Ischaemic colitis: Practical challenges and evidence-based recommendations for management

Ischaemic colitis (IC) is a common condition with rising incidence, and in severe cases a high mortality rate. Its presentation, severity and disease behaviour can vary widely, and there exists significant heterogeneity in treatment strategies and resultant outcomes. In this article we explore practical challenges in the management of IC, and where available make evidence-based recommendations for its management based on a comprehensive review of available literature. An optimal approach to initial management requires early recognition of the diagnosis followed by prompt and appropriate investigation. Ideally, this should involve the input of both gastroenterology and surgery. CT with intravenous contrast is the imaging modality of choice. It can support clinical diagnosis, define the severity and distribution of ischaemia, and has prognostic value. In all but fulminant cases, this should be followed (within 48 hours) by lower gastrointestinal endoscopy to reach the distal-most extent of the disease, providing endoscopic (and histological) confirmation. The mainstay of medical management is conservative/supportive treatment, with bowel rest, fluid resuscitation and antibiotics. Specific laboratory, radiological and endoscopic features are recognised to correlate with more severe disease, higher rates of surgical intervention and ultimately worse outcomes. These factors should be carefully considered when deciding on the need for and timing of surgical intervention

Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BackgroundOnce-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments.ObjectivesTo evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed.MethodsIn two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose.ResultsAmong 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant.ConclusionsAssessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity

Online Disturbance Estimation for Improving Kinematic Accuracy in Continuum Manipulators

Continuum manipulators are flexible robots which undergo continuous deformation as they are actuated. To describe the elastic deformation of such robots, kinematic models have been developed and successfully applied to a large variety of designs and to various levels of constitutive stiffness. Independent of the design, kinematic models need to be calibrated to best describe the deformation of the manipulator. However, even after calibration, unmodeled effects such as friction, nonlinear elastic and/or spatially varying material properties as well as manufacturing imprecision reduce the accuracy of these models. In this letter, we present a method for improving the accuracy of kinematic models of continuum manipulators through the incorporation of orientation sensor feedback. We achieve this through the use of a “disturbance wrench,” which is used to compensate for these unmodeled effects, and is continuously estimated based on orientation sensor feedback as the robot moves through its workspace. The presented method is applied to the HydroJet, a waterjet-actuated soft continuum manipulator, and shows an average of 40% reduction in root mean square position and orientation error in the two most common types of kinematic models for continuum manipulators, a Cosserat rod model and a pseudo-rigid body model

Teleoperation and Contact Detection of a Waterjet-Actuated Soft Continuum Manipulator for Low-Cost Gastroscopy

Gastric cancer is the third leading cause of cancer deaths worldwide, with most new cases occurring in low and middle income countries, where access to screening programs is hindered by the high cost of conventional endoscopy. The waterjet-actuated HydroJet endoscopic platform was developed as a low-cost, disposable alternative for inspection of the gastric cavity in low-resource settings. In this work, we present a teleoperation scheme and contact detection algorithm that work together to enable intuitive teleoperation of the HydroJet within the confined space of the stomach. Using a geometrically accurate stomach model and realistic anatomical inspection targets, we demonstrate that, using these methods, a novice user can complete a gastroscopy in approximately the same amount of time with the HydroJet as with a conventional endoscope

Factors Affecting a Recently Purchased Handgun’s Risk for Use in Crime under Circumstances That Suggest Gun Trafficking

While many handguns are used in crime each year in the USA, most are not. We conducted this study to identify factors present at the time of a handgun’s most recent retail sale that were associated with its subsequent use in crime under circumstances suggesting that the handgun had been trafficked—purchased with the intent of diverting it to criminal use. Handguns acquired in multiple-gun purchases were of particular interest. Using data for 180,321 handguns purchased from federally licensed retailers in California in 1996, we studied attributes of the handguns, the retailers selling them, the purchasers, and the sales transactions. Our outcome measure was a handgun’s recovery by a police agency, followed by a gun ownership trace, conducted by the Bureau of Alcohol, Tobacco, Firearms and Explosives, that determined (a) that the recovery had occurred within 3 years of the handgun’s most recent purchase from a licensed retailer and (b) that the person who possessed the gun when it was recovered by police was not its most recent purchaser. Altogether, 722 handguns were recovered and had trace results that met the additional criteria. Handguns acquired in multiple-gun, same-day transactions were more likely to be traced than were single-purchase handguns (odds ratio [OR] 1.33, 95% confidence intervals [CI] 1.08 to 1.63). This was not the case for multiple-purchase handguns defined more broadly as multiple handguns purchased by one individual over any 30-day period as used in “one-gun-a-month” laws. Bivariate regressions indicated increased risk of a handgun being traced when it sold new for $150 or less (OR 4.28, 95% CI 3.59 to 5.11) or had been purchased by a woman (OR 2.02, 95% CI 1.62 to 2.52). Handguns sold by retailers who also had a relatively high proportion (≥2%) of purchases denied because the prospective purchasers were prohibited from owning firearms were more likely to be traced than were those sold by other retailers (OR 4.09, 95% CI 3.39 to 4.94). These findings persisted in multivariate analyses. Our findings suggest specific strategies for intervention to prevent gun violence

Adrenal suppression in patients taking inhaled glucocorticoids is highly prevalent and management can be guided by morning cortisol

Context Up to 3% of US and UK populations are prescribed glucocorticoids (GC). Suppression of the hypothalamo–pituitary–adrenal axis with the potential risk of adrenal crisis is a recognized complication of therapy. The 250 μg short Synacthen stimulation test (SST) is the most commonly used dynamic assessment to diagnose adrenal insufficiency. There are challenges to the use of the SST in routine clinical practice, including both the staff and time constraints and a significant recent increase in Synacthen cost. Methods We performed a retrospective analysis to determine the prevalence of adrenal suppression due to prescribed GCs and the utility of a morning serum cortisol for rapid assessment of adrenal reserve in the routine clinical setting. Results In total, 2773 patients underwent 3603 SSTs in a large secondary/tertiary centre between 2008 and 2013 and 17.9% (n=496) failed the SST. Of 404 patients taking oral, topical, intranasal or inhaled GC therapy for non-endocrine conditions, 33.2% (n=134) had a subnormal SST response. In patients taking inhaled GCs without additional GC therapy, 20.5% (34/166) failed an SST and suppression of adrenal function increased in a dose-dependent fashion. Using receiver operating characteristic curve analysis in patients currently taking inhaled GCs, a basal cortisol ≥348 nmol/l provided 100% specificity for passing the SST; a cortisol value <34 nmol/l had 100% sensitivity for SST failure. Using these cut-offs, 50% (n=83) of SSTs performed on patients prescribed inhaled GCs were unnecessary. Conclusion Adrenal suppression due to GC treatment, particularly inhaled GCs, is common. A basal serum cortisol concentration has utility in helping determine which patients should undergo dynamic assessment of adrenal function

Focused Deterrence and the Prevention of Violent Gun Injuries: Practice, Theoretical Principles, and Scientific Evidence

Focused deterrence strategies are a relatively new addition to a growing portfolio of evidence-based violent gun injury prevention practices available to policy makers and practitioners. These strategies seek to change offender behavior by understanding the underlying violence-producing dynamics and conditions that sustain recurring violent gun injury problems and by implementing a blended strategy of law enforcement, community mobilization, and social service actions. Consistent with documented public health practice, the focused deterrence approach identifies underlying risk factors and causes of recurring violent gun injury problems, develops tailored responses to these underlying conditions, and measures the impact of implemented interventions. This article reviews the practice, theoretical principles, and evaluation evidence on focused deterrence strategies. Although more rigorous randomized studies are needed, the available empirical evidence suggests that these strategies generate noteworthy gun violence reduction impacts and should be part of a broader portfolio of violence prevention strategies available to policy makers and practitioners

Generation of Ultrastable Microwaves via Optical Frequency Division

There has been increased interest in the use and manipulation of optical fields to address challenging problems that have traditionally been approached with microwave electronics. Some examples that benefit from the low transmission loss, agile modulation and large bandwidths accessible with coherent optical systems include signal distribution, arbitrary waveform generation, and novel imaging. We extend these advantages to demonstrate a microwave generator based on a high-Q optical resonator and a frequency comb functioning as an optical-to-microwave divider. This provides a 10 GHz electrical signal with fractional frequency instability <8e-16 at 1 s, a value comparable to that produced by the best microwave oscillators, but without the need for cryogenic temperatures. Such a low-noise source can benefit radar systems, improve the bandwidth and resolution of communications and digital sampling systems, and be valuable for large baseline interferometry, precision spectroscopy and the realization of atomic time

Closed-loop control of soft continuum manipulators under tip follower actuation

Continuum manipulators, inspired by nature, have drawn significant interest within the robotics community. They can facilitate motion within complex environments where traditional rigid robots may be ineffective, while maintaining a reasonable degree of precision. Soft continuum manipulators have emerged as a growing subfield of continuum robotics, with promise for applications requiring high compliance, including certain medical procedures. This has driven demand for new control schemes designed to precisely control these highly flexible manipulators, whose kinematics may be sensitive to external loads, such as gravity. This article presents one such approach, utilizing a rapidly computed kinematic model based on Cosserat rod theory, coupled with sensor feedback to facilitate closed-loop control, for a soft continuum manipulator under tip follower actuation and external loading. This approach is suited to soft manipulators undergoing quasi-static deployment, where actuators apply a follower wrench (i.e., one that is in a constant body frame direction regardless of robot configuration) anywhere along the continuum structure, as can be done in water-jet propulsion. In this article we apply the framework specifically to a tip actuated soft continuum manipulator. The proposed control scheme employs both actuator feedback and pose feedback. The actuator feedback is utilized to both regulate the follower load and to compensate for non-linearities of the actuation system that can introduce kinematic model error. Pose feedback is required to maintain accurate path following. Experimental results demonstrate successful path following with the closed-loop control scheme, with significant performance improvements gained through the use of sensor feedback when compared with the open-loop case

Dynamic self-assembly of DNA minor groove-binding ligand DB921 into nanotubes triggered by an alkali halide.

We describe a novel self-assembling supramolecular nanotube system formed by a heterocyclic cationic molecule which was originally designed for its potential as an antiparasitic and DNA sequence recognition agent. Our structural characterisation work indicates that the nanotubes form via a hierarchical assembly mechanism that can be triggered and tuned by well-defined concentrations of simple alkali halide salts in water. The nanotubes assembled in NaCl have inner and outer diameters of ca. 22 nm and 26 nm respectively, with lengths that reach into several microns. Our results suggest the tubes consist of DB921 molecules stacked along the direction of the nanotube long axis. The tubes are stabilised by face-to-face π-π stacking and ionic interactions between the charged amidinium groups of the ligand and the negative halide ions. The assembly process of the nanotubes was followed using small-angle X-ray and neutron scattering, transmission electron microscopy and ultraviolet/visible spectroscopy. Our data demonstrate that assembly occurs through the formation of intermediate ribbon-like structures that in turn form helices that tighten and compact to form the final stable filament. This assembly process was tested using different alkali-metal salts, showing a strong preference for chloride or bromide anions and with little dependency on the type of cation. Our data further demonstrates the existence of a critical anion concentration above which the rate of self-assembly is greatly enhanced