The effects of noise from combined traffic sources on annoyance: the case of interactions between rail and road noise (invited paper)

C

The effects of railway noise on sleep medication intake: results from the ALPNAP-study

In the 1980s/90s, a number of socio-acoustic surveys and laboratory studies on railway noise effects have observed less reported disturbance/interference with sleep at the same exposure level compared with other modes of transportation. This lower grade of disturbance has received the label "railway bonus", was implemented in noise legislation in a number of European countries and was applied in planning and environmental impact assessments. However, majority of the studies investigating physiological outcomes did not find the bespoke difference. In a telephone survey (N=1643) we investigated the relationship between railway noise and sleep medication intake and the impact of railway noise events on motility parameters during night was assessed with contact-free high resolution actimetry devices. Multiple logistic regression analysis with cubic splines was applied to assess the probability of sleep medication use based on railway sound level and nine covariates. The non-linear exposure-response curve showed a statistically significant leveling off around 60 dB (A), Lden. Age, health status and trauma history were the most important covariates. The results were supported also by a similar analysis based on the indicator "night time noise annoyance". No railway bonus could be observed above 55 dB(A), Lden. In the actimetry study, the slope of rise of train noise events proved to be almost as important a predictor for motility reactions as was the maximum sound pressure level - an observation which confirms similar findings from laboratory experiments and field studies on aircraft noise and sleep disturbance. Legislation using a railway bonus will underestimate the noise impact by about 10 dB (A), Lden under the conditions comparable with those in the survey study. The choice of the noise calculation method may influence the threshold for guideline setting

Influence of land-use intensification on vegetation C-stocks in an alpine valley from 1865 to 2003

The role of ecosystems as carbon (C) sinks or sources is intrinsically related to land-use intensity, which determines the land required for biomass production. Here, we systematically investigate the role of different land-use types including their land-use intensities on vegetation C-stocks (SCact) in the Stubai valley, located in the Austrian central Alps. After a period of high land-use impacts until 1954, indicated by massive C-depletion, land-use shifted to completely new courses. Polarization into high-intensity low-land areas and extensification at higher altitudes allowed for a tripling of SCact until 2003. The most important land-use change was the intensification of the livestock sector accompanied by abandonment of extensive grasslands and reduced harvest pressure on forests after WWII. Market integration, abundance of fossil energy carriers, as well as structural change of the economy were important underlying socio-economic drivers of these trends. However, despite this remarkable SCact increase, SCact amounted to only 62% of the potential carbon stocks (SCpot) in 2003. Although conversion of forests to agriculture clearly contributed the lion's share to this SC-gap, forest management explains roughly one quarter of the SC-difference. We found that time-lags between land-use shifts and the establishment of a new C-climax had fundamental repercussions on recent C-dynamics in the study region. Apparently, the land system is still net-accumulating C, although land-use changes have peaked decades earlier. Our findings are crucial for the understanding of C-dynamics, including the role of land management and time-lags in mountainous regions, which are regarded key areas for terrestrial C-sequestration

Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach

The serine protease Factor XI (FXI) is a prominent drug target as it holds promise to deliver efficacious anti-coagulation without an enhanced risk of major bleeds. Several efforts have been described targeting the active form of the enzyme, FXIa. Herein we disclose our efforts to identify potent, selective, and orally bioavailable inhibitors of FXIa. Compound 1, identified from a diverse library of internal serine protease inhibitors, was originally designed as a complement Factor D inhibitor and exhibited sub-micromolar FXIa activity and an encouraging ADME profile while being devoid of peptidomimetic architecture. Optimization of interactions in the S1, S1β, and S1` pockets of FXIa through a combination of structure-based drug design and traditional medicinal chemistry led to the discovery of compound 23 with sub-nanomolar potency on FXIa, enhanced selectivity over other coagulation proteases, and a pre-clinical PK profile consistent with bid dosing in patients