Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects.

The increasing prevalence of functional and motility gastrointestinal (GI) disorders is at odds with bottlenecks in their diagnosis, treatment, and follow-up. Lack of noninvasive approaches means that only specialized centers can perform objective assessment procedures. Abnormal GI muscular activity, which is coordinated by electrical slow-waves, may play a key role in symptoms. As such, the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric electrical activity, can be used to inform diagnoses over broader populations. However, it is seldom used due to technical issues: inconsistent results from single-channel measurements and signal artifacts that make interpretation difficult and limit prolonged monitoring. Here, we overcome these limitations with a wearable multi-channel system and artifact removal signal processing methods. Our approach yields an increase of 0.56 in the mean correlation coefficient between EGG and the clinical "gold standard", gastric manometry, across 11 subjects (p < 0.001). We also demonstrate this system's usage for ambulatory monitoring, which reveals myoelectric dynamics in response to meals akin to gastric emptying patterns and circadian-related oscillations. Our approach is noninvasive, easy to administer, and has promise to widen the scope of populations with GI disorders for which clinicians can screen patients, diagnose disorders, and refine treatments objectively

Clinical Outcomes of Superior Capsular Reconstruction for Massive, Irreparable Rotator Cuff Tears: A Systematic Review Comparing Acellular Dermal Allograft and Autograft Fascia Lata

Purpose: To investigate clinical outcomes after superior capsular reconstruction (SCR) for the treatment of massive and/or irreparable rotator cuff tears treated with either allograft or autograft. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, in April 2020 a systematic review was performed using PubMed, MEDLINE, EMBASE, and Cochrane databases. Clinical studies were assessed for patient-reported outcomes and range of motion, comparing dermal allografts to fascia lata autografts, with a minimum follow-up of 12 months. Results: A total of 16 clinical studies involving 598 patients (606 shoulders) were included for data analysis, with a weighted mean follow-up of 36.9 months (range 12 to 60). Visual analogue scale (VAS) pain scores decreased from 4.0 to 6.9 mm preoperatively to 0 to 2.5 mm postoperatively. American Shoulder & Elbow Surgeons score increased from 20.3 to 54.5 preoperatively to 73.7 to 97.0 postoperatively. Forward flexion increased from 27.0° to 142.7° preoperatively to 134.5° to 167.0° postoperatively. External rotation increased from 13.2° to 41.0° preoperatively to 30.0° to 59.0° postoperatively. Acromiohumeral distance increased from 3.4 to 7.1 mm preoperatively to 6.0 to 9.7 mm postoperatively. The total rates of complications, graft failure, and revision surgery were 5.6%, 13.9%, and 6.9%, respectively. Conclusions: Irrespective of tissue source, SCR serves as a reasonable joint-preserving option for massive, irreparable rotator cuff tears, with favorable short- to midterm improvements in patient-reported outcomes and range of motion. Level of Evidence: IV, systematic review of level III and IV studies

Phenomenological aspects of composite Higgs scenarios: exotic scalars and vector-like quarks

Composite Higgs models usually contain additional pseudo Nambu Goldstone bosons and vector-like quarks. We discuss various aspects related to their LHC phenomenology and provide summary plots of exclusion limits using currently available information. We also describe a general parametrisation implemented in a software for Monte Carlo simulations and study the SU(5)/SO(5) scenario as a concrete example.Comment: contribution to Snowmass 2021. V2: Fig. 4 update

Simulation of potential impacts of man-made land use changes on U.S. summer climate under various synoptic regimes

This study evaluates impacts of land use changes due to human settlement on regional summer climate over the central and western United States by performing 30-day simulations during normal, drought, and flood years. Under current land use the simulated evapotranspiration increased noticeably over the central United States where grassland has been replaced by crops. Simulated evapotranspiration decreased slightly in the western United States. These changes produced wetter and cooler surface air over the central United States and slightly drier and warmer air over the western United States. Responses of surface fluxes and thus screen height variables to land use changes were consistent from year to year, whereas rainfall showed strong interannual variations because of the combination of various dynamic processes involved in precipitation. For normal year conditions, average evapotranspiration and rainfall under current land use increased by 18% and 8%, respectively, over the central United States, whereas they slightly decreased in the western United States. In both flood and drought years, current land use exhibited a rainfall increase in the western United States and a decrease over the central United States. The decrease of rainfall with increased evapotranspiration in the central United States was likely associated with weakening of the dynamic forcing needed to produce precipitation

Dystrophin Is a Tumor Suppressor in Human Cancers with Myogenic Programs

Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS), and leiomyosarcoma (LMS), feature myogenic differentiation1–3. Here we report that intragenic deletion of the dystrophin-encoding and muscular dystrophy-associated DMD gene is a frequent mechanism by which myogenic tumors progress to high-grade, lethal sarcomas. Dystrophin is expressed in nonneoplastic and benign counterparts for GIST, RMS and LMS, and the DMD deletions inactivate larger dystrophin isoforms, including 427kDa dystrophin, while preserving expression of an essential 71kDa isoform. Dystrophin inhibits myogenic sarcoma cell migration, invasion, anchorage independence, and invadopodia formation, and dystrophin inactivation was found in 96%, 100%, and 62% of metastatic GIST, embryonal RMS, and LMS, respectively. These findings validate dystrophin as a tumor suppressor and likely anti-metastatic factor, suggesting that therapies in development for muscular dystrophies may also have relevance in treatment of cancer

DNA models of trinucleotide frameshift deletions: the formation of loops and bulges at the primer–template junction

Although mechanisms of single-nucleotide residue deletion have been investigated, processes involved in the loss of longer nucleotide sequences during DNA replication are poorly understood. Previous reports have shown that in vitro replication of a 3′-TGC TGC template sequence can result in the deletion of one 3′-TGC. We have used low-energy circular dichroism (CD) and fluorescence spectroscopy to investigate the conformations and stabilities of DNA models of the replication intermediates that may be implicated in this frameshift. Pyrrolocytosine or 2-aminopurine residues, site-specifically substituted for cytosine or adenine in the vicinity of extruded base sequences, were used as spectroscopic probes to examine local DNA conformations. An equilibrium mixture of four hybridization conformations was observed when template bases looped-out as a bulge, i.e. a structure flanked on both sides by duplex DNA. In contrast, a single-loop structure with an unusual unstacked DNA conformation at its downstream edge was observed when the extruded bases were positioned at the primer–template junction, showing that misalignments can be modified by neighboring DNA secondary structure. These results must be taken into account in considering the genetic and biochemical mechanisms of frameshift mutagenesis in polymerase-driven DNA replication

Ideologies of time: How elite corporate actors engage the future

Our paper deals with how elite corporate actors in a Western capitalist-democratic society conceive of and prepare for the future. Paying attention to how senior officers of ten important Danish companies make sense of the future will help us to identify how particular temporal narratives are ideologically marked. This ideological dimension offers a common sense frame that is structured around a perceived inevitability of capitalism, a market economy as the basic organizational structure of the social and economic order, and an assumption of confident access to the future. Managers envisage their organization?s future and make plans for organizational action in a space where ?business as usual? reigns, and there is little engagement with the future as fundamentally open; as a time-yet-to-come. In using a conceptual lens inspired by the work of Fredric Jameson, we first explore the details of this presentism and a particular colonization of the future, and then linger over small disruptions in the narratives of our interviewees which point to what escapes or jars their common sense frame, explore the implicit meanings they assign to their agency, and also find clues and traces of temporal actions and strategies in their narratives that point to a subtly different engagement with time

Climate Science Special Report: Fourth National Climate Assessment (NCA4), Volume I

New observations and new research have increased our understanding of past, current, and future climate change since the Third U.S. National Climate Assessment (NCA3) was published in May 2014. This Climate Science Special Report (CSSR) is designed to capture that new information and build on the existing body of science in order to summarize the current state of knowledge and provide the scientific foundation for the Fourth National Climate Assessment (NCA4)

Large-Scale simulations of plastic neural networks on neuromorphic hardware

SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Rather than using bespoke analog or digital hardware, the basic computational unit of a SpiNNaker system is a general-purpose ARM processor, allowing it to be programmed to simulate a wide variety of neuron and synapse models. This flexibility is particularly valuable in the study of biological plasticity phenomena. A recently proposed learning rule based on the Bayesian Confidence Propagation Neural Network (BCPNN) paradigm offers a generic framework for modeling the interaction of different plasticity mechanisms using spiking neurons. However, it can be computationally expensive to simulate large networks with BCPNN learning since it requires multiple state variables for each synapse, each of which needs to be updated every simulation time-step. We discuss the trade-offs in efficiency and accuracy involved in developing an event-based BCPNN implementation for SpiNNaker based on an analytical solution to the BCPNN equations, and detail the steps taken to fit this within the limited computational and memory resources of the SpiNNaker architecture. We demonstrate this learning rule by learning temporal sequences of neural activity within a recurrent attractor network which we simulate at scales of up to 2.0 × 104 neurons and 5.1 × 107 plastic synapses: the largest plastic neural network ever to be simulated on neuromorphic hardware. We also run a comparable simulation on a Cray XC-30 supercomputer system and find that, if it is to match the run-time of our SpiNNaker simulation, the super computer system uses approximately 45× more power. This suggests that cheaper, more power efficient neuromorphic systems are becoming useful discovery tools in the study of plasticity in large-scale brain models

Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma

Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor β, and the late-stage maturity marker α smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this