Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging

While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 € - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets

Cadomian metabasites of the Eastern Pyrenees revisited

This study presents a new geochemical, petrological, and geochronological U–Pb dataset from Ediacaran metabasites of the Canigó and Cap de Creus massifs, Eastern Pyrenees. The rocks are composed of calcic amphibole + plagioclase + chlorite + epidote ± quartz plus titanite + apatite + ilmenite ± biotite ± rutile as accessory phases and show relict igneous textures. Peak pressure-temperature determinations share common conditions, ranging 452–482ºC and 5.2–7.7kbar. These intermediate P-T conditions suggest Barrovian-type metamorphism, most likely related to a collisional setting. The metabasites correspond to evolved basaltic rocks (Mg#<0.55) with moderate TiO2 content (up to 2.08wt.%) and relatively low Cr (43–416ppm). The rocks are moderately enriched in light rare earth elements (LREE) relative to heavy rare earth elements (HREE) (average (La/Lu)n of 2.7) and the N-MORB normalized multi-element patterns show negative slopes, with prominent negative Nb anomalies ((Nb/La)NMORB=0.33–0.78). These variations are akin to island arc tholeiites generated in back-arc basins and to other metabasites described in the Eastern Pyrenees with a putative Ediacaran age, and they differ from the Ordovician tholeiitic metabasites from the Canigó massif, which derived from a contaminated E-MORB source. The positive ƐNd(T) values (0.82–3.05) of the studied metabasites preclude a notable contribution from an older continental crust. U-Pb dating (LA-ICP-MS) of one chlorite-rich schist sample in contact with the metabasites from the Canigó massif yielded a main peak at ca. 632Ma. We argue that the Cadomian metabasites from the Pyrenees formed during back-arc extension in the continental margin of Gondwana and were later affected by (probably early Variscan) medium-P metamorphism before the HT-LP metamorphism classically described in the Pyrenees

Cadomian metabasites of the Eastern Pyrenees revisited

This study presents a new geochemical, petrological, and geochronological U–Pb dataset from Ediacaran metabasites of the Canigó and Cap de Creus massifs, Eastern Pyrenees. The rocks are composed of calcic amphibole + plagioclase + chlorite + epidote ± quartz plus titanite + apatite + ilmenite ± biotite ± rutile as accessory phases and show relict igneous textures. Peak pressure-temperature determinations share common conditions, ranging 452–482ºC and 5.2–7.7kbar. These intermediate P-T conditions suggest Barrovian-type metamorphism, most likely related to a collisional setting. The metabasites correspond to evolved basaltic rocks (Mg#<0.55) with moderate TiO2 content (up to 2.08wt.%) and relatively low Cr (43–416ppm). The rocks are moderately enriched in light rare earth elements (LREE) relative to heavy rare earth elements (HREE) (average (La/Lu)n of 2.7) and the N-MORB normalized multi-element patterns show negative slopes, with prominent negative Nb anomalies ((Nb/La)NMORB=0.33–0.78). These variations are akin to island arc tholeiites generated in back-arc basins and to other metabasites described in the Eastern Pyrenees with a putative Ediacaran age, and they differ from the Ordovician tholeiitic metabasites from the Canigó massif, which derived from a contaminated E-MORB source. The positive ƐNd(T) values (0.82–3.05) of the studied metabasites preclude a notable contribution from an older continental crust. U-Pb dating (LA-ICP-MS) of one chlorite-rich schist sample in contact with the metabasites from the Canigó massif yielded a main peak at ca. 632Ma. We argue that the Cadomian metabasites from the Pyrenees formed during back-arc extension in the continental margin of Gondwana and were later affected by (probably early Variscan) medium-P metamorphism before the HT-LP metamorphism classically described in the Pyrenees.This research was financially supported by the Spanish Projects CGL2017-87631-P and PGC2018-093903-B-C22, Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional, Unión Europea. Additional funding was provided by a Margarita Salas grant to NPS by the Universitat de Barcelona with funds from the Ministerio de Universidades/NextGenerationEU/PRTR/Plan de recuperación, transformación y resiliencia

Cadomian metabasites of the Eastern Pyrenees revisited

This study presents a new geochemical, petrological, and geochronological U-Pb dataset from Ediacaran metabasites and associated rocks of the Canigó and Cap de Creus massifs, Eastern Pyrenees. Metabasites are composed of calcic amphibole + plagioclase + chlorite + epidote ± quartz plus titanite + apatite + ilmenite ± biotite ± rutile as accessory phases and show relict igneous textures. Peak pressure-temperature determinations share common conditions, ranging 452-482ºC and 5.2-7.7kbar, which suggest Barrovian-type metamorphism, most likely related to a collisional setting. The metabasites correspond to evolved basaltic rocks (Mg#&lt;0.55) with moderate TiO2 content (up to 2.08wt.%) and relatively low Cr (43-416ppm). The rocks are moderately enriched in Light Rare Earth Elements (LREE) relative to Heavy Rare Earth Elements (HREE) (average (La/Lu)n of 2.7) and the N-MORB normalized multi-element patterns show negative slopes, with prominent negative Nb anomalies ((Nb/La)NMORB=0.33–0.78). These variations are akin to island arc tholeiites generated in back-arc basins and to other metabasites described in the Eastern Pyrenees with a putative Ediacaran age, and they differ from the Ordovician tholeiitic metabasites from the Canigó massif, which derived from a contaminated E-MORB source. The positive ƐNd(T) values (0.82-3.05) of the studied metabasites preclude a notable contribution from an older continental crust. Detrital zircon U-Pb dating Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) of one chlorite-rich schist sample in contact with the metabasites from the Canigó massif yielded a main peak at ca. 632Ma and apparent maximum age of deposition at ca. 550Ma. We argue that the Cadomian metabasites from the Pyrenees formed during back-arc extension in the continental margin of Gondwana and were later affected by (probably early Variscan) medium-P metamorphism before the Low-Pressure High-Temperature (LP-HT) metamorphism classically described in the Pyrenees

New strategies invonving upconverting nanoparticles for determining moderate temperatures by luminescence thermometry

Producción CientíficaHere we analyze alternative luminescence thermometry techniques to FIR, such as intensity ratio luminescence thermometry between the emission arising from two electronic levels that are not necessarily thermally coupled, but that show different evolutions with temperature, and lifetime luminescence nanothermometry in (Ho,Tm,Yb):KLu(WO4)2 and (Er,Yb):NaY2F5O nanoparticles. (Ho,Tm,Yb):KLu(WO4)2 nanoparticles exhibited a maximum relative sensitivity of 0.61% K−1, similar to that achievable in Er-doped systems, which are the upconverting systems presenting the highest sensitivity. From another side, (Er,Yb):NaY2F5O nanocrystals show great potentiality as thermal sensors at the nanoscale for moderate temperatures due to the incorporation of additional non-radiative relaxation mechanisms that shorten the emission lifetime generated by the oxygen present in the structure when compared to (Er,Yb):NaYF4 nanoparticles exhibiting the highest upconversion efficiency. We used those nanoparticles for ex-vivo temperature determination by laser induced heating in chicken breast using lifetime-based thermometry. The results obtained indicate that these techniques might constitute alternatives to FIR with potential applications for the determination of moderate temperatures, with sensitivities comparable to those that can be achieved by FIR or even higher.Ministerio de Economía, Industria y Competitividad (Projects MAT2013-47395-C4-1-4-R, and TEC2014-55948-R)Catalan Government (Projects no. 2014SGR1358 and 2013FI_B 01032

New conservation viewpoints when plants are viewed at one level higher. Integration of phylogeographic structure, niche modeling and genetic diversity in conservation planning of W Mediterranean larkspurs

Protection and management of closely related endangered species and subspecies at a very narrow regional scale is the origin of multiple dysfunctional conservation decisions. These include artificially increased IUCN risk assessment categories and derived consequences: poor effectiveness in allocating public and private funds or repeat of unnecessary actions/facilities. Data provided by the revisited study of a group of W Mediterranean larkspurs (Delphinium ser. Fissa), including new data on demography, niche modeling, genetic diversity and phylogeography, contributed to a new and wider analysis of causes of threat. Although current IUCN Red List regulations did not allow for assessments at levels higher than a specific rank, scientific information suggests that in some cases this could be a better approach for sound scientifically-based biodiversity conservation planning and action

Psychometric properties of a test in evidence based practice: the Spanish version of the Fresno test

<p>Abstract</p> <p>Background</p> <p>Validated instruments are needed to evaluate the programmatic impact of Evidence Based Practice (EBP) training and to document the competence of individual trainees. This study aimed to translate the Fresno test into Spanish and subsequently validate it, in order to ensure the equivalence of the Spanish version against the original English version.</p> <p>Methods</p> <p>Before and after study performed between October 2007 and June 2008. Three groups of participants: (a) Mentors of family medicine residents (expert group) (n = 56); (b) Family medicine physicians (intermediate experience group) (n = 17); (c) Family medicine residents (novice group) (n = 202); Medical residents attended an EBP course, and two sets of the test were administered before and after the course. The Fresno test is a performance based measure for use in medical education that assesses EBP skills. The outcome measures were: inter-rater and intra-rater reliability, internal consistency, item analyses, construct validity, feasibility of administration, and responsiveness.</p> <p>Results</p> <p>Inter-rater correlations were 0.95 and 0.85 in the pre-test and the post-test respectively. The overall intra-rater reliability was 0.71 and 0.81 in the pre-test and post-test questionnaire, respectively. Cronbach's alpha was 0.88 and 0.77, respectively. 152 residents (75.2%) returned both sets of the questionnaire. The observed effect size for the residents was 1.77 (CI 95%: 1.57-1.95), the standardised response mean was 1.65 (CI 95%:1.47-1.82).</p> <p>Conclusions</p> <p>The Spanish version of the Fresno test is a useful tool in assessing the knowledge and skills of EBP in Spanish-speaking residents of Family Medicine.</p

Glucose Restriction Promotes Osteocyte Specification by Activating a PGC-1α-Dependent Transcriptional Program.

Osteocytes, the most abundant of bone cells, differentiate while they remain buried within the bonematrix. This encasement limits their access to nutrients and likely affects their differentiation, a pro-cess that remains poorly defined. Here, we show that restriction in glucose supply promotes the oste-ocyte transcriptional program while also being associated with increased mitochondrial DNA levels.Glucose deprivation triggered the activation of the AMPK/PGC-1 pathway. AMPK and SIRT1 activa-tors or PGC-1aoverexpression are sufficient to enhance osteocyte gene expression in IDG-SW3 cells,murine primary osteoblasts, osteocytes, and organotypic/ex vivobone cultures. Conversely, osteo-blasts and osteocytes deficient inPpargc1aandbwere refractory to the effects of glucose restriction.Finally, conditional ablation of both genes in osteoblasts and osteocytes generate osteopenia andreduce osteocytic gene expression in mice. Altogether, we uncovered a role for PGC-1 in the regula-tion of osteocyte gene expression

Social features of online networks: the strength of intermediary ties in online social media

An increasing fraction of today social interactions occur using online social media as communication channels. Recent worldwide events, such as social movements in Spain or revolts in the Middle East, highlight their capacity to boost people coordination. Online networks display in general a rich internal structure where users can choose among different types and intensity of interactions. Despite of this, there are still open questions regarding the social value of online interactions. For example, the existence of users with millions of online friends sheds doubts on the relevance of these relations. In this work, we focus on Twitter, one of the most popular online social networks, and find that the network formed by the basic type of connections is organized in groups. The activity of the users conforms to the landscape determined by such groups. Furthermore, Twitter's distinction between different types of interactions allows us to establish a parallelism between online and offline social networks: personal interactions are more likely to occur on internal links to the groups (the weakness of strong ties), events transmitting new information go preferentially through links connecting different groups (the strength of weak ties) or even more through links connecting to users belonging to several groups that act as brokers (the strength of intermediary ties).Comment: 14 pages, 18 figure

HMGA1 overexpression in adipose tissue impairs adipogenesis and prevents diet-induced obesity and insulin resistance

High-Mobility-Group-A1 (HMGA1) proteins are non-histone proteins that regulate chromatin structure and gene expression during embryogenesis, tumourigenesis and immune responses. In vitro studies suggest that HMGA1 proteins may be required to regulate adipogenesis. To examine the role of HMGA1 in vivo, we generated transgenic mice overexpressing HMGA1 in adipose tissues. HMGA1 transgenic mice showed a marked reduction in white and brown adipose tissue mass that was associated with downregulation of genes involved in adipogenesis and concomitant upregulation of preadipocyte markers. Reduced adipogenesis and decreased fat mass were not associated with altered glucose homeostasis since HMGA1 transgenic mice fed a regular-chow diet exhibited normal glucose tolerance and insulin sensitivity. However, when fed a high-fat diet, overexpression of HMGA1 resulted in decreased body-weight gain, reduced fat mass, but improved insulin sensitivity and glucose tolerance. Although HMGA1 transgenic mice exhibited impaired glucose uptake in adipose tissue due to impaired adipogenesis, the increased glucose uptake observed in skeletal muscle may account for the improved glucose homeostasis. Our results indicate that HMGA1 plays an important function in the regulation of white and brown adipogenesis in vivo and suggests that impaired adipocyte differentiation and decreased fat mass is not always associated with impaired whole-body glucose homeostasis