V/STOL flight control functionality research to improve handling qualities in the jetborne and semi-jetborne flight regimes

Since the 1950\u27s, several nations have attempted to build Vertical and Short Takeoff and Landing (V/STOL) jet fighter aircraft in a variety of configurations. One of the greatest challenges of each design team was in designing and implementing a flight control system that reduced pilot workload to an acceptable level during the transition from conventional flight to fully jetborne flight. Not all the ideas worked, and even the more successful aircraft were difficult and dangerous to fly. Pilot workload of the only currently operated V/STOL attack fighter design, the Harrier, was reduced by installing limited authority augmented flight controls to increase aircraft stability, but still it remains more difficult to fly than conventional aircraft. The United States Marine Corps (USMC) and the United Kingdom\u27s Royal Air Force (RAF) and Royal Navy (RN) have decided to replace their aging Harrier fleet of aircraft with an affordable next generation Short Takeoff and Vertical Landing (STOVL) strike fighter. All three services require the new STOVL aircraft to possess vast improvements in handling qualities over the Harrier. This thesis examines the solutions to reduce the excessive workload associated with V/STOL flight. In this thesis, specific comments on individual evaluated mode effects on handling qualities will be addressed, while deficiencies due to individual inceptor mechanical characteristics will be minimized. The analysis and solutions are based on the author\u27s research, extensive Harrier flight time, and recent V/STOL flight test experience. The coupling of a highly augmented digital flight control system with STOVL task optimized, blended control response types controlled by an intuitive flight control inceptor scheme would greatly improve the handling qualities of an advanced STOVL strike fighter. The preferred inceptor scheme includes a left inceptor, a right center inceptor with an attitude trim switch and a thumbwheel, and control pedals. During STOVL operations, the recommended response type blended flight control design includes: sideslip command blended into yaw rate command on the control pedals, flightpath command blended into height rate command on the left inceptor, roll rate command with attitude hold blended into roll attitude command with natural ground referenced lateral acceleration coupling on the right inceptor lateral axis with crosswind compensation, flightpath command blended into pitch attitude command with augmented natural ground referenced longitudinal acceleration coupling on the right inceptor longitudinal axis, pitch and roll attitude right inceptor trim switch for use in the slow speed flight region, Translational Rate Command sub-mode option with the right inceptor, and flightpath referenced acceleration command blended into ground referenced acceleration command on the right inceptor located thumbwheel with speed hold detent. Implementation of the above concepts would greatly improve handling qualities in the STOVL flight regime. It has been decided that there is an advantage for the next generation of strike fighter to have a STOVL flight capability, but without increased operational cost or risk. To insure these requirements are satisfied, the aircraft contractors and military must use the existing technologies available to vastly reduce the pilot workload over past and current V/STOL aircraft designs

Vaginal cuff recurrence after radical cystectomy: an under - studied site of bladder cancer relapse

Vaginal cuff recurrence of tumor following radical cystectomy is a rare site of disease recurrence, however it has never been specifically studied. The aim of the study is to evaluate incidence, risk factors, and long-term oncologic outcomes of vaginal cuff recurrence in a cohort of female patients treated with radical cystectomy for invasive urothelial carcinoma of the bladder

Lymph node dissection in urological cancers: one topic, many controversies

n/

Age and Prostate-Specific Antigen Level Prior to Diagnosis Predict Risk of Death from Prostate Cancer.

A single early prostate-specific antigen (PSA) level has been correlated with a higher likelihood of prostate cancer diagnosis and death in younger men. PSA testing in older men has been considered of limited utility. We evaluated prostate cancer death in relation to age and PSA level immediately prior to prostate cancer diagnosis. Using the Veterans Affairs database, we identified 230,081 men aged 50-89 years diagnosed with prostate cancer and at least one prior PSA test between 1999 and 2009. Prostate cancer-specific death over time was calculated for patients stratified by age group (e.g., 50-59 years, through 80-89 years) and PSA range at diagnosis (10 ranges) using Kaplan-Meier methods. Risk of 10-year prostate cancer mortality across age and PSA was compared using log-rank tests with a Bonferroni adjustment for multiple testing. 10.5% of men diagnosed with prostate cancer died of cancer during the 10-year study period (mean follow-up = 3.7 years). Higher PSA values prior to diagnosis predict a higher risk of death in all age groups (p < 0.0001). Within the same PSA range, older age groups are at increased risk for death from prostate cancer (p < 0.0001). For PSA of 7-10 ng/mL, cancer-specific death, 10 years after diagnosis, increased from 7% for age 50-59 years to 51% for age 80-89 years. Men older than 70 years are more likely to die of prostate cancer at any PSA level than younger men, suggesting prostate cancer remains a significant problem among older men (even those aged 80+) and deserves additional study

Surgical strategies for lymphocele prevention in minimally-invasive radical prostatectomy and lymph-node dissection: a systematic review

PURPOSE: Pelvic lymph node dissection (PLND) is an important step during robotic radical prostatectomy (RARP). The collection of lymphatic fluid (lymphocele) is the most common complication with potentially severe impact; therefore different strategies have been proposed to reduce its incidence. MATERIAL AND METHODS: In this systematic review EMBASE, MEDLINE, Cochrane Library and NIH Registry of Clinical Trials were searched for papers including the following interventions: transperitoneal vs extraperitoneal approach, any reconfiguration of the peritoneum, the use of pelvic drains and the use of different sealing techniques and sealing agents. The outcome evaluated was the incidence of symptomatic lymphocele. Both randomized and non-randomized and/or retrospective studies. RESULTS: Twelve studies were included (including one ongoing RCT). Due to the heterogeneity of included studies no meta-analysis was performed. No significant impact was reported by different sealing techniques and agents or by surgical approach. Three retrospective, non-randomized studies showed a potential benefit of peritoneal reconfiguration in order to maximize the peritoneal surface of reabsorption. CONCLUSION: Lymphocele formation is a multi-step and multifactorial event, high quality literature analyzing risk factors and preventive measures is rather scarce. Peritoneal reconfiguration could represent a reasonable option that deserves further evaluation; no other preventive measure is supported by current evidence

Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P \u3c .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score \u3e 0.6 were independent predictors of CR (all P \u3c .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy

High Serine-arginine Protein Kinase 1 Expression with PTEN Loss Defines Aggressive Phenotype of Prostate Cancer Associated with Lethal Outcome and Decreased Overall Survival

Background: Serine-arginine protein kinase 1 (SRPK1) has been implicated in prostate cancer (PCa) progression. However, its prognostic value and association with ERG and PTEN expression, two of the most common genetic alterations, have not been explored fully. Objective: We assessed the prognostic value of SRPK1 in association with ERG and PTEN in a cohort of patients managed nonsurgically by androgen deprivation therapy (ADT) for advanced disease. Design, setting, and participants: The study cohort consisted of men diagnosed with PCa by transurethral resection of the prostate (TURP; n = 480). The patients were divided into three main groups: incidental (patients with Gleason score [GS] ≤7 with no prior ADT), advanced (patients with GS ≥8 with no prior ADT), and castrate-resistant PCa (patients with prior ADT). Outcome measurements and statistical analysis: A total of 480 TURP samples were assessed by immunohistochemistry for SRPK1, ERG, and PTEN, and results were correlated with Gleason grade group (GG), overall survival (OS), and PCa-specific mortality (PCSM). Results and limitations: High SRPK1 expression was noted in 105/455 (23%) available patient cores. Expression of SRPK1 was associated with Gleason grade grouping (p \u3c 0.0001) with high expression detected in 22/74 (33%) with GG 5. High SRPK1 was not associated with ERG positivity (p = 0.18) but was significantly associated with PTEN intensity (p = 0.001). High SRPK1 was associated with OS (hazard ratio [HR] 1.99; confidence interval [CI]: 1.57–2.54, p \u3c 0.0001) and PCSM (HR 1.64; CI: 1.19–2.26, p \u3c 0.002). Adjusting for Gleason score, patients with high SRPK1 and negative PTEN had the worst clinical outcome for both OS and PCSM compared with other patients (p \u3c 0.0001, HR: 3.02; CI: 1.87–4.88 and HR: 6.40, CI: 3.19–12.85, respectively). Conclusions: High SRPK1 is associated with worse OS and PCSM. Moreover, patients with high SRPK1 expression and loss of PTEN had the worst clinical outcome for OS and cancer-specific mortality. Combined status of SRPK1 and PTEN may provide added value in stratifying patients into various prognostic groups. Patient summary: The expression of serine-arginine protein kinase 1 (SRPK1) combined with PTEN has a significant prognostic role in prostate cancer patients. Patients with high SRPK1 expression and negative PTEN had the worst clinical outcome for overall survival and cancer-specific mortality

A noninvasive multi-analyte diagnostic assay: Combining protein and DNA markers to stratify bladder cancer patients

Purpose: The authors recently reported the development of a noninvasive diagnostic assay using urinary matrix metalloproteinases (MMPs) as monitors of disease-free status and bladder cancer in high-risk populations. Using an approach called clinical intervention determining diagnostic (CIDD), they identified with high confidence those patients who could be excluded from additional intervention. To maximize performance, MMPs were combined with DNAbased markers and CIDD was applied to a population of patients undergoing monitoring for recurrence. Patients and methods: Urine samples were obtained from 323 patients, 48 of whom had a recurrence and 275 of whom did not have cancer upon cytoscopic evaluation. Twist1 and Nid2 methylation status was determined using methylation-specific polymerase chain reaction, FGFR3 mutational status by quantitative PCR, and MMP levels by enzyme-linked immunosorbent assay. Results: Using a combination of these DNA and protein markers, the authors identified with high confidence (97% negative predicted value) those patients who do not have cancer. Cutoffs were adjusted such that at 92% sensitivity, 51% of disease-free patients might be triaged from receiving further tests. Conclusion: The multi-analyte diagnostic readout assay described here is the first to combine protein and DNA biomarkers into one assay for optimal clinical performance. Using this approach, the detection of FGFR3 mutations and Twist1 and Nid2 methylation in the urine of patients undergoing bladder cancer recurrence screening increase the sensitivity and negative predictive value at an established MMP protein cutoff. This noninvasive urinary diagnostic assay could lead to the more efficient triage of patients undergoing recurrence monitoring