The geometry of antisymplectic involutions, I

We study fixed loci of antisymplectic involutions on projective hyperkahler manifolds of K3([n])-type. When the involution is induced by an ample class of square 2 in the Beauville-Bogomolov-Fujiki lattice, we show that the number of connected components of the fixed locus is equal to the divisibility of the class, which is either 1 or 2

Adoption of the personas technique in the open source software development process

The growth in the number of non-developer open source software (OSS) application users and the escalating use of these applications have led to the need and interest in developing usable OSS. OSS communities do not generally know how to apply usability techniques and are unclear about which techniques to use in each activity of the development process. The aim of our research is to adopt the Personas usability technique in the PSeInt OSS project and determine the feasibility of adapting the technique for application. To do this, we participated as volunteers in the project. We used the case study research method during technique application and participation in the community. As a result, we identified adverse conditions that were an obstacle to technique application and modified the technique to make it applicable. We can conclude from our experience that these changes were helpful for applying the technique, although it was not easy to recruit OSS users to participate in usability technique applicationThis research has been partly funded by several organizations, including the Government of Ecuador’s Secretariat of Higher Education, Science, Technology and Innovation (SENESCYT) through a scholarship and the State Technical University of Quevedo through doctoral training scholarships for university professors. Also this research was funded by the Spanish Ministry of Education, Culture and Sports FLEXOR and “Realizando Experimentos en la Industria del Software: Comprensión del Paso de Laboratorio a la Realidad” projects (TIN2014-52129-R and TIN2014-60490-P, respectively) and the eMadrid-CM “Investi-gación y Desarrollo de Tecnologías Educativas en la Comunidad de Madrid” project (S2013/ICE-2715

Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study

BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients. OBJECTIVE: To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. METHODS: The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation). CONCLUSIONS: The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin

Muscle sympathetic nerve activity in patients with acromegaly

Muscle sympathetic nerve activity was measured in nine acromegalic patients (age, 35 +/- 4 yr; body mass index, 28 +/- 2 kg/m2) and eight healthy subjects (age, 32 +/- 3 yr; body mass index, 25 +/- 2 kg/m2) by combining the forearm arterial-venous difference technique with the tracer method [infusion of tritiated norepinephrine (NE)]. Muscle NE release was quantified both at rest and during physiological hyperinsulinemia while maintaining euglycemia (approximately 90 mg/dL) by means of the euglycemic clamp. Arterial plasma NE was similar in the two groups at rest (197 +/- 28 and 200 +/- 27 pg/mL (-1) and slightly increased during insulin infusion. Forearm NE release was 2.33 +/- 0.55 ng x liter(-1) x min(-1) in healthy subjects and 2.67 +/- 0.61 ng x liter(-1) x min(-1) in acromegalic subjects in the basal state and increased to a similar extent during insulin infusion in both groups (3.13 +/- 0.71 and 3.32 +/- 0.75 ng x L(-1) x min(-1), P < 0.05 vs. basal), indicating a normal stimulatory effect of insulin on muscle sympathetic activity. In contrast, insulin-stimulated forearm glucose uptake was markedly lower in acromegalic patients (2.3 +/- 0.4 mg x L(-1) x min(-1)) than in control subjects (7.9 +/- 1.3 mg x L(-1) x min(-1), P < 0.001), indicating the presence of severe insulin resistance involving glucose metabolism. Our data demonstrate that patients with long-term acromegaly have normal sympathetic activity in the skeletal muscle in the basal, postabsorptive state and normal increments in NE spillover in response to the sympatho-excitatory effect of insulin. Thus, the presence of severe insulin resistance in acromegaly is not accounted for by adrenergic mechanisms

Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab

The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index ≥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index ≥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p &lt; 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies

A new fluorescent oligonucleotide probe for in-situ identification of Microcystis aeruginosa in freshwater.

contaminated water bodies (freshwater, brackish and marine areas). Among 150 known cyanobacteria genera,>40 species are able to produce toxins, which are natural compounds that differ from both a chemical and toxicological point of view and are responsible for acute and chronic poisoning in animals and humans. Among the main classes of cyanotoxins, microcystins are frequently found in the environment. Fast and accurate methods for unequivocally identifying microcystin-producing cyanobacteria, such as Microcystis aeruginosa in water bodies, are necessary to distinguish them from other non-toxic cyanobacteria and to manage and monitor algal blooms. For this purpose, we designed, developed and validated an oligonucleotide probe for FISH (Fluorescence In Situ Hybridization) analysis to detect Microcystis aeruginosa at the species level even at relatively low concentrations in freshwater. The FISH probe, MicAerD03, was designed using the ARB software with the Silva database within the framework of the MicroCoKit project, also with the intention of adding it to the microarray from the EU project, μAQUA, for freshwater pathogens, which had only genus level probes for Microcystis. We tested various fixative methods to minimize the natural autofluorescence from chlorophyll-a and certain accessory pigments (viz., phycobilins and carotenoids). The FISH probe was tested on pure cultures of Microcystis aeruginosa, and then successfully applied to water samples collected from different sampling points of the Tiber River (Italy), using a laser confocal microscope. Subsequently, the probe was also conjugated at the 5′ end with horse-radish peroxidase (HRP-MicAerD03) to apply the CAtalysed Reported Deposition-FISH (CARD-FISH) for increasing the fluorescence signal of the mono-fluorescently labelled probe and make it possible to detect M. aeruginosa using an epifluorescence microscope. Samples taken within the EU MicroCokit project indicated thatmicroarray signals for Microcystis were coming from single cells and not colonial cells. We confirmed this with the CARD-FISH protocol used here to validate the microarray signals for Microcystis detected at the genus level in MicroCokit. This paper provides a new early warning tool for investigating M. aeruginosa at the species level even at low cell concentrations in surface water, which can be added to the μAqua microarray for all freshwater pathogens to complete the probe hierarchy for Microcystis aeruginosa

A real-life experience with eculizumab and efgartigimod in generalized myasthenia gravis patients

Introduction: Eculizumab, a complement active antibody, and efgartigimod, an Fc fragment that blocks neonatal Fc receptor, are both approved to treat generalized myasthenia gravis (gMG) patients. The objective of this study is to describe the clinical response to both treatments in a real-life setting. Methods: We collected baseline and follow-up clinical data using the Myasthenia Gravis-Activities of Daily Living (MG-ADL), and Quantitative Myasthenia Gravis (QMG). We included 63 patients, 32 treated with eculizumab and 31 with efgartigimod. Of the efgartigimod-treated patients, 22 were anti-acetylcholine receptor antibody-positive (AChR-Ab +) and 9 were AChR-Ab- (3 MuSK-Ab + and 6 seronegative). Results: Both treatments showed similar efficacy relative to the MG-ADL scale reduction (p = 0.237). Efgartigimod had a similar effect on both AChR-Ab + and AChR-Ab- (p = 0.280). Eculizumab was superior to efgartigimod relative to the QMG score reduction for the entire dataset (p = 0.003) and was more likely to achieve a clinical response at the QMG compared to efgartigimod (OR 1.373; p = 0.016). Steroid-sparing effect was higher for eculizumab than efgartigimod (– 16.7 vs – 5.2&nbsp;mg of the baseline daily dose at follow-up; p = 0.001). Mean speed of prednisone reduction was – 13.1&nbsp;mg of the daily dose for each month of follow-up for eculizumab-treated patients and – 3.2 for efgartigimod (p = 0.001). We found three serious events, all not related to treatment in the investigator’s opinion. One eculizumab-treated patient experienced a severe pneumonia and died despite treatment. Conclusions: Our study provides evidence that eculizumab and efgartigimod can be used in clinical practice to reduce disability in gMG patients. Eculizumab-treated patients had a higher QMG response and steroid sparing effect. Efgartigimod may offer a more flexible schedule due to its cyclical use, no need for vaccination, and efficacy in AChR-Ab- patients

Benign hereditary chorea: clinical and neuroimaging features in an Italian family.

Abstract: Benign hereditary chorea is an autosomal domi- nant disorder characterized by early onset nonprogressive chorea, caused by mutations of the thyroid transcription factor-1 (TITF-1) gene. Clinical heterogeneity has been reported and thyroid and respiratory abnormalities may be present. We describe 3 patients of an Italian family carrying the S145X mutation in the TITF-1 gene with mild motor delay, childhood onset dyskinesias, and subtle cognitive impairment. A child in the third generation pre- sented with congenital hypothyroidism and neonatal respi- ratory distress. Imaging studies in 2 patients showed mild ventricular enlargement and empty sella at magnetic reso- nance imaging and hypometabolism of basal ganglia and cortex at 18-Fluoro-2-deoxy-glucose positron emission tomography