Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 mu g/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 mu g/l, P = 0.0004; itself higher than the normal level (3.4 mu g/l, range from 0.5 to 17.2 mu g/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level >= 7 mu g/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels >= 7 mu g/l is 46%. Therefore, selection of patients with an AFP level above 7 mu g/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy

Synthesis of Carboxymethyl Starch for increasing drilling mud quality in drilling oil and gas wells

This paper describes the impact of carboxymethyl starch preparation conditions on physicochemical properties of polysaccharide reagent, widely used as fluid loss reducing agent in drilling mud. Variation of the main parameters of carboxymethylation is researched in the experiment. The following conditions such as temperature and reaction time, amount of water, as well as ratio of NaOH to monochloracetic acid define the characteristics of carboxymethyl starch. The degree of substitution is defined for polysaccharides, as well as the characteristics of samples have been studied by infrared spectroscopy. Rheological characteristics and fluid loss indicator have been investigated to study the impact of the reagents on drilling mud quality

Petrophysics of Chicxulub Impact Crater's Peak Ring

A new set of physical property measurements was undertaken on 29 peak-ring samples from the IODP-ICDP Expedition 364. Among the studied lithologies, the dominant one recovered in the peak ring consists of shocked granitoid rocks (19 samples). Porosity measurements with two independent methods (triple weight and C-14-PMMA porosity mapping) concur and bring new observations on the intensity and distribution of fracturing and porosity in these shocked target rocks. Characterization of the porous network is taken a step further with two other independent methods (electrical and permeability measurements). Electrical properties such as the cementation exponent (1.59 m < 1.87) and the formation factor (21 F < 103) do not compare with other granites from the published literature; they point at a type of porosity closer to clastic sedimentary rocks than to crystalline rocks. Permeabilities of the granitoid rocks range from 0.1 to 7.1 mD under an effective pressure of similar to 10 MPa. Unlike other fresh to deformed and altered granitoid rocks from the literature compared in this study, this permeability appears to be relatively insensitive to increasing stress (up to similar to 40 MPa), with implications for the nature of the porous network, again, behaving more like cemented clastic rocks than fractured crystalline rocks. Other analyzed lithologies include suevite and impact melt rocks. Relatively low permeability (10(-3) mD) measured in melt-rich facies suggest that, at the matrix scale, these lithologies cutting through more permeable peak-ring granitoid rocks may have been a barrier to fluid flow, with implications for hydrothermal systems.Peer reviewe

A pilot study of medical student attitudes to, and use of, commercial movies that address public health issues

<p>Abstract</p> <p>Background</p> <p>An innovative approach to learning public health by using feature-length commercial movies was piloted in the fourth year of a medical degree. We aimed to explore how students responded to this approach and the relative effectiveness of two promotional strategies. Firstly we placed DVDs of 15 movies (with public health-related content) in the medical school library. Then alternating groups of students (total n = 82 students) were exposed to either a brief promotional intervention or a more intensive intervention involving a class presentation. The response rates were 99% at baseline and 85% at follow-up.</p> <p>Findings</p> <p>The level and strength of support for using movies in public health training increased after exposure to the public health module with significantly more students "strongly agreeing". Student behaviour, in terms of movies viewed or accessed from the library, also suggested student interest. While there were no statistically significant differences in median viewing or library access rates between the two intervention groups, the distribution of viewing patterns was shifted favourably. Those exposed to the more intensive intervention (class presentation) were significantly more likely to have reported watching at least one movie (97% vs. 81%; p = 0.033) or to having accessed at least one movie from the library (100% vs. 70%, p = 0.0001).</p> <p>Conclusions</p> <p>This pilot study found that the students had very positive attitudes towards viewing public health-related commercial movies. Movie access rates from the library were also favourable.</p

Social preferences, accountability, and wage bargaining

We assess the extent of preferences for employment in a collective wage bargaining situation with heterogeneous workers. We vary the size of the union and introduce a treatment mechanism transforming the voting game into an individual allocation task. Our results show that highly productive workers do not take employment of low productive workers into account when making wage proposals, regardless of whether insiders determine the wage or all workers. The level of pro-social preferences is small in the voting game, while it increases as the game is transformed into an individual allocation task. We interpret this as an accountability effect

TMEM106B a Novel Risk Factor for Frontotemporal Lobar Degeneration

Recently, the first genome-wide association (GWA) study in frontotemporal lobar degeneration (FTLD) identified common genetic variability at the TMEM106B gene on chromosome 7p21.3 as a potential important risk-modifying factor for FTLD with pathologic inclusions of TAR DNA-binding protein (FTLD-TDP), the most common pathological subtype in FTLD. To gather additional evidence for the implication of TMEM106B in FTLD risk, multiple replication studies in geographically distinct populations were set up. In this review, we revise all recent replication and follow-up studies of the FTLD-TDP GWA study and summarize the growing body of evidence that establish TMEM106B as a bona fide risk factor for FTLD. With the TMEM106B gene, a new player has been identified in the pathogenic cascade of FTLD which could hold important implications for the future development of disease-modifying therapies

Symmetrical Corticobasal Syndrome Caused by a Novel c.314dup Progranulin Mutation

Corticobasal syndrome (CBS) is characterised by asymmetrical parkinsonism and cognitive impairment. The underlying pathology varies between corticobasal degeneration, progressive supranuclear palsy, Alzheimer’s disease, Creutzfeldt–Jakob disease and frontotemporal lobar degeneration sometimes in association with GRN mutations. A 61-year-old male underwent neurological examination, neuropsychological assessment, MRI, and HMPAO-SPECT at our medical centre. After his death at the age of 63, brain autopsy, genetic screening and mRNA expression analysis were performed. The patient presented with slow progressive walking disabilities, non-fluent language problems, behavioural changes and forgetfulness. His family history was negative. He had primitive reflexes, rigidity of his arms and postural instability. Later in the disease course he developed dystonia of his left leg, pathological crying, mutism and dysphagia. Neuropsychological assessment revealed prominent ideomotor and ideational apraxia, executive dysfunction, non-fluent aphasia and memory deficits. Neuroimaging showed symmetrical predominant frontoparietal atrophy and hypoperfusion. Frontotemporal lobar degeneration (FTLD)-TDP type 3 pathology was found at autopsy. GRN sequencing revealed a novel frameshift mutation c.314dup, p.Cys105fs and GRN mRNA levels showed a 50% decrease. We found a novel GRN mutation in a patient with an atypical (CBS) presentation with symmetric neuroimaging findings. GRN mutations are an important cause of CBS associated with FTLD-TDP type 3 pathology, sometimes in sporadic cases. Screening for GRN mutations should also be considered in CBS patients without a positive family history

A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study

Objectives: Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies have shown that a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon-γ-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections. Methods: This prospective, multicentre cohort study, entitled AutoPilot-Dx, aimed to validate signature performance and to estimate its potential impact on antibiotic use across a broad paediatric population (&gt;90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data. Results: In total, 1140 patients were recruited (February 2017–December 2018), of which 1008 met the eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with a sensitivity of 93.7% (95%CI 88.7–98.7), a specificity of 94.2% (92.2–96.1), positive predictive value of 73.0% (65.0–81.0), and negative predictive value of 98.9% (98.0–99.8); in 9.8% the test results were equivocal. The signature performed consistently across different patient subgroups and detected bacterial immune responses in viral PCR-positive patients. Conclusions: The findings validate the high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort, and support its potential to reduce antibiotic overuse in children with viral infections

The complex light-curve of the afterglow of GRB071010A

We present and discuss the results of an extensive observational campaign devoted to GRB071010A, a long-duration gamma-ray burst detected by the Swift satellite. This event was followed for almost a month in the optical/near-infrared (NIR) with various telescopes starting from about 2min after the high-energy event. Swift-XRT observations started only later at about 0.4d. The light-curve evolution allows us to single out an initial rising phase with a maximum at about 7min, possibly the afterglow onset in the context of the standard fireball model, which is then followed by a smooth decay interrupted by a sharp rebrightening at about 0.6d. The rebrightening was visible in both the optical/NIR and X-rays and can be interpreted as an episode of discrete energy injection, although various alternatives are possible. A steepening of the afterglow light curve is recorded at about 1d. The entire evolution of the optical/NIR afterglow is consistent with being achromatic. This could be one of the few identified GRB afterglows with an achromatic break in the X-ray through the optical/NIR bands. Polarimetry was also obtained at about 1d, just after the rebrightening and almost coincident with the steepening. This provided a fairly tight upper limit of 0.9% for the polarized-flux fraction.Comment: 11 pages, 3 figures, MNRAS, in pres

The complex light-curve of the afterglow of GRB071010A

We present and discuss the results of an extensive observational campaign devoted to GRB071010A, a long-duration gamma-ray burst detected by the Swift satellite. This event was followed for almost a month in the optical/near-infrared (NIR) with various telescopes starting from about 2min after the high-energy event. Swift-XRT observations started only later at about 0.4d. The light-curve evolution allows us to single out an initial rising phase with a maximum at about 7min, possibly the afterglow onset in the context of the standard fireball model, which is then followed by a smooth decay interrupted by a sharp rebrightening at about 0.6d. The rebrightening was visible in both the optical/NIR and X-rays and can be interpreted as an episode of discrete energy injection, although various alternatives are possible. A steepening of the afterglow light curve is recorded at about 1d. The entire evolution of the optical/NIR afterglow is consistent with being achromatic. This could be one of the few identified GRB afterglows with an achromatic break in the X-ray through the optical/NIR bands. Polarimetry was also obtained at about 1d, just after the rebrightening and almost coincident with the steepening. This provided a fairly tight upper limit of 0.9% for the polarized-flux fraction.Comment: 11 pages, 3 figures, MNRAS, in pres