Multi-energy reconstructions, central electron temperature measurements, and early detection of the birth and growth of runaway electrons using a versatile soft x-ray pinhole camera at MST.

A multi-energy soft x-ray pinhole camera has been designed, built, and deployed at the Madison Symmetric Torus to aid the study of particle and thermal transport, as well as MHD stability physics. This novel imaging diagnostic technique employs a pixelated x-ray detector in which the lower energy threshold for photon detection can be adjusted independently on each pixel. The detector of choice is a PILATUS3 100 K with a 450 µm thick silicon sensor and nearly 100 000 pixels sensitive to photon energies between 1.6 and 30 keV. An ensemble of cubic spline smoothing functions has been applied to the line-integrated data for each time-frame and energy-range, obtaining a reduced standard-deviation when compared to that dominated by photon-noise. The multi-energy local emissivity profiles are obtained from a 1D matrix-based Abel-inversion procedure. Central values of Te can be obtained by modeling the slope of the continuum radiation from ratios of the inverted radial emissivity profiles over multiple energy ranges with no a priori assumptions of plasma profiles, magnetic field reconstruction constraints, high-density limitations, or need of shot-to-shot reproducibility. In tokamak plasmas, a novel application has recently been tested for early detection, 1D imaging, and study of the birth, exponential growth, and saturation of runaway electrons at energies comparable to 100 × Te,0; thus, early results are also presented.

Long-term outcomes of biological mesh repair following extra levator abdominoperineal excision of the rectum: an observational study of 100 patients.

BACKGROUND: Current evidence suggests that pelvic floor reconstruction following extralevator abdominoperineal excision of rectum (ELAPER) may reduce the risk of perineal herniation of intra-abdominal contents. Options for reconstruction include mesh and myocutaneous flaps, for which long-term follow-up data is lacking. The aim of this study was to evaluate the long-term outcomes of biological mesh (Surgisis®, Biodesign™) reconstruction following ELAPER. METHODS: A retrospective review of all patients having ELAPER in a single institution between 2008 and 2018 was perfomed. Clinic letters were scrutinised for wound complications and all available cross sectional imaging was reviewed to identify evidence of perineal herniation (defined as presence of intra-abdominal content below a line between the coccyx and the lower margin of the pubic symphysis on sagittal view). RESULTS: One hundred patients were identified (median age 66, IQR 59-72 years, 70% male). Median length of follow-up was 4.9 years (IQR 2.3-6.7 years). One, 2- and 5-year mortality rates were 3, 8 and 12%, respectively. Thirty three perineal wounds had not healed by 1 month, but no mesh was infected and no mesh needed to be removed. Only one patient developed a symptomatic perineal hernia requiring repair. On review of imaging a further 7 asymptomatic perineal hernias were detected. At 4 years the cumulative radiologically detected perineal hernia rate was 8%. CONCLUSIONS: This study demonstrates that pelvic floor reconstruction using biological mesh following ELAPER is both safe and effective as a long-term solution, with low major complication rates. Symptomatic perineal herniation is rare following mesh reconstruction, but may develop sub clinically and be detectable on cross-sectional imaging.

Laparoscopic cholecystectomy: a prospective cohort study assessing the impact of grade of operating surgeon on operative time and 30-day morbidity.

Introduction There is an increasing trend towards day case surgery for uncomplicated gallstone disease. The challenges of maximising training opportunities are well recognised by surgical trainees and the need to demonstrate timely progression of competencies is essential. Laparoscopic cholecystectomy provides the potential for excellent trainee learning opportunities. Our study builds upon previous work by assessing whether measures of outcome are still affected when cases are stratified based on procedural difficulty. Material and methods A prospective cohort study of all laparoscopic cholecystectomies conducted at a district general hospital between 2009 and 2014, performed under the care of a single consultant. The operative difficulty was determined using the Cuschieri classification. The primary endpoint was duration of operation. Secondary endpoints included length of hospital stay, delayed discharge rate and 30-day morbidity. Results A total of 266 laparoscopic cholecystectomies were performed during the study period. Mean operative time for all consultant-led cases was 52.5 minutes compared with 51.4 minutes for trainees (P = 0.67 unpaired t-test). When cases were stratified for difficulty, consultant-led cases were on average 5 minutes faster. Median duration of hospital stay was equivalent in both groups and there was no statistical difference in re-attendance (12.9% vs. 15.3% P = 0.59) or re-admission rates (3.2% vs. 8.1% P = 0.10) at 30 days. Conclusions Our study provides evidence that laparoscopic cholecystectomy provides a good training opportunity for surgical trainees without being detrimental to patient outcome. We recommend that, in selected patients, under consultant supervision, laparoscopic cholecystectomy can be performed primarily by the surgical trainee without impacting on patient outcome or theatre scheduling.

Robotic colorectal surgery: previous laparoscopic colorectal experience is not essential.

A background in minimally invasive colorectal surgery (MICS) has been thought to be essential prior to robotic-assisted colorectal surgery (RACS). Our aim was to determine whether MICS is essential prior to starting RACS training based on results from our initial experience with RACS. Two surgeons from our centre received robotic training through the European Academy of Robotic Colorectal Surgery (EARCS). One surgeon had no prior formal MICS training. We reviewed the first 30 consecutive robotic colorectal procedures from a prospectively maintained database between November 2014 and January 2016 at our institution. Fourteen patients were male. Median age was 64.5 years (range 36-82) and BMI was 27.5 (range 20-32.5). Twelve procedures (40%) were performed by the non-MICS-trained surgeon: ten high anterior resections (one conversion), one low anterior resection and one abdomino-perineal resection of rectum (APER). The MICS-trained surgeon performed nine high and four low anterior resections, one APER and in addition three right hemicolectomies and one abdominal suture rectopexy. There were no intra-operative complications and two patients required re-operation. Median post-operative stay was five days (range 1-26). There were two 30-day re-admissions. All oncological resections had clear margins and median node harvest was 18 (range 9-39). Our case series demonstrates that a background in MICS is not essential prior to starting RACS training. Not having prior MICS training should not discourage surgeons from considering applying for a robotic training programme. Safe and successful robotic colorectal services can be established after completing a formal structured robotic training programme.

Population Modeling of Selexipag Pharmacokinetics and Clinical Response Parameters in Patients With Pulmonary Arterial Hypertension.

Selexipag (Uptravi) is an oral selective IP prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension (PAH). The pivotal GRIPHON study was the largest clinical study ever conducted in PAH patients, providing long-term data from 1,156 patients. PAH comedication did not affect exposure to selexipag, while exposure to its active metabolite ACT-333679 was reduced by 30% when taken in combination, clinically not relevant in the context of individual dose up-titration. Using log-linear regression models linking model-predicted steady-state exposure to pharmacodynamics (PD), exposure to selexipag and ACT-333679 showed some statistically significant, albeit not clinically relevant, effects on exercise capacity, laboratory values, and the occurrence of prostacyclin-related adverse events, but not on vital signs or adverse events denoting hemorrhage. Using suitable modeling techniques, the GRIPHON study yielded clinically relevant data with limited burden of pharmacokinetics (PK) blood sampling, demonstrating that PK/PD modeling enables firm conclusions even with sparse PK and PD sampling.

Evolution of a Vortex in a Strain Flow.

Experiments and vortex-in-cell simulations are used to study an initially axisymmetric, spatially distributed vortex subject to an externally imposed strain flow. The experiments use a magnetized pure electron plasma to model an inviscid two-dimensional fluid. The results are compared to a theory assuming an elliptical region of constant vorticity. For relatively flat vorticity profiles, the dynamics and stability threshold are in close quantitative agreement with the theory. Physics beyond the constant-vorticity model, such as vortex stripping, is investigated by studying the behavior of nonflat vorticity profiles.

Day-case closure of ileostomy: feasible, safe and efficient.

AIM: Over 5000 loop ileostomy closures were performed in the UK in 2013 with a median inpatient stay of 5 days. Previously we have successfully implemented a 23-h protocol for loop ileostomy closure which was modified for same-day discharge. We present our early experience of day-case loop ileostomy closure. METHOD: A specific patient pathway for day-case discharge following loop ileostomy closure was implemented with inclusion criteria to conform with British Association of Day Surgery guidelines. Exclusion criteria included postoperative chemoradiotherapy, multiple comorbidities and social care needs. Follow-up consisted of telephone contact (24 and 72 h after discharge) and a routine outpatient appointment. Patients were provided with a 24-h contact point in case of emergency. RESULTS: Fifteen (12 male) patients were enrolled of median age 67 (39-80) years. The median operating time was 41 (23-80) min. The indication for ileostomy formation was to cover a low anterior resection for adenocarcinoma (13), reversal of Hartmann's procedure (1) and functional bowel disorder (1). The median interval from the primary procedure to day-case loop ileostomy closure was 8 (3-14) months. Every patient was discharged on the day of surgery. There were no complications related to the surgery and there was one readmission due to a urinary tract infection. The median length of follow-up was 4 (2-16) months. CONCLUSION: Our early experience shows that day-case loop ileostomy closure is feasible, safe and efficient. This protocol will become standard within our institution for suitable patients, saving on average five inpatient bed days per patient.

Post receptor determinants of acute platelet response to clopidogrel in patients with symptomatic myocardial ischemia.

BACKGROUND: Clopidogrel resistance is more common in patients with loss-of-function CYP2C19 genotypes. Since adenylate cyclase (AC) and soluble guanylate cyclase (sGC) pathways are variably impaired in patients with ischaemic heart disease, we tested the relevance of these determinants in patients undergoing acute loading with clopidogrel (600 mg) prior to non-emergent coronary stenting. METHODS: Inhibitory effects of prostaglandin E1 (PGE1, an AC activator) and sodium nitroprusside (NP, a sGC activator) on platelet aggregation were determined at baseline and compared with platelet responses to clopidogrel (4 h after administration) assessed as ∆ADP, and Platelet Reactivity Index (∆PRI). Data were analysed according to CYP2C19 genotype. RESULTS: In patients without loss of function mutations (n=18), ∆ADP but not ∆PRI, was directly correlated with baseline PGE1 responsiveness (rs=0.62, p=0.005)). NP responsiveness did not predict ∆ADP. However there was no relationship between clopidogrel responses and either PGE1 or NP responsiveness in patients with loss of function mutations. Multivariate correlates of clopidogrel response were both the genotype status (ß=-0.609, p<0.001) and the baseline response to PGE1 (ß=0.303, p=0.03). CONCLUSIONS: While genetically impaired bio-activation markedly limits acute (4 h) clopidogrel response, impaired AC signalling provides an additional cause for clopidogrel resistance.

One-third of patients fail to return to work 1 year after surgery for colorectal cancer.

BACKGROUND: Achieving full recovery after colorectal cancer surgery means a return to normal physical and psychological health and to a normal social life. Recovery data focusses on time to discharge rather than longer term functionality including return to work (RTW). We aim to assess return to normal holistic function at 1 year after colorectal cancer surgery. METHOD: Questionnaires were created and dispatched to 204 patients who had undergone surgery with curative intent for colorectal cancer, in 2011-2012, in a single teaching hospital. RESULTS: Response rate was 75 % (153/204), 82 % (129/157) for open surgery (OS) and 51 % (24/47) for laparoscopic surgery (LS). Median age was 68 (48-91) years for OS and 65 (36-84) for LS. Eighty-four per cent of patients felt 'ready' and 95 % had adequate pain control upon discharge (no difference between groups). LS reported earlier 'return to full fitness' (1-3 months) than OS (>6 months; Mann-Whitney U, p < 0.05). Recovery from LS was 'better than expected' compared to OS 'worse than expected' (Mann-Whitney U test, p < 0.05). Forty-nine patients were employed preoperatively and 61 % (n = 30) returned to work. RTW was more frequent after LS (Chi-square test, p < 0.05). Length of time to RTW was significantly less after LS [44 (6-84) days] than OS [71 (14-252) days] (t test, p < 0.05). Levels of self-employment were equal between groups. CONCLUSIONS: One-third of patients failed to RTW at 1 year post-surgery. Patients having LS returned to full fitness faster, felt recovery was shorter and returned to work earlier than OS. We must invest more in managing expectations and provide better post-discharge support to improve RTW.

Electron plasma orbits from competing diocotron drifts.

The perpendicular dynamics of a pure electron plasma column are investigated when the plasma spans two Penning-Malmberg traps with noncoinciding axes. The plasma executes noncircular orbits described by competing image-charge electric-field (diocotron) drifts from the two traps. A simple model is presented that predicts a set of nested orbits in agreement with observed plasma trajectories.

Outcomes after biological mesh reconstruction of the pelvic floor following extra-levator abdominoperineal excision of rectum (APER).

BACKGROUND: Extra-levator abdominoperineal excision of the rectum (ELAPER) for low rectal cancer is used to avoid the adverse oncological outcomes of inadvertent perforation and a positive circumferential resection margin associated with the conventional APER technique. This wider excision creates a large defect requiring pelvic floor reconstruction, and there is still controversy regarding the best method of closure. The aim of this study is to present outcomes of biological mesh pelvic floor reconstruction following ELAPER. METHODS: Prospective data on consecutive patients having ELAPER for low rectal cancer at a single UK institution between October 2008 and March 2013 were collected. The perineum was reconstructed using a biological mesh and the short-term outcomes were evaluated, focusing particularly on perineal wound complications and perineal hernias. RESULTS: Thirty-four patients were included [median age 62 years, range 40-72 years, 27 males (79 %)]. The median operative time was 248 min (range 120-340 min). The median length of hospital stay was 9 days (range 4-20 days). There were three perineal complications (9 %) requiring surgical intervention, but no meshes were removed. There were no perineal hernias. The median length of follow-up was 21 months (range 1-54 months). The overall mortality was 9 % from distant metastases. CONCLUSIONS: Our series adds to the increasing evidence that good outcomes can be achieved for pelvic floor reconstruction with biological mesh following ELAPER without the additional use of myocutaneous flaps. The low serious complication rate, good outcomes in perineal wound healing and the absence of perineal hernias demonstrates that this is a safe and feasible procedure.

Laparoscopic Rectopexy for Rectal Prolapse: Will it be the Gold Standard?

A review of the current literature is presented regarding the surgical management of full thickness rectal prolapse, comparing laparoscopic rectopexy with open abdominal operations and perineal procedures. Outcome measures include length of stay, short- and long-term outcomes and financial burdens. Current evidence suggests that laparoscopic rectopexy as treatment for full thickness rectal prolapse is a safe alternative to the other options.

Clopidogrel "resistance": pre- vs post-receptor determinants.

The clinical efficacy of the P2Y12 receptor antagonist clopidogrel as an agent to prevent thrombotic events predominantly reflects its anti-aggregatory effects. Stent thrombosis in particular is more likely to occur in patients in whom clopidogrel effect is limited. "Resistance" to clopidogrel in general should theoretically arise either because of a reduction in plasma concentration of the active metabolite and/or of the downstream intracellular biochemical changes underlying antiplatelet effects. We therefore postulate that "resistance" to clopidogrel arises via a combination of pharmacogenetic, pharmacokinetic and intracellular biochemical mechanisms. Considerable attention has been so far directed to the finding that stent thrombosis occurs more frequently in patients with loss-of-function mutations of CYP2C19, thus limiting clopidogrel bioactivation. Furthermore, a number of drug-drug interactions may marginally impair responsiveness to clopidogrel, largely via impairment of bioactivation. However, population data also suggest that clopidogrel "resistance" occurs more frequently in patients with acute coronary syndromes than in normal subjects, and that "resistance" is particularly common in obese subjects and with diabetes. Here we critically review available literature and speculate on the possibility that non-genetic causes of clopidogrel "resistance" may arise from impairments of the intracellular signaling cascade initiated by P2Y12 receptor inhibition. In such cases, "resistance" to clopidogrel may also theoretically occur with other P2Y12 receptor antagonists, irrespective of the need for bioactivation. Delineation of this non-genetic component of "resistance" to P2Y12 inhibitors may facilitate the development of optimal therapeutic strategies for high-risk cardiovascular patients.

Twenty-three-hour stay loop ileostomy closures: a pilot study.

BACKGROUND: In UK in 2010-2011, 4,463 ileostomy closures were performed (35,442 bed days) with a median inpatient stay of 5 days (Hospital Episode Statistics data). This seems anomalous when there are reports of 23-h stay colectomies. We present our early experience of 23-h discharge for loop ileostomy closures. METHODS: A specific patient journey/pathway for 23-h discharge following loop ileostomy closure was implemented at a single UK institution between August 2011 and April 2012. Follow-up was by telephone contact 24-48 h postdischarge and by routine outpatient appointment, and patients were also provided with a 24-h contact point in case of emergency. RESULTS: Twenty-three patients were included (18 male patients; median age, 63 years; range, 28-78 years). Fifteen were discharged within 23 h. The remaining 8 patients were all discharged within 48 h of surgery. Four patients were readmitted with superficial wound infection (1), slight wound discharge (1), Clostridium difficile diarrhoea (1) and an anastomotic leak 8 days after surgery (1). Median length of follow-up was 3 months (range, 1-10 months). CONCLUSIONS: A specific 23-h discharge protocol for loop ileostomy closures is feasible and safe. Improved primary care and out-of-hours hospital support would have prevented both minor wound complications requiring readmission. The anastomotic leak presented at postoperative day 8 and would have occurred in the community even if a standard protocol was used. Additional patient information and support via stoma care have been introduced to build on our experience, and 23-h stay has been introduced as standard care.

Improvements to the calibration of the MST Thomson scattering diagnostic.

Calibration of the Madison Symmetric Torus Thomson scattering system has been refined to improve temperature fluctuation measurements. Multiple avalanche photodiodes have been directly calibrated for use as reference detectors during calibration, improving accuracy and ease of use. From the absolute calibration we calculate corrections to the gain for variation in detector operating temperature. We also measure the spatial uniformity of detector responsivity for several photodiodes, and present a method of accounting for non-uniformity in the calibration process. Finally, the gain and noise enhancement are measured at multiple wavelengths to improve temperature and uncertainty measurements.

Biological mesh reconstruction of perineal wounds following enhanced abdominoperineal excision of rectum (APER).

INTRODUCTION: An abdominoperineal excision of rectum (APER) may be required for rectal tumours less than 6 cm from the anal verge. Recently, the cylindrical APER has been used to prevent the "surgical waist" and so decrease margin involvement. However, removal of the levators leaves a large defect. Myocutaneous flaps [e.g. vertical rectus abdominis (VRAM)] are often used to fill the cylindrical resection defect, but have disadvantages associated with operative time, expertise and morbidity. We report our early experience of pelvic floor reconstruction with a biological mesh following cylindrical APER. METHODS: Data on consecutive patients having cylindrical APER between January 2008 and November 2010 were collected. Outcomes were compared between a VRAM reconstruction group and a mesh group. RESULTS: In 15 consecutive patients with low rectal cancer, five patients had VRAM pelvic floor reconstruction prior to ten patients having biosynthetic mesh repairs. The median operative time for the VRAM cohort was 405 min, compared with 259 min for the mesh (p = 0.0013). The median length of postoperative stay was 20 days for VRAM and 10 days for the mesh group (p = 0.067). There were four early complications for the VRAM group compared with seven for the mesh cohort (p = 0.37). The median cost per patient for the VRAM cohort was £11,075 compared to a median cost of £6,513 for the Mesh (p = 0.0097). CONCLUSION: The use of a biological mesh for pelvic floor reconstruction following cylindrical APER is feasible with morbidity comparable to VRAM reconstruction. There is significant cost-saving using a biosynthetic mesh, mainly due to reduced length of stay.

Breastmilk cultures and infection in extremely premature infants.

OBJECTIVE: As expressed mother's milk (MM) is known to be colonized by microbial species, it is occasionally considered as a source of infection in premature infants, prompting some clinicians to obtain milk bacterial culture results before infant feeding. To determine whether serial microbial cultures of MM predict infection in premature infants. STUDY DESIGN: Milk microbial flora was determined by plate counts from aliquots of MM obtained from 161 mothers of infants born <30 weeks gestation (n = 209). Pathogens isolated from the same infant were tabulated. RESULT: Milk samples (n = 813) yielded 1963 isolates. There were no relationships between microbial counts and maternal age, ethnicity, education, skin-to-skin contact and infant infection. In 64 infants, milk and pathological isolates had presumptively the same Gram-positive organism, yet the odds of infection before or after exposure to milk containing that Gram-positive organism were not significant (1.18; 95% confidence interval=0.51, 2.76). In eight infants, milk and pathological isolates had presumptively the same Gram-negative organism, which appeared sporadically in milk, either before or after isolation in the infant. CONCLUSION: Results of initial milk cultures do not predict subsequent culture results. Random milk cultures, even if obtained at any time during hospitalization, are not predictive of infection in premature infants. The sporadic nature of the appearance of certain isolates, however, suggests common exposure of both mother and infant. Routine milk cultures do not provide sufficient data to be useful in clinical management.

Initial operation of a pulse-burst laser system for high-repetition-rate Thomson scattering.

A pulse-burst laser has been installed for Thomson scattering measurements on the Madison Symmetric Torus reversed-field pinch. The laser design is a master-oscillator power-amplifier. The master oscillator is a commercial Nd:YVO(4) laser (1064 nm) which is capable of Q-switching at frequencies between 5 and 250 kHz. Four Nd:YAG (yttrium aluminum garnet) amplifier stages are in place to amplify the Nd:YVO(4) emission. Single pulses through the Nd:YAG amplifier stages gives energies up to 1.5 J and the gain for each stage has been measured. Repetitive pulsing at 10 kHz has also been performed for 2 ms bursts, giving average pulse energies of 0.53 J with ΔE/E of 4.6%, where ΔE is the standard deviation between pulses. The next step will be to add one of two Nd:glass (silicate) amplifier stages to produce final pulse energies of 1-2 J for bursts up to 250 kHz.