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Summary: In people with HIV-1 (PWH), Mycobacterium tuberculosis (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals. Functional annotation identified alterations in IL-6, TNF, and KRAS pathways. Notably, MTB-related genes displayed an inverse correlation with HIV-1 viremia, at both individual and signature score levels. These findings suggest that MTB infection in PWH induces a shift in immune system activation, inversely related to HIV-1 viral load. These results may explain the observed enhanced antiretroviral control in MTB-infected PWH. This study highlights the complex interplay between MTB and HIV-1, emphasizing the importance of understanding their interaction for managing co-infections in this population.

Abstract Background One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation. Methods “POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)” is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU. Discussion POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients. Trial registration Clinicaltrials.gov NCT06178510 . Registered on December 4, 2023.

Abstract Communal bird roosts serve as information centres and a means of thermoregulation for many species. While some communally roosting species are major pests and cause dis‐amenities, others are of conservation concern. Estimating the population of roosting birds can provide a useful proxy of population size and possibly a more reliable estimate than other sampling techniques. However, estimating these populations is challenging as some roosts are large and often occluded in foliage. Previous acoustic methods such as paired sampling, microphone arrays and use of call rate have been used to estimate bird abundances; however, these are less suited for estimating large roost populations where hundreds of individuals are calling in unison. To address this challenge, we explored using machine learning techniques to estimate a roost population of the Javan myna, Acridotheres javanicus, an invasive species in Singapore. While one may expect to use sound intensity to estimate roost sizes, it is affected by various factors such as distance to the recorder, local propagation conditions (e.g. buildings and trees), weather conditions, and noise from other sources. Here, we used a deep neural network to extract higher order statistics from the sound recordings and use those to help estimate roost sizes. Additionally, we validated our method using automated visual analysis with a dual‐camera setup and manual bird counts. Our estimated bird counts over time using our acoustic model matched the automated visual estimates and manual bird counts at a selected Javan myna roost, thus validating our approach. Our acoustic model estimated close to 400 individual mynas roosting in a single tree. Analyses of additional recordings of Javan myna roosts conducted on two separate occasions and at a different roost location using our acoustic model showed that our roost estimates over time also matched our automated visual estimates well. Practical implication: Our novel approach of estimating communal roost sizes can be achieved robustly using a simple portable acoustic recording system. Our method has multiple applications such as testing the efficacy of avian roost population control measures (e.g. roost tree pruning) and monitoring the populations of threatened bird species that roost communally.

The pathogenesis of HIV-1 infection is governed by a highly dynamic, time-dependent interaction between the host and the viral genome. In this study, we developed a novel systematic approach to assess the host-virus interaction, using average pairwise viral diversity as a proxy for time since infection, and applied this method to nearly whole viral genome sequences (n = 4,464), human leukocyte antigen (HLA) genotyping data (n = 1,044), and viral RNA load (VL) measurements during the untreated chronic phase (n = 829) of Swiss HIV Cohort Study participants. Our systematic genome-wide screen revealed for 98 HLA/viral-variant pairs a signature of immune-driven selection in the form of an HLA-dependent effect of infection time on the presence of HIV amino acid variants. Of these pairs, 12 were found to have an effect on VL. Furthermore, 28/58 pairs were validated by time-to-event analyses and 48/92 by computational HLA-epitope predictions. Our diversity-based approach allows a powerful and systematic investigation of the interaction between the virus and cellular immunity, revealing a notable subset of such interaction effects. From an evolutionary perspective, these observations underscore the complexity of HLA-mediated selection pressures on the virus that shape viral evolution and pathogenesis.

Abstract Underwater imaging sonars are widely used for oceanic exploration but are bulky and expensive for some applications. The sonar system of dolphins, which uses sound pulses called clicks to investigate their environment, offers superior shape discrimination capability compared to human-derived imaging sonars of similar size and frequency. In order to gain better understanding of dolphin sonar imaging, we train a dolphin to acoustically interrogate certain objects and match them visually. We record the echoes the dolphin receives and are able to extract object shape information from these recordings. We find that infusing prior information into the processing, specifically the sparsity of the shapes, yields a clearer interpretation of the echoes than conventional signal processing. We subsequently develop a biomimetic sonar system that combines sparsity-aware signal processing with high-frequency broadband click signals similar to that of dolphins, emitted by an array of transmitters. Our findings offer insights and tools towards compact higher resolution sonar imaging technologies.

Abstract Effective vaccines for human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) remain a significant challenge for these infectious diseases. Given that the innate immune response is key to controlling the scale and nature of developing adaptive immune responses, targeting natural killer (NK) cells that can promote a T-helper type 1 (Th1)-type immune response through the production of interferon-γ (IFNγ) remains an untapped strategic target for improved vaccination approaches. Here, we investigate metabolic and functional responses of NK cells to simian adenovirus prime and MVA boost vaccination in a cohort of healthy volunteers receiving a dual HCV-HIV-1 vaccine. Early and late timepoints demonstrated metabolic changes that contributed to the sustained proliferation of all NK cells. However, a strong impact of human cytomegalovirus (HCMV) on some metabolic and functional responses in NK cells was observed in HCMV seropositive participants. These changes were not restricted to molecularly defined adaptive NK cells; indeed, canonical NK cells that produced most IFNγ in response to vaccination were equally impacted in individuals with latent HCMV. In summary, NK cells undergo metabolic changes in response to vaccination, and understanding these in the context of HCMV is an important step towards rational vaccine design against a range of human viral pathogens.

Abstract Background Despite successful combined antiretroviral therapy (cART), the risk of non-AIDS defining cancers (NADCs) remains higher for HIV-infected individuals than the general population. The reason for this increase is highly disputed. Here, we hypothesized that T-cell receptor (TCR) γδ cells and/or mucosal-associated invariant T (MAIT) cells might be associated with the increased risk of NADCs. γδ T cells and MAIT cells both serve as a link between the adaptive and the innate immune system, and also to exert direct anti-viral and anti-tumor activity. Methods We performed a longitudinal phenotypic characterization of TCR γδ cells and MAIT cells in HIV-infected individuals developing Hodgkin’s lymphoma (HL), the most common type of NADCs. Cryopreserved PBMCs of HIV-infected individuals developing HL, matched HIV-infected controls without (w/o) HL and healthy controls were used for immunophenotyping by polychromatic flow cytometry, including markers for activation, exhaustion and chemokine receptors. Results We identified significant differences in the CD4+ T cell count between HIV-infected individuals developing HL and HIV-infected matched controls within 1 year before cancer diagnosis. We observed substantial differences in the cellular phenotype mainly between healthy controls and HIV infection irrespective of HL. A number of markers tended to be different in Vδ1 and MAIT cells in HIV+HL+ patients vs. HIV+ w/o HL patients; notably, we observed significant differences for the expression of CCR5, CCR6 and CD16 between these two groups of HIV+ patients. Conclusion TCR Vδ1 and MAIT cells in HIV-infected individuals developing HL show subtle phenotypical differences as compared to the ones in HIV-infected controls, which may go along with functional impairment and thereby may be less efficient in detecting and eliminating malignant cells. Further, our results support the potential of longitudinal CD4+ T cell count analysis for the identification of patients at higher risk to develop HL.

Abstract Dolphins use their biosonar to discriminate objects with different features through the returning echoes. Cross-modal matching experiments were conducted with a resident bottlenose dolphin (Tursiops aduncus). Four types of objects composed of different materials (water-filled PVC pipes, air-filled PVC pipes, foam ball arrays, and PVC pipes wrapped in closed-cell foam) were used in the experiments, respectively. The size and position of the objects remained the same in each case. The data collected in the experiment showed that the dolphin’s matching accuracy was significantly different across the cases. To gain insight into the underlying mechanism in the experiments, we used finite element methods to construct two-dimensional target detection models of an echolocating dolphin in the vertical plane, based on computed tomography scan data. The acoustic processes of the click’s interaction with the objects and the surrounding media in the four cases were simulated and compared. The simulation results provide some possible explanations for why the dolphin performed differently when discriminating the objects that only differed in material composition in the previous matching experiments.

Summary: Background: Loss of intestinal epithelial barrier integrity is a critical component of Inflammatory Bowel Disease (IBD) pathogenesis. Co-expression regulation of ligand-receptor pairs in IBD mucosa has not been systematically studied. Targeting ligand-receptor pairs which are induced in IBD mucosa and function in intestinal epithelial barrier integrity may provide novel therapeutics for IBD. Methods: We performed transcriptomic meta-analysis on public IBD datasets combined with cell surface protein-protein-interaction (PPI) databases. We explored primary human/mouse intestinal organoids and Caco-2 cells for expression and function studies of uPA-uPAR (prime hits from the meta-analysis). Epithelial barrier integrity was measured by Trans-Epithelial Electrical Resistance (TEER), FITC-Dextran permeability and tight junction assessment. Genetic (CRISPR, siRNA and KO mice) and pharmacological (small molecules, neutralizing antibody and peptide inhibitors) approaches were applied. Mice deficient of uPAR were studied using the Dextran Sulfate Sodium (DSS)-induced colitis model. Findings: The IBD ligand-receptor meta-analysis led to the discovery of a coordinated upregulation of uPA and uPAR in IBD mucosa. Both genes were significantly upregulated during epithelial barrier breakdown in primary intestinal organoids and decreased during barrier formation. Genetic inhibition of uPAR or uPA, or pharmacologically blocking uPA-uPAR interaction protects against cytokine-induced barrier breakdown. Deficiency of uPAR in epithelial cells leads to enhanced EGF/EGFR signalling, a known regulator of epithelial homeostasis and repair. Mice deficient of uPAR display improved intestinal barrier function in vitro and during DSS-induced colitis in vivo. Interpretation: Our findings suggest that blocking uPA-uPAR interaction via pharmacological agents protects the epithelial barrier from inflammation-induced damage, indicating a potential therapeutic target for IBD. Funding: The study was funded by Boehringer Ingelheim.

AIMS OF THE STUDY: Vaccination is regarded as the most promising response to the COVID-19 pandemic. We assessed opinions about COVID-19 vaccination, willingness to be vaccinated, and reasons for vaccination hesitancy among healthcare workers. METHODS: We conducted a cross-sectional, web-based survey among 3,793 healthcare workers in December 2020 in the Canton of Solothurn, Switzerland, before the start of the national COVID-19 vaccination campaign. RESULTS: Median age was 43 years (interquartile range [IQR] 31–53), 2,841 were female (74.9%). A total of 1,511 healthcare workers (39.8%) reported willingness to accept vaccination, whereas 1,114 (29.4%) were unsure and 1,168 (30.8%) would decline vaccination. Among medical doctors, 76.1% were willing, whereas only 27.8% of nurses expressed willingness. Among the 1,168 healthcare workers who would decline vaccination, 1,073 (91.9%) expressed concerns about vaccine safety and side effects. The willingness of healthcare workers to be vaccinated was associated with older age (adjusted odds ratio [aOR] 1.97, 95% confidence interval [Cl] 1.71–2.27) and having been vaccinated for influenza this year (aOR 2.70, 95% Cl 2.20–3.31). Healthcare workers who reported a lack of confidence in government were less likely to be willing to be vaccinated (aOR 0.58, 95% Cl 0.40–0.84), and women were less willing to be vaccinated than men (OR 0.33, 95% CI 0.28–0.38). CONCLUSION: Less than half of healthcare workers reported willingness to be vaccinated before the campaign start, but proportions varied greatly depending on profession and workplace. Strategies with clear and objective messages that particularly address the concerns of healthcare workers are needed if their willingness to be vaccinated against COVID-19 is to be further increased.

BACKGROUND: Healthcare workers are more frequently exposed to SARS-CoV-2 than the general population. Little is known about healthcare settings outside of hospitals. We studied the seroprevalence of SARS-CoV-2 among healthcare workers in outpatient facilities and retirement or nursing homes in the Canton of Solothurn, Switzerland in the first wave of the COVID-19 pandemic. METHODS: Longitudinal seroprevalence study among healthcare workers with examinations at baseline and 2 months between June and September 2020. The Abbott SARS-CoV-2 IgG and Liaison/Diasorin SARS-CoV-2 S1/S2 IgG assay were used to detect antibodies against SARS-CoV-2. All participants provided demographic information. We report descriptive statistics and calculated the seroprevalence with 95% confidence intervals. RESULTS: We included 357 healthcare workers; their median age was 43 years (interquartile range 29–54), and 315 (88.2%) were female. Forty-nine (13.7%) were physicians, 87 (24.4%) practice assistants and 221 (61.9%) nurses. Overall seroprevalence among healthcare workers in outpatient facilities and retirement or nursing homes was 3.4% (12/357). The 12 seropositive healthcare workers were all nurses (12/221, 5.5%); 11 worked at retirement or nursing homes and one at the hospital's outpatient clinic. Symptoms such as loss of smell or taste, shortness of breath, and fever were more prevalent among seropositive healthcare workers than seronegative healthcare workers. No close contact had detectable antibodies against SARS-CoV-2. CONCLUSIONS: Seroprevalence among healthcare workers was low, but higher among nursing staff of retirement or nursing homes. Healthcare workers at private practices were able to protect themselves well during the first wave of the COVID-19 pandemic.

Here, Bachmann et al. provide data on long-term dynamics of the HIV-1 reservoir in 1,057 individuals on suppressive antiretroviral therapy and show that in 26.6% of individuals the reservoir increases. Viral blips and low-level viremia are significantly associated with a slower reservoir decay.

We present a new two-step approach for automatized a posteriori decision making in multi-objective optimization problems, i.e., selecting a solution from the Pareto front. In the first step, a knee region is determined based on the normalized Euclidean distance from a hyperplane defined by the furthest Pareto solution and the negative unit vector. The size of the knee region depends on the Pareto front’s shape and a design parameter. In the second step, preferences for all objectives formulated by the decision maker, e.g., 50–20–30 for a 3D problem, are translated into a hyperplane which is then used to choose a final solution from the knee region. This way, the decision maker’s preference can be incorporated, while its influence depends on the Pareto front’s shape and a design parameter, at the same time favorizing knee points if they exist. The proposed approach is applied in simulation for the multi-objective model predictive control (MPC) of the two-dimensional rocket car example and the energy management system of a building.

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.

Background: Coronavirus disease 2019 (COVID-19) presents with a wide range of illness severity, from asymptomatic disease to severe acute respiratory distress syndrome (ARDS). Immunosuppression is considered a risk factor for severe COVID-19, but there are only few reports on disease progression in immunocompromised patients. Case Summary: We report the case of a 50-year-old patient with acute COVID-19 pneumonia, who had iatrogenic, clinically relevant bone marrow suppression due to accidental overdose with hydroxyurea, and decreased lung capacity due to a left-sided pneumonectomy 6 months earlier. Symptomatic treatment with oxygen supplementation and pulmonary physical therapy was initiated, and hydroxyurea was discontinued. Over 14 days, the patient’s blood counts slowly recovered, and his clinical condition gradually improved, such that supplemental oxygen was no longer necessary and he could be discharged. Discussion: A gradual increase in neutrophil and lymphocyte counts may be preferable to dampen a potentially detrimental immunological response triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether patients with severe COVID-19 benefit from immunosuppressive therapy should be further evaluated.

Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.

BACKGROUND The coronavirus disease (COVID)-19 epidemic is evolving rapidly. Healthcare workers are at increased risk for infection, and specific requirements for their protection are advisable to ensure the functioning of the basic healthcare system, including the availability of general practitioners (GPs). Understanding the transmission risk is particularly important for guiding evidence-based protective measures in the primary healthcare setting. METHODS Healthcare worker contacts of an initially undiagnosed COVID-19 case, who were without personal protective equipment, in particular not wearing facemasks, were screened with nasopharyngeal swabs and polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), irrespective of respiratory symptoms or fever seven days after initial contact. The details of exposure to the index case were obtained during routine contact investigation after unintentional pathogen exposure. RESULTS Twenty-one healthcare workers reported contacts with the index case. Three healthcare workers reported respiratory symptoms (cough) or low-grade fever within 4 days. None of them tested positive for SARS-CoV-2 at the time of symptom onset. All 21 healthcare workers tested SARS-CoV-2 negative 7 days after initial index case contact, including the three healthcare workers with previous symptoms. Ten of the 21 healthcare workers reported a cumulative exposure time of >15 minutes. Longer cumulative contact times were associated with more individual contacts, reduced contact time per contact and activities with physical patient contact. The closest relative of the index patient tested SARS-CoV-2 positive 2 days after the index case presented at the hospital emergency department. CONCLUSION We found a low risk of SARS-CoV-2 transmission in a primary care setting. These findings are compatible with previous reports of the highest transmission probability in household settings with prolonged close contacts. The current protective measures for healthcare workers, including strict adherence to basic standard hygiene and facemasks, offer considerable protection during short periods of contact with symptomatic COVID-19 cases by diminishing the risk of direct and indirect transmission.

Alzheimer's disease (AD) is a multifactorial disease and the most common form of dementia. There are no treatments to cure, prevent or slow down the progression of the disease. Natural products hold considerable interest for the development of preventive neuroprotectants to treat neurodegenerative disorders like AD, due to their low toxicity and general beneficial effects on human health with their anti-inflammatory and antioxidant features. In this work we describe regioselective synthesis of 7-O-ester hybrids of the flavonoid taxifolin with the phenolic acids cinnamic and ferulic acid, namely 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin. The compounds show pronounced overadditive neuroprotective effects against oxytosis, ferroptosis and ATP depletion in the murine hippocampal neuron HT22 cell model. Furthermore, 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin reduced LPS-induced neuroinflammation in BV-2 microglia cells as assessed by effects on the levels of NO, IL6 and TNFα. In all in vitro assays the 7-O-esters of taxifolin and ferulic or cinnamic acid showed strong overadditive activity, significantly exceeding the effects of the individual components and the equimolar mixtures thereof, which were almost inactive in all of the assays at the tested concentrations. In vivo studies confirmed this overadditive effect. Treatment of an AD mouse model based on the injection of oligomerized Aβ25-35 peptide into the brain to cause neurotoxicity and subsequently memory deficits with 7-O-cinnamoyltaxifolin or 7-O-feruloyltaxifolin resulted in improved performance in an assay for short-term memory as compared to vehicle and mice treated with the respective equimolar mixtures. These results highlight the benefits of natural product hybrids as a novel compound class with potential use for drug discovery in neurodegenerative diseases due to their pharmacological profile that is distinct from the individual natural components. Keywords: Alzheimer's disease, Natural product hybrids, Flavonoids, Phenolic acids, Microglia, In vivo studies

A new device that combined high-resolution (1080p) wide-angle video and three channels of high-frequency acoustic recordings (at 500 kHz per channel) in a portable underwater housing was designed and tested with wild bottlenose and spotted dolphins in the Bahamas. It consisted of three hydrophones, a GoPro camera, a small Fit PC, a set of custom preamplifiers and a high-frequency data acquisition board. Recordings were obtained to identify individual vocalizing animals through time-delay-of-arrival localizing in post-processing. The calculated source positions were then overlaid onto the video – providing the ability to identify the vocalizing animal on the recorded video. The new tool allowed for much clearer analysis of the acoustic behavior of cetaceans than was possible before.

Background: Nearly 3 million people worldwide are coinfected with HIV and HCV. Affordable strategies for prevention are needed. We developed a novel vaccination regimen involving replication-defective and serologically distinct chimpanzee adenovirus (ChAd3, ChAd63) vector priming followed by modified vaccinia Ankara (MVA) boosts, for simultaneous delivery of HCV non-structural (NSmut) and HIV-1 conserved (HIVconsv) region immunogens.Methods: We conducted a phase I trial in which 33 healthy volunteers were sequentially enrolled and vaccinated via the intramuscular route as follows: 9 received ChAd3-NSmut [2.5 × 1010 vp] and MVA-NSmut [2 × 108 pfu] at weeks 0 and 8, respectively; 8 received ChAdV63.HIVconsv [5 × 1010 vp] and MVA.HIVconsv [2 × 108 pfu] at the same interval; 16 were co-primed with ChAd3-NSmut [2.5 × 1010 vp] and ChAdV63.HIVconsv [5 × 1010 vp] followed at week 8 by MVA-NSmut and MVA.HIVconsv [both 1 × 108 pfu]. Immunogenicity was assessed using peptide pools in ex vivo ELISpot and intracellular cytokine assays. Vaccine-induced whole blood transcriptome changes were assessed by microarray analysis.Results: All vaccines were well tolerated and no vaccine-related serious adverse events occurred. Co-administration of the prime-boost vaccine regimens induced high magnitude and broad T cell responses that were similar to those observed following immunization with either regimen alone. Median (interquartile range, IQR) peak responses to NSmut were 3,480 (2,728–4,464) and 3,405 (2,307–7,804) spot-forming cells (SFC)/106 PBMC for single and combined HCV vaccinations, respectively (p = 0.8). Median (IQR) peak responses to HIVconsv were 1,305 (1,095–4,967) and 1,005 (169–2,482) SFC/106 PBMC for single and combined HIV-1 vaccinations, respectively (p = 0.5). Responses were maintained above baseline to 34 weeks post-vaccination. Intracellular cytokine analysis indicated that the responding populations comprised polyfunctional CD4+ and CD8+ T cells. Canonical pathway analysis showed that in the single and combined vaccination groups, pathways associated with antiviral and innate immune responses were enriched for upregulated interferon-stimulated genes 24 h after priming and boosting vaccinations.Conclusions: Serologically distinct adenoviral vectors encoding HCV and HIV-1 immunogens can be safely co-administered without reducing the immunogenicity of either vaccine. This provides a novel strategy for targeting these viruses simultaneously and for other pathogens that affect the same populations.Clinical trial registration:https://clinicaltrials.gov, identifier: NCT02362217

Summary We examine to what extent mortgage lending is characterized by strong relationships between banks and their borrowers. Our analysis is based on survey data covering all current bank relations for a sample of 1,481 Swiss households out of which 687 have a mortgage. We document that mortgage borrowers maintain significantly more bank relations than comparable households without a mortgage. However, this does not imply that mortgage relations are loose. Comparing mortgage relations to other bank relations of the same households we find that mortgage relations are used for a broader scope of transactions and are held with banks that are located closer to the household. Examining the heterogeneity of mortgage relations across households, we find that financially sophisticated households are less likely to hold their mortgage with a local bank.

Assessing the danger of transition of HIV transmission from a concentrated to a generalized epidemic is of major importance for public health. In this study, we develop a phylogeny-based statistical approach to address this question. As a case study, we use this to investigate the trends and determinants of HIV transmission among Swiss heterosexuals. We extract the corresponding transmission clusters from a phylogenetic tree. To capture the incomplete sampling, the delayed introduction of imported infections to Switzerland, and potential factors associated with basic reproductive number [Formula: see text], we extend the branching process model to infer transmission parameters. Overall, the [Formula: see text] is estimated to be [Formula: see text] ([Formula: see text]-confidence interval [Formula: see text]—[Formula: see text]) and it is decreasing by [Formula: see text] per [Formula: see text] years ([Formula: see text]—[Formula: see text]). Our findings indicate rather diminishing HIV transmission among Swiss heterosexuals far below the epidemic threshold. Generally, our approach allows to assess the danger of self-sustained epidemics from any viral sequence data.