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Abstract Background Multiple clinician adjustable parameters impact upon glycemia in people with type 1 diabetes (T1D) using Medtronic Mini Med 780G (MM780G) AHCL. These include glucose targets, carbohydrate ratios (CR), and active insulin time (AIT). Algorithm-based decision support advising upon potential settings adjustments may enhance clinical decision-making. Methods Single-arm, two-phase exploratory study developing decision support to commence and sustain AHCL. Participants commenced investigational MM780G, then 8 weeks Phase 1-initial optimization tool evaluation, involving algorithm-based decision support with weekly AIT and CR recommendations. Clinicians approved or rejected CR and AIT recommendations based on perceived safety per protocol. Co-design resulted in a refined algorithm evaluated in a further identically configured Phase 2. Phase 2 participants also transitioned to commercial MM780G following “Quick Start” (algorithm-derived tool determining initial AHCL settings using daily insulin dose and weight). We assessed efficacy, safety, and acceptability of decision support using glycemic metrics, and the proportion of accepted CR and AIT settings per phase. Results Fifty three participants commenced Phase 1 (mean age 24.4; Hba1c 61.5mmol/7.7%). The proportion of CR and AIT accepted by clinicians increased between Phases 1 and 2 respectively: CR 89.2% vs. 98.6%, p

Abstract As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.

Abstract Background Use of Continuous Subcutaneous Insulin Infusion (CSII) has been shown to improve glycemic outcomes in Type 1 Diabetes (T1D), but high costs limit accessibility. To address this issue, an inter-operable, open-source Ultra-Low-Cost Insulin Pump (ULCIP) was developed and previously shown to demonstrate comparable delivery accuracy to commercial models in standardised laboratory tests. This study aims to evaluate the updated ULCIP in-vivo, assessing its viability as an affordable alternative for those who cannot afford commercially available devices. Methods This first-in-human feasibility study recruited six participants with T1D. During a nine-hour inpatient stay, participants used the ULCIP under clinical supervision. Venous glucose, insulin, and β-Hydroxybutyrate were monitored to assess device performance. Results Participants displayed expected blood glucose and blood insulin levels in response to programmed basal and bolus insulin dosing. One participant developed mild ketosis, which was treated and did not recur when a new pump reservoir was placed. All other participants maintained β-Hydroxybutyrate

Noncommunicable Chronic Diseases (NCD) are a socioeconomic burden and considered one of the major health challenges for coming decades. Mitochondrial dysfunction has been implicated mechanistically in their pathophysiology. Therefore, targeting mitochondria holds great promise to improve clinical outcomes in NCDs. SUL-138, an orally bioavailable small molecule efficacious from 0.5 mg/kg, improves mitochondrial function during disease in several preclinical animal models. As preparation for a First-in-Human (FIH) trial, SUL-138 was investigated in 30-day GLP repeated dose toxicity studies in rat and minipig, selected based on their comparability with human metabolism, to determine toxicokinetics, potential toxicity and its reversibility. Rats were allocated to either vehicle, 27, 136 or 682 mg/kg SUL-138 dose groups and minipigs were allocated to either vehicle, 16, 82 or 409 mg/kg. Treatment occurred orally for 30 days followed by a recovery period of 14 days. During these studies clinical observations, toxicokinetic, clinical pathology, necropsy and histopathology evaluations were performed. There was significant systemic exposure to SUL-138 and toxicokinetics was characterized by a rapid absorption and elimination. In the rat, toxicokinetics was dose-proportional and AUC0-tlast ratios in both species indicated that SUL-138 does not accumulate in vivo. No treatment-related adverse effects were observed for dose levels up to 136 and 82 mg/kg/day in rat and minipig respectively. In conclusion, these preclinical studies demonstrate that SUL-138 is well tolerated after repeated administration in rat and minipig, with NOAELs of 136 and 82 mg/kg/day, respectively.

Bemisia tabaci (whitefly) is a polyphagous agroeconomic pest species complex. Two members of this species complex, Mediterranean (MED) and Middle-East-Asia Minor 1 (MEAM1), have a worldwide distribution and have been shown to manipulate plant defenses through effectors. In this study, we used three different strategies to identify three MEAM1 proteins that can act as effectors. Effector B1 was identified using a bioinformatics-driven effector-mining strategy, whereas effectors S1 and P1 were identified in the saliva of whiteflies collected from artificial diet and in phloem exudate of tomato on which nymphs were feeding, respectively. These three effectors were B. tabaci specific and able to increase whitefly fecundity when transiently expressed in tobacco plants (Nicotiana tabacum). Moreover, they reduced growth of Pseudomonas syringae pv. tabaci in Nicotiana benthamiana. All three effectors changed gene expression in planta, and B1 and S1 also changed phytohormone levels. Gene ontology and KEGG pathway enrichment analysis pinpointed plant–pathogen interaction and photosynthesis as the main enriched pathways for all three effectors. Our data thus show the discovery and validation of three new B. tabaci MEAM1 effectors that increase whitefly fecundity and modulate plant immunity. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Introduction Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications.Methods and analysis The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age

To improve current data systems for institutional decision-making, the Adult Liver Transplant Registry was established at the Hospital Italiano de Buenos Aires, Argentina. This article describes its design and implementation and reports on the outcomes for patients transplanted since its January 2020 launch. A multidisciplinary team designed the registry by identifying key variables from a literature review while considering balance between data depth and feasibility. Rigorous quality control measures were enforced, including monthly audits and staff training. Benchmark indicators for post-transplant outcomes were established. As of November 2023, the registry included 136 transplants. Its implementation and maintenance were straightforward, with no significant difficulties encountered. Cirrhosis was the predominant indication (77%) for transplant. Only one living donor transplantation was performed. Post-transplant results generally aligned with benchmarks, but rates of biliary complications slightly exceeded the recommended thresholds. The one-year post-transplant survival rate was 87%. The successful registry implementation provides a robust framework for research, treatment management, and patient care enhancement within a liver transplant unit.

Estimating the economic risks of climate shocks and climate stressors on spatially heterogeneous cities over time remains highly challenging. The purpose of this paper is to present a practical methodology to assess the economic risks of climate change in middle-income cities to inform municipal climate response strategies. Building on a capital-based framework (CBF), spatially disaggregated baseline and future scenario scores for economic wealth and its exposure to climate change are developed for six different classes of capital across 77 major suburbs in Cape Town, South Africa. Capital-at-risk was calculated by combining relative exposure and capital scores across different scenarios, with population impacted for major suburbs and the city’s eight main planning districts. The economic risk assessment presented here provides a generic approach to assist city managers through an enhanced understanding of the relative levels of capital endowment across the city vis-à-vis relative levels of exposure to climate-related hazards over time.

Background & Aims: Malnutrition, sarcopenia, and frailty are prevalent in cirrhosis. We aimed to assess the correlation between assessment tools for malnutrition, sarcopenia, and frailty in patients on the liver transplant (LT) waiting list (WL), and to identify a predictive model for acute-on-chronic liver failure (ACLF) development. Methods: This prospective single-center study enrolled consecutive patients with cirrhosis on the WL for LT (May 2019-November 2021). Assessments included subjective global assessment, CT body composition, skeletal muscle index (SMI), ultrasound thigh muscle thickness, sarcopenia HIBA score, liver frailty index (LFI), hand grip strength, and 6-minute walk test at enrollment. Correlations were analyzed using Pearson's correlation. Competing risk regression analysis was used to assess the predictive ability of the liver- and functional physiological reserve-related variables for ACLF. Results: A total of 132 patients, predominantly with decompensated cirrhosis (87%), were included. Our study revealed a high prevalence of malnutrition (61%), sarcopenia (61%), visceral obesity (20%), sarcopenic visceral obesity (17%), and frailty (10%) among participants. Correlations between the assessment tools for sarcopenia and frailty were poor. Sarcopenia by SMI remained prevalent when frailty assessments were not usable. After a median follow-up of 10 months, 39% of the patients developed ACLF on WL, while 28% experienced dropouts without ACLF. Multivariate analysis identified MELD-Na, SMI, and LFI as independent predictors of ACLF on the WL. The predictive model MELD-Na-sarcopenia-LFI had a C-statistic of 0.85. Conclusions: The poor correlation between sarcopenia assessment tools and frailty underscores the importance of a comprehensive evaluation. The SMI, LFI, and MELD-Na independently predicted ACLF development in WL. These findings enhance our understanding of the relationship between sarcopenia, frailty, and ACLF in patients awaiting LT, emphasizing the need for early detection and intervention to improve WL outcomes. Impact and implications: The relationship between sarcopenia and frailty assessment tools, as well as their ability to predict acute-on-chronic liver failure (ACLF) in patients on the liver transplant (LT) waiting list (WL), remains poorly understood. Existing objective frailty screening tests have limitations when applied to critically ill patients. The correlation between sarcopenia and frailty assessment tools was weak, suggesting that they may capture different phenotypes. Sarcopenia assessed by skeletal muscle index, frailty evaluated using the liver frailty index, and the model for end-stage liver disease-Na score independently predicted the development of ACLF in patients on the WL. Our findings support the integration of liver frailty index and skeletal muscle index assessments at the time of inclusion on the WL for LT. This combined approach allows for the identification of a specific patient subgroup with an increased susceptibility to ACLF, underscoring the importance of early implementation of targeted treatment strategies to improve outcomes for patients awaiting LT.

Abstract Background Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO. Methods This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018–Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100–150·109/L), moderate (50–100·109/L) and severe (

Introduction Multiple automated insulin delivery (AID) systems have become commercially available following randomised controlled trials demonstrating benefits in people with type 1 diabetes (T1D). However, their real-world utility may be undermined by user-associated burdens, including the need to carbohydrate count and deliver manual insulin boluses. There is an important need for a ‘fully automated closed loop’ (FCL) AID system, without manual mealtime boluses. The (Closed Loop Open SourcE In Type 1 diabetes) trial is a randomised trial comparing an FCL AID system to the same system used as a hybrid closed loop (HCL) in people with T1D, in an outpatient setting over an extended time frame.Methods and analysis Randomised, open-label, parallel, non-inferiority trial comparing the Android Artificial Pancreas System (AAPS) AID algorithm used as FCL to the same algorithm used as HCL. Seventy-five participants aged 18–70 will be randomised (1:1) to one of two treatment arms for 12 weeks: (a) FCL—participants will be advised not to bolus for meals and (b) HCL—participants will use the AAPS AID algorithm as HCL with announced meals. The primary outcome is the percentage of time in target sensor glucose range (3.9–10.0 mmol/L). Secondary outcomes include other glycaemic metrics, safety, psychosocial factors, platform performance and user dietary factors. Twenty FCL arm participants will participate in a 4-week extension phase comparing glycaemic and dietary outcomes using NovoRapid (insulin aspart) to Fiasp (insulin aspart and niacinamide).Ethics and dissemination Approvals are by the Alfred Health Ethics Committee (615/22) (Australia) and Health and Disability Ethics Committees (2022 FULL 13832) (New Zealand). Each participant will provide written informed consent. Data protection and confidentiality will be ensured. Study results will be disseminated by publications, conferences and patient advocacy groups.Trial registration numbers ACTRN12622001400752 and ACTRN12622001401741.

The initial peopling of South America is a topic of intense archaeological debate. Among the most contentious issues remain the nature of the human-megafauna interaction and the possible role of humans, along with climatic change, in the extinction of several megamammal genera at the end of the Pleistocene. In this study, we present the analysis of fossil remains with cutmarks belonging to a specimen of Neosclerocalyptus (Xenarthra, Glyptodontidae), found on the banks of the Reconquista River, northeast of the Pampean region (Argentina), whose AMS 14C dating corresponds to the Last Glacial Maximum (21,090-20,811 cal YBP). Paleoenvironmental reconstructions, stratigraphic descriptions, absolute chronological dating of bone materials, and deposits suggest a relatively rapid burial event of the bone assemblage in a semi-dry climate during a wet season. Quantitative and qualitative analyses of the cut marks, reconstruction of butchering sequences, and assessments of the possible agents involved in the observed bone surface modifications indicate anthropic activities. Our results provide new elements for discussing the earliest peopling of southern South America and specifically for the interaction between humans and local megafauna in the Pampean region during the Last Glacial Maximum.

Repurposing is one of the key opportunities to address the unmet rare diseases therapeutic need. Based on cases of drug repurposing in small population conditions, and previous work in drug repurposing, we analyzed the most important lessons learned, such as the sharing of clinical observations, reaching out to regulatory scientific advice at an early stage, and public-private collaboration. In addition, current upcoming trends in the field of drug repurposing in rare diseases were analyzed, including the role these trends could play in the rare diseases’ ecosystem. Specifically, we cover the opportunities of innovation platforms, the use of real-world data, the use of artificial intelligence, regulatory initiatives in repurposing, and patient engagement throughout the repurposing project. The outcomes from these emerging activities will help progress the field of drug repurposing for the benefit of patients, public health and medicines development.

There is broad agreement that one important aspect of responsible innovation (RI) is to provide training on its principles and practices to current and future researchers and innovators, notably including doctoral students. Much less agreement can be observed concerning the question of what this training should consist of, how it should be delivered and how it could be assessed. The increasing institutional embedding of RI leads to calls for the alignment of RI training with training in other subjects. One can therefore observe a push towards the official assessment of RI training, for example in the recent call for proposals for centres for doctoral training by UK Research and Innovation. This editorial article takes its point of departure from the recognition that the RI community will need to react to the call for assessment of RI training. It provides an overview of the background and open questions around RI training and assessment as a background of examples of RI training assessment at doctoral level. There is unlikely to be one right way of assessing RI training across institutions and disciplines, but we expect that the examples provided in this article can help RI scholars and practitioners orient their training and its assessment in ways that are academically viable as well as supportive of the overall aims of RI.

While advancements in the treatment of diabetes continue to rapidly evolve, many of the newer technologies have financial barriers to care, opposing the egalitarian ethos of Banting who sold his patent on insulin for a nominal cost to allow it to be made widely available. Inequity in access to new therapies drives disparity in diabetes burden with potential for these gaps to widen in the future. The 2023 International Conference on Advanced Technologies and Treatments of Diabetes (ATTD) presented ground-breaking and current research in diabetes technology. Oral presentations of the ATTD conference 2023 were analyzed to describe what percentage of speakers discussed equity in their talks. Overall, less than a quarter of presenters discussed equity, though there was regional variation. To ensure that diabetes technologies reduce disparity and improve outcomes, we encourage future speakers at diabetes (technology) conferences to consider equity of diabetes care and incorporate this into their presentations.

Introduction Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO.Methods and analysis The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged

OBJECTIVES:. To achieve optimal hemostatic balance in patients on extracorporeal membrane oxygenation (ECMO), a liberal transfusion practice is currently applied despite clear evidence. We aimed to give an overview of the current use of plasma, fibrinogen concentrate, tranexamic acid (TXA), and prothrombin complex concentrate (PCC) in patients on ECMO. DESIGN:. A prespecified subanalysis of a multicenter retrospective study. Venovenous (VV)-ECMO and venoarterial (VA)-ECMO are analyzed as separate populations, comparing patients with and without bleeding and with and without thrombotic complications. SETTING:. Sixteen international ICUs. PATIENTS:. Adult patients on VA-ECMO or VV-ECMO. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 420 VA-ECMO patients, 59% (n = 247) received plasma, 20% (n = 82) received fibrinogen concentrate, 17% (n = 70) received TXA, and 7% of patients (n = 28) received PCC. Fifty percent of patients (n = 208) suffered bleeding complications and 27% (n = 112) suffered thrombotic complications. More patients with bleeding complications than patients without bleeding complications received plasma (77% vs. 41%, p < 0.001), fibrinogen concentrate (28% vs 11%, p < 0.001), and TXA (23% vs 10%, p < 0.001). More patients with than without thrombotic complications received TXA (24% vs 14%, p = 0.02, odds ratio 1.75) in VA-ECMO, where no difference was seen in VV-ECMO. Of 205 VV-ECMO patients, 40% (n = 81) received plasma, 6% (n = 12) fibrinogen concentrate, 7% (n = 14) TXA, and 5% (n = 10) PCC. Thirty-nine percent (n = 80) of VV-ECMO patients suffered bleeding complications and 23% (n = 48) of patients suffered thrombotic complications. More patients with than without bleeding complications received plasma (58% vs 28%, p < 0.001), fibrinogen concentrate (13% vs 2%, p < 0.01), and TXA (11% vs 2%, p < 0.01). CONCLUSIONS:. The majority of patients on ECMO receive transfusions of plasma, procoagulant products, or antifibrinolytics. In a significant part of the plasma transfused patients, this was in the absence of bleeding or prolonged international normalized ratio. This poses the question if these plasma transfusions were administered for another indication or could have been avoided.

Abstract The objective of this work was to develop an index of adequacy to minimum biosecurity conditions (IAB) to express the external biosecurity level of pig farms in the state of Santa Catarina, Brazil. Pig farms of producers registered in the database of Companhia Integrada de Desenvolvimento Agrícola de Santa Catarina were sampled through an online questionnaire, with 76 questions on farm identification, production system, relationship with the agroindustry, herd size, and external biosecurity. One hundred questionnaires were answered by the farmers, showing the existence, partial existence, or absence of biosecurity practices, with scores of 1.0, 0.5, and 0.0, respectively, used to calculate the IAB of each farm. The farrow to weaning farms were grouped into three categories of production units (farrow to finishing, farrow to rearing, or farrow to weaning) and two of relationships with the production chain (integrated or independent). The investments necessary to achieve the ideal biosecurity practices were estimated. The farms with a low IAB (< 40%) represented 33% of the total, and the remaining 67% of the farms were classified with a medium or high index, evidencing a good external biosecurity. The IAB can be used to measure the biosecurity of pig farms and, based on their classification, to support the design of intervention plans.

IntroductionTo evaluate the experiences of patients with type 1 diabetes following transition from a calibration-requiring to a calibration-free sensor and remote monitoring in the context of using automated insulin delivery (AID).Research design and methodsFifteen participants aged 7–65 years with type 1 diabetes participating in a longitudinal study used a Medtronic® advanced hybrid closed loop (AHCL) device with initially calibration-requiring then calibration-free sensors. Qualitative interviews were conducted ≥20 weeks following use of the calibration-requiring and ≥4 weeks after use of the calibration-free sensors/remote monitoring. Thematic analysis was used to identify key themes and subthemes.ResultsAt baseline, mean diabetes duration was 14.5 years ( ± 10.9), mean Hba1c 54.8 mmol/mol ( ± 10.2) (7.2 ± 0.9%) and Time in range 75.4% ( ± 11.6). Participants reported a progressive improvement in digital and lifestyle integration, and device trust following transition to calibration-free sensors with remote monitoring potential. They also reported a reduced need for capillary glucose, increased device satisfaction and trust, and reduced burden of diabetes care. Negative aspects reported included periodic early sensor loss, and for some, impaired integration with mobile devices.ConclusionTransitioning to calibration-free sensors with remote monitoring while using AHCL was associated with better user experience, including perceptions of improved quality of life and a reduced burden of diabetes care. Appropriate expectation setting, training, and ongoing support allow for the optimal user experience while using AHCL.Clinical trial registrationhttps://www.anzctr.org.au, identifier ACTRN12621000360819

In the following we seek to consider the ways in which the cultural representations about punk lives in Ciudad Nezahualcóyotl represent an inquiry around female precariousness that refers to economically superfluous stocks, unproductive jobs and garbage jobs closer to the universe of anonymous and imperceptible lives. And that marking supposes a potentiality in relation to the feminine condition and gendered in juxtaposition to the condition of workers. Punks are fundamentally lazy, indifferent and apathetic towards labor relations, hence work is that absent sign that makes it work and becomes an explanatory principle. The series of cultural materials in question examines the filmic work of Sarah Minter in her first video art films that are Nadie es inocente (1987) and Alma Punk (1992) crossing different analyzes from of the wandering becoming of its protagonists.

Abstract Sarcopenia is a prevalent condition that predicts prognosis in patients awaiting liver transplantation (LT). The gold standard for the diagnosis of sarcopenia is the assessment of the muscular area at L3 with computed tomography (CT) scan (skeletal muscle index [SMI]), but the routine use of CT scan is limited in clinical practice. Thus, we designed a single‐center observational study aimed to evaluate the clinical factors associated with the presence of sarcopenia by SMI, and to build a score capable of predicting or excluding the presence of sarcopenia in patients on the LT waiting list (WL). Binary logistic regression analysis was performed to establish the factors independently associated with sarcopenia, and the Sarcopenia Hospital Italiano de Buenos Aires (HIBA) score was built from the resulting model after internal validation analysis by bootstrapping and correction for optimism. The predictive capability of mortality on the WL was evaluated with competing risk regression analysis. A total of 215 patients with cirrhosis on the LT WL were included. The independent factors associated with the presence of sarcopenia were male sex (odds ratio [OR]: 6.09, p < 0.001), body mass index (OR: 0.74, p < 0.001), Child Pugh (OR: 1.44, p < 0.001), and the ratio creatinine/Cystatin C (OR: 0.03, p = 0.007). The Sarcopenia HIBA score constructed with these variables showed an area under the curve of 0.862. During follow‐up, 77 (36%) patients underwent LT, 46 (21%) died, and 92 (43%) remained alive. After adjusting for Model for End‐Stage Liver Disease–Sodium, Sarcopenia HIBA score was an independent predictor of WL mortality (subhazard ratio: 1.19; 95% confidence interval 1.01–1.40; p = 0.042). Sarcopenia HIBA score is an easy‐to‐use, objective, and reliable diagnostic and predictive tool that can be useful to improve the prognostic evaluation and allow identifying a group of patients with a higher risk of death while awaiting LT.

Tree ring data from a network of beech tree stands across Europe show evidence for a recent growth decline from 1986-2016 and project up to 50% growth reductions in some areas of Europe with future climate change.

Abstract The sixth Intergovernmental Panel on Climate Change (IPCC) assessment report confirms that global warming drives widespread changes in the global terrestrial hydrological cycle, and that changes are regionally diverse. However, reported trends and changes in the hydrological cycle suffer from significant inconsistencies. This is associated with the lack of a rigorous observationally-based assessment of simultaneous trends in the different components of the hydrological cycle. Here, we reconcile these different estimates of historical changes by simultaneously analysing trends in all the major components of the hydrological cycle, coupled with vegetation greenness for the period 1980–2012. We use observationally constrained, conserving estimates of the closure of the hydrological cycle, combined with a data assimilation approach and observationally-driven uncertainty estimates. We find robust changes in the hydrological cycle across more than 50% of the land area, with evapotranspiration (ET) changing the most and precipitation (P) the least. We find many instances of unambiguous trends in ET and runoff (Q) without robust trends in P, a result broadly consistent with a “wet gets wetter, but dry does not get drier”. These findings provide important opportunities for water resources management and climate risk assessment over a significant fraction of the land surface where hydrological trends have previously been uncertain.

With rapid high-speed railway (HSR) developments in China, HSR-based transit-oriented development (TOD) has proliferated across the country. Although local governments claim that HSR station areas are planned according to TOD principles, some scholars argue that these station areas actually contribute to unsustainable development. This study investigates two main questions: (1) what success factors should be included in a TOD plan for HSR station areas? (2) to what extent are these factors considered in the plans of Chinese HSR station areas? To answer these questions, we use content analysis to compare spatial plans for 15 HSR station areas across China, triangulating the findings via in-depth interviews and field investigations. This study reveals that most of the factors in the plans for HSR station areas deviate from TOD principles, especially in small- and medium-sized cities. We find that Chinese local governments mainly use TODs as a tool to promote suburban expansion around HSR stations.

Abstract Background A new more highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium falciparum malaria (Alere™/Abbott Malaria Ag P.f RDT [05FK140], now called NxTek™ Eliminate Malaria Ag Pf) was launched in 2017. The test has already been used in many research studies in a wide range of geographies and use cases. Methods In this study, we collate all published and available unpublished studies that use the HS-RDT and assess its performance in (i) prevalence surveys, (ii) clinical diagnosis, (iii) screening pregnant women, and (iv) active case detection. Two individual-level data sets from asymptomatic populations are used to fit logistic regression models to estimate the probability of HS-RDT positivity based on histidine-rich protein 2 (HRP2) concentration and parasite density. The performance of the HS-RDT in prevalence surveys is estimated by calculating the sensitivity and positive proportion in comparison to polymerase chain reaction (PCR) and conventional malaria RDTs. Results We find that across 18 studies, in prevalence surveys, the mean sensitivity of the HS-RDT is estimated to be 56.1% (95% confidence interval [CI] 46.9–65.4%) compared to 44.3% (95% CI 32.6–56.0%) for a conventional RDT (co-RDT) when using nucleic acid amplification techniques as the reference standard. In studies where prevalence was estimated using both the HS-RDT and a co-RDT, we found that prevalence was on average 46% higher using a HS-RDT compared to a co-RDT. For use in clinical diagnosis and screening pregnant women, the HS-RDT was not significantly more sensitive than a co-RDT. Conclusions Overall, the evidence presented here suggests that the HS-RDT is more sensitive in asymptomatic populations and could provide a marginal improvement in clinical diagnosis and screening pregnant women. Although the HS-RDT has limited temperature stability and shelf-life claims compared to co-RDTs, there is no evidence to suggest, given this test has the same cost as current RDTs, it would have any negative impacts in terms of malaria misdiagnosis if it were widely used in all four population groups explored here.

Introduction: The South African government enforced various alcohol sale restrictions during the COVID-19 lockdown in order to reduce hospital admissions related to alcohol-associated injuries. A cross-sectional study was performed to describe the temporal changes in trauma according to alcohol sale restrictions during the South African national COVID-19 lockdown. Methods: Data from all trauma-related patients presenting to the emergency centre of Mitchells Plain Hospital from 01/03/2020 till 29/9/2020 and corresponding periods during 2019 were exported from an existing database. The relationship between variables was determined with the χ2-test, Fisher's exact test, independent samples median test or t-test. A sub-analysis compared similar 2020 lockdown levels when a second alcohol ban were instituted while most business were allowed to operate (level 3b – alcohol banned versus level 3 – alcohol restricted). Results: Total number of trauma presentations were 539 (14.6%) less in 2020 (n = 3160) than in 2019 (n = 3699); the mean number decreased by 2.5 per day (95% CI −2.9 to −2.1). Lockdown levels with an alcohol ban had on average 4.8 less patients per day than corresponding periods in 2019 (p

Mature B-cell lymphomas are highly dependent upon the protective lymphoid organ microenvironment for their growth and survival. Targeting integrin-mediated homing and retention of the malignant B cells in the lymphoid organs, using the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, is a highly efficacious FDA-approved therapy for chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM). Unfortunately, a significant subset of patients is intrinsically resistant to ibrutinib or will develop resistance upon prolonged treatment. Here, we describe an unbiased functional genomic CRISPR-Cas9 screening method to identify novel proteins involved in B-cell receptor–controlled integrin-mediated adhesion, which provides novel therapeutic targets to overcome ibrutinib resistance. This screening method is highly flexible and can be easily adapted to identify cell adhesion–regulatory proteins and signaling pathways for other stimuli, adhesion molecules, and cell types.Graphical abstract:

This paper presents the flow and flame characteristics of a highly turbulent reactive flow over a backward-facing step inside a windowed combustor. Flow and combustion experiments were performed at Re = 15,000 and Re = 30,000 using high-resolution 10 kHz PIV and 10 kHz PLIF diagnostic techniques. Grid turbulators (Grid) with two different hole diameters (HD of 1.5 mm and 3 mm) and blockage ratios (BR of 46%, 48%, 62%, and 63%) were considered for the turbulence study. Grids introduced different turbulent length scales (LT) in the flow, causing the small eddies and turbulence intensity to increase downstream. The backward-facing step increased the turbulence level in the recirculation zone. This helped to anchor the flame in that zone. The small HD grids (Grids 1 and 3) produced continuous fluid structures (small-scale), whereas the larger HD grids (Grids 2 and 4) produced large-scale fluid structures. Consequently, the velocity fluctuation was lower (~25.6 m/s) under small HD grids and higher (~27.7 m/s) under large HD grids. The flame study was performed at Φ = 0.8, 1.0, and 1.2 using C-X CH PLIF. An Adaptive MATLAB-based flame imaging scheme has been developed for turbulent reacting flows. Grids 1 and 3 induced more wrinkles in the flame due to higher thermal instabilities, pressure fluctuation, and diffusion under those grids. The flamelet breakdown and burnout events were higher under Grids 2 and 4 due to higher thermal diffusivity and a slower diffusion rate. It was observed that the flame wrinkling and flame stretching are higher at Re = 30,000 compared to Re = 15,000. The Borghi–Peters diagram showed that the flames were within the thin reaction zone except for Grid 1 at Re = 15,000, where flames fell in the corrugated zone. It was observed from PIV and PLIF analyses that Re and LT mostly controlled the flame and flow characteristics.

El objetivo general es analizar la cultura de la seguridad del paciente (SP) para promover la implementación de planes de mejora en los servicios de salud. Se efectuó una medición cuantitativa mediante la adaptación local del Cuestionario Hospital Survey on Patient Safety Culture de la Agency of Healthcare Research and Quality 2.0 (AHRQ, 2016), aplicado a una muestra de trabajadores pertenecientes a una clínica polivalente de la Ciudad de Buenos Aires. Se obtuvieron estos hallazgos: a) Existe una red de apoyo grupal percibida para actuar ante eventos que pueden afectar la SP; b) El interés por la seguridad es manifiesto en todos los equipos y niveles jerárquicos, pero las intervenciones suelen efectuarse luego de que se produzcan incidentes adversos, no en su prevención; d) Las respuestas se centran habitualmente en la culpabilización del personal involucrado, reflejando una carencia de contención psicológica y capacitación al mismo.

The dendrochronological climate signal of Norway spruce (Picea abies), European larch (Larix decidua), and European beech (Fagus sylvatica), among others, depends on altitude, therefore we have to collect dendrochronological data systematically for each species along altitude gradients. To this end, we established local tree-ring chronologies for the three species along two elevation gradients: (1) Kokra – Jezersko with sites at 750, 780, 950, 1200, 1250, 1380, 1600 m a.s.l., and (2) Bled – Radovna – Krma with sites at 518, 550, 580, 700, 750, 900, 950, 1000, 1200, 1400, 1600, 1760, 1900, 2040 m a.s.l. We present the main characteristics of the chronologies and the results of the dendroclimatological analyses, which show how the climatic factors influence the variation of the tree rings in dependence of altitude and species. We also present the agreement of the different chronologies in terms of standard dendrochronological parameters such as the t-value and discuss the potential use of the presented database.

This data article presents a tripartite dataset that formed the empirical basis for a comprehensive bibliometric analysis of the use of city labels denoting sustainable urbanism in the scientific literature (Schraven, 2021). The tripartite dataset was generated using the abstract and citation database Scopus (Elsevier). Dataset A lists 148 city labels denoting different approaches to urban planning and development. It was used to select 35 city labels that specifically address sustainable urbanism (‘sustainable city’, ‘smart city’, ‘compact city’ etc.). Dataset B references 11,337 journal and review articles spanning the period 1990–2019. All retrieved articles contain at least one of the 35 city labels in the title, abstract, and author keywords. This database was used to calculate the frequency of the selected city labels across time, and to analyze the co-occurrences of city labels. It was further used to calculate the future trajectory of scientific outputs using the Logistic Growth Model (LGM). Dataset C entails 22,820 author keywords extracted from across the 11,337 articles. This was used to analyze the co-occurrences of keywords with city labels. The data article describes the methods of data collection and curation, the analysis performed, and the potential for reusing the data for further research. The comprehensiveness of the bibliometric corpus – spanning three decades and 35 city labels – lends itself to further investigation of how sustainable urban development has evolved as a topic in the scientific literature since the 1990s. Furthermore, the robust methodology developed could be adapted to other scientific repositories and, indeed, other research problems and questions.

Abstract Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. Results Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. Conclusion In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

Abstract. Background:. Minimally invasive pancreatic surgery (MIPS) has developed over the last 3 decades and is nowadays experiencing an increased interest from the surgical community. With increasing awareness of both the public and the surgical community on patient safety, optimization of training has gained importance. For implementation of MIPS we propose 3 training phases. The first phase focuses on developing basic skills and procedure specific skills with the help of simulation, biotissue drills, video libraries, live case observations, and training courses. The second phase consists of index procedures, fellowships, and proctoring programs to ensure patient safety during the first procedures. During the third phase the surgeons aim is to safely implement the procedure into standard practice while minimizing learning curve related excess morbidity and mortality. Case selection, skills assessment, feedback, and mentoring are important methods to optimize this phase. The residual learning curve can reach up to 100 cases depending on the surgeons’ previous experience, selection of cases, and definition of the parameters used to assess the learning curve. Adequate training and high procedural volume are key to implementing MIPS safely.

B cell receptors (BCRs) and T cell receptors (TCRs) make up an essential network of defense molecules that, collectively, can distinguish self from non-self and facilitate destruction of antigen-bearing cells such as pathogens or tumors. The analysis of BCR and TCR repertoires plays an important role in both basic immunology as well as in biotechnology. Because the repertoires are highly diverse, specialized software methods are needed to extract meaningful information from BCR and TCR sequence data. Here, we review recent developments in bioinformatics tools for analysis of BCR and TCR repertoires, with an emphasis on those that incorporate structural features. After describing the recent sequencing technologies for immune receptor repertoires, we survey structural modeling methods for BCR and TCRs, along with methods for clustering such models. We review downstream analyses, including BCR and TCR epitope prediction, antibody-antigen docking and TCR-peptide-MHC Modeling. We also briefly discuss molecular dynamics in this context.

Comprar, vender, interagir, integrar, enfim, relacionar-se. As empresas atuam em processo de ampla adaptação, uma vez que as diferentes formas de interação com seus clientes sofrem modificações sistemáticas em função da revolução que a tecnologia, em especial a internet, impõe ao mercado. Entender esta complexidade sobre o aspecto do varejo omnichannel é o principal objetivo deste trabalho. Com a utilização de estratégias metodológicas da bibliometria e revisão sistemática, este estudo apresenta um levantamento sobre o referido tema, considerando a lente do marketing como principal abordagem. A pesquisa foi realizada em sete bases de dados com intuito de elencar os principais artigos sobre o tema. Os termos pesquisados foram omnichannel e sua principal variação omni-channel. As bases utilizadas foram: Google Scholar, Webof Science, Scopus, Periódicos Capes, Scielo, Ebsco Host e Spell. Os principais resultados indicam que os pesquisadores de marketing tratam de omnichannel sob a perspectiva do consumidor (experiências de consumo e a importância da jornada do cliente no varejo omnichannel), das estratégias empresariais adotadas pelas empresas para atuar neste formato de varejo (investimentos em tecnologia para integrar a atuação em diferentes canais) e da interação do marketing com outras áreas organizacionais (integração da área de marketing com outras áreas para atuar neste contexto de varejo). Como conclusão sugere-se as seguintes pesquisas futuras: a) tópicos de entendimento da jornada do cliente; b) as etapas percorridas e, decifrar como as experiências do consumidor podem impactar em novas compras; c) entender como as empresas estão se preparando para lidar com este cenário omnichannel.

Dados de mercado revelam crescimento no acesso à internet e na conectividade de pessoas e empresas. Neste contexto, o marketing digital tem sido incorporado nas estratégias de diversas empresas. Em face da importância do tema, buscou-se, neste estudo, através de uma pesquisa bibliométrica seguida de uma revisão sistemática integrativa, mapear a compreensão da influência do marketing digital no comportamento de compra dos consumidores e propor uma agenda de pesquisa acerca do tema. Para isto, foram avaliados artigos publicados nas bases de dados: Ebsco, Periódicos Capes, Scopus, Spell e Web of Science entre os anos de 2000 a 2019. Os resultados apontaram que mais de 60% das publicações foram realizadas entre os anos de 2016 e 2019 e que temas emergentes como “IOT”, “economia compartilhada” e “marketing sensorial digital” são passiveis de melhor investigação. Estudos transculturais e longitudinais de temas como “influenciadores digitais” e “marketing boca a boca on-line” figuraram entre importantes gaps teóricos. Sugere-se estudos transculturais que permitam evidenciar características e gatilhos na utilização do marketing boca a boca digital, opção por modalidade de compra em grupo, opções por empresas com iniciativas sustentáveis e envolvendo a compra por impulso.

Gene therapy for severe hemophilia B is advancing and offers sustained disease amelioration with a single treatment. We have reported the efficacy and safety of AMT-060, an investigational gene therapy comprising an adeno-associated virus serotype 5 capsid encapsidating the codon-optimized wild-type human factor IX (WT hFIX) gene with a liver-specific promoter, in patients with severe hemophilia B. Treatment with 2 × 1013 gc/kg AMT-060 showed sustained and durable FIX activity of 3%–13% and a substantial reduction in spontaneous bleeds without T cell-mediated hepatoxicity. To achieve higher FIX activity, we modified AMT-060 to encode the R338L “Padua” FIX variant that has increased specific activity (AMT-061). We report the safety and increased FIX activity of AMT-061 in non-human primates. Animals (n = 3/group) received intravenous AMT-060 (5 × 1012 gc/kg), AMT-061 (ranging from 5 × 1011 to 9 × 1013 gc/kg), or vehicle. Human FIX protein expression, FIX activity, and coagulation markers including D-dimer and thrombin-antithrombin complexes were measured. At equal doses, AMT-060 and AMT-061 resulted in similar human FIX protein expression, but FIX activity was 6.5-fold enhanced using AMT-061. Both vectors show similar safety and transduction profiles. Thus, AMT-061 holds great promise as a more potent FIX replacement gene therapy with a favorable safety profile. Keywords: AAV, AAV5, AMT-060, AMT-061, adeno-associated virus, factor IX, gene therapy, hemophilia B, non-human primate

O estudo tem como objetivo analisar o efeito do humor no engajamento dos usuários em relação a publicações do perfil Globo Rural no Twitter. Trata-se de uma pesquisa quantitativa, conclusiva, descritiva, com coleta de dados por observação e análise via estatística descritiva e Teste-T. Foram coletadas e analisadas 1.100 publicações da revista Globo Rural no Twitter. Os resultados do estudo revelaram que há diferença estatística significativa e positiva nas três variáveis de engajamento em relação à presença de humor nas publicações analisadas. Observou-se também uma diferença nas médias de engajamento em relação ao dia e tipo de conteúdo da publicação: as médias nas publicações sem humor em finais de semana são maiores comparadas as publicações em dias úteis na semana, enquanto nas publicações com humor as médias em finais de semana são menores se comparadas as publicações em dias úteis na semana.

The California Current System (CCS) has experienced large fluctuations in environmental conditions in recent years that have dramatically affected the biological community. Here we synthesize remotely sensed, hydrographic, and biological survey data from throughout the CCS in 2019–2020 to evaluate how recent changes in environmental conditions have affected community dynamics at multiple trophic levels. A marine heatwave formed in the north Pacific in 2019 and reached the second greatest area ever recorded by the end of summer 2020. However, high atmospheric pressure in early 2020 drove relatively strong Ekman-driven coastal upwelling in the northern portion of the CCS and warm temperature anomalies remained far offshore. Upwelling and cooler temperatures in the northern CCS created relatively productive conditions in which the biomass of lipid-rich copepod species increased, adult krill size increased, and several seabird species experienced positive reproductive success. Despite these conditions, the composition of the fish community in the northern CCS remained a mixture of both warm- and cool-water-associated species. In the southern CCS, ocean temperatures remained above average for the seventh consecutive year. Abundances of juvenile fish species associated with productive conditions were relatively low, and the ichthyoplankton community was dominated by a mixture of oceanic warm-water and cosmopolitan species. Seabird species associated with warm water also occurred at greater densities than cool-water species in the southern CCS. The population of northern anchovy, which has been resurgent since 2017, continued to provide an important forage base for piscivorous fishes, offshore colonies of seabirds, and marine mammals throughout the CCS. Coastal upwelling in the north, and a longer-term trend in warming in the south, appeared to be controlling the community to a much greater extent than the marine heatwave itself.

Abstract Background Synthesis of the hemostatic protein von Willebrand factor (VWF) drives formation of endothelial storage organelles called Weibel‐Palade bodies (WPBs). In the absence of VWF, angiogenic and inflammatory mediators that are costored in WPBs are subject to alternative trafficking routes. In patients with von Willebrand disease (VWD), partial or complete absence of VWF/WPBs may lead to additional bleeding complications, such as angiodysplasia. Studies addressing the role of VWF using VWD patient–derived blood outgrowth endothelial cells (BOECs) have reported conflicting results due to the intrinsic heterogeneity of patient‐derived BOECs. Objective To generate a VWF‐deficient endothelial cell model using clustered regularly interspaced short palindromic repeats (CRISPR) genome engineering of blood outgrowth endothelial cells. Methods We used CRISPR/CRISPR‐associated protein 9 editing in single‐donor cord blood–derived BOECs (cbBOECs) to generate clonal VWF−/− cbBOECs. Clones were selected using high‐throughput screening, VWF mutations were validated by sequencing, and cells were phenotypically characterized. Results Two VWF−/− BOEC clones were obtained and were entirely devoid of WPBs, while their overall cell morphology was unaltered. Several WPB proteins, including CD63, syntaxin‐3 and the cargo proteins angiopoietin (Ang)‐2, interleukin (IL)‐6, and IL‐8 showed alternative trafficking and secretion in the absence of VWF. Interestingly, Ang‐2 was relocated to the cell periphery and colocalized with Tie‐2. Conclusions CRISPR editing of VWF provides a robust method to create VWF‐ deficient BOECs that can be directly compared to their wild‐type counterparts. Results obtained with our model system confirmed alternative trafficking of several WPB proteins in the absence of VWF and support the theory that increased Ang‐2/Tie‐2 interaction contributes to angiogenic abnormalities in VWD patients.

Huntington disease (HD) is a fatal neurodegenerative disorder caused by an autosomal dominant CAG repeat expansion in the huntingtin (HTT) gene. The translated expanded polyglutamine repeat in the HTT protein is known to cause toxic gain of function. We showed previously that strong HTT lowering prevented neuronal dysfunction in HD rodents and minipigs after single intracranial injection of adeno-associated viral vector serotype 5 expressing a microRNA targeting human HTT (AAV5-miHTT). To evaluate long-term efficacy, AAV5-miHTT was injected into the striatum of knockin Q175 HD mice, and the mice were sacrificed 12 months post-injection. AAV5-miHTT caused a dose-dependent and sustained HTT protein reduction with subsequent suppression of mutant HTT aggregate formation in the striatum and cortex. Functional proof of concept was shown in transgenic R6/2 HD mice. Eight weeks after AAV5-miHTT treatment, a significant improvement in motor coordination on the rotarod was observed. Survival analysis showed that a single AAV5-miHTT treatment resulted in a significant 4-week increase in median survival compared with vehicle-treated R6/2 HD mice. The combination of long-term HTT lowering, reduction in aggregation, prevention of neuronal dysfunction, alleviation of HD-like symptoms, and beneficial survival observed in HD rodents treated with AAV5-miHTT supports the continued development of HTT-lowering gene therapies for HD. Keywords: Huntington disease, gene silencing, HD mouse model, gene therapy, therapeutic microRNAs, adeno-associated viral vector serotype 5

Abstract Background Teenagers and young adults with type 1 diabetes (T1D) experience significant burden managing this serious chronic condition and glycaemic control is at its unhealthiest during this life stage. Flash glucose monitoring (FGM) is a new technology that reduces the burden of glucose monitoring by easily and discreetly displaying glucose information when an interstitial glucose sensor worn on the upper arm is scanned with a handheld reader, as opposed to traditional capillary glucose sampling by finger prick (otherwise known as self-monitored blood glucose, SMBG). The effectiveness of this technology and impacts of its long-term use in youth with pre-existing suboptimal glycaemic control are unknown. This study therefore aims to investigate the effectiveness of FGM in addition to standard care in young people with T1D. Methods This is a two phase study programme including a multi-centre randomised, parallel-group study consisting of a 6-month comparison between SMBG and FGM, with an additional 6-month continuation phase. We will enrol adolescents with T1D aged 13–20 years (inclusive), with suboptimal glycaemic control (mean glycated haemoglobin (HbA1c) in past 6 months ≥75 mmol/mol [≥9%]). Participants will be randomly allocated (1:1) to FGM (FreeStyle Libre; intervention group) or to continue SMBG with capillary blood glucose testing (usual care group). All participants will continue other aspects of standard care with the study only providing the FreeStyle Libre. At 6 months, the control group will cross over to the intervention. The primary outcome is the between group difference in changes in HbA1c at 6 months. Additional outcomes include a range of psychosocial and health economic measures as well as FGM acceptability. Discussion >If improvements are found, this will further encourage steps towards integrating FGM into regular diabetes care for youth with unhealthy glycaemic control, with the expectation it will reduce daily diabetes management burden and improve short- and long-term health outcomes in this high-risk group. Trial registration This trial was registered with the Australian New Zealand Clinical Trials Registry on 5 March 2018 (ACTRN12618000320257p) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1205-5784).

O objetivo deste trabalho é analisar como propagandas com humor incongruente veiculadas no Facebook atuam no engajamento, nas atitudes e na intenção de compra das consumidoras brasileiras. Um experimento realizado no Facebook, com 269 consumidoras brasileiras, permitiu testar se a presença de humor incongruente influencia a efetividade das propagandas, confirmando tal hipótese, além de demonstrar que se trata de um apelo humorístico com efeitos positivos sobre o público feminino. Entre as contribuições deste artigo, destaca-se que, seus achados confirmam que engajamento, atitudes e intenção de compra conformam importantes medidas da efetividade das propagandas no contexto virtual; revelam novas facetas sobre a percepção das mulheres quanto a estímulos tradicionalmente destinados aos homens; e apontam as redes sociais como elementos fundamentais à tomada de decisão do consumidor. Evidencia-se, assim, o papel da internet como plataforma de interação entre empresas e usuários e a necessidade de construção de um relacionamento nesta conjuntura, contexto em que o humor incongruente mostra-se capaz de chamar atenção, despertar engajamento, provocar atitudes favoráveis e, deste modo, conduzir a intenção de compra.

Triggered by frequent high temperatures and scarce precipitation, droughts are a recurrent phenomenon in the Mediterranean Basin, causing significant impacts on forests. We analyzed the effects of drought intensity, duration, and seasonality on tree growth by investigating the relationship between the Standardized Precipitation-Evapotranspiration Index (SPEI) at different time scales and tree-ring width (TRW) in three pine species (Pinus halepensis Mill., P. sylvestris L, and P. uncinata Ramond ex A.DC) throughout a dense dendrochronological network in the Mediterranean Basin. We used generalized linear mixed models to predict such values over the entire distribution of the analyzed species. Furthermore, in areas where the species coexist, we analyzed the same parameters to highlight differences in their responses to similar climatic conditions. Our results showed that the maximum intensity of drought-affected conifers occurred more in the southern areas of the Spanish Mediterranean coast, especially P. halepensis, with maximum values of r = 0.67, while in the rest of the study area, the intensity decreased with elevation; we obtained maximum values of r = 0.40 and r = 0.33 for P. sylvestris and P. uncinata, respectively. This spatial distribution was also related to the duration of the drought impacts, showing that areas with lower intensity had shorter durations (2–4 months). We observed a latitudinal pattern in the seasonality of the drought impacts, with earlier growing seasons at high elevations (June–August) and later ones in the semi-arid Mediterranean. Similar intensity impacts were found in P. halepensis and P. sylvestris coexistence zones, although P. halepensis had a much longer duration and an earlier beginning of seasonality. Higher intensity, duration, and seasonality of drought effects were observed for P. sylvestris in areas where P. sylvestris and P. uncinata are distributed sympatrically. Understanding the plasticity and climatic response of these common southern European species to different types of droughts is crucial in the context of climate change where droughts are increasing in frequency and intensity.