–125.62), >1 LR type (aOR = 4.14; 95%CI = 1.60–10.69), being

Abstract Background Polyvictimisation (PV) – exposure to violence across multiple contexts – causes considerable morbidity and mortality among adolescents. Despite high levels of violence in urban disadvantaged settings, gender differences in associations between PV and mental health have not been well established. Methods We analysed data from a survey with 2393 adolescents aged 15-19 years, recruited using respondent-driven sampling from urban disadvantaged settings in Baltimore (USA), Delhi (India), Ibadan (Nigeria), Johannesburg (South Africa) and Shanghai (China). PV was defined as exposure to two or more types of violence in the past 12 months with family, peers, in the community, or from intimate partners and non-partner sexual violence. Weighted logistic regression models are presented by gender to evaluate whether PV is associated with posttraumatic stress, depression, suicidal thoughts and perceived health status. Results PV was extremely common overall, but ranged widely, from 74.5% of boys and 82.0% of girls in Johannesburg, to 25.8 and 23.9% respectively in Shanghai. Community violence was the predominant violence type, affecting 72.8–93.7% across the sites. More than half of girls (53.7%) and 45.9% of boys had at least one adverse mental health outcome. Compared to those that did not report violence, boys exposed to PV had 11.4 higher odds of having a negative perception of health (95%CI adjusted OR = 2.45-53.2), whilst this figure was 2.58 times in girls (95%CI = 1.62-4.12). Among girls, PV was associated with suicidal thoughts (adjusted OR = 4.68; 95%CI = 2.29-9.54), posttraumatic stress (aOR = 4.53; 95%CI = 2.44-8.41) and depression (aOR = 2.65; 95%CI = 1.25-5.63). Among boys, an association was only detected between PV and depression (aOR = 1.82; 95%CI = 1.00-3.33). Conclusion The findings demonstrate that PV is common among both sexes in urban disadvantaged settings across the world, and that it is associated with poor mental health outcomes in girls, and with poor health status in both girls and boys. Clearly, prevention interventions are failing to address violence exposure across multiple contexts, but especially within community settings and in Johannesburg. Interventions are needed to identify adolescents exposed to PV and link them to care, with services targeting a range of mental health conditions among girls and perhaps focusing on depression among boys.

Cellular responses are governed by regulatory networks subject to external signals from surrounding cells and to other micro-environmental cues. The logical (Boolean or multi-valued) framework proved well suited to study such processes at the cellular level, by specifying qualitative models of involved signalling pathways and gene regulatory networks. Here, we describe and illustrate the main features of EpiLog, a computational tool that implements an extension of the logical framework to the tissue level. EpiLog defines a collection of hexagonal cells over a 2D grid, which embodies a mono-layer epithelium. Basically, it defines a cellular automaton in which cell behaviours are driven by associated logical models subject to external signals. EpiLog is freely available on the web at http://epilog-tool.org. It is implemented in Java (version ≥1.7 required) and the source code is provided at https://github.com/epilog-tool/epilog under a GNU General Public License v3.0.

BackgroundSeveral lines of evidence indicate that medical schools have been failing to adequately nurture empathy and the ethical dimension in their graduates, the lack of which may play a central role in the genesis of medical errors, itself a major source of avoidable deaths, incapacity and wasted resources. It has been widely proposed that medical schools should adopt evaluation strategies as a means to promote a culture of respectful relationships. However, it is not clear if evaluation strategies in medical schools have addressed key domains related to that aim, such as ethics, through the perspective of their students. Hence, we conducted a national survey of instruments used by Brazilian medical schools to assess clerkship rotations from the perspective of students, with a main focus on the ethical domain.MethodsThe authors invited 121 randomly selected institutions to participate in the study. Key informants answered a questionnaire about clerkship rotations and sent copies of any instrument used to assess the quality of clerkship rotations according to the students' perspectives.ResultsTwenty-six (53%) of 49 participating schools used an instrument to assess the quality of clerkship rotations according to the perspective of students. Just 13 (27%) schools had instruments containing at least one question encompassing the ethical domain. Only 2 (4%) schools asked students specifically about the occurrence of any negative experience concerning the ethical domain during rotations. Merely 1 (2%) school asked students about having witnessed patient mistreatment and none asked about mistreatment against students themselves.ConclusionsThere are several missed opportunities in the way medical schools assess the quality of clerkship rotations regarding the ethical domain. Closing the gap between usual institutional discourses regarding ethics and how that dimension is assessed within clerkship rotations might represent an important step towards the improvement of medical education and healthcare systems.

ObjectiveTo estimate the prevalence, incidence and persistence of anal HPV infection and squamous intra-epithelial lesions (SILs) among men living with HIV (MLHIV), and determine their risk factors.MethodsWe enrolled MLHIV ≥18 years, who attended 6-monthly visits for 18 months. Socio-behavioural data were collected by questionnaire. Clinicians collected blood sample (CD4+ count and HIV plasma viral load), anal swabs (HPV DNA testing) and anal smears (Bethesda classification) at each visit. HPV DNA testing and classification of smears were done at enrolment and last follow-up visit (two time points). Factors associated with persistent anal HPV infection and SILs were evaluated with generalized estimating equations logistic regression and standard logistic regression respectively.ResultsMean age of 304 participants was 38 (Standard Deviation, 8) years; 25% reported >1 sexual partner in the past 3 months. Only 5% reported ever having sex with other men. Most (65%) participants were taking antiretroviral treatment (ART), with a median CD4+ count of 445 cells/μL (IQR, 328-567). Prevalence of any-HPV infection at enrolment was 39% (88/227). In total, 226 men had anal HPV DNA results at both enrolment and final visits. Persistence of any-anal HPV infection among 80 men who had infection at enrolment was 26% (21/80). Any persistent anal HPV infection was more frequent among MLHIV with low CD4+ count (500 cells/μL; aOR = 6.58; 95%CI: 2.41-17.94). Prevalence of anal SILs at enrolment was 49% (118/242) while incidence of SILs among MLHIV who had no anal dysplasia at enrolment was 27% (34/124). Of the 118 men who had anal dysplasia at enrolment, 15% had regressed and 38% persisted by month 18. Persistent anal HPV infection was associated with persistent SILs (aOR = 2.95; 95%CI: 1.08-10.89). ART status or duration at enrolment were not associated with persistent anal HPV infection or persistent SILs during follow-up.ConclusionIn spite of a high prevalence of anal HPV, HIV-positive heterosexual men have a low burden of anal HPV related disease. HPV vaccine and effective ART with immunological reconstitution could reduce this burden of infection.

Microtubules are important drug targets in tumor cells, owing to their role in supporting and determining the cell shape, organelle movement and cell division. The complementarity-determining regions (CDRs) of immunoglobulins have been reported to be a source of anti-tumor peptide sequences, independently of the original antibody specificity for a given antigen. We found that, the anti-Lewis B mAb light-chain CDR1 synthetic peptide Rb44, interacted with microtubules and induced depolymerization, with subsequent degradation of actin filaments, leading to depolarization of mitochondrial membrane-potential, increase of ROS, cell cycle arrest at G2/M, cleavage of caspase-9, caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-2, altogether resulting in intrinsic apoptosis of melanoma cells. The in vitro inhibition of angiogenesis was also an Rb44 effect. Peritumoral injection of Rb44L1 delayed growth of subcutaneously grafted melanoma cells in a syngeneic mouse model. L1-CDRs from immunoglobulins and their interactions with tubulin-dimers were explored to interpret effects on microtubule stability. The opening motion of tubulin monomers allowed for efficient L1-CDR docking, impairment of dimer formation and microtubule dissociation. We conclude that Rb44 VL-CDR1 is a novel peptide that acts on melanoma microtubule network causing cell apoptosis in vitro and melanoma growth inhibition in vivo.

This paper discusses the problem of room usage optimization for university timetables: given a timetable, we want to optimize the room occupation by determining the events allocated to each room, while ensuring that the rooms have enough capacity to “seat” all people participating in those events. This paper contributes with two approaches to the problem of optimizing the timetable scheduled for each room. The first approach consists of a two-stage Integer Linear Programming (ILP) which applies a lexicographic optimization wherein the goal of the first stage is to maximize the number of students seated and that of the second stage is to optimize the room occupation. This is provably optimal, in both optimization criteria. However, it is computationally demanding, requiring significant computation time for large problems. To address this issue, we propose a second approach, consisting of a greedy algorithm. The algorithm assigns lectures to rooms greedily, according to a specific cost function that seeks to maximize the number of students seated. We show that the proposed cost function guarantees that the greedy algorithm performs within 63% of the total number of students. We apply both algorithms in a case study involving real data from Instituto Superior Técnico (IST), the engineering school from Universidade de Lisboa. Our results confirm that the greedy algorithm is two orders of magnitude faster than ILP when considering large data sets. Comparing the performance of the two methods we observe that the performance of the greedy algorithm, when compared to the ILP-based approach, is within 2% for the number of seated students and 34% for the room occupation. The GRASP algorithm is a good extension of the greedy algorithm, which is able to improve in 12% the quality of the solution (in terms of compactness) without adding significant CPU time. Overall, the two proposed approaches provide significant gains for both optimization criteria when compared to the current hand-made solutions. Keywords: University timetabling, Room usage optimization, Integer linear programming, Greedy algorithms

Although monitoring insect pest populations in the fields is essential in crop management, it is still a laborious and sometimes ineffective process. Imprecise decision-making in an integrated pest management program may lead to ineffective control in infested areas or the excessive use of insecticides. In addition, high infestation levels may diminish the photosynthetic activity of soybean, reducing their development and yield. Therefore, we proposed that levels of infested soybean areas could be identified and classified in a field using hyperspectral proximal sensing. Thus, the goals of this study were to investigate and discriminate the reflectance characteristics of soybean non-infested and infested with Bemisia tabaci using hyperspectral sensing data. Therefore, cages were placed over soybean plants in a commercial field and artificial whitefly infestations were created. Later, samples of infested and non-infested soybean leaves were collected and transported to the laboratory to obtain the hyperspectral curves. The results allowed us to discriminate the different levels of infestation and to separate healthy from whitefly infested soybean leaves based on their reflectance. In conclusion, these results show that hyperspectral sensing can potentially be used to monitor whitefly populations in soybean fields.

Abstract Background The prevalence of overweight and obesity is on the rise in South Africa, particularly among females living in urban environments. The purpose of this qualitative study was to explore the emic perspectives of black young adult daughter and mother pairs living in Soweto, South Africa on diet, physical activity, and obesity-related health within their social and cultural context. Methods Purposeful sampling was used to recruit daughters with a normal body mass index (BMI) who have obese mothers. Individual semi-structured in-depth interviews were conducted with 17 daughters (age 24 years) and 15 of their mothers in Soweto, South Africa. Interview questions related to: a) eating and physical activity behaviors and perceptions, b) perceptions of social and community level factors, c) cultural beliefs about diet and body image, and d) intergenerational relationships. Data were analyzed using four-phases of thematic analysis and the constant comparison approach. Results Daughters and mothers had similar ideas of the definition of healthy food and the importance of eating healthy, but mothers were more likely to report eating healthy because of their age, adverse health experiences, and a desire to live longer. Daughters and mothers engaged in physical activity for reasons related to weight maintenance and feeling better, but mothers reported being more likely to start exercising as a result of a health concern. Daughters and mothers had comparable views of what makes a person healthy. Daughters and mothers relied on each other for food purchasing and food preparation. Conclusion Daughters and mothers shared some similar perceptions of diet, physical activity, and health that were rooted in their daily life in Soweto. However, mothers generally reported being more likely to exhibit healthy eating and physical activity behaviors despite being obese. The mothers may have adopted these perceptions and behaviors later in life linked to ageing and ill-health. It is possible that through exposure, their daughters have assimilated these perceptions earlier in childhood or adolescence. It is important to focus health promotion efforts around preventing the otherwise expected increase of obesity among the young adult generation.

O objetivo deste estudo foi analisar o efeito de fatores de ordem biológica, sociocultural e motora na prestação da habilidade motora fundamental lançamento, em crianças de 10 e 11 anos de idade. Tratou-se de um estudo transversal envolvendo 96 crianças, 49 rapazes e 47 raparigas (idade decimal, 10.94 ± 0.52). Foi avaliado o produto (distância) e processo (padrão motor) do lançamento. A comparação entre grupos no que respeita à distância do lançamento foi realizada com o t-teste enquanto no que se refere ao padrão de lançamento envolveu os testes de U Mann-Whitney e Kruskal-Wallis Recorreu-se à correlação de Pearson para analisar as associações entre as variáveis experimentais. A análise do efeito dos fatores na prestação da habilidade de lançamento envolveu o Modelo Geral Linear. As crianças situadas no estádio maduro de todos os componentes do lançamento tiveram o melhor desempenho (p

The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)

Logical models are well-suited to capture salient dynamical properties of regulatory networks. For networks controlling cell fate decisions, cell fates are associated with model attractors (stable states or cyclic attractors) whose identification and reachability properties are particularly relevant. While synchronous updates assume unlikely instantaneous or identical rates associated with component changes, the consideration of asynchronous updates is more realistic but, for large models, may hinder the analysis of the resulting non-deterministic concurrent dynamics. This complexity hampers the study of asymptotical behaviors, and most existing approaches suffer from efficiency bottlenecks, being generally unable to handle cyclical attractors and quantify attractor reachability. Here, we propose two algorithms providing probability estimates of attractor reachability in asynchronous dynamics. The first algorithm, named Firefront, exhaustively explores the state space from an initial state, and provides quasi-exact evaluations of the reachability probabilities of model attractors. The algorithm progresses in breadth, propagating the probabilities of each encountered state to its successors. Second, Avatar is an adapted Monte Carlo approach, better suited for models with large and intertwined transient and terminal cycles. Avatar iteratively explores the state space by randomly selecting trajectories and by using these random walks to estimate the likelihood of reaching an attractor. Unlike Monte Carlo simulations, Avatar is equipped to avoid getting trapped in transient cycles and to identify cyclic attractors. Firefront and Avatar are validated and compared to related methods, using as test cases logical models of synthetic and biological networks. Both algorithms are implemented as new functionalities of GINsim 3.0, a well-established software tool for logical modeling, providing executable GUI, Java API, and scripting facilities.

Cellular responses are governed by regulatory networks subject to external signals from surrounding cells and to other micro-environmental cues. The logical (Boolean or multi-valued) framework proved well suited to study such processes at the cellular level, by specifying qualitative models of involved signalling pathways and gene regulatory networks. Here, we describe and illustrate the main features of EpiLog, a computational tool that implements an extension of the logical framework to the tissue level. EpiLog defines a collection of hexagonal cells over a 2D grid, which embodies a mono-layer epithelium. Basically, it defines a cellular automaton in which cell behaviours are driven by associated logical models subject to external signals. EpiLog is freely available on the web at http://epilog-tool.org. It is implemented in Java (version ≥1.7 required) and the source code is provided at https://github.com/epilog-tool/epilog under a GNU General Public License v3.0.