Sedimentology and kinematics of a large, retrogressive growth-fault system in Upper Carboniferous deltaic sediments, western Ireland

Growth faulting is a common feature of many deltaic environments and is vital in determining local sediment dispersal and accumulation, and hence in controlling the resultant sedimentary facies distribution and architecture. Growth faults occur on a range of scales, from a few centimetres to hundreds of metres, with the largest growth faults frequently being under-represented in outcrops that are often smaller than the scale of feature under investigation. This paper presents data from the exceptionally large outcrops of the Cliffs of Moher, western Ireland, where a growth-fault complex affects strata up to 60 m in thickness and extends laterally for 3 km. Study of this Namurian (Upper Carboniferous) growth-fault system enables the relationship between growth faulting and sedimentation to be detailed and permits reconstruction of the kinematic history of faulting. Growth faulting was initiated with the onset of sandstone deposition on a succession of silty mudstones that overlie a thin, marine shale. The decollement horizon developed at the top of the marine shale contact for the first nine faults, by which time aggradation in the hangingwall exceeded 60 m in thickness. After this time, failure planes developed at higher stratigraphic levels and were associated with smaller scale faults. The fault complex shows a dominantly landward retrogressive movement, in which only one fault was largely active at any one time. There is no evidence of compressional features at the base of the growth faults, thus suggesting open-ended slides, and the faults display both disintegrative and non-disintegrative structure. Thin-bedded, distal mouth bar facies dominate the hangingwall stratigraphy and, in the final stages of growth-fault movement, erosion of the crests of rollover structures resulted in the highest strata being restricted to the proximity of the fault. These upper erosion surfaces on the fault scarp developed erosive chutes that were cut parallel to flow and are downlapped by the distal hangingwall strata of younger growth faults

Differential diagnosis in spinal and bulbar muscular atrophy clinical and molecular aspects

Kennedy disease is caused by an enlarged trinucleotide repeat sequence within the androgen receptor gene. We report here seven male patients with a benign motor neuron syndrome highly analogous to Kennedy disease but with a normal trinucleotide repeat

Flavor changing Z-decays from scalar interactions at a Giga-Z Linear Collider

The flavor changing decay Z -> d_I \bar{d}_J is investigated with special emphasis on the b \bar{s} final state. Various models for flavor violation are considered: two Higgs doublet models (2HDM's), supersymmetry (SUSY) with flavor violation in the up and down-type squark mass matrices and SUSY with flavor violation mediated by R-parity-violating interaction. We find that, within the SUSY scenarios for flavor violation, the branching ratio for the decay Z -> b \bar{s} can reach 10^{-6} for large \tan\beta values, while the typical size for this branching ratio in the 2HDM's considered is about two orders of magnitudes smaller at best. Thus, flavor changing SUSY signatures in radiative Z decays such as Z -> b \bar{s} may be accessible to future ``Z factories'' such as a Giga-Z version of the TESLA design.Comment: 27 pages, 15 figures, REVTeX4. A new section added and a few minor corrections were made in the tex

The clinical spectrum of limb girdle muscular dystrophy. A survey in the Netherlands

A cross-sectional study was performed in the Netherlands to define the clinical characteristics of the various subtypes within the broad and heterogeneous entity of limb girdle muscular dystrophy (LGMD). An attempt was made to include all known cases of LGMD in the Netherlands. Out of the reported 200 patients, 105 who fulfilled strictly defined criteria were included. Forty-nine patients, mostly suffering from dystrophinopathies and facioscapulohumeral muscular dystrophy, appeared to be misdiagnosed. Thirty-four cases were sporadic, 42 patients came from autosomal recessive and 29 from autosomal dominant families. The estimated prevalence of LGMD in the Netherlands was at least 8.1 x 10-6. The clinical features of the autosomal recessive and sporadic cases were indistinguishable from those of the autosomal dominant patients, although half hypertrophy was seen more frequently, and the course of the disease was more severe in autosomal recessive and sporadic cases. The pectoralis, iliopsoas and gluteal muscles, hip adductors and hamstrings were the most affected muscles. Distal muscle involvement occurred late in the course of the disease. Facial weakness was a rare phenomenon. The severity of the clinical picture was correlated with a deteriorating lung function. All autosomal dominantly inherited cases showed a mild course, although in two families life-expectancy was reduced because of concomitant cardiac involvement

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1):a multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods: IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies. Results: In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p Pathophysiology and treatment of rheumatic disease

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

J/psi production as a function of charged-particle pseudorapidity density in p-Pb collisions at root s(NN)=5.02 TeV

We report measurements of the inclusive J/ψ yield and average transverse momentum as a function of charged-particle pseudorapidity density dNch/dη in p–Pb collisions at sNN=5.02TeV with ALICE at the LHC. The observables are normalised to their corresponding averages in non-single diffractive events. An increase of the normalised J/ψ yield with normalised dNch/dη, measured at mid-rapidity, is observed at mid-rapidity and backward rapidity. At forward rapidity, a saturation of the relative yield is observed for high charged-particle multiplicities. The normalised average transverse momentum at forward and backward rapidities increases with multiplicity at low multiplicities and saturates beyond moderate multiplicities. In addition, the forward-to-backward nuclear modification factor ratio is also reported, showing an increasing suppression of J/ψ production at forward rapidity with respect to backward rapidity for increasing charged-particle multiplicity