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The impact of the collaboration between photographer Eadweard Muybridge and neurologist Francis Dercum is detailed within the context of a photographic study of an artificially induced psychogenic non-epileptic seizure. Their contribution served as inspiration to other contemporary European neurologists and photographers to use motion photography to further understand psychogenic neurological disorders, such as seizures.

Chip floorplanning is the engineering task of designing the physical layout of a computer chip. Despite five decades of research1, chip floorplanning has defied automation, requiring months of intense effort by physical design engineers to produce manufacturable layouts. Here we present a deep reinforcement learning approach to chip floorplanning. In under six hours, our method automatically generates chip floorplans that are superior or comparable to those produced by humans in all key metrics, including power consumption, performance and chip area. To achieve this, we pose chip floorplanning as a reinforcement learning problem, and develop an edge-based graph convolutional neural network architecture capable of learning rich and transferable representations of the chip. As a result, our method utilizes past experience to become better and faster at solving new instances of the problem, allowing chip design to be performed by artificial agents with more experience than any human designer. Our method was used to design the next generation of Google’s artificial intelligence (AI) accelerators, and has the potential to save thousands of hours of human effort for each new generation. Finally, we believe that more powerful AI-designed hardware will fuel advances in AI, creating a symbiotic relationship between the two fields. Machine learning tools are used to greatly accelerate chip layout design, by posing chip floorplanning as a reinforcement learning problem and using neural networks to generate high-performance chip layouts.

Patients with psychogenic non-epileptic seizures (PNES) experience significant morbidity and early mortality, secondary to delayed diagnosis. Better characterizing risk factors and exploring how PNES differentially affects sex and racial strata may facilitate earlier diagnosis.From a Hawai'i neuroscience institution, 101 PNES patients were investigated in relation to sociodemographic and medical comorbidities. Cases were compared to 202 sex-, age-, and race-matched controls-representing patients with neurological disorders (general controls)-, as well as 404 unmatched epilepsy controls.Relative to general controls, PNES patients had increased odds (p 0.05) of being: female, younger age, Native Hawaiian or other Pacific Islander (NHPI), suburban origin, from the lowest income quartile, Medicaid beneficiaries, homeless, current/former smoker, illicit drug users (marijuana, opioids/narcotics, polysubstance abuse), have anxiety, depression, post-traumatic stress disorder, bipolar disorder, traumatic history, World Health Organization obesity class 3, traumatic brain injury, epilepsy, and somatoform disorder. In relation to epilepsy controls, PNES patients exhibited increased odds of being: employed, having attention-deficit/hyperactivity disorder, asthma, migraines, and chronic pain. Relative to females, male PNES patients exhibited increased odds of military insurance, diabetes mellitus type 2, and hypertension. Relative to Whites, the NHPI and Asian PNES patients presented increased odds of asthma, migraines, chronic pain, gastroesophageal reflux disease, and thyroid disease. Per multivariable logistic regression, anxiety was the only consistent predictor of PNES across all sex and race strata.Predictors of PNES's vary amongst the strata of race and sex. Lower socioeconomic status, along with several psychiatric and medical comorbidities, could increase a clinician's suspicion for earlier medical workup and diagnosis of PNES.

The utility of Multiparametric magnetic resonance imaging (mpMRI) guided prostate biopsy among patients with prostate cancer (CaP) managed with active surveillance (AS) with low-suspicion lesions remains unsettled.We performed a retrospective analysis of 415 men with low-risk CaP managed with active surveillance. We selected men with mpMRI visible index lesions scored as 2 or 3 according to Prostate Imaging Reporting and Data System (PI-RADS) version 2. The primary outcome was detection of clinically significant prostate cancer (csCaP) was defined as Gleason grade group ≥ 2. We assessed the diagnostic accuracy of biopsy approaches using area under the receiver operator characteristic (ROC) curve and evaluated factors associated with csCaP in these patients using multivariate logistic regression.CsCaP was identified in 22 of 125 patients (17.6%) with PI-RADS 2 or 3 index lesions during surveillance prostate biopsies. These included 10 (45.5%) diagnosed by systematic biopsy alone, 9 (40.9%) by targeted alone, and 3 (13.6%) by both approaches. On multivariable analysis, the only significant variable predicting the detection of csCaP in men with low-risk imaging mpMRI characteristics was higher PSAD (OR per 0.1 unit=2.26, 95% CI 1.25-4.06, P = 0.007. A PSAD cutoff of 0.1, 0.12 and 0.15 resulted in a negative predictive value (NPV) of 90.9%, 87.1% and 86.2%, respectively. When stratified by PI-RADS score, a PSAD cutoff of 0.1, 0.12 and 0.15 resulted in NPV of 96.2%, 90.6% and 89.7% and 86.2%, 84.2% and 83.3% for detection of csCaP in PI-RADS 2 and 3 lesions, respectively. In patients with PIRDAS 2 lesions, using a PSAD of 0.1 would potentially allow 51% of patients to avoid biopsy with only a 3.8% chance of missing csCaP.In men with clinical low-risk prostate cancer on active surveillance with PI-RADS 2 and 3 lesions, there is an almost 18% risk of upgrade to csCaP. Integration of PSAD may be a useful adjunctive tool in identifying patients at highest risk for upgrade despite favorable imaging findings. In men with PIRADS 2 lesions with PSAD ≤0.12 biopsy can be avoided. For men with PIRADS 2 lesions with PSAD ≤0.15 informed decision making regarding the AS intensity should include that these patients have a low risk (10%) of developing csCaP. In men with PIRADS 3 lesions with PSAD0.1, shared decision making should include discussion of a10% miss rate of csCaP.

Background The concept of “advanced polyps” is well accepted and is defined as polyps ≥10 mm and/or those having a villous component and/or demonstrating areas of dysplasia. Of these parameters, computed tomography colonography (CTC) can only document size. The accepted management of CTC-detected “advanced polyps” is to recommend excision if feasible, whereas the management of “intermediate” (6–9 mm) polyps is more controversial, and interval surveillance may be acceptable. Therefore, distinction between 6-9 mm and ≥10 mm is important. Methods Datasets containing 26 polyps originally reported as between 8-12 mm in diameter were reviewed independently by 4 CTC-accredited radiologists. Observers tabulated the largest measurement for each polyp on axial, coronal, sagittal, and endoluminal views at lung-window settings. These measurements were also compared to those determined by the computer-aided detection (CAD) software. Results The interobserver reliability intra-class correlation coefficient (ICC) for sagittal projection was 0.80 (“excellent” category of Hosmer and Lemeshow [2004]), 0.71 for axial (“acceptable”), 0.69 for coronal, and 0.41 for endoluminal (“unacceptable”). The largest of sagittal/axial/coronal measurement gave the best reliability with the smallest variance (ICC = 0.80; 95% CI 0.67–0.89). For 8 of 26 polyps, at least one radiologist's measurement placed the polyp in a different category compared to a colleague. For the majority of the polyps, the CAD significantly overestimated the readings compared to the largest of the manual measurements with an average difference of 1.6 mm ( P < .0001 for sagittal/axial/coronal). This resulted in 33% of polyps falling into a different category—10% were lower and 23% were higher ( P < .034). Conclusion It is apparent that around the cutoff point of 10 mm between “advanced” and “intermediate” polyps, interobserver performance is variable.

Video sharing (e.g., YouTube, Vimeo, Facebook, TikTok) accounts for the majority of internet traffic, and video processing is also foundational to several other key workloads (video conferencing, virtual/augmented reality, cloud gaming, video in Internet-of-Things devices, etc.). The importance of these workloads motivates larger video processing infrastructures and – with the slowing of Moore’s law – specialized hardware accelerators to deliver more computing at higher efficiencies. This paper describes the design and deployment, at scale, of a new accelerator targeted at warehouse-scale video transcoding. We present our hardware design including a new accelerator building block – the video coding unit (VCU) – and discuss key design trade-offs for balanced systems at data center scale and co-designing accelerators with large-scale distributed software systems. We evaluate these accelerators “in the wild" serving live data center jobs, demonstrating 20-33x improved efficiency over our prior well-tuned non-accelerated baseline. Our design also enables effective adaptation to changing bottlenecks and improved failure management, and new workload capabilities not otherwise possible with prior systems. To the best of our knowledge, this is the first work to discuss video acceleration at scale in large warehouse-scale environments.

Chip floorplanning is the engineering task of designing the physical layout of a computer chip. Despite five decades of research

Objective To determine whether supplemental biopsy of hypoechoic ultrasound lesions (HUL) incidentally found during magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion-targeted prostate biopsy results in improved prostate cancer (PCa) detection. Methods Patients underwent MRI-TRUS-targeted biopsy as part of an ongoing prospective trial from August 2007 to February 2015. For men with HUL, the biopsy pathology of HUL and MRI lesions was classified according to the updated 2014 International Society of Urological Pathology (ISUP) grading system. The detection of PCa by MRI-targeted biopsy with and without HUL biopsy was compared. Results Of 1260 men in the trial, 106 underwent biopsy of 119 HULs. PCa was diagnosed in 52 out of 106 men (49%) by biopsy of either MRI lesions or HUL. Biopsy of HUL in addition to MRI lesions resulted in 4 additional diagnoses of high-grade (ISUP grades 3-5) PCa versus biopsy of MRI lesions alone (20 vs 16 men, P = .046). Three of these cases were upgraded from lower grade (ISUP grades 1-2) PCa on MRI-guided biopsy alone, and only 1 case (1% of cohort) was diagnosed that would have been missed by MRI-guided biopsy alone. Supplemental biopsy of HUL did not change the PCa risk category in 96% (102 out of 106) of men with HUL. Conclusion Supplemental biopsy of HUL yields a small increase in the detection of higher grade PCa as compared with biopsy of MRI lesions alone. As upgrading is rare, routinely screening for HUL during MRI-targeted biopsy remains controversial.

Many architects believe that major improvements in cost-energy-performance must now come from domain-specific hardware. This paper evaluates a custom ASIC---called a Tensor Processing Unit (TPU) --- deployed in datacenters since 2015 that accelerates the inference phase of neural networks (NN). The heart of the TPU is a 65,536 8-bit MAC matrix multiply unit that offers a peak throughput of 92 TeraOps/second (TOPS) and a large (28 MiB) software-managed on-chip memory. The TPU's deterministic execution model is a better match to the 99th-percentile response-time requirement of our NN applications than are the time-varying optimizations of CPUs and GPUs that help average throughput more than guaranteed latency. The lack of such features helps explain why, despite having myriad MACs and a big memory, the TPU is relatively small and low power. We compare the TPU to a server-class Intel Haswell CPU and an Nvidia K80 GPU, which are contemporaries deployed in the same datacenters. Our workload, written in the high-level TensorFlow framework, uses production NN applications (MLPs, CNNs, and LSTMs) that represent 95% of our datacenters' NN inference demand. Despite low utilization for some applications, the TPU is on average about 15X -- 30X faster than its contemporary GPU or CPU, with TOPS/Watt about 30X -- 80X higher. Moreover, using the CPU's GDDR5 memory in the TPU would triple achieved TOPS and raise TOPS/Watt to nearly 70X the GPU and 200X the CPU.

High vesicovaginal fistulas (VVF) in the setting of good apical support are best repaired via a transabdominal approach. Laparoscopic VVF repair was first reported in 1998. Several series of robot-assisted VVF repairs have since been published. The robot-assisted approach allows repair of high apical vaginal fistulas while avoiding the morbidity of laparotomy, shortening convalescence, and facilitating the use of omental interposition flaps. This video presents the technique for robot-assisted extravesical VVF repair utilizing a laparoscopically mobilized omental flap.A 43-year-old woman developed a VVF after a total abdominal hysterectomy for fibroids. Pre-operative CT urogram and office cystoscopy confirmed the diagnosis and ruled out ureteral involvement. She underwent a robot-assisted extravesical VVF repair utilizing a laparoscopically mobilized omental flap.The surgery was uncomplicated, and the patient was discharged on post-operative day 1. A cystogram 2 weeks post-operatively revealed no evidence of a fistula. At 3 months follow-up, the patient denied any urinary incontinence.Robot-assisted extravesical VVF repair avoids the morbidity of a laparotomy, provides excellent exposure, and avoids a large cystotomy. It maintains vaginal length and allows for significantly better visualization compared with the transvaginal approach. This repair offers improved outcomes for certain patients depending on their history, anatomy, and the surgeon's experience.

Large breasts may increase the likelihood of thoracic vertebral fractures by increasing the mechanical loading of the spine. We examined breast size as a factor associated with prevalent thoracic vertebral fractures, also considering its relationship with thoracic kyphosis and upper back extensor muscle endurance. Using a cross‐sectional study, the design measurements collected were thoracic vertebral fractures (≥20% loss in vertebral body height on lateral radiograph), breast size (bra size converted to an ordinal breast size score), BMD (g/cm2 averaged femoral neck, DXA), upper back extensor muscle endurance (isometric chest raise test), body composition (DXA), thoracic kyphosis (radiograph), and upper back pain (numerical rating scale). Correlations and multivariable logistic regression examined relationships between characteristics and their association with vertebral fracture. Participants were 117 healthy postmenopausal women. The 17 (15%) women with ≥1 thoracic vertebral fracture had larger breast size (mean difference [MD]: 2.2 sizes; 95% CI, 0.6 to 3.8 sizes), less upper back extensor muscle endurance (MD: −38.6 s; 95% CI, −62.9 to −14.3 s), and greater thoracic kyphosis (MD: 7.3°; 95% CI, 1.7° to 12.8°) than those without vertebral fracture. There were no between group differences in age, height, weight, and BMD. Breast size (r = −0.233, p = 0.012) and thoracic kyphosis (r = −0.241, p = 0.009) correlated negatively with upper back extensor muscle endurance. Breast size was unrelated to thoracic kyphosis (r = 0.057, p = 0.542). A (final) multivariable model containing breast size (OR 1.85; 95% CI, 1.10 to 3.10) and thoracic kyphosis (OR 2.04; 95%CI, 1.12 to 3.70) explained 18% of the variance in vertebral fracture. Breast size had a significant, but weak relationship with vertebral fracture (R 2 = 0.10), which was independent of BMD and unrelated to thoracic kyphosis. Further work is needed to confirm larger breast size as a risk factor for vertebral fracture. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Purpose This exploratory study compared the semiology of psychogenic nonepileptic seizures (PNES) between a diverse group of patients in the state of Hawaii. This study may expand understanding of PNES across different ethnocultural and gender groups. Methods A retrospective chart review of patients admitted to our Epilepsy Monitoring Unit (EMU) over a 4-year period was performed to compare semiology in different ethnic groups and gender. Results A total of 139 patients were included in this study, 37% (n = 51) with PNES, 34% (n = 47) with epilepsy only, and 29% (n = 41) with other non-PNES, nonepilepsy diagnosis. The number of Asians with PNES were found to differ when compared with the patients with epilepsy and the patients with non-PNES, nonepilepsy diagnosis. A positive trend was found in the number of Native Hawaiians and Caucasians with PNES in comparison with patients with non-PNES, nonepilepsy diagnosis. In addition, three semiology of PNES in Native Hawaiians were found to differ in comparison with other ethnic groups with PNES: rhythmic motor, mixed semiology, and nonepileptic aura. There is a significant difference in all motor manifestation between males and females in Native Hawaiians. Between patients with PNES, patients with epilepsy, and patients with non-PNES, nonepilepsy diagnosis, significant correlation was found in psychiatric disorders including posttraumatic stress disorder (PTSD), anxiety, and any psychiatric disorder. Conclusion This cross-cultural study found significant differences in the expression of PNES across key ethnoracial groups for the Islands of Hawaii. These findings have implications to the diagnosis and treatment of PNES for Native Hawaiians and other Pacific Islanders in the United States.

Spigelian hernia (SH) is a rare entity accounting for 1â2% of ventral abdominal wall hernias. Elusive clinical signs and symptoms pose a diagnostic challenge and a consequent risk of strangulation. We present an emergent case of a Spigelian hernia involving the appendix. Keywords: Spigelian hernia, Appendix, Ultrasound, Computed tomography

This chapter examines several options available to financially troubled companies in connection with out-of-court restructurings in the US and the UK, and provides practical guidance for each option. Specifically, we discuss tender offers, exchange offers and amendments of outstanding debt securities, including the use of exit consents, and their use in conjunction with prepackaged or prearranged bankruptcies in the US. We also discuss the principal legal framework surrounding bond repurchases, issues relating to such repurchases, and the liability management strategy of combining the consensual nature of the tender offer with an exit consent in the UK.

OBJECTIVES:To evaluate the utility of preoperative multiparametric magnetic resonance imaging (MP-MRI) in predicting biochemical recurrence (BCR) following radical prostatectomy (RP). MATERIALS/METHODS:From March 2007 to January 2015, 421 consecutive patients with prostate cancer (PCa) underwent preoperative MP-MRI and RP. BCR-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to identify clinical and imaging variables predictive of BCR. Logistic regression was performed to generate a nomogram to predict three-year BCR probability. RESULTS:Of the total cohort, 370 patients met inclusion criteria with 39 (10.5%) patients experiencing BCR. On multivariate analysis, preoperative prostate-specific antigen (PSA) (p = 0.01), biopsy Gleason score (p = 0.0008), MP-MRI suspicion score (p = 0.03), and extracapsular extension on MP-MRI (p = 0.03) were significantly associated with time to BCR. A nomogram integrating these factors to predict BCR at three years after RP demonstrated a c-index of 0.84, outperforming the predictive value of Gleason score and PSA alone (c-index 0.74, p = 0.02). CONCLUSION:The addition of MP-MRI to standard clinical factors significantly improves prediction of BCR in a post-prostatectomy PCa cohort. This could serve as a valuable tool to support clinical decision-making in patients with moderate and high-risk cancers.

PURPOSE: As the adoption of magnetic resonance imaging/ultrasound fusion guided biopsy expands, the reproducibility of outcomes at expert centers becomes essential. We sought to validate the comprehensive NCI (National Cancer Institute) experience with multiparametric magnetic resonance imaging and fusion guided biopsy in an external, independent, matched cohort of patients. MATERIALS AND METHODS: We compared 620 patients enrolled in a prospective trial comparing systematic biopsy to fusion guided biopsy at NCI to 310 who underwent a similar procedure at Long Island Jewish Medical Center. The propensity score, defined as the probability of being treated outside NCI, was calculated using the estimated logistic regression model. Patients from the hospital were matched 1:1 for age, prostate specific antigen, magnetic resonance imaging suspicion score and prior negative biopsies. Clinically significant disease was defined as Gleason 3 + 4 or greater. RESULTS: Before matching we found differences between the cohorts in age, magnetic resonance imaging suspicion score (each p

Prostate cancer (PCa) continues to be the leading non-cutaneous cancer in men in the United States and responsible for nearly 30,000 deaths and 230,000 new cases per year. The widespread use of prostate-specific antigen (PSA) testing has led to an overall increase in the proportion of men diagnosed with low-risk disease with concurrent decrease in disease-specific mortality. According to the Surveillance, Epidemiology, and End Results (SEER) database, the advent of PSA screening in 1987 has since resulted in approximately a sevenfold increase in PCa incidence when compared to the pre-PSA era. The increased detection of low-risk disease has also corresponded to a greater proportion of men diagnosed with PCa undergoing radical prostatectomy (RP) or radiation therapy (RT). The complications associated with these procedures such as urinary incontinence (20 % for RP and 5 % for RT) and erectile dysfunction (64 % for RP and 66 % for RT) in many cases outweigh the benefits. The European Randomized Study of Screening for Prostate Cancer (ERSPC) trial also found that approximately half of those who underwent surgery were found to have cancers that were defined to be clinically indolent (

Objectives The clinical utility of urine markers in urothelial cancer (UC) surveillance is not established. We previously evaluated the use of fluorescence in situ hybridization (FISH) in managing patients with atypical cytology at risk for UC. This study evaluates its role in patients with negative cytology with a history of UC. Materials and methods Between June 2007 and January 2009, every patient with a history of UC who underwent cystoscopy and cytology with UroVysion test were identified. A comprehensive chart review was performed on each patient with negative cytology. Results The population comprised 142 patients undergoing cancer surveillance; 111 patients with negative cystoscopy, 19 with equivocal cystoscopy, and 12 with positive cystoscopy. In patients with negative cystoscopy, there was cancer in only 1 of 111 patients. UroVysion could detect the only patient with UC with sensitivity of 100% and had a negative predictive value (NPV) of 100%. In patients with equivocal cystoscopy, it detected 2 tumors that would be missed by cytology. There were 4 false negative results (sensitivity 33.3% and NPV 66.7%). In patients with obvious lesion on cystoscopy, there were 9 false negative results (sensitivity 10% and NPV 18.2%). Conclusions Few patients with negative cystoscopy and negative cytology have cancer. Patients with equivocal and positive cystoscopy and negative cytology frequently have cancer and the UroVysion FISH assay was not helpful in these cases. The cost-effectiveness of the FISH assay needs to be assessed prior to widespread use in patients with negative cytology.

The Caenorhabditis elegans distal tip cells (DTCs) are an in vivo model for the study of developmentally regulated cell migration. In this study, we characterize a novel role for CCDC-55, a conserved coiled-coil domain containing protein, in DTC migration and larval development in C. elegans. Although animals homozygous for a probable null allele, ccdc-55(ok2851), display an early larval arrest, RNAi depletion experiments allow the analysis of later phenotypes and suggest that CCDC-55 is needed within the DTC for migration to cease at the end of larval morphogenesis. The ccdc-55 gene is found in an operon with rnf-121 and rnf-5, E3 ubiquitin ligases that target cell migration genes such as the β-integrin PAT-3. Genetic interaction studies using RNAi depletion and the deletion alleles rnf-121(ok848) and rnf-5(tm794) indicate that CCDC-55 and the RNF genes act at least partially in parallel to promote termination of cell migration in the adult DTC.

Background: Mutated p53 tumor suppressor protein is involved in >50% of all malignancies; however, only recently have candidate drugs designed to target p53 mutations entered clinical trials. COTI-2, an orally bioavailable "third-generation" thiosemicarbazone, was shown to restore the structure and function of mutant p53 proteins and induced growth inhibition in a number of p53 mutant cell lines. Thus, a three-part phase I dose escalation trial of COTI-2 was initiated with Part 1 reported herein. Methods: A multicenter, open label, 3+3 dose escalation trial enrolling patients with recurrent gynecological cancers with adequate performance status and bone marrow function. Patients could have unlimited prior therapies. Patients received COTI-2 5x/week orally over a 28-day cycle. Disease response was assessed by RECIST 1.1 every 8 weeks. Results: Twenty-four patients received study treatment: 19 ovarian, 3 cervical, and 2 endometrial cancers. Median age was 60 years (45-73 yrs) and patients had received a median of 5 prior chemotherapy regimens. After 4 dose cohorts (0.25, 0.5, 1.0, and 1.7 mg/kg), the Recommended phase II Dose (R2PD) for gynecologic cancer was 1.0 mg/kg. Dose-limiting toxicities (DLT) were encountered at 1.0 mg/kg (G3 abdominal pain, G3 sensory peripheral neuropathy, n=1) and 1.7 mg/kg, (G3 neuralgia n=1, G3 myalgia n=1). All DLTs resolved off treatment. Most common adverse events (> 10%) were nausea (67%), vomiting (67%), fatigue (54%), abdominal pain (46%), constipation (29%), anemia (29%), dyspnea (29%), anorexia (29%), urinary tract infection (21%), and hypokalemia (20%), myalgia (16%), diarrhea (16%), pyrexia (17%), peripheral neuropathy (17%), increased creatinine (13%), and weight loss (13%). Pharmacokinetic assessment showed oral administration of COTI-2 yielded a Tmax between 15-90 minutes and a half-life of 8-10 hours. Fifteen patients were evaluable for efficacy, having received at least one cycle of treatment. Of these, 13 had ovarian, 1 had cervical, and 1 had endometrial cancer. Eight patients had received one or more bevacizumab combinations, and two had received immune checkpoint inhibitors. Following COTI-2 treatment, 10 patients showed signs of possible activity: 1 patient had stable disease, 4 had stable target lesions, and 5 had stable non-target lesions. Twelve patients had comprehensive genomic profiling by next generation sequencing: 3 had wild-type p53 and 9 had either hotspot or non-hotspot mutations. Conclusions: COTI-2 was deemed generally safe and well-tolerated. Part 2 of the study is currently underway in HNSCC patients, with additional data expected in 2018, and Part 3 will follow with expansion to combination treatment of ovarian and HNSCC patients. Clinical trial information: NCT02433626. Citation Format: Shannon N. Westin, Wilberto Nieves-Neira, Christian Lynam, Kowthar Y. Salim, Alison D. Silva, Richard T. Ho, Gordon B. Mills, Robert L. Coleman, Filip Janku, Daniela Matei. Safety and early efficacy signals for COTI-2, an orally available small molecule targeting p53, in a phase I trial of recurrent gynecologic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT033.

6040Background: The p53 tumor suppressor is mutated in more than half of all cancers. COTI-2, an oral 3rd-generation thiosemicarbazone, restores the structure and function of mutant p53 proteins an...

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To study guideline recommendation (GR)-concordance rates of treatment in elderly patients with urothelial carcinoma of the bladder (UCB) and to identify predictors of survival. PATIENTS AND METHODS The records of 206 consecutive patients aged ≥75 years (median age 79 years; range 75–95) were reviewed. All patients underwent transurethral resection (TUR) or biopsy of UCB. The European Association of Urology and American Urological Association guidelines were used as reference when evaluating concordance with GRs and clinical outcome. Univariable and multivariable analyses were performed to identify predictors of survival. RESULTS The overall GR-concordance rate of treatment was 88.8% (183 of 206 patients). Patients who were older (P= 0.017), who underwent prior treatment for UCB (P= 0.010), and had greater comorbidities (P= 0.001) were less likely to undergo treatment following GRs. With a median (mean; range) follow-up of 14.7 (22.6; 0.3–111.5) months, 79 patients died (38.3%). More comorbidities (unadjusted Charlson comorbidity index; P= 0.007), a Karnofsky performance status (KPS) score of ≤80 (P= 0.001) and more advanced initial pathological tumour stage (P= 0.019) independently predicted reduced overall survival (OS). In the subgroup of patients with indication for cystectomy (n= 99), there was a trend for longer OS in patients treated with curative intent (cystectomy or radio-chemotherapy) compared with conservative treatment with TUR ± intravesical therapy only (P= 0.095). CONCLUSIONS The vast majority of elderly patients with UCB received adequate treatment at our tertiary institution. The KPS score, more comorbidities and more advanced pathological tumour stage are predictors for reduced OS and should be considered to optimize patient care.

BACKGROUND: To determine whether high-risk patients with hematuria receive evaluation according to guideline recommendations. METHODS: We recently performed a screening study for bladder cancer using a urine-based tumor marker in 1502 subjects at high risk based on aged ≥50 years, ≥10-year smoking history, and/or a 15-year or more environmental exposure. We evaluated use of urinalysis (UA) within 3 years preceding the screening study. Chart review was performed to determine if this subset with microhematuria received any additional evaluation. RESULTS: Of 1502 study participants, routine urinalysis was performed in 73.2% and 164 (14.9%) subjects had documented hematuria (>3 red blood cells / high-power field) before inclusion. Of these, 42.1% had no further evaluation. Additional testing included repeat urinalysis (36%), urine culture (15.2%), cytology (10.4%), imaging (22.6% overall: 15.9% computed tomography, 4.3% intravenous pyelography; 2.4% magnetic resonance imaging), and cystoscopy (12.8%). Three subjects with microscopic hematuria (2%) were subsequently found to have bladder cancer during the screening study but were not referred for evaluation based on their hematuria. The source of hematuria was unknown in 65%, infection in 22%, benign prostatic enlargement in 10%, and renal stone disease in 4%, but these results are based on incomplete evaluation since only 12.8% underwent cystoscopy. CONCLUSIONS: Subjects at high risk for bladder cancer based on ≥10 years of smoking or environmental exposure with microscopic hematuria are rarely evaluated thoroughly and only 12.8% were referred for urologic evaluation. Further studies are needed to evaluate both the utilization and effectiveness of guidelines for hematuria. Cancer 2010. © 2010 American Cancer Society.

Cancer Epidemiol Biomarkers Prev 2010; 19: 2164 –2171. Background: The knowledge about and use of chemopreventive agents for prostate cancer by physicians has not been described. The Prostate Cancer Prevention Trial (PCPT) showed that finasteride was effective in reducing the incidence of prostate cancer. We examined the influence of the PCPT on finasteride prescribing within the Veterans Health Administration (VHA). Methods: We assessed trends on monthly new and total prescriptions for finasteride filled within the VHA from January 2000 to December 2005. Additionally, all VHA urologists and a random sample of VHA primary care physicians (PCP) were surveyed about their use of finasteride. Results: The number of men starting finasteride grew over the study period. Publication of the PCPT was not significantly associated with any change in this pattern (P 0.45). Fifty-seven percent of urologists and 40% of PCPs endorsed prescribing finasteride more frequently in 2006 than 5 years prior. However, among those who reported changing prescribing patterns, fewer than 2% reported being influenced by the PCPT. Sixty-four percent of urologists and 80% of PCPs never prescribe finasteride for prostate cancer chemoprevention; 55% of urologists cited concerns of inducing high-grade tumors, whereas 52% of PCPs did not know it could be used for chemoprevention. Conclusions: The number of men starting finasteride in the VHA increased over time, but the change did not seem to be due to increased use of finasteride for chemoprevention. Publication of the PCPT seemed to have little influence over the study period. Editorial Comment: The analysis of the Veterans Health Administration drives home 2 key points. Despite publication of the PCPT in 2003, the medical community did not immediately embrace finasteride chemoprevention for prostate cancer. Given the recent Food and Drug Administration decision not to give dutasteride a chemoprevention indication, it is probably a good thing that doctors did not increase the use of finasteride for prostate cancer chemoprevention. The second and somewhat more interesting point is the gradual increase in use of finasteride throughout the study period. I suspect this increase may be related to the findings of the MTOPS (Medical Therapy of Prostatic Symptoms) trial, which concluded at roughly the same time. MTOPS was much less controversial and was consistent with the labeled indication for finasteride. I suspect it was this study that was responsible for the gradual increase in use of finasteride seen in the Veterans Administration.

OBJECTIVE To test whether the expression of human epidermal growth factor receptor 2 (HER-2) is of prognostic value in a contemporary cohort of patients with urothelial carcinoma of the urinary bladder (UCB). PATIENTS AND METHODS Tissue microarrays of 198 patients were constructed and immunohistochemical stainings were performed on the primary tumours and on lymphatic nodal metastases. All patients were treated with radical cystectomy (RC) and regional lymphadenectomy for UCB. HER-2 expression was assessed using continuous HER-2 expression scores (ranging from 0.1 to 3.9) generated using an automated cellular imaging system. Scores of ≥1.0 in at least 10% of tumour cells were regarded as HER-2 positive. We correlated HER-2 scores with pathological and clinical variables, including disease recurrence and cancer-specific mortality. RESULTS Of 198 patients undergoing RC with lymphadenectomy, there was HER-2 positivity in 55 primary tumours (27.8%) compared with 44.2% of the evaluable positive lymph nodes (P < 0.001). HER-2 positivity was significantly associated with the presence of lymphovascular invasion (LVI; P= 0.026). With a median (range) follow-up of 35.4 (1.3–176.1) months, 101 patients (51.0%) had UCB recurrence and 82 patients (41.4%) died from the disease. In multivariable analyses that adjusted for the effects of pathological tumour stage, grade, LVI, lymph node metastasis and adjuvant chemotherapy, HER-2 positive patients were at increased risk for both UCB recurrence (hazard ratio [HR] 1.955, P= 0.003) and UCB-specific mortality (HR 2.066, P= 0.004) compared with patients with negative HER-2 expression. CONCLUSION A positive HER-2 status is associated with aggressive UCB and provides independent prognostic information for UCB recurrence and mortality. Assessment of HER-2 status can be used to identify patients at high risk of disease progression who may benefit from adjuvant HER-2-targeted mono- or combined therapy after RC.

Study Type – Therapy (economics analysis) Level of Evidence 2b OBJECTIVE To evaluate the profit margins for radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic prostatectomy (RALP), and the effect on the reimbursement to the urologist, as there has been a dramatic increase in use of RALP, with the cost of the robot borne by hospitals. METHODS Data on costs and payments to hospital and surgeon from 2003 to 2008 for RRP, LRP and RALP were obtained from the hospital and urology department. We determined the profit based on the difference between payments received and total cost. RESULTS Between 2000 and 2008, 1279 RPs were performed at our private hospital. The introduction of RALP increased total number of RPs and replaced most RRPs. RRP represents the only procedure where payments exceed total costs. For RRP there was a significantly higher profit for patients with comorbidities. The type of payer had a large effect on profit. Medicare provides a small profit for RRP but a significant loss of >US$4000 for RALP. While all insurance companies resulted in losses for LRP and RALP, there was variability of almost $600/case for LRP and >$1400/case for RALP. RALP provided the highest reimbursement for the surgeon due to additional reimbursement for the S2900 code (use of robot). CONCLUSIONS The introduction of RALP has increased the case volume at our hospital and improved profits for the surgeon. The hospital loses money on each LRP and RALP case compared with RRP, which provides a small profit.

Objective To validate the use of biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) and prostate-specific antigen (PSA) or PSA density (PSAD) in a biopsy-naive cohort at risk for prostate cancer (PCa). Methods All patients (n = 59) underwent PSA screening and digital rectal exam prior to a B-MRI followed by MRI or transrectal ultrasound fusion-guided targeted biopsy. Previously reported composite formulas incorporating screen positive lesions (SPL) on B-MRI and PSA or PSAD were developed to maximize PCa detection. For PSA, a patient was considered screen positive if PSA level + 6 × (the number of SPL) >14. For PSAD, screening was positive if PSAD × 14 + (the number of SPL) >4.25. These schemes were employed in this new test set to validate the initial formulas. Performance assessment of these formulas was determined for all cancer detection and for tumors with Gleason ≥3 + 4. Results Screen positive lesions on B-MRI had the highest sensitivity (95.5%) and negative predictive value of 71.4% compared with PSA and PSAD. B-MRI significantly improved sensitivity (43.2-72.7%, P = .0002) when combined with PSAD. The negative predictive value of PSA increased with B-MRI, achieving 91.7% for B-MRI and PSA for Gleason ≥3 + 4. Overall accuracies of the composite equations were 81.4% (B-MRI and PSA) and 78.0% (B-MRI and PSAD). Conclusion Validation with a biopsy-naive cohort demonstrates the parameter SPL performed better than PSA or PSAD alone in accurately detecting PCa. The combined use of B-MRI, PSA, and PSAD resulted in improved accuracy for detecting clinically significant PCa.

Anton 2 is a second-generation special-purpose supercomputer for molecular dynamics simulations that achieves significant gains in performance, programmability, and capacity compared to its predecessor, Anton 1. The architecture of Anton 2 is tailored for fine-grained event-driven operation, which improves performance by increasing the overlap of computation with communication, and also allows a wider range of algorithms to run efficiently, enabling many new software-based optimizations. A 512-node Anton 2 machine, currently in operation, is up to ten times faster than Anton 1 with the same number of nodes, greatly expanding the reach of all-atom bio molecular simulations. Anton 2 is the first platform to achieve simulation rates of multiple microseconds of physical time per day for systems with millions of atoms. Demonstrating strong scaling, the machine simulates a standard 23,558-atom benchmark system at a rate of 85 µs/day -- 180 times faster than any commodity hardware platform or general-purpose supercomputer.

Financial markets are highly interdependent and for many decades portfolio managers have scrutinised the comovements between markets. It is regrettable, however, that traditional quantitative portfolio construction still heavily relies on the analysis of correlations for modelling the complex interdependences between financial assets. Admittedly, the application of the concept of correlation has been improved and, over the last ten years, following the generalised use of the JP Morgan (1994) RiskMetrics approach, quantitative portfolio managers have made increasing use of conditional correlations.

The widespread activity involving the Internet and the Web causes large amounts of electronic data to be generated every day. This includes, in particular, semi-structured textual data such as electronic documents, computer programs, log files, transaction records, literature citations, and emails. Storing and manipulating the data thus produced has proven difficult. As conventional DBMSs are not suitable for handling semi-structured data, there is a strong demand for systems that are capable of handling large volumes of complex data in an efficient and reliable way. The Extensible Markup Language (XML) provides such solution. In this paper, we present the concept of a ‘vertical view model’ and its uses as a mapping mechanism for converting complex XML data to relational database tables, and as a standalone data model for storing complex XML data. Copyright © 2003 John Wiley & Sons, Ltd.

BACKGROUND: The high-spatial resolution of multiparametric magnetic resonance imaging (mpMRI) has improved the detection of clinically significant prostate cancer. mpMRI characteristics (extraprostatic extension [EPE], number of lesions, etc.) may predict final pathological findings (positive lymph node [pLN] and pathological ECE [pECE]) and biochemical recurrence (BCR). Tumor contact length (TCL) on MRI, defined as the length of a lesion in contact with the prostatic capsule, is a novel marker with promising early results. We aimed to evaluate TCL as a predictor of +pathological EPE (+pEPE), +pathological LN (+pLN), and BCR in patients undergoing robotic-assisted laparoscopic radical prostatectomy. MATERIALS AND METHODS: A review was performed of a prospectively maintained single-institution database of men with prostate cancer who underwent prostate mpMRI followed by robotic-assisted laparoscopic radical prostatectomy without prior therapy from 2007 to 2015. TCL was measured using T2-weighted magnetic resonance images. Logistic and Cox regression analysis were used to assess associations of clinical, imaging, and histopathological variables with pEPE, pLN, and BCR. Receiver operating characteristic curves were used to characterize and compare TCL performance with Partin tables. RESULTS: There were 87/379 (23.0%) +pEPE, 18/384 (4.7%) +pLN, and 33/371 (8.9%) BCR patients. Patients with adverse pathology/oncologic outcomes had longer TCL compared to those without adverse outcomes (+pEPE: 19.8 vs. 10.1 mm, P < 0.0001, +pLN: 38.0 vs. 11.7 mm, P < 0.0001, and BCR: 19.2 vs. 11.2 mm, P = 0.001). On multivariate analysis, TCL remained a predictor of +pEPE (odds ratio: 1.04, P = 0.001), +pLN (odds ratio: 1.07, P < 0.0001), and BCR (hazard ratio: 1.03, P = 0.02). TCL thresholds for predicting +pEPE and +pLN were 12.5 and 19.7 mm, respectively. TCL alone was found to have good predictive ability for +pEPE and +PLN (pEPE: TCL(AUC): 0.71 vs. Partin(AUC): 0.66, P = 0.21; pLN:TCL(AUC): 0.77 vs. Partin(AUC): 0.88, P = 0.04). CONCLUSION: We demonstrate that TCL is an independent predictor of +pEPE, +pLN, and BCR. If validated, this imaging biomarker may facilitate and inform patient counseling and decision-making.

Upper Jurassic-Lower Cretaceous sponge biostromes and bafflestone mounds were common and widespread in European temperate to tropical marine environments. They declined markedly during the Late Cretaceous. Most sponge frameworks were paucispecific and ecologically simple, with only basic levels of succession or tiering. The occurrence of ecologically complex, lithistid sponge biostromes and mounds in the Cenomanian Quadersandstein Member, Regensburger Grunsandstein of the Saal Quarry, Bavaria, is therefore of special significance. These are ecologically the most complex sponge frameworks yet reported from the Cretaceous. Their size, morphology and ecological organization compare favorably with shallow-water, sponge-dominated frameworks in modern seas. The Saal Quarry sponge frameworks are generally associated with firmgrounds and condensed intervals in the transgressive systems tract of the Cenomanian-Turonian, tectonoeustatic supercycle UZA-2. The lowest sponge frameworks are up to 1 m high bafflestone mounds consisting of large, irregular, sheet- and mound-like recumbent sponges overlain by diverse, cylindrical, pyriform, upward-branching forms of Jerea and Siphonia. These biostromes overlie a condensed interval or firmground which locally contains small, in situ pyriform sponges (Jerea pyriformis Lamouroux) as well as Middle Cenomanian Inoceramus etheridgei Woods. The upper sponge frameworks consist of bafflestone mounds up to 4.4 m wide and 1.3 m high, composed of six lithistid sponge morphotypes, possibly representing several species of Jerea and Siphonia. The occurrence of Rotalipora cushmanni in strata overlying the upper sponge framework indicates a Late Cenomanian age. Morphotypes preserve internal sponge morphologies and partially dissolved spicules surrounded by a diagenetic halo of silicified, pelletoid grainstone and/or packstone. Silica cements were derived from spicule dissolution. Different combinations of these morphotypes dominate three to four successional stages of sponge framework growth, and show vertical ecological tiering within communities. This ecological zonation is consistent among frameworks, and is partially or wholly repeated between storm-related disturbance events.

Introduction African-American (AA) men tend to harbor high-risk prostate cancer (PCa) and exhibit worse outcomes when compared to other groups. It has been postulated that AA men may harbor more anterior prostate lesions (APLs) that are undersampled by the standard transrectal ultrasound guided-biopsy (SBx), potentially resulting in greater degree of Gleason score (GS) upgrading at radical prostatectomy. We aimed to evaluate the detection rate of anterior PCa significance of APLs in AA men on multiparametric magnetic resonance imaging (mpMRI) and compare it to a matched cohort of White/Other (W/O) men. Materials and methods A review of 1,267 men who had an mpMRI with suspicious prostate lesions and who underwent magnetic resonance transrectal ultrasound fusion-guided biopsy (FBx) with concurrent SBx in the same biopsy session was performed. All AA men were matched to a control group of W/O using a 1:1 propensity score-matching algorithm with age, prostate-specific antigen, and prostate volume as matching variables. Logistic regression analysis was used to determine predictors of APLs in AA men. Results Of the 195 AA men who underwent mpMRI, 93 (47.7%) men had a total of 109 APLs. Prior negative SBx was associated with the presence of APLs in AA men (Odds ratio = 1.81; 95% CI: 1.03–3.20; P = 0.04). On multivariate logistic regression analysis, smaller prostate (P = 0.001) and rising prostate-specific antigen (P = 0.007) were independent predictors of cancer-positive APLs in AA men. Comparative analysis of AA (93/195, 47.7%) vs. W/O (100/194, 52%) showed no difference in the rates of APLs (P = 0.44) or in cancer detection rate within those lesions or the distribution of GS within those cancers (P = 0.63) despite an overall higher cancer detection rate in AA men (AA: 124/195 [63.6%] vs. W/O: 97/194 [50.0%], P = 0.007). In cases where APLs were positive for PCa on FBx, the GS of APL was equal to the highest GS of the entire gland in 82.9% (29/35) and 90.9% (30/33) of the time in AA and W/O men, respectively. Conclusion Cancer-positive APLs represented the highest risk GS in most cases. AA men with prior negative SBx are twice as likely to harbor a concerning APL. In our cohort, AA and W/O men had comparable rates of APLs on mpMRI. Thus, differences in APLs do not explain the higher risk of AA men for deahth due to PCa. However, targeting of APLs via FBx can clinically improve PCa risk stratification and guide appropriate treatment options.

DNA damage activates a signalling network that blocks cell-cycle progression, recruits DNA repair factors and/or triggers senescence or programmed cell death. Alterations in chromatin structure are implicated in the initiation and propagation of the DNA damage response. Here we further investigate the role of chromatin structure in the DNA damage response by monitoring ionizing-radiation-induced signalling and response events with a high-content multiplex RNA-mediated interference screen of chromatin-modifying and -interacting genes. We discover that an isoform of Brd4, a bromodomain and extra-terminal (BET) family member, functions as an endogenous inhibitor of DNA damage response signalling by recruiting the condensin II chromatin remodelling complex to acetylated histones through bromodomain interactions. Loss of this isoform results in relaxed chromatin structure, rapid cell-cycle checkpoint recovery and enhanced survival after irradiation, whereas functional gain of this isoform compacted chromatin, attenuated DNA damage response signalling and enhanced radiation-induced lethality. These data implicate Brd4, previously known for its role in transcriptional control, as an insulator of chromatin that can modulate the signalling response to DNA damage.

To study guideline recommendation (GR)-concordance rates of treatment in elderly patients with urothelial carcinoma of the bladder (UCB) and to identify predictors of survival.The records of 206 consecutive patients aged ≥ 75 years (median age 79 years; range 75-95) were reviewed. All patients underwent transurethral resection (TUR) or biopsy of UCB. The European Association of Urology and American Urological Association guidelines were used as reference when evaluating concordance with GRs and clinical outcome. Univariable and multivariable analyses were performed to identify predictors of survival.The overall GR-concordance rate of treatment was 88.8% (183 of 206 patients). Patients who were older (P = 0.017), who underwent prior treatment for UCB (P = 0.010), and had greater comorbidities (P = 0.001) were less likely to undergo treatment following GRs. With a median (mean; range) follow-up of 14.7 (22.6; 0.3-111.5) months, 79 patients died (38.3%). More comorbidities (unadjusted Charlson comorbidity index; P = 0.007), a Karnofsky performance status (KPS) score of ≤ 80 (P = 0.001) and more advanced initial pathological tumour stage (P = 0.019) independently predicted reduced overall survival (OS). In the subgroup of patients with indication for cystectomy (n = 99), there was a trend for longer OS in patients treated with curative intent (cystectomy or radio-chemotherapy) compared with conservative treatment with TUR ± intravesical therapy only (P = 0.095).The vast majority of elderly patients with UCB received adequate treatment at our tertiary institution. The KPS score, more comorbidities and more advanced pathological tumour stage are predictors for reduced OS and should be considered to optimize patient care.

to evaluate the impact of obesity on the costs of robotic-assisted (RALP), laparoscopic (LRP) and open retropubic radical prostatectomy (RRP).the charts of 629 patients who underwent RP (262 RALP, 211 LRP and 156 RRP) between September 2003 and April 2008 at our institution were reviewed. Clinical and pathological data were collected, including age, American Society of Anesthesiologists score, body mass index (BMI), tumour stage, complications and length of stay. Direct and component costs (anaesthesia, laboratory, operating room service, radiology, room and board, pharmacy and surgical supplies) were obtained. Differences in costs were evaluated using three BMI categories (25, normal weight; 25-30, overweight; and ≥30 kg/m(2) , obese).of 629 patients, 136 (21.6%) had normal weight, 320 (50.9%) were overweight, and 173 (27.5%) were obese. Clinical and pathological characteristics were similar in the three BMI categories of the entire cohort. The median direct cost was higher for obese patients (P= 0.035). On further stratification by type of RP, costs were higher amongst obese than the other groups undergoing LRP (median US$5703 vs $5347; P= 0.002) and RRP (median $4885 vs $4377; P= 0.004). In patients who underwent RALP there were no significant differences in direct costs (median $6761 in obese vs $6745 in non-obese; P= 0.64).obesity influenced the costs in patients who underwent LRP and RRP, mainly due to increased operating room service and anaesthesia costs in obese patients. RALP can be performed with no additional financial burden in obese patients.

to test whether the expression of human epidermal growth factor receptor 2 (HER-2) is of prognostic value in a contemporary cohort of patients with urothelial carcinoma of the urinary bladder (UCB).tissue microarrays of 198 patients were constructed and immunohistochemical stainings were performed on the primary tumours and on lymphatic nodal metastases. All patients were treated with radical cystectomy (RC) and regional lymphadenectomy for UCB. HER-2 expression was assessed using continuous HER-2 expression scores (ranging from 0.1 to 3.9) generated using an automated cellular imaging system. Scores of ≥ 1.0 in at least 10% of tumour cells were regarded as HER-2 positive. We correlated HER-2 scores with pathological and clinical variables, including disease recurrence and cancer-specific mortality.of 198 patients undergoing RC with lymphadenectomy, there was HER-2 positivity in 55 primary tumours (27.8%) compared with 44.2% of the evaluable positive lymph nodes (P0.001). HER-2 positivity was significantly associated with the presence of lymphovascular invasion (LVI; P= 0.026). With a median (range) follow-up of 35.4 (1.3-176.1) months, 101 patients (51.0%) had UCB recurrence and 82 patients (41.4%) died from the disease. In multivariable analyses that adjusted for the effects of pathological tumour stage, grade, LVI, lymph node metastasis and adjuvant chemotherapy, HER-2 positive patients were at increased risk for both UCB recurrence (hazard ratio [HR] 1.955, P= 0.003) and UCB-specific mortality (HR 2.066, P= 0.004) compared with patients with negative HER-2 expression.a positive HER-2 status is associated with aggressive UCB and provides independent prognostic information for UCB recurrence and mortality. Assessment of HER-2 status can be used to identify patients at high risk of disease progression who may benefit from adjuvant HER-2-targeted mono- or combined therapy after RC.

Demand and utilization of minimally invasive approaches to radical prostatectomy have increased in recent years, but comparative studies on cost are lacking.To compare costs associated with robotic-assisted laparoscopic radical prostatectomy (RALP), laparoscopic radical prostatectomy (LRP), and open retropubic radical prostatectomy (RRP).The study included 643 consecutive patients who underwent radical prostatectomy (262 RALP, 220 LRP, and 161 RRP) between September 2003 and April 2008.Direct and component costs were compared. Costs were adjusted for changes over the time of the study.Disease characteristics (body mass index, preoperative prostate-specific antigen, prostate size, and Gleason sum score 8-10) were similar in the three groups. Nerve sparing was performed in 85% of RALP procedures, 96% of LRP procedures, and 90% of RRP procedures (p0.001). Lymphadenectomy was more commonly performed in RRP (100%) compared to LRP (22%) and RALP (11%) (p0.001). Mean length of hospital stay was higher for RRP than for LRP and RALP. The median direct cost was higher for RALP compared to LRP or RRP (RALP: $6752 [interquartile range (IQR): $6283-7369]; LRP: $5687 [IQR: $4941-5905]; RRP: $4437 [IQR: $3989-5141]; p0.001). The main difference was in surgical supply cost (RALP: $2015; LRP: $725; RRP: $185) and operating room (OR) cost (RALP: $2798; LRP: $2453; RRP: $1611; p0.001). When considering purchase and maintenance costs for the robot, the financial burden would increase by $2698 per patient, given an average of 126 cases per year.RALP is associated with higher cost, predominantly due to increased surgical supply and OR costs. These costs may have a significant impact on overall cost of prostate cancer care.

The ability to perform long, accurate molecular dynamics (MD) simulations involving proteins and other biological macro-molecules could in principle provide answers to some of the most important currently outstanding questions in the fields of biology, chemistry and medicine. A wide range of biologically interesting phenomena, however, occur over time scales on the order of a millisecond--about three orders of magnitude beyond the duration of the longest current MD simulations. In this paper, we describe a massively parallel machine called Anton, which should be capable of executing millisecond-scale classical MD simulations of such biomolecular systems. The machine, which is scheduled for completion by the end of 2008, is based on 512 identical MD-specific ASICs that interact in a tightly coupled manner using a specialized high-speed communication network. Anton has been designed to use both novel parallel algorithms and special-purpose logic to dramatically accelerate those calculations that dominate the time required for a typical MD simulation. The remainder of the simulation algorithm is executed by a programmable portion of each chip that achieves a substantial degree of parallelism while preserving the flexibility necessary to accommodate anticipated advances in physical models and simulation methods.

e16128 Background: The majority of patients with low risk prostate cancer (CaP) harbor indolent disease and maybe safely observed on active surveillance (AS). However more than 30% of those on AS will ultimately receive definitive treatment. Focal therapy offers a treatment alternative that may provide oncologic control while avoiding treatment-related morbidity. The objective of this study was to determine the safety and feasibility of magnetic resonance (MR) image-guided focal laser ablation (FLA) of biopsy confirmed and MR visible prostate cancer. Methods: MR image-guided FLA was performed for men with Gleason < 7(3+4) when < 3 cores were positive in a standard 12 core biopsy corresponding to locations of MR lesions, or < 4 cores positive on MR image-guided biopsy. MR localization of biopsy-positive lesions were targeted via a transperineal approach and treated with a laser thermal ablation system. Validated quality of life questionnaires were completed pre-procedure and at each subsequent followup vis...