High-resolution manometry-observations after 15 years of personal use-has advancement reached a plateau?

PURPOSE OF REVIEW: In the absence of mucosal or structural disease, the aim of investigating the oesophagus is to provide clinically relevant measurements of function that can explain the cause of symptoms, identify pathology and guide effective management. One of the most notable recent advances in the field of oesophageal function has been high-resolution manometry (HRM). This review explores how innovation in HRM has progressed and has far from reached a plateau. RECENT FINDINGS: HRM technology, methodology and utility continue to evolve; simple additions to the swallow protocol (e.g. eating and drinking), shifting position, targeting symptoms and adding impedance sensors to the HRM catheter have led to improved diagnoses, therapeutic decision-making and outcomes. Progress in HRM persists and shows little sign of abating. The next iteration of the Chicago Classification of motor disorders will highlight these advances and will also identify opportunities for further research and innovation

A resonant Lyapunov centre theorem with an application to doubly periodic travelling hydroelastic waves

We present a Lyapunov centre theorem for an antisymplectically reversible Hamiltonian system exhibiting a nondegenerate $1:1$ or $1:-1$ semisimple resonance as a detuning parameter is varied. The system can be finite- or infinite dimensional (and quasilinear) and have a non-constant symplectic structure. We allow the origin to be a "trivial" eigenvalue arising from a translational symmetry or, in an infinite-dimensional setting, to lie in the continuous spectrum of the linearised Hamiltonian vector field provided a compatibility condition on its range is satisfied. As an application we show how Kirchg\"{a}ssner's spatial dynamics approach can be used to construct doubly periodic travelling waves on the surface of a three-dimensional body of water (of finite or infinite depth) beneath a thin ice sheet (hydroelastic waves). The hydrodynamic problem is formulated as a reversible Hamiltonian system in which an arbitrary horizontal spatial direction is the time-like variable and the infinite-dimensional phase space consists of wave profiles which are periodic (with fixed period) in a second, different horizontal direction. Applying our Lyapunov centre theorem at a point in parameter space associated with a $1:1$ or $1:-1$ semisimple resonance yields a periodic solution of the spatial Hamiltonian system corresponding to a doubly periodic hydroelastic wave

Catalogue of 55-80 MeV solar proton events extending through solar cycles 23 and 24

We present a new catalogue of solar energetic particle events near the Earth, covering solar cycle 23 and the majority of solar cycle 24 (1996-2016), based on the 55-80 MeV proton intensity data gathered by the SOHO/ERNE experiment. In addition to ERNE proton and heavy ion observations, data from the ACE/EPAM (near-relativistic electrons), SOHO/EPHIN (relativistic electrons), SOHO/LASCO (coronal mass ejections, CMEs), and GOES soft X-ray experiments are also considered and the associations between the particle and CME/X-ray events deduced to obtain a better understanding of each event. A total of 176 SEP events have been identified as having occurred during the time period of interest; their onset and solar release times have been estimated using both velocity dispersion analysis (VDA) and time-shifting analysis (TSA) for protons, as well as TSA for near-relativistic electrons. Additionally, a brief statistical analysis has been performed on the VDA and TSA results, as well as the X-rays and CMEs associated with the proton/electron events, both to test the viability of the VDA and to investigate possible differences between the two solar cycles. We find, in confirmation of a number of previous studies, that VDA results for protons that yield an apparent path length of 1 AU < s <~ 3 AU seem to be useful, but those outside this range are probably unreliable, as evidenced by the anticorrelation between apparent path length and release time estimated from the X-ray activity. It also appears that even the first-arriving energetic protons apparently undergo significant pitch angle scattering in the interplanetary medium, with the resulting apparent path length being on average about twice the length of the spiral magnetic field. The analysis indicates an increase in high-energy SEP events originating from the far eastern solar hemisphere; e.g., such an event...Comment: 33 pages, 12 figures (2 with multiple image files), 1 appendix as an external PDF file. Article is in the accepted manuscript/referee (single column) forma

Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A phase 2, randomized, sham-controlled trial

Background -In non-randomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), less symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and mid-range or preserved ejection fraction (EF ≥ 40%). We conducted the first randomized, sham-controlled trial to evaluate the IASD in HF with EF ≥ 40%. Methods -REDUCE LAP-HF I was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, EF ≥ 40%, exercise PCWP ≥ 25 mmHg, and PCWP-right atrial pressure gradient ≥ 5 mmHg. Participants were randomized (1:1) to the IASD vs. a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness endpoint was exercise PCWP at 1 month. The primary safety endpoint was major adverse cardiac, cerebrovascular, and renal events (MACCRE) at 1 month. PCWP during exercise was compared between treatment groups using a mixed effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results -A total of 94 patients were enrolled, of which n=44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared to sham-control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mmHg in the treatment group vs. 0.5±5.0 mmHg in the control group (P=0.14). There were no peri-procedural or 1-month MACCRE in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). Conclusions -In patients with HF and EF ≥ 40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration -URL: http://clinicaltrials.gov. Unique identifier: NCT02600234

Vascular Regeneration by Local Growth Factor Release Is Self-Limited by Microvascular Clearance

Background— The challenge of angiogenesis science is that stable sustained vascular regeneration in humans has not been realized despite promising preclinical findings. We hypothesized that angiogenic therapies powerfully self-regulate by dynamically altering tissue characteristics. Induced neocapillaries increase drug clearance and limit tissue retention and subsequent angiogenesis even in the face of sustained delivery. Methods and Results— We quantified how capillary flow clears fibroblast growth factor after local epicardial delivery. Fibroblast growth factor spatial loading was significantly reduced with intact coronary perfusion. Penetration and retention decreased with transendothelial permeability, a trend diametrically opposite to intravascular delivery, in which factor delivery depends on vascular leak, but consistent with a continuum model of drug transport in perfused tissues. Model predictions of fibroblast growth factor sensitivity to manipulations of its diffusivity and transendothelial permeability were validated by conjugation to sucrose octasulfate. Induction of neocapillaries adds pharmacokinetic complexity. Sustained local fibroblast growth factor delivery in vivo produced a burst of neovascularization in ischemic myocardium but was followed by drug washout and a 5-fold decrease in fibroblast growth factor penetration depth. Conclusions— The very efficacy of proangiogenic compounds enhances their clearance and abrogates their pharmacological benefit. This self-limiting property of angiogenesis may explain the failures of promising proangiogenic therapies.National Institutes of Health (U.S.) (Grant R01 GM 49039

The detectability of free-phase migrating CO₂:A rock physics and seismic modelling feasibility study

AbstractSubsurface monitoring is essential for the successful implementation and public acceptance of CO2 storage. Injected CO2 will need to be monitored to verify the successful containment within its intended formation, and to ensure no loss of containment within the storage complex. The ability for seismic techniques to monitor structurally trapped CO2 has been successfully demonstrated due to the changes in the acoustic properties of the reservoir produced by the displacement of brine by less dense and more compressible CO2. However, the ability for seismic methods to detect free-phase migrating CO2 is still moderately understood. In order to assess the feasibility for seismic monitoring of a migrating front, we estimate the time-lapse signal over a theoretical, clean, homogeneous sandstone reservoir through the application of a three-stage model-driven workflow consisting of fluid-flow, rock physics and seismic forward modelling. To capture the range of responses which could be encountered, two end-member fluid distribution models were used: uniform saturation and the modified patchy saturation model. Analysis of the time- lapse survey highlights the importance of determining and understanding the fluid distribution model impacting the range of velocities prior to generating and interpreting the seismic response. This change in velocity is shown to be directly related to the volume of CO2 occupying the pore-space of a migrating plume front. This highlights the fact that the detectability of a migrating front is a site specific issue which not only depends on the geophysical parameters of the seismic survey but also on the geological variations and spatial distribution in the reservoir