Galaxies in voids assemble their stars slowly.

Galaxies in the Universe are distributed in a web-like structure characterized by different large-scale environments: dense clusters, elongated filaments, sheetlike walls and under-dense regions, called voids1-5. The low density in voids is expected to affect the properties of their galaxies. Indeed, previous studies6-14 have shown that galaxies in voids are, on average, bluer and less massive, and have later morphologies and higher current star formation rates than galaxies in denser large-scale environments. However, it has never been observationally proved that the star formation histories (SFHs) in voids are substantially different from those in filaments, walls and clusters. Here we show that void galaxies have had, on average, slower SFHs than galaxies in denser large-scale environments. We also find two main SFH types present in all the environments: 'short-timescale' galaxies are not affected by their large-scale environment at early times but only later in their lives; 'long-timescale' galaxies have been continuously affected by their environment and stellar mass. Both types have evolved more slowly in voids than in filaments, walls and clusters.

Decay of HIV RNA in Seminal Plasma and Rectal Fluid in Treatment-Naive Adults Starting Antiretroviral Therapy With Dolutegravir Plus Lamivudine or Bictegravir/Emtricitabine/Tenofovir Alafenamide.

BACKGROUND: Decay of HIV in seminal plasma (SP) and rectal fluid (RF) has not yet been described for the antiretroviral combination of dolutegravir (DTG) + lamivudine (3TC). METHODS: In this randomized multicenter pilot trial, males who were antiretroviral naive were randomized (2:1) to DTG + 3TC or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). HIV-1 RNA was measured in blood plasma (BP), SP, and RF at baseline; days 3, 7, 14, and 28; and weeks 12 and 24. RESULTS: Of 25 individuals enrolled, 24 completed the study (DTG + 3TC, n = 16; BIC/FTC/TAF, n = 8). No significant differences were observed between groups for median decline in HIV-1 RNA from baseline at each time point or median time to achieve HIV-1 RNA <20 copies/mL in BP and SP and <20 copies/swab in RF. HIV-1 RNA decay patterns were compared in individuals receiving DTG + 3TC. Despite significantly higher percentages for changes from baseline in BP, median (IQR) times to HIV-1 RNA suppression were shorter in SP (7 days; 0-8.75) and RF (10.5 days; 3-17.5) than in BP (28 days; 14-84; P < .001). CONCLUSIONS: Comparable HIV-1 RNA decay in BP, SP, and RF was observed between DTG + 3TC and BIC/FTC/TAF. As shown with triple-drug integrase inhibitor-based regimens, rapid HIV-1 RNA suppression in SP and RF is achieved with DTG + 3TC, despite decay patterns differing from those of BP. CLINICAL TRIALS REGISTRATION: EudraCT 2019-004109-28.

Case report: BA.1 subvariant showing a BA.2-like pattern using a variant-specific PCR assay due to a single point mutation downstream the spike 69/70 deletion.

BACKGROUND: SARS-CoV-2 variant tracking is key to the genomic surveillance of the COVID-19 pandemic. While next-generation sequencing (NGS) is commonly used for variant determination, it is expensive and time-consuming. Variant-specific PCR (vsPCR) is a faster, cheaper method that detects specific mutations that are considered variant-defining. These tests usually rely on specific amplification when a mutation is present or a specific melting temperature peak after amplification. CASE PRESENTATION: A discrepant result between vsPCR and NGS was found in seventeen SARS-CoV-2 samples from Galicia, Spain. A cluster of BA.1 Omicron SARS-CoV-2 variant showed a BA.2-like melting temperature pattern due to a point mutation (C21772T) downstream the deletion of the spike amino acids 69/70. As the 69/70 deletion is widely used for differentiation between BA.1 and BA.2 by vsPCR, C21772T can cause BA.1 samples to be misinterpreted as BA.2. Over a thousand BA.1 sequences in the EpiCoV database contain this mutation. CONCLUSIONS: To our knowledge, this is the first case of a point mutation causing a vsPCR algorithm to misclassify BA.1 samples as BA.2. This is an example of how mutations in the probe target area of vsPCR tests based on melting curve analysis can lead to variant misclassification. NGS confirmation of vsPCR results is relevant for the accuracy of the epidemiological surveillance. In order to overcome the possible impact of novel mutations, diagnostic tools must be constantly updated.

Dynamics of the Decay of Human Immunodeficiency Virus (HIV) RNA and Distribution of Bictegravir in the Genital Tract and Rectum in Antiretroviral-naive Adults Living With HIV-1 Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (Spanish HIV/AIDS Research Network, PreEC/RIS 58).

BACKGROUND: The pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)-1 RNA in genital fluids and the rectum have not yet been addressed. METHODS: We conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: The study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41-3.79), 4.19 (2.98-4.70), and 2.56 (1.61-3.56) log10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1-923) ng/mL, 74.1 (6.0-478.5) ng/g, and 61.6 (14.4-1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively. CONCLUSIONS: BIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL). CLINICAL TRIALS REGISTRATION: EudraCT 2018-002310-12.

[Health consequences (mortality and institutionalization) of hip fracture among the elderly people: Population cohort study in Segovia]. / Consecuencias en salud (mortalidad e institucionalización) de la fractura de cadera en la población anciana. Estudio de cohortes poblacional en Segovia.

OBJECTIVE: In order to know the social and health consequences of hip fractures (HF). DESIGN: A retrospective cohort study of an entire health area was carried out in patients aged 75 or more, over a period of 5 years. SITE: Segovia Health Area. PARTICIPANTS: All patients older than 75 years with a diagnosis of HF, excluding displaced and passerby. INTERVENTIONS: The socio-sanitary changes that occur after the HF in respect to their baseline situation (family situation, comorbidities, dependence and mental situation) and the variables which most influence mortality and institutionalization after the HF were analyzed. MAIN MEASUREMENTS: One thousand one hundred fifty-nine HF were recorded, with a constant annual incidence of 10.7‰. The prevalence was higher in women: 7.4% versus 3.7%. RESULTS: The baseline profile is a pluripatological, non-institutionalized, 87-year-old woman, who retains her independent in her daily life and suffers from a HF due to an accidental fall in her home. At the end of the study period 51% were permanently institutionalized, negatively influencing having worse mental deterioration, worse dependence and subsequent readmissions and in addition, 45.5% died, 25.5% during the first year. The most unfavorable conditions were being previously dependent, having severe mental deterioration, male and within the comorbidities the most influential was previously having an anemia. CONCLUSIONS: Our data confirms the deterioration of the autonomy-functional capacity after a HF, in line with what has been published, and has allowed to identify which elderly people are at the greatest risk of complications in the short and medium term (institutionalization and death).

Total and Unbound Bictegravir Concentrations and Viral Suppression in Cerebrospinal Fluid of Human Immunodeficiency Virus-Infected Patients (Spanish HIV/AIDS Research Network, PreEC/RIS 56).

We determined total and unbound concentrations of bictegravir (BIC) in cerebrospinal fluid (CSF) in 15 asymptomatic, virologically suppressed patients. The median plasma and CSF total BIC concentrations were 1837.1 ng/mL (interquartile range [IQR], 1237.2-2586.7) and 6.9 (IQR, 4.8-10.9), respectively. Median unbound BIC concentration was 2.48 ng/mL (IQR, 1.6-3.7). Total and unbound BIC CSF concentrations were above the half-maximal effective concentration value in all patients, and all subjects had human immunodeficiency virus viral suppression in plasma and CSF. Bictegravir may contribute to inhibit viral replication in this compartment.

Spatial Charge Separation as the Origin of Anomalous Stark Effect in Fluorous 2D Hybrid Perovskites.

2D hybrid perovskites (2DP) are versatile materials, whose electronic and optical properties can be tuned through the nature of the organic cations (even when those are seemingly electronically inert). Here, it is demonstrated that fluorination of the organic ligands yields glassy 2DP materials featuring long-lived correlated electron-hole pairs. Such states have a marked charge-transfer character, as revealed by the persistent Stark effect in the form of a second derivative in electroabsorption. Modeling shows that electrostatic effects associated with fluorination, combined with the steric hindrance due to the bulky side groups, drive the formation of spatially dislocated charge pairs with reduced recombination rates. This work enriches and broadens the current knowledge of the photophysics of 2DP, which will hopefully guide synthesis efforts toward novel materials with improved functionalities.

Azatruxene-Based, Dumbbell-Shaped, Donor-π-Bridge-Donor Hole-Transporting Materials for Perovskite Solar Cells.

Three novel donor-π-bridge-donor (D-π-D) hole-transporting materials (HTMs) featuring triazatruxene electron-donating units bridged by different 3,4-ethylenedioxythiophene (EDOT) π-conjugated linkers have been synthesized, characterized, and implemented in mesoporous perovskite solar cells (PSCs). The optoelectronic properties of the new dumbbell-shaped derivatives (DTTXs) are highly influenced by the chemical structure of the EDOT-based linker. Red-shifted absorption and emission and a stronger donor ability were observed in passing from DTTX-1 to DTTX-2 due to the extended π-conjugation. DTTX-3 featured an intramolecular charge transfer between the external triazatruxene units and the azomethine-EDOT central scaffold, resulting in a more pronounced redshift. The three new derivatives have been tested in combination with the state-of-the-art triple-cation perovskite [(FAPbI3 )0.87 (MAPbBr3 )0.13 ]0.92 [CsPbI3 ]0.08 in standard mesoporous PSCs. Remarkable power conversion efficiencies of 17.48 % and 18.30 % were measured for DTTX-1 and DTTX-2, respectively, close to that measured for the benchmarking HTM spiro-OMeTAD (18.92 %), under 100 mA cm-2 AM 1.5G solar illumination. PSCs with DTTX-3 reached a PCE value of 12.68 %, which is attributed to the poorer film formation in comparison to DTTX-1 and DTTX-2. These PCE values are in perfect agreement with the conductivity and hole mobility values determined for the new compounds and spiro-OMeTAD. Steady-state photoluminescence further confirmed the potential of DTTX-1 and DTTX-2 for hole-transport applications as an alternative to spiro-OMeTAD.

Tetrasubstituted Thieno[3,2-b]thiophenes as Hole-Transporting Materials for Perovskite Solar Cells.

Three hole-transporting materials (HTMs) were prepared following a straightforward synthetic route by cross-linking arylamine-based ligands with a simple thieno[3,2-b]thiophene (TbT) core. The novel HTMs were fully characterized with standard techniques to gain insight into their optical and electrochemical properties and were incorporated in solution-processed mesoporous (FAPbI3)0.85(MAPbBr3)0.15 perovskite-based solar cells. The similar molecular structure of the synthesized HTMs was leveraged to investigate the role that the bridging units between the conjugated TbT core and the peripheral arylamine units plays on their properties and thereby on the photovoltaic response. A remarkable power conversion efficiency exceeding 18% was achieved for one of the TbT derivatives, which was slightly higher than the value measured for the benchmark spiro-OMeTAD.

Pooling for SARS-CoV-2 control in care institutions.

BACKGROUND: Workers and residents in Care Homes are considered at special risk for the acquisition of SARS-CoV-2 infection, due to the infectivity and high mortality rate in the case of residents, compared to other containment areas. The role of presymptomatic people in transmission has been shown to be important and the early detection of these people is critical for the control of new outbreaks. Pooling strategies have proven to preserve SARS-CoV-2 testing resources. The aims of the present study, based in our local experience, were (a) to describe SARS-CoV-2 prevalence in institutionalized people in Galicia (Spain) during the Coronavirus pandemic and (b) to evaluate the expected performance of a pooling strategy using RT-PCR for the next rounds of screening of institutionalized people. METHODS: A total of 25,386 Nasopharyngeal swab samples from the total of the residents and workers at Care Homes in Galicia (March to May 2020) were individually tested using RT-PCR. Prevalence and quantification cycle (Cq) value distribution of positives was calculated. Besides, 26 pools of 20 samples and 14 pools of 5 samples were tested using RT-PCR as well (1 positive/pool). Pooling proof of concept was performed in two populations with 1.7 and 2% prevalence. RESULTS: Distribution of SARS-CoV-2 infection at Care Homes was uneven (0-60%). As the virus circulation global rate was low in our area (3.32%), the number of people at risk of acquiring the infection continues to be very high. In this work, we have successfully demonstrated that pooling of different groups of samples at low prevalence clusters, can be done with a small average delay on Cq values (5 and 2.85 cycles for pools of 20 and 5 samples, respectively). CONCLUSIONS: A new screening system with guaranteed protection is required for small clusters, previously covered with individual testing. Our proposal for Care Homes, once prevalence zero is achieved, would include successive rounds of testing using a pooling solution for transmission control preserving testing resources. Scale-up of this method may be of utility to confront larger clusters to avoid the viral circulation and keeping them operative.

Seminal Tenofovir Concentrations, Viral Suppression, and Semen Quality With Tenofovir Alafenamide, Compared With Tenofovir Disoproxil Fumarate (Spanish HIV/AIDS Research Network, PreEC/RIS 40).

BACKGROUND: This study assessed the penetration and efficacy of tenofovir alafenamide (TAF) in the male genital tract (MGT) and the semen quality of individuals infected with human immunodeficiency virus (HIV)-1 who were treated with a TAF-containing regimen. METHODS: This was a prospective, open-label, single-arm study of 14 virologically-suppressed, HIV-1-infected men on stable antiretroviral therapy with elvitegravir, cobicistat, emtricitabine (E/C/F) and tenofovir disoproxil fumarate (TDF) who switched to E/C/F and TAF. At baseline (pre-switch) and at 12 weeks post-switch, we measured HIV-1 RNA in seminal plasma (SP) and blood plasma (BP), tenofovir (TFV) in SP and BP, and TFV-diphosphate (dp) in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs) at the end of the dosing interval (C24h). Semen quality was assessed before switching and after 12 weeks on TAF. RESULTS: With TAF, TFV C24 was 11.9-fold higher in SP than in BP. This concentration was significantly lower than TFV C24 in SP with TDF, but 9.6-fold higher than the 50% inhibitory concentration (IC50) (11.5 ng/mL). By contrast, the median TFV-dp concentration achieved with TAF in SMCs was 6% that of TFV-dp in PBMCs. The TFV-dp SMC:PBMC ratio was also significantly lower with TAF. Nonetheless, TFV-dp C24 in SMC was comparable with TAF and TDF. All the patients had HIV-1 RNA <40 copies/mL in BP and SP at baseline and at 12 weeks post-switch. No significant differences were observed in semen quality between TAF and TDF. CONCLUSIONS: Extracellular and intracellular seminal TFV distribution differs between TAF and TDF. Nevertheless, both formulations, combined with elvitegravir/cobicistat/emtricitabine, maintained HIV-1 RNA suppression in semen. Differences in MGT distribution were not associated with differences in semen quality. CLINICAL TRIALS REGISTRATION: EudraCT: 2016-001371-69.

Wine markers in archeological potteries: detection by GC-MS at ultratrace levels.

The detection of organic residues that remain absorbed into the pores of ceramic artifacts constitutes a source of information regarding their management. Taking into account the poor conservation state of the potteries and the low amount of the organic tracers together with the main drawbacks to get the relevant information concerning different aspects of past societies, the detection of organic biomarkers is still an analytical challenge. In this work, an improved analytical methodology to maximize the recovery of organic markers related to wine in archeological ceramics is presented. The developed method consists on the extraction of wine-related organic compounds including tartaric acid, malic acid, fumaric acid, succinic acid, citric acid, and syringic acid by means of ultrasonic probe-assisted extraction (UPAE) followed by a preconcentration step by mixed-mode strong anion exchange and reversed-phase solid-phase extraction (SPE) and a derivatization step prior to analysis by means of gas chromatography-mass spectrometry (GC-MS). Finally, the method was applied to real archeological ceramic fragments (two dolia), suspected to have been used to store wine, together with organic residues found inside two amphorae from Zaragoza (Spain). Graphical abstract.

Disability and quality of life in heart failure patients: a cross-sectional study.

BACKGROUND: Although both hospitalization and mortality due to heart failure (HF) have been widely studied, less is known about the impact of HF on disability and quality of life. AIM: To assess the degree of disability and quality of life in HF patients attended at family medicine centres. DESIGN AND SETTING: Cross-sectional study of a cohort of HF patients attended at family medicine centres. METHODS: Disability was assessed with the WHODAS 2 questionnaire, which provides a global and six domain scores that is understanding and communication, getting around, self-care, getting along with people, life activities and participation in society. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire, which furnishes a global and two domain scores, physical and emotional. RESULTS: A breakdown of the results showed that 28% of patients had moderate disability and 16.7% had severe disability, with the most important areas affected being: life activities, 8.9% extreme disability and 30.3% severe disability; getting around, 34.6% severe disability and 2% extreme disability; and participation in society, 53.3% moderate-severe disability. Quality of life was mildly affected. New York Heart Association (NYHA) Functional Classification and sex were the major determinants of disability and quality of life. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists were associated with better scores in the "getting around" and "life activity" domains. CONCLUSION: HF patients in primary care show an important degree of disability and an acceptable quality of life.

Requirements and applications of accurate modeling of the optical transmission of transparent conducting coatings.

A comprehensive model for the optical transmission is constructed and used to investigate the requirements for fitting accurately the experimental data of the optical transmittance at normal incidence of transparent conducting coatings of ZnO:Al deposited on glass substrates by ultrasonic spray pyrolysis. The model takes into account the Urbach tail absorption edge at the low wavelength region, the contribution of free carrier concentration to the weak absorption in the visible and near-infrared ranges, and the effect of scattering of light originated by the surface roughness of the films. The carrier concentration of the ZnO:Al films was measured experimentally by the Hall effect and dc-electrical conductivity measurements in the Van der Paw configuration. It is shown that all mentioned physical effects must be included in order to fit accurately the transmittance spectrum in the VIS-NIR spectral window. The full expression for the optical transmittance was used for choosing the optimal thickness of these films as transparent conductive contacts and the calculation of the figure of merit.

Hole transporting materials for perovskite solar cells: a chemical approach.

Photovoltaic solar cells based on perovskites have come to the forefront in science by achieving exceptional power conversion efficiencies (PCEs) in less than a decade of research. This "still young" generation of solar cells is currently rivalling, in PCEs, well-established technologies, such as cadmium telluride (CdTe) and silicon. Further improvements in device stability by means of innovative materials are yet to come, with technology becoming closer to meeting the market requirements. Emerging from this groundbreaking discovery, a great number of charge transporting materials have flourished, which is particularly true for hole transporting materials (HTMs). The huge number of molecules prepared stem from design and engineering of a wide variety of new and also chemically modified old molecules where organic synthesis has played a fundamental role. In this review, the contribution of chemistry through those synthetic protocols used for producing new and innovative HTMs from relatively simple organic molecules is presented in a rational and systematic manner. The variety and impact of synthetic strategies followed, the structure-property relationship and stability, conductivity and device performance are highlighted from a chemical viewpoint.

Cerebrospinal fluid drug concentrations and viral suppression in HIV-1-infected patients receiving ritonavir-boosted atazanavir plus lamivudine dual antiretroviral therapy (Spanish HIV/AIDS Research Network, PreEC/RIS 39).

This study aimed to assess cerebrospinal fluid (CSF) drug concentrations and viral suppression in HIV-1-infected patients on ritonavir-boosted atazanavir (ATV/r) plus lamivudine (3TC) dual therapy. HIV-1-infected adults with suppressed plasma HIV-1 RNA who switched to ATV/r plus 3TC were studied. Total ATV and 3TC concentrations at the end of the dosing interval (C24h), using a validated LC-MS/MS method, and HIV-1 RNA were measured in paired CSF and plasma samples 12 weeks after switching. Ten individuals were included. Median (range) age was 42.5 (33-70) years, time on ART was 39.5 (11-197) months, and time with plasma HIV-1 RNA < 40 copies/mL was 15.5 (6-46) months. At baseline, CSF HIV-1 RNA was < 40 copies/mL in all patients. Twelve weeks after switching to ATV/r plus 3TC, HIV-1 RNA remained at < 40 copies/mL in both plasma and CSF in 9/10 patients. One patient with suboptimal adherence to ART had HIV-1 RNA rebound in both plasma and CSF. The median CSF-to-plasma concentration ratios of ATV and 3TC were 0.013 and 0.417, respectively. Median ATV C24h in CSF was 10.4 (3.7-33.4) ng/mL (in vitro ATV IC50 range, 1-11 ng/mL). Median 3TC C24h in CSF was 43.4 (16.2-99.3) ng/mL (in vitro 3TC IC50 range, 0.68-20.6 ng/mL). Most patients maintained HIV-1 RNA in CSF < 40 copies/mL despite CSF ATV C24h close to or within the IC50 range in the majority. ATV PK data in CSF should be considered and rigorous patient selection is advisable to assure effective CSF viral suppression with this two-drug simplification regimen.

Influence of Mechanical Ventilation on the Pharmacokinetics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients.

Pathophysiological changes involved in drug disposition in critically ill patients should be considered in order to optimize the dosing of vancomycin administered by continuous infusion, and certain strategies must be applied to reach therapeutic targets on the first day of treatment. The aim of this study was to develop a population pharmacokinetic model of vancomycin to determine clinical covariates, including mechanical ventilation, that influence the wide variability of this antimicrobial. Plasma vancomycin concentrations from 54 critically ill patients were analyzed simultaneously by a population pharmacokinetic approach. A nomogram for dosing recommendations was developed and was internally evaluated through stochastic simulations. The plasma vancomycin concentration-versus-time data were best described by a one-compartment open model with exponential interindividual variability associated with vancomycin clearance and the volume of distribution. Residual error followed a homoscedastic trend. Creatinine clearance and body weight significantly dropped the objective function value, showing their influence on vancomycin clearance and the volume of distribution, respectively. Characterization based on the presence of mechanical ventilation demonstrated a 20% decrease in vancomycin clearance. External validation (n = 18) was performed to evaluate the predictive ability of the model; median bias and precision values were 0.7 mg/liter (95% confidence interval [CI], -0.4, 1.7) and 5.9 mg/liter (95% CI, 5.4, 6.4), respectively. A population pharmacokinetic model was developed for the administration of vancomycin by continuous infusion to critically ill patients, demonstrating the influence of creatinine clearance and mechanical ventilation on vancomycin clearance, as well as the implications for targeting dosing rates to reach the therapeutic range (20 to 30 mg/liter).

Effect of Continuous Positive Airway Pressure on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial.

RATIONALE: Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in patients with diabetes. OBJECTIVES: To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants. METHODS: In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels equal to or exceeding 6.5% were randomized to CPAP (n = 26) or no CPAP (control; n = 24), while their usual medication for diabetes remained unchanged. MEASUREMENTS AND MAIN RESULTS: HbA1c levels, Homeostasis Model Assessment and Qualitative Insulin Sensitivity Check Index scores, systemic biomarkers, and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1ß, IL-6, and adiponectin also improved in the CPAP group compared with the control group after 6 months. In patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1ß were independently related to the 6-month change in HbA1c levels (r(2) = 0.510, P = 0.002). CONCLUSIONS: Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months resulted in improved glycemic control and insulin resistance compared with results for a control group. Clinical trial registered with www.clinicaltrials.gov (NCT01801150).

Pharmacokinetics of vancomycin and dosing recommendations for trauma patients.

OBJECTIVES: The objectives of this study were to characterize the population pharmacokinetics of vancomycin in trauma patients and to propose dosing schemes to optimize therapy. PATIENTS AND METHODS: Trauma patients from Hospital Universitario Severo Ochoa (Spain) receiving intravenous vancomycin and routine therapeutic drug monitoring were included. Concentrations and time data were retrospectively collected, and population modelling was performed with NONMEM 7.2; internal and external validations were performed to probe the final model. Finally, several simulations were executed to propose dosing guidelines to reach expected vancomycin concentrations. RESULTS: A total of 118 trauma patients were included; the population was 45% males, with a mean age of 77 years (range 37-100 years) and a mean total body weight (TBW) of 72 kg (range 38-110 kg). The pharmacokinetics of vancomycin was best described by a two-compartment open model; creatinine clearance (CLCR) was related to vancomycin clearance (0.49 ± 0.04 L/h), being diminished by the presence of furosemide (0.34 ± 0.05 L/h). TBW influenced both the central volume of distribution (V1 = 0.74 ± 0.1 L/kg) and peripheral volume of distribution (V2 = 5.9 ± 2 L/kg), but patients with age >65 years showed a larger V1 (1.07 ± 0.1 L/kg). Bootstrapping was performed to internally validate the stability of the final model. External validation was developed using an alternate population of 40 patients with the same characteristics. The validated model was compared with population pharmacokinetic models previously published and showed better predictive performance for trauma patients than the current one. This final model allowed us to propose a new practical dose guideline to reach higher trough concentrations (15-20 mg/L) and AUC0-24/MIC ratios of more than 400 after 4 days of vancomycin treatment. CONCLUSIONS: A new population model was described for trauma patients to optimize vancomycin therapy, showing precise predictive performance to be applied for therapeutic drug monitoring and providing a new practical dose guideline that considers CLCR and concomitant administration of furosemide for these patients.

Benzotrithiophene-Based Hole-Transporting Materials for 18.2 % Perovskite Solar Cells.

New star-shaped benzotrithiophene (BTT)-based hole-transporting materials (HTM) BTT-1, BTT-2 and BTT-3 have been obtained through a facile synthetic route by crosslinking triarylamine-based donor groups with a benzotrithiophene (BTT) core. The BTT HTMs were tested on solution-processed lead trihalide perovskite-based solar cells. Power conversion efficiencies in the range of 16 % to 18.2 % were achieved under AM 1.5 sun with the three derivatives. These values are comparable to those obtained with today's most commonly used HTM spiro-OMeTAD, which point them out as promising candidates to be used as readily available and cost-effective alternatives in perovskite solar cells (PSCs).