Efficacy and safety of LAU-7b in a Phase 2 trial in adults with cystic fibrosis.

Background: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF.

Methods: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF.

Adaptive designs in dermatology clinical trials: Current status and future perspectives.

Current drug development strategies present many challenges that can impede drug approval by regulatory agencies. Alternative study models, such as adaptive trial designs, have recently sparked interest, as they provide a flexible and more efficient approach in conducting clinical trials. Adaptive trial designs offer several potential benefits over traditional randomized controlled trials, which include decrease in costs, reduced clinical development time and limiting exposure of patients to potentially ineffective treatments allowing completion of studies with fewer patients.

Phase II study investigating the efficacy and safety of glesatinib (MGCD265) in patients with advanced NSCLC containing MET activating alterations.

Objectives: Dysregulated signaling by mesenchymal epithelial transition factor (MET) and heightened AXL activation are implicated in the pathogenesis of non-small cell lung cancer (NSCLC). Glesatinib (MGCD265) is an investigational, oral inhibitor of MET and AXL.

Materials And Methods: This open-label, Phase II study investigated glesatinib (free-base suspension [FBS] capsule 1050 mg BID or spray-dried dispersion [SDD] tablet 750 mg BID) in patients with advanced, previously treated NSCLC across four cohorts grouped according to presence of MET activating mutations or amplification in tumor or ctDNA.

Candidate gene polymorphisms are linked to dispersive and migratory behaviour: Searching for a mechanism behind the "paradox of the great speciators".

The "paradox of the great speciators" has puzzled evolutionary biologists for over half a century. A great speciator requires excellent dispersal propensity to explain its occurrence on multiple islands, but reduced dispersal ability to explain its high number of subspecies. A rapid reduction in dispersal ability is often invoked to solve this apparent paradox, but a proximate mechanism has not been identified yet.

Adaptive significance of affiliative behaviour differs between sexes in a wild reptile population.

In recent years, we have begun to appreciate that social behaviours might exhibit repeatable among-individual variation. Such behavioural traits may even covary and have critical evolutionary implications. Importantly, some social behaviours such as aggressiveness have been shown to provide fitness benefits, including higher reproductive success and survival.

Effect of tesamorelin in people with HIV with and without dorsocervical fat: Post hoc analysis of phase III double-blind placebo-controlled trial.

Tesamorelin, a synthetic growth hormone-releasing hormone, is indicated for the reduction of visceral adipose tissue (VAT) in people with HIV. Here, we performed a post hoc analysis of participants receiving tesamorelin for 26 weeks in a phase III clinical trial. Efficacy data were compared between individuals with and without dorsocervical fat, stratified by tesamorelin response.

Unexpected Pathogen Diversity Detected in Australian Avifauna Highlights Potential Biosecurity Challenges.

Birds may act as hosts for numerous pathogens, including members of the family , (BFDV), avipoxviruses, (CoAHV1) and (PsAHV1), all of which are a significant biosecurity concern in Australia. While and BFDV have previously been detected in Australian avian taxa, the prevalence and host range of avipoxviruses, CoAHV1 and PsAHV1 in Australian birds remain undetermined. To better understand the occurrence of these pathogens, we screened 486 wild birds (kingfisher, parrot, pigeon and raptor species) presented to two wildlife hospitals between May 2019 and December 2021.

Phase I Study Evaluating Glesatinib (MGCD265), An Inhibitor of MET and AXL, in Patients with Non-small Cell Lung Cancer and Other Advanced Solid Tumors.

Background: Heightened signaling by mesenchymal epithelial transition factor (MET) is implicated in tumorigenesis. Glesatinib is an investigational, oral inhibitor of MET and AXL.

Objective: This phase I study determined the maximum tolerated dose (MTD), recommended phase II dose (RP2D), and safety profile of glesatinib in patients with advanced or unresectable solid tumors.

First Randomized, Multicenter, Placebo-Controlled Study of Self-Administered Intranasal Etripamil for Acute Conversion of Spontaneous Paroxysmal Supraventricular Tachycardia (NODE-301).

Background: Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT.

A new candling procedure for thick and opaque eggs and its application to avian conservation management.

The ability to monitor developing avian embryos and their associated vascular system via candling enables the application of important reproductive management techniques. Egg candling facilitates the confirmation of egg viability throughout the incubation process and identification of a precise position on a vein for the safe extraction of blood. Blood samples may then be analysed to retrieve vital health and genetic information to assist in conservation management.

Phase I Study of Glesatinib (MGCD265) in Combination with Erlotinib or Docetaxel in Patients with Advanced Solid Tumors.

Background: Oncogenic drivers in solid tumors include aberrant activation of mesenchymal epithelial transition factor (MET) and AXL.

Objective: This study investigated the safety and antitumor activity of glesatinib, a multitargeted receptor tyrosine kinase inhibitor that inhibits MET and AXL at clinically relevant doses, in combination with erlotinib or docetaxel.

Patients And Methods: The phase I portion of this open-label, multicenter study included two parallel arms in which ascending doses of oral glesatinib (starting dose 96 mg/m) were administered with erlotinib or docetaxel (starting doses 100 mg once daily and 50 mg/m, respectively) using a modified 3 + 3 design.

Limited effects of traffic noise on behavioural responses to conspecific mating calls in the eastern sedge frog .

Unlabelled: Anthropogenic noise is a pervasive environmental feature across both urban and non-urban habitats and presents a novel challenge especially for acoustically communicating species. While it is known that some species adjust acoustic signals to communicate more effectively in noisy habitats, we know very little about how the receivers of these signals might be impacted by anthropogenic noise. Here, we investigated female and male frogs' ability to distinguish between high- and low-quality acoustic signals during the presence of background traffic noise and without.

Use of anthropogenic-related nest material and nest parasite prevalence have increased over the past two centuries in Australian birds.

Global plastic production has increased exponentially since the 1940s, resulting in the increased presence of anthropogenic debris in the environment. Recent studies have shown that birds incorporate anthropogenic debris into their nests, which can reduce nest ectoparasite loads. However, we know little about the long-term history of interactions among birds, anthropogenic debris, and ectoparasites.

Characteristics and relationship between hyperphagia, anxiety, behavioral challenges and caregiver burden in Prader-Willi syndrome.

Objectives: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by maladaptive behaviors, amongst which hyperphagia is a life-long concern for individuals with PWS and their caregivers. The current study examined the contribution of hyperphagia and other factors to caregiver burden across lifespan, in 204 caregivers of individuals with PWS living in the US, using the Zarit Burden Interview (ZBI) and the hyperphagia questionnaire (HQ-CT).

Results: We found a strong relationship between ZBI and HQ-CT especially in individuals with PWS older than 4 y and showed that HQ-CT scores of individuals with PWS is positively correlated with ZBI scores of their caregivers.

Parents report fewer executive functioning problems and repetitive behaviors in young dual-language speakers with autism.

More dual language learners (DLLs) are being identified early with autism spectrum disorder (ASD). However, many families are still being advised against dual language exposure, despite a lack of evidence of negative impacts on language development in ASD. Research in typically developing children has noted advantages for bilinguals in domains such as executive functioning and social skills, but less is known about the effects in ASD.

Production of recycled manure solids for use as bedding in Canadian dairy farms: II. Composting methods.

Recent technological advances in the dairy industry have enabled Canadian farms with liquid manure systems to use mechanical solid-liquid separation paired with composting of the separated solids for on-farm production of low-cost bedding material. However, because several approaches are available, it is difficult for farmers to select the appropriate one to achieve high quality recycled manure solids (RMS). Whereas 3 solid-liquid manure separators were compared in part I of the series (companion paper in this issue), the present study (part II) aims to assess the performance of 4 composting methods (static or turned windrow and drum composter for 24 or 72 h) under laboratory conditions.

Mocetinostat for patients with previously treated, locally advanced/metastatic urothelial carcinoma and inactivating alterations of acetyltransferase genes.

Background: The authors evaluated mocetinostat (a class I/IV histone deacetylase inhibitor) in patients with urothelial carcinoma harboring inactivating mutations or deletions in CREB binding protein [CREBBP] and/or E1A binding protein p300 [EP300] histone acetyltransferase genes in a single-arm, open-label phase 2 study.

Methods: Eligible patients with platinum-treated, advanced/metastatic disease received oral mocetinostat (at a dose of 70 mg 3 times per week [TIW] escalating to 90 mg TIW) in 28-day cycles in a 3-stage study (ClinicalTrials.gov identifier NCT02236195).

Birds Learn Socially to Recognize Heterospecific Alarm Calls by Acoustic Association.

Animals in natural communities gain information from members of other species facing similar ecological challenges [1-5], including many vertebrates that recognize the alarm calls of heterospecifics vulnerable to the same predators [6]. Learning is critical in explaining this widespread recognition [7-13], but there has been no test of the role of social learning in alarm-call recognition, despite the fact that it is predicted to be important in this context [14, 15]. We show experimentally that wild superb fairy-wrens, Malurus cyaneus, learn socially to recognize new alarm calls and can do so through the previously undemonstrated mechanism of acoustic-acoustic association of unfamiliar with known alarm calls.