Multifractal characterization of nystagmus eye movements.

In this work, we investigate the multifractal properties of eye movement dynamics of children with infantile nystagmus, particularly the fluctuations of its velocity. The eye movements of three children and one adult with infantile nystagmus were evaluated in a simple task in comparison with 28 children with no ocular pathologies. Four indices emerge from the analysis: the classical Hurst exponent, the singularity strength corresponding to the maximum of the singularity spectrum, the asymmetry of the singularity spectrum, and the multifractal strength, each of which characterizes a particular aspect of eye movement dynamics. Our findings indicate that, when compared to children with no ocular pathologies, patients with infantile nystagmus present lower values of all indices. Except for the multifractal strength, the difference in the remaining indices is statistically significant. To test whether the characterization of patients with infantile nystagmus in terms of multifractality indices allows them to be distinguished from children without ocular pathologies, we performed an unsupervised clustering analysis and classified the subjects using supervised clustering techniques. The results indicate that these indices do, indeed, distinctively characterize the eye movements of patients with infantile nystagmus.

The importance of prevalence and pre-test probability on the microbiological diagnosis of SARS-CoV-2: the case of Spain in 2020.

OBJECTIVE: The aim of this work was to estimate the conditioned probability for the diagnosis of SARS-CoV-2 infection with reverse transcription polymerase chain reaction (RT-PCR), viral antigen rapid diagnostic tests (Ag-RDT), and antibody detection tests depending on the prevalence in the specific healthcare settings in Spain in 2020, and on the pre-test probability (PTP) according to the clinical situation, age and unknown or close contacts of the patient. METHODS: Performance parameters of tests were obtained from literature. Prevalence data and PTP were obtained from Spanish sources and a survey, respectively. The post-test probability is the positive predictive value (PPV) when test is positive. For negative result, we also calculated the probability of having the infection (false negatives). RESULTS: For both RT-PCR and viral Ag-RDT, the lowest PPV values were for the population screenings. This strategy proved to be useful in ruling out infection but generates a high number of false positives. At individual level, both tools provided high PPV (≥ 97%) when the PTP values are over 35%. In seroprevalence studies, though the specificity of IgG alone tests is high, under low seroprevalence, false positives cannot be avoided. Total antibodies tests are useful for diagnosis of COVID-19 in those doubtful cases with RT-PCR or Ag-RDT tests being repeatedly negative. CONCLUSIONS: The interpretating of results depends not only on the accuracy of the test, but also on the prevalence of the infection in different settings, and the PTP associated to the patient before performing the test.

Realising the European network of biodosimetry: RENEB-status quo.

Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed.

Exploration of plant growth and development using the European Modular Cultivation System facility on the International Space Station.

Space experiments provide a unique opportunity to advance our knowledge of how plants respond to the space environment, and specifically to the absence of gravity. The European Modular Cultivation System (EMCS) has been designed as a dedicated facility to improve and standardise plant growth in the International Space Station (ISS). The EMCS is equipped with two centrifuges to perform experiments in microgravity and with variable gravity levels up to 2.0 g. Seven experiments have been performed since the EMCS was operational on the ISS. The objectives of these experiments aimed to elucidate phototropic responses (experiments TROPI-1 and -2), root gravitropic sensing (GRAVI-1), circumnutation (MULTIGEN-1), cell wall dynamics and gravity resistance (Cell wall/Resist wall), proteomic identification of signalling players (GENARA-A) and mechanism of InsP3 signalling (Plant signalling). The role of light in cell proliferation and plant development in the absence of gravity is being analysed in an on-going experiment (Seedling growth). Based on the lessons learned from the acquired experience, three preselected ISS experiments have been merged and implemented as a single project (Plant development) to study early phases of seedling development. A Topical Team initiated by European Space Agency (ESA), involving experienced scientists on Arabidopsis space research experiments, aims at establishing a coordinated, long-term scientific strategy to understand the role of gravity in Arabidopsis growth and development using already existing or planned new hardware.

Post-chemoradiation anastomotic recurrence in locally advanced rectal cancer: no increased risk associated with distal margin.

BACKGROUND AND PURPOSE: Anastomotic recurrence after radical sphincter-preserving surgery preceded by neoadjuvant therapy in locally advanced rectal cancer is an uncommon event that merits further assessment. The aim of this study is to analyze the effect of preoperative chemoradiation on the risk of anastomotic recurrence. Based on the initial extension of the tumor, we analyzed whether the distal surgical section was calculated through the virtual initial extension of the rectal tumor. PATIENTS AND METHODS: Eligible patients with locally advanced rectal cancer were offered preoperative chemoradiation, sphincter sparing surgery and intraoperative radiation therapy boost. RESULTS: 180 patients were treated with anterior resection (40 %), low anterior resection (45.6 %) and ultra-low anterior resection (14.4 %). With a median follow-up of 41.1 months (0.36-143 months), anastomotic recurrence was diagnosed in 9 patients (5 %). There was no statistical correlation with downstaging (T or N), downsizing effects, or with distance from the lower limit of the residual lesion to the distal margin. Virtual intratumoral surgical section was speculated in 44 patients (3 developed anastomotic recurrence; 6.8 vs 4.8 %, p = 0.482). CONCLUSION: Anastomotic recurrence in patients with rectal cancer treated with neoadjuvant chemoradiation is an infrequent event. Virtual intratumoral surgical sections followed by anastomosis do not contribute to an excessive risk of recurrence. Our findings encourage the development of policies for preservation of the ano-rectal complex in rectal cancer patients.

Cell proliferation and plant development under novel altered gravity environments.

Gravity is a key factor for life on Earth. It is the only environmental factor that has remained constant throughout evolution, and plants use it to modulate important physiological activities; gravity removal or alteration produces substantial changes in essential functions. For root gravitropism, gravity is sensed in specialised cells, which are capable of detecting magnitudes of the g vector lower than 10(-3) . Then, the mechanosignal is transduced to upper zones of the root, resulting in changes in the lateral distribution of auxin and in the rate of auxin polar transport. Gravity alteration has consequences for cell growth and proliferation rates in root meristems, which are the basis of the developmental programme of a plant, in which regulation via auxin is involved. The effect is disruption of meristematic competence, i.e. the strict coordination between cell proliferation and growth, which characterises meristematic cells. This effect can be related to changes in the transport and distribution of auxin throughout the root. However, similar effects of gravity alteration have been found in plant cell cultures in vitro, in which neither specialised structures for gravity sensing and signal transduction, nor apparent gravitropism have been described. We postulate that gravity resistance, a general mechanism of cellular origin for developing rigid structures in plants capable of resisting the gravity force, could also be responsible for the changes in cell growth and proliferation parameters detected in non-specialised cells. The mechanisms of gravitropism and graviresistance are complementary, the first being mostly sensitive to the direction of the gravity vector, and the second to its magnitude. At a global molecular level, the consequence of gravity alteration is that the genome should be finely tuned to counteract a type of stress that plants have never encountered before throughout evolution. Multigene families and redundant genes present an advantage in that they can experience changes without the risk of being deleterious and, for this reason, they should play a key role in the response to gravitational stress.

Intraoperative radiotherapy with electrons: fundamentals, results, and innovation.

RATIONALE AND OBJECTIVES: To analyse the programme activity and clinical innovation and/or technology developed over a period of 17 years with regard to the introduction and the use of intraoperative radiotherapy (IORT) as a therapeutic component in a medical-surgical multidisciplinary cancer hospital. MATERIAL AND METHODS: To standardise and record this procedure, the Radiation Oncology service has an institutional programme and protocols that must be completed by the different specialists involved. For 17 years, IORT procedures were recorded on a specific database that includes 23 variables with information recorded on institutional protocols. As part of the development and innovation activity, two technological tools were implemented (RADIANCE and MEDTING) in line with the standardisation of this modality in clinical practice. RESULTS: During the 17 years studied, 1,004 patients were treated through 1,036 IORT procedures. The state of the disease at the time of IORT was 77% primary and 23% recurrent. The origin and distribution of cancers were 62% gastrointestinal, 18% sarcomas, 5% pancreatic, 2% paediatric, 3% breast, 7% less common locations, and 2% others. The research and development projects have generated a patent on virtual planning (RADIANCE) and proof of concept to explore as a professional social network (MEDTING). During 2012, there were 69 IORT procedures. There was defined treatment volume (target or target region) in all of them, and 43 were conducted by the virtual planning RADIANCE system. Eighteen have been registered on the platform MEDTING as clinical cases. CONCLUSION: The IORT programme, developed in a university hospital with an academic tradition, and interdisciplinary surgical oncology, is a feasible care initiative, able to generate the necessary intense clinical activity for tending to the cancer patient. Moreover, it is a competitive source for research, development, and scientific innovation.

Research opportunities in intraoperative radiation therapy: the next decade 2013-2023.

The reality of intraoperative radiation therapy (IORT) practice is consistent with an efficient and highly precise radiation therapy technique to safely boost areas at risk for local recurrence. Long-term clinical experience has shown that IORT-containing multi-modality regimens appear to improve local disease control, if not survival in many diseases. Research with IORT is a multidisciplinary scenario that covers knowledge from radiation beam adapted development to advance molecular biology for bio-predictability of outcome. The technical parameters employed in IORT procedures are important information to be recorded for quality assurance and clinical results analysis. In addition, specific treatment planning systems for IORT procedures are available, to help in the treatment decision-making process. A systematic revision of opportunities for research and innovation in IORT is reported including radiation beam modulation, delivery, dosimetry and planning; infrastructure and treatment factors; experimental and clinical radiobiology; clinical trials, innovation and translational research development.

Collateral circulation on perfusion-computed tomography-source images predicts the response to stroke intravenous thrombolysis.

BACKGROUND AND PURPOSE: Perfusion-computed tomography-source images (PCT-SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT-SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis. METHODS: We studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color-coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT-SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2-3) vs. poor (scores 0-1) collaterals. The predetermined primary end-point was a good 3-month functional outcome, while early neurological recovery, transcranial duplex-assessed 24-h MCA recanalization, 24-h hypodensity volume and hemorrhagic transformation were considered secondary end-points. RESULTS: Fifty-four patients were included (55.5% women, median NIHSS 10), and 4-13-23-14 patients had LMC score (LMCs) of 0-1-2-3, respectively. The probability of a good long-term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, P = 0.004. Good-LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23-197.75), P = 0.008]. Patients with good LMCs had better early neurological recovery (P = 0.001), smaller hypodensity volumes (P < 0.001) and a clear trend towards a higher recanalization rate. CONCLUSIONS: A higher degree of LMC assessed by PCT-SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients.

Realising the European Network of Biodosimetry (RENEB).

In Europe, a network for biological dosimetry has been created to strengthen the emergency preparedness and response capabilities in case of a large-scale nuclear accident or radiological emergency. Through the RENEB (Realising the European Network of Biodosimetry) project, 23 experienced laboratories from 16 European countries will establish a sustainable network for rapid, comprehensive and standardised biodosimetry provision that would be urgently required in an emergency situation on European ground. The foundation of the network is formed by five main pillars: (1) the ad hoc operational basis, (2) a basis of future developments, (3) an effective quality-management system, (4) arrangements to guarantee long-term sustainability and (5) awareness of the existence of RENEB. RENEB will thus provide a mechanism for quick, efficient and reliable support within the European radiation emergency management. The scientific basis of RENEB will concurrently contribute to increased safety in the field of radiation protection.

[Change of treatment in patients with multiple sclerosis and its consequences in clinical practice]. / Cambio de tratamiento en pacientes con esclerosis multiple y sus consecuencias en la practica clinica.

INTRODUCTION: Thirty per cent of patients with multiple sclerosis (MS) present a suboptimal response to treatment in the first few years. The real impact of the change of treatment has still not been well established. AIMS: To describe our clinical practice with regard to the change of treatment in MS patients with a suboptimal response and to analyse their progress depending on our therapeutic decisions. PATIENTS AND METHODS: The study is observation-based and retrospective. The sample was made up of patients with relapsing-remitting MS and at least one event after establishing immunomodulatory treatment. Both the intention to change treatment and the delays until the actual change took place were taken into account. The theoretical consequences of these strategies were measured by the changes in the expected curve of the Multiple Sclerosis Severity Scale (MSSS). RESULTS: A comparison of those who changed immunomodulator with those that did not showed that 64.3% versus 35.3%, respectively, improved on the expected curve of the MSSS (p > 0.05). Patients who improved the expected curve of the MSSS had changed treatment before those who did not improve (1.9 months versus 6 months), although the differences were not significant. The mean time that elapsed between taking the decision to change and actually changing the treatment was 2.70 ± 3.55 months. CONCLUSIONS: Despite limitations due to the size of the sample, the patients with a suboptimal response who changed treatment early could benefit from an improvement in their expected progression on the MSSS.

Comparative analysis of Drosophila melanogaster and Caenorhabditis elegans gene expression experiments in the European Soyuz flights to the International Space Station.

The European Soyuz missions have been one of the main routes for conducting scientific experiments onboard the International Space Station, which is currently in the construction phase. A relatively large number of life and physical sciences experiments as well as technology demonstrations have been carried out during these missions. Included among these experiments are the Gene experiment during the Spanish "Cervantes" Soyuz mission and the ICE-1st experiment during the Dutch "Delta" mission. In both experiments, full genome microarray analyses were carried out on RNA extracted from whole animals recovered from the flight. These experiments indicated relatively large scale changes in gene expression levels in response to spaceflight for two popular model systems, Drosophila melanogaster (Gene) and Caenorabditis elegans (ICE-1st). Here we report a comparative analysis of results from these two experiments. Finding orthologous genes between the fruit fly and the nematode was far from straightforward, reducing the number of genes that we could compare to roughly 20% of the full comparative genome. Within this sub-set of the data (2286 genes), only six genes were found to display identical changes between species (decreased) while 1809 genes displayed no change in either species. Future experiments using ground simulation techniques will allow producing a better, more comprehensive picture of the putative set of genes affected in multicellular organisms by changes in gravity and getting a deeper understanding of how animals respond and adapt to spaceflight.

[Refractive surprise after LASIK]. / Sorpresa refractiva tras LASIK.

CASE REPORT: A female patient underwent laser in situ keratomileusis (LASIK) in both eyes. The final degree of astigmatism in her left eye was double the preoperative value due to an error in data management. Complex surgery to both eyes was necessary to resolve the mistake. DISCUSSION: Complications in refractive surgery can occur, however errors in data management must be minimized by double-checking. Solutions to resolve the errors made can be difficult and the entire staff must share responsibility to avoid these undesirable outcomes.

Pharmacological study of IQM-97,423, a potent and selective CCK1 receptor antagonist with protective effect in experimental acute pancreatitis.

The pharmacological profile of the new CCK1 receptor antagonist IQM-97,423, (4aS,5R)-2-benzyl-5-(tert-butylaminocarbonyl-tryptophyl)amino-1,3-dioxoperhydropyrido-[1,2-c]pyrimidine, was examined in in vitro and in vivo studies and compared with typical CCK1 antagonists such as devazepide and lorglumide. IQM-97,423 showed a high affinity at [3H]-pCCK8-labeled rat pancreatic CCK1 receptors, and was virtually devoid of affinity at brain CCK2 receptors. IQM-97,423 antagonized CCK8S-stimulated alpha-amylase release from rat pancreatic acini with a potency similar to devazepide and much higher than lorglumide. In the guinea pig isolated longitudinal muscle-myenteric plexus preparation, IQM-97,423 produced a full antagonism of the contractile response elicited by CCK8S and a weaker effect on the contraction elicited by CCK4, suggesting a selective antagonism at CCK1 receptors. The protective effect of IQM-97,423 and devazepide was tested in two models of acute pancreatitis in rats, induced by injection of cerulein or by combined bile and pancreatic duct obstruction. The new compound fully prevented the cerulein-induced increase in plasma pancreatic enzymes and in pancreas weight with a potency similar to devazepide. In common bile-pancreatic duct ligature-induced acute pancreatitis, IQM-97,423 partially prevented, like devazepide, the increase in plasma pancreatic enzyme activity and in pancreas weight. Consequently, the pyridopyrimidine derivative IQM-97,423 is a potent and highly selective CCK1 receptor antagonist with preventive effects in two experimental models of acute pancreatitis and a potential therapeutic interest.

The long-term adaptation of multicellular model organisms to non-terrestrial and space environments.

The main point in this presentation is the following: It is of crucial importance that the Space Agencies define and support the long-term directions for Space Biology Research. The development and upgrading of Facilities and Carriers should be coordinated with the preparatory activities of scientific groups interested in tackling major questions using the future opportunities in the Space Exploration Programs. The current effort in establishing larger Research Networks may lead the way to a successful Space Program in the XXI Century.

Towards the establishment of a permanent colony of Drosophila in the International Space Station: hardware tests and adaptation of techniques.

Our group has the long-term goal of establishing a permanent colony of Drosophila melanogaster in the International Space Station (ISS) to study its long-term adaptation to this unusual environment. We are currently building an enhanced version of an automatic cultivation unit (ESE1) in which we can grow flies with minimal crew involvement. We are working on a fixation unit as well. We are also adapting current protocols to maintain fixed animals during at least three months, the minimal refurbishment shuttle flight time, with minimal handling and maximal automatization, that can be used for inmuno-cytochemistry, ultrastructure or molecular experiments.

Pathologic downstaging of T3-4Nx rectal cancer after chemoradiation: 5-fluorouracil vs. Tegafur.

PURPOSE: To describe downstaging effects in locally advanced rectal cancer induced by 2 fluopirimidine radiosensitizing agents given through different routes in conjunction with preoperative radiotherapy. METHODS AND MATERIALS: From March 1995 to December 1999, two consecutive groups of patients with cT3-4Nx rectal cancer (94% CT scan, 71% endorectal ultrasound) were treated with either (1) 45-50 Gy (1.8 Gy/day, 25 fractions) and 5-fluorouracil (5-FU) (500-1,000 mg/m2 by 24-h continuous i.v. infusion on Days 1-4 and 21-25) or (2) oral Tegafur (1,200 mg/day on Days 1-35, including weekends). Surgery was performed 4 to 6 weeks after the completion of chemoradiation. RESULTS: The total T downstaging rate was 46% in the 5-FU group and 53% in the Tegafur group. Subcategories were downstaged by the sensitizing agents (5-FU vs. Tegafur) as follows: pT0-1, 14% vs. 23%; pT2, 32% vs. 32%; pT3, 49% vs. 37%; pT4, 5% vs. 7%; and N(0), 74% vs. 86%. Analysis of residual malignant disease in the specimen discriminated mic/mac subgroups (mic: <20% of microscopic cancer residue), with evident superior downstaging effects in the Tegafur-treated group: pTmic 23% vs. 58% (p = 0.002). CONCLUSIONS: When administered concurrent with pelvic irradiation, oral Tegafur induced downstaging rates in both T and N categories superior to those induced by intermediate doses of 5-FU by continuous i.v. infusion. In this pilot experience, oral Tegafur reproduced the characteristics of downstaging described previously when full doses of 5-FU have been combined with radiotherapy.

Gamma-detecting probe used intraoperatively to locate the sentinel lymph node in patients with malignant melanoma.

OBJECTIVE: To assess the usefulness of lymphoscintigraphy and intraoperative gamma probe in the detection of sentinel lymph nodes. DESIGN: Prospective open study. SETTING: University hospital, Spain. SUBJECTS: 40 patients with malignant melanoma (24 stage I/II, 16 stage III). INTERVENTION: The day before operation a lymphoscintigram with 99mTc-nanocolloid was taken and the first lymph node identified was considered to be the sentinel node. A hand-held gamma probe was used for intraoperative mapping. MAIN OUTCOME MEASURE: Identification of the sentinel node. RESULTS: Sentinel nodes were identified in 39/40 patients (98%). In 24 patients with stage I/II disease, 34 sentinel nodes were found (6 invaded and 28 clear of melanoma). A total number of 161 regional lymph nodes were harvested, none of them invaded by melanoma. In 16 patients with stage III disease, 22 sentinel nodes were located (14 invaded and 8 clear of melanoma). A total of 89 regional lymph nodes were excised in patients with invaded sentinel nodes (44 of which were invaded and 45 clear of disease). 41 lymph nodes were excised from patients with clear sentinel nodes, and all were also clear of melanoma. CONCLUSIONS: We conclude that this is a useful technique for the selection of patients with melanoma who may require lymphadenectomy.