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Summary Background Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy. Methods We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0–1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov , NCT00860652 . Findings Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3–7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81–92) in the adjuvant radiotherapy group versus 87% (82–93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65–1·90; pnon-inferiority=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%]). Interpretation Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity. Funding New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia.

Background In adults, anti–tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. Methods Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients Results Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn’s disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti–TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti–TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1–20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46–66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. Conclusions LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti–TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.

Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P p P P

Caveolae are specialized domains of the vertebrate cell surface with a well-defined morphology and crucial roles in cell migration and mechanoprotection. Unique compositions of proteins and lipids determine membrane architectures. The precise caveolar lipid profile and the roles of the major caveolar structural proteins, caveolins and cavins, in selectively sorting lipids have not been defined. Here we used quantitative nanoscale lipid mapping together with molecular dynamic simulations to define the caveolar lipid profile. We show that caveolin1 (CAV1) and cavin1 individually sort distinct plasma membrane lipids. Intact caveolar structures composed of both CAV1 and cavin1 further generate a unique lipid nano-environment. The caveolar lipid sorting capability includes selectivities for lipid headgroups and acyl chains. Because lipid headgroup metabolism and acyl chain remodelling are tightly regulated, this selective lipid sorting may allow caveolae to act as transit hubs to direct communications among lipid metabolism, vesicular trafficking and signalling.

The paper, Specialist Nursing Improves Outcomes in Heart Failure considers the question What is Heart Failure? and examines the symptoms, global incidence and typical interventions alongside the emergent role of the Heart Failure Nurse Specialist and their positive impact on patient care. Three clinical case studies are explored examining the treatment and management of a patient with 1. Non-Ischaemic viral heart failure, 2. Non-Ischaemic alcohol related heart failure and 3. Ischaemic heart disease causing heart failure. The case studies illustrate the complex interventions made by specialist heart failure nurse specialist and provide 10 reasons why Heart Failure Nurse Specialists are an important and impactful addition to the nursing workforce.

The shortage of registered nurses is a global concern and so understanding and developing innovative and effective ways to prepare, recruit and retain nurses has become critical. As nurse shortages compromise healthcare systems, workers’ wellbeing, patient care and the reputation of the profession, it is as much an issue for nurse educators as for health service providers. This plenary session describes a collaboration between a UK University and a large health service provider to develop and test an innovative evidence-based model for improving nurse retention: TRACS (Transition, Resilience, Authentic leadership, Commitment, Support). This is a mixed method study with six phases across two years. Phase 1 involved analyzing current evidence and collecting base line data (retention, recruitment, job satisfaction, exit interviews). It revealed that absentee (sickness) rates, monthly staff turnover, % of vacant posts were highest in the Older Person’s Medicine (OPM) directorate. Phase 2 employed two tools (PES-NWI and Maslach) to survey the practice environment and perceptions of burnout in two directorates, Surgical and OPM (response rate= 44%). Results indicated that nurses perceived supportive managers, teamwork and staff development were most strongly linked with a positive practice environment. Lack of staff/resources had the most negative effect. Nurses within OPM reported higher levels of burnout than those within the surgical directorate. Phase 3 involved consultation with a range of staff and patients to co-create a retention strategy to inform the TRACS toolkit. We will explore interventions and the final evaluative phases of the study. Evidence-based strategies to address nurse retention are a priority. The TRACS model involves strong collaboration between service providers and nurse educators and aims to strengthen loyalty, recruitment and transition in a competitive employment market.

We present a case of pulmonary sclerosing pneumocytoma (PSP) - (Formerly known as pulmonary sclerosing haemangioma) which was successfully treated with definitive radical external beam radiation therapy (EBRT). To our knowledge, such a treatment response has not been described in the literature.

© 2018 Sigma Theta Tau International Background: Although teamwork and interprofessional collaboration are critical to patient safety, nursing, medical, and allied health graduates often feel ill-prepared to confidently communicate and collaborate with other team members. While interprofessional education (IPE) has been advocated as a way of addressing this issue, there are multiple barriers to its systematic and sustained integration in undergraduate healthcare programs. Despite these challenges, examples of effective IPE initiatives have emerged. Innovation: This article profiles seven case studies of innovative interprofessional education activities that have been successfully implemented across five countries, for a variety of learners, using different delivery modalities, and with evaluation results attesting to their success. Conclusions: The case studies demonstrate innovative ideas that have the potential to overcome some of the barriers to IPE through the use of creative and targeted approaches. This article provides a wealth of ideas for the successful design and implementation of IPE initiatives and will be of benefit to educators wishing to expand their repertoire of teaching approaches. Clinical Relevance: A body of research attests to the relationship between interprofessional communication, teamwork, and patient outcomes. IPE is imperative for facilitating the development of nursing graduates’ communication and teamwork skills; however, innovative approaches are needed to overcome the perceived and actual impediments to its implementation.

To test the hypothesis that observation with early salvage radiotherapy (SRT) is not inferior to 'standard' treatment with adjuvant RT (ART) with respect to biochemical failure in patients with pT3 disease and/or positive surgical margins (SMs) after radical prostatectomy (RP). To compare the following secondary endpoints between the two arms: patient-reported outcomes, adverse events, biochemical failure-free survival, overall survival, disease-specific survival, time to distant failure, time to local failure, cost utility analysis, quality adjusted life years and time to androgen deprivation.The Radiotherapy - Adjuvant Versus Early Salvage (RAVES) trial is a phase III multicentre randomised controlled trial led by the Trans Tasman Radiation Oncology Group (TROG), in collaboration with the Urological Society of Australia and New Zealand (USANZ), and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). In all, 470 patients are planned to be randomised 1:1 to either ART commenced at ≤4 months of RP (standard of care) or close observation with early SRT triggered by a PSA level of0.20 ng/mL (experimental arm). Eligible patients have had a RP for adenocarcinoma of the prostate with at least one of the following risk factors: positive SMs ± extraprostatic extension ± seminal vesicle involvement. The postoperative PSA level must be ≤0.10 ng/mL. Rigorous investigator credentialing and a quality assurance programme are designed to promote consistent RT delivery among patients.Trial is currently underway, with 258 patients randomised as of 31 October 2013. International collaborations have developed, including a planned meta-analysis to be undertaken with the UK Medical Research Council/National Cancer Institute of Canada Clinical Trials Group RADICALS (Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial and an innovative psycho-oncology sub-study to investigate a patient decision aid resource.On the current evidence available, it remains unclear if ART is equivalent or superior to observation with early SRT.

The reliability of wire bond is very significant due to its function of providing interconnection and signal passage to the integrated circuit. Wire bond shear test are utilized to evaluate the reliability and bond strength of bonded wires. In this study, the wire bond shear test is simulated. The effects of shear tool height on the stress response of bonded wires are examined through simulation. Ansys version 11 was utilized for the simulation. The stress response of two wire materials, gold(Au) and copper(Cu) at varied shear tool height during the wire bond shear test were evaluated.A 3D non-linear finite element model was developed for the simulation. The shear tool height of 0.29µm and 8.71µm were employed in this study.The simulation results shows that shear tool height has a significant effects on the stress response of bonded wires.

Cone beam digital tomosynthesis (CBDT) is a new imaging technique proposed recently as a rapid approach for creating tomographic images of a patient in the radiotherapy treatment room. The purpose of this work is to investigate the feasibility of performing megavoltage (MV) CBDT clinically. A clinical investigational MV-CBDT system was installed on an existing LINAC. After the installation, the treatment machine can be operated in two distinct modes: (1) normal clinical treatment mode; (2) CBDT mode, in which tomographic images of the patient can be obtained using MV-CBDT. Various calibration and phantom measurements were performed on the system, followed by a patient study. Our phantom measurements have shown that: (1) for the same imaging dose, MV-CBDT has the same signal-difference-to-noise ratio as megavoltage cone beam computed tomography (MV-CBCT); (2) MV-CBDT has a better spatial resolution than MV-CBCT in the planes of reconstruction but a worse spatial resolution in the direction perpendicular to the planes of reconstruction. MV-CBDT patient images were also obtained and compared to that of MV-CBCT. We have demonstrated that it is clinically feasible to perform MV-CBDT in the treatment room for image-guided radiotherapy.

Purpose To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score ≥8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence ( n = 1), urinary frequency/urgency ( n = 3), and urinary retention ( n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.

Ureteric peristalsis transports a urinary bolus from the renal pelvis to the bladder. We developed an intraluminal catheter with a pressure transducer on it to study intraluminal pressure changes and a twin bipolar electrode to record the ureteric EMG and impedance (Z) changes during a peristaltic wave. Five female New Yorkshire pigs (50-60 kg) were studied under light halothane anesthesia (5% at induction/1% for maintenance). A steady state of hydration was maintained using intravenous saline infusion. EMG spike burst activity was studied at a 10-cm interval using low (0-30) Hz filters. Impedance between the same electrodes is measured simultaneously in higher frequencies (1-5 KHz) as a function of ureteric motor activity. Pressure generation in the ureteric lumen was also measured simultaneously by a transducer on the same catheter. A digital signal processing program (Poly 4.9) was used for analysis. Parenteral furosemide was used to induce diuresis. Resting ureteric impedance (Z(R)) decreases to Z(B) (Z bolus) during the passage of the urinary bolus. Passage of a contractile zone during a peristaltic wave increases impedance from Z(B) to its Z(R) level and initiates a pressure rise. Bolus length (the length Z(B)) is not constant and decreases distally. EMG corresponds well in time to impedance. Z(R) disappears after infusion of furosemide because of increased urine load and changes of intraluminal ionic environment. The contractile segment of a ureteric peristaltic wave appears to be represented by an elevated Z segment (Z(C)). Pressure rise is recorded only at the beginning of a contractile zone. A specially adapted intraluminal catheter can be used to study peristalsis in the upper urinary tract. One can study all the three components of ureteric peristalsis (excitation, contraction, and intraluminal pressure rise) using such a catheter