Стратегії та моделі розвитку інноваційної сфери регіональних економічних систем в умовах трансформаційної економіки

Метою даного роботи є дослідження можливих стратегій та моделей розвитку інноваційної сфери регіональних економічних систем в умовах трансформацій економіки, що охоплюють майже всі сфери економіко-господарської діяльності

Estimating post-pandemic effects of working from home and teleconferencing on travel behaviour

Like in many other countries, the Dutch government instructed people to work from home where possible during the COVID-19 pandemic to halt the transmission of the virus. This policy seems to have resulted in a structural increase in working from home and teleconferencing that will outlast the pandemic. However, the longer-term effects on travel behaviour are still unclear. Making use of panel data collected using the Netherlands Mobility Panel, this paper has two main aims. First, it analyses developments in working from home and teleconferencing since COVID-19. Second, it estimates the expected post-pandemic effects on travel behaviour. The results show that compared to before the pandemic, the average number of hours that people work from home has doubled and roughly two-thirds of respondents indicate that they teleconference more often. We estimate that structural, post-pandemic increases in working from home and teleconferencing will result in a negative effect on distances travelled by train (-3% to -9%), by bus, tram, and metro (-1% to -5%) and car (-1 to -5%). The estimated effect on the distance travelled by bicycle (-2% to 0%), and walking (0% to +1%) is smaller or even positive, due to people making more complementary trips for other purposes when working from home. When interpreting these results, we should keep in mind that due to various other factors, such as population growth, total travel demand will still grow in the near future

Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy

Objective To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. Design Single centre, double blind, cluster randomised, placebo controlled trial. SettingLeprosy control programme in two districts of northwest Bangladesh with a population of more than four million. Participants28 092 close contacts of 1037 patients with newly diagnosed leprosy. 21 711 contacts fulfilled the study requirements. Interventions A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient’s treatment, with follow-up for four years. Main outcome measure Development of clinical leprosy. Results 18 869 of the 21 711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT. ConclusionA single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years. Trial registration Current Controlled Trials ISRCTN61223447

Quantitative lateral flow strip assays as user-friendly tools to detect biomarker profiles for leprosy

Leprosy is a debilitating, infectious disease caused by Mycobacterium leprae. Despite the availability of multidrug therapy, transmission is unremitting. Thus, early identification of M. leprae infection is essential to reduce transmission. The immune response to M. leprae is determined by host genetics, resulting in paucibacillary (PB) and multibacillary (MB) leprosy associated with dominant cellular or humoral immunity, respectively. This spectral pathology of leprosy compels detection of immunity to M. leprae to be based on multiple, diverse biomarkers. In this study we have applied quantitative user friendly lateral flow assays (LFAs) for four immune markers (anti-PGL-I antibodies, IL-10, CCL4 and IP-10) for whole blood samples from a longitudinal BCG vaccination field-trial in Bangladesh. Different biomarker profiles, in contrast to single markers, distinguished M. leprae infected from non-infected test groups, patients from household contacts (HHC) and endemic controls (EC), or MB from PB patients. The test protocol presented in this study merging detection of innate, adaptive cellular as well as humoral immunity, thus provides a convenient tool to measure specific biomarker profiles for M. leprae infection and leprosy utilizing a field-friendly technology

Effectiveness of single-dose rifampicin after BCG vaccination to prevent leprosy in close contacts of patients with newly diagnosed leprosy: A cluster randomized controlled trial

Objective: To assess the effectiveness of single-dose rifampicin (SDR) after bacillus Calmette–Guérin (BCG) vaccination in preventing leprosy in contacts. Methods: This was a single-centre, cluster-randomized controlled trial at a leprosy control programme in northwest Bangladesh. Participants were the 14 988 contacts of 1552 new leprosy patients who were randomized into the SDR − arm (n = 7379) and the SDR + arm (n = 7609). In the intervention group, BCG vaccination was followed by SDR 8–12 weeks later. In the control group, BCG vaccination only was given. Follow-up was performed at 1 year and 2 years after intake. The main outcome measure was the occurrence of leprosy. Results: The incidence rate per 10 000 person-years at risk was 44 in the SDR − arm and 31 in the SDR + arm at 1 year; the incidence rate was 34 in the SDR − arm and 41 in the SDR + arm at 2 years. There was a statistically non-significant (p = 0.148; 42%) reduction for paucibacillary (PB) leprosy in the SDR+ arm at 1 year. Of all new cases, 33.6% appeared within 8–12 weeks after BCG vaccination. Conclusions: In the first year, SDR after BCG vaccination reduced the incidence of PB leprosy among contacts by 42%. This was a statistically non-significant reduction due to the limited number of cases after SDR was administered. To what extent SDR suppresses excess leprosy cases after BCG vaccination is difficult to establish because many cases appeared before the SDR intervention. Trial registration: Netherlands Trial Register: NTR3087

Application of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field

Background: Transmission of Mycobacterium leprae, the pathogen causing leprosy, is still persistent. To facilitate timely (prophylactic) treatment and reduce transmission it is vital to both early diagnose leprosy, and identify infected individuals lacking clinical symptoms. However, leprosy-specific biomarkers are limited, particularly for paucibacillary disease. Therefore, our objective was to identify new biomarkers for leprosy and assess their applicability in point-of-care (POC) tests. Methods: Using multiplex-bead-arrays, 60 host-proteins were measured in a cross-sectional approach in 24-h whole blood assays (WBAs) collected in Bangladesh (79 patients; 54 contacts; 51 endemic controls (EC)). Next, 17 promising biomarkers were validated in WBAs of a separate cohort (55 patients; 27 EC). Finally, in a third cohort (36 patients; 20 EC), five candidate markers detectable in plasma were assessed for application in POC tests. Findings: This study identified three new biomarkers for leprosy (ApoA1, IL-1Ra, S100A12), and confirmed five previously described biomarkers (CCL4, CRP, IL-10, IP-10, αPGL-I IgM). Overnight stimulation in WBAs provided increased specificity for leprosy and was required for IL-10, IL-1Ra and CCL4. The remaining five biomarkers were directly detectable in plasma, hence suitable for rapid POC tests. Indeed, lateral flow assays (LFAs) utilizing this five-marker profile detected both multi- and paucibacillary leprosy patients with variable immune responses. Interpretation: Application of novel host-biomarker profiles to rapid, quantitative LFAs improves leprosy diagnosis and allows POC testing in low-resource settings. This platform can thus aid diagnosis and classification of leprosy and also provides a tool to detect M.leprae infection in large-scale contact screening in the field

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The influence of weather on travel behaviour - a multi-method analysis

Societal and political attention to the effects of climate change and possible mitigation and adaptationpolicies has increased sharply in the last decades, resulting partly from increasing awareness about therole of humanity and partly from the ever more noticeable changes in our world caused by climatechange. This societal interest has highlighted a lack of knowledge about the effects that a changingclimate will have on many aspects of our lifes, one of which is the transport section. To understand theimpact climate change will have on our transport system we need to know how travel behaviours areaffected by weather circumstances, which is the main topic of our research.We focus on four aspects of the relationship between weather and travel behaviour: (1) how weatheris taken into account in the decision-making process (2) if the influence of singular weather variables(such as temperature) depend on the value of other parameters (3) if the influence of weather is differentfor urban and rural areas and (4) whether there are groups of people whose response to travelbehaviour are distinctly different from one-another. This knowledge can be used for climate changeadaptation measures, such as ensuring that our supply of travel infrastructure will be able to copewith changes in travel demand resulting from a changed climate, and mitigation measures, such asincreasing the number of people that use more sustainable travel options like the bicycle.For our analyses we use travel data provided by the KiM Netherlands Institute for Transport PolicyAnalysis, which is the result from a travel diary survey held in autumn. We use weather data asmeasured by weather stations, provided by the Royal Netherlands Meteorological Institute (KNMI).This data is used to estimate the influence of weather on travel demand and mode choice in the Netherlands,using regression and choice models respectively. Within our analyses we try to find factorsthat moderate the relationship between weather and travel behaviour, such as urban density and sociodemographics.With respect to the four aspects identified above, we report the following findings:(1) that people use a general perception of the weather during the whole day for their mode choicetravel decisions, which contrasts with the most common practice of using the weather at the trips’departure time.(2) by accounting for the fact that meteorological variables always co-occur in our models we areable to more accurately capture its effect on travel behaviour. The difference with the current practiceof estimating separate effects for each weather variable is particularly stark for days at the extreme endof the observed range of weather variables.(3) The influence of weather on travel behaviour differs more qualitatively between rural and urbanareas: the total effect size of the weather similar, but they are brought upon by different weathervariables. The difference is also very specific to travel modes. For bicyclists the effects of wind speedseem to be more sizeable in urban environments, whilst temperature, rain, and sunshine have smallereffects in urban environments.(4)We find multiple groups of travellers whose responses to weather variations are different from oneanother. These differences seem to be caused by the set of travel modes that are used during averageweather conditions. People that only use the car during average conditions are not very affected, withonly enjoyable weather conditions prompting increased bicycle use. If the car and the bicycle are usedoften people swap between the modes, although use of the bicycle during inclement conditions isrelatively much higher than for the other two groups. The last group has a more multi-modal travelpattern, which results in the largest variations caused by weather. Inclement conditions favour bothpublic transport and the car, with car use increasing quite sharply during wet weather with high windspeeds.Additionally we find that weather variations account for differences in travel behaviour across boththe spatial and temporal dimensions. A particularly surprising finding is that the smaller number ofbike trips in the western provinces of the Netherlands can be fully explained by the fact that there arehigher average wind speeds and lower temperatures in this part of the country.Our results have several implications for the research community and policy makers. We advice researchersto account for the fact that the weather is perceived as a whole and thus that the effect ofone single variable (such as temperature) will depend on the values of other variables. We also foundinteresting subgroups with different reactions with regards to weather. We advice researchers to moreclosely investigate the effects of weather for the separate subgroups. Finally we find sizeable differencesin the effect of weather between different regions, even within the relatively small country of theNetherlands. Researchers studying a relatively large study area would do well to estimate separateeffects for regions within their study area, for example based on population density and geographicallocation.For policy makers our findings imply that there is a sizeable effect of weather that could be usedto improve the forecasts of future travel demand, both in the short- and long terms. Whilst policymakers obviously can’t control the weather, we have found that changing travel patterns or attitudesto travel modes will have repercussions for the effect weather has on travel behaviour. We think thatpolicies aimed at allowing commuters to gain experience with using the bicycle for their daily commuteduring summer, coupled with temporary financial incentives when weather conditions becomeless favourable, could be one way of achieving more cyclists during inclement conditions. Policy makerscould even target younger professionals specifically, as they are much more likely to have alreadydeveloped such habits during their education.Engineering and Policy Analysi