Experimental Validation of a Kinetic Ballooning Mode in High-Performance High-Bootstrap Current Fraction Fusion Plasmas.

We report the observation of a set of coherent high frequency electromagnetic fluctuations that leads to a turbulence induced self-regulating phenomenon in the DIII-D high bootstrap current fraction plasma. The fluctuations have frequency of 130-220 kHz, the poloidal wavelength and phase velocity are 16-30 m^{-1} and ∼30 km/s, respectively, in the outboard midplane with the estimated toroidal mode number n∼5-9. The fluctuations are located in the internal transport barrier (ITB) region at large radius and are experimentally validated to be kinetic ballooning modes (KBM). Quasilinear estimation predicts the KBM to be able to drive experimental particle flux and non-negligible thermal flux, suggesting its significant role in regulating the ITB saturation.

Diagnostic accuracy of magnetic resonance imaging targeted biopsy techniques compared to transrectal ultrasound guided biopsy of the prostate: a systematic review and meta-analysis.

BACKGROUND: Multiparametric MRI localizes cancer in the prostate, allowing for MRI guided biopsy (MRI-GB) 43 alongside transrectal ultrasound-guided systematic biopsy (TRUS-GB). Three MRI-GB approaches exist; visual estimation (COG-TB); fusion software-assisted (FUS-TB) and MRI 'in-bore' biopsy (IB-TB). It is unknown whether any of these are superior. We conducted a systematic review and meta-analysis to address three questions. First, whether MRI-GB is superior to TRUS-GB at detecting clinically significant PCa (csPCa). Second, whether MRI-GB is superior to TRUS-GB at avoiding detection of insignificant PCa. Third, whether any MRI-GB strategy is superior at detecting csPCa. METHODS: A systematic literature review from 2015 to 2019 was performed in accordance with the START recommendations. Studies reporting PCa detection rates, employing MRI-GB and TRUS-GB were included and evaluated using the QUADAS-2 checklist. 1553 studies were found, of which 43 were included in the meta-analysis. RESULTS: For csPCa, MRI-GB was superior in detection to TRUS-GB (0.83 vs. 0.63 [p = 0.02]). MRI-GB was superior in detection to TRUS-GB at avoiding detection of insignificant PCa. No MRI-GB technique was superior at detecting csPCa (IB-TB 0.87; COG TB 0.81; FUS-TB 0.81, [p = 0.55]). There was significant heterogeneity observed between the included studies. CONCLUSIONS: In patients with suspected PCa on MRI, MRI-GB offers superior rates of csPCa detection and reduces detection of insignificant PCa compared to TRUS-GB. No individual MRI-GB technique was found to be better in csPCa detection. Prospective adequately powered randomized controlled trials are required.

PROState Pathway Embedded Comparative Trial: The IP3-PROSPECT study.

INTRODUCTION: The traditional double blind RCT is the 'gold standard' trial design. For a variety of reasons, these designs often fail to accrue enough participants to conclude. This is particularly challenging in localized prostate cancer. The cohort multiple randomised controlled trial (cmRCT) trial design may represent an alternative approach to delivering robust comparative data in prostate cancer. PATIENTS AND METHODS: IP3-PROSPECT is a cmRCT designed to test multiple prostate cancer interventions from eligible men in one cohort. Key to the design is two points of consent. First, at point of consent one, men referred for prostate cancer investigations are invited to join the cohort. They may then be randomly invited at a later date to consider an intervention at point of consent two. In the pilot phase we will test the acceptability and feasibility of developing the cohort. RESULTS: Acceptability and feasibility of the study will be measured by a combination of quantitative and qualitative methods. The primary outcome measure is the rate of consent to inclusion to the IP3-PROSPECT cohort. Secondary outcome measures include the completeness of data collection at sites and return rates of patient questionnaires. We will also interview patients and healthcare professionals to explore their thoughts on the implementation, practicality and efficiency of IP3-PROSPECT. CONCLUSION: The IP3-PROSPECT study will evaluate the cmRCT design in prostate cancer. Initially we will pilot the design, assessing for acceptability and feasibility. The cmRCT is an innovative design that offers potential for building a modern comparative evidence base for prostate cancer.

A systematic review and meta-analysis of the diagnostic accuracy of biparametric prostate MRI for prostate cancer in men at risk.

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI), the use of three multiple imaging sequences, typically T2-weighted, diffusion weighted (DWI) and dynamic contrast enhanced (DCE) images, has a high sensitivity and specificity for detecting significant cancer. Current guidance now recommends its use prior to biopsy. However, the impact of DCE is currently under debate regarding test accuracy. Biparametric MRI (bpMRI), using only T2 and DWI has been proposed as a viable alternative. We conducted a contemporary systematic review and meta-analysis to further examine the diagnostic performance of bpMRI in the diagnosis of any and clinically significant prostate cancer. METHODS: A systematic review of the literature from 01/01/2017 to 06/07/2019 was performed by two independent reviewers using predefined search criteria. The index test was biparametric MRI and the reference standard whole-mount prostatectomy or prostate biopsy. Quality of included studies was assessed by the QUADAS-2 tool. Statistical analysis included pooled diagnostic performance (sensitivity; specificity; AUC), meta-regression of possible covariates and head-to-head comparisons of bpMRI and mpMRI where both were performed in the same study. RESULTS: Forty-four articles were included in the analysis. The pooled sensitivity for any cancer detection was 0.84 (95% CI, 0.80-0.88), specificity 0.75 (95% CI, 0.68-0.81) for bpMRI. The summary ROC curve yielded a high AUC value (AUC = 0.86). The pooled sensitivity for clinically significant prostate cancer was 0.87 (95% CI, 0.78-0.93), specificity 0.72 (95% CI, 0.56-0.84) and the AUC value was 0.87. Meta-regression analysis revealed no difference in the pooled diagnostic estimates between bpMRI and mpMRI. CONCLUSIONS: This meta-analysis on contemporary studies shows that bpMRI offers comparable test accuracies to mpMRI in detecting prostate cancer. These data are broadly supportive of the bpMRI approach but heterogeneity does not allow definitive recommendations to be made. There is a need for prospective multicentre studies of bpMRI in biopsy naïve men.

A Multicenter Study of the Clinical Utility of Nontargeted Systematic Transperineal Prostate Biopsies in Patients Undergoing Pre-Biopsy Multiparametric Magnetic Resonance Imaging.

PURPOSE: The added value of nontargeted systematic prostate biopsies when performed alongside magnetic resonance imaging targeted biopsies in men referred with a suspicion of prostate cancer is unclear. We aimed to determine the clinical utility of transperineal nontargeted systematic prostate biopsies, when performed alongside targeted systematic prostate biopsies, using pre-biopsy multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Consecutive patients referred with a suspicion of prostate cancer (April 2017 to October 2019) underwent pre-biopsy multiparametric magnetic resonance imaging. A transperineal biopsy was advised if multiparametric magnetic resonance imaging PI-RADS® (v.2.0) score was 4 or 5, and score 3 required a prostate specific antigen density 0.12 ng/ml or greater. Primary threshold for clinically significant prostate cancer was defined as any Gleason 3+4 or greater. Multivariable logistic regression analysis identified pre-biopsy predictors of clinically significant prostate cancer in nontargeted systematic prostate biopsies, regardless of targeted pathology (p <0.05, R, version 3.5.1). RESULTS: A total of 1,719 men underwent a pre-biopsy multiparametric magnetic resonance imaging, with 679 (39.5%) proceeding to combined targeted systematic prostate biopsies and nontargeted systematic prostate biopsies. In these men clinically significant prostate cancer was detected in 333 (49%) and 139 (20.5%) with targeted systematic prostate biopsies and nontargeted systematic prostate biopsies, respectively. In those men with clinically significant prostate cancer in targeted systematic prostate biopsies, clinically significant prostate cancer was also present in nontargeted systematic prostate biopsies in 117 (17.2%); Gleason 3+3 was present in 50 (7.4%). In 287 men without any cancer in the targeted systematic prostate biopsies, 13 (1.9%) had clinically significant prostate cancer in nontargeted systematic prostate biopsies. In addition 18/679 (2.7%) had Gleason 3+3 disease and no Gleason greater than 4+3 was detected. Predictors associated with clinically significant prostate cancer in nontargeted systematic prostate biopsies were prostate specific antigen 5 ng/ml or greater (OR 2.05, 95% CI 1.13-3.73, p=0.02), PI-RADS score 5 (OR 2.26, 95% CI 1.51-3.38, p <0.001) and prostate volume less than 50 cc (OR 2.47, 95% CI 1.57-3.87, p <0.001). CONCLUSIONS: Detection of clinically significant prostate cancer in exclusively nontargeted transperineal systematic biopsies in a pre-biopsy multiparametric magnetic resonance imaging pathway was low (1.9%).

Magnetic resonance imaging targeted transperineal prostate biopsy: a local anaesthetic approach.

BACKGROUND: Despite high rates of disease misclassification and sepsis, the use of transrectal biopsy remains commonplace. Transperineal mapping biopsies mitigate these problems but carry increased cost and patient burden. Local anaesthetic, multiparametric magnetic resonance imaging (MRI)-targeted transperineal biopsy may offer an alternative. Here, we aim to determine the feasibility, tolerability and detection rates of clinically significant prostate cancer using a local anaesthetic, transperineal, MRI-targeted biopsy technique. METHODS: Tertiary referral centre in which 181 consecutive men underwent local anaesthetic, transperineal MRI-targeted prostate biopsy (September 2014 to January 2016). A standardized local anaesthetic technique was used to obtain targeted biopsies using visual estimation with the number of targeted cores determined by each of a number of users. We assessed adverse events, patient visual analogue pain scores and detection rates of clinically significant cancer (defined by University College London (UCL) definitions one and two and separately by the presence of dominant and non-dominant Gleason pattern 4). We secondarily assessed detection of any cancer, rates of detection by MRI (Likert) score and by presenting PSA. Differences were assessed using Chi-squared tests (P<0.05). RESULTS: One hundred eighty-one men with 243 lesions were included. There were no episodes of sepsis or re-admissions and one procedure was abandoned owing to patient discomfort. Twenty-three out of 25 (92%) men would recommend the procedure to another. Median visual analogue pain score was 1.0 (interquartile range: 0.0-2.4). A total 104/181 (57%) had UCL definition 1 disease (Gleason ⩾4+3 and/or maximum cancer length ⩾6 mm) and 129/181 (71%) had UCL definition 2 cancer (Gleason ⩾3+4 and/or maximum cancer length ⩾4 mm). Fifty-four out of 181 (30%) and 124/181 (69%) had dominant and non-dominant pattern 4 disease or greater (irrespective of cancer length). Any cancer was detected in 142/181 (78%). Significant disease was more likely in higher MRI-scoring lesions and in men with PSAs ⩾10 ng ml-1. CONCLUSIONS: This approach to prostate biopsy is feasible, tolerable and can be performed in ambulatory settings.

Adequacy of information transferred at resident sign-out (in-hospital handover of care): a prospective survey.

BACKGROUND: During sign-out (handover of care), information and responsibility about patients is transferred from one set of caregivers to another. Few residency training programmes formally teach resident physicians how to sign out or assess their ability to sign out, and little research has examined the sign-out process. OBJECTIVE: To characterise the effectiveness of the sign-out process between resident physicians on an acute care ward. Design/ METHODS: Resident physicians rotating on a paediatric acute care ward participated in a prospective study. Immediately after an on-call night, they completed a confidential survey characterising their night on call, the adequacy of the sign-out they received, and where they went to get information they had not received during sign-out. RESULTS: 158 of 196 (81%) potential surveys were collected. On 49/158 surveys (31%), residents indicated something happened while on call they were not adequately prepared for. In 40/49 instances residents did not receive information during sign-out that would have been helpful, and in 33/40 the situation could have been anticipated and discussed during sign-out. The quality of sign-out (assessed using a five-point Likert scale from 1 = inadequate to answer call questions to 5 = adequate to answer call questions) on the nights when something happened the resident was not adequately prepared for were significantly different than the nights they felt adequately prepared (mean (SD) score 3.58 (0.92) and 4.48 (0.70); p = 0.001). There were no significant differences in: how busy the nights were; numbers of patients on service at the beginning of the call shift; numbers of admissions during a call shift; numbers of transfers to an intensive care unit; whether residents were "cross-covering" or were members of the general ward team; or whether the resident had cared for the patient previously. CONCLUSION: Although sign-out between resident physicians is a frequent activity, there are many times when important information is not transmitted. Analysis of these "missed opportunities" can be used to help develop an educational programme for resident physicians on how to sign out more effectively.

WITHDRAWN: Anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter.

BACKGROUND: Atrial fibrillation (AF) carries a high risk of stroke and other thromboembolic events. Appropriate use of drugs to prevent thromboembolism in patients with AF involves comparing the patient's risk of stroke to the risk of hemorrhage from medication use. OBJECTIVES: To quantify risk of stroke, major hemorrhage and death from using medications that have been rigorously evaluated for prevention of thromboembolism in AF. SEARCH STRATEGY: Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until December 1999. SELECTION CRITERIA: Included Randomized controlled trials of drugs to prevent thromboembolism in adults with non-postoperative AF. Excluded RCTS of patients with rheumatic valvular disease. DATA COLLECTION AND ANALYSIS: Data were abstracted by two reviewers. Odds ratios from all qualitatively similar studies were combined, with weighting by study size, to yield aggregate odds ratios for stroke, major hemorrhage, and death for each drug. MAIN RESULTS: Fourteen articles were included in this review. Warfarin was more efficacious than placebo for primary stroke prevention {aggregate odds ratio (OR) of stroke=0.30 [95% Confidence Interval (C.I.) 0.19,0.48]}, with moderate evidence of more major bleeding { OR= 1.90 [95% C.I. 0.89,4.04].}. Aspirin was inconclusively more efficacious than placebo for stroke prevention {OR=0.68 [95% C.I. 0.29,1.57]}, with inconclusive evidence regarding more major bleeds {OR=0.81[95% C.I. 0.37,1.78]}. For primary prevention, assuming a baseline risk of 45 strokes per 1000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was moderate evidence for fewer strokes among patients on warfarin than on aspirin {aggregate OR=0.64[95% C.I. 0.43,0.96]}, with only suggestive evidence for more major hemorrhage {OR =1.58 [95% C.I. 0.76,3.27]}. However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared to aspirin was low (5.5 per 1000 person-years) compared to an older group (15 per 1000 person-years). Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarin. AUTHORS' CONCLUSIONS: The evidence strongly supports warfarin in AF for patients at average or greater risk of stroke, although clearly there is a risk of hemorrhage. Although not definitively supported by the evidence, aspirin may prove to be useful for stroke prevention in sub-groups with a low risk of stroke, with less risk of hemorrhage than with warfarin. Further studies are needed of low- molecular weight heparin and aspirin in lower risk patients.

Biaxial testing of human annulus fibrosus and its implications for a constitutive formulation.

Internal pressure in the healthy human annulus fibrosus leads to multiaxial stress in vivo, yet uniaxial tests have been used exclusively to characterize its in vitro mechanical response and to determine its elastic strain energy function (W). We expected that biaxial tension tests would provide unique and necessary data for characterizing the annular material response, and thereby, for determining W. We performed uniaxial and biaxial tests on specimens of annulus, then developed an objective methodology for defining an appropriate form for W that considers data from multiple experiments simultaneously and allows the data to dictate more directly the form and the number of parameters needed. We found that the stresses attained in the biaxial tests were higher, while the strains were considerably lower, than those observed in the uniaxial tests. A comparison of strain energy functions determined from the different data sets demonstrated that constitutive models derived from uniaxial data could not predict annulus behavior in biaxial tension and vice versa. Since the annulus is in a state of multaxial stress in vivo, we conclude that uniaxial tests alone are insufficient to prescribe a physiologically relevant W for this tissue.

Treatment of venous thromboembolism with low-molecular-weight heparin: a synthesis of the evidence published in systematic literature reviews.

OBJECTIVE: To evaluate the methodology and cumulative evidence presented in systematic reviews of clinical trials comparing low-molecular-weight heparin (LMWH) with unfractionated heparin (UFH) for the treatment of venous thromboembolism. METHODS: We reviewed all systematic reviews of clinical trials published until March 2002. Fourteen systematic literature reviews were published between 1994 and 2000. Deficiencies in methodological quality were common, particularly in the description of search strategies, assessment of clinical trial quality, and methods used to combine results. RESULTS: Results of reviews indicate that LMWH is superior to UFH for the treatment of venous thromboembolism, particularly in reducing mortality. Patients with isolated deep venous thrombosis or deep venous thrombosis with concomitant pulmonary embolism seemed to have similar benefit. However, the benefits of LMWH over UFH were smaller in magnitude in reviews that included more recent clinical trials.

Patient preferences for anaesthesia management during cataract surgery.

BACKGROUND/AIMS: To assess patient preferences for different anaesthesia management strategies during cataract surgery. METHODS: Cross sectional clinic based study of patient preferences for anaesthesia management strategies. Patients rated their preferences using a linear rating scale from 0 to 100. RESULTS: Subjects tended to prefer block to topical anaesthesia and oral to intravenous sedation. On a scale from 0 to 100, subjects preferred oral to intravenous sedation and block to topical anaesthesia by about 8 points. CONCLUSIONS: When given the choice of four different anaesthesia management strategies, 72% of the study subjects preferred block anaesthesia to topical anaesthesia. More patients chose to have oral sedation than intravenous sedation. These findings indicate that patients may prefer anaesthesia management approaches other than the ones they are currently being offered.

VF-14 item specific responses in patients undergoing first eye cataract surgery: can the length of the VF-14 be reduced?

AIMS: To report the item specific responses of the VF-14 in a population of patients undergoing cataract surgery in their first eye and to determine whether or not the VF-14 can be reduced without compromising its performance as an index of cataract related visual impairment. METHODS: The item specific responses to the VF-14 were analysed before (771 patients) and 4 months after (552 patients) cataract surgery in one eye to determine if the VF-14 index can be reduced without compromising its performance. Patients studied were selected from a cross sectional longitudinal study of patients undergoing cataract surgery in 72 ophthalmologist's offices located in three metropolitan regions of the United States. RESULTS: Pairwise correlations between items in the VF-14 were all less than 0.6, indicating that no items could be removed solely on the basis of redundancy. 10 items correlated moderately with change in trouble, and 11 correlated moderately with change in satisfaction (r >0.15) at 4 months after cataract extraction. Eleven items demonstrated an effect size >0.4 at 4 months. These 11 items were either important for detecting cataract related functional disability or for quantifying the extent to which cataract impaired function. Additionally, 11 items were needed to detect adequately individuals with functional impairment. Three items (recognising people, cooking, and reading large print) were less responsive to cataract extraction and were more strongly associated with ocular comorbidities. CONCLUSIONS: While previous reports indicate that the VF-14 can be significantly shortened, our analysis only justifies removing three items. While the resulting VF-11 has properties similar to the VF-14, the limited time savings do not justify altering this already validated instrument.

Cast post and core foundation for the badly broken down molar tooth.

BACKGROUND: This article addresses the difficult clinical problem of restoration of endodontically treated posterior teeth, where there is nothing left of the clinical crown. METHODS: A step by step procedure, including instrumentation and materials and a new impression technique, is described in detail, with clinical photographs. RESULTS: This technique results in the fabrication of a robust and extremely retentive post and core on which to place fixed prosthodontic restorations. CONCLUSIONS: The author has placed over 600 restorations of this type over a five year period, without any reported failures. With the 'greying' of the population there are increased demands on dentists to restore structurally compromised teeth, and increasing expectations of the performance of these restorations. This technique is offered as a superior alternative to conventional post and core constructions methods.