Nitrogen source apportionment for the catchment, estuary and adjacent coastal waters of the Scheldt.

Using the systems approach framework (SAF), a coupled model suite was developed for simulating land-use decision making in response to nutrient abatement costs and water and nutrient fluxes in the hydrological network of the Scheldt River, and nutrient fluxes in the estuary and adjacent coastal sea. The purpose was to assess the efficiency of different long-term water quality improvement measures in current and future climate and societal settings, targeting nitrogen (N) load reduction. The spatial-dynamic model suite consists of two dynamically linked modules: PCRaster is used for the drainage network and is combined with ExtendSim modules for farming decision making and estuarine N dispersal. Model predictions of annual mean flow and total N concentrations compared well with data available for river and estuary (r² ≥ 0.83). Source apportionment was carried out to societal sectors and administrative regions; both households and agriculture are the major sources of N, with the regions of Flanders and Wallonia contributing most. Load reductions by different measures implemented in the model were comparable (~75% remaining after 30 yr), but costs differed greatly. Increasing domestic sewage connectivity was more effective, at comparatively low cost (47% remaining). The two climate scenarios did not lead to major differences in load compared with the business-as-usual scenario (~88% remaining). Thus, this spatially explicit model of water flow and N fluxes in the Scheldt catchment can be used to compare different long-term policy options for N load reduction to river, estuary, and receiving sea in terms of their effectiveness, cost, and optimal location of implementation

Isolated eyelid closure myotonia in two families with sodium channel myotonia

Sodium channelopathies (NaCh), as part of the non-dystrophic myotonic syndromes (NDMs), reflect a heterogeneous group of clinical phenotypes accompanied by a generalized myotonia. Because of recent availability of diagnostic genetic testing in NDM, there is a need for identification of clear clinical genotype–phenotype correlations. This will enable clinicians to distinguish NDMs from myotonic dystrophy, thus allowing them to inform patients promptly about the disease, perform genetic counseling, and orient therapy (Vicart et al. Neurol Sci 26:194–202, 2005). We describe the first distinctive clinical genotype–phenotype correlation within NaCh: a strictly isolated eyelid closure myotonia associated with the L250P mutation in SCN4A. Using clinical assessment and needle EMG, we identified this genotype–phenotype correlation in six L250P patients from one NaCh family and confirmed this finding in another, unrelated NaCh family with three L250P patients

Measuring primordial gravitational waves from CMB B-modes in cosmologies with generalized expansion histories

We evaluate our capability to constrain the abundance of primordial tensor perturbations in cosmologies with generalized expansion histories in the epoch of cosmic acceleration. Forthcoming satellite and sub-orbital experiments probing polarization in the CMB are expected to measure the B-mode power in CMB polarization, coming from PGWs on the degree scale, as well as gravitational lensing on arcmin scales; the latter is the main competitor for the measurement of PGWs, and is directly affected by the underlying expansion history, determined by the presence of a DE component. In particular, we consider early DE possible scenarios, in which the expansion history is substantially modified at the epoch in which the CMB lensing is most relevant. We show that the introduction of a parametrized DE may induce a variation as large as 30% in the ratio of the power of lensing and PGWs on the degree scale. We find that adopting the nominal specifications of upcoming satellite measurements the constraining power on PGWs is weakened by the inclusion of the extra degrees of freedom, resulting in a reduction of about 10% of the upper limits on r in fiducial models with no GWs, as well as a comparable increase in the error bars in models with non-zero r. Moreover, we find that the inclusion of sub-orbital CMB experiments, capable of mapping the B-mode power up to the angular scales affected by lensing, can restore the forecasted performances with a cosmological constant. Finally, we show how the combination of CMB data with Type Ia SNe, BAO and Hubble constant allows to constrain simultaneously r and the DE quantities in the parametrization we consider, consisting of present abundance and first redshift derivative of the energy density. We compare this study with results obtained using the forecasted lensing potential measurement precision from CMB satellite observations, finding consistent results.Comment: 17 pages, 9 figures, accepted for publication by JCAP. Modified version after the referee's comment

Guidelines on clinical presentation and management of non-dystrophic myotonias

The non‐dystrophic myotonias (NDMs) are rare muscle hyperexcitability disorders caused by gain‐of‐function mutations in the SCN4A gene or loss‐of‐function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography (EMG), and genetic confirmation. In the absence of genetic confirmation, the diagnosis is supported by detailed electrophysiological testing, exclusion of other related disorders, and analysis of a variant of uncertain significance (VUS) if present. Symptomatic treatment with a sodium channel blocker, such as mexiletine, is usually the first step in management, as well as educating patients about potential anesthetic complications

Anti‐cN‐1A autoantibodies are absent in juvenile dermatomyositis

Objectives: To assess anti‐cytosolic 5′‐nucleotidase 1A (cN‐1A/NTC51A) autoantibodies in children with juvenile dermatomyositis (JDM) and healthy controls, using three different methods of antibody detection, as well as verification of the results in an independent cohort. / Methods: Anti‐cN‐1A reactivity was assessed in 34 Dutch JDM patients and 20 healthy juvenile controls by a commercially available full‐length cN‐1A ELISA, a synthetic peptide ELISA and by immunoblotting using a lysate from cN‐1A expressing HEK‐293 cells. Sera from JDM patients with active disease and in remission were analysed. An independent British cohort of 110 JDM patients and 43 healthy juvenile controls was assessed by an in‐house full‐length cN‐1A ELISA. / Results: Anti‐cN‐1A reactivity was not present in JDM patients’ sera or in healthy controls when tested with the commercially available full‐length cN‐1A ELISA or by immunoblotting, both in active disease and in remission. Also, in the British JDM cohort anti‐cN‐1A reactivity was not detected. Three Dutch JDM patients tested weakly positive for one of the three synthetic cN‐1A peptides measured by ELISA. / Conclusion: JDM patients and young healthy individuals do not show anti‐cN‐1A reactivity as assessed by different antibody detection techniques

High disease impact of myotonic dystrophy type 2 on physical and mental functioning

The aim of the study was to investigate health status in patients with myotonic dystrophy type 2 (DM2) and determine its relationship to pain and fatigue. Data on health status (SF-36), pain (MPQ) and fatigue (CIS-fatigue) were collected for the Dutch DM2 population (n = 32). Results were compared with those of sex- and age-matched adult-onset myotonic dystrophy type 1 (DM1) patients. In addition, we compared the obtained scores on health status of the DM2 group with normative data of the Dutch general population (n = 1742). Compared to DM1, the SF-36 score for bodily pain was significantly (p = 0.04) lower in DM2, indicating more body pain in DM2. DM2 did not differ from DM1 on any other SF-36 scales. In comparison to the Dutch population, DM2 patients reported lower scores (indicating worse clinical condition) on the physical functioning, role functioning-physical, bodily pain, general health, vitality, social functioning, and role functioning-emotional scales (p < 0.01 on all scales). The difference was most profound for the physical functioning scale. In the DM2 group the severity of pain was significantly correlated with SF-36 scores for bodily pain (p = 0.003). Fatigue was significantly correlated with the SF-36 scores for role functioning-physical (p = 0.001), general health (p = 0.02), and vitality (p = 0.02). The impact of DM2 on a patients’ physical, psychological and social functioning is significant and as high as in adult-onset DM1 patients. From the perspective of health-related quality of life, DM2 should not be considered a benign disease. Management of DM2 patients should include screening for pain and fatigue. Symptomatic treatment of pain and fatigue may decrease disease impact and help improve health status in DM2, even if the disease itself cannot be treated

The Halo Mass of Optically Luminous Quasars at z ,F≈ ,F1-2 Measured via Gravitational Deflection of the Cosmic Microwave Background

© 2019. The American Astronomical Society. All rights reserved.We measure the average deflection of cosmic microwave background photons by quasars at 〈Z〉= 1.7. Our sample is selected from the Sloan Digital Sky Survey to cover the redshift range 0.9 ≤z≤2.2 with absolute i-band magnitudes of M i ≤-24 (K-corrected to z = 2). A stack of nearly 200,000 targets reveals an 8δ detection of Planck's estimate of the lensing convergence toward the quasars. We fit the signal with a model comprising a Navarro-Frenk-White density profile and a two-halo term accounting for correlated large-scale structure, which dominates the observed signal. The best-fitting model is described by an average halo mass log 10 (M h h -1 M)12.6 ±0.2 = and linear bias b=2.7±0.3 at 〈Z 〉= 1.7, in excellent agreement with clustering studies. We also report a hint, at a 90% confidence level, of a correlation between the convergence amplitude and luminosity, indicating that quasars brighter than Mi≲ -26 reside in halos of typical mass M h ≈ 10 13 h -1 M, scaling roughly as M h ∞ L opt 3/4 at M i ≲-24 mag, in good agreement with physically motivated quasar demography models. Although we acknowledge that this luminosity dependence is a marginal result, the observed Mh-L opt relationship could be interpreted as a reflection of the cutoff in the distribution of black hole accretion rates toward high Eddington ratios: the weak trend of Mh with Lopt observed at low luminosity becomes stronger for the most powerful quasars, which tend to be accreting close to the Eddington limit.Peer reviewedFinal Accepted Versio

Familial co-occurrence of congenital heart defects follows distinct patterns

Aims Congenital heart defects (CHD) affect almost 1% of all live born children and the number of adults with CHD is increasing. In families where CHD has occurred previously, estimates of recurrence risk, and the type of recurring malformation are important for counselling and clinical decision-making, but the recurrence patterns in families are poorly understood. We aimed to determine recurrence patterns, by investigating the co-occurrences of CHD in 1163 families with known malformations, comprising 3080 individuals with clinically confirmed diagnosis. Methods and results We calculated rates of concordance and discordance for 41 specific types of malformations, observing a high variability in the rates of concordance and discordance. By calculating odds ratios for each of 1640 pairs of discordant lesions observed between affected family members, we were able to identify 178 pairs of malformations that co-occurred significantly more or less often than expected in families. The data show that distinct groups of cardiac malformations co-occur in families, suggesting influence from underlying developmental mechanisms. Analysis of human and mouse susceptibility genes showed that they were shared in 19% and 20% of pairs of co-occurring discordant malformations, respectively, but none of malformations that rarely co-occur, suggesting that a significant proportion of co-occurring lesions in families is caused by overlapping susceptibility genes. Conclusion Familial CHD follow specific patterns of recurrence, suggesting a strong influence from genetically regulated developmental mechanisms. Co-occurrence of malformations in families is caused by shared susceptibility genes

Effects of training and albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy

Contains fulltext : 51802.pdf (publisher's version ) (Closed access)BACKGROUND : We recently reported a randomised controlled trial on the efficacy of strength training and the beta2-adrenergic agonist albuterol in patients with facioscapulohumeral muscular dystrophy (FSHD). Strength training and albuterol appeared safe interventions with limited positive effect on muscle strength and volume. We concurrently explored the prevalence and the characteristics of pain and fatigue in the participating FSHD patients, because these are probably underreported but clinically relevant symptoms in this disorder. Next, we studied the effects of albuterol and strength training on pain, experienced fatigue, health-related functional status and psychological distress. METHODS : Sixty-five patients were randomised to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks, albuterol (sustained-release, 8 mg bid) was added in a randomised, double-blind, placebo-controlled design. Outcomes comprised self-reported pain, experienced fatigue, functional status and psychological distress obtained with validated questionnaires at 52 weeks. RESULTS : Eighty percent of patients reported chronic persistent or periodic, multifocal pains. Thirty-four percent of the participants were severely fatigued. Strength training and albuterol failed to have a significant effect on all outcomes. CONCLUSIONS : Pain and fatigue are important features in FSHD. Strength training and albuterol do not have a positive or negative effect on pain, experienced fatigue, functional status and psychological distress