MXCuBE2: the dawn of MXCuBE Collaboration.

MXCuBE2 is the second-generation evolution of the MXCuBE beamline control software, initially developed and used at ESRF - the European Synchrotron. MXCuBE2 extends, in an intuitive graphical user interface (GUI), the functionalities and data collection methods available to users while keeping all previously available features and allowing for the straightforward incorporation of ongoing and future developments. MXCuBE2 introduces an extended abstraction layer that allows easy interfacing of any kind of macromolecular crystallography (MX) hardware component, whether this is a diffractometer, sample changer, detector or optical element. MXCuBE2 also works in strong synergy with the ISPyB Laboratory Information Management System, accessing the list of samples available for a particular experimental session and associating, either from instructions contained in ISPyB or from user input via the MXCuBE2 GUI, different data collection types to them. The development of MXCuBE2 forms the core of a fruitful collaboration which brings together several European synchrotrons and a software development factory and, as such, defines a new paradigm for the development of beamline control platforms for the European MX user community.

Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial.

OBJECTIVES: To demonstrate non-inferiority of iobitridol 350 for coronary CT angiography (CTA) compared to higher iodine content contrast media regarding rate of patients evaluable for the presence of coronary artery stenoses. METHODS: In this multicentre trial, 452 patients were randomized to receive iobitridol 350, iopromide 370 or iomeprol 400 and underwent coronary CTA using CT systems with 64-detector rows or more. Two core lab readers assessed 18 coronary segments per patient regarding image quality (score 0 = non diagnostic to 4 = excellent quality), vascular attenuation, signal and contrast to noise ratio (SNR, CNR). Patients were considered evaluable if no segment had a score of 0. RESULTS: Per-patient, the rate of fully evaluable CT scans was 92.1, 95.4 and 94.6 % for iobitridol, iopromide and iomeprol, respectively. Non-inferiority of iobitridol over the best comparator was demonstrated with a 95 % CI of the difference of [-8.8 to 2.1], with a pre-specified non-inferiority margin of -10 %. Although average attenuation increased with higher iodine concentrations, average SNR and CNR did not differ between groups. CONCLUSIONS: With current CT technology, iobitridol 350 mg iodine/ml is not inferior to contrast media with higher iodine concentrations in terms of image quality for coronary stenosis assessment. KEY POINTS: • Iodine concentration is an important parameter for image quality in coronary CTA. • Contrast enhancement must be balanced against the amount of iodine injected. • Iobitridol 350 is non-inferior compared to CM with higher iodine concentrations. • Higher attenuation with higher iodine concentrations, but no SNR or CNR differences.

Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study.

BACKGROUND: Pleurofibrinolysis has been reported to be potentially beneficial in the management of complicated parapneumonic effusions (CPPE) and empyemas in the adult population. METHODS: Prospective, controlled, randomized, and double-blind study, to evaluate intrapleural alteplase 10 mg (initially 20 mg was considered but bleeding events forced dose reduction) versus 100,000 UI urokinase every 24 h for a maximum of 6 days in patients with CPPE or empyemas. The primary aim was to evaluate the success rate of each fibrinolytic agent at 3 and 6 days. Success of therapy was defined as the presence of both clinical and radiological improvement, making additional fibrinolytic doses unnecessary, and eventually leading to resolution. Secondary outcomes included the safety profile of intrapleural fibrinolytics, referral for surgery, length of hospital stay, and mortality. RESULTS: A total of 99 patients were included, of whom 51 received alteplase and 48 urokinase. Success rates for urokinase and alteplase at 3 and 6 days were not significantly different, but when only the subgroup of CPPE was considered, urokinase resulted in a high proportion of cures. There were no differences in mortality or surgical need (overall, 3 %). Five (28 %) patients receiving 20 mg of alteplase and 4 (12 %) receiving 10 mg presented serious bleeding events. CONCLUSIONS: If intrapleural fibrinolytics are intended to be used, urokinase may be more effective than alteplase in patients with non-purulent CPPE and have a lower rate of adverse events.

[Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders]. / Documento de consenso sobre el manejo clínico de los trastornos neurocognitivos asociados a la infección por el virus de la inmunodeficiencia humana (enero 2013).

OBJECTIVE: To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). METHODS: We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. RESULTS: Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. CONCLUSIONS: Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective.

Level of distress, somatisation and beliefs on health-disease in newly arrived immigrant patients attended in primary care centres in Catalonia and definition of professional competences for their most effective management: PROMISE Project.

BACKGROUND: Newly arrived immigrant patients who frequently use primary health care resources have difficulties in verbal communication. Also, they have a system of beliefs related to health and disease that makes difficult for health care professionals to comprehend their reasons for consultation, especially when consulting for somatic manifestations. Consequently, this is an important barrier to achieve optimum care to these groups. The current project has two main objectives: 1. To define the different stressors, the level of distress perceived, and its impact in terms of discomfort and somatisation affecting the main communities of immigrants in our area, and 2. To identify the characteristics of cross-cultural competence of primary health care professionals to best approach these reasons for consultation. METHODS/DESIGN: It will be a transversal, observational, multicentre, qualitative-quantitative study in a sample of 980 people from the five main non-European Union immigrant communities residing in Catalonia: Maghrebis, Sub-Saharans, Andean South Americans, Hindustanis, and Chinese. Sociodemographic data, level of distress, information on the different stressors and their somatic manifestations will be collected in specific questionnaires. Through a semi-structured interview and qualitative methodology, it will be studied the relation between somatic manifestations and particular beliefs of each group and how these are associated with the processes of disease and seeking for care. A qualitative methodology based on individual interviews centred on critical incidents, focal groups and in situ questionnaires will be used to study the cross-cultural competences of the professionals. DISCUSSION: It is expected a high level of chronic stress associated with the level of somatisations in the different non-European Union immigrant communities. The results will provide better knowledge of these populations and will improve the comprehension and the efficacy of the health care providers in prevention, communication, care management and management of resources.

Experience and results after the implementation of a radiology day unit in a reference hospital.

BACKGROUND: Interventional radiological procedures have significantly increased in recent years. Most of them are minimally invasive and require a short hospitalization, mainly done in other non-radiological units nowadays. Limited bed availability and high occupancy rates in these units create longer waiting lists and cancellations. The aim of this retrospective study is to assess the creation and functioning of a Radiology Day Unit (RDU) and evaluating its outcomes. For this purpose, data about interventional procedures and its complications, incidents, patient safety, quality and satisfaction rates were collected from May 2018 to December 2020, and posteriorly analyzed to evaluate its implementation. RESULTS: During the assessed period, 3841 patients were admitted into the RDU, with a net increase of 13% and 26% in the second and third year, respectively. Procedures performed by the Abdominal Radiology section were the most frequent (76-85%) followed by Interventional Vascular Radiology and Thoracic Radiology. Complication rates were low (1.5%) and most of them were self-limited and managed in the own department. Waiting lists were significantly reduced, from 2 months to 1 week in case of procedures performed by the Abdominal Radiology section. Patient satisfaction was higher than 80% in all the items evaluated with a global satisfaction of 93%. CONCLUSION: The RDU in our hospital has become a vital section for the management and post-procedure caring of patients undergoing interventional procedures in the Radiology Service with low complication rates and overall high levels of quality and patient safety, allowing the reduction of waiting lists and occupancy rates.

The role of oxidative stress in neurodegenerative diseases and potential antioxidant therapies.

Objectives: The central nervous system (CNS) is essential for homeostasis and controls the physiological functions of the body. However, the biochemical characteristics of the CNS make it especially vulnerable to oxidative damage (OS). This phenomenon compromises correct CNS functioning, leading to neurodegeneration and neuronal death. Contents: OS plays a crucial role in the physiopathology of neurodegenerative diseases. It is involved in multiple mechanisms of nucleic acid, protein, and lipid oxidation, thereby contributing to progressive brain damage. These mechanisms include mitochondrial dysfunction; excessive production of reactive oxygen and nitrogen species; deficiency of antioxidant defenses; protein oligomerization; cytokine production and inflammatory response; blood-brain barrier abnormalities; and proteasome dysfunction. All these dysfunctions are involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, or amyotrophic lateral sclerosis. Summary and outlook: A curative treatment is currently not available. Research is focused on the search for therapies that reduce oxidative damage and delay disease progression. In the recent years, researchers have focused their attention on the effects of antioxidant therapies.

Lung Ultrasound as a First-Line Test in the Evaluation of Post-COVID-19 Pulmonary Sequelae.

Background: Interstitial lung sequelae are increasingly being reported in survivors of COVID-19 pneumonia. An early detection of these lesions may help prevent the development of irreversible lung fibrosis. Lung ultrasound (LUS) has shown high diagnostic accuracy in interstitial lung disease (ILD) and could likely be used as a first-line test for post-COVID-19 lung sequelae. Methods: Single-center observational prospective study. Follow-up assessments of consecutive patients hospitalized for COVID-19 pneumonia were conducted 2-5 months after the hospitalization. All patients underwent pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and LUS. Radiological alterations in HRCT were quantified using the Warrick score. The LUS score was obtained by evaluating the presence of pathological B-lines in 12 thoracic areas (range, 0-12). The correlation between the LUS and Warrick scores was analyzed. Results: Three hundred and fifty-two patients who recovered from COVID-19 pneumonia were recruited between July and September 2020. At follow-up, dyspnea was the most frequent symptom (69.3%). FVC and DLCO alterations were present in 79 (22.4%) and 234 (66.5%) patients, respectively. HRCT showed relevant interstitial lung sequelae (RILS) in 154 (43.8%) patients (Warrick score ≥ 7). The LUS score was strongly correlated with the HRCT Warrick score (r = 0.77) and showed a moderate inverse correlation with DLCO (r = -0.55). The ROC curve analysis revealed that a LUS score ≥ 3 indicated an excellent ability to discriminate patients with RILS (sensitivity, 94.2%; specificity, 81.8%; negative predictive value, 94.7%). Conclusions: LUS could be implemented as a first-line procedure in the evaluation of Post-COVID-19 interstitial lung sequelae. A normal LUS examination rules out the presence of these sequelae in COVID-19 survivors, avoiding the need for additional diagnostic tests such as HRCT.

Influence of Co-Sputtered Ag:Al Ultra-Thin Layers in Transparent V2O5/Ag:Al/AZO Hole-Selective Electrodes for Silicon Solar Cells.

As optoelectronic devices continue to improve, control over film thickness has become crucial, especially in applications that require ultra-thin films. A variety of undesired effects may arise depending on the specific growth mechanism of each material, for instance a percolation threshold thickness is present in Volmer-Webber growth of materials such as silver. In this paper, we explore the introduction of aluminum in silver films as a mechanism to grow ultrathin metallic films of high transparency and low sheet resistance, suitable for many optoelectronic applications. Furthermore, we implemented such ultra-thin metallic films in Dielectric/Metal/Dielectric (DMD) structures based on Aluminum-doped Zinc Oxide (AZO) as the dielectric with an ultra-thin silver aluminum (Ag:Al) metallic interlayer. The multilayer structures were deposited by magnetron sputtering, which offers an industrial advantage and superior reliability over thermally evaporated DMDs. Finally, we tested the optimized DMD structures as a front contact for n-type silicon solar cells by introducing a hole-selective vanadium pentoxide (V2O5) dielectric layer.

Phase I pharmacokinetic/pharmacodynamic study of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in first-line treatment of patients with metastatic colorectal cancer.

PURPOSE: To determine the recommended dose (RD) of EKB-569, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer (mCRC). METHODS: Patients with previously untreated mCRC received FOLFIRI and EKB-569 at doses of 10, 25, 50, and 75 mg/day (EKB started on day 3). Three sequential skin biopsies were obtained in selected patients to assess the pharmacodynamic effects on EGFR signaling of FOLFIRI alone and with EKB-569. Complete pharmacokinetic sampling and tumor biopsies, when feasible, were conducted. RESULTS: Forty-seven patients were enrolled. Dose-limiting toxicities (grade 3 diarrhea or asthenia) were observed in 1/7 patients at 50 mg EKB-569 and in 2/3 at 75 mg. Two additional dose levels (35 mg EKB-569/day and 50 mg EKB-569/day plus modified FOLFIRI) were evaluated. The RD was 25 mg EKB-569/full dose FOLFIRI. Grades 3 to 4 toxicities in >10% of patients were diarrhea (30%), neutropenia (21%), and asthenia (17%). Twenty-one patients had an objective response [48%; 95% confidence interval (95% CI), 32-65%]. The median time to tumor progression was 7.7 months. At the RD, EKB-569 resulted in complete inhibition of phosphorylated EGFR (pEGFR) and downstream receptor signaling in skin and tumor samples. FOLFIRI alone did not affect pEGFR, but inhibited epidermal proliferation and activated mitogen-activated protein kinase (MAPK) and induced p27 expression in the skin. CONCLUSION: The RD of EKB-569 is 25 mg/day when combined with FOLFIRI and results in complete EGFR inhibition. Chemotherapy alone interferes with pharmacodynamic markers, an observation to be taken into account in future studies of targeted agents with chemotherapy.

[Neurocognitive disorders related to human immunodeficiency virus infection]. / Trastornos neurocognitivos en la infección por el virus de la inmunodeficiencia humana.

Disruption of neurocognitive functioning is one of most frequent complications in patients with HIV infection nowadays. The Highly Active Antiretroviral Therapy (HAART) has demonstrated an improvement associated with its use, although there are different works that show this improvement is achieved in a low proportion of individuals who initiate therapy. The most known characterization of neurocognitive dysfunction is the HIV-associated Dementia (HAD), yet there may also exist the asymptomatic neurocognitive impairment (ANI) or the Minor Cognitive-Motor Disorder (MCMD). This review describes the disorders related to HIV infection, and comments on possible interventions focused on the protection of neurocognitive functioning in HIV-infected people.

Modeling the solubility behavior of CO(2), H(2), and Xe in [C(n)-mim][Tf(2)N] ionic liquids.

We present here a new model for the imidazolium-based ionic liquids (ILs) with the bis(trifluoromethylsulfonyl)imide anion [Tf(2)N](-) in the context of the soft-SAFT EoS. The model is used to predict the solubility of several compounds in these ILs, and results are compared to available experimental data. Since in the soft-SAFT EoS an associating site is used to represent a short-range and highly directional attractive force among molecules, we have used this feature to mimic the main interactions between the anion and the cation for the alkylimidazolium-[Tf(2)N] ILs. The members of the alkylimidazolium-[Tf(2)N] family are modeled as Lennard-Jones chains with three associating sites in each molecule (one "A" site and two "B" sites). An "A" site represents the nitrogen atom interactions with the cation, and a "B" site represents the delocalized charge due the oxygen molecules on the anion. Each type of associating site is identically defined, but only AB interactions between different IL molecules are allowed. Model parameters for the ionic liquids were estimated with experimental density data from different authors, following a similar approach taken in our previous work [Andreu and Vega, J. Phys. Chem. C 2007, 111, 16028]. The new set of parameters was used to study the solubility behavior of hydrogen, carbon dioxide, and xenon in these ILs over a wide range of temperature and pressure. It has been observed that no binary parameters are needed to correlate the solubility of hydrogen in [C(6)-mim][Tf(2)N] at different temperatures, and predictions up to 100 MPa are presented here. The model is able to correlate with very good agreement the experimental data for the systems [C(n)-mim][Tf(2)N] + CO(2) with only one temperature-independent mixture parameter, while two temperature-independent mixture parameters are needed to correlate the experimental solubility data for the systems IL + Xe, attaining an excellent agreement in a wide range of temperatures. The work presented here reinforces previous results, proving that a reasonable simple model for the IL within the framework of soft-SAFT is able to describe the physical absorption of different gases in ILs with good accuracy, in spite of the most complex nature of the anion, without the need of further parameters or terms. In addition, since these parameters do not depend on the particular conditions at which they were fitted, soft-SAFT is used then to analyze the solubility dependence of these gases in ILs, according to the anion nature and the alkyl chain length of the imidazolium cation by the use of the models developed within this approach.

Lesions of the cardiophrenic space: findings at cross-sectional imaging.

Cross-sectional imaging techniques allow excellent visualization of the cardiophrenic space. Under normal conditions, the cardiophrenic space is occupied by fat, the amount of which is usually increased in overweight individuals. It has been suggested that this fat accumulation correlates with the risk of cardiovascular disease. Several alterations originating above or below the diaphragm can affect the cardiophrenic space. Inflammatory lesions such as pericardial fat necrosis and tumoral masses are sometimes seen. Lymphoma is a major but not exclusive cause of cardiophrenic adenopathy and must be differentiated from lymphatic seeding of supradiaphragmatic and infradiaphragmatic malignancies. In patients with portal hypertension, cardiophrenic space varices are not uncommon. Other masses or pseudomasses occurring in this region include pericardial cysts, mediastinal tumors, and diaphragmatic hernia. Computed tomography and magnetic resonance imaging of the thorax are helpful in characterizing cardiophrenic lesions initially identified at plain radiography. Such characterization helps narrow the differential diagnosis when lesions are detected in this location.

Radiological findings of unilateral tuberculous lung destruction.

OBJECTIVES: The aim of this report is to identify the radiological findings of unilateral tuberculous lung destruction (UTLD). MATERIALS AND METHODS: Thirteen patients with (UTLD) were reviewed from 1999 to 2014. Only patients with radiological evidence of absence of pulmonary parenchyma preserved were included. Clinical and demographic data were obtained and radiological studies (chest radiograph and CT) were retrospectively reviewed. RESULTS: The left lung was more commonly involved (85%). The following radiological findings were found in all cases: a decrease in the diameter of the pulmonary vessels of the affected lung, herniation of the contralateral lung and hypertrophy of the ribs and/or thickening of extrapleural fat. Two radiological patterns were identified: UTLD with cystic bronchiectasis (85%) and UTLD without residual cystic bronchiectasis (15%). Forty-six per cent of cases had respiratory infection symptoms with presence of air-fluid levels in the affected lung as the most common finding in these patients. CONCLUSIONS: Total unilateral post-tuberculous lung destruction is an irreversible complication with the following main radiological features: predominantly left-sided location, decreases in the diameter of the ipsilateral pulmonary vessels, herniation of the contralateral lung and hypertrophy of the ribs and/or thickening of extrapleural fat. TEACHING POINTS: • Unilateral tuberculous lung destruction is an irreversible complication of tuberculosis. • Left-side predominance and herniation of the contralateral lung are characteristic. • Decreased diameter of the ipsilateral pulmonary vessels occurred in all patients. • The pattern with residual cystic bronchiectasis is the most frequent. • Superimposed non-tuberculous infections may affect the destroyed lung.

Phase I pharmacokinetic and pharmacodynamic study of weekly 1-hour and 24-hour infusion BMS-214662, a farnesyltransferase inhibitor, in patients with advanced solid tumors.

PURPOSE: BMS-214662 is a potent, nonpeptide, small molecule inhibitor of human farnesyltransferase (FT). We have conducted a phase I pharmacokinetic (PK) and pharmacodynamic study of BMS-214662 administered intravenously weekly with 1- and 24-hour infusions. The objectives were to determine the dose-limiting toxicities and the recommended dose (RD), to describe PKs, and to evaluate the relationships between BMS-214662 exposure, FT inhibition, downstream signaling, and induction of apoptosis in tumor samples. PATIENTS AND METHODS: Patients with advanced solid tumors and adequate organ function were eligible. The dose was escalated according to a modified Fibonacci schedule. RESULTS: high (> 80%) but short-lived (< or = 6 hours) in the 1-hour infusion and moderate (> 40%) but long-lived (24 hours) in the 24-hour infusion. BMS-214662 induced apoptosis in tumors but did not inhibit MAPK signaling. CONCLUSION: BMS-214662 can be safely delivered in both the 1-hour and 24-hour infusions at biologically active doses, with the preclinical, PK, and pharmacodynamic profiles favoring the 24-hour schedule.

Hypofractionated 3D radiotherapy for inoperable T1-3 N0-1 non-small-cell lung cancer.

OBJECTIVE: This study assessed the toxicity and clinical outcomes of three-dimensional (3D) hypofractionated radiotherapy (HFRT) for medically inoperable T1-3 N0-1 non-small-cell lung cancer (NSCLC). METHODS: 34 patients with inoperable early-stage NSCLC were treated from August 2008 to April 2013. Prior to enrolment, patients were required to be evaluated by an experienced thoracic surgeon to determine the "operability". All received 57 Gy in 19 fractions followed by escalated doses of 3-Gy fractions, up to a total dose of 66 Gy using a 3D conformal technique. Toxicities were measured using the Common Terminology Criteria for Adverse Effects v. 4.0. RESULTS: The median follow-up was 33 months (7-74 months). Toxicity grades ≥3 were not observed. Local control (LC) was 80.4% at 2 years, whereas regional control (RC) was 78%. The overall survival (OS), time to progression (TTP) and time to distant metastasis (TTM) at 2 years were 60%, 59% and 80%, respectively. For patients with T1-2 N0 and a tumour size <45 mm (n = 19), rates of OS, TTP and TTM at 2 years were 71%, 75% and 94%, respectively. LC and RC at 2 years were 85% and 94%, respectively. CONCLUSION: HFRT using 3.0-Gy fractions amounting to a total dose of 66 Gy is the recommended dose. A Phase 2 trial is warranted in order to assess the safety and efficacy of this fractionation scheme. ADVANCES IN KNOWLEDGE: HFRT results in a favourable outcome in early-stage lung cancer without the usual restrictions in tumour size and/or location associated with previous treatment methods. No special equipment is required, therefore permitting its application in any centre.