Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Eyes, ears, or nose? Comparison of three non-invasive methods to survey wolf recolonisation

The development and use of cost-effective and appropriate survey methods to assess species distribution and to monitor range expansion and contraction of wild populations is crucial due to the limited financial resources for conservation. Of particular importance, yet little studied, is the ability to collect information before a wild population is well established, i.e. at the early stages of recolonisation. During 2018 and 2019, we used camera traps, audio recorders, and scat detection dogs simultaneously to investigate composition, detection probability, and territorial extent of a pack of wolves in the Swiss Alps. We compared the efficacy of these survey methods by assessing sampling effort, data obtained, and costs. We show that, under the presented setup, camera traps and scat detection dogs substantially outperformed audio recorders in detecting wolves, representing the packs’ territorial extent, and revealing the number of adult wolves. The detection dogs did not detect pups but, unlike the other methods, allowed the identification of single individuals. The use of four camera traps during 13 weeks, a 24-km-long transect walked with the detection dog, or the use of one audio recorder during 148 weeks were necessary to obtain a comparable wolf detection probability. Our results show that no single method was able to return all information that we hoped to collect. Comprehensive and cost-effective information was best obtained by combining data from camera traps and detection dogs. We suggest both methods to be simultaneously used to successfully investigate wolf recolonisation into historical range

Spatiotemporal spread of sarcoptic mange in the red fox (Vulpes vulpes) in Switzerland over more than 60 years: lessons learnt from comparative analysis of multiple surveillance tools.

BACKGROUND Sarcoptic mange is a contagious skin disease of wild and domestic mammals caused by the mite Sarcoptes scabiei. Reports of sarcoptic mange in wildlife increased worldwide in the second half of the 20th century, especially since the 1990s. The aim of this study was to provide new insights into the epidemiology of mange by (i) documenting the emergence of sarcoptic mange in the red fox (Vulpes vulpes) in the last decades in Switzerland; and (ii) describing its spatiotemporal spread combining data obtained through different surveillance methods. METHODS Retrospective analysis of archived material together with prospective data collection delivered a large dataset from the 19th century to 2018. Methods included: (i) a review of historical literature; (ii) screening of necropsy reports from general health surveillance (1958-2018); (iii) screening of data on mange (1968-1992) collected during the sylvatic rabies eradication campaign; (iv) a questionnaire survey (<1980-2017) and (v) evaluation of camera-trap bycatch data (2005-2018). RESULTS Sarcoptic mange in red foxes was reported as early as 1835 in Switzerland. The first case diagnosed in the framework of the general health surveillance was in 1959. Prior to 1980, sarcoptic mange occurred in non-adjacent surveillance districts scattered all over the country. During the period of the rabies epidemic (1970s-early 1990s), the percentage of foxes tested for rabies with sarcoptic mange significantly decreased in subregions with rabies, whereas it remained high in the few rabies-free subregions. Sarcoptic mange re-emerged in the mid-1990s and continuously spread during the 2000-2010s, to finally extend to the whole country in 2017. The yearly prevalence of mange in foxes estimated by camera-trapping ranged from 0.1-12%. CONCLUSIONS Sarcoptic mange has likely been endemic in Switzerland as well as in other European countries at least since the mid-19th century. The rabies epidemics seem to have influenced the pattern of spread of mange in several locations, revealing an interesting example of disease interaction in free-ranging wildlife populations. The combination of multiple surveillance tools to study the long-term dynamics of sarcoptic mange in red foxes in Switzerland proved to be a successful strategy, which underlined the usefulness of questionnaire surveys

Hydrotrope-Induced Inversion of Salt Effects on the Cloud Point of an Extended Surfactant

The authors report on the effects of electrolytes spanning a range of (NaOc, NaSCN, NaNO3, NaBr, NaCl, NaBu, NaOAc, Na2SO4, Na2HPO4, and Na2CO3) and (LiCl, NaCl, KCl, CsCl, and choline chloride) on the aq. soly. of an extended surfactant. The surfactant is anionic with a long hydrophobic tail as well as a significant fraction of propylene oxide groups and ethylene oxide groups (C12-14-PO16-EO2-SO4Na, X-AES). In the absence of electrolytes, X-AES exhibits a cloud-point temp. that decreases with increasing surfactant concn. After the addn. of salts to the surfactant solns., various shifts in the soly. curves are obsd. These shifts follow precisely the same Hofmeister series that is found for salting-in and salting-out effects in protein solns. In the presence of different concns. of sodium xylene sulfonate (SXS), the soly. of the surfactant increases. In this context, SXS can be considered to be a salting-in salt. However, when the electrolytes are added to an aq. soln. of X-AES and SXS the Hofmeister series reverses for divalent anions such as Na2SO4, Na2HPO4, and Na2CO3. Studies on the phase behavior and micelle structures using polarization microscopy, freeze-etch TEM, and NMR measurements indicate a dramatic change in the coexisting phases on the addn. of SXS

Specific Anion and Cation Binding to Lipid Membranes Investigated on a Solid Supported Membrane

Ion binding to a lipid membrane is studied by application of a rapid soln. exchange on a solid supported membrane. The resulting charge displacement is analyzed in terms of the affinity of the applied ions to the lipid surface. The authors find that chaotropic anions and kosmotropic cations are attracted to the membrane independent of the membrane compn. In particular, the same behavior is found for lipid headgroups bearing no charge, like monoolein. This general trend is modulated by electrostatic interaction of the ions with the lipid headgroup charge. These results cannot be explained with the current models of specific ion interactions