Scalable stable comb-to-tone integrated RF photonic drive for superconducting qubits.

The recent advent of quantum computing has the potential to overhaul security, communications, and scientific modeling. Superconducting qubits are a leading platform that is advancing noise-tolerant intermediate-scale quantum processors. The implementation requires scaling to large numbers of superconducting qubits, circuit depths, and gate speeds, wherein high-purity RF signal generation and effective cabling transport are desirable. Fiber photonic-enhanced RF signal generation has demonstrated the principle of addressing both signal generation and transport requirements, supporting intermediate qubit numbers and robust packaging efforts; however, fiber-based approaches to RF signal distribution are often bounded by their phase instability. Here, we present a silicon photonic integrated circuit-based version of a photonic-enhanced RF signal generator that demonstrates the requisite stability, as well as a path towards the necessary signal fidelity.

Forest disturbance regimes and trends in continental Spain (1985-2023) using dense landsat time series.

Forest disturbance regimes across biomes are being altered by interactive effects of global change. Establishing baselines for assessing change requires detailed quantitative data on past disturbance events, but such data are scarce and difficult to obtain over large spatial and temporal scales. The integration of remote sensing with dense time series analysis and cloud computing platforms is enhancing the ability to monitor historical disturbances, and especially non-stand replacing events along climatic gradients. Since the integration of such tools is still scarce in Mediterranean regions, here, we combine dense Landsat time series and the Continuous Change Detection and Classification - Spectral Mixture Analysis (CCDC-SMA) method to monitor forest disturbance in continental Spain from 1985 to 2023. We adapted the CCDC-SMA method for improved disturbance detection creating new spectral libraries representative of the study region, and quantified the year, month, severity, return interval, and type of disturbance (stand replacing, non-stand replacing) at a 30 m resolution. In addition, we characterised forest disturbance regimes and trends (patch size and severity, and frequency of events) of events larger than 0.5 ha at the national scale by biome (Mediterranean and temperate) and forest type (broadleaf, needleleaf and mixed). We quantified more than 2.9 million patches of disturbed forest, covering 4.6 Mha over the region and period studied. Forest disturbances were on average larger but less severe in the Mediterranean than in the temperate biome, and significantly larger and more severe in needleleaf than in mixed and broadleaf forests. Since the late 1980s, forest disturbances have decreased in size and severity while increasing in frequency across all biomes and forest types. These results have important implications as they confirm that disturbance regimes in continental Spain are changing and should therefore be considered in forest strategic planning for policy development and implementation.

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Tau Appearance from High-Energy Neutrino Interactions.

High-energy muon and electron neutrinos yield a non-negligible flux of tau neutrinos as they propagate through Earth. In this Letter, we address the impact of this additional component in the PeV and EeV energy regimes for the first time. Above 300 TeV, this contribution is predicted to be significantly larger than the atmospheric background, and it alters current and future neutrino telescopes' capabilities to discover a cosmic tau-neutrino flux. Further, we demonstrate that Earth-skimming neutrino experiments, designed to observe tau neutrinos, will be sensitive to cosmogenic neutrinos even in extreme scenarios without a primary tau-neutrino component.

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Trends in mortality from stroke in the European Union, 1996-2015.

BACKGROUND AND PURPOSE: Stroke is the second largest single cause of death in Europe, responsible for 9% and 13% of all deaths in men and women, respectively. There have been large overall declines in stroke mortality rates in the majority of European countries in recent decades. The aim of this study was to analyse trends in mortality caused by stroke in the 28 member countries of the European Union (EU) over the last two decades. METHODS: We extracted data for age-standardized stroke mortality rates per 100 000 in the EU for the period 1996-2015 from the World Health Organization database. Joinpoint regression analysis was used to analyse the trends and compute the annual percent change (APC) in the EU as a whole and by country. Analyses were conducted by gender and by European region. RESULTS: Mortality from stroke has decreased in the EU over the study period by an average APC of 4.2%. All countries showed downward trends, with the sharpest decreases in Estonia, Portugal and Austria. We recorded statistically significant decreases of 4.2% and 4.3% in mortality rates in men and women, respectively, in the whole EU. Southern and western countries showed the steepest decreases, whereas mortality has increased in northern countries in recent years. CONCLUSIONS: Stroke mortality has decreased in the EU, in both sexes, especially in southern and western European countries. Our results could be a reference for the development of primary prevention and acute management of stroke policies focused on countries with higher mortality.

Cross-modality and in-vivo validation of 4D flow MRI evaluation of uterine artery blood flow in human pregnancy.

OBJECTIVES: Clinical assessment of uterine artery (UtA) hemodynamics is currently limited to Doppler ultrasound (US) velocimetry. We have demonstrated previously the feasibility of applying four-dimensional (4D) flow magnetic resonance imaging (MRI) to evaluate UtA hemodynamics during pregnancy, allowing flow quantification of the entire course of the vessel. In this study, we sought to further validate the physiological relevance of 4D flow MRI measurement of UtA blood flow by exploring its association with pregnancy outcome relative to US-based metrics. METHODS: Recruited into this prospective, cross-sectional study were 87 women with a singleton pregnancy who underwent 4D flow MRI between May 2016 and April 2019 to measure the UtA pulsatility index (MRI-PI) and blood flow rate (MRI-flow, in mL/min). UtA-PI was also measured using US (US-PI). The primary outcome was a composite (COMP) of pre-eclampsia (PE) and/or small-for-gestational-age (SGA) neonate, and secondary outcomes were PE and SGA neonate individually. We assessed the ability of MRI-flow, MRI-PI and US-PI to distinguish between outcomes, and evaluated whether MRI-flow changed as gestation progressed. RESULTS: Following 4D flow postprocessing and exclusions from the analysis, 74 women had 4D flow MRI data analyzed for both UtAs. Of these, 18 developed a COMP outcome: three developed PE only, 11 had a SGA neonate only and four had both. A comparison of the COMP group vs the no-COMP group found no differences in maternal age, body mass index, nulliparity, gravidity or race. For 66 of the 74 subjects, US data were also available. In these subjects, both median MRI-PI (0.95 vs 0.70; P < 0.01) and median US-PI (0.95 vs 0.73; P < 0.01) were significantly increased in subjects in the COMP group compared with those in the no-COMP group. The UtA blood-flow rate, as measured by MRI, did not increase significantly from the second to the third trimester (median flow (interquartile range (IQR)), 543 (419-698) vs 575 (440-746) mL/min; P = 0.77), but it was significantly lower overall in the COMP compared with the no-COMP group (median flow (IQR), 486 (366-598) vs 624 (457-749) mL/min; P = 0.04). The areas under the receiver-operating-characteristics curves for MRI-flow, MRI-PI and US-PI in predicting COMP were not significantly different (0.694, 0.737 and 0.731, respectively; P = 0.87). CONCLUSIONS: 4D flow MRI can yield physiological measures of UtA blood-flow rate and PI that are associated with adverse pregnancy outcome. This may open up new avenues in the future to expand the potential of this technique as a robust tool with which to evaluate UtA hemodynamics in pregnancy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Seroprevalences of antibodies against ToRCH infectious pathogens in women of childbearing age residing in Brazil, Mexico, Germany, Poland, Turkey and China.

Determination of antibodies against ToRCH antigens at the beginning of pregnancy allows assessment of both the maternal immune status and the risks to an adverse pregnancy outcome. Age-standardised seroprevalences were determined in sera from 1009 women of childbearing age residing in Mexico, Brazil, Germany, Poland, Turkey or China using a multiparametric immunoblot containing antigen substrates for antibodies against Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex viruses (HSV-1, HSV-2), Bordetella pertussis, Chlamydia trachomatis, parvovirus B19, Treponema pallidum and varicella zoster virus (VZV). Seroprevalences for antibodies against HSV-1 were >90% in samples from Brazil and Turkey, whereas the other four countries showed lower mean age-adjusted seroprevalences (range: 62.5-87.9%). Samples from Brazilian women showed elevated seroprevalences of antibodies against HSV-2 (40.1%), C. trachomatis (46.8%) and B. pertussis (56.6%) compared to the other five countries. Seroprevalences of anti-T. gondii antibodies (0.5%) and anti-parvovirus B19 antibodies (7.5%) were low in samples from Chinese women, compared to the other five countries. Samples from German women revealed a low age-standardised seroprevalence of anti-CMV antibodies (28.8%) compared to the other five countries. These global differences in immune status of women in childbearing age advocate country-specific prophylaxis strategies to avoid infection with ToRCH pathogens.

Prevalence of Spasticity and Postural Patterns in the Upper Extremity Post Stroke.

INTRODUCTION: A high number of patients with stroke develop upper extremity spasticity, causing abnormal postures and patterns. These alterations limit the use of arm in functional activities and affect social participation. AIM: To determine the prevalence of spasticity and postural patterns of the upper extremity post stroke. MATERIALS AND METHODS: A cross-sectional descriptive design was used with a prospective follow-up. The sample included 136 patients. The study included 3 measuring times; at 10 days (T1), applying a record with sociodemographic-clinical data, the evaluation of muscle tone in the elbow and wrist and the postural patterns of the UE, and at 3 months (T2) and 12 months (T3) post stroke, re-evaluating tone and patterns. Prevalence was calculated through the one-sample chi-squared (χ2) test followed by inspection of the standardized residuals (z) in each cell. The Kappa coefficient evaluated the degree of agreement in elbow and wrist tone. RESULTS: The prevalence of spasticity in the elbow was 37.5% at T1, 57.4% at T2, and 57.4% at T3. At each time there was a high degree of agreement between elbow and wrist tone. Patients developed increased elbow tone between T1 and T2, with maintained tone between T2 and T3. Postural pattern III was the most prevalent according to Hefter's classification. CONCLUSION: The prevalence of spasticity in the elbow and wrist increases between 10 days and 3 months post stroke, and is maintained between 3 and 12 months. The onset of spasticity occurs in almost half of patients during the first 10 days post stroke. Postural pattern III according to Hefter's classification presented the greatest prevalence in the spastic UE.

Estimation of the age of majority through radiographic evaluation of the third molar maturation degree.

BACKGROUND: Although the third molar is the tooth with the greatest anatomical and developmental variability, some authors consider it important to estimate whether a subject is of legal age or not. The Demirjian's technique is the most widely used tool to estimate dental age and was therefore used in our study to assess possible correlation between the age of majority and the maturational degree of the lower third molars, evaluated through radiographic images. MATERIAL AND METHODS: This observational transversal study was conducted on 180 panoramic radiographs from consecutive patients. The degree of maturation of the lower third molar was independently classified by two observers, according to the Demirjian´s maturational stage method. RESULTS: A total of 180 patients - 65 men (36.12%) and 115 women (63.88%) - were included (mean age 21.6 years; standard deviation 5.2). The age range of our subjects corresponded to maturational stages D to H in the Demirjian's classification. A logistic regression analysis showed that subjects classified into the highest maturational stage H had a significantly higher probability of being considered of legal age by both observers, as compared with subjects in the lowest stage D. Inter-observer agreement was very high. Gender predictive capacity was not observed. CONCLUSIONS: Our results showed that subjects with the lower third molars in the highest maturational stage could be estimated to be older than 18 years and therefore considered of legal age, a finding also reported by other authorsThe Demirjian´s tooth maturational stage method, applied to the lower third molars, can be reliably used to estimate whether an individual is of legal age (18 years or older). High concordance between different observers using this method can be expected.

Immunotolerance induction effectivity in hemophilia A children and neutralizing alloantibodies. / Efectividad de inducción de tolerancia inmune en niños con hemofilia A y aloanticuerpos neutralizantes.

INTRODUCTION: The development of anti-factor VIII neutralizing antibodies in hemophilia A is the most severe com plication related to treatment. Immune tolerance induction (ITI) is the only known treatment for eradicating inhibitors. A successful ITI allows using factor VIII (FVIII) again for the treatment or prophylaxis of hemorrhagic events. OBJECTIVE: To report the experience of pediatric patients who underwent ITI in the country's public health care network. PATIENTS AND METHOD: Retrospective and descriptive analysis of 13 pediatric patients with severe Hemophilia A and high-titer inhibitors persis tence who underwent ITI and complete follow-up. Plasma-derived FVIII concentrate was used at 70 180 IU/kg/day doses. The success of the treatment is defined by achieving a negative titer and a half life recovery of the FVIII. The results were expressed in median (range). RESULTS: In 13 patients, the inhibitor was identified at an average age of 17.6 months, after 35.2 days of exposure to the FVIII. 11 patients (84.6%) recovered the half-life of FVIII after 49.6 months of treatment. In the patients who responded to treatment, the inhibitor titer was negative at 6 months on average. CONCLUSIONS: ITI is the treatment of choice for patients with hemophilia A and inhibitors persistence. ITI must be perso nalized since the time response is variable in each patient.

Osteoporotic vertebral fractures: A diagnostic challenge in the 21ST century. / Fracturas vertebrales osteoporóticas: un reto diagnóstico en el siglo XXI.

Vertebral fractures are the most prevalent osteoporotic fractures and are paradoxically the most underdiagnosed. While only one-third of patients have acute pain, they can present other associated chronic complications. Vertrebal fractures are associated with the onset of new fractures, both vertebral and nonvertebral. Radiography of the dorsal-lumbar spine is a useful tool for detecting them but depends on the subjective interpretation of the physician conducting the assessment. New techniques, such as vertebral morphometry, have recently demonstrated greater efficacy in detecting v vertebral fractures and are performed concomitantly with bone densitometry. Knowing how to identify vertebral fractures is essential for the secondary prevention of new fractures and improving our patients' quality of life.

Phase II randomized study of PM01183 versus topotecan in patients with platinum-resistant/refractory advanced ovarian cancer.

BACKGROUND: PM01183 is a new compound that blocks active transcription, produces DNA breaks and apoptosis, and affects the inflammatory microenvironment. PM01183 showed strong antitumor activity in preclinical models of cisplatin-resistant epithelial ovarian cancer. PATIENTS AND METHODS: Patients with platinum-resistant/refractory ovarian cancer were included in a two-stage, controlled, randomized (in a second stage), multicenter, phase II study. Primary endpoint was overall response rate (ORR) by RECIST and/or GCIG criteria. The exploratory first stage (n = 22) confirmed the activity of PM01183 as a single agent at 7.0 mg flat dose every 3 weeks (q3wk). The second stage (n = 59) was randomized and controlled with topotecan on days 1-5 q3wk or weekly (every 4 weeks, q4wk). RESULTS: ORR was 23% (95% CI, 13%-37%) for 52 PM01183-treated patients. Median duration of response was 4.6 months (95% CI, 2.5-6.9 months), and 23% (95% CI, 0%-51%) of responses lasted 6 months or more. Ten of the 12 confirmed responses were reported for 33 patients with platinum-resistant disease [ORR = 30% (95% CI, 16%-49%)]; for the 29 patients treated with topotecan in the second stage, no responses were found. Median PFS for all PM01183-treated patients was 4.0 months (95% CI, 2.7-5.6 months), and 5.0 months (95% CI, 2.7-6.9 months) for patients with platinum-resistant disease. Grade 3/4 neutropenia in 85% of patients; febrile neutropenia in 21% and fatigue (grade 3 in 35%) were the principal safety findings for PM01183. CONCLUSION: PM01183 is an active drug in platinum-resistant/refractory ovarian cancer and warrants further development. The highest activity was observed in platinum-resistant disease. Its safety profile indicates the dose should be adjusted to body surface area (mg/m2). TRIAL CODE: EudraCT 2011-002172-16.

Transcriptomic analysis of wound xylem formation in Pinus canariensis.

BACKGROUND: Woody plants, especially trees, usually must face several injuries caused by different agents during their lives. Healing of injuries in stem and branches, affecting the vascular cambium and xylem can take several years. In conifers, healing takes place mainly from the remaining vascular cambium in the margin of the wound. The woundwood formed in conifers during healing usually presents malformed and disordered tracheids as well as abundant traumatic resin ducts. These characteristics affect its functionality as water conductor and its technological properties. RESULTS: In this work we analyze for the first time the transcriptomic basis of the formation of traumatic wood in conifers, and reveal some differences with normal early- and late-wood. Microarray analysis of the differentiating traumatic wood, confirmed by quantitative RT-PCR, has revealed alterations in the transcription profile of up to 1408 genes during the first period of healing. We have grouped these genes in twelve clusters, according to their transcription profiles, and have distinguished accordingly two main phases during this first healing. CONCLUSIONS: Wounding induces a complete rearrangement of the transcriptional program in the cambial zone close to the injuries. At the first instance, radial growth is stopped, and a complete set of defensive genes, mostly related to biotic stress, are induced. Later on, cambial activity is restored in the lateral borders of the wound, even at a high rate. During this second stage certain genes related to early-wood formation, including genes involved in cell wall formation and transcription factors, are significantly overexpressed, while certain late-wood related genes are repressed. Additionally, significant alterations in the transcription profile of abundant non annotated genes are reported.

Haemoglobin responses to transfusion in severe iron deficiency anaemia: potential impact of gastrointestinal disorders.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) transfusion may be justified in iron deficiency anaemia (IDA) when an increase in oxygen delivery is needed, as sometimes occurs in subjects with haemoglobin <8·0 mg/dL, serious comorbidities or at risk of cardiovascular instability. Earlier investigations showed that some patients with severe IDA requiring transfusion had lower than expected post-transfusion haemoglobin levels with poorer clinical outcomes than other patients. After hypothesizing that haemoglobin responses to transfusion were different and that the underlying gastrointestinal (GI) disorders causing IDA could be a confounder explaining this association, these responses were analysed in a prospective cohort of IDA adults referred for outpatient GI investigation. MATERIALS AND METHODS: Transfused patients with proven IDA, baseline haemoglobin at referral <9·0 g/dL and no extraintestinal bleeding were eligible. To assess a homogeneous population, only GI disorders known to cause occult bleeding were considered. Haemoglobin increments per 100 mL of RBCs were investigated. RESULTS: In total, 2818 patients were enrolled over 10·5 years. On multivariable regression, diffuse angiodysplasias and GI cancer independently predicted for reduced increments in post-transfusion haemoglobin [adjusted regression coefficients: -0·082 (95% confidence interval, -0·093 to -0·072) and -0·073 (95% confidence interval, -0·081 to -0·066), respectively, P < 0·001 in both]. Haemoglobin responses in the remaining bleeding disorders were adequate and agreed with the principle that one RBC unit increases the haemoglobin an average of 1 g/dL. CONCLUSION: The potential differential impact of GI disorders on changes in haemoglobin levels after RBC transfusion could be useful for transfusing physicians, especially for diagnostic purposes.

Impact of the implementation of a Sepsis Code hospital protocol in antibiotic prescription and clinical outcomes in an intensive care unit. / Impacto de la implantación de un Código Sepsis intrahospitalario en la prescripción de antibióticos y los resultados clínicos en una unidad de cuidados intensivos.

INTRODUCTION: A study was performed to analyze the impact of an in-hospital Sepsis Code (SC) program on use of antibiotic and clinical outcomes. DESIGN: Quasi-experimental observational retrospective study. SETTING: Polyvalent 11 beds ICU belonging to a tertiary Universitary hospital. PATIENTS: Patients admitted consecutively to the ICU with diagnosis of severe sepsis or septic shock. INTERVENTIONS: A post intervention group (POST-SC) (September 2012-August 2013) was compared with a historical group (PRE-SC) used as control (January-December 2010). VARIABLES: Antibiotic treatment, therapeutic antibiotic strategy, mortality and length of stay. Antibiotic consumption was expressed as defined daily doses (DDD)/ 100 stays. RESULTS: 42 patients with SS/SS in POST-SC group and 50 patients in PRE-SC group were consecutively recluted and further analyzed. Total antibiotic consumption (DDD) was similar in both groups. Rate of de-escalation therapy was significantly higher in POST-SC group (75% vs 30,8%, p<0,005) while prescription of restricted antibiotics was significantly lower (74% vs 52%, p=0,031). Finally POST-SC patients showed a significantly decrease in hospital and 28 days mortality rates [23% vs 44%, (p=0,035) and 31% vs 56% (p=0,014) respectively] as well as a reduction in ICU length of stay compared to PRE-SC cohort (5 days vs 10,5 days, p=0,05). CONCLUSION: The implementation of a Sepsis Code-hospital protocol is associated to an improvement in the management of antibiotic therapy with a significant increase in de-escalation therapy and lesser utilization of restricted use antibiotics, as well as a significant reduction in mortality, and a tendency towards shorter ICU length stay.

Inappropriate prescribing in elderly people with diabetes admitted to hospital.

AIMS: To assess inappropriate prescribing in older people with diabetes mellitus during the month prior to a hospitalization, using tools on potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs) and comparing inappropriate prescribing in patients with without diabetes. METHODS: In an observational, prospective multicentric study, we assessed inappropriate prescribing in 672 patients aged 75 years and older during hospital admission. The Beers, Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert Doctors to Right Treatment (START) criteria and Assessing Care of Vulnerable Elders (ACOVE-3) medicine quality indicators were used. We analysed demographic and clinical factors associated with inappropriate prescribing. RESULTS: Of 672 patients, 249 (mean age 82.4 years, 62.9% female) had a diagnosis of diabetes mellitus. The mean number of prescribing drugs per patient with diabetes was 12.6 (4.5) vs. 9.4 (4.3) in patients without diabetes (P < 0.001). Of those patients with diabetes, 74.2% used 10 or more medications; 54.5% of patients with diabetes had at least one Beers-listed PIM, 68.1% had at least one STOPP-listed PIM, 64.6% had at least one START-listed PPO and 62.8% had at least one ACOVE-3-listed PPO. Except for the Beers criteria, these prevalences were significantly higher in patients with diabetes than in those without. After excluding diabetes-related items from these tools, only STOPP-listed PIMs remained significantly higher among patients with diabetes (P = 0.04). CONCLUSIONS: Polypharmacy is common among older patients with diabetes mellitus. Inappropriate prescribing is higher in older patients with diabetes, even when diabetes-related treatment is excluded from the inappropriate prescribing evaluation.

Correlation of three-liquid-phase equilibria involving ionic liquids.

The difficulty in achieving a good thermodynamic description of phase equilibria is finding a model that can be extended to a large variety of chemical families and conditions. This problem worsens in the case of systems containing more than two phases or involving complex compounds such as ionic liquids. However, there are interesting applications that involve multiphasic systems, and the promising features of ionic liquids suggest that they will play an important role in many future processes. In this work, for the first time, the simultaneous correlation of liquid-liquid and liquid-liquid-liquid equilibrium data for ternary systems involving ionic liquids has been carried out. To that end, the phase diagram of the water + [P6 6 6 14][DCA] + hexane system has been determined at 298.15 K and 323.15 K and atmospheric pressure. The importance of this system lies in the possibility of using the surface active ionic liquid to improve surfactant enhanced oil recovery methods. With those and previous measurements, thirteen sets of equilibrium data for water + ionic liquid + oil ternary systems have been correlated. The isoactivity equilibrium condition, using the NRTL model, and some pivotal strategies are proposed to correlate these complex systems. Good agreement has been found between experimental and calculated data in all the regions (one triphasic and two biphasic) of the diagrams. The geometric aspects related to the Gibbs energy of mixing function obtained using the model, together with the minor common tangent plane equilibrium condition, are valuable tools to check the consistency of the obtained correlation results.