Improving graph-based detection of singular events for photochemical smog agents

Recently, a set of graph-based tools have been introduced for the identification of singular events of O3, NO2 and temperature time series, as well as description of their dynamics. These are based on the use of the Visibility Graphs (VG). In this work, an improvement of the original approach is proposed, being called Upside-Down Visibility Graph (UDVG). It adds the possibility of investigating the singular lowest episodes, instead of the highest. Results confirm the applicability of the new method for describing the multifractal nature of the underlying O3, NO2, and temperature. Asymmetries in the NO2 degree distribution are observed, possibly due to the interaction with different chemicals. Furthermore, a comparison of VG and UDVG has been performed and the outcomes show that they describe opposite subsets of the time series (low and high values) as expected. The combination of the results from the two networks is proposed and evaluated, with the aim of obtaining all the information at once. It turns out to be a more complete tool for singularity detection in photochemical time series, which could be a valuable asset for future research.Comment: 35 pages, 7 figure

Switching from natalizumab to fingolimod: an observational study

Background – Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known. Aims of the study – We report on clinical and MRI data and patient safety in a group of relapsing–remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks. Methods – The test for JC virus antibodies was performed in 18 relapsing–remitting multiple sclerosis patients who were being treated with natalizumab for more than 1 year. Eight seropositive patients switched to fingolimod while the seronegative patients continued with natalizumab. Results – After switching to fingolimod, five of eight patients (63%) experienced clinical relapses, and MRI activity was detected in six of eight patients (75%). Neither clinical relapses nor MRI activity was observed in the patients who continued with natalizumab. No serious adverse effects were detected. Conclusions – Natalizumab is an effective treatment for relapsing–remitting multiple sclerosis, but its discontinuation continues to be a complex problem. All of the therapies tried thus far, including fingolimod, have been unable to control the reactivation of the disease. Further studies addressing alternative therapies after natalizumab discontinuation are necessary

Desperately seeking a cure: Treatment seeking and appraisal in irritable bowel syndrome

© 2018 The British Psychological Society Objectives: Irritable bowel syndrome (IBS) is common and adversely affects patients' quality of life. Multiple potential treatment options exist for patients (and clinicians) to choose from, with limited evidence to inform treatment selection. The aim was to explore how patients with IBS go about seeking and appraising different treatment modalities, with a view to elucidating the psychological processes involved and identifying opportunities to improve clinical practice. Design: Qualitative study nested within a randomized controlled trial of therapist-delivered and web-based cognitive behavioural therapy versus treatment-as-usual for IBS. Methods: A total of 52 people participated in semi-structured interviews about their prior experiences of treatments for IBS. Transcripts were analysed using inductive thematic analysis. Results: Key themes (desperation for a cure, disappointment at lack of cure, appraising the effects of diverse treatments, and hope for positive effects) clustered around an overarching theme of being trapped within a vicious cycle of hope and despair on treatment seeking. A desperation and willingness drove interviewees to try any treatment modality available that might potentially offer relief. Coming to accept there is no cure for IBS helped interviewees escape the vicious cycle. Treatments were appraised for their effects on symptoms and quality of life while also considering, but rarely prioritizing, other aspects including convenience of the regimen itself, whether it addressed the perceived root causes of IBS, perceived side-effects, and cost. Conclusion: Treatment seeking in IBS can be challenging for patients. Supportive discussions with health care professionals about illness perceptions, treatment beliefs, and goals could improve patients' experiences. Statement of contribution What is already known on this subject? Irritable bowel syndrome (IBS) is a highly prevalent chronic relapsing functional gastrointestinal disorder. Studies show few treatment modalities provide complete symptom relief. IBS is associated with emotional and physical distress, and negatively impacts personal, social, and professional aspects of quality of life. What does this study add? Patients appraise IBS treatments for impact on quality of life and treatment characteristics. Developing acceptance and coping strategies helps escape treatment-seeking vicious cycles of hope and despair. Clinicians could better support patients by discussing their illness perceptions, treatment goals, and values

A new method to quantify and compare the multiple components of fitness-A study case with kelp niche partition by divergent microstage adaptations to Temperature

Point 1 Management of crops, commercialized or protected species, plagues or life-cycle evolution are subjects requiring comparisons among different demographic strategies. The simpler methods fail in relating changes in vital rates with changes in population viability whereas more complex methods lack accuracy by neglecting interactions among vital rates. Point 2 The difference between the fitness (evaluated by the population growth rate.) of two alternative demographies is decomposed into the contributions of the differences between the pair-wised vital rates and their interactions. This is achieved through a full Taylor expansion (i.e. remainder = 0) of the demographic model. The significance of each term is determined by permutation tests under the null hypothesis that all demographies come from the same pool. Point 3 An example is given with periodic demographic matrices of the microscopic haploid phase of two kelp cryptic species observed to partition their niche occupation along the Chilean coast. The method provided clear and synthetic results showing conditional differentiation of reproduction is an important driver for their differences in fitness along the latitudinal temperature gradient. But it also demonstrated that interactions among vital rates cannot be neglected as they compose a significant part of the differences between demographies. Point 4 This method allows researchers to access the effects of multiple effective changes in a life-cycle from only two experiments. Evolutionists can determine with confidence the effective causes for changes in fitness whereas population managers can determine best strategies from simpler experimental designs.CONICYT-FRENCH EMBASSADY Ph.D. gran

Physiological lentiviral vectors for the generation of improved CAR-T cells

Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome and neuroinflammation) and relapse of 40%-50% of the treated patients. Most CAR-T cells are generated using retroviral vectors with strong promoters that lead to high CAR expression levels, tonic signaling, premature exhaustion, and overstimulation, reducing efficacy and increasing side effects. Here, we show that lentiviral vectors (LVs) expressing the transgene through a WAS gene promoter (AW-LVs) closely mimic the T cell receptor (TCR)/CD3 expression kinetic upon stimulation. These AW-LVs can generate improved CAR-T cells as a consequence of their moderate and TCR-like expression profile. Compared with CAR-T cells generated with human elongation factor alpha (EF1 alpha)-driven-LVs, AW-CAR-T cells exhibited lower tonic signaling, higher proportion of naive and stem cell memory T cells, less exhausted phenotype, and milder secretion of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN)-gamma after efficient destruction of CD19(+) lymphoma cells, both in vitro and in vivo. Moreover, we also showed their improved efficiency using an in vitro CD19(+) pancreatic tumor model. We finally demonstrated the feasibility of large-scale manufacturing of AW-CAR-T cells in guanosine monophosphate (GMP)-like conditions. Based on these data, we propose the use of AWLVs for the generation of improved CAR-T products

First bounds on the very high energy gamma-ray emission from Arp 220

Using the Major Atmospheric Gamma Imaging Cherenkov Telescope (MAGIC), we have observed the nearest ultra-luminous infrared galaxy Arp 220 for about 15 hours. No significant signal was detected within the dedicated amount of observation time. The first upper limits to the very high energy $\gamma$-ray flux of Arp 220 are herein reported and compared with theoretical expectations.Comment: Accepted for publication in Ap

Treatments for irritable bowel syndrome: patients' attitudes and acceptability

<p>Abstract</p> <p>Background</p> <p>Irritable Bowel Syndrome, a highly prevalent chronic disorder, places significant burden on the health service and the individual. Symptomatic distress and reduced quality of life are compounded by few efficacious treatments available. As researchers continue to demonstrate the clinical efficacy of alternative therapies, it would be useful to gain a patient-perspective of treatment acceptability and identify patient's attitudes towards those modalities considered not acceptable.</p> <p>Methods</p> <p>Six hundred and forty-five participants identified from an earlier IBS-prevalence study received a postal questionnaire to evaluate preferences and acceptability of nine forms of treatment. Proportions accepting each form of treatment were calculated and thematic analysis of qualitative data undertaken.</p> <p>Results</p> <p>A total of 256 (39.7%) of 645 potential respondents completed the questionnaire (mean age 55.9 years, 73% female). Tablets were most acceptable (84%), followed by lifestyle changes (diet (82%), yoga (77%)). Acupuncture (59%) and suppositories (57%) were less acceptable.</p> <p>When explaining lack of acceptability, patient views fell into four broad categories: dislike treatment modality, do not perceive benefit, general barriers and insufficient knowledge. Scepticism, lack of scientific rationale and fear of CAM were mentioned, although others expressed a dislike of conventional medical treatments. Past experiences, age and health concerns, and need for proof of efficacy were reported.</p> <p>Conclusion</p> <p>Most patients were willing to accept various forms of treatment. However, the reservations expressed by this patient-population must be recognised with particular focus directed towards allaying fears and misconceptions, seeking further evidence base for certain therapies and incorporating physician support and advice.</p

Constraints on the steady and pulsed very high energy gamma-ray emission from observations of PSR B1951+32/CTB 80 with the MAGIC Telescope

We report on very high energy gamma-observations with the MAGIC Telescope of the pulsar PSR B1951+32 and its associated nebula, CTB 80. Our data constrain the cutoff energy of the pulsar to be less than 32 GeV, assuming the pulsed gamma-ray emission to be exponentially cut off. The upper limit on the flux of pulsed gamma-ray emission above 75 GeV is 4.3*10^-11 photons cm^-2 sec^-1, and the upper limit on the flux of steady emission above 140 GeV is 1.5*10^-11 photons cm^-2 sec^-1. We discuss our results in the framework of recent model predictions and other studies.Comment: 7 pages, 7 figures, replaced with published versio

MAGIC upper limits on the very high energy emission from GRBs

The fast repositioning system of the MAGIC Telescope has allowed during its first data cycle, between 2005 and the beginning of year 2006, observing nine different GRBs as possible sources of very high energy gammas. These observations were triggered by alerts from Swift, HETE-II, and Integral; they started as fast as possible after the alerts and lasted for several minutes, with an energy threshold varying between 80 and 200 GeV, depending upon the zenith angle of the burst. No evidence for gamma signals was found, and upper limits for the flux were derived for all events, using the standard analysis chain of MAGIC. For the bursts with measured redshift, the upper limits are compatible with a power law extrapolation, when the intrinsic fluxes are evaluated taking into account the attenuation due to the scattering in the Metagalactic Radiation Field (MRF).Comment: 25 pages, 9 figures, final version accepted by ApJ. Changet title to "MAGIC upped limits on the VERY high energy emission from GRBs", re-organized chapter with description of observation, removed non necessaries figures, added plot of effective area depending on zenith angle, added an appendix explaining the upper limit calculation, added some reference