Upgrading on Per Protocol versus For Cause surveillance prostate biopsies: An opportunity to decreasing the burden of active surveillance.

BACKGROUND: Most prostate cancer (PC) active surveillance (AS) protocols recommend "Per Protocol" surveillance biopsy (PPSBx) every 1-3 years, even if clinical and imaging parameters remained stable. Herein, we compared the incidence of upgrading on biopsies that met criteria for "For Cause" surveillance biopsy (FCSBx) versus PPSBx. METHODS: We retrospectively reviewed men with GG1 PC on AS in the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Surveillance prostate biopsies obtained 1 year after diagnosis were classified as either PPSBx or FCSBx. Biopsies were retrospectively deemed FCSBx if any of these criteria were met: PSA velocity > 0.75 ng/mL/year; rise in PSA > 3 ng from baseline; surveillance magnetic resonance imaging (MRI) (sMRI) with a PIRADS ≥ 4; change in DRE. Biopsies were classified PPSBx if none of these criteria were met. The primary outcome was upgrading to ≥GG2 or ≥GG3 on surveillance biopsy. The secondary objective was to assess for the association of reassuring (PIRADS ≤ 3) confirmatory or surveillance MRI findings and upgrading for patients undergoing PPSBx. Proportions were compared with the chi-squared test. RESULTS: We identified 1773 men with GG1 PC in MUSIC who underwent a surveillance biopsy. Men meeting criteria for FCSBx had more upgrading to ≥GG2 (45%) and ≥GG3 (12%) compared with those meeting criteria for PPSBx (26% and 4.9%, respectively, p < 0.001 and p < 0.001). Men with a reassuring confirmatory or surveillance MRI undergoing PPSBx had less upgrading to ≥GG2 (17% and 17%, respectively) and ≥GG3 (2.9% and 1.8%, respectively) disease compared with men without an MRI (31% and 7.4%, respectively). CONCLUSIONS: Patients undergoing PPSBx had significantly less upgrading compared with men undergoing FCSBx. Confirmatory and surveillance MRI seem to be valuable tools to stratify the intensity of surveillance biopsies for men on AS. These data may help inform the development of a risk-stratified, data driven AS protocol.

Quantized Grain Boundary States Promote Nanoparticle Alignment During Imperfect Oriented Attachment.

Oriented attachment (OA) has become a well-recognized mechanism for the growth of metal, ceramic, and biomineral crystals. While many computational and experimental studies of OA have shown that particles can attach with some misorientation then rotate to remove adjoining grain boundaries, the underlying atomistic pathways for this "imperfect OA" process remain the subject of debate. In this study, molecular dynamics and in situ transmission electron microscopy (TEM) are used to probe the crystallographic evolution of up to 30 gold nanoparticles during aggregation. It is found that Imperfect OA occurs because 1) grain boundaries become quantized when their size is comparable to the separation between constituent dislocations and 2) kinetic barriers associated with the glide of grain boundary dislocations are small. In support of these findings, TEM experiments show the formation of a single crystal aggregate after annealing nine initially misoriented, agglomerated particles with evidence of dislocation activity and twin formation during particle/grain alignment. These observations motivate future work on assembled nanocrystals with tailored defects and call for a revision of Read-Shockley models for grain boundary energies in nanocrystalline materials.

Thermally ruggedized ITO transparent electrode films for high power optoelectronics.

We present two strategies to minimize laser damage in transparent conductive films. The first consists of improving heat dissipation by selection of substrates with high thermal diffusivity or by addition of capping layer heatsinks. The second is reduction of bulk energy absorption by lowering free carrier density and increasing mobility, while maintaining film conductance with thicker films. Multi-pulse laser damage tests were performed on tin-doped indium oxide (ITO) films configured to improve optical lifetime damage performance. Conditions where improvements were not observed are also described. When bulk heating is not the dominant damage process, discrete defect-induced damage limits damage behavior.

Effect of an aerodynamic helmet on head temperature, core temperature, and cycling power compared with a traditional helmet.

Nonvented "aerodynamic helmets" reduce wind resistance but may increase head (Th) and gastrointestinal (Tgi) temperature and reduce performance when worn in hot conditions. This study tested the hypothesis that Th and Tgi would be greater during low-intensity cycling (LIC) in the heat while wearing an aero helmet (AERO) vs. a traditional vented racing helmet (REG). This study also tested the hypothesis that Th, Tgi, and finish time would be greater, and power output would be reduced during a self-paced time trial in the heat with AERO vs. REG. Ten highly trained heat-acclimated endurance athletes conducted LIC (50% V[Combining Dot Above]O2max, LIC) and a high-intensity 12-km self-paced time trial (12-km TT) on a cycle ergometer in 39° C on 2 different days (AERO and REG), separated by >48 hours. During LIC, Th was higher at minute 7.5 and all time points thereafter in AERO vs. REG (p < 0.05). Similarly, during the 12-km TT, Th was higher at minutes 12.5, 15, and 17.5 in AERO vs. REG (p < 0.05). Heart rate (HR) and Tgi increased during LIC and during 12-km TT (both p < 0.001); however, no significant interaction (helmet × time) existed for HR or Tgi at either intensity (all p > 0.05). No group differences existed for finish time or power output during the 12-km TT (both p > 0.05). In conclusion, Th becomes elevated during cycling in the heat with an aero helmet compared with a traditional vented racing helmet during LIC and high-intensity cycling, yet Tgi and HR responses are similar irrespective of helmet type and Th. Furthermore, the higher Th that develops when an aero helmet is worn during cycling in the heat does not affect power output or cycling performance during short-duration high-intensity events.

Disseminated Histoplasmosis Mimicking Acute Liver Failure in a Patient Treated With a Tumor Necrosis Factor Inhibitor.

Disseminated histoplasmosis (DH) is typically seen in patients with organ transplantation or human immunodeficiency virus and rarely presents with acute liver failure. Tumor necrosis factor inhibitors may be immunosuppressive but unlikely to result in DH. A 70-year-old woman with a history of psoriatic arthritis on infliximab presented with altered mental status, fevers, and severe liver injury. She was found to have DH, which resolved on antifungal agents. Because the use of tumor necrosis factor inhibitors has increased, providers should consider this uncommon infection in patients who present with cryptogenic severe liver injury.

Safety of Bariatric Surgery in Morbidly Obese Patients with Human Immunodeficiency Virus: A Nationwide Inpatient Sample Analysis, 2004-2014.

Background: Despite rising rates of obesity among human immunodeficiency virus (HIV)-positive individuals, the safety and tolerability of surgery in this population have not been established. The primary aim of this study was to examine the safety of bariatric surgery and rate of in-hospital postoperative complications in morbidly obese patients with HIV. Materials and Methods: The U.S. Nationwide Inpatient Sample database was queried between 2004 and 2014 for discharges with codiagnoses of morbid obesity and bariatric surgery. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, hospitalization costs, and multiple categories of complications, including systemic complications, surgical complications, and nutritional and behavioral complications. Results: Among 267,082 patients with discharge diagnoses of morbid obesity and bariatric surgery, 346 (0.13%) were diagnosed with HIV. On multivariable analysis, HIV did not influence in-hospital mortality (p = 0.530). HIV was not associated with increased risk of renal failure (p = 0.274), thromboembolism (p = 0.713), myocardial infarction (p = 0.635), sepsis (p = 0.757), hemorrhage (p = 0.303), or wound infection (p = 0.229). Other measured surgical complications were not significantly different (p > 0.05). Notably, HIV-positive patients had an increased risk for postoperative pneumonia (p = 0.002), pancreatitis (p = 0.049), and thiamine deficiency (p = 0.016). Conclusion: Bariatric surgery among HIV-positive patients appears to be acceptably safe with the risk of postoperative complications comparable with non-HIV patients.

Additive Manufacturing of Optical Quality Germania-Silica Glasses.

Direct ink writing (DIW) three-dimensional (3D) printing provides a revolutionary approach to fabricating components with gradients in material properties. Herein, we report a method for generating colloidal germania feedstock and germania-silica inks for the production of optical quality germania-silica (GeO2-SiO2) glasses by DIW, making available a new material composition for the development of multimaterial and functionally graded optical quality glasses and ceramics by additive manufacturing. Colloidal germania and silica particles are prepared by a base-catalyzed sol-gel method and converted to printable shear-thinning suspensions with desired viscoelastic properties for DIW. The volatile solvents are then evaporated, and the green bodies are calcined and sintered to produce transparent, crack-free glasses. Chemical and structural evolution of GeO2-SiO2 glasses is confirmed by nuclear magnetic resonance, X-ray diffraction, and Raman spectroscopy. UV-vis transmission and optical homogeneity measurements reveal comparable performance of the 3D printed GeO2-SiO2 glasses to glasses produced using conventional approaches and improved performance over 3D printed TiO2-SiO2 inks. Moreover, because GeO2-SiO2 inks are compatible with DIW technology, they offer exciting options for forming new materials with patterned compositions such as gradients in the refractive index that cannot be achieved with conventional manufacturing approaches.

Endoscopic Ultrasound for the Diagnosis and Staging of Liver Tumors.

Endoscopic ultrasound examination may provide complementary information to cross-sectional imaging in lesions of the liver, portal vein, and surrounding lymph nodes. With fine needle aspiration, endoscopic ultrasound examination is a powerful tool for the diagnosis of focal liver lesions and has usefulness in the evaluation of indeterminate liver lesions. Endoscopic ultrasound examination may influence hepatocellular cancer staging and Endoscopic ultrasound examination with fine needle aspiration of locoregional nodes and portal vein thromboses changes management. Contrast-enhanced endoscopic ultrasound examination and endoscopic ultrasound examination elastography are likely to expand the usefulness of endoscopic ultrasound examination in evaluating liver malignancy with technologic improvements.

Impact of bariatric surgery on outcomes of patients with celiac disease: a nationwide inpatient sample analysis, 2004-2014.

BACKGROUND: While patients with celiac disease have increasingly developed an atypical pattern of weight gain and obesity, the role of bariatric surgery remains unclear. The primary aim of this study was to evaluate the effect of bariatric surgery on clinical outcomes among hospitalized patients with celiac disease. METHODS: The United States Nationwide Inpatient Sample database was queried for discharges with co-diagnoses of morbid obesity and celiac disease between 2004 and 2014. The primary outcome was in-hospital mortality. Secondary outcomes included renal failure, urinary tract infection, malnutrition, sepsis, pneumonia, respiratory failure, thromboembolic events, strictures, micronutrient deficiency, length of stay, and hospitalization costs. Using Poisson regression, adjusted incidence risk ratios (IRR) were derived for clinical outcomes in patients with prior bariatric surgery compared to those without bariatric surgery. RESULTS: Among 1499 patients with a discharge diagnosis of celiac disease and morbid obesity, 126 patients (8.4%) underwent bariatric surgery. Despite an increase in morbid obesity over the study period, the proportion of morbidly obese patients with celiac disease who had bariatric surgery declined by 18.5% (Ptrend<0.05). On multivariable analysis, bariatric surgery did not influence mortality (P=0.98), but was associated with a lower risk of renal failure, pneumonia, sepsis, urinary tract infection and respiratory failure (all P<0.05). Bariatric surgery increased the risk of vitamin D deficiency (IRR 3.5; 95% confidence interval [CI] 1.6-7.7; P=0.002) and post-operative strictures (IRR 3.3; 95%CI 1.5-7.5; P=0.004). CONCLUSION: Despite the underutilization of bariatric surgery in morbidly obese celiac disease patients, the procedure is safe and appears to significantly reduce morbidity.

Effect of frequent interruptions of sedentary time on nutrient metabolism in sedentary overweight male and female adults.

This study compared 24-h nutrient oxidation responses between a sedentary condition (SED) and a condition in which short 5-min bouts of moderate-intensity physical activity were performed hourly for nine consecutive hours over 4 days (MICRO). To determine whether any shifts in fuel use were due solely to increases in energy expenditure, we also studied a condition consisting of a single isoenergetic 45-min bout of moderate-intensity exercise (ONE). Twenty sedentary overweight or obese adults (10 men/10 women; 32.4 ± 6.3 yr; BMI, 30.6 ± 2.9 kg/m2) completed all three conditions (MICRO, SED, and ONE) in a randomized order. Each condition consisted of a 3-day free-living run-in followed by a 24-h stay in a whole-room calorimeter to measure total energy expenditure (TEE) and substrate utilization. Dietary fat oxidation was also assessed during the chamber stay by administering a [1-13C] oleic acid tracer at breakfast. Energy intake was matched across conditions. Both MICRO and ONE increased TEE relative to SED, resulting in a negative energy balance. HOMA-IR improved in both activity conditions. MICRO increased 24-h carbohydrate oxidation compared with both ONE and SED ( P < 0.01 for both). ONE was associated with higher 24-h total fat oxidation compared with SED, and higher 24-h dietary fat oxidation compared with both SED and MICRO. Differences in substrate oxidation remained significant after adjusting for energy balance. In overweight and obese men and women, breaking up sitting time increased reliance upon carbohydrate as fuel over 24 h, while a single energy-matched continuous bout of exercise preferentially relies upon fat over 24 h. NEW & NOTEWORTHY Insulin sensitivity, as assessed by HOMA-IR, was improved after 4 days of physical activity, independent of frequency and duration of activity bouts. Temporal patterns of activity across the day differentially affect substrate oxidation. Frequent interruptions of sedentary time with short bouts of walking primarily increase 24-h carbohydrate oxidation, whereas an energy-matched single continuous bout of moderate intensity walking primarily increased 24-h fat oxidation.

Initial test results on bolometers for the Planck high frequency instrument.

We summarize the fabrication, flight qualification, and dark performance of bolometers completed at the Jet Propulsion Laboratory for the High Frequency Instrument (HFI) of the joint ESA/NASA Herschel/Planck mission to be launched in 2009. The HFI is a multicolor focal plane which consists of 52 bolometers operated at 100 mK. Each bolometer is mounted to a feedhorn-filter assembly which defines one of six frequency bands centered between 100-857 GHz. Four detectors in each of five bands from 143-857 GHz are coupled to both linear polarizations and thus measure the total intensity. In addition, eight detectors in each of four bands (100, 143, 217, and 353 GHz) couple only to a single linear polarization and thus provide measurements of the Stokes parameters, Q and U, as well as the total intensity. The measured noise equivalent power (NEP) of all detectors is at or below the background limit for the telescope and time constants are a few ms, short enough to resolve point sources as the 5 to 9 arc min beams move across the sky at 1 rpm.

Impact of bariatric surgery on outcomes of patients with nonalcoholic fatty liver disease: a nationwide inpatient sample analysis, 2004-2012.

BACKGROUND: Bariatric surgery in eligible morbidly obese individuals may improve liver steatosis, inflammation, and fibrosis; however, population-based data on the clinical benefits of bariatric surgery in patients with nonalcoholic fatty liver disease (NAFLD) are lacking. OBJECTIVES: To assess the relationship between bariatric surgery and clinical outcomes in hospitalized patients with NAFLD. SETTING: United States inpatient care database. METHODS: The Nationwide Inpatient Sample database was queried from 2004 to 2012 with co-diagnoses of NAFLD and morbid obesity. Hospitalizations with a history of prior bariatric surgery (Roux-en-Y gastric bypass, gastric band, and sleeve gastrectomy) were also identified. The primary outcome was in-hospital mortality. Secondary outcomes included cirrhosis, myocardial infarction, stroke, and renal failure. Poisson regression was used to derive adjusted incidence risk ratios for clinical outcomes in patients with prior bariatric surgery compared with those without bariatric surgery. RESULTS: Among 45,462 patients with a discharge diagnosis of NAFLD and morbid obesity, 18,618 patients (41.0%) had prior bariatric surgery. There was a downward trend in bariatric surgery procedures (percent annual change of -5.94% from 2004 to 2012). In a multivariable analysis, prior bariatric surgery was associated with decreased inpatient mortality compared with no bariatric surgery (incidence risk ratios = .08; 95% confidence interval, .03-.20, P<.001). Prior bariatric surgery was also associated with decreased incidence risk ratios for cirrhosis, myocardial infarction, stroke, and renal failure (all P<.001). CONCLUSIONS: Prior bariatric surgery is associated with decreased in-hospital morbidity and mortality in morbidly obese NAFLD patients. Despite this, the proportion of NAFLD patients with bariatric surgery has declined from 2004 to 2012.

Bariatric Surgery and Hepatocellular Carcinoma: a Propensity Score-Matched Analysis.

BACKGROUND: The association between obesity and rising incidence of hepatocellular carcinoma (HCC) in the USA has been documented; however, the role of bariatric surgery remains less clear. AIM: To evaluate the cross-sectional association of prior-bariatric surgery and HCC. METHODS: The United States Nationwide Inpatient Sample (NIS) database was queried from 2004 to 2014 for discharges with a diagnosis of morbid obesity. Primary outcomes of interest were HCC and in-hospital mortality rate. Secondary outcomes were length of stay and cost. Baseline characteristics were balanced using propensity score matching (PSM). Using Poisson and logistic regressions, adjusted HCC prevalence ratio (PR) and mortality odds ratio (OR) were derived in patients with prior-bariatric surgery compared to those without bariatric surgery. RESULTS: Of the 2,881,414 patients included in our study, 267,082 (9.3%) underwent bariatric surgery. From 2004 to 2014, there was a threefold increase in age-adjusted prevalence of HCC from 27 per 100,000 to 72 per 100,000 (PTrend < 0.001). After PSM, 230,956 patients with prior-bariatric surgery were matched with 230,956 patients without bariatric surgery. Prior-bariatric surgery was associated with lower prevalence of HCC (PR 0.11; 95% CI, 0.03-0.48; P < 0.001). In-hospital mortality was also lower for patients with surgery (OR 0.22; 95% CI, 0.20-0.26; P < 0.001). The occurrence of HCC added $18,840 extra cost, increased mean length of stay by 2 (95% CI; 1-3) days, and increased risk of death by 65% (aOR 1.65; 95% CI 1.18-2.29). CONCLUSION: In this nationwide study of morbidly obese patients, prior-bariatric surgery was associated with a lower prevalence of HCC and lower in-patient mortality.

Individualized Physical 3-dimensional Kidney Tumor Models Constructed From 3-dimensional Printers Result in Improved Trainee Anatomic Understanding.

OBJECTIVE: To evaluate the effect of 3-dimensionally (3D) printed physical renal models with enhancing masses on medical trainee characterization, localization, and understanding of renal malignancy. METHODS: Proprietary software was used to import standard computed tomography (CT) cross-sectional imaging into 3D printers to create physical models of renal units with enhancing renal lesions in situ. Six different models were printed from a transparent plastic resin; the normal parenchyma was printed in a clear, translucent plastic, with a red hue delineating the suspicious renal lesion. Medical students, who had completed their first year of training, were given an overview and tasked with completion of RENAL nephrometry scores, separately using CT imaging and 3D models. Trainees were also asked to complete a questionnaire about their experience. Variability between trainees was assessed by intraclass correlation coefficients (ICCs), and kappa statistics were used to compare the trainee to experts. RESULTS: Overall trainee nephrometry score accuracy was significantly improved with the 3D model vs CT scan (P <.01). Furthermore, 3 of the 4 components of the nephrometry score (radius, nearness to collecting system, and location) showed significant improvement (P <.001) using the models. There was also more consistent agreement among trainees when using the 3D models compared with CT scans to assess the nephrometry score (intraclass correlation coefficient, 0.28 for CT scan vs 0.72 for 3D models). Qualitative evaluation with questionnaires filled out by the trainees further confirmed that the 3D models improved their ability to understand and conceptualize the renal mass. CONCLUSION: Physical 3D models using readily available printing techniques improve trainees' understanding and characterization of individual patients' enhancing renal lesions.

A homogeneity study using NIR spectroscopy: tracking magnesium stearate in Bohle bin-blender.

A method was developed for studying mixing of cohesive pharmaceutical mixtures. A combination of accurate sampling and NIR spectroscopic analysis was developed as a suitable method to determine homogenization of magnesium stearate as a function of blending variables. A typical pharmaceutical blend containing a ratio 35:64:1 lactose, avicel, and magnesium stearate was used as a model system. The method accounted for variability of the concentration of magnesium stearate as well as variability of the excipients. Levels of magnesium stearate as low as 0.05% could be resolved by the method, and showed a predicting confidence interval above 98%.

Spectroscopic approach for on-line monitoring of particle size during the processing of pharmaceutical nanoparticles.

A novel application of near-infrared (near-IR) spectroscopy for the on-line determination of nanoparticle size of a drug compound in a high solids dispersion is described. The on-line spectroscopic technique provides real-time data for process monitoring and control and overcomes the limitations that are encountered using laboratory-based instrumentation for nanoparticle size determination. Near-IR spectroscopy is capable of providing an accuracy of 2.4 nm near the endpoint of particle production, where the volume-weighted D90 particle size is determined to be 200-220 nm. The accuracy is adequate for endpoint control, which minimizes excess processing and provides control over the particle size throughout nanoparticle production.

Numerical optimization of integrating cavities for diffraction-limited millimeter-wave bolometer arrays.

Far-infrared to millimeter-wave bolometers designed to make astronomical observations are typically encased in integrating cavities at the termination of feedhorns or Winston cones. This photometer combination maximizes absorption of radiation, enables the absorber area to be minimized, and controls the directivity of absorption, thereby reducing susceptibility to stray light. In the next decade, arrays of hundreds of silicon nitride micromesh bolometers with planar architectures will be used in ground-based, suborbital, and orbital platforms for astronomy. The optimization of integrating cavity designs is required for achieving the highest possible sensitivity for these arrays. We report numerical simulations of the electromagnetic fields in integrating cavities with an infinite plane-parallel geometry formed by a solid reflecting backshort and the back surface of a feedhorn array block. Performance of this architecture for the bolometer array camera (Bolocam) for cosmology at a frequency of 214 GHz is investigated. We explore the sensitivity of absorption efficiency to absorber impedance and backshort location and the magnitude of leakage from cavities. The simulations are compared with experimental data from a room-temperature scale model and with the performance of Bolocam at a temperature of 300 mK. The main results of the simulations for Bolocam-type cavities are that (1) monochromatic absorptions as high as 95% are achievable with <1% cross talk between neighboring cavities, (2) the optimum absorber impedances are 400 ohms/sq, but with a broad maximum from approximately 150 to approximately 700 ohms/sq, and (3) maximum absorption is achieved with absorber diameters > or = 1.5 lambda. Good general agreement between the simulations and the experiments was found.

Predicting the response of a submillimeter bolometer to cosmic rays.

Bolometers designed to detect submillimeter radiation also respond to cosmic, gamma, and x rays. Because detectors cannot be fully shielded from such energy sources, it is necessary to understand the effect of a photon or cosmic-ray particle being absorbed. The resulting signal (known as a glitch) can then be removed from raw data. We present measurements using an Americium-241 gamma radiation source to irradiate a prototype bolometer for the High Frequency Instrument in the Planck Surveyor satellite. Our measurements showed no variation in response depending on where the radiation was absorbed, demonstrating that the bolometer absorber and thermistor thermalize quickly. The bolometer has previously been fully characterized both electrically and optically. We find that using optically measured time constants underestimates the time taken for the detector to recover from a radiation absorption event. However, a full thermal model for the bolometer, with parameters taken from electrical and optical measurements, provides accurate time constants. Slight deviations from the model were seen at high energies; these can be accounted for by use of an extended model.