Early Cretaceous rift basins of the incipient South Atlantic have been the focus of intense hydrocarbon exploration and production activities and host some large oil accumulations in sections predating an interval of major salt deposition, particularly in the central segment of the South Atlantic. Understanding the timing (and associated uncertainties) of source rock and reservoir deposition and their relationship with rift evolution is critical for successful exploration. However, there are still many unresolved issues and data gaps regarding the precise age and duration of salt deposition. Better chronological constraints are particularly needed to determine the timing of deposition of Pre-Salt reservoirs and the primary evaporites, as well as the secondary phase of halokinensis that resulted in variable reservoir sealing potential. To help address this gap, stable carbon isotope (δ¹³C) records from bulk organic matter and insoluble kerogen were generated for the Early Cretaceous salt and Pre-Salt intervals from two exploration wells offshore of Gabon. The bulk organic δ¹³C stratigraphies for the two wells were then integrated with palynological and ostracod biostratigraphy and placed within a sequence stratigraphic and regional tectonic framework, providing new constraints on the timing of rift lake evolution and salt deposition. The good correlation between the offshore Gabon δ¹³C record with other published sections calibrated to the current Geologic Time Scale as well as other regional sections from NE Brazil, supports the reliability of our new Gabon δ¹³C record. Several δ¹³C excursions are identified in the Pre-Salt sequence and are correlated with the Valanginian Weissert event and Early Aptian δ¹³C event(s). Salt deposition on the Gabon margin is interpreted to have occurred during an interval straddling the Early-Late Aptian boundary (∼118.4–116.8 Ma). These findings are comparable with other published estimates for salt deposition from northeast Brazil but differ from published estimates from the Campos-Santos basins; the latter are critically discussed. This study provides an important stratigraphic dataset for offshore Gabon and contributes to the ongoing debate regarding the timing of rifting and salt deposition in the Early Cretaceous of the South Atlantic passive margin system.
A tournament H is quasirandom-forcing if the following holds for every sequence (Gn)n∈N of tournaments of growing orders: if the density of H in Gn converges to the expected density of H in a random tournament, then (Gn)n∈N is quasirandom. Every transitive tournament with at least 4 vertices is quasirandom-forcing, and Coregliano (2019) showed that there is also a non-transitive 5-vertex tournament with the property. We show that no additional tournament has this property. This extends the result of Bucić (2021) that the non-transitive tournaments with seven or more vertices do not have this property.
A famous result by Rödl, Ruciński, and Szemerédi guarantees a (tight) Hamilton cycle in k-uniform hypergraphs H on n vertices with minimum (k−1)-degree δk−1(H)⩾(1/2+o(1))n, thereby extending Dirac's result from graphs to hypergraphs. For graphs, much more is known; each graph on n vertices with δ(G)⩾(1/2+o(1))n contains (1−o(1))r edge-disjoint Hamilton cycles where r is the largest integer such that G contains a spanning 2r-regular subgraph, which is clearly asymptotically optimal. This was proved by Ferber, Krivelevich, and Sudakov answering a question raised by Kühn, Lapinskas, and Osthus. We extend this result to hypergraphs; every k-uniform hypergraph H on n vertices with δk−1(H)⩾(1/2+o(1))n contains (1−o(1))r edge-disjoint (tight) Hamilton cycles where r is the largest integer such that H contains a spanning subgraph with each vertex belonging to kr edges. In particular, this yields an asymptotic solution to a question of Glock, Kühn, and Osthus. In fact, our main result applies to approximately vertex-regular k-uniform hypergraphs with a weak quasirandom property and provides approximate decompositions into cycle factors without too short cycles.
Objective In multiple sclerosis (MS), iron rim lesions (IRLs) on magnetic resonance imaging (MRI) are associated with pronounced intralesional tissue damage. The aim of this study was to investigate (peri-)lesional and structural connectivity tissue damage in IRLs compared to non-IRLs. Material and methods MRI was acquired on a 3 T system. Tissue integrity was assessed using the T1/T2-weighted (T1/T2w) ratio. Furthermore, we assessed the impact on structural network connectivity accounting for differences in lesion volumes and T1/T2w values. Results Seventy-six patients (38 with at least one IRL and 38 age- and sex-matched patients without IRLs) were included. In the IRL-group, T1/T2w ratios of IRLs were significantly lower compared to non-IRLs (p < 0.05). When comparing the T1/T2w ratios in non-IRLs between the IRL-group and non-IRL group, there was no significant difference (p = 0.887). We observed a centrifugal decrease in microstructural damage from lesions to the perilesional white matter. In the IRL-group, T1/T2w ratios in the perilesional white matter 3–8 mm distant to the lesion were significantly lower in IRLs compared to non-IRLs. We found no significant differences in the amount of network disruption between both lesion types (p = 0.122). Conclusion T1/T2w represents an interesting candidate to capture a pronounced intra- and perilesional tissue damage of IRLs. However, our preliminary results suggest that a pronounced tissue damage might not result in a higher disruption to structural connectivity networks in IRLs.
Background The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled “International Natural Product Sciences Taskforce” (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week “2021 INPST Twitter Networking Event” (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events.
In this work we present the homogenization of a reaction-diffusion model that includes an evolving microstructure. Such type of problems model, for example, mineral dissolution and precipitation in a porous medium. In the initial state, the microscopic geometry is a periodically perforated domain, each perforation being a spherical solid grains. A small parameter ϵ is characterizing both the distance between two neighboring grains, and the radii of the grains. For each grain, the radius depends on the unknown (the solute concentration) at its surface. Therefore, the radii of the grains change in time and are model unknowns, so the model involves free boundaries at the micro scale. In a first step, we transform the evolving micro domain to a fixed, periodically domain. Using the Rothe-method, we prove the existence of a weak solution and obtain a priori estimates that are uniform with respect to ϵ. Finally, letting ϵ→0, we derive a macroscopic model, the solution of which approximates the micro-scale solution. For this, we use the method of two-scale convergence, and obtain strong compactness results enabling to pass to the limit in the nonlinear terms.
Aberrant limbic circuit reactivity to negative stimuli might be related to alterations in emotion processing and regulation in alcohol use disorder (AUD). The current study tested for the first time in AUD the hypothesis of aberrant amygdala habituation to repeated aversive stimuli—a robust and reliable neuroimaging marker for emotion processing. We explored the link between deficits in habituation to adverse childhood experience (ACE), a common risk factor for impaired emotion regulation and AUD. AUD individuals (N = 36) and healthy controls (HC; N = 26) participated in an observational case–control functional magnetic resonance imaging (fMRI) study. An established habituation index was used to investigate processing of aversive emotional faces of the amygdala. AUD individuals showed an overall deficit in amygdala habituation (right: t = 4.26, pFWE = 0.004; left: t = 4.79, pFWE ≤ 0.001). Amygdala habituation was significantly related to increased exposure to ACE in HC (t = 3.88, pFWE = 0.012), whereas this association was not observed in AUD individuals (T = 1.80, pFWE = 0.662). Further, a significant association between higher alcohol consumption and reduced amygdala habituation (right: R2 = −0.356, F = 8.736, p = 0.004; left: R2 = −0.309, F = 6.332, p = 0.015) was observed. We found novel evidence for neural alterations in emotion processing in AUD individuals, indexed by deficient amygdala habituation to negative emotional content. We replicated a prior report on a link between ACE and amygdala habituation, a well‐established environmental risk factor for mental disorders and emotion dysregulation, in our control sample. Additionally, deficient amygdala habituation related to the amount of alcohol consumption in the overall sample might indicate a short‐term substance effect. Aberrant limbic circuit reactivity to negative stimuli relates to alterations in emotion processing and regulation in alcohol use disorder (AUD). We observed deficient amygdala habituation to negative emotional content in AUD individuals. This further related to the amount of alcohol consumption in the overall sample, possibly indicating a short‐term substance effect. We replicated a prior report on a link between ACE and amygdala habituation, a well‐established environmental risk factor for mental disorders and emotion dysregulation, in our control sample.
Mental health comorbidities are frequent in epilepsy. Consequently, psychotherapy is becoming increasingly important. To address the psychological needs of people with epilepsy (PwE) it is essential to understand the subjective experiences of seizures better. There is little research on how people report seizures, and which psychological representations they have. We conducted a thematic analysis based on 42 (micro-phenomenological) interviews with 15 participants on their experiences of seizures. In these interviews, we identified three categories of seizure descriptions: (1) phenomena related to the body and emotions; (2) the moments that are difficult to describe; and (3) the use of figurative language and metaphors. Paroxysmal physical and psychological sensations were often reported spontaneously by the participants. The moments that were difficult to describe were expressed, among other things, through the use of paradoxes or the report of a ‘strange’ feeling and led participants to use figurative language. As these metaphors can reveal important information about people’s subjective experiences, they were analyzed in detail. We identified the three main types of metaphors that the participants used most frequently: (1) perception, (2) nature, and (3) battle. The theme of battle was most frequently used in different forms and was closely related to the metaphors from the fields of perception and nature, thus representing a key point in the personal experience of seizures. These findings can contribute to developing psychotherapeutic approaches for the treatment of seizure disorders.
Background In clinically node-negative breast cancer patients, the INSEMA trial (NCT02466737) assessed the non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Here we present patient-reported outcomes (PROs) as a secondary endpoint. Methods PROs were assessed for patients with no axillary surgery, SLNB alone, and ALND. Quality of life (QoL) questionnaire EORTC QLQ-C30 and its breast cancer module (BR23) were used at baseline (pre-surgery) and 1, 3, 6, 12, and 18 months after surgery. The QoL scores were compared using repeated measures mixed models based on the safety set. Findings Between 2015 and 2019, 5502 patients were recruited for the first randomization, and 5154 were included in the intent-to-treat set (4124 SLNB versus 1030 no SLNB). In the case of one to three macrometastases after SLNB, 485 patients underwent second randomization (242 SLNB alone versus 243 ALND). Questionnaire completion response remained high throughout the trial: over 70% at all time points for the first randomization. There were significant differences for the BRBS (breast symptoms) and BRAS (arm symptoms) scores favoring the no SLNB group in all post-baseline assessments. Patients in the SLNB group showed significantly and clinically relevant higher scores for BRAS (differences in mean values ≥5.0 points at all times), including pain, arm swelling, and impaired mobility in all postoperative visits, with the highest difference at one month after surgery. Scoring of the QLQ-C30 questionnaire revealed no relevant differences between the treatment groups, although some comparisons were statistically significant. Interpretation This is one of the first randomized trials investigating the omission of SLNB in clinically node-negative patients and the first to report comprehensive QoL data. Patients with no SLNB benefitted regarding arm symptoms/functioning, while no relevant differences in other scales were seen. Funding Supported by German Cancer Aid (Deutsche Krebshilfe, Bonn, Germany), Grant No. 110580 and Grant No. 70110580 to University Medicine Rostock.
The paper focuses on the archaeometric analyses of the gold objects from the famous so-called ‘treasures’ of Troy and Poliochni on the island of Lemnos. Altogether 61 Early Bronze Age (EBA) gold objects dating between 2500 and 2000 BCE were investigated in this study. They were primarily sampled with a portable laser ablation (pLA) unit in the National Archaeological Museum in Athens and analyzed with ICP-MS at the Curt-Engelhorn-Centre Archaeometry (CEZA) in Mannheim. The main advantage of this approach is the possibility to obtain samples on site without the necessity of transport. It is a minimally invasive method that leaves no visible damage on the objects. As an additional advantage there are no restrictions on the size of the objects under study. The central goal of the study was to obtain high-quality compositional analyses of gold objects from the sites Troy and Poliochni to investigate, if the typological similarity is paralleled by the elemental composition of the gold, including the trace elements. This would suggest not only similar procurement of the metal across these sites but also potential exchange of objects and/or specialist workers. In a second step, the results were compared with data from contemporary gold objects from Ur in southern Mesopotamia, from where LA-ICP-MS data have recently become available. Finally, a survey of such data for gold objects from gold-rich regions is used to narrow down the possible origin of Early Bronze Age gold in the Old World.
Pancreatic ductal adenocarcinoma (PDA) is usually unresponsive to immunotherapeutic approaches. However, tertiary lymphoid structures (TLS) are associated with favorable patient outcomes in PDA. A better understanding of the B cell infiltrate and biological features of TLS formation is needed to further explore their potential and improve patient management. We analyzed tumor tissues (n = 55) and corresponding blood samples (n = 51) from PDA patients by systematical immunohistochemistry and multiplex cytokine measurements. The tissue was compartmentalized in "tumor" and "stroma" and separately examined. Clinical patient information was used to perform survival analyses. We found that the mere number of B cells is not associated with patient survival, but formation of TLS in the peritumoral stroma is a prognostic favorable marker in PDA patients. TLS-positive tissues show a higher density of CD8+ T cells and CD20+ B cells and a higher IL2 level in the peritumoral stroma than tissues without TLS. Compartmental assessment shows that gradients of IL2 expression differ with regard to TLS formation: TLS presence is associated with higher IL2 levels in the stromal than in the tumoral compartment, while no difference is seen in patients without TLS. Focusing on the stroma-to-serum gradient, only patients without TLS show significantly higher IL2 levels in the serum than in stroma. Finally, low circulatory IL2 levels are associated with local TLS formation. Our findings highlight that TLS are prognostic favorable and associated with antitumoral features in the microenvironment of PDA. Also, we propose easily accessible serum IL2 levels as a potential marker for TLS prediction.
Lung carcinoids are neuroendocrine tumors representing 1 to 2% of lung cancers. This study outlines the case of a patient with a metastatic lung atypical carcinoid who presented with a pleural effusion and progression of liver metastases after developing resistance to conventional treatments. Personalized functional profiling (PFP), i.e. drug screening, was performed in ex-vivo spheroids obtained from the patient’s liver metastasis to identify potential therapeutic options. The drug screening results revealed cediranib, an antiangiogenic drug, as a hit drug for this patient, from a library of 66 Food and Drug Administration (FDA)-approved and investigational drugs. Based on the PFP results and the reported evidence of clinical efficacy of bevacizumab and capecitabine combination in gastro-intestinal neuroendocrine tumors, this combination was given to the patient. Four months later, the pleural effusion and pleura carcinosis regressed and the liver metastasis did not progress. The patient experienced 2 years of a stable disease under the PFP-guided personalized treatment.
Immune checkpoint molecule B7-H1 plays a decisive immune regulatory role in different pathologies including cancer, and manipulation of B7-H1 expression became an attractive approach in cancer immunotherapy. Pancreatic cancer (PDAC) is characterized by pronounced immunosuppressive environment and B7-H1 expression correlates with PDAC prognosis. However, the first attempts to diminish B7-H1 expression in patients were not so successful. This points the complicity of PDAC immunosuppressive network and requires further examinations. We investigated the effect of B7-H1 deficiency in PDAC. Our results clearly show that partial or complete B7-H1 inhibition in vivo let to reduced tumor volume and improved survival of PDAC-bearing mice. This oncological benefit is due to the abrogation of immunosuppression provided by MDSC, macrophages, DC and Treg, which resulted in simultaneous restoration of anti-tumor immune response, namely improved accumulation and functionality of effector-memory CD4 and CD8 T cells. Our results underline the potential of B7-H1 molecule to control immunosuppressive network in PDAC and provide new issues for further clinical investigations.
The transcription factor p53 exerts its tumour suppressive effect through transcriptional activation of numerous target genes controlling cell cycle arrest, apoptosis, cellular senescence and DNA repair. In addition, there is evidence that p53 influences the translation of specific mRNAs, including translational inhibition of ribosomal protein synthesis and translational activation of MDM2. A challenge in the analysis of translational control is that changes in mRNA abundance exert a kinetic (passive) effect on ribosome densities. In order to separate these passive effects from active regulation of translation efficiency in response to p53 activation, we conducted a comprehensive analysis of translational regulation by comparative analysis of mRNA levels and ribosome densities upon DNA damage induced by neocarzinostatin in wild-type and TP53-/- HCT116 colorectal carcinoma cells. Thereby, we identified a specific group of mRNAs that are preferentially translated in response to p53 activation, many of which correspond to p53 target genes including MDM2, SESN1 and CDKN1A. By subsequent polysome profile analysis of SESN1 and CDKN1A mRNA, we could demonstrate that p53-dependent translational activation relies on a combination of inducing the expression of translationally advantageous isoforms and trans-acting mechanisms that further enhance the translation of these mRNAs.
The small ribosomal subunit protein Rps15/uS19 is involved in early nucleolar ribosome biogenesis and subsequent nuclear export of pre-40S particles to the cytoplasm. In addition, the C-terminal tail of Rps15 was suggested to play a role in mature ribosomes, namely during translation elongation. Here, we show that Rps15 not only functions in nucleolar ribosome assembly but also in cytoplasmic pre-40S maturation, which is indicated by a strong genetic interaction between Rps15 and the 40S assembly factor Ltv1. Specifically, mutations either in the globular or C-terminal domain of Rps15 when combined with the non-essential ltv1 null allele are lethal or display a strong growth defect. However, not only rps15 ltv1 double mutants but also single rps15 C-terminal deletion mutants exhibit an accumulation of the 20S pre-rRNA in the cytoplasm, indicative of a cytoplasmic pre-40S maturation defect. Since in pre-40S particles, the C-terminal tail of Rps15 is positioned between assembly factors Rio2 and Tsr1, we further tested whether Tsr1 is genetically linked to Rps15, which indeed could be demonstrated. Thus, the integrity of the Rps15 C-terminal tail plays an important role during late pre-40S maturation, perhaps in a quality control step to ensure that only 40S ribosomal subunits with functional Rps15 C-terminal tail can efficiently enter translation. As mutations in the C-terminal tail of human RPS15 have been observed in connection with chronic lymphocytic leukaemia, it is possible that apart from defects in translation, an impaired late pre-40S maturation step in the cytoplasm could also be a reason for this disease.
Eukaryotic ribosome biogenesis involves the synthesis of ribosomal RNA (rRNA) and its stepwise folding into the unique structure present in mature ribosomes. rRNA folding starts already co-transcriptionally in the nucleolus and continues when pre-ribosomal particles further maturate in the nucleolus and upon their transit to the nucleoplasm and cytoplasm. While the approximate order of folding of rRNA subdomains is known, especially from cryo-EM structures of pre-ribosomal particles, the actual mechanisms of rRNA folding are less well understood. Both small nucleolar RNAs (snoRNAs) and proteins have been implicated in rRNA folding. snoRNAs hybridize to precursor rRNAs (pre-rRNAs) and thereby prevent premature folding of the respective rRNA elements. Ribosomal proteins (r-proteins) and ribosome assembly factors might have a similar function by binding to rRNA elements and preventing their premature folding. Besides that, a small group of ribosome assembly factors are thought to play a more active role in rRNA folding. In particular, multiple RNA helicases participate in individual ribosome assembly steps, where they are believed to coordinate RNA folding/unfolding events or the release of proteins from the rRNA. In this review, we summarize the current knowledge on mechanisms of RNA folding and on the specific function of the individual RNA helicases involved. As the yeast Saccharomyces cerevisiae is the organism in which ribosome biogenesis and the role of RNA helicases in this process is best studied, we focused our review on insights from this model organism, but also make comparisons to other organisms where applicable.
Objective. The study sought to assess the prognostic value of treatment with digitalis on long-term prognosis in patients with ventricular tachyarrhythmias and atrial fibrillation (AF) and/or heart failure (HF). Background. Data regarding the outcome of digitalis therapy following ventricular tachyarrhythmias is limited. Methods. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with digitalis were compared to patients without. The primary prognostic endpoint was all-cause mortality at 3 years, secondary endpoints comprised a composite arrhythmic endpoint (i.e. recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies, sudden cardiac death) and cardiac rehospitalization. Kaplan Mayer survival curves, multivariable cox regression, and time trend analyses were applied for statistics. Results. Eight hundred and thirty-one patients were included (20% treated with digitalis and 80% without). At 3 years, digitalis treatment was not associated with all-cause mortality following ventricular tachyarrhythmias (24 vs. 21%, log-rank p = .736; HR = 1.063; 95% CI 0.746–1.515; p = .736). However, digitalis therapy was associated with an increased risk of the composite arrhythmic endpoint (38 vs. 23%; log-rank p = .001; HR = 1.719; 95% CI 1.279–2.311; p = .001) and cardiac rehospitalization (31 vs. 18%; log-rank p = .001; HR = 1.829; 95% CI 1.318–2.538; p = .001), which was still evident within multivariable Cox regression analyses. Finally, digitoxin may be associated with a worse prognosis than digoxin. Conclusion. Digitalis therapy was not associated with mortality in patients with ventricular tachyarrhythmias, but with increased risk of the composite arrhythmic endpoint and cardiac rehospitalization at 3 years.
Background: Difficulties in emotion regulation are a core symptom of borderline personality disorder (BPD) and often interfere with cognitive functions, such as working memory (WM). Traumatic childhood experiences, including severe maltreatment, can contribute to emotion dysregulation, possibly mediated by changes in high-frequency heart rate variability (HF-HRV). However, it is not yet entirely understood if HF-HRV alterations underlie impaired WM during emotional distraction in BPD and if this is related to traumatic childhood experiences and to comorbid post-traumatic stress disorder (PTSD). Objective: Our aim was to investigate performance (reaction times, RTs) and HF-HRV during an emotional working memory task (EWMT) in relation to childhood maltreatment severity and comorbid PTSD in BPD. Method: Eighty-one women (n = 28 healthy controls (HC) and n = 53 BPD patients of which n = 18 had comorbid PTSD) performed an adapted Sternberg item recognition WM task with neutral and negative social cues (interpersonal scenes from the International Affective Picture System (IAPS), and neutral, fearful, and angry faces) as distractors. Dependent variables were RTs of correct trials and HF-HRV. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire. Results: Compared to healthy participants, patients with BPD showed prolonged RTs across all distractor conditions with social cues, regardless of their emotional valence. Patients with BPD, especially those with PTSD, demonstrated reduced HF-HRV both at rest and during EWMT. Severity of childhood maltreatment predicted longer RTs and lower HF-HRV during the EWMT. Conclusions: Findings suggest that adverse childhood experiences accelerate difficulties in shifting attention away from social information and that these are more pronounced in individuals with BPD. Reduced HF-HRV (low parasympathetic-tonus) may be an important psychophysiological mechanism underlying impaired WM in the presence of distracting social cues in patients with BPD, especially in those with comorbid PTSD. Highlights: This study provides evidence that childhood maltreatment experiences are associated with hypersensitivity to social information and reduced high-frequency heart rate variability during a working memory task in borderline personality disorder.
Background Vaccine scares undermine longstanding global health achievements. Remarkably little data has documented the lived experiences of policymakers working amidst vaccine scares and navigating their fallout. As a result, chances and challenges of large-scale national recuperation efforts are poorly understood. Objective This study aims to explore the perspectives of policymakers involved in ongoing efforts to boost vaccine confidence in the Philippines following a 2017 Dengvaxia scare and the current COVID-19 pandemic. Methods Between August and November 2020, we conducted 19 semi-structured narrative interviews with purposively selected policymakers from governmental agencies and non-governmental organizations in the Philippines. Interviews were conducted online, transcribed, and analyzed following the tenets of reflexive thematic analysis. Results We present results as an emerging model that draws on a chronology conveyed by policymakers in their own words. The Dengvaxia scare proved ‘a decisive wedge’ that splintered Filipino society and pitted governmental agencies against one another. The scare stoked distorted vaccination narratives, which were ‘accelerated rapidly’ via social media, and ignited feelings of uncertainty among policymakers of how to convey clear, accurate health messaging and how to prevent drops in care-seeking more broadly. Conclusions Efforts to regain trust placed exceptional burdens on an already-strained health system. Respondent-driven recommendations on how to reinforce vaccine confidence and improve vaccination rollout include: developing clear vaccine messages, fostering healthcare providers’ and policymakers’ communication skills, and rebuilding trust within, toward and across governmental agencies. Further research on how to build enabling environments and rebuild trust in and across institutions remains paramount.
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