Ontogeny of postcranial morphology and locomotor behavior in Propithecus verreauxi coquereli and Lemur catta

Despite living under the same environmental pressures and sympatrically in many cases, Propithecus verreauxi and Lemur catta have evolved very different strategies for survival in stochastic environmental conditions. P. verreauxi show slow somatic growth, low maternal investment, and rapid dental growth while L. catta show faster somatic growth, high maternal investment, and slower dental growth. P. v. coquereli are highly specialized for vertical clinging and leaping (VCL) among lemurs, while L. catta, the most terrestrial of lemurs, use a wider variety of locomotor types including quadrupedalism, climbing, and leaping. P. v. coquereli have unusually long legs and muscular thighs while L. catta have more similar limb lengths and muscular proximal limb segments (Lessertisseur and Jouffroy, 1973; Jouffroy, 1975). Little is known of the ontogenetic trajectories by which these adult forms are acquired. Because selection acts on the entire life cycle of an animal, it is important to investigate the morphological and locomotor changes occurring early in development. These changes might be important components to each species’ survival strategy that allow infant primates to travel with a group of larger adults and survive to adulthood. I examined changes in locomotor behavior and limb morphology from 0-2 years in L. catta and P. v. coquereli. Limb segment lengths, limb segment circumferences, and body mass were recorded every 2 weeks in infants and every 4 weeks in yearlings at the Duke Lemur Center (DLC). Locomotor data were collected on infants transitioning to locomotor independence and yearlings of each species in free-ranging enclosures at the DLC using locomotor bout sampling. Results indicate that both species are born with upper limb lengths similar to lower limb lengths, whereas only P. v. coquereli dissociates upper- and lower limb growth to reach adult limb proportions. P. v. coquereli transitional infants and yearlings use similar overall locomotor behavior and undergo rapid postcranial growth to achieve the limb proportions necessary for VCL by the time of locomotor independence. Relative to upper limb length, lower limb length is even longer in juveniles first leaping independently than in yearlings and adults. Relatively long hindlimbs may allow juveniles to achieve leaping take-off velocity similar to adults despite absolutely smaller size. L. catta transitional infants exhibit a different distribution of locomotor behavior than yearlings despite similarities in limb proportions. Much like P. v. coquereli juveniles are “ecological adults” in terms of their rapid dental development, they seem to also be “ecological adults” in terms of locomotor behavior. Because of the demand for using VCL at a young age, and despite overall slow postcranial growth, P. v. coquereli transitional infants are on a rapid growth trajectory towards achieving the limb proportions necessary for specialized leaping. Lowest IMI values at locomotor independence, increased leap frequency paired with decreased leap distance, and high positive allometric growth of the tail are three key findings that provide evidence as to how P. v. coquereli transitional infants are able to display similar locomotor repertoires as yearlings in order to keep up with the group to survive, despite being absolutely smaller

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients — the randomized, EU-wide, placebo-controlled, phase II study design of IXION

Background: More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients. Methods: IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (>= 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4-6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 x 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability. Discussion: With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for