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INTRODUCTION: The functional luminal imaging probe (FLIP) is a novel catheter-based device that measures esophagogastric junction (EGJ) distensibility index (DI) in real-time. Previous studies have demonstrated DI to be a predictor of post-treatment clinical outcomes in patients with achalasia. We sought to evaluate EGJ DI in patients with achalasia before, during and after per-oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) and to assess the correlation of DI with postoperative outcomes. METHODS: DI (defined as the minimum cross-sectional area at the EGJ divided by distensive pressure) was measured at four time points in patients undergoing surgical myotomy for achalasia: 1) during outpatient preoperative endoscopy (preoperative DI), 2) at the start of each operation after the induction of anesthesia (induction DI), 3) at the conclusion of each operation (post-myotomy DI), and 4) at routine follow-up endoscopy 12 months postoperatively (follow-up DI). Routine Eckardt symptom score, endoscopy, timed barium esophagram, and pH study were obtained 12 months postoperatively. RESULTS: Forty-six patients (35 POEM, 11 LHM) underwent FLIP measurements at all four time points. Preop and induction mean DI were similar for both groups (POEM: 1 vs. 0.9 and LHM: 1.7 vs. 1.5 mm(2)/mmHg). POEM resulted in a significant increase in DI (induction 0.9 vs. post-myotomy 7 mm(2)/mmHg, p

Hybrid small-molecule/quantum dot films have the potential to reduce thermalization losses in single-junction photovoltaics as photon multiplication devices. Here grazing incidence X-ray scattering, optical microscopy and IR fluorescence microscopy (probing materials at two distinct wavelengths), provide new insight into highly complex morphologies across nm and μm lengthscales to provide direct links between morphologies and photon multiplication performance. Results show that within the small molecule crystallites three different QD morphologies may be identified; (i) large quantum dot aggregates at the crystallite nucleus, (ii) relatively well-dispersed quantum dots and (iii) as aggregated quantum dots “swept” from the growing crystallite and that regions containing aggregate quantum dot features lead to relatively poor photon multiplication performance. These results establish how combinations of scattering and microscopy may be employed to reveal new insights into the structure and function of small molecule:quantum dot blends.

OBJECTIVE: We aim to describe the long-term follow up data from our institution’s POEM experience. SUMMARY BACKGROUND DATA: Per-oral endoscopic myotomy (POEM) is a well-established endoscopic therapy for achalasia with excellent short-term efficacy, but long-term outcomes data are limited. METHODS: Patients greater than 4 years removed from POEM for treatment of achalasia were studied. Clinical success was defined as an Eckardt Symptom (ES) score ≤ 3 and freedom from reintervention for achalasia. Patients underwent esophagogastroduodenoscopy (EGD), high-resolution manometry, impedance planimetry, and timed barium esophagram (TBE) pre-operatively and at least 4 years post-operatively. Objective GERD was defined LA Grade B or worse esophagitis on EGD. RESULTS: One hundred and nineteen consecutive patients were included. Five patients died or had catastrophic events unrelated to achalasia or POEM. One hundred of the remaining patients (88%, 100/114) had long-term data available. Clinical follow up for all patients was greater than 4 years post-operatively and the mean was 55 months. Mean current ES was significantly improved from preop (n=100, 1 ± 1 vs 7 ± 2, p 3 and 4 patients required procedural reintervention on the lower esophageal sphincter. Reinterventions were successful in 75% of patients (3/4), with current ES ≤ 3. The rate of objective GERD was 33% (15/45). Esophageal physiology was improved with a decrease in median IRP (11 ± 4 vs 33 ± 15 mmHg, p

Background:\ud Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1.\ud \ud Objectives:\ud To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP.\ud \ud Methods:\ud This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks.\ud \ud Results:\ud A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator’s global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [–1·65, 95% confidence interval (CI) –4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI –26·44 to 32·33; favouring anakinra), total pustule count (–30·08, 95% CI –83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was –3·80 (95% CI –10·76 to 3·16; P = 0·285). No serious adverse events occurred.\ud \ud Conclusions:\ud No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Esophagogastric junction distensibility index (DI), measured using the functional luminal imaging probe (FLIP), correlates with symptomatic outcomes after interventions for achalasia. The objective of this study was to determine if the intraoperative measurement of DI using FLIP was associated with improved clinical outcomes following per-oral endoscopic myotomy (POEM) for achalasia when compared with procedures in which FLIP was not utilized. Patients undergoing POEM from 2012 to 2017 at a single institution by a single surgeon were studied. Use of FLIP during this time period was based on catheter and technician availability, resulting in two patient cohorts. In patients in whom FLIP was used, operative video recordings were reviewed to determine when DI measurements led to the performance of additional myotomy. Postoperative Eckardt symptom scores (ES) at 12 months and postoperative physiologic studies were compared between patients with and without intraoperative FLIP. Associations were assessed using Mann–Whitney U and Chi-square tests. 143 patients were included in the analysis (61 with intraoperative FLIP and 82 without FLIP). Video recordings were available for 85% of the FLIP cohort. Review of these operative recordings revealed that 65% of patients who underwent FLIP had additional myotomy performed following the initial postmyotomy FLIP measurement. At 12 months after POEM, the FLIP cohort had significantly more clinical successes (defined as ES ≤ 3) than patients in whom FLIP was not used (93% vs. 81%, p

The functional luminal imaging probe (FLIP) can be used to measure the esophagogastric junction distensibility index (DI) during myotomy for achalasia and increased DI has been shown to predict superior clinical outcomes. The objective of this study was to determine if the intraoperative DI and the changes produced by per oral endoscopic myotomy (POEM) differed between achalasia subtypes. FLIP measurements were performed during POEM for achalasia at a single institution. DI (defined as the minimum cross-sectional area (CSA) at the EGJ divided by distensive pressure) was measured at three time points: after induction of anesthesia, after submucosal tunneling, and after myotomy. Measurements were reported at the 40 mL fill volume for the 8 cm FLIP (EF-325) and at the 60 mL fill volume for the 16 cm FLIP (EF-322). Measurements were compared using chi-square and Kruskal–Wallis tests. 142 patients had intraoperative FLIP performed during POEM for achalasia between 2012 and 2019 (30 type I, 68 type II, 27 type III, and 17 variant). Patients with type I achalasia had a significantly higher induction DI (median 1.7 mm2/mmHg) than type II (0.8 mm2/mmHg), type III (0.9 mm2/mmHg), and variants (1.1 mm2/mmHg; p

The introduction of reusable packaging systems (both refill and return) has the potential to significantly reduce waste from single-use plastic packaging. However, for these schemes to be successful, both the environmental impact and the willingness of consumers to engage with such systems need to be carefully considered. This paper combines and discusses two complementary studies: (i) a life cycle assessment comparing the environmental impacts of single-use, refillable, and returnable containers for a takeaway meal, and (ii) a large online survey of UK adults exploring what types of product and packaging consumers are willing to reuse, how, and why. The findings of the life cycle assessment indicate that reusable containers outperform single-use plastic containers on most measures of environmental impact. The survey found that given the choice of disposal, reuse or recycling, that recycling is the preferred method of dealing with packaging once empty in the UK, and that people's decisions with regards to what types of packaging they are willing to reuse are largely driven by the aspects of the packaging itself (e.g., material and type) rather than the nature of the product inside of the packaging (e.g., state of matter of the contents). The survey also showed that people were more willing to engage in reuse systems with which they were already familiar. Additionally the language used to describe these schemes and the term ‘reuse’ needs to be considered. Combined, these factors can be used to determine the best packaging reuse system for a given product and situation.

It is well known that reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) enables the rational design of diblock copolymer worm gels. Moreover, such hydrogels can undergo degelation on cooling below ambient temperature as a result of a worm-to-sphere transition. However, only a subset of such block copolymer worms exhibit thermoresponsive behavior. For example, PMPC26–PHPMA280 worm gels prepared using a poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC26) precursor do not undergo degelation on cooling to 6 °C (see S. Sugihara et al., J. Am. Chem. Soc., 2011, 133, 15707–15713). Informed by our recent studies (N. J. Warren et al., Macromolecules, 2018, 51, 8357–8371), we decided to reduce the mean degrees of polymerization of both the PMPC steric stabilizer block and the structure-directing PHPMA block when targeting a pure worm morphology. This rational approach reduces the hydrophobic character of the PHPMA block and hence introduces the desired thermoresponsive character, as evidenced by the worm-to-sphere transition (and concomitant degelation) that occurs on cooling a PMPC15–PHPMA150 worm gel from 40 °C to 6 °C. Moreover, worms are reconstituted on returning to 40 °C and the original gel modulus is restored. This augurs well for potential biomedical applications, which will be examined in due course. Finally, small-angle X-ray scattering studies indicated a scaling law exponent of 0.67 (≈2/3) for the relationship between the worm core cross-sectional diameter and the PHPMA DP for a series of PHPMA-based worms prepared using a range of steric stabilizer blocks, which is consistent with the strong segregation regime for such systems.

To compare the utility of the distensibility index (DI) on functional lumen imaging probe (FLIP) topography to other esophagogastric junction (EGJ) metrics in assessing treatment response in achalasia in the context of esophageal anatomy.We prospectively evaluated 79 patients (at ages 17-81 years; 47% female patients) with achalasia during follow-up after pneumatic dilation, Heller myotomy, or per-oral endoscopic myotomy with timed barium esophagram, high-resolution impedance manometry, and FLIP. Anatomic deformities were identified based on consensus expert opinion. Patients were classified based on anatomy and EGJ opening to determine the association with radiographic outcome and Eckardt score (ES).Twenty-seven patients (34.1%) had an anatomic deformity-10 pseudodiverticula at myotomy, 7 epiphrenic diverticula, 5 sigmoid, and 5 sinktrap. A 5-minute column area of5 cm was best associated with an ES of3, with a sensitivity of 84% (P = 0.0013). Area under the curve for EGJ metrics in association with retention was as follows: DI, 0.90; maximal EGJ diameter, 0.76; integrated relaxation pressure, 0.64; and basal esophagogastric junction pressure, 0.53. Only FLIP metrics were associated with retention given normal anatomy (DI 2.4 vs 5.2 mm/mm Hg and maximal EGJ diameter 13.1 vs 16.6 mm in patients with and without retention, respectively; P values0.0001 and 0.002). Using a DI cutoff of2.8 as abnormal, 40 of 45 patients with retention (P = 0.0001) and 23 of 25 patients with an ES of3 (P = 0.02) had a low DI and/or anatomic deformity. With normal anatomy, 21 of 22 patients with retention had a low or borderline low DI.The FLIP DI is most useful metric for assessing the effect of achalasia treatment on EGJ opening. However, abnormal anatomy is an important mediator of outcome and treatment success will be modulated by anatomic defects that impede bolus emptying.

Nanocrystal quantum dots (QD) functionalised with active organic ligands hold significant promise as solar energy conversion materials, capable of multiexcitonic processes that could improve the efficiencies of single-junction photovoltaic devices. Small-angle X-ray and neutron scattering (SAXS and SANS) were used to characterize the structure of lead sulphide QDs post ligand-exchange with model acene-carboxylic acid ligands (benzoic acid, hydrocinnamic acid and naphthoic acid). Results demonstrate that hydrocinnamic acid and naphthoic acid ligated QDs form monolayer ligand shells, whilst benzoic acid ligated QDs possess ligand shells thicker than a monolayer. Further, the formation of a range of nanocomposite materials through the self-assembly of such acene-ligated QDs with an organic small-molecule semiconductor [5,12-bis((triisopropylsilyl)ethynyl)tetracene (TIPS-Tc)] is investigated. These materials are representative of a wider set of functional solar energy materials; here the focus is on structural studies, and their optoelectronic function is not investigated. As TIPS-Tc concentrations are increased, approaching the solubility limit, SANS data show that QD fractal-like features form, with structures possibly consistent with a diffusion limited aggregation mechanism. These, it is likely, act as heterogeneous nucleation agents for TIPS-Tc crystallization, generating agglomerates containing both QDs and TIPS-Tc. Within the TIPS-Tc crystals there seem to be three distinct QD morphologies: (i) at the crystallite centre (fractal-like QD aggregates acting as nucleating agents), (ii) trapped within the growing crystallite (giving rise to QD features ordered as sticky hard spheres), and (iii) a population of aggregate QDs at the periphery of the crystalline interface that were expelled from the growing TIPS-Tc crystal. Exposure of the QD:TIPS-Tc crystals to DMF vapour, a solvent known to be able to strip ligands from QDs, alters the spacing between PbS–hydrocinnamic acid and PbS–naphthoic acid ligated QD aggregate features. In contrast, for PbS–benzoic acid ligated QDs, DMF vapour exposure promotes the formation of ordered QD colloidal crystal type phases. This work thus demonstrates how different QD ligand chemistries control the interactions between QDs and an organic small molecule, leading to widely differing self-assembly processes. It highlights the unique capabilities of multiscale X-ray and neutron scattering in characterising such composite materials.

Synthetic polymers are thoroughly embedded in the modern society and their consumption grows annually. Efficient routes to their production and processing have never been more important. In this respect, silk protein fibrillation is superior to conventional polymer processing, not only by achieving outstanding physical properties of materials, such as high tensile strength and toughness, but also improved process energy efficiency. Natural silk solidifies in response to flow of the liquid using conformation-dependent intermolecular interactions to desolvate (denature) protein chains. This mechanism is reproduced here by an aqueous poly(ethylene oxide) (PEO) solution, which solidifies at ambient conditions when subjected to flow. The transition requires that an energy threshold is exceeded by the flow conditions, which disrupts a protective hydration shell around polymer molecules, releasing them from a metastable state into the thermodynamically favoured crystalline state. This mechanism requires vastly lower energy inputs and demonstrates an alternative route for polymer processing.

Polymerization‐induced self‐assembly (PISA) enables the scalable synthesis of functional block copolymer nanoparticles with various morphologies. Herein we exploit this versatile technique to produce so‐called “high χ –low N ” diblock copolymers that undergo nanoscale phase separation in the solid state to produce sub‐10 nm surface features. By varying the degree of polymerization of the stabilizer and core‐forming blocks, PISA provides rapid access to a wide range of diblock copolymers, and enables fundamental thermodynamic parameters to be determined. In addition, the pre‐organization of copolymer chains within sterically‐stabilized nanoparticles that occurs during PISA leads to enhanced phase separation relative to that achieved using solution‐cast molecularly‐dissolved copolymer chains.

Background and Aims Although laparoscopic Heller myotomy (LHM) or peroral endoscopic myotomy (POEM) is highly effective, 10% to 20% of patients with achalasia remain symptomatic after treatment. In evaluating such patients, we have observed a pattern of failure associated with a pseudodiverticulum, or blown-out myotomy (BOM), in the distal esophagus. We aimed to assess risk factors and patient-reported outcomes associated with a BOM. Methods We reviewed our manometry database for patients with achalasia previously treated with LHM or POEM. We included patients who had a post-treatment esophagram within 1 year of their follow-up manometry. A BOM was defined radiographically as a wide-mouthed outpouching (>50% increase in esophageal diameter) in the area of the myotomy. Results One hundred twenty-nine patients with achalasia who underwent treatment were included; 23 (17.8%) had a BOM. Comparing patients with a BOM with those without, post-treatment Eckardt scores were significantly greater (5 vs 2, P = .002), type III achalasia was more common (39.1% vs 14.2%, P = .005), and LHM was more common than POEM (73.9% vs 26.1%, P = .013). The integrated relaxation pressure was also significantly greater in the BOM group (15.0 mm Hg vs 11.0 mm Hg, P = .025). Conclusions BOM is a common adverse event after myotomy for achalasia but is not seen after pneumatic dilation. Pretreatment type III achalasia, LHM as opposed to POEM, and a greater post-treatment integrated relaxation pressure were risk factors for developing a BOM. We speculate that esophageal wall strain in the area weakened by myotomy, whether from residual spastic contractility or continued esophageal outflow obstruction, may be the underlying mechanism of BOM development.

Achalasia is an esophageal motility disorder characterized by a non-relaxing lower esophageal sphincter and absent or significantly altered peristalsis. The underlying cause of most cases is unknown, with a small minority secondary to infectious, genetic, or obstructive etiologies. There is no cure. Palliative treatments include medical therapies and disruption of the lower esophageal sphincter. Botulinum toxin injection provides effective short-term relief but often lacks durability, thus lending itself to highly comorbid patients or in select diagnostic scenarios. Serial pneumatic dilations offer excellent symptom relief and durability, with rates comparable to surgical myotomy in appropriately selected patients. Peroral esophageal myotomy (POEM) is an established endoscopic therapy that offers robust dysphagia relief with minimized surgical morbidity. Patients who require reoperative achalasia surgery are at high risk for vagal nerve injury and gastroparesis. Emerging endoscopic therapies, such peroral pyloromyotomy (POP), may be an effective tool in this challenging patient population.

BACKGROUND: The functional luminal imaging probe (FLIP) can evaluate esophagogastric junction (EGJ) distensibility and esophageal peristalsis in real time. FLIP measurements performed during diagnostic endoscopy can accurately discriminate between healthy controls and patients with achalasia, based on EGJ distensibility and distinct motility patterns termed repetitive antegrade contractions (RACs) and repetitive retrograde contractions (RRCs). We sought to evaluate real time motility changes in patients undergoing surgical myotomy for achalasia. METHODS: FLIP measurements using a stepwise volumetric distention protocol were performed at three time points during assessment and performance of laparoscopic Heller myotomy and POEM: 1) During preoperative outpatient endoscopy, 2) Intraoperatively following induction of anesthesia, and 3) Intraoperatively after myotomy completion. EGJ-Distensibility, contractility, RACs, and RRCs were measured. RESULTS: FLIP measurements were performed in 32 patients. The EGJ-distensibility index was similar between the preoperative and initial operative measurements (1.1 vs 1.4 mm(2)/mmHg, p = NS). There was a significant increase in distensibility following surgical myotomy (1.1 to 4.7 mm(2)/mmHg, p < 0.01). Intraoperative contractile patterns varied between achalasia subtypes. Contractility was seen in < 20% of assessments in patients with types I and II achalasia. Type III patients demonstrated contractility in 100% of assessments, with 70% exhibiting RRCs and 60% RACs. There was a reduction in the frequency of RRC presence (70% to 20%), and contractile vigor (80% to 0% of patients with lumen occluding contractions) in type III patients following surgical myotomy. CONCLUSIONS: This first report of real time intraoperative measurement of esophageal motility using FLIP demonstrates the feasibility of such assessments during surgical myotomy for achalasia. Patients with type I and II achalasia exhibited rare intraoperative contractility, while the presence of motility was the norm in those with type III. Patients with type III achalasia demonstrated an immediate reduction in repetitive contraction motility patterns and contractile vigor following myotomy.

© 2018 American Chemical Society. Triacrylglycerols (TAGs) are ubiquitous and naturally occurring fat molecules that can make materials with diverse textural, mechanical, and optical properties. These properties are intimately linked to their complex hierarchical crystal structures, which can be controlled by additives that interfere with crystallization. A series of semicrystalline, bottlebrush-like copolymers have been developed to modify TAG crystallization and influence crystal habit. Synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, these copolymer additives combine crystalline poly(stearyl methacrylate) with amorphous poly(oleyl methacrylate) in either block or statistical architecture. Upon cooling mixtures of these copolymers with solutions of tristearin (SSS) in triolein (OOO), the polymeric additives affected SSS crystallization at multiple length-scales. Microscopy analysis revealed control over SSS crystal morphology indicative of crystal aggregation, while small and wide-angle X-ray diffraction (SAXD/WAXD) offered insight into the underlying mechanism of action. Analyzing the physical broadening of lamellar peaks suggested that the fraction of amorphous poly(oleyl methacrylate) controls the thickness of primary nanoplatelets, and crystal structures derived from WAXD showed that the less stable α- or β′-polymorphs of SSS are stabilized by block or statistical copolymers, respectively. Exploiting these additives to simultaneously manipulate the packing of TAG molecules within lamellae, the size of primary crystallites, and the aggregation of crystallites could diversify fat material properties and supplement wide-ranging applications.

Laparoscopic common bile duct exploration (LCBDE) is an underutilized therapy for choledocholithiasis. The driving factors of this practice gap are poorly defined. We sought to evaluate the attitudes and practice patterns of surgeons who underwent training courses using an LCBDE simulator. Surgeons completed a half-day simulator-based LCBDE curriculum at national courses, including the American College of Surgeons Advanced Skills Training for Rural Surgeons and the Society of American Gastrointestinal and Endoscopic Surgeons annual meeting. Attitudes were assessed with Likert surveys immediately before and after curriculum completion. Follow-up surveys were distributed electronically. 159 surgeons completed training during six courses. Surgeon attitudes regarding the overall superiority of LCBDE vs. ERCP shifted towards favoring LCBDE after course participation (4.0 vs 3.3; Likert scale 1–5, p

A poly(behenyl methacrylate)37 (PBeMA37) macromolecular chain transfer agent is utilized for the reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) directly in mineral oil at 90 °C. Polymerization-induced self-assembly (PISA) occurs under these conditions, yielding a series of sterically-stabilized PBeMA37–PBzMAx diblock copolymer spheres of tunable diameter as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. Rheological studies indicate that a relatively transparent, free-flowing, concentrated dispersion of non-interacting 32 nm PBeMA37–PBzMA100 spheres at 50 °C forms a turbid, paste-like dispersion on cooling to 20 °C. Turbidimetry and differential scanning calorimetry (DSC) studies conducted on solutions of PBeMA37 homopolymer in mineral oil suggest that this switchable colloidal stability is linked to crystallization-induced phase separation exhibited by this stabilizer block. Indeed, variable-temperature small-angle X-ray scattering (SAXS) indicates that a loose mass fractal network of strongly interacting spheres is formed on cooling to 20 °C, which accounts for this thermoreversible sol–gel transition. Moreover, SAXS, DSC and wide-angle X-ray scattering (WAXS) analyses indicate that the behenyl (C22H45) side-chains first form crystalline domains comprising adjacent stabilizer chains within individual spherical nanoparticles, with subsequent crystallization between neighboring nanoparticles leading to the formation of the mass fractal aggregates.

PEDOT:PSS is a high-conductivity hole-transporting polymer that is widely used in polymer and perovskite photovoltaic devices, as well as in a host of other antistatic applications. Here we show that modification of PEDOT:PSS inks using ternary solvents and by the addition of small amounts of a high molecular weight polymer make it possible to deposit highly uniform thin films via ultrasonic spray coating. Such films can be deposited using a single pass in the wet phase without the use of surfactants; a process that greatly simplifies their deposition. Using this technique we create films having thickness and roughness comparable to that of spin coated films, whilst properties such as the conductivity and stability can be improved.