Population genetics and distribution data reveal conservation concerns to the sky island endemic <Emphasis Type="Italic">Pithecopus megacephalus</Emphasis> (Anura,Phyllomedusidae)

Pithecopus megacephalus is a reticulated monkey–frog species endemic to the highlands of the Espinhaço Mountain Range in southeastern Brazil, an important centre of endemism in South America. This species has a discontinuous distribution and is considered “data-deficient” by the IUCN Red List, raising concerns about its conservation. Understanding the historical dynamics and connectivity of P. megacephalus populations can provide guidelines for preservation of this species in the wild. To investigate the population dynamics of P. megacephalus, we obtained multilocus DNA data for 55 individuals from different locations along the species’ known distribution. Spatial population structure, genetic diversity and demographic parameters were evaluated using population genetic and phylogeographical tools. We also evaluated its extent of occurrence and area of occupancy to investigate extinction risk of this species. We found genetic structure along P. megacephalus’ spatial distribution in the South Espinhaço Mountain Range corresponding to three population groups: northern, central and southern. Our results could provide important data on geographic distribution and population dynamics for a Data Deficient species. Therefore, we suggest these population data, together with the species’ limited occurrence in sky island environments could be used for a more accurate classification of P. megacephalus in the IUCN list, and conservation strategies for the species should be planned accordingly.     

Determining the value contribution of selexipag for the treatment of pulmonary arterial hypertension (PAH) in Spain using reflective multi-criteria decision analysis (MCDA)

Background

Pulmonary Arterial Hypertension (PAH) is a chronic rare disease that can lead to serious cardiovascular problems and death. Additional treatments that increase effectiveness, that are safe and with a convenient administration that improve outcomes and quality of life for patients are needed. The aim of this study was to assess the value contribution of the new, oral prostacyclin receptor agonist, selexipag, for PAH treatment in Spain through reflective Multicriteria Decision Analysis (MCDA) methodology.

Methods

A comprehensive literature review was performed to develop an evidence matrix, composed of twelve quantitative criteria and four contextual criteria, based on an EVIDEM MCDA framework adapted to orphan drugs evaluation by the Spanish region of Catalonia. Quantitative performance scores, qualitative impact of contextual criteria and individual reflections from stakeholders were collected for each MCDA framework criteria. The value contribution of selexipag to PAH treatment compared to inhaled iloprost was calculated.

Results

Oral selexipag for PAH treatment was considered as a treatment which adds value, compared to iloprost, in the following MCDA quantitative criteria: comparative efficacy, patient reported outcomes, preventive benefit, therapeutic benefit, other medical costs and other non-medical costs, without significant differences in safety profile but with a higher acquisition cost than inhaled iloprost.

Conclusions

Selexipag was considered to provide value to PAH treatment. It was perceived as an intervention indicated for a severe rare disease with high unmet needs, supported by high quality clinical evidence. When compared to inhaled iloprost, oral selexipag has demonstrated improvements in efficacy and patient reported outcomes, with a similar safety profile and some additional costs.Reflective MCDA provided a standardised, transparent approach to evaluate multiple criteria relating to the overall value contribution of selexipag to PAH treatment facilitating decision-making.

     

A systematic revision of the <Emphasis Type="Italic">Encyclia adenocarpos</Emphasis> complex (Orchidaceae: Laeliinae) from Megamexico,including two new species from Mexico

The Encyclia adenocarpos complex is restricted to the Pacific slopes of Megamexico, from Sonora, Mexico, to northern Nicaragua. It is characterized by pyriform to suborbicular pseudobulbs, (1-)2-3(4) thickly coriaceous, narrow leaves (> 15 times longer than wide), thin, verruculose inflorescences, and a verruculose ovary. The column is broad and wingless, fused to the labellum at its proximal 1/4. The flowers of the Encyclia adenocarpos complex feature what is here dubbed the Tupperware© labellum-column morphology, where the columnar ventral face is concave and fits tightly around the rim or upper margins of the callus, similar to the seal of this plasticware. All species grow on dry forests at low elevations from sea level to ca. 1500 m; most populations occurring below 500 m. The complex consists of six species, two of which are newly described herein: E. acapulcensis sp. nov., from southern Guerrero and E. enriquearcilae sp. nov., from western Oaxaca and neighboring Guerrero, Mexico. Encyclia rodolfoi is the correct name for populations of the Tehuantepec Isthmus whereas E. × nizandensis is here regarded as a natural hybrid between E. rodolfoi and E. parviflora; the evidence is presented and discussed. Encyclia schaeferi is treated as a morph of E. papillosa and included in its synonymy. A neotype is selected for Epidendrum adenocarpos and Epidendrum crispatum is rejected as a synonym thereof. All species are illustrated and discussed, and a key to the species is presented. Furthermore, the conservation status of each species is analyzed under the IUCN methodology. Other aspects of the biology of this complex are also discussed.     

Assessment of an ultra-sensitive IFNγ immunoassay prototype for latent tuberculosis diagnosis

Worldwide there are about 1.7 billion individuals with latent tuberculosis infection (LTBI) and only 5% to 15% will develop active tuberculosis (TB). It is recommended to treat only those most at risk of developing active TB to avoid problems of drug resistance. LTBI diagnosis involves reviewing the individual’s medical history, physical examination, and biological tests. Interferon gamma release assays (IGRA) can yield “undeterminate” or “uncertain” results, which makes clinical management decisions difficult. We assessed an ultra-sensitive immunoassay prototype based on single molecule array (SiMoA) technology to evaluate its overall performance, and in particular, its performance for indeterminate and uncertain positive or negative samples, as classified by the results from the current ELISA technique used for IFNγ quantification. We analyzed samples from hospitalized or consulting patients and healthcare workers from three hospitals in Paris, previously classified as negative (n = 30), positive (n = 35), uncertain negative (n = 25), uncertain positive (n = 31), or indeterminate (n = 30). We observed that with the SiMoA assay 83.3% of the indeterminate samples became interpretable and could be classified as negative, whereas 74% of uncertain positive samples were classified as positive. Most uncertain negative samples (72%) were reclassified as uncertain positive (68%) or positive (4%). The results suggest that the ultra-sensitive SiMoA IFNγ assay could represent a useful tool for the identification of true positive and negative samples among those giving indeterminate or uncertain results with the TB IGRA assay currently used.     

Efficiency and Significance of Multiple Vocal Signals in Sibling Competition

Animals can compete for resources by displaying various acoustic signals that may differentially affect the outcome of competition. We propose the hypothesis that the most efficient signal to deter opponents should be the one that most honestly reveals motivation to compete. We tested this hypothesis in the barn owl (Tyto alba) in which nestlings produce more calls of longer duration than siblings to compete for priority access to the indivisible prey item their parents will deliver next. Because nestlings increase call rate to a larger extent than call duration when they become hungrier, call rate would signal more accurately hunger level. This leads us to propose three predictions. First, a high number of calls should be more efficient in deterring siblings to compete than long calls. Second, the rate at which an individual calls should be more sensitive to variation in the intensity of the sibling vocal competition than the duration of its calls. Third, call rate should influence competitors’ vocalization for a longer period of time than call duration. To test these three predictions we performed playback experiments by broadcasting to singleton nestlings calls of varying durations and at different rates. According to the first prediction, singleton nestlings became less vocal to a larger extent when we broadcasted more calls compared to longer calls. In line with the second prediction, nestlings reduced vocalization rate to a larger extent than call duration when we broadcasted more or longer calls. Finally, call rate had a longer influence on opponent’s vocal behavior than call duration. Young animals thus actively and differentially use multiple signaling components to compete with their siblings over parental resources.     

Polymorphism of DNA conformation inside the bacteriophage capsid

Double-stranded DNA bacteriophage genomes are packaged into their icosahedral capsids at the highest densities known so far (about 50 % w:v). How the molecule is folded at such density and how its conformation changes upon ejection or packaging are fascinating questions still largely open. We review cryo-TEM analyses of DNA conformation inside partially filled capsids as a function of the physico-chemical environment (ions, osmotic pressure, temperature). We show that there exists a wide variety of DNA conformations. Strikingly, the different observed structures can be described by some of the different models proposed over the years for DNA organisation inside bacteriophage capsids: either spool-like structures with axial or concentric symmetries, or liquid crystalline structures characterised by a DNA homogeneous density. The relevance of these conformations for the understanding of DNA folding and unfolding upon ejection and packaging in vivo is discussed.     

Mitochondrial membrane lipid remodeling in pathophysiology: A new target for diet and therapeutic interventions

Mitochondria are arbiters in the fragile balance between cell life and death. These organelles present an intricate membrane system, with a peculiar lipid composition and displaying transverse as well as lateral asymmetry. Some lipids are synthesized inside mitochondria, while others have to be imported or acquired in the form of precursors. Here, we review different processes, including external interventions (e.g., diet) and a range of biological events (apoptosis, disease and aging), which may result in alterations of mitochondrial membrane lipid content. Cardiolipin, the mitochondria lipid trademark, whose biosynthetic pathway is highly regulated, will deserve special attention in this review. The modulation of mitochondrial membrane lipid composition, especially by diet, as a therapeutic strategy for the treatment of some pathologies will be also addressed.     

Material and Energy Flows and Environmental Impacts of the Internet in Switzerland

The Internet leads to material and energy consumption as well as various environmental impacts on both the regional and global scale. Yet, assessments of the Internet's energy consumption and resulting greenhouse gas emissions are still rare, and assessments of material flows and further environmental impacts are virtually non‐existent. This article investigates material flows, the direct energy consumption during the use phase, as well as environmental impacts linked to the service, “Internet in Switzerland.” In our model, the service, Internet in Switzerland, is divided into various Internet participant categories. All devices used to access or provide Internet services are merged in a limited number of equipment families and, as such, included in an inventory of the existing infrastructure (stock). Based on this inventory, a material flow analysis (MFA) is performed, which includes the current stock as well as flows resulting from growth and disposal. The direct energy consumption for the operation of the infrastructure is quantified. Environmental impacts are calculated with a life cycle assessment approach, using the ecoinvent database and the software, SimaPro, applying four different methods. The MFA results in a 2009 stock of 98,100 tonnes. Approximately 4,130 gigawatt hours per year, or 7% of the total Swiss electricity consumption, were used in 2009 to operate the Swiss infrastructure. The environmental impacts caused during the production and use phases vary significantly depending on the assessment method chosen. The disposal phase had mainly positive impacts as a result of material recovery.     

Seasonal Variation of Suicide in Brazil

Most of what is known about the seasonal variation in suicide rate originates from studies conducted in the northern hemisphere; very few studies have been done in the southern hemisphere. The purpose of the present study was to explore the possibility that in Brazil, the seasonal variation of suicides is a function of photoperiod. This was accomplished by analyzing monthly suicide data for a 12 yr period (1979 to 1990), within latitudes ranging from 2°N to 33°S. Single cosinor analyses with periods of 12 or 6 months were applied to time series of monthly total and suicidal deaths, separated by gender and state. Significant spring or early summer peaks of suicide were found only in the south of Brazil for both men and women, except for the latter in one state. These peaks did not coincide with those found for total deaths, which occurred in the autumn or winter in all areas. No significant six‐month period was found. In the present study, the chance of a suicide was typically 10–17% higher during the peak period than during the other months of the year. Although this moderate seasonal effect might not be sufficient to justify planning large scale prophylactic interventions, those dealing with patients who have suicide ideation should be aware of this high risk time.